Human resources section9-textbook_on_public_health_and_community_medicine
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AFMC WHO Textbook Community Medicine

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Human resources section9-textbook_on_public_health_and_community_medicine Human resources section9-textbook_on_public_health_and_community_medicine Document Transcript

  • 10095752550
  • Section 9 : Communicable Diseases167 Principles of Infectious Diseases Epidemiology RajVir Bhalwar 976168 Immunization Rajesh Vaidya 982169 General Prevention and Control Measures Rajesh Vaidya and VK Bhatti 1001 Aniruddha Hazra, LS Vaz,170 Public Health Laboratory : Microbiological Procedures 1008 Nandita Hazra171 Malaria Rajesh Vaidya 1025172 Lymphatic Filariasis Rajesh Vaidya 1032173 Leishmaniasis Rajesh Vaidya 1036174 Dengue & Dengue Haemorrhagic Fever Rajesh Vaidya 1040175 Chikungunya Rajesh Vaidya 1044176 Japanese Encephalitis Rajesh Vaidya 1046177 Rickettsial Diseases Rajesh Vaidya 1049178 Yellow Fever Rajesh Vaidya 1054179 Viral Hepatitis Rajesh Vaidya 1057180 Anthrax Rajesh Vaidya 1066181 Tetanus Rajesh Vaidya 1068182 Plague Rajesh Vaidya 1071183 Rabies Rajesh Vaidya 1075184 Leptospirosis Rajesh Vaidya 1080185 Brucellosis Rajesh Vaidya 1082186 Mechanism of Air - borne Infections Rajesh Vaidya 1085187 Measles Rajesh Vaidya 1086188 Rubella Rajesh Vaidya 1089189 Chicken Pox and Herpes Zoster Rajesh Vaidya 1091190 Smallpox Rajesh Vaidya 1094191 Diphtheria Rajesh Vaidya 1095192 Mumps Rajesh Vaidya 1098193 Meningococcal Meningitis Rajesh Vaidya 1101194 Tuberculosis Rajesh Vaidya 1104195 Avian Influenza Rajesh Vaidya 1113196 Severe Acute Respiratory Syndrome (SARS) Rajesh Vaidya 1117197 Acute Gastroenteritis Rajesh Kunwar 1119198 Cholera Rajesh Kunwar 1125199 Food Poisoning Rajesh Kunwar, Rajul Gupta 1129200 Enteric Group of Fevers Rajesh Kunwar 1132201 Shigellosis Rajesh Kunwar 1135202 Helminthiasis Rajesh Kunwar 1137203 Amoebiasis & Giardiasis Rajesh Kunwar 1148204 Sexually Transmitted Infections (STI) Sunil Agrawal 1151205 Yaws : The Story of Successful Elimination Sunil Agrawal 1159206 Acquired Immuno-Deficiency Syndrome (AIDS) Sunil Agrawal 1163207 Leprosy (Hansen’s Disease) Sunil Agrawal 1173208 Trachoma Sunil Agrawal 1177
  • be transmitted to a human being either directly, or indirectly Principles of Infectious Diseases 167 Epidemiology (through food, water, insect vectors, soil), or else a disease which can be transmitted between humans and animals. All infectious diseases are not necessarily communicable; e.g. RajVir Bhalwar osteomyelitis or brain abscess are infectious diseases but not communicable. Similarly, an infectious disease may be communicable in one form (e.g. pneumonic plague) but not inOne way of broadly classifying human diseases is according to the other form (e.g. bubonic plague).whether they are “infectious (communicable)” or else, “non -communicable”. Out of these two, infectious diseases account Dead-End Infection : A state when an infectious disease,for lion’s share of death, ill - health and suffering in the which is usually “communicable”, cannot be transmitted anydeveloping countries. For this reason an epidemiologist must further between human beings or from humans to animals orhave a sound understanding of the epidemiologic principles vice versa, for various agent, host and environmental reasons.concerning infectious disease practice. Examples are Japanese Encephalitis, Rabies, Tetanus, Bubonic plague, Scrub typhus in humans.General Terms and Definitions Subclinical Infection (Inapparent infection) : It is a stateInfection & Infectious Disease : This refers to the entry when there is a host immune response following entry of theand development or multiplication of an infectious agent in infectious agent; the agent may also multiply in the host body,the human (or, animal) body, with an implied response (e.g. but there are no clinical manifestations of the disease. Thus,immunological response) on the part of the human or animal. the presence of infection cannot be recognized clinically thoughIt must be remembered that “infection” by itself does not the infectious agent is constantly passed out of the humanmean “infectious disease”. An infectious disease is that part body and hence a person with subclinical infection is a greaterof the spectrum of “infection” which is clinically apparent. health hazard for community than those having apparentIn fact, this is the basic difference between epidemiologic disease (since the latter can be identified, treated and isolatedpractice and clinical practice as regards infectious disease - the if required). Diseases like Viral hepatitis A, have large numberclinician is mainly interested in “infectious disease” while the of subclinical infections; on the other hand, diseases likeepidemiologist is interested in “infection” and its dynamics - measles hardly have any subclinical infections. Thus, infectionsincluding the subclinical cases, the carriers, the reservoirs or which have a large proportion of subclinical infections in theirthe infectious agent and its modes of transmission. spectrum are less amenable to prevention; on the other hand,Colonisation : Colonisation indicates presence of infectious diseases which have very few or no subclinical infections areagent in the human body but without any evidence of specific more amenable to prevention by surveillance immune responses to the agent. In short, colonization Latent Infection : This refers to a state when the infectiousmeans “infection less specific immune response”. agent lies “dormant” within the host body, without any clinicalEndogenous Infection : Infection due to a colonizing agent; manifestations but does not come out of the human body (thuse.g. E Coli normally colonises the human GIT; however, under it is different form subclinical infection). After a period of time,certain circumstances, it may enter the blood stream and cause under certain circumstances, the agent which had been lyingendogenous infection. dormant, reactivates and produces a different type of diseaseContamination : Refers to an infectious agent being present in (e.g. Herpes Zoster; Brill - Zinser disease) or else the same typeinanimate articles like food, water, linen, patient care items or of disease (e.g. reactivation Tuberculosis).routine usage items like cutlery, toys etc. often, the term is also Zoonoses : Zoonoses are infections which are normallyused to denote presence of infectious agent on skin surface, transmitted between vertebrate animals, either directly, orparticularly on hands. indirectly through a vehicle or insect vector. Those which arePollution : Refers to presence of either infectious agent or of health importance are the ones that are transmitted to mansuch other disease causing noxious agents (as industrial from vertebrate animals, either directly, or indirectly througheffluents) or mechanical agents (as sound), usually in the vehicle or vectors. These are called “anthropozoonoses” andgeneral environment, air or water (e.g. sound pollution, water include a long list of infections like Rabies, Plague, Bovine TB,pollution, air pollution). Salmonellosis, Japanese Encephalitis, Scrub and Murine typhus,Infestation : Infestation may refer to human beings, animals Echinococosis, Anthrax, Brucellosis and so on. The secondor personal usage items, wherein it implies either the presence group are infections which primarily infect man but can beand development of insect vectors on the body or linen (e.g. transmitted to animals; these are called as zooanthroponoses.louse infestation) or else on the mucus membranes (e.g. The third group is amphixenosis which includes infections thatroundworm infestation). Infestation is also sometimes used for may be transmitted from man to animals and vice versa.describing a state wherein an accommodation or such articles Opportunistic Infections : The term refers to disease, causedas containers have the presence of arthropods or vectors (e.g. by infectious agents, which are normally not pathogenic, duecockroach or rat infestation in the houses). to a decline in the general or specific immune status of theCommunicable Disease : A communicable disease is one host. The term has assumed greater importance followingthat is caused by an infectious agent (or its toxic products, identification of HIV infection whose clinical manifestationse.g. preformed toxins of B cereus or C botulinum) which can comprise of a wide variety of such opportunistic infections like P carini, T gondi, CMV etc. • 976 •
  • Nosocomial Infection : This is an infection contracted while in to another human so as to further propagate the species. Thehospital, as a result of health care or related procedure. Such worms do not depend primarily for survival and multiplicationinfections would include those whose clinical presentation on any other animal, soil, plants, etc. Thus, the “reservoir ofmay start after discharge from the hospital but NOT those infection” is “human being, infected with Hookworm”, (humanwhich were “incubating” in the patient’s body at the time of reservoir). On the other hand, infection of another humanadmission. The field of “Nosocomial Epidemiology” is fast being occurs due to skin contact with soil contaminated withbecoming a specialized one. Hospital epidemiologists should infective stage larvae. Thus, the “source” is “soil contaminatedensure prevention and control of such hospital infections. with infective stage larvae”.Eradication : The term refers to a complete cessation of Types of “Reservoir of Infection” : The most importanttransmission of the infectious agent. Usually this would imply “reservoir” for large majority of human infectious agents isthat the infectious agent as well as the disease has also been the human being himself. The “human reservoir” of infectiouscompletely reduced to zero. Small pox is the only example agents can occur in two forms, viz. Cases and Carriers :wherein eradication has been achieved. a) Cases : Those who have clinically apparent disease.Control : This refers to reducing the transmission of a disease b) Carriers : A carrier is a human being who harbours anto a level when it no longer remains a “public health problem”. infectious agent and sheds it, thus becoming a potential sourceControl is more pragmatic then eradication but needs ongoing of infection for other human beings, but does not exhibit anypreventive measures, and consequently continuing expenditure, manifestation of the disease. The fact that they cannot bealongwith an efficient surveillance system to give an early detected despite being a potential source of infection for otherwarning of increase in the level of transmission. makes carriers extremely important from epidemiologicalElimination : Elimination implies either a ‘regional eradication” point of view. Depending on the stage of disease in its natural(say from a country or continent), or else reduction of disease progression, a person may be a carrier either during theto zero without total removal of infectious agent. incubation period (incubatory carriers) as occurs in measles,Epidemiologic “Chain” of Infection mumps, Hepatitis A, etc. The importance of the incubatory carrier state lies in the fact that after the incubation period isThere are 4 inter - related factors, which together are referred over and the disease manifestations come up, we may isolateto as the “epidemiologic chain of infection’ : and treat the person, but the damage has already been done by(a) The infectious agent and its characteristics. him, by transmitting the infection during incubation period.(b) The human host who is susceptible to the infectious agent, Secondly, he may be having subclinical or clinically inapparent and various factors which determine such susceptibility. disease (contact or healthy carrier) e.g. Hepatitis A, Cholera,(c) Characteristics of the infectious process which are Poliomyelitis, Diphtheria etc. A subclinical carrier should be determined by the interactions between agent and the differentiated from a subclinical case, which refers to a person host. who has the infection beyond the incubation period but do not(d) Inter - connecting the agent and host are the “channels show clinical manifestations and do not shed the organisms (or modes) of transmission of the agent to the host. Let so that the infection cannot be transmitted to other human us discuss the details of each of these components of the hosts; e.g. subclinical case of Japanese Encephalititis in which chain of infection. the infectious agent is present in the body, but the low titerAgent viraemia is inadequate to infect the mosquito vector. Thirdly,There are three broad groups of characteristics that are the person may continue to shed the infectious agent even afterimportant in respect of infectious disease agent viz. the reservoir apparent recovery, during the convalescent stage, and henceand immediate sources of the agent; the characteristics of an known as convalescent carrier as occurs in cholera, typhoidagent that are connected with its survival in environment; and and bacillary dysentery. Such “convalescent carriers” may bethe characteristics of agent which determine the production short term or temporary carriers (lasting upto 4 weeks or so) orof infection and consequent to infection, the production of chronic carriers (lasting beyond 4 weeks; may be upto years asdisease. in chronic typhoid infection of gall bladder) (103).Reservoir and Immediate Source of Agent : Any infectious Animals and Other Forms of Reservoir : Besides humanagent has a primary habitat, called the “reservoir of infectious beings, animals form another reservoir wherein the infectiousagent” which can be defined as “a person, animal, or inanimate agent lives primarily, thrives, multiplies and is available forenvironment (like soil), where an infectious agent lives, being transmitted to the human host. Such diseases fit in thedepending primarily for its survival, and where it propagates scope of “zoonoses” as has been already described. Finallyitself so that it can be transmitted to a human host”. On the some infectious agents like fungi may primarily thrive andother hand, a source of infection is the person, animal, or their multiply in the contaminated soil.excretions or inanimate environment from where the infective Characteristics of Agent Concerned with Survival in Nature:form of the agent is immediately available to the susceptible The capability of an agent to thrive outside the reservoir andhuman host. Let us take the example of hookworm. The adult withstand adverse environmental effects like drying, heat,forms live in human gut, depending primarily on the human acidity, etc is known as “survival capacity in nature”. Somebeing for their survival; they multiply there and propagate agents can hardly survive outside the human body (e.g.themselves, the eggs being passed out for further transmission measles, chicken pox). Others may survive for limited time • 977 •
  • provided conditions are favourable (e.g. cholera vibrio, polio Host Factorsvirus, Hepatitis A, etc. can survive in water, ice, sewage, milk, Like the agent is on one end of the epidemiological chain ofetc; HIV can survive in blood and blood products; however all infection, the “HOST” is at the other end of the chain. The hostof them are quite vulnerable to drying, heat and disinfectants). factors which determine the dynamics of infection fall into twoFinally some organisms or their intermediate forms are quite broad categories :sturdy and can withstand adverse environment very well (a) Host Attributes which Affect the Probability of Being(e.g. clostridal spores, cysts of intestinal protozoans, ova of Exposed to the Infectious Agent : These include age (e.g.helminthes etc). Usually, agents which have very poor survival young children, because of hygienic innocence and habit ofin nature tend to adopt the direct modes of transmission like “orally exploring” the items, are more susceptible to exposuredroplet infection or direct mucous contact. Survival in nature to soil transmitted helminthic infections); Sex (e.g. females,becomes all the more crucial for the agent, if human being is by virtue of leading a mainly indoor life may be less exposedthe only reservoir. to sylvatic zoonoses like Kyasanur Forest Disease), EconomicCharacteristics of Agent Involved in Production of Infection status (poverty, squalor and infection form an almost invincibleand Disease : The various characteristics of an infectious trinity and this needs no further highlighting), Occupationagent which determine the production of infection, as well as (e.g. agricultural workers and veterinarians are much morethe causation of disease are (104) : likely to be exposed to certain zoonoses), Education (by way ofInfectiousness : this is the relative ease with which the agent improving the knowledge regarding causation and preventionis transmitted to the host. Infectiousness is more of function of infection, may help in reducing the chances of exposure),of environmental factors; e.g. infectiousness of measles would Living conditions (Poor housing, overcrowding, lack of sanitarybe higher in overcrowded conditions but lesser in affluent eating and drinking facilities will all increase the chances ofcommunities. exposure), Life style and behavioural factors (e.g. permissiveInfectivity : This is the ability of the agent to cause infection, attitude toward sex will increase the probability of exposurei.e. to enter, survive and multiply in the host. A useful to reservoir of STDs), and use of Personal protective measuresepidemiologic measure of infectivity is Secondary Attack (e.g. use of mosquito nets and repellents decrease the chancesRate (SAR). It is defined as the number of susceptible persons of exposure to mosquito borne diseases).who, within the duration of one incubation period, following (b) Host Factors that Influence Occurrence of Infection andexposure, develop the disease out of the total susceptibles who Disease : Once the host has been “exposed” to the infectiouswere exposed. SAR is usually measured by conducting studies agent, certain factors will determine whether disease willin closed communities or families wherein the first case which actually occur and the severity of the same. These includebrings in the infection is called the index case. “status of host immunity”, whether actively or passively (orThus, naturally or artificially) acquired; Age (In general, extremes of age viz. the very young, i.e. < 2 years and the old, > 65 years are No. of susceptible exposed to index Case, more susceptible); Genetic make up (known to occur in respect who develop the disease, of diseases like tuberculosis and malaria); and Availability & within the duration of maximum utilization of health services (by providing chemoprophylaxis, incubation period of the disease immunization and health education at the primary preventive SAR = X 100 level and early diagnosis and prompt treatment) Total number of susceptibles exposed to the Index case Herd Immunity : Herd immunity refers to the level of immunity that is present in a population against an infectious agent. ItPathogenecity : It is the ability of the agent to produce manifest is, thus, concerned with the protection of a “population” fromdisease out of those who have been infected. Generally, agents infection, the protection being brought about by the presencewhich have high pathogenecity have features which protect of immune individuals. It may be defined as “the resistancethem from non - specific host defenses, and elaborate toxins of a group to attack by a disease to which a large proportionor similar products (e.g. Diphtheria, Tetanus) or else, may of the members are immune, thus decreasing the probabilitycause such host immune response that leads to disease (e.g. that a person having the infectious agent will transmit it toRheumatic fever, Glomerulonephritis). another susceptible person in the same population”. In general,Virulence : Higher in order, from infectivity and pathogenecity, while dealing with childhood infectious diseases amenable tois virulence. It is the ability of the agent to produce severe prevention by immunization, vaccination coverage of aboutdisease. If “serious’ infection is being measured in terms of 85% is likely to provide adequate herd immunity, which willdeath, then Case Fatality Ratio (CFR) becomes a reasonably effectively block the disease transmission, even if remaininggood measure of virulence. 15% children are not immunized (though there may be many exceptions to this generally held belief).Infective Dose : Infective dose is important for certaininfectious disease agents like V cholera and S typhi in which, if Factors Affecting the Process of Infection as a Resultthe inoculum is not adequate, then infection may not settle, or of Interaction Between Agent and Hostat least, manifest disease may not occur. On the other hand, in There are certain features which are peculiar to each infectiousinfections like plague, even a very small dose may be enough disease as follows :to cause infection. • 978 •
  • Incubation Period : Incubation period is the time period between Frequency of Disease : As has been repeatedly stressed in thisthe entry of infectious agent (or its toxin) into the human chapter, the epidemiologist should not go simply by observedbody to the point when the earliest clinical manifestations number of cases of a disease but convert it into some form ofof the disease are apparent. During this period, the host does frequency measure (like incidence or prevalence) by relatingnot exhibit any outwardly clinical manifestations, though the number of cases to a denominator (the population at risk).immunological and histopathological changes within the body Depending on the “frequency” of the disease, the occurrencewould definitely occur. If, during this period, the organism is may bealso shed from the body of the host, the host qualifies to be an ●● “Epidemic” : This is the occurrence of disease frequency,“incubatory carrier”. Incubation period is usually measured in in a defined population or area, which is clearly in excessterms of “median incubation period”, i.e. the time in which half of the normal expectation.of the infected subjects will develop clinical manifestations, ●● “Endemic” frequency refers to continued transmission offollowing entry of the organism into the body. Alongwith a disease, in a defined population or area, at a relativelythe median incubation period, a “range” is also given which low level (without any importation from an outside area orindicates the minimum and maximum incubation periods. population). It would also be appreciated that the differenceIncubation period of a disease is found out by studying the between an epidemic and an endemic situation is dependenttime taken for onset of secondary cases following exposure to on two factors - firstly, the high frequency and the “abruptthe index case, in family groups or in closed communities, or increase” which occurs in epidemic situation, compared toelse during investigation of “common - vehicle, point source “continued transmission” in endemic settings. Dependingepidemics”. Different diseases have different values of median on the “frequency” with which this continued transmissionincubation period and range, and a specialist in Public health is going on in an endemic scenario, the endemicity could beshould remember them well. described as “hypoendemic” or “low endemic”, (incidenceLatent Period : In infectious disease epidemiology, latent being low), mesoendemic, hyperendemic, and holoendemic.period refers to the time that elapses between the entry of the In both hyperendemic as well as holoendemic situations, theagent in the human body to the point when the shedding of transmission continues at a very high frequency; howeverorganism starts. in the latter situation, exposure to infection generallyPeriod of Communicability (Infectious Period) : This is occurs during early childhood so that by the time adulthoodthe duration for which the host sheds the agent, i.e. remains is achieved, the population becomes immune and a highinfectious. This may be very long in case of diseases like leprosy level of herd immunity occurs. For this reason, epidemicand HIV infection. outbreaks of the disease are not likely in holoendemic situations (the classical example being “stable malaria”Generation Time : The generation time is the duration between situations). The epidemiologist should note that half -the entry of infectious agent into the body to the peak infectivity hearted or unscientific measures (e.g. sudden introductionof the host. As a crude calculation, generation time (G) is equal of insecticidal spray programs without full coverage andto (latent period + period of maximum communicability). without concurrent coverage with surveillance for promptThe relationship between the various landmarks of a typical diagnosis and treatment for a disease like Malaria) wouldinfectious disease is depicted as follows : tend to convert a “stable”, holoendemic situation into an “unstable” meso - endemic one, thus increasing theI ----------- I ----------- I ----------- I ----------- I ----------- I ---------- I propensity to epidemic outbreaks. ●● “Sporadic” frequency which refers to few, scattered casesLandmarks : A = Entry of agent into host; B = Shedding of agent starts; C of infection, which do not have any relation to each other= Clinical manifestations start; D = Maximum infectivity of host; E = Clinicaldisease ends; F =Shedding of agent ends; G = Convalescence ends; A to B = Latent temporally or spatially (i.e. according to place or time). Theperiod; A to C = Incubation period; A to D = Generation time; C to E = Clinical difference between a “low endemic” disease and sporadicphase; E to G = Convalescence phase; B to F = Period of communicability; B to C disease is based on this fine dividing line - that in a low= Incubatory carrier phase; E to F = Convalescent carrier; E to G = convalescentphase; C to F = Subclinical (healthy) carrier phase (if clinical disease did not endemic disease, the frequency of disease is low but theoccur). cases would show a reasonable relation to each otherBiological Gradient (Gradient of Infection) : Biological according to place or time which will not be the case ingradient of a disease refers to the range of manifestations sporadic situations.that may occur in the host as a result of infection. Thus, it is Channels of Transmissionlike a “spectrum”, ranging from inapparent infection at one The two end points in the epidemiological chain of infectionend, and passing through mild illness, clinical disease, serious are the infectious agent and the (susceptible) host. Now, toforms of disease, to death at the other extreme of the spectrum. complete this link, the infectious agent must be transmitted toDiseases like viral Hepatitis - A, poliomyelitis and cholera the susceptible host. Such establishment of the link betweenhave a classically wide biological gradient with all varieties of agent and host is of two types, viz “direct” and “indirect”severity as outlined above being present. On the other hand, modes of transmission.measles and chicken pox tend to have only the middle part (a) Direct Modes of Transmission : A direct mode ofof the spectrum with either subclinical cases or deaths being transmission is one in which the infectious agent has to be inuncommon. Diseases like rabies occupy only the other extreme a state of actual physical or physiological proximity with theof the spectrum, having a very serious biological gradient, with susceptible host, or even if not in such proximity, should becertain death being the only outcome. • 979 •
  • within a very close distance so as to be able to directly come survive environmental adversaries like drying or heat, it can bein contact with the host. There are five methods of such direct carried for long distances by air currents, alongwith the dusttransmission or droplet nuclei; and if deposited on the portal of entry of a●● Contact of host skin or mucous membranes with the susceptible host, can initiate infection. Important examples infectious agent contained in a living tissue; e.g. sexually are legionnaires disease, ‘Q’ fever, tuberculosis, nosocomial transmitted diseases. infections. Air borne infected nuclei and dust should be●● Contact of skin or mucous membranes with the infectious differentiated from “droplet infection”. As explained, the form of the agent contained in inanimate environment. latter is a ‘direct” method of transmission in which the agent The examples include transmission of hookworm (infective is directly deposited from the immediate source of infection form in soil) and leptospirosis (infective form in water or onto the portal of entry of a susceptible host, the intervening soil contaminated with urine ). distance being very short (maximum 1 meter). On the other●● Inoculation of the agent, directly from the reservoir into hand, in an air borne transmission the agent is not directly the skin or mucous as in Rabies. deposited from the source of infection on to the portal of entry●● “Vertical transmission” from mother to child, through the of susceptible host but transported indirectly by air over long placenta, e.g. HIV, syphilis, “TORCH” agents etc. distances.●● Direct transmission due to the agent being within a Vector Borne Indirect Transmission : A vector is a living reasonably close distance of the host, as occurs in “droplet invertebrate which transfers the infectious agent from the infection”. Droplets are actually very finely dispersed source of infection to another susceptible host. Usually the term aerosol containing the infectious agent, which are formed encompasses arthropods, and to a smaller extent, molluscs when a person harbouring the agent in his respiratory tract like snails. Such transmission by a vector could be either undertakes such activities like coughing, sneezing, talking “mechanical”, in which the vector simply acts as a “fomite”, etc. if another susceptible host is within a ‘reasonably transferring the infectious agent from the host on to another close’ distance (usually taken to be 1 meter at the most), vehicle like food, by carrying the agent on its body surface or such infective droplets can be directly deposited on to the in the gut (finally excreting them in the faeces). The common mucous membrane of oral cavity or respiratory passage example is of the housefly, which mechanically transmits a (i.e. the relevant portal of the respiratory tract infections). number of oro - faecal disease agents from the faeces to the TB, common cold, influenza, measles, mumps, pertusis, food. Secondly, it could be a “biological” transmission, wherein diphtheria, meningococcal infection, leprosy etc. are the infectious agent is transmitted, not simply in a mechanical transmitted by such mode. form, but undergoes, within the body of the vector, one or more(b) Indirect Modes of Transmission : An indirect mode of of the biological changes pertaining to the stages in its lifetransmission can be defined as one in which its infectious agent cycle. Such biological changes may occur in one of the followingrequires an “intermediary agency” to convey it from the source three ways :of infection to the susceptible host. Like for direct modes, there ●● Take the example of plague bacillus. After being taken upcan be five types of indirect modes of transmission : by the rat flea following a blood meal on the rodent, theVehicle Borne : The various types of “vehicles” which can bacilli so taken up with the blood, multiply enormously,convey the infectious agent, from the source of infection to the increasing in number, in the mouth parts of the rat flea.susceptible host include anything which is eaten (e.g. food, However, there is no developmental change as regardssweets, milk products, confectioneries and so on, or anything stages of life cycle of the bacillus. Such a method ofwhich is drunk (e.g. milk, ice, water, beverages etc). Infections biological transmission in which the agent “multiplies”of the gastrointestinal tract are classically transmitted by this but does not “develop” in the body of the vector beforemode and include such common examples as cholera, typhoid, being finally transmitted to the susceptible host, is knownhepatitis - A, ascarisis, amoebiasis and so on. A vehicle also as “propagative” mode.would include anything which can be “injected” (e.g. blood and ●● As another example, once a female culex mosquito takes inblood products, drugs, vaccines, diluents; examples are HIV, a microfilaria along with the blood meal, the microfilaria soHepatitis B, Malaria etc). taken up will undergo developmental changes of life cycle“Fomites” : These are defined as inanimate objects of general in the body of the mosquito (the three larval stages, finallyuse by the infected person (e.g. utensils, linen, fountain becoming the infective stage larva). However, there is nopens, tooth brushes etc.) The infectious agent may remain multiplication and for each one microfilaria taken up withon the surface of such fomites and may be transmitted to the blood meal, there will be, finally, only one infective formsusceptible host usually when such objects are put into the larva. Thus, if the agent undergoes developmental changesmouth or come in contact with conjunctiva. in the body of the vector but no multiplication, the same is known as “developmental” or “cyclo developmental”Fingers : Fingers form a very important mode of indirect method.transmission. If Contaminated, they can transport a number ●● Finally, let us consider the sequence of events that occurof gastrointestinal infection (especially, shigella, Salmonella following ingestion of malarial male and female gametocytestyphi, vibrio and Entamoeba). along with blood meal by a mosquito. The gametocytesAir : Often droplets containing the infectious agent may dry transform into gametes, form a zygote, followed by oocystup, or may settle down on the dust. Now, if the agent can and sporozoites. Thus, there are developmental changes • 980 •
  • pertaining to the life cycle of the agent. In addition, for The “human reservoir” of infectious agents can occur in two one each of male and female gametocyte taken in by the forms, viz. Cases and Carriers. Those who have clinically mosquito, there will be formed, not one but thousands of apparent disease are cases, whereas a carrier is a human sporozoites; thus, if in addition to developmental changes, being who harbours an infectious agent and sheds it, thus there is multiplication, it is know as “cyclo - propogative”. becoming a potential source of infection for other human beings, but does not exhibit any manifestation of the disease.Summary Carriers are of various types - subclinical, incubatory and soInfection/ Infectious disease refers to the entry and development on. Infectiousness is the relative ease with which the agent isor multiplication of an infectious agent in the human (or animal) transmitted to the host ; whereas Infectivity is the ability ofbody, with an implied response (e.g. immunological response) the agent to cause infection, a useful measure being Secondaryon the part of the human or animal. An infectious disease Attack Rate (SAR). Pathogenecity is the ability of the agent tois that part of the spectrum of “infection” which is clinically produce manifest disease out of those who have been infected.apparent. Colonization indicates presence of infectious agent Virulence is the ability of the agent to produce severe the human body but without any evidence of specific host The host factors which determine the dynamics of infectionimmune responses to the agent. Infection due to a colonizing fall into two broad categories - Host attributes which affectagent is called endogenous infection. Contamination refers to the probability of being exposed to the infectious agent (likean infectious agent being present on inanimate articles. age, sex, SES etc.) and host factors that influence occurrencePollution refers to presence of either infectious agent or such of infection and disease ( like status of host immunity, geneticother disease causing noxious or mechanical agents, usually make - up etc.). Herd immunity refers to the level of immunityin the general environment, air or water. Infestation may refer that is present in a population against an infectious human beings, animals or personal usage items, wherein it Certain features which are peculiar to each infectious diseaseimplies either the presence and development of insect vectors are as follows : Incubation period is the time period betweenon the body or linen or on the mucous membranes. the entry of infectious agent (or its toxin) into the human bodyA communicable disease is one that is caused by an infectious to the point when the earliest clinical manifestations of theagent or its toxic products which can be transmitted to a human disease are apparent; whereas, Latent period refers to the timebeing either directly, or indirectly . Dead - end infection is a state that elapses between the entry of the agent in the human bodywhen an infectious disease, which is usually “communicable”, to the point when the shedding of organism starts.cannot be transmitted any further between human beings or Infectious period is the duration for which the host sheds thefrom humans to animals or vice versa, for various agent, host agent. Generation time is the duration between the entry ofand environmental reasons. Subclinical infection is a state when infectious agent into the body to the peak infectivity of the host.the agent may also multiply in the host body, but there are no Depending on the “frequency” of the disease, the occurrenceclinical manifestations of the disease; whereas Latent infection may be either Epidemic, which is the occurrence of diseaserefers to a state when the infectious agent lies “dormant” frequency, in a defined population or area, which is clearly inwithin the host body, without any clinical manifestations but excess of the normal expectation; or Endemic frequency refersdoes not come out of the human body. Zoonoses are infections to continued transmission of a disease, in a defined populationwhich are normally transmitted between vertebrate animals, or area, at a relatively low level (without any importation fromeither directly, or indirectly through a vehicle or insect vector. an outside area or population). Depending on the “frequency”Opportunistic infection refers to disease, caused by infectious with which this continued transmission is going on, theagents, which are normally not pathogenic, due to a decline in endemicity could be described as hypoendemic, mesoendemic,the general or specific immune status of the host . hyperendemic and holoendemic. Sporadic frequency refers toNosocomial infections are those contracted while in hospital, few, scattered cases of infection, which do not have any relationas a result of health care or related procedure. The term to each other temporally or spatially.Eradication refers to a complete cessation of transmission of the There are two broad modes of disease transmission - directinfectious agent. Control refers to reducing the transmission of and indirect; A direct mode of transmission is one in whicha disease to a level when it no longer remains a “public health the infectious agent has to be in a state of actual physical orproblem”. Elimination implies either a ‘regional eradication” physiological proximity with the susceptible host (for example,or else reduction of disease to zero without total removal of inoculation or vertical transmission), whereas an indirect modeinfectious agent . of transmission can be defined as one in which its infectiousFour inter-related factors are together referred to as the agent requires an “intermediary agency” to convey it from the“epidemiologic chain of infection” - these are : agent, host, source of infection to the susceptible host (for example, vehicleinteraction between agent and host; and modes of transmission. or vector - borne). Vector - borne transmission may be of manyThere are three broad groups of characteristics that are important types - cyclo - developmental, propagative or cyclo - propagative,in respect of infectious disease agent, viz. the reservoir and depending on whether only development or multiplication orimmediate sources of the agent; the characteristics of an agent both (of the causative organism) occurs in the vector.that are connected with its survival in environment; and,the characteristics of agent which determine the productionof infection and, consequent to infection, the production ofdisease. • 981 •
  • Study Exercises 8. Case Fatality Ratio (CFR) is a reasonably good measure of (a) Pathogenecity (b) Infectivity (c) VirulenceLong Question : Discuss, with suitable examples, the various (d) Infectiousnessmodes of transmission of infectious diseases. 9. Epidemiologic chain of infection usually involves all of theShort Notes : (1) Herd Immunity (2) Survival of infectious following factors except (a) Disinfectatnts (b) Infectiousagent in nature (3) Nosocomial infections (4) Incubation period agent (c) Human host (d) Modes of transmission(5) Carriers. 10. The presence and development of insect vectors onMCQs & Exercises the body or linen e.g. louse is known as (a) Infection1. Presence of an infectious agent in an inanimate article or (b) Infestation (c) Infectiousness (d) Infectivity on skin surface, particularly hands, is called (a) pollution 11. A significantly large amount of subclinical infection occurs (b) contamination (c) infection (d) infestation in all of the following diseases except (a) Hepatitis A2. Which mode of transmission is followed in transmission (b) Hepatitis B (c) Rubella (d) Measles of microfilaria through female culex mosquito (a) cyclo 12. All of the following diseases are examples of - propagative (b) propagative (c) cyclo - developmental Anthropozoonoses except (a) Tryponosoma cruzi (d) vehicle - borne (b) Hydatid disease (c) Trichinosis (d) Plague.3. Malaria and Filariasis are mainly transmitted through 13. All of the following organisms are quite sturdy and vehicle - borne mode of transmission . Yes/ No can withstand adverse environment very well, except4. All of the following are examples of direct modes of (a) Clostridal spores (b) Cysts of intestinal protozoans transmission except (a) Fomites (b) inoculation into skin (c) Ova of helminths (d) Hepatitis A virus or mucus membranes (c) droplet infection (d) vertical 14. The time in which half of the infected subjects will develop transmission clinical manifestations, following entry of the organism5. Latent period + period of maximum communicability into the body, is known as (a) Lead time (b) Median Latent will give a crude estimate of the (a) lead time (b) lag time period (c) Median Incubation Period (d) Generation time (c) generation time (d) incubation period 15. That subset of Endemic frequency, wherein exposure to6. The level of immunity that is present in a population infection generally occurs during early childhood so that against an infectious agent is known as (a) innate by the time adulthood is achieved, the population becomes immunity (b) acquired immunity (c) selective immunity (d) immune and a high level of herd immunity occurs, is herd immunity known as (a) Hyper - endemic (b) Holo - endemic (c) Meso7. In calculation of secondary attack rate, exposure to which - endemic(d) Hypo - endemic case is being taken into account (a) primary case (b) index Answers : (1) b; (2) c; (3) No; (4) a; (5).c; (6) d; (7) b; (8) c; case (c) secondary case (d) subclinical case (9) a; (10) b; (11) d; (12) a; (13) d; (14) c; (15) b. fatal result” (3). The term “immunes”, is also found in the epic 168 Immunization poem “Pharsalia” written around 60 B.C. by the poet Marcus Annaeus Lucanus to describe a North African tribe’s resistance to snake venom (2). The first clinical description of immunity Rajesh Vaidya which arose from a specific disease causing organism is probably Kitab fi al-jadari wa-al-hasbah (4) written by theHistory Islamic physician Al-Razi in the 9th century. However, it wasThe concept of immunity has intrigued mankind for thousands with Louis Pasteur’s Germ theory of disease that the fledglingof years. According to the prehistoric views, disease was caused science of immunology began to explain how bacteria causedby supernatural forces and illness was a form of punishment disease, and how, following infection, the human body gainedfor “bad deeds” or “evil thoughts” visited upon the soul by the the ability to resist further insults (3). Gods or by one’s enemies (1). The first written descriptions of Burnet and Medawar, Nobel Prize winners in 1960 put forth thethe concept of immunity may have been made by the Athenian concept that man had learnt to tolerate his own tissues (self)Thucydides who, in 430 BC, described that when the plague and was intolerant to foreign tissues (i.e. not self). The concepthit Athens “the sick and the dying were tended by the pitying of ‘self’ and ‘not self’, therefore, means that under normalcare of those who had recovered, because they knew the course conditions the body tolerates its own tissues (immunologicalof the disease and were themselves free from apprehensions. tolerance), and recognizes and destroys foreign tissues. In theFor no one was ever attacked a second time, or not with a • 982 •
  • modern sense, therefore, immunity has been defined as the with the same antigen, which provokes its production. Theability of the body to recognize, destroy and eliminate antigenic sites of maximum antibody formation are the lymph nodesmaterial foreign to its own (5, 6). and spleen. Smaller collections of antibody producing cells are widely scattered in various tissues throughout the body. PlasmaThe Immune System cells also produce antibodies. Antibodies may be antitoxicThe immune system is a collection of mechanisms within an such as diphtheria and tetanus, antibacterial like typhoid ororganism that protects against infection by identifying and antiviral such as polio.killing pathogens and tumour cells. ImmunoglobulinsStructure and Function of Immune System These comprise of families of closely related globulin molecules,Tissues and organs important for the immune function which are synthesized by cells of reticulo-endothelial systeminclude: (RES). The human immunoglobulin system is divided into five●● Cells derived from stem cells : liver, bone marrow major classes IgG, IgA, IgM, IgD and IgE. The molecule of each●● Cells that are stored, multiply, interact and mature in : immunoglobulin is understood to consist of K (Kappa) and L thymus, spleen, lymph nodes, blood (Lamda) polypeptide chain (10).●● Transport : lymphatic vessels (a) IgG : Repeated exposure to antigen leads to its accumulation●● Accessory organs in serum. It comprises about 80 per cent of serum antibodies●● Appendix, tonsils, intestines in an adult. Antibodies to gram positive pyogenic bacteria,The immune system protects organisms from infection antiviral and antitoxic antibodies are found exclusively amongwith layered defenses of increasing specificity. Most simply, IgG globulins. This is the immunoglobulin, which is transportedphysical barriers prevent pathogens such as bacteria and across the placenta. Maternally derived IgG is slowly replacedviruses from entering the body. If a pathogen breaches these by actively synthesized IgG which appears at 1-3 months of agebarriers, the innate immune system provides an immediate, and then rapidly rises and adult level is reached by the age ofbut non-specific response. Innate immune systems are found one or two years. Normal adult serum level of IgG is 600-1800in all plants and animals. However, if pathogens successfully mg/100 ml.evade the innate response, vertebrates possess a third layer (b) IgA : This fraction has been found to containof protection, the adaptive immune system. Here, the immune isohaemagglutinins, anti-brucella, anti-diphtheria antibodiessystem adapts its response during an infection to improve its and comprises about 10 per cent of the serum antibodies.recognition of the pathogen. This improved response is then Saliva, colostrum and tears are relatively rich in this fraction.retained after the pathogen has been eliminated, in the form Nasal and bronchial secretions, bile, intestinal juices andof an immunological memory, and allows the adaptive immune prostatic fluid also contain IgA. It seems to play a decisive rolesystem to mount faster and stronger attacks each time this in local immunity. IgA synthesis begins two weeks after birth.pathogen is encountered (7,8). Normal adult serum level is 70-380 mg/100 ml.Antigen (c) IgM : This fraction is found to have high agglutinatingAntigen is defined as a substance which when introduced into and complement fixation ability. Wasserman antibodies andthe tissues stimulates the production of specific antibodies and bactericidal antibodies against Gram negative organismscombines specifically with the antibody so produced (3). By far (endotoxins) are almost exclusively found in IgM. It accountsthe best antigens are proteins (e.g. diphtheria toxin, tetanus for 5 to 10 per cent of serum antibodies. It cannot pass throughtoxin); others are polysaccharides (e.g. blood group antigens), placenta. Normal adult serum level is 20-130 mg/100 ml.lipids and nucleic acids. There are also incomplete antigens (d) IgD : Not much is known about it. Normal adult serum levelcalled ‘haptens’ which by themselves are not antigenic but can is 4-40 mg/100 ml.provoke an immune response by combining with one of the (e) IgE : The antibodies in this fraction have the ability to fixbody’s proteins in such a way that the protein becomes ‘foreign’ themselves firmly to tissues and remain so. They are likely toto the body. Penicillin is an example of ‘hapten’. On contact play an important role in allergic reactions.with an antigen the host can respond in three different ways :(a) Circulating antibody is formed. Immunity(b) A delayed-type cell mediated hypersensitivity reaction may The word “immunity” derives from the latin immunis, meaning result on second contact with the antigen. exemption from military service, tax payments or other public(c) Tolerance, which means that on second contact with the services and is defined as “Ability of an organism to recognize same antigen no response will be provoked. and defend itself against specific pathogens or antigens (11)The type of response in a particular case will depend largely on (Box - 1).the antigen itself, the dosage, and the route of application and Types of Immunitypossibly on other lesser-known factors (9). The normal individual has two levels of defence against foreignAntibody agents. Natural or innate immunity, - which is present inAntibody is a protein substance that appears in the body as a neonatal animals and in invertebrates. Adaptive or acquiredresult of invasion of antigen. It is capable of reacting specifically immunity - that is confined to vertebrates (Box - 2). • 983 •
  • Acquired (Adaptive) immunity : This Box - 1 develops only after exposure to inducing Specific Defense Mechanisms agents such as microbes, toxins, or other Nonspecific Defense Mechanisms (Immune System) foreign substances. First line of defense Second line of defense Third line of defense Active Immunity ●● Skin ●● Phagocytic White ●● Lymphocytes Naturally acquired active immunity ●● Mucous blood cells ●● Antibodies : It occurs when a person is exposed membranes ●● Antimicrobial to a live pathogen, and develops a ●● Secretions of proteins primary immune response, which leads skin and mucous ●● The inflammatory to immunological memory. This type of membranes response immunity is “natural” because it is not induced by man. Box - 2 : Types of immune defenses (12,13) Artificially acquired active immunity : It can be induced by a vaccine, a substance that contains antigen. A vaccine Immunity stimulates a primary response against the antigen without causing symptoms of the disease. Innate Acquired Passive Immunity : Passive immunity is the transfer of active immunity, in the form of readymade antibodies, from one Passive Active individual to another. Naturally acquired passive immunity : Passive immunity can Artificial Natural Artificial Natural occur naturally, when maternal antibodies are transferred to the fetus through the placenta or through breast milk (14,15).Innate (natural) Immunity : This is made up of several Artificially acquired passive immunity : This is a short-termcomponents. immunization induced by the transfer of antibodies, which can●● Physical barriers are the first line of defense against be administered in several forms; as human or animal plasma infection. The skin and mucous membranes provide a or serum, as pooled human immunoglobulin (16). continuous surface which must be breached and back this Active versus Passive Immunity : Some differentiating points up with mechanical protection through cilia and mucous. between active and passive immunity are given in Table - 1.●● Physiological factors such as pH, temperature and oxygen tension limit microbial growth. The acid environment of Host Defenses the stomach combined with microbial competition from There are two different types of host defenses that the body the commensal flora inhibits gut infection. exhibits as a result of exposure to an antigen. These are :●● Protein secretions into external body fluids such as ●● The humoral immune response involves the activation and lysozyme also help resist invasion. Soluble factors within clonal selection of B cells, resulting in the production of the body such as complement, interferons and other antibodies. molecules such as C-reactive protein are of considerable ●● The cell-mediated immune response involves the activation importance in protection against infection. and clonal selection of cytotoxic T cells (17).●● Phagocytic cells are critical in the defense against Humoral Immunity : An immunocompetent but as yet bacterial and simple eukaryotic pathogens. Macrophages immature B-lymphocyte is stimulated to maturity when an and Polymorphonuclear leucocytes (PMN) can recognise antigen binds to its surface receptors and there is a T helper bacterial and yeast cell walls through broadly specific cell nearby (to release a cytokine). This sensitizes or primes the receptors (usually for carbohydrate structures) and this B cell and it undergoes clonal selection. Most of the family of recognition is greatly enhanced by activated complement clones becomes plasma cells. These cells, after an initial lag, (opsonin) (7). produce highly specific antibodies at a rate of as many as 2000 Table-1: Comparison between Active & Passive Immunity Active Immunity Passive Immunity Usually produced in response to bacteria, viruses, toxins or Produced by serum containing already prepared antibodies toxoids. Body cells take an active part in the production of immunity. Cells of body do not take part in the production of antibodies. No time is lapsed to get the antibodies circulating in the It takes sometime to develop the antibody in the system. system. Immunity lasts long Immunity lasts for a short period, usually 10-14 days. Used for pre-pathogenic prophylaxis and treatment of sub- Used for treatment of acute infection and for tiding over the acute or chronic infections in order to increase crisis or incubation period. • 984 •
  • molecules per second for four to five days. The other B cells process weeds out only those T cells with the correct set ofbecome long-lived memory. Humoral immunity is active when receptors that can recognize the MHC molecules responsiblethe organism generates its own antibodies and passive when for self-recognition. Then a negative selection process beginsantibodies are transferred between individuals. Similarly, cell whereby T cells that can recognize MHC molecules complexedmediated immunity is active when the organisms’ own T-cells with foreign peptides are allowed to pass out of the thymus.are stimulated and passive when T cells come from another Cytotoxic or killer T cells (CD8+) do their work by releasingorganism (17, 18). lymphotoxins, which cause cell lysis. Helper T cells (CD4+)Cell-mediated Immunity : Macrophages engulf antigens and serve as managers, directing the immune response. Theprocess them internally. This sensitizes the T cells to recognize process by which T cells and B cells interact with antigens isthese antigens. T cells are primed in the thymus, where they summarized in Fig. - 1.undergo two selection processes. The first positive selection Fig. - 1 Immature inactive helper and Pathogen Immature inactive B-cells killer T-cells Engulfed by Macrophage In thymus In bone marrow Pieces of pathogen presented Mature inactive helper and on surface of antigen- Mature inactive B-cells Free antigen in blood killer T-cells presenting cell (macrophage) Helper and Killer T-cells are activated by antigen-presenting B-cells are activated by antigen, but only if B-cells recognize macrophage, but only if T-cells recognize specific antigen specific antigen. Active helper T-cell is required for B-cell presented by microphage. activation. Helper T-cell Activates B-cell Active helper and Killer T-cells replicate, including information of memory cells Active B-cells replicate and produce antibody molecules that can bind to specific antigens Killer T-cells require helper T-cells for activation Memory T-cells can respond to Killer T-cells kill any body cell Memory B-cells can respond to Antibody binds to antigen subsequent infection by that infected with that specific kind subsequent infection by that (“tagging”) kind of pathogen of antigen kind of pathogen Complement system destroys Phagocytic cells engulf the the antigen tagged antigen • 985 •
  • Local Immunity : Local immunity is believed to be produced by immunization, it was British dairy farmer Benjamin Jesteyfixation of various specific humoral antibodies in tissues, cells; who noticed that “milkmaids” did not become infected withor it may be nonspecific response of local tissues, induced by smallpox, or displayed a milder form. Jestey took the pus froma local application of antigen, against a subsequent infection an infected cow’s udder and inoculated his wife and childrenthreatening systemic disease e.g. oral poliomyelitis vaccine with cowpox, thereby making them immune to smallpox. By(OPV) used for producing immunity against poliomyelitis. injecting a human with the cowpox virus (which was harmlessHerd Immunity : Herd Immunity is the immunity of a group of to humans), Jenner swiftly found that the immunized humanpeople or a community taken as a whole. In the epidemiology was then also immune to smallpox.of infectious diseases, consideration of herd immunity is of Vaccines : These are immunobiological substances designedgreater importance than that of individual immunity. Epidemics to produce specific protection against diseases by stimulatingdisappear from a community long before 100 per cent of its production of protective antibody or other immune mechanisms.members become immune, either naturally or artificially A number of agents can be used to provide protection againstthrough mass immunization. Epidemiological immunity is diseases. This protection can be active where antibodiesusually established even when, say only 80 to 85 % people in are produced by our own body in response to vaccines orthe community become immune. The other 20 % people enjoy passive where antibodies are received in ready made form offreedom from infection by virtue of their belonging to the immunoglobulins or non-human antisera (See Box - 3).‘herd’. Herd immunity can also develop through the process ofnatural selection by weeding out of the susceptible successive Box - 3 : Milestones in vaccinationgenerations due to death from disease. The level of herd 1798 Smallpoximmunity at a given time depends on the herd structure whichis constantly changing. (19). 1885 RabiesTypes of Immune Response 1897 PlagueThe first encounter with an antigen is known as the primary 1923 Diphtheriaresponse. Re-encounter with the same antigen causes a 1926 Pertussissecondary response that is more rapid and powerful (20) 1927 Tuberculosis (BCG)(Fig. - 2). Immune response depends on●● Nature and dose of antigen 1927 Tetanus●● Route of administration 1935 Yellow Fever●● Type of adjuvants used After World War II●● Nutritional status of the recipient 1955 Injectable Polio Vaccine (IPV) Fig. - 2 : Immune Response 1962 Oral Polio Vaccine (OPV) Secondary immune response 1964 Measles Second exposure to antigen A 104 to antigen A, 1967 Mumps first exposure to 1970 RubellaAntibody concentration antigen B First exposure to antigen A 1981 Hepatitis B (arbitrary units) 10 3 Immune Response to Vaccination : The vaccine mimics 10 2 Primary immune Primary immune infection with the respective pathogen, but without risk of the response to response to antigen A antigen B disease. The consequent immune response may be manifested 101 through antibody (humoral immunity) or cell mediated immunity (CMI), or both. Maternal CMI is not transferred to Antibodies Antibodies to A to B the foetus. Therefore BCG can be given at birth, OPV is given 10 by mouth; it establishes local infection in a proportion of 0 0 7 14 21 28 35 42 49 56 children. Maternal antibody in the infant’s circulation is a Time (Days) very weak inhibitory factor; hence OPV also can be given at birth. Hepatitis B surface antigen is an excellent immunogen,Immunisation overcoming, to a large extent, the inhibiting effect of maternalImmunisation is the process by which an individual is exposed antibody; hence that too can be given at birth. On the otherto an agent that is designed to fortify his or her immune system hand, live measles vaccine may be completely inhibited inagainst that agent. The material is known as an immunogen. the presence of detectable maternal antibody in the infant’sImmunization is the same as inoculation and vaccination in circulation. Therefore measles vaccine is given after a delay ofthat inoculation and vaccination use a viable infecting agent 9 months from birth and MMR only after 12 months (8).like immunization does. The goal of all vaccines is to promote a primary immuneHistory of Immunization : While Dr. Edward Jenner (1749- reaction so that when the organism is again exposed to the1823) has been recognized as the first doctor to give sophisticated antigen, a much stronger secondary immune response will • 986 •
  • be elicited. Any subsequent immune response to an antigen Table - 2 : Immunizing Agentsis called a secondary response and it exhibits the followingfeatures : Live attenuated Vaccinesa) A shorter lag time BCGb) More rapid buildup Typhoid, oral Bacterialc) A higher overall level of responsed) A more specific or better “fit” to the invading antigen Plaguee) Utilizes IgG instead of the large multipurpose antibody Oral polio (Sabin) IgM Yellow feverTypes of vaccines : Traditionally, there are four types ofvaccines (Table - 2). Measles●● Live (attenuated) Rubella Viral●● Inactivated (killed) Mumps●● Toxoids Influenza●● Subunit and recombinantLive Vaccines : These are prepared from live attenuated Chickenpoxorganisms. They are very potent immunizing agents because : Epidemic Typhus Rickettsial●● Live organisms multiply in the host Inactivated or Killed Vaccines●● All major and minor antigenic components are present●● Target organs may be colonized Typhoid●● May replace wild strains in the community CholeraDrawbacks : Safety is an issue because mutation may take Pertussis Bacterialplace resulting in disease. Live vaccines can not be used for C.S. meningitisimmuno-deficient patients as well as during pregnancy.Precautions : Two live vaccines are usually not used together. PlagueThey are to be given at different sites or three weeks apart. Hepatitis ABesides, live vaccines have exacting storage requirements. Hepatitis BExample : Rabies●● Bacterial Salk (polio) Viral - BCG - Typhoid oral Influenza●● Viral Japanese Encephalitis - Measles, Mumps, Rubella KFD - Oral Polio Toxoids - Yellow fever, Influenza Diphtheria●● Rickettsial Bacterial Tetanus - Epidemic typhus Human ImmunoglobulinsInactivated (Killed) Vaccines : These are prepared fromorganisms killed by heat or chemicals. Killed vaccines are Hepatitis Avery safe but less efficacious than live vaccines. They require Measlesmultiple doses which may be administered as a series of Human normal Rabiesprimary doses followed by regular booster doses. The only Immuno-globulinabsolute contraindication is hypersensitivity. TetanusExample : Mumps●● Bacterial Hepatitis B - Typhoid, Pertussis, Cholera Human specific Varicella●● Viral Immuno-globulin Diphtheria - Rabies, Hepatitis B, Japanese encephalitis Non Human (Antisera)Toxoids : These are produced from detoxicated toxins. Thebody produces antibodies against the toxin in response to Diphtheriatoxoids. They offer no protection against infection. Toxoids are Tetanusvery safe and highly effective. Bacterial Gas gangreneExample : Diphtheria, Tetanus Botulism Rabies Viral • 987 •
  • Passive Immunisation : Passive immunization may be Storage of Vaccinesadministered using human or animal products. Conventionally Sensitivity to heat : All vaccines are sensitive to heat to somehuman products are called immunoglobulins and animal extent, but some are more sensitive than others. The commonlyproducts are called anti-sera. Animal products are cheaper but used EPI vaccines may be ranked according to their sensitivitysuffer from the disadvantage of greater chances of immediate to heat as given in Box - 4.or delayed hypersensitivity.Human Immunoglobulins : Non-specific or generalized Box - 4 : Sensitivity to Heatprotection is offered by normal immunoglobulins whileprotection against specific diseases is given by using hyper- Most Sensitiveimmune immunoglobulins. OPVNormal Immunoglobulins : These provide non specific Measlesimmediate ready made protection for upto three weeks. No livevaccine should be given for 12 weeks following administration DPT, Yellow Feverof immunoglobulins. They should be administered at least two BCGweeks after a live vaccine Hib, DTExample : Measles, Hepatitis A Td, TT, Hepatitis BSpecific Hyperimmune Immunoglobulins : These are madefrom plasma of recently recovered patients. They are to begiven immediately after exposure. Peak blood levels are usually (Note : However, that all freeze-dried vaccines become much more heat-achieved in two days. They have a half life three to five weeks sensitive after they have been reconstituted, and it is then even more important that they are not exposed to heat.)Example : HBIG, VZIG, Rabies, TetanusAnimal anti-sera or anti-toxin : Animal anti-sera are Sensitivity to Cold : Some vaccines are also sensitive to beinggenerally equine in origin. Their biggest draw back is that they too cold. For these vaccines, freezing or exposure to temperaturesmay cause anaphylactic reactions or serum sickness. < 0°C can also cause loss of potency, and again, the vaccineExamples : Diphtheria, Tetanus, Rabies, Botulism, Gas will become useless. For these vaccines, it is therefore essentialgangrene, Snake Bite. to protect them not only from heat, but also from freezing. TheNational Immunization Schedule vaccines sensitive to freezing (as well as to heat) are as given in Box - 5.Any immunization schedule is drawn up keeping two importantfactors in mind. Firstly the vaccines need to be administered indoses and schedules which produce an adequate immunological Box - 5 : Sensitivity to Coldresponse in the recipient. Secondly the schedule should be Most Sensitiveadministratively convenient and one which is likely to be most Hep Bacceptable to the target population. The National ImmunizationSchedule drawn up for India factors in both these aspects (21)(Table - 3). Hib (Liquid) DTP Table - 3 : Schedule DT At Birth BCG, OPV - 0 Td (Institutional delivery) TT 6 weeks BCG (If not given at birth) DPT - 1, OPV - 1 Least Sensitive Infants 10 Weeks DPT - 2, OPV - 2 Sensitivity to Light : Some vaccines are also very sensitive 14 Weeks DPT - 3, OPV - 3 to strong light, so they must always be protected against 09 months Measles sunlight or fluorescent (neon) light. BCG, measles, MR, MMR and rubella vaccines are sensitive to light (as well as to heat). 16 - 24 mths DPT and OPV Normally, these vaccines are supplied in vials made from dark 5 - 6 yrs DT* brown glass, which gives them some protection against light Children damage, but care must still be taken to keep them covered and 10 yrs TT* protected from strong light at all times (22,23). 16 yrs TT * Recommended Storage Temperatures (If there is no clear evidence of previous immunization two doses one month apart to be given) The recommended conditions for storing vaccines are shown Early pregnancy TT - 1 in Table - 4. This table indicates the maximum times and Pregnant temperatures in each case (24). Women One month later TT - 2 Each time some damage due to heat occurs, the loss of potency (In case of clear evidence of primary immunization or two doses during accumulates, and eventually, if the cold chain is not correctly previous pregnancy, only single dose to be given) • 988 •
  • Table - 4 : WHO recommended vaccine storage conditions Primary Intermediate Health Centre Health Post Region District 6 monthsa 3 months 1 month 1 month Daily use OPV -15°C to -25°C BCG Measles WHO no longer recommends that freeze-dried MMR vaccines be stored at -20°C. Storing them at -20°C is not harmful but it is unnecessary. Instead, MR these vaccines should be kept in refrigeration and Yellow Fever transported at +2°C to +8°C. Hib freeze-dried +2°C to +8°C HepB DTP-HepB Hib liquid DTP      +2°C to +8°C DT TT Td Diluent vials must NEVER be frozen. When the manufacturer supplies a freeze-dried vaccine packed together with its diluent, ALWAYS store the product at between +2°C and +8°C. Where space permits, diluents supplied separately from the vaccine may safely be stored in the cold chain at between +2°C to +8°C Note a : 6 months is the maximum recommended storage time at primary level. This includes the period required to obtain clearance from the National Regulatory Authority.maintained, all potency will be lost, and the vaccine becomes Cold chain includes :useless. ●● Walk in cold rooms (WICs)Expiry Date : Even when stored at the correct temperature, ●● Deep freezersvaccines do not retain their potency forever, and therefore all ●● Ice - lined refrigerators (ILRs)vaccines have an expiry date (24). ●● RefrigeratorsDiluents for Vaccines : Diluents for vaccines are less sensitive ●● Cold boxto storage temperatures than the vaccines with which they ●● Vaccine carrierare used, but may be kept in the cold chain between +2°C to ●● Day carrier+8°C if space permits. When vaccines are reconstituted, the ●● Ice packsdiluent should be at same temperature as the vaccine, so Walk In Cold Rooms : These are used for the storage of largesufficient diluent for daily needs should be kept in the cold quantities of vaccines. They require constant electric supply.chain at the point of vaccine use. However, diluent vials must Vaccines can be stored up to 3 months. They serve a region ofnever be frozen. This will risk cracking the glass and allowing 4-5 districts.contamination of the contents, so diluent vials must never be Deep Freezers and ILRs : These are provided at the districtkept in a freezer, or allowed to be in contact with any frozen and CHC level and can store up to 1 month supply of vaccines.surface (25). Each vaccine requires a specific diluent and Capacity is 300/240 L. They can be used for storing OPV andtherefore, diluents are not interchangeable. Likewise, diluent measles. Ice packs are also prepared.made by one manufacturer for use with a certain vaccine cannot Small Deep Freezers and ILRs : These are provided at the PHCbe used for reconstituting the same type of vaccine produced by and can store up to 1 month supply of vaccines. Capacity isanother manufacturer. 140L. They do not have a freezer compartment.Cold Chain Refrigerators : While using a refrigerator for the purpose ofCold chain is a system of transporting and storing vaccines at keeping vaccines, certain Do’s and Don’ts have to be followedrecommended temperature from manufacturer to the point of as shown in the box.use. All the vaccines can be stored at temperatures between Vaccine Carriers : Used for transporting small quantity of+2°C to 8°C. However for long term storage, OPV and measles vaccines to sub center. These are made of insulating material.can be stored at sub zero temperatures in deep freezers. DPT, Each carries four ice packs. The vaccines should be used on theDT and TT should never be frozen. BCG and diluent ampoules same day. They should be kept away from direct sunlight.should not be frozen. Diluents required for measles and BCG Day Carriers : These are made of insulating material and carryshould be stored at +2°C to +8°C in the refrigerator. two ice packs. They can keep few vials for 6-8 hrs at a time. • 989 •
  • Adverse Events : Complications following BCG vaccination Using refrigerator to keep vaccines - Do’s and Don’ts are rare : Significant local reactions, such as extensive local Do’s ulceration and regional lymphadenitis occur in <1 : 1000 ●● Keep in cool room away from sunlight persons (31). ●● At least 10 cm away from the wall Indications and Contraindications as recommended by ●● Keep ice pack in freezer WHO ●● Defrost periodically ●● For all infants living in areas where TB is highly endemic ●● Check temp. and maintain record ●● For infants and children at particular risk of TB exposure Dont’s in otherwise low-endemic areas ●● For persons exposed to multi-drug-resistant Mtb BCG ●● Open unless necessary vaccination is contraindicated ●● Keep vaccine in the door ●● For persons with impaired immunity (symptomatic HIV ●● Keep food inside infection, known or suspected congenital immunodeficiency, ●● Keep more than one month’s requirement leukaemia, lymphoma or generalized malignant disease); ●● Keep expired vaccines ●● For patients under immunosupressive treatment (corticosteroids, alkylating agents, anti-metabolites,Ice Packs : These are flat plastic water bottles filled with water. radiation);They are available in three capacities : 400ml, 500ml and ●● In pregnancy.600ml. They are prepared by keeping in freezer. New vaccines against TB : In recent years, there has beenQuality of Cold Chain : The quality of the cold chain is a dramatic increase in the number of candidate TB vaccinesmonitored by the National Quality Control Lab located at evaluated in research laboratories. Currently, the mostKasauli. The quality check is done before release of the vaccines. favoured research strategies include recombinant modifiedReverse Cold Chain is also maintained to check vaccines for BCG vaccines, attenuated strains of MTB, subunit vaccines andtheir potency. DNA vaccines.Vaccine stock management : Vaccine stock management isdone at three points : BCG Vaccine (Summary)●● When vaccine consignments arrive at the storage point ●● Attenuated M. tuberculosis var bovis developed in 1921.●● While vaccines and diluents remain in storage ●● Protects against TB Meningitis, Miliary TB especially in●● When vaccine & diluent stocks leave a storage point (26). ChildrenUIP Vaccines ●● Maternal antibodies do not interfere with BCG vaccine as CMI is not transferred trans-placentally, hence should beBCG Vaccine given as early as possible after birthThe BCG vaccine was first used to immunize humans in 1921. ●● Vaccine efficacy ranges from 0 to 80 percent. NeonatalFollowing its introduction into the WHO Expanded Programme immunization induces long term protectionon Immunization in 1974, the vaccine soon reached global ●● Supplied freeze dried, store frozen or refrigeratedcoverage rates exceeding 80% in countries endemic for TB. At ●● Use reconstituted BCG within 4-6 hourspresent, about 100 million children receive BCG vaccine each ●● Inject intra-dermally over left shoulder at the insertionyear. Although the oldest of currently used vaccines, BCG is still of deltoid.controversial in that there are conflicting data on its protective ●● Local lesion due to bacterial multiplication; Heals leavingefficacy. (27). A number of BCG vaccine strains are available, scars; If no scar, repeat BCGalthough the French Pasteur strain 1173 P2, the Danish strain1331, the Glaxo strain 1077 and the Tokyo strain 172 account Polio Vaccinefor about 90% of BCG vaccinations worldwide. An effective IPV (Salk vaccine), comprising all three serotypes,Administration of the Vaccine : WHO recommends intra- was licensed after large-scale field trials in 1955. Starting indermal application of the vaccine, preferably on the deltoid 1963, trivalent OPV (Sabin vaccine) replaced IPV as the primaryregion of the arm using special syringe as early as possible means of prevention of poliomyelitis in most countries,after birth. Newborn vaccinees should receive half the dose because of the ease of administration, enhanced mucosalgiven to older children. Within a few months of vaccination, immunity providing a more effective barrier to transmissionthe local reaction is replaced by a small scar. Presence of a and community wide circulation of wild poliovirus, secondarytypical scar is used as a marker of previous BCG vaccination spread of Sabin-derived vaccine virus from vaccinees to closebut is not a marker of protection against TB. contacts thus immunizing some unvaccinated contacts andVaccine Efficacy : Vaccine efficacy ranges from 0 to 80 lower cost (32).percent. Oral Polio Vaccine : The oral polio vaccine is a suspension ofDuration of Protection : The duration of protection after over 1 million particles of polioviruses type 1, 2 and 3 together.neonatal BCG vaccination is not well known but commonly It is supplied with a stabilizing agent - magnesium chloride.believed to decline gradually to non-significant levels after 10- The virus survives the acidity of the stomach and confers20 years. local immunity. However, for reasons not clearly understood, • 990 •
  • the ‘take’ rate is relatively low in our children. For the above of diphtheria toxoid, whole cell killed pertussis vaccine andreason, multiple doses of OPV are necessary before 90 - 95% of tetanus toxoid is popularly known as the triple antigen. Whilechildren develop immune responses to all 3 poliovirus types. In the two toxoids are highly immunogenic and antibodies to themaddition to the “Routine OPV doses”, “Pulse OPV doses every are almost completely protective, the pertussis vaccine, givenyear on National Immunization days (NID’s) till the age of 5 in 3 doses, has a protective efficacy of about 70-80% only.years are also mandatory. The risks due to OPV comprise cases Administration of the vaccine : DPT must be injected IM.of Vaccine-Associated Paralytic Poliomyelitis (VAPP), outbreaks The preferred site is the antero-lateral aspect of the thigh.of circulating vaccine-derived polioviruses (cVDPVs) and long- Immunization should begin by six weeks of life and completedterm carriers of VDPVs identified among immunodeficient before the ninth month at the latest, although it can be givenpersons (iVDPVs) (33). at any period before 5 years of age. Initially three doses atEradication is defined as no case of paralytic poliomyelitis by monthly intervals are injected intramuscularly. Booster doseswild polio virus in last 3 calendar years along with absence of are given during the second year and just before the child startswild polio virus in the community, where excellent clinical and going to school (34).virological surveillance exists and the coverage of routine OPV Adverse events and Contraindications : Local pain, rednessis more than 80%. and fever after DPT are almost entirely due to the pertussisPolio elimination is defined as zero case of paralytic poliomyelitis component. Convulsions following DPT vaccine are rare, andby the wild polio virus in one calendar year with other criteria when occur they may be the earliest signs of some incipientsame as in eradication. neurological disease in the infant. For these reasons, progressivePulse Polio Immunization : On National Immunization Days neurological diseases are the only contraindication to first dose(NIDs), pulse doses of oral polio vaccine has to be administered, of DPT immunization (35-39).simultaneously to all susceptible infants and children whichwould produce immunity to all. DPT Vaccine (Summary)Injectable Killed Polio Vaccine (IPV) : IPV is formaldehyde ●● Diphtheria toxoid (Ramon & Glenny, 1923)killed poliovirus grown in monkey kidney cell/human ●● Killed Bordetella pertussis (Madsen, 1923)diploid cells containing 20, 8 & 32 D antigen against type ●● Tetanus toxoid (Ramon & Zoeller, 1927)1, 2 and 3 poliovirus, respectively. It is highly immunogenic. ●● Toxoids adjuvanted (Aluminium hydroxide/phosphate)Seroconversion is 90-95%, after 2 doses and 99% after 3 ●● DPT vaccine supplied as liquid, store refrigerateddoses. It produces excellent humoral immunity as well as local ●● Aluminium adjuvanted vaccines should not be frozenpharyngeal and possible intestinal immunity. The vaccine ●● Inject intramuscularly, antero-lateral thighis very safe. However, it is not available at present in the ●● Alert parents about local reaction and fever; ParacetamolIndian market for routine use and is licensed only for use in to be given to reduce pain/feverimmunocompromised children. ●● Progressive neurological disease or serious adverse reaction to earlier dose are contraindications for DPT; Oral Polio Vaccine (Summary) replace with DT Vaccine ●● Live attenuated Poliovirus types 1, 2 and 3 developed by Sabin, 1961 Tetanus Toxoid ●● Temperature sensitive, store frozen or refrigerated Indian Academy of Paediatrics recommends TT at 10 and 16 ●● Can be given simultaneously with any other vaccine years. After completing the full course of 7 doses, there is no ●● Multiple doses necessary to ensure vaccine virus take need for additional doses during pregnancy, at least for the and antibody response to all 3 types of polioviruses next 10 years. Thereafter a single booster would be sufficient ●● First dose is recommended in the newborn period or as to extend immunity for another 10 years. For pregnant women early as possible who have not had previous immunization, at least 2 doses ●● IAP recommends additional doses of OPV as a part of should be given during pregnancy so that protective antibody Pulse Polio programme every year till the age of 5 yrs. would be transferred to the infant in order to prevent neonatal Injectable (Killed) Oral Polio Vaccine (Summary) tetanus. Td is the preferred preparation for active tetanus immunization in wound management of patients greater than ●● Formaldehyde Killed Polio Virus grown in monkey kidney or equal to 7 years of age. or human diploid cell ●● Contains 20, 8 and 32 D antigen units against type 1, 2 Tetanus Immunoglobulin (TIG) and 3 Polio Viruses respectively It is a liquid or freeze-dried preparation containing ●● Seroconversion 90-95% after 2 doses and 99% after 3 immunoglobulins, mainly IgG obtained from plasma or serum doses containing specific antibodies against the toxin of Clostridium ●● Thermostable and is indicated in immunocompromised tetani. individuals, HIV infection and disease. Adverse Effects : Local pain, fever, flushing, headache and chills may occur.DPT Vaccine Indications : Subjects already sensitized with serums of animalDiphtheria is a potentially acute disease caused by exotoxin origin, existence of prior or present allergic manifestationsproducing Corynebacterium diphtheriae. The combination • 991 •
  • (asthma, eczema etc.), burns, injuries, open and compound Non UIP Vaccinesfractures, unimmunised or inadequately immunised mothers. Mumps VaccineDosage : Prophylaxis 250 - 500 I.U. IM. Therapeutic : Tetanus Mumps can be prevented by vaccination given either as aneonatorum 500 - 1000 I.U. intramuscular or 250 I.U. monovalent vaccine or as part of MMR vaccine. A live attenuatedintrathecal. In adults and children : 500 - 1000 I.U. IM and / or monovalent mumps vaccine was first developed by Hilleman in250 - 500 I.U. intrathecally. 1966. The mumps component in MMR vaccine contains liveMeasles Vaccine attenuated mumps virus. Mumps vaccines are recommendedMeasles vaccine consists of live attenuated Measles virus, for use in a 1-dose schedule, given at age 12-18 months (42)developed by Enders, in 1960. The original virus strain was Adverse Reactions : In general, adverse reactions to mumpsisolated from a child by the name Edmonston; therefore the vaccination are rare and mild. The most common adversevirus strain was also named Edmonston. In liquid suspension reactions following mumps vaccination are parotitis and low-the vaccine virus is very heat-labile; in the freeze-dried state grade fever.the shelf life of the vaccine is one to two years. The vaccinemay be stored frozen or refrigerated. But, after reconstitution, Rubella Vaccinethe vaccine should be injected within 4-6 hours. During such A live attenuated Rubella vaccine was developed by Waller ininterval the liquid vaccine should be kept cold, either in the 1962. The current rubella vaccine available commercially isrefrigerator or vaccine carrier. derived from RA 27/3 vaccine strain grown in human diploid cell cultures. It is available either as a monovalent vaccineAdministration of the vaccine : The vaccine should be or as a part of combination vaccine - MMR. It contains liveinjected subcutaneously. The preferred site is right upper arm. attenuated virus not less than 1000 TCID50. It is a highlyIt can also be injected over the antero-lateral thigh, but SC. The immunogenic vaccine with positive antibody response in 95%vaccine induces both humoral and cellular immune responses of susceptible vaccinees. It provides long term and probably lifecomparable to those following natural infection. long protection (43, 44, 45,46).Vaccination schedule and vaccine efficacy : The optimum age The primary purpose of rubella vaccination is to prevent thefor measles vaccination depends on the local epidemiological occurrence of congenital rubella infection including CRS. Twosituation and on programmatic considerations. Given the approaches are recommended by WHO :immaturity of the immune system as well as the presence ofneutralizing maternal antibodies, vaccination of infants before (a) Prevention of CRS only, through immunization of adolescentor at 6 months of age may often fail to induce immunity. In girls and/or women of childbearing agemost developing countries, children are vaccinated against (b) Elimination of rubella as well as CRS through universalmeasles at 9 months of age, when seroconversion rates of 80- vaccination of infants and young children (with/ without85% may be expected. A single dose of live, attenuated measles mass campaigns), surveillance, and assuring immunity invaccine is generally felt to provide lifelong protection (40,41). women of childbearing age.Adverse Reactions : Adverse reactions following measles MMR Vaccinevaccination, alone or in fixed combinations, are generally mild MMR Vaccine is available as single as well as multidose (5 dose)and transient. Slight pain and tenderness at the site of injection vial. The diluent for injection is available separately. The dose ofmay occur within 24 hours, sometimes followed by mild fever the reconstituted vaccine is 0.5 ml per dose, to be administeredand local lymphadenopathy. Thrombocytopenia purpura occurs subcutaneously in the upper arm. The vaccine should be storedin approximately 1 in 30,000 vaccinated individuals. between +2 to +8°C in the ordinary compartment of the fridge. Reconstituted vaccine should be used within 6 hours. Measles Vaccine (Summary) IAP recommends a dose of MMR vaccine to all children. For ●● Live attenuated Measles virus vaccine developed by infants given measles vaccine at 9 months, MMR vaccine may Enders, 1960 be given between 12-15 months of age. If measles vaccine is ●● Vaccine further attenuated (e.g. Schwarz, Edmonston- given later, a 3 months gap is advisable. If measles vaccine was Zagreb) missed altogether, one MMR dose should be given at or after 12 ●● MV supplied freeze dried, Store frozen or refrigerated months. The vaccine can be given along with any other vaccine ●● Use reconstituted vaccine within 4-6 hours (Refrigerate, like DPT, OPV but at different sites using different syringes and do not freeze) needles (47). ●● Inject SC, preferably right upper arm Hepatitis B Vaccine ●● Recommended age 9 months (270 days ) plus The main objective of hepatitis B immunization strategies is to ●● During Measles outbreak, may be given at 6 months prevent chronic hepatitis B virus (HBV) infection and its serious Plus consequences, including liver cirrhosis and hepatocellular ●● If given at < 9 months, repeat dose after interval of at cancer (HCC) (49). Younger the age at infection, higher the least 3 months chance of becoming chronically infected as carrier. The World ●● Alert parents of fever 5-10 days later; Paracetamol may Health Organization recommends universal Hepatitis B be given vaccination. • 992 •
  • Administration of the Vaccine Neonates : Initial dose is 100 - 200 I.U. The first dose shouldTwo types of hepatitis B vaccines are available - plasma derived be administered within 5 days after birth. The booster dosevaccines and recombinant vaccines. The two vaccines show should be 32 - 48 I.U./kg of body wt., between 2 & 3 monthsno differences in terms of reactogenicity, efficacy or duration after initial dose.of protection. The complete vaccine series induces protectiveantibody levels in >95% of infants, children and young adults. Hepatitis B Vaccine (Summary)Hepatitis B vaccine should be given IM at antero-lateral thigh ●● Safe, immunogenic, effective HB vaccine available sincein infants. In older children/adults it should be administered at 1982deltoid region. The minimum recommended interval between ●● Highly purified preparation of HBsAgthe doses is four weeks. Longer dose intervals may increase ●● HBsAg is a glycoprotein that makes up outer envelopethe final anti-HBs titres but not the seroconversion rates (49). of HBVAs an adjuvanated vaccine, it should not be frozen. If frozen ●● Two types of vaccine : Plasma derived and Recombinantaccidentally, the vaccine should be discarded. DNAUsing the principles described, the IAP recommends the ●● To be shipped and stored at 2° C - 8° Ccommencement of HB immunization at birth. Two alternate ●● IM Injection at deltoid in adults, adolescents and childrenschedules are available : and antero-lateral thigh in neonates and infants upto 2a) Infants years ●● Immunogenicity is > 95% in a variety of vaccination1. Birth, 6 and 14 weeks schedules2. 6, 10 and 14 weeks. (Combined DTPw/Hepatitis B vaccine ●● No booster dose recommended can be preferred)b) For older children, adolescents and adults : The Typhoid Vaccinerecommended schedule is elected date, 1 month and 6 months The choice of vaccine depends upon the age of commencementBooster dose is not recommended as of date. of the vaccine and the availability.Adverse Events : In placebo-controlled studies, with the 1. The Whole Cell Typhoid Vaccine : The heat-killed phenol-exception of local pain, reported events such as myalgia and preserved and the acetone killed lyophilized whole celltransient fever have not been more frequent than in the placebo Salmonella typhi vaccine was developed one century ago. Thisgroup. Reports of severe anaphylactic reactions are also very typhoid vaccine is extremely safe from serious reactions and israre. reasonably effective.Contraindications and Precautions : Hepatitis B vaccination Primary course include 2 doses, 4 or more weeks apart andis contraindicated for persons with a history of hypersensitivity a single booster dose is recommended every 3 years. In fieldto yeast or to any vaccine component. Pregnancy is not a trials the vaccine has been associated with fever and systemiccontraindication to vaccination. Limited data indicate no reactions in 9%-34% of the recipients, and with short absencesapparent risk for adverse events to developing foetuses when from work or school in 2%-17% of cases. This vaccine is extremelyhepatitis B vaccine is administered to pregnant women (50). cheap and well suited for giving to children of families whoPassive immunization against hepatitis B : Temporary cannot afford more expensive vaccines (51).immunity may be obtained using hepatitis B immune globulin 2. The Vi Polysaccharide Vaccine : The Vi polysaccharide,(HBIG) for post-exposure prophylaxis. HBIG prophylaxis may purified and adjuvanted is another satisfactory typhoidbe indicated : vaccine with reasonable efficacy & low reactogenicity. As(i) For newborn infants whose mothers are HBsAg-positive. polysaccharide antigens are T cell independent, this vaccine is(ii) Following percutaneous or mucous membrane exposure to non-immunogenic below 2 years of age, induces IgM response HBsAg-positive blood or body fluids. without IgG response, not able to induce immunological(iii) Following sexual exposure to an HBsAg-positive person. memory; hence not able to induce booster effect. When a dose(iv) To protect patients from recurrent HBV infection following is repeated 3-5 years later, it induces response similar to the liver transplantation. first dose. Adverse reactions seem limited to fever (0%-1%),HBIG does not interfere with generation of antibody response headache (1.5%-3%) and erythema or induration >1 cm at theto hepatitis B vaccine. As a rule, HBIG should be used as an site of injection (7%) (52).adjunct to hepatitis B vaccine. However, in full-term newborns, 3. Oral Ty21a Vaccine : This is a live attenuated strain ofthe protection against perinatally acquired infection achieved S. typhi Ty21a that was developed in the early 1970s by chemicalby immediate (<24 hours) hepatitis B vaccination is not mutagenesis. It is genetically stable, and does not revert tosignificantly improved by the addition of HBIG. virulence. Indeed it does not induce a true “infection” as onlyDosage : Following exposure to HBsAg. very limited multiplication occurs in the gastrointestinal tractAdults : 1000 - 2000 I.U., IM. after oral feeding. It is not excreted in large numbers and isChildren : 32-48 I.U.,/kg body wt. This should be administered non-transmissible under natural conditions. Very large numberwithin 7 days (preferably within 48 hrs) after exposure to of bacteria are necessary as oral doses in order to achieveHBsAg. sufficient degree of local immunity, which is the main basis of protection afforded by this vaccine. The bacteria are acid- • 993 •
  • labile. Hence the stomach acidity has to be either neutralised or Japanese B Encephalitis Vaccinebypassed when Ty21a is fed orally. The vaccine is administrated Currently, the three types of JE vaccines in large scale use areorally as enteric coated capsules and is registered for use from (59) :6 years of age. The vaccine is to be given in three sittings, (i) The mouse brain-derived, purified and inactivated vaccine,on alternate days. The protective efficacy is as good as other which is based on either the Nakayama or Beijing strainsavailable typhoid vaccines. Immunization needs to be repeated of the JE virus and produced in several Asian countriesevery 3-5 years (53,54). (ii) The cell culture-derived, inactivated JE vaccine based on the Beijing P-3 strain Typhoid Vaccines (Summary) (iii) The cell culture-derived, live attenuated vaccine based on Whole Cell the SA 14-14-2 strain of the JE virus. ●● Killed S. typhi, often with S. paratyphi A (TA) Both the mouse-brain derived and the cell culture-based ●● Developed by Wright, 1896 vaccines are considered efficacious and to have an acceptable ●● Liquid, store refrigerated, inject subcutaneously safety profile for use in children. However, with the mouse- ●● Primary course : 2 doses 4 weeks brain derived vaccine, rare cases of potentially fatal acute ●● Boosters : Once in 3-5 years disseminated encephalomyelitis and hypersensitivity reactions ●● Dose : 0.5 ml SC have been reported among vaccinated children in endemic Vi polysaccharide regions and in travellers from non endemic locations (60-62). ●● Vi polysaccharide, developed by Robbins, 1984 Many Asian countries have adopted a schedule of 2 primary ●● Liquid, adjuvanted, store refrigerated doses preferably 4 weeks apart, followed by a booster after 1 ●● Inject IM; give at or after 2 years of age year. In some countries, subsequent boosters are recommended, ●● Dose 0.5 ml usually at about 3-year intervals up to the age of 10-15 years ●● To be repeated 3 years later (59). Oral This vaccine is based on the genetically stable, neuro ●● Live attenuated S.typhi, developed by Germanier, 1975 attenuated SA 14-14-2 strain of the JE virus, which elicits ●● Strain name : Ty 21 a broad immunity against heterologous JE viruses. Case control ●● Enteric coated capsules : store refrigerated, administered studies and numerous large-scale field trials in China have orally on alternate days, 3 doses consistently shown an efficacy of at least 95% following 2 ●● To be repeated 3-5 years later doses administered at an interval of 1 year (63). ●● Recommended age : 6 years and above The Indian strain of the Japanese B Encephalitis vaccine produced by Central Research Insititute, Kasauli, is availableHib Conjugate Vaccine through central and state health authorities for use in endemicHaemophilus influenzae type b vaccine is a very effective and areas during epidemic situation in the specific regions of thesafe vaccine. Both PRP-T and PRP - CRM 197 conjugate Hib country where the infection is prevalent.vaccine are now available in India. All Hib-containing vaccines Meningococcal Vaccineshould be stored at between +2°C and +8°C. Liquid Hib vaccine Meningococcal meningitis and septicaemia are caused byshould never be frozen (55). various sero groups of Neisseria meningitidis. Endemic diseaseVaccine Administration : As Hib disease is age dependant and occurs worldwide and is mostly caused by meningococciHib immunization involves boosting of natural immunity, 3 of serogroups A, B or C. The group A meningococcus is thedoses when initiated below 6 months, 2 doses between 6 to 12 predominant cause of large epidemics. Vaccines are availablemonths and 1 dose between 12 to 15 months should be given. against four serogroups of meningococci A, C, W-135 and Y.A booster is recommended at 15 to 18 months. Beyond 18 No effective serogroup B vaccine is presently available. Themonths, a single dose is recommended up to 5 years of age and vaccines are either monovalent i.e. A, C, etc. or polyvalent i.e.above 5 years Hib vaccination is not recommended (56,57). A-C, A-C-Y, A-C-Y-W135 etc. The efficacy rate of a single doseHib vaccine has not been associated with any serious adverse of serogroup A or serogroup C vaccine is 90% in adults andeffects. However, redness, swelling and pain at the site of children over 2 years of age. The four polysaccharide antigensinjection may occur in as many as 25% of those who have been (A, C, Y and W135) have been combined into a tetravalentvaccinated (58). vaccine. It is available in single-dose and multi-dose vials distributed as lyophilized powder that contains 50 micrograms Hib Vaccine (Summary) of each component per dose. The vaccine should be stored at -20°C (64, 65). ●● H. influenzae b capsular polysaccharide ●● Conjugated to protein antigens to improve Dosage and Route of Administration : For both adults and immunogenicity children, vaccine is administered s.c. as a 0.5 ml dose. Protective ●● Monovalent or DPT / Hib conjugate levels of antibody can be expected after 7-10 days. ●● 3 doses 1-2 months apart Indications ●● Booster at 15-18 months (i) Routine immunisation of recruits may be considered (66). ●● Beyond 18 month a single dose up to 5 years (ii) In household contacts, as an adjunct to chemoprophylaxis. • 994 •
  • (iii) Routine immunization for asplenic people and those with Hepatitis A Vaccine (Summary) previously described immunodeficiencies.(iv) Vaccination is recommended for outbreak control for ●● Inactivated vaccine containing HM 175 strain grown in disease caused by any of the serotypes carried by the MRC5 cell line vaccine. ●● 2-dose series, 6-18 months apart.(v) Travellers to hyperendemic or endemic areas. ●● Efficacy - 94-100%Precautions and Contra-indications : Adverse reactions are ●● No booster dosemild and consist of pain and tenderness at the site of injection Pneumococcal Vaccinefor 1-2 days (67,68). No adverse effects have been documentedamong women vaccinated during pregnancy or their newborns. Two types of vaccine are currently available - a 23 valentThere are no known contraindications. The vaccine is not polysaccharide vaccine (available in India) and a 7 valentrecommended for use in children under 2 years of age (69,70). conjugate polysaccharide vaccine in some countries of the world (78). 23-valent polysaccharide vaccine is capable of preventionRevaccination : The need for revaccination of older children of 85% of meningitis and bacteremia caused by pneumococcus.and adults has not been determined, antibody levels decline Each dose is 0.5 ml containing 25 µg of individual serotyperapidly over 2 to 3 years and if indications still exist for polysaccharide. A single IM injection is recommended after theimmunisation, revaccination may be considered within 3 to 5 age of 2 years with booster every 3-5 years till the age of 10years (71). years (79, 80). The 7 valent conjugate polysaccharide vaccineVaricella Vaccine manufacturer recommends three IM injections in infants agedTakahashi et al developed a live attenuated vaccine for under 6 months, the first dose usually given at 2 months ofvaricella from Oka strain in Japan. The recommended dose is age, with an interval of at least 1 month between doses.0.5 ml which provides at least 1350 plaque forming units of the Influenza Vaccinevirus. The vaccine is administered SC in the upper arm/thigh Both inactivated and live, attenuated influenza vaccines areregion. It is recommended after the age of 1 year. Up to the age available. There are 3 types of inactivated influenza vaccine,of 12 years, one dose is required and if given after 12 years, namely whole virus vaccines, split virus vaccines and subunit2 doses are needed at an interval of 1 month. Both humoral vaccines. In most countries, whole virus vaccines have beenand cell mediated immunity develops in more than 95% cases replaced by less reactogenic split virus and subunit vaccines.after a single dose between 1-12 years and 99% after 2 doses in The multivalent vaccine usually contains 3 virus strainschildren 13 years and above (72-74). (usually 2 type A and 1 type B) with composition changed periodically in anticipation of the prevalent influenza strains Varicella Vaccine (Summary) expected to circulate in the country (81, 82). The vaccine is given in 2 doses in children 6 months to 9 years of age and ●● Developed by Takahashi in 1971 in Japan one dose above 9 years of age. The dose is 0.25 ml between 6 ●● Live attenuated Oka Strain months to 3 years IM and 0.5 ml after the age of 3 years (83). ●● Vaccine available as lyophilized powder ●● Dissolve in 0.5 ml diluent Live, Attenuated Influenza Caccines : For several years, live, ●● SC Injection attenuated influenza vaccines for nasal application have been ●● Single dose 12 months - 12 years used successfully in the Russian Federation. The temperature- ●● Two doses beyond 13 years; 1 month apart sensitive vaccine virus will replicate well in the relatively ●● Efficacy 95- 99% cool environment of the nasopharynx, but poorly in the lower ●● No booster dose recommended respiratory tract. This vaccine is reported to be safe and highly efficacious following 1 single dose in adults and children >3 years of age (84-86). Based on data from industrializedHepatitis A Vaccine countries, and listed in order of priority, the following groups ofSeveral inactivated or live attenuated vaccines against hepatitis individuals may be targeted for vaccination in order to reduceA have been developed, but only 4 inactivated hepatitis A the incidence of severe illness and premature death.vaccines are currently available internationally. All 4 vaccines 1. Residents of institutions for elderly people and theare similar in terms of efficacy and side-effect profile. The disabled.vaccines are given parenterally, as a 2-dose series, 6-18 months 2. Elderly, non-institutionalized individuals with chronicapart. The dose of vaccine, vaccination schedule, ages for which heart or lung diseases, metabolic or renal disease, orthe vaccine is licensed, and whether there is a paediatric and formulation varies from manufacturer to manufacturer. 3. All individuals >6 months of age with any of the conditionsNo vaccine is licensed for children aged < 1 year (75, 76). listed above.Vaccine efficacy is 94-100% and the duration of protection 4. Elderly individuals above a nationally defined age limit,is long lasting, hence no booster dose is recommended at irrespective of other risk factors.present. The current vaccines are well tolerated and no serious Rabies Vaccineadverse events have been statistically linked to their use.Contraindications to hepatitis A vaccination include a known There are 2 types of rabies vaccines available in India :allergy to any of the vaccine components (77). 1. Nerve tissue vaccine • 995 •
  • 2. Tissue culture vaccines Immunization against Cholera●● Human diploid cell vaccine Until recently, the only available cholera vaccines was phenol-●● Purified chick embryo cell vaccine killed whole cell killed vaccine, administered in 2 doses, 2●● Vero cell vaccine weeks apart. Unfortunately, the protective efficacy of vaccineNerve tissue vaccine is no longer recommended because of is only about 50%; duration of protection hardly exceeds 6its poor efficacy and life threatening adverse reactions in the months.form of neuroparalytic conditions of 1 : 2000 to 1 : 8000 doses Live, Attenuated CVD 103-HgR vaccine : A live, attenuated(87,88). oral cholera vaccine containing the genetically manipulatedTissue Culture Vaccines Classical V. cholerae strain CVD 103-HgR has been availableAll tissue culture vaccines are having almost equal efficacy and since 1994 which confers a high level of protection (> 90%)any one of them can be used. against moderate and severe cholera. Both the whole cellPost exposure prophylaxis : After thoroughly cleaning killed and the CVD 103-HgR vaccines may be recommended forthe wound with soap and water and appropriate tetanus travellers to high-risk regions (93).prophylaxis, rabies immunoglobulin either human or equine Development of New Vaccines : Currentin the dose of 20 IU and 40 IU/kg body weight respectivelyis infiltrated around the wound in case of severe bite or bites Situationin the upper extremities, trunk, head and face. Currently IM Rotavirus Vaccineinjection of RIG is not recommended (89,90). Acute diarrhoea is responsible for nearly 1.9 million deaths perPre-exposure prophylaxis : 1 ml of any of the tissue culture year in children under age five. Rotavirus is responsible for asvaccine is given IM over the deltoid region on day 0, 7 and 28 much as one fourth of these casualties, almost all of whichfor the high risk group. occur in developing countries.In order to reduce the cost of post-exposure treatment, Status of vaccine development : RotaRix, a vaccine developedintradermal multisite regimens using a fraction of the by GlaxoSmithKline (GSK), and RotaTeq vaccine developed byintramuscular volume per intradermal inoculation site have Merck against rotavirus diarrhoea are now licensed in manybeen developed (91). countries. In addition to being available in the private market, it has now been introduced in the public sector immunization Rabies Vaccine - Tissue Culture Vaccine (Summary) programmes of many countries (94). Post exposure Prophylaxis Recommendations : Routine immunization of all infants ●● 1 ml per dose irrespective of age in deltoid region in without contraindications. It is provided as a single 2ml oral infants >2 years; and in anterolateral aspect of thigh in dose in a buffered stabilizer solution. It is stored at 36-46°F (2- infants< 2 years. 8°C), and administered at 2, 4, and 6 months of age. Minimum ●● Schedule Day 0, 3, 7, 14 and 28 age of first doses is 6 weeks. First dose should be administered ●● Re-exposure within 5 years - 2 doses - day 0 and 7; after between 6 and 12 weeks of age (until age 13 weeks). Minimum 5 years full course. Earlier if anti rabies antibody titer interval between doses is 4 weeks. Maximum age for any dose falls below 0.5 IU / ml is 32 weeks (95). Pre exposure Prophylaxis Challenges : A vaccine must be effective against numerous rotavirus strains (serotypes), including those prominent in ●● 1 ml per dose, any Tissue Culture Vaccine, IM developing countries. These vaccines, since they are live, oral ●● Schedule Day 0, 7 and 28 ones, must be shown not to interfere with oral polio vaccine & ●● Indicated for High Risk Group must be efficacious. Even more importantly, they must be shown - Laboratory staff working with Rabies Virus to be safe in general, and in HIV-infected children in particular. - Veterinarians Price will also be an issue for large-scale introduction (94). - Wild life staff Human Papillomavirus (HPV) VaccineRabies Immunoglobulin : It is a liquid or freeze dried Sexually transmitted HPV is the major cause of cervical cancer,preparation containing immunoglobulins mainly IgG obtained the most common cause of cancer deaths among women infrom plasma or serum of donors immunised against rabies and developing countries. About 500,000 cases occur each year,contains specific antibodies that neutralise the rabies virus. 80% of them in developing countries. Cervical cancer kills someIt provides passive protection when given immediately to 240,000 women annually.individuals exposed to rabies virus with minimum interference Status of vaccine development : Gardasil, an HPV vaccineof active immunization with human diploid - cell vaccine (92). recently licensed by Merck, covers four types of HPV, includingAdverse Effects : Local tenderness, muscle soreness or the cancer-causing types 16 and 18 and types 6 and 11 forstiffness at the injection site, low grade fever, sensitization non-cancerous genital warts. A second vaccine, developed byto repeated injections of human globulin in immunoglobulin GSK, covers HPV types 16 and 18 alone and is expected to bedeficient patients. licensed in 2007.Indications : All injuries, even licks, on mucous membranes Challenges : HPV types 16 and 18 cause around 70% of HPVby wild animals (or even pet animals) suspected to be suffering cervical cancers globally, but the vaccines in development willfrom rabies. • 996 •
  • not cover the 30% of cancers attributed to other HPV types. almost immediately and its efficacy lasts for six months. ActiveBecause these other types are numerous and individually only immunisation with HAVRIX is available in our country.contribute a small percentage, significantly expanding vaccinecoverage against them may present technical challenges for Table - 5 : Validity of International Certificate ofmanufacturers. The duration of the immunity conferred by the Vaccinationvaccines is not yet known, and only time and follow up studies Certificatewill provide this critical information. Access to the vaccines Type of vaccinationis likely to be an issue in developing countries due to limited Valid for Valid fromresources for the implementation of vaccination programmes Yellow fever-primary 10 days after(94). 10 years vaccination vaccinationInternational Vaccination Requirement Yellow fever-re-vaccination 10 years at once after revaccinationImmunization Against Yellow FeverYellow fever (YF) is endemic in tropical regions of Africa and (d) Tetanus : A booster dose of Tetanus toxoid should be takenSouth America. Vaccination is the most effective method for the if 5 years or more have elapsed since the last injection of aprevention of spread of the disease by international travel (96). complete course or booster.Two types of vaccines are available (97). Immunization in Special Circumstances (99)(i) 17 D Vaccine : This is the approved vaccine for international 1. Immunization in preterm infants : All vaccines should betravel. It is a live, attenuated chick embryo grown 17D-strain administered as per schedule irrespective of birth weight orfreeze-dried vaccine. For storage at WHO approved centers, the period of gestation except Hepatitis B. If the weight of the babyvaccine can be kept for 3 months at +4°C. If the storage is for is less than 2 kg and mother is HBsAg negative, then Hepatitisa longer duration, a temperature of -25°C is to be maintained. B vaccine is postponed till the baby attains a weight of 2 kgAfter reconstitution, it should be used within half an hour. or 2 months of age. However, if the mother is HBsAg positive,(ii) Dakar Vaccine : It is also called French Neurotropic Vaccine then both Hepatitis B vaccine and Hepatitis B immunoglobulindeveloped at the Pasteur Institute Dakar. It is theremostable is administered within 12 hours of birth followed by 3 moreand can be easily transported. However, it has produced post- doses at 1, 2 and 6-12 months.vaccinial encephalitis in children. WHO has not approved use 2. Children receiving corticosteroids : Children receivingof this vaccine for international travel. corticosteroids at the dose of 2 mg/kg/day for more than 14Administration of vaccine : 17-D vaccine is given SC at the days should not receive live virus vaccines until steroid hasinsertion of deltoid in a single dose of 0.5 ml. Immunity begins been discontinued for at least 1 month.within 10-12 days and lasts for at least 10 years however 3. Vaccination in HIV/AIDS : Following table summarizesthe persistence of neutralizing antibody 30-35 years after the recommendation of WHO and Advisory Committee onimmunization with 17D yellow fever vaccine has been observed Immunization Practices and American Academy of Paediatrics.(98). Yellow fever vaccination is available at designated centerscertified by the Government of India. Armed Forces Clinic, New Vaccination recommendations in HIV infected symptomatic andDelhi is one of such centers. asymptomatic Children (Table - 6).International certificate of vaccinationis required only for one disease i.e. Table - 6 : Vaccination recommendations in HIV infected symptomatic andyellow fever. The period of validity of asymptomatic Childrenthe certificate is shown in Table - 5. Known Asymptomatic Known SymptomaticProtection is recommended against Vaccine WHO ACIP / AAP WHO ACIP / AAPcertain other diseases for internationaltravellers although the international BCG Yes* No No Nocertificate is not required. These DPT/DtaP Yes Yes Yes Yesdiseases are as under : OPV Yes No No No(a) Cholera : Cholera vaccine may Measles / MMR Yes Yes Yes Yesbe taken by all travellers proceedingto endemic areas. It offers partial IPV - Yes - Yesprotection against the disease. Hepatitis B Yes Yes Yes Yes(b) Enteric Infections : Vaccination Hib - Yes - Yesand revaccination against typhoid Pneumococcal - Yes - Yesis strongly advised for all travellersproceeding to endemic areas. Influenza - Yes - Yes(c) Hepatitis A : A single IM injection Varicella - Consider - Considerof human normal immunoglobulin 500 Hepatitis A - Yes - Yesmg or 1.2 mg/kg body weight is effective * For regions where risk of TB is high • 997 •
  • 4. Vaccination schedule for children not immunized in time : an illiterate person should be indicated by his left thumb markTable - 7 depicts the schedule which should be followed in case certified by another person. The certificates requires signatureof unimmunized child. of medical practitioner; his official stamp is not accepted as a substitute nor is the signature of the clinical nurse. The Table-7: Vaccination schedule of an Unimmunized Child correct procedure for the doctor is to do the vaccination himself and sign the certificate as the vaccinator. On all international Age Less than 5 years More than 5 years vaccination certificates, name of manufacturer of vaccine First Visit BCG, OPV, DPT, HB TT/ Td, HB as well as the batch number must be given. Medical officers 2nd visit (1 OPV, DPT, HB TT/ Td, HB are also advised to refer to standard WHO publication on month later) requirements for international travellers (100). 3rd visit (1 OPV, DPT, MMR, MMR, Typhoid Summary month later) Typhoid The modern word “immunity” derives from the latin immunis, 1 Year later OPV, DPT, HB HB meaning exemption from military service, tax payments or Every 3 years Typhoid booster Typhoid booster other public services and is defined as “Ability of an organism to recognize and defend itself against specific pathogens or5. Lapsed Immunization : A lapse in the immunization antigens”. The immune system is a collection of mechanismsschedule does not require reinstitution of the entire series. within an organism that protects against infection by identifyingImmunizations should be given at the next visit as if the usual and killing pathogens and tumour cells. The physical barriersinterval had elapsed and the immunization schedule should prevent pathogens entering the body. If a pathogen breachesbe completed at the next available opportunity. In case of an these barriers, the innate immune system provides anuncertain immunization status, it is appropriate to start the immediate, but non-specific response. However, if pathogensschedule of unimmunized child. successfully evade the innate response, vertebrates possess a third layer of protection, the adaptive immune system.6. Immunization of Adolescents : Reasons for adolescentimmunization fall into the following broad categories : An antigen is defined as a substance which when introduceda. To boost the waning immunity by giving booster doses. into the tissues stimulates the production of specific antibodiesb. To counter a specific risk e.g. due to travel, life style etc. and combines specifically with the antibody so produced. By far the best antigens are proteins; others are poly-saccharides, Table - 8 : Vaccination Schedule in Adolescents lipids and nucleic acids. There are also incomplete antigens called ‘haptens’ which by themselves are not antigenic but can Vaccine Age provoke an immune response. Tetanus Toxoid Booster at 10 and 16 years An antibody is a protein substance that appears in the Rubella vaccine As part of MMR vaccine or body as a result of invasion by an antigen. It is capable of (Monovalent) 1 dose to girls at 12-13 reacting specifically with the same antigen, which provokes years of age, if not given earlier its production. The sites of maximum antibody formation MMR Vaccine 1 dose at 12-13 years of age. (if not are the lymph nodes and spleen. Immunoglobulins comprise given earlier) of families of closely related globulin molecules, which are synthesized by cells of reticuloendothelial system. The human Hepatitis B. Vaccine 3 Doses (0, 1 and 6 m) if not given immunoglobulin system is divided into five major classes IgG, earlier IgA, IgM, IgD and IgE. Typhoid Vaccine TA, Vi or Oral typhoid vaccine every Types of immune defenses can broadly be divided into Innate 3 years and Acquired Immunity. Acquired Immunity can further be Varicella Vaccine* 1 dose upto 12-13 years, and 2 doses divided into Active and Passive immunity with Artificial and after 13 years of age. (if not given Natural types in each. Active immunity : (a) Naturally acquired earlier) active immunity occurs when a person is exposed to a live pathogen, and develops a primary immune response, which Hepatitis A Vaccine* 2 doses (0 and 6 months) if not given leads to immunological memory. (b) Artificially acquired earlier active immunity can be induced by a vaccine, a substance that Varicella* and Hepatitis A* vaccine are additional vaccines. These vaccines are contains antigen. Passive immunity is the transfer of active recommended depending upon the epidemiology of these diseases especially in the adolescent age group where fatal complications are likely to occur. immunity, in the form of readymade antibodies, from one individual to another.International Certificate of Vaccination : These are individual Two different types of Host defenses that the body exhibits as acertificates and should not be used collectively. Certificates are result of exposure to antigen : (a) The humoral immune responseprinted in English and French; an additional language may be (b) The cell-mediated immune response. The cells of the tissueused. The dates should be recorded in the following sequence; attacked are as much concerned in offering resistance to theDay, Month, Year, the month to be written in letters e.g. 20 infecting agent as the antibodies or phagocytes; this is the localMarch 1999. A certificate issued to a child who is unable to write immunity. Herd Immunity is the immunity of a group of peopleshould be signed by the parent or guardian. The signature of or a community taken as a whole. The first encounter with an • 998 •
  • antigen is known as the primary response. Re-encounter with of the cold chain is monitored by the National Quality Controlthe same antigen causes a secondary response that is more Lab at Kasauli. The quality check is done before release ofrapid and powerful. the vaccines. Reverse Cold Chain is also maintained to checkImmunisation is the process by which an individual is exposed vaccines for their an agent that is designed to fortify his or her immune system UIP VACCINES includes BCG Vaccine, Oral PolioVaccine, DPTagainst that agent. The material is known as an immunogen. Vaccine and Measles Vaccine. NON UIP VACCINES includesImmunization is the same as inoculation and vaccination. Mumps Vaccine, Rubella, MMR, Hepatitis B Vaccine, TyphoidVaccines are immunobiological substances designed to produce Vaccine, Japanese B Encephalitis, Meningococcal Vaccine,specific protection against diseases by stimulating production Hepatitis A, Varicella, Pneumococcal, Rabies and Influenzaof protective antibody or other immune mechanisms. The Vaccine. International Vaccination Requirement is for YellowVaccine mimics the infection with the respective pathogen, fever (YF) which is a mosquito-borne, viral haemorrhagicbut without risk of the disease. The goal of all vaccines is to fever that is endemic in tropical regions of Africa and Southpromote a primary immune reaction so that when the organism again exposed to the antigen, a much stronger secondaryimmune response will be elicited. Study ExercisesThere are four types of traditional vaccines : Live (attenuated), MCQs & ExercisesInactivated (killed), Toxoids, Subunit and recombinant. Live 1. Wasserman antibodies and bactericidal antibodiesVaccines are prepared from live attenuated organisms and against Gram negative organisms (endotoxins) are almostare very potent immunizing agents. Safety is an issue and exclusively found in (a) IgG (b) IgM (c) IgA (d) IgEthey cannot be used for immunodeficient patients and during 2. Cytotoxic or killer T cells (CD8+) do their work bypregnancy. Examples include BCG, Typhoid oral, Measles, releasing __________ , which cause cell lysis.Mumps, Rubella and Oral Polio. Inactivated (Killed) Vaccines are 3. Antibody binds to antigen & this is called __________ . prepared from organisms killed by heat or chemicals, are very 4. Influx of susceptible people and occurrence of new birthssafe but less efficacious than live vaccines. They require multiple increase the herd immunity. True/ Falsedoses. The only absolute contraindication is hypersensitivity, 5. Tuberculosis (BCG) was discovered in (a) 1923 (b) 1927e.g. Typhoid, Rabies, Hepatitis B. Toxoids are produced from (c) 1935 (d) 1943detoxicated toxins. The body produces antibodies against the 6. Hepatitis B (a) 1963 (b) 1971 (c) 1981 (d) 1993toxin in response to toxoids. They offer no protection against 7. World Health Organization (WHO) certified the eradicationinfection, are very safe and highly effective, e.g. Diphtheria, of smallpox in (a) 1975 (b) 1977 (c) 1979 (d) 1981Tetanus. 8. The immunization against quarantinable disease under the International Health Regulations, is carried outPassive immunization may be administered using human or for which disease? (a) Polio (b) Yellow fever (c) Plagueanimal products. Conventionally human products are called (d) Malariaimmunoglobulins and animal products are called anti sera. 9. When vaccines are reconstituted, the diluent should be atNon specific or generalized protection is offered by normal same temperature as the vaccine. True/ Falseimmunoglobulins while protection against specific diseases is 10. The vaccines must be kept in the cold chain betweengiven by using hyperimmune immunoglobulins. __________ at all times, or optionally, at -15 to -25°C ifImmunization schedule drawn up keeping two important cold chain space permits. (a) 0 and +4°C (b) +2 and +6°Cfactors in mind - the vaccines need to be administered in doses (c) +2 and +8°C (d) +6 and +10°Cand schedules which produce an adequate immunological 11. While vaccines and diluents remain in storage it isresponse in the recipient; and secondly the schedule should be necessary to follow the principle of “EEFO” which standadministratively the most convenient and one which is likely for __________ .to be most acceptable to the target population. The National 12. The BCG vaccine was first used to immunize humans in Immunization schedule drawn up for India factors in both (a) 1971 (b) 1941 (c) 1931 (d) 1921these aspects. 13. Eradication is defined as no case of paralytic poliomyelitisCold chain is a system of transporting and storing vaccines at by wild polio virus in last __________ years along withrecommended temperature from manufacturer to the point of absence of wild polio virus in the community, whereuse. All the vaccines can be stored at temperatures between excellent clinical and virological surveillance exists and+2 to +8°C. However, long term storage of OPV and Measles the coverage of routine OPV is more than 80%.requires them to be stored at sub zero temperatures in deep 14. Polio elimination is defined as __________ cases of paralyticfreezers. DPT, DT and TT poliomyelitis by the wild polio virus in one calendar yearshould never be frozen. BCG and diluent ampoules should not with other criteria same as in frozen, as ampoules are likely to crack. Diluents required 15. Indian Academy of Paediatrics recommend _ _ _ _ _ _ _ _ _ _ _for measles and BCG should be stored at +2 to +8°C in the at 10 and 16 yearsrefrigerator. Cold Chain includes Walk in cold rooms (WICs), Answers : (1) b; (2) lymphotoxins; (3) Tagging; (4) False; (5) b;Deep freezers, Ice - lined refrigerators (ILRs), Refrigerators, (6) c; (7) c; (8) b; (9) True; (10) c; (11) “earliest expiry first out”;Cold box, Vaccine carrier, Day carrier and Ice packs. The quality (12) d; (13) 3 calendar; (14) Zero; (15) TT. • 999 •
  • References 36. Long SS, DeForest A, Pennridge Paediatric Associates, Smith DG, Lazaro C, Wassilak SGF. Longitudinal study of adverse reactions following diphtheria-1. Lindquester, Gary J. Introduction to the History of disease. Disease and tetanus-pertussis vaccine in infancy. Paediatrics 1990;85 : 294-302. Immunity, Rhodes College (2006). 37. Cody CL, Baraff LJ, Cherry JD, Marcy SM, Manclark CR. The nature and rate of2. Silverstein, Arthur M. History of Immunology (Hardcover) Academic Press adverse reactions associated with DTP and DT immunization in infants and (1989). children. Paediatrics 1981;68 : 650-60.3. Gherardi E. The Concept of Immunity. History and Applications. Immunology 38. Walker AM, Jick H, Perera DR, Knauss TA, Thompson RS. Neurologic events Course Medical School, University of Pavia. following diphtheria-tetanus-pertussis immunization. Paediatrics 1988; 814. A “al-Razi.” 2003 The Columbia Electronic Encyclopedia, Sixth Edition. : 345-9. Columbia University Press (2006). 39. Stetler HC, Orenstein WA, Bart KJ, Brink EW, Brennan J-P Hinman AT. History ,5. Youmans GP Paterson M, Sommers HM. The biologic and clinical basis of , of convulsions and use of pertussis vaccine. J Pediatr 1985;107 : 175-9. infections diseases. WB Saunders Company, Phildelphia, USA. 3rd Ed 1985. 40. The National Vaccine Advisory Committee. The measles epidemic : the6. Ada GL. The immunological principles of vaccination. Lancet 1990; 335 : problems, barriers, and recommendations. JAMA 1991;266 : 1547-52. 523-6. 41. Measles--United States, 1995. MMWR 1996;45 : 305-7.7. Mayer, Gene. Immunology - Chapter One : Innate (non-specific) Immunity. 42. WHO Position paper on Mumps Vaccine WER 2007;82 : 41-48. Microbiology and Immunology On-Line Textbook. USC School of Medicine. 43. CDC. Rubella and congenital rubella syndrome-United States, 1984-1985. Retrieved on 2007-01-01. MMWR 1986; 35 : 129-35.8. Litman G, Cannon J, Dishaw L (2005). “Reconstructing immune phylogeny : 44. Lee SH, Ewert DP Frederick PD, Mascola L. Resurgence of congenital rubella , new perspectives.” Nat Rev Immunol 5 (11) : 866-79. syndrome in the 1990’s : report on missed opportunities and failed prevention9. Roitt I M. Essential Immunology 8th edition. policies among women of childbearing age. JAMA 1992; 267 : 2616-20.10. Goodman JW 1991. Immunoglobulin structure and function. Chapter 9. 45. Plotkin SA, Farquhar JD, Ogra PL. Immunologic properties of RA 27/3 rubella Basic and clinical immunology, 7th edition. virus vaccine. A comparison with strains presently licensed in the U.S. JAMA11. Male DK Et al, 1991 advanced Immunology, 2nd edition 1973; 225 : 585-9012. Nossal GV L The basic component of immune system. New Eng J Med 46. Greaves WL, Orenstein WA, Hinman AR, Nersesian WS. Clinical efficacy of 1987;316 : 1320 rubella vaccine. Pediatr Infect Dis 1983; 2 : 284-6.13. Barret JT 1988.textbook of Immunology, Chapter 2. 47. King GE, Hadler SC. Simultaneous administration of childhood vaccines : an14. Saji F, Samejima Y, Kamiura S, Koyama M. Dynamics of immunoglobulins at important public health policy that is safe and efficacious. Pediatr Infect Dis the feto-maternal interface. Rev Reprod 1994;4(2) : 81-9. J 1994; 13 : 394-407.15. Van de Perre P “Transfer of antibody via mother’s milk.” Vaccine 2003; 21 . 48. Alward WL, McMahon BJ, Hall DB, Heyward WL, Francis DP Bender TR. The , (24) : 3374-6. long-term serological course of asymptomatic hepatitis B virus carriers and16. Keller, Margerate A, Richard E. Passive immunity in prevention and treatment the development of primary hepatocellular carcinoma. J Infect Dis 1985; 151 of diseases. Clinical microbiology review 2000; 13(4) : 602-14. : 604-9.17. Holtmeier W, Kabelitz D. “T cells link innate and adaptive immune responses”. 49. WHO Position Paper on Hepatitic B Vaccine WER 2004; 79 : 253-264 Chem Immunol Allergy2005; 86 : 151-183. 50. Levy M, Koren G. Hepatitis B vaccine in pregnancy : maternal and fetal18. Cooper MD B lymphocytes : normal development and function. New Eng J safety. Am J Perinatol 1991;8 : 227-32. Med 1987;317 : 1452 51. WHO Position Paper on Typhoid vaccines WER 2000; 75 : 257-26419. Friis RH, Sellers TA. Epidemiology for Public Health Practice. Jones and 52. Klugman KP Gilbertson IT, Koornhof HJ, et al. Protective activity of Vi , Bartlett, Publishers,Sudbury, Massachusets, Boston, USA. Third Ed 2004 : capsular polysaccharide vaccine against typhoid fever. Lancet 1987; 330 : 397 - 444. 1165-9.20. Janeway CA, Jr. et al Immunobiology, 6th ed., Garland Science (2005). 53. Murphy JR, Grez L, Schlesinger L, et al. Immunogenicity of Salmonella typhi21. Govt of India : Health information of India. Ministry of health and family Ty21a vaccine for young children. Infect Immun 1991;59 : 4291-3. welfare 2006. 54. Cryz SJ, Vanprapar N, Thisyakorn U, et al. Safety and immunogenicity of22. Ellenberg SS, Chen RT.  The complicated task of monitoring vaccine safety.  Salmonella-typhi Ty21a vaccine in young Thai children. Infect Immun Public Health Reports.  Jan/Feb 1997; 112 : 10-19. 1993;61 : 1149-51.23. Casto DT, Brunell PA. Safe handling of vaccines. Paediatrics 1991;87 : 108- 55. The WHO Position Paper on Haemophilus influenzae type b conjugate 12. vaccines. WER 1998;73 : 64-68.24. Bishai DM, Bhatt S, Miller LT et al. Vaccine storage practices in paediatric 56. Wenger JD, Ward JI, Broome CV. Prevention of Haemophilus influenzae type offices. Paediatrics 1992; 89 : 193-96. b disease : vaccines and passive prophylaxis. In : Remington JS, Swartz25. Milhomme P and the Childhood Immunization Division, LCDC. Cold chain MN, eds. Current clinical topics in infectious diseases. Boston : Blackwell study : danger of freezing vaccines. CCDR 1993; 19 : 33-38. Scientific Publications, 1989 : 306-39.26. “Manual on the Management, Maintenance and Use of Cold Chain 57. Ward JI, Broome CV, Harrison LH, Shinefield HR, Black SB. Haemophilus Equipment”, World Health Organization, 2005. influenzae type b vaccines : lessons for the future. Paediatrics 1988; 81 : 886-93.27. CDC. Use of BCG vaccines in the control of tuberculosis : a joint statement by the ACIP and the Advisory Committee for Elimination of Tuberculosis. 58. Madore DV, Johnson CL, Phipps DC, et al. Safety and immunologic response MMWR 1988; 37 : 663-4, 669-75. to Haemophilus influenzae type b OligosaccharideCRM197 conjugate vaccine in 1-to 6-month-old infants. Paediatrics 1990; 85 : 331-7.28. Shapiro C, Cook N, Evans D, et al. A case-control study of BCG and childhood tuberculosis in Cali, Colombia. Int J Epidemiol 1985; 14 : 441-6. 59. The WHO Position Paper on Japanese Encephalitis Vaccines. WER 2006; 81 : 325-34029. Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis : meta-analysis of the published literature. JAMA 60. Hoke CH, Nisalak A, Sangawhipa N, et al. Protection against Japanese 1994;271 : 698-702. encephalitis by inactivated vaccines. N Engl J Med 1988; 319 : 609-14.30. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against 61. Rao Bhau LN, Singh F, Gowal D, et al. Safety and efficacy of Japanese tuberculous meningitis and miliary tuberculosis : a meta-analysis. Int J encephalitis vaccine produced in India. Indian J Med Res 1988; 88 : 301-7. Epidemiol 1993; 22 : 1154-8. 62. Andersen MM, Rone T. Side effects with Japanese encephalitis vaccine.31. Lotte A, Wasz-Hockert O, Poisson N, et al. Second IUATLD study on Lancet 1991;337 : 1,044. complications induced by intradermal BCG-vaccination. Bull Int Union 63. Yu YX, Ming AG, Pen GY, et al. Safety of a live-attenuated Japanese Tuberc 1988; 63 : 47-59. encephalitis virus vaccine (SA14-14-2) for children. Am J Trop Med Hyg32. Polio General Recommendations on Immunization. MMWR 2006; 51 : 1-48. 1988; 39 : 214-7.33. Sutter RW et al The Role of Routine Polio Immunization in the Post- 64. WHO Position Paper on Meningococcal vaccines : Polysaccharide and Certification Era . Bulletin of the World Health Organization, 2004;.82(1) polysaccharide conjugate vaccines .WER 2002; 77 : 329-340 : 31-39. 65. Armand J, Arminjon F, Mynard MC, Lefaix C. Tetravalent meningococcal34. Diphtheria, tetanus, and pertussis : guidelines for vaccine prophylaxis and polysaccharide vaccine groups A, C, Y, W 135 : clinical and serologic other preventive measures : recommendations of the Immunization Practices evaluation. J Biol Stand 1982; 10 : 335-9. Advisory Committee (ACIP). MMWR 1985;34 : 405-14, 419-26. 66. Brundage JF, Zollinger WD. Evolution of meningococcal disease epidemiology35. Hirtz DG, Nelson KB, Ellenberg JH. Seizures following childhood in the U.S. Army. In : Vedros NA, ed. Evolution of meningococcal disease, immunizations. J Pediatr 1983;102 : 14-8. volume 1. Boca Raton, FL : CRC Press, Inc.; 1987 : 5--25. • 1000 •
  • 67. Scheifele DW, Bjornson G, Boraston S. Local adverse effects of meningococcal 84. King JC Jr, Lagos R, Bernstein DI, et al. Safety and immunogenicity of low vaccine. CMAJ 1994; 150 : 14-5. and high doses of trivalent live cold-adapted influenza vaccine administered68. Yergeau A, Alain L, Press R, Robert Y. Adverse events temporally associated intranasally as drops or spray to healthy children. J Infect Dis 1998; 177 : with meningococcal vaccines. CMAJ 1996; 154 : 503-7. 1394-7.69. Leston GW, Little JR, Ottman J, Miller GL. Meningococcal vaccine in pregnancy 85. Belshe RB, Gruber WC, Mendelman PM, et al. Correlates of immune protection : an assessment of infant risk. Pediatr Infect Dis J 1998; 17 : 261-3. induced by live, attenuated, cold-adapted, trivalent, intranasal influenza70. McCormick JB, Gusmao HH, Nakamura S, et al. Antibody response to virus vaccine. J Infect Dis 2000; 181 : 1133-7. serogroup A and C meningococcal polysaccharide vaccines in infants born of 86. Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated mothers vaccinated during pregnancy. J Clin Invest 1980; 65 : 1141-4. influenza vaccine in infants and young children. N Engl J Med 2007; 356 :71. Borrow R, Joseh H, Andrews N, et al. Reduced antibody response to 729-31. Rabies revaccination with meningococcal serogroup A polysaccharide vaccine in 87. WHO Expert Committee on Rabies, 8th report. Geneva : World Health adults. Vaccine 2000; 19 : 1129-32. Organization, 1992; TRS 824.72. Asano Y, Nagai T, Miyata T, et al. Long-term protective immunity of recipients 88. Fishbein DB, Arcangeli S. Rabies prevention in primary care. A four-step of the OKA strain of live varicella vaccine. Paediatrics 1985; 75 : 667-71. approach. Postgrad Med 1987; 82 : 83-90, 93-5.73. Asano Y, Suga S, Yoshikawa T, et al. Experience and reason : twenty-year 89. Berlin BS. Rabies vaccine adsorbed : neutralizing antibody titers after three- follow-up of protective immunity of the Oka strain live varicella vaccine. dose pre-exposure vaccination. Am J Pub Health 1990;80 : 476-8. Paediatrics 1994; 94 : 524-6. 90. Dreesen DW, Fishbein DB, Kemp DT, Brown J. Two-year comparative trial on74. Watson B, Rothstein E, Bernstein H, et al. Safety and cellular and humoral the immunogenicity and adverse effects of purified chick embryo cell rabies immune responses of a booster dose of varicella vaccine 6 years after primary vaccine for pre-exposure immunization. Vaccine 1989;7 : 397-400. immunization. J Infect Dis 1995; 172 : 217-9. 91. Warrell MJ, Nicholson KG, Warrell DA, et al. Economical multiple-site75. D’Hondt E. Possible approaches to develop vaccines against hepatitis A. intradermal immunisation with human diploid-cell-strain vaccine is effective Vaccine 1992;10(Suppl 1) : S48-52. for post-exposure rabies prophylaxis. Lancet 1985;1 : 1059-62.76. Innis BL, Snitbhan R, Kunasol P et al. Protection against hepatitis A by an , 92. Chutivongse S, Wilde H, Supich C, Baer GM, Fishbein DB. Post-exposure inactivated vaccine. JAMA 1994;271 : 1328-34. prophylaxis for rabies with antiserum and intradermal vaccination. Lancet77. Balcarek KB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and 1990; 335 : 896-8. immunogenicity of an inactivated hepatitis A vaccine in preschool children. 93. WHO Position Paper on Cholera vaccines WER 2001; 76 : 117-124. J Infect Dis 1995;171(Suppl 1) : S70-2. 94. WHO Fact sheet No. 289. Revised December 2006.78. WHO Position Paper on Pneumococcal vaccines WER 2003; 78 : 97-120 95. MMWR 2006;55 : (RR-12) : 1-13.79. CDC. Pneumococcal polysaccharide vaccine usage, United States. MMWR 96. World Health Organization. Yellow fever,998-1999. Wkly Epidem Rec 1984; 33 : 273-6,281. 2000;75 : 322-7.80. Fedson DS, Musher DM. Pneumococcal vaccine. In : Plotkin SA, Mortimer EA 97. Monath TP Yellow fever. In : Plotkin SA, Orenstein WA, eds. Vaccines. 3rd ed. . Jr, eds. Vaccines. 2nd ed. Philadelphia, PA : WB Saunders, 1994 : 517-63. Philadelphia, PA : W.B. Saunders, 1999;815--79.81. Glezen WP Serious morbidity and mortality associated with influenza . 98. Poland JD, Calisher CH, Monath TP Downs WG, Murphy K. Persistence of , epidemics. Epidemiol Rev 1982; 4 : 25-44. neutralizing antibody 30--35 years after immunization with 17D yellow82. Daubeney P Taylor CJ, McGaw J, et al. Immunogenicity and tolerability of a , fever vaccine. Bull World Health Organ 1981;59 : 895—900. trivalent influenza subunit vaccine (Influvac) in high-risk children aged 6 99. Indian Academy of Paediatrics’ : Guidebook on Immunization, published in months to 4 years. Br J Clin Pract. 1997; 51 : 87-90. 2001.83. WHO Position Paper on Influenza vaccines 2005; 80 : 277-288. 100. World Health Organisation. International travel requirements. WHO Geneva. occurs from a source reservoir by direct or indirect means. Non General Prevention and Control 169 Measures - communicable Diseases are diseases, which are not caused by specific microorganisms and are not spread from one person to the other. These diseases may be metabolic, degenerative, Rajesh Vaidya and VK Bhatti neoplastic, mental, allergic, constitutional or accidental. Principles of Prevention and ControlThe fields of preventive medicine and public health share the The practical application and aim of epidemiologicalgoals of promoting general health, preventing specific diseases, investigation and intelligence are to prevent and control theand applying the concepts and techniques of epidemiology entry and spread of diseases in communities. The amenabilityto attain these goals. Preventive medicine seeks to enhance of a disease to prevention and control depends upon thethe lives of individuals by helping them improve their own knowledge of its aetiology, epidemiology, mode of contraction,health, whereas public health attempts to promote health in route and mode of transmission of the aetiological agent, thepopulations through the application of organized community natural history or course of the disease and the incubationefforts. period. The better the knowledge of these factors, the greaterClassification of Diseases is the amenability of the disease to prevention and control. The principles of prevention and control are applicable to nonDiseases can broadly be classified as communicable and - communicable diseases as well as communicable diseases.non - communicable. Communicable Diseases are illnesses However, a better knowledge of the specific aetiological agentcaused due to invasion by specific microorganisms or their and epidemiology makes it easier to apply the principles oftoxic products. The transmission of the agent or its products • 1001 •
  • prevention and control to most communicable diseases. The ever measures can be applied (1 - 3).increasing knowledge of the aetiological and epidemiological The objective in the pre - pathogenic phase is to achievefactors involved in the causation of non communicable primary prevention, firstly through health promotion by sociodiseases has now made the control and prevention of many - economic improvement and providing healthful housing,non communicable diseases possible as well. adequate nutrition, clothing, healthy living & workingNatural History of Disease environments, and secondly by giving specific protectionThe disease process is a dynamic one and is initiated by a through immunization, environmental sanitation, use ofdisturbance of the balance between man and environment. The specific nutrients, protection against occupational hazards,term ‘natural history of disease’ is applied to its course in man. accidents, protection from carcinogens or allergens and soDisease as seen in the hospital is but an episode in the natural on. In the pathogenic phase, secondary prevention aims athistory. The natural history of disease can be seen as having early case detection & treatment as well as uncovering thethree stages : The pre disease stage, the latent (asymptomatic) vulnerable community in the submerged part of the iceberg.disease stage, and the symptomatic disease stage. Another It limits dissemination of infection and prevents occurrence ofclassification of the natural history is the pre pathogenesis secondary cases in the community by reducing the infectiousphase (pre disease phase), the pathogenesis phase (the latent pool. The methods employed in early case detection are :and symptomatic disease stage) and the post pathogenesis (a) Case finding measures - individual or mass or by contactphase. In the pre disease stage the individual possesses tracing.various factors that promote or resist disease, these include (b) Screening surveys.genetic make up, demographic characteristics (especially (c) Surveillance techniques andage), environmental exposures, nutritional history, social (d) Selective examination of high risk groups.environment, immunologic capability and behavioural patterns. In the post - pathogenic phase, disability limitation helps earlyOver time, these and other factors may cause a disease process rehabilitation of the patients. The objective is to halt the furtherto begin. Thus potentially man is always in the midst of disease progress of the disease process by instituting adequate therapybut only when the agent, host and environmental factors, the to limit the disability, prevent further complications throughthree components of the epidemiological triad, interact that the physiotherapy and other techniques of physical medicine. Adisease process is initiated. The pathogenic period begins with rapid rehabilitation prevents the recovered individual fromthe entry of disease agent in the human host as a result of lapsing back into ill health, both physical and mental andthe disease provoking stimuli. If the disease producing process protects the community from social disruption and underway but no symptoms of disease are apparent, the Rehabilitation aims not only at restoring and retraining adisease is said to be in the latent stage. This stage represents patient to live and work within the limits of his disability buta window of opportunity during which detection followed to the maximum of his residual capacity. This is termed as theby treatment provides a better chance of cure or at least of tertiary prevention. The various levels and stages of preventioneffective treatment. Once the agent becomes established and in relation to the periods in the natural history of disease aremultiplies, there are tissues or physiologic changes in the host shown in Table - 1.and the disease process is advanced enough to produce clinicalmanifestations, it is said to be in the symptomatic stage. The Table 1 : Levels of Preventionend result of the disease process may be complete recovery, Period in thechronicity, disability or death. (1 - 3). Levels of Appropriate response natural history preventionLevels of Prevention and Control where appliedThe modern concept of health as ‘the state of complete physical, Primary Health promotion (e.g. Pre -mental and social well being and not merely the absence of prevention encourage healthy lifestyle pathogenesisdisease or infirmity’ warrants the application of preventive and changes, balanced nutritioncontrol measures in the three phases in the natural history of and clean environment)disease discussed above. Prevention of disease means barring Specific Protectionor preventing its initial entry into man or a community while (e.g. immunization,‘control’ means arresting the further progress and propagation Occupational andafter its entry in an individual host or a community at large. automobile safety measuresPrevention entails anticipatory action to remove the possibility Secondary Early Diagnosis & treatment Pathogenesisthat a disease will ever occur. Control entails action to prevent preventioninvasion of the non - affected but exposed individuals in theaffected community. As far as the non - communicable diseases Tertiary Disability limitation Pathogenesisare concerned, some are amenable to simple means of protection prevention (i.e. institute medical or and Post - surgical treatment to limit pathogenesise.g. ill effects of cold and heat, while others require more damage from the disease)intricate and elaborate preventive and control measures. Thenatural history and epidemiology of the non - communicable Rehabilitation (i.e. identifydiseases such as cancer, cardiovascular diseases, accidental and teach Methods toinjuries and occupational diseases, have to be studied in detail reduce physical andto detect vulnerable points or links where preventive or control social disability) • 1002 •
  • Communicable diseases can be classified according to the (a) Early detection of case.aetiological agent or as per the route and mode of transmission. (b) Isolation of the case for the entire period of infectivity.Usually both methods are employed. However, as they have (c) Prompt and effective treatment of case.a definite chain of transmission from the reservoir or source (d) Disinfection of discharges and fomites.through a route upto the susceptible host or recipient, it is more (e) Notification.convenient from the point of view of prevention and control, to (f) Surveillance of contacts.classify them according to their mode of transmission. (g) Mass immunization of the vulnerable community.The later, which also indicates the portal of entry & venue of (h) Investigation of the current outbreak.exit of the infecting organism is as follows : (j) Survey to assess endemicity.(a) Contact transmission - direct and indirect. Immunization : One of the most satisfactory control measures(b) Vehicle transmission - water, food, milk etc. is that it renders the host immune from infectious disease(c) Vector transmission - by arthropods. by an infectious agent. Active immunization is a cornerstone(d) Air-borne transmission - droplet, droplet nuclei and of public health measures for the control of many infectious infected dust. diseases and is considered one of the most cost - effective(e) Animal-borne transmission - zoonoses methods of individual, institutional, and community protection(f) Trans placental transmission from many infectious diseases. Immunization is dealt with in detail in other sections of this book.Control Measures Chemoprophylaxis : Chemoprophylaxis is the preventionThese aim at exterminating the causative agent in its reservoir of infection or its progression to clinically manifest diseaseat the source of its production, its destruction soon after through the administration of chemical substances, includingexit and before it starts its spread by interrupting its path of antibiotics. Chemoprophylaxis may be specifically directedtransmission. Action at these levels requires knowledge of the against a particular infectious agent or it may be non -multifarious factors concerned with the inanimate or animate specifically directed against many infectious agents. The usereservoir or source, various links in the chain of transmission of antibiotics before surgical procedures is an example of nonand different approaches to the recipient susceptible host. The - specific Chemoprophylaxis to prevent wound infections in thepractical measure of control broadly fall under three main postoperative period. Examples of specific Chemoprophylaxisheads. One or all of these measures may be applied according are as follows (9) :to the circumstances of the case (1, 4 - 6). Use of Chemoprophylaxis to prevent development ofControl of Reservoir and Source of Infection : The first link infectionin the chain of causation is the existence of infected persons,cases (clinical or subclinical) or carriers, who constitute the ●● Using chloroquine to prevent malarial parasitaemia.primary source of infection. The general measures of control of ●● The use of silver nitrate, erythromycin or tetracyclinethe reservoir of infection are : instilled into the eyes of a newborn to prevent gonococcal ophthalmia by transmission of Nisseria gonorrhoeae from(a) Early detection of cases. an infected mother during birth.(b) Notification ●● To use of tetracycline, sulfonamides or streptomycin in(c) Isolation close contacts of confirmed or suspected cases of plague(d) Treatment. pneumonia to prevent plague.(e) Quarantine. ●● Use of Rifampicin in close contacts of meningococcal(f) Surveillance. meningitis patients.(g) Disinfection. Chemoprophylaxis to prevent the progression of an infectionBlock the channels of Transmission : This may be achieved to active manifest diseaseby general environmental control, specific control measuressuch as safe water supply, sanitary disposal of sewage & ●● Use of co - trimoxazole or pentamidine to preventother waste products, high standard of food hygiene, vector subclinical latent infection with Pneumocystis cariniicontrol, personal hygiene, proper ventilation, prevention of from progression to clinically manifest pneumocystisovercrowding and dust control. pneumonia in immunosuppressed persons such as HlV - infected individuals.Protection of Susceptible Population : This is carried out ●● Use of pyrimethamine - sulfadiazine - folinic acid toby immunization, chemoprophylaxis, good nutrition, health prevent asymptomatic infants congenitally infected witheducation and personal protection. Toxoplasma gondii from clinically manifest chorioretinitisControl Measures on the Occurrence of an Infectious and other sequelae of congenital toxoplasmosis.Disease Chemoprophylaxis to treat an infectious disease to preventIn public health practice, the action to control the communicable complications of the diseasediseases has to be crystallized into the form of a ‘drill’ which ●● Penicillin to treat streptococcal sore throats caused byshould involve no elaborate thought or preparation because Streptococcus pyogenes group A to prevent acute rheumaticthe etiological agents travel fast and gain momentum and fever.invasive force as they proceed from person to person. The ●● Benzathine penicillin for treatment of syphilis in itsusual sequence of action to control the spread of an infectious primary, secondary, or early latency period to preventdisease is as follows : • 1003 •
  • late manifestations of the disease such as cardiovascular Terminal Disinfection : It means the disinfection of the room syphilis. or premises and their contents after the patient has recovered, died or has been removed elsewhere. This includes the vehicleDisinfection or ambulance, the wheel chairs and stretcher used by theDefinitions (4) patient. This is either ‘local’ or ‘complete’.(a) Disinfection : This means destruction outside the body, of (i) Local : It is the disinfection of the bedding and the bedsheetspecific microorganisms, which cause communicable diseases. occupied by the patient, the walls, floor, furniture including the(b) Disinfectants : These are the agents used for disinfection. kit box, shelf, lockers and their contents and all other surfaces(c) Antiseptics : These are the chemical agents, which inhibit or articles within 2 meters all round the bed.the growth and multiplication of microorganisms, but are (ii) Complete : It is the disinfection of the whole room and allnot strong enough to destroy them completely. A sufficiently its contents.diluted or weakened disinfectant becomes an antiseptic. Prophylactic Disinfection : It means chemical treatment or(d) Disinfestations : This means destruction of undesirable boiling of water, pasteurization of milk, washing of hands andanimal forms, especially arthropod ectoparasites present upon so on.the persons or on domestic animals. The term also includes Classification of Disinfecting Agents : Disinfecting agentsdestruction or avoidance of endoparasites like helminthes, and can be classified as follows :rodent destruction. However, in practice this term mainly refers (a) Natural Agentsto the destruction of ectoparasites like lice, sarcoptes, bugs and ●● Fresh airfleas and their ova and eggs. ●● Sunlight(e) Disinfestants : These are the agents used for disinfestation. (b) Physical AgentsDisinfestants which are specially used against arthopods are ●● Dry Heat : Burning; Hot dry air; Contact heat - ironingcalled ‘insecticides’ and ‘acaricides’ depending on their special ●● Moist Heat : Boiling (with or without chemical agent);values in practice. A number of disinfectants are disinfestants if Steaming - current steam and steam under Pressure.used in adequate strength, but all disinfestants or insecticides ●● Radiation : Ionizing radiation; Ultraviolet rays.are not disinfectants. (c) Chemical Agents(f) Detergents : These are surface cleansers and degreasers. ●● SolidsThey dissolve grease and oily matter and thereby help removal ●● Liquidsof dirt etc., from any material when rinsed or washed with ●● Gaseswater consequently removing the micro - organisms sheltered ●● Aerosolsby grease and dirt. It will not, however, be correct to suppose that the action of(g) Deodorants : These are substances, which mask the any agent is circumscribed in or confined to its particularunpleasant odours without having disinfecting or antiseptic group only. Many disinfectants act both by physical actionpowers. Many disinfectants and antiseptics mask putrefactive and chemical action e.g. soap acts by physically removing theodours also. grease and dirt which shelter the organisms as well as by itsObjective chemical action. Often, in practice, disinfection by chemical agents can be complemented or supplemented by physicalThe object of these processes is to cut the links in the chain agents. Thus clothing can first be soaked in a chemical agent,of the spread of communicable diseases and reduce nuisance. then steamed and finally washed, dried in the sun and ironed.They can, therefore, be considered as supplementary to Similarly disinfection by boiling can be accelerated or aided byenvironmental sanitation. The main objective can be achieved the addition of a chemical or soap.with minimum effort and maximum success if the aetiologyand mode of transmission of each disease is clearly understood, Natural Agentsecology and bionomics of their agents are known, procedures Fresh air dilutes the bacterial content in enclosed places andare rational and specifically directed against the paths of its desiccates micro - organisms by dehumidification. Sunlightspread and not employed merely as placebos to appease the disinfects due to the desiccating effect of its heat rays and theignorant mind. Much time, energy and money are wasted action of its ultraviolet rays. Indeed, this disinfecting poweron disinfection of places which only require ventilation and of the sun has made life possible in the unsanitary tropicalcleansing. Some situations may need only the disinfection and and subtropical environments. Although these agents are slowother may need only disinfestation while a few may need both. in action and frequently unreliable owing to the resistanceAgents and procedures adopted will, therefore, depend upon of certain organisms, they are valuable adjuncts to artificialthe situation as well as nature of the problem. Disinfection is methods. In their absence the saprophytic life of all germs isdiscussed hereunder. prolonged. Thus, during epidemics, cinema theatres act as fociDisinfection Procedures for the dissemination of infection since they usually admit no direct sunlight and little fresh air, whilst respiratory moistureConcurrent Disinfection : It means the disinfection of the delays desiccation.patient himself, of his excreta & discharges & of all articles usedby him or likely to have been contaminated during the course Physical Agentsof his illness, including hands and clothing of attendants. Heat kills ectoparasites and micro - organisms by coagulating • 1004 •
  • their protoplasm. It may be employed in a dry or moist form. or ‘unconfined’ steam; and at pressure in excess of that is calledTo ensure perfect sterility, the former demands a higher ‘pressure’ or ‘confined steam’. The penetration of the pressuretemperature and / or longer exposure than the latter. Heat, steam is no better than the current steam unless the chamberespecially in the moist form, is the only physical agent that is vacuumised. By increasing pressure after creating vacuumis reliably used for artificial disinfection and disinfestation in much higher temperatures can be attained than the 100°Cpreventive medical practice. obtained with current steam. This renders ‘pressure steam’Dry Heat : Burning is a certain and rapid method of disinfecting disinfection more effective. This temperature of steam with aand disinfestation but has only a limited scope. It may, 0.33 kg per square cm rise of pressure above the atmosphere ishowever, be the only available method on active service. For 109°C, at 0.66 kg it is 115°C, at 1 kg 121°C, at 1.33 kg 126°C,example, clothing contaminated by excreta of cholera patients and at 2.66 kg per square cm it goes upto 141°C and so on.may be burnt, or the ground which has been contaminated Chemical Agentsby an anthrax carcass may be disinfected by burning straw Chemical disinfectants may be solid, liquids, gases or aerosols.or oil on the top of it. Contact heat applied by pressing irons Solids act as disinfectants only in solution. A few disinfectantsover clothing may be used to disinfest louse and mites. Hot as powders, act better when dissolved. Gases like sulphurair ovens are used to disinfect glass ware such as petridishes, dioxide and formaldehyde also act as better disinfectants insharp instruments, swabs, dressing, chalk, Vaseline etc. The the presence of adequate moisture. The disinfecting powertemperature of the air in the oven should be maintained at of a chemical depends upon its basic toxicity, concentration,160°C for at least one hour. penetrating power, the medium in which it is to act, the resistanceMoist Heat : Boiling is quite effective in killing all non- of organism required to be killed, the extent to which thesporing organisms, spores being very resistant require boiling organism is protected by organic matter like pus or faeces, andfor an hour and a half. Boiling is largely used for sterilizing the period of contact allowed. The ideal chemical disinfectantinstruments and is useful for disinfecting bed clothing, should be capable of destroying all micro - organisms in allunderwear and similar articles. Blood stains become fixed probable media within half an hour; it should be harmless toby boiling owing to the coagulation of protein; these should, man and higher animals; it should not spoil metals, clothingtherefore, be first removed by soaking in cold soapy water. and other household goods in the concentration usuallyAnother disadvantage of boiling is that it is unsuitable for employed; for convenience of transportation. It should bethick bedding of woolens. The effect of boiling can be enhanced obtainable in a highly concentrated form; it should be capableby adding soap or washing soda to water. Steaming is the most of forming a solution or stable emulsion in water (even inefficient procedure of disinfection and disinfestation. The usual hard water); and finally it should be cheap. The main problemmethod is to expose the infected articles to ‘saturated steam’ in with any disinfectant, however, is the ability of its particles‘current steam’ or ‘under pressure’. to gain contact with bacteria. Capsulated organisms resistRadiation penetration to a marked degree; the organisms locked up evenIonizing Radiation : Gamma radiation or electron beams have in microscopic masses of pus, mucus, faeces etc. are protectedthe advantage of combining great penetrative power with little against most disinfectants unless the time of contact is longor no effect on the object to be sterilized. Bandages, catgut, and the concentration high. Disinfection by chemicals is thusdressing and surgical instruments may be sterilized by ionizing a complex process and the estimation of the true disinfectingradiation. These methods are used commercially. The isotope power of any chemical agent is difficult (7, 8).used is Cobalt 60. Estimation of Germicidal Power : The best known test forUltraviolet Rays : Ultraviolet rays delivered from an apparatus assessing germicidal power is the ‘Rideal - Walker phenolhung in the ceiling at the entrance of special purpose rooms coefficient test’ (RW). In this test the bactericidal power oflike the one in which premature infants are kept or in operation any chemical is compared with that of phenol under identicaltheatres, temporarily disinfect the objects and air entering conditions. This is done by observing the comparativeinside. sterilizing effects of a series of dilutions of the particular chemical and those of phenol against a standard dose ofSteam Disinfection : Steam in contact with boiling water a standard culture of the Lister strain of B. typhosum, in afrom which it is generated has the temperature of 100°C and standard time, at a standard temperature. The RW coefficientis called as ‘saturated steam’. When it comes in contact with is obtained by dividing the highest sterilizing dilution of thecolder objects it immediately condenses and every gram of agent under test by the highest dilution of phenol sterilizingit transfers a latent heat of 537 calories to that object and it in the same time. For example, if cresol diluted 1 : 1200 andcontracts to about 0.0015th of its volume and creates a partial phenol diluted 1 : 100 both produce sterility, say, in 15 min,vacuum. To fill the empty space more steam immediately the RW coefficient of cresol would be 12 i.e. cresol has 12rushes, condenses, releases the latent heat and again creates times the disinfecting power of phenol. The test, however, doesa partial vacuum. Continued repetition of this process achieves not indicate the disinfecting powers of disinfectants underpenetration of steam throughout the mass of the fabric. Heat natural conditions. For example, the mercurial salts show ais thus transferred to the exposed articles until its temperature high RW coefficient but their disinfecting action is arrested byis raised to 100°C. Intimate contact with saturated steam is albuminous materials. Chlorine and potassium permanganateinstantly fatal to all non - sporing organisms. loose a great deal of potency in the presence of organic matter,Steam introduced at atmospheric pressure is known as ‘current’ while others like cresol are only slightly handicapped. Various • 1005 •
  • modified tests, like Chick - Martin’s test, take into account the Commercial Formalin : This is a 40 percent aqueous solutioneffects of extraneous material. However, the unmodified Rideal of formaldehyde. It is a powerful disinfectant, but since it is- Walker test is useful for comparing the germicidal power of very irritating to the hands, eyes and respiratory passages, itdifferent batches of the same disinfectant. is not used as a general disinfectant. It can be used in a 5Solids per cent dilution for disinfecting rooms, tents, huts, or vehicles and for spraying fur - coats, leather, rubber, metal and similarQuicklime : It is used in the burial of animals dead of anthrax; articles which are destroyed by steam. It is used for disinfectingfor disinfecting byres and stables after the occurrence of a case valuables like jewellery, gold and ornaments and watches. It isof anthrax; and as 25 per cent lime wash for walls, ceiling used for preserving tissues required to be sent to the laboratoryand floors of barns, sheds, stables, kitchen, stores and so on. for examination.Slaked lime is used as a deodorant in and around urinals,soakage pits, grease traps; to promote bacterial growth by Gasesretarding acidity in deep trench latrines; and as a final spread Sulphur Dioxide : This gas has been used for fumigationover shallow trenches. against rats in ships and warehouses by the Clayton apparatusChlorine Compounds : Bleaching powder, water sterilizing in which a forced draft from a blower ensures completepowder, sodium hypochlorite and many other kindred combustion of sulphur. By means of pipes led from the generator,substances containing chlorine are used to sterilize water and a concentration of 15 per cent sulphur dioxide is attained invegetables. Bleaching powder in combination with boric acid the air in enclosed places. Sulphur dioxide is not dangerous tohas been used as eusol in surgery. The practice of sprinkling human life, but tarnishes metals, discolours paints, destroysbleaching powder in drains, gutters, latrine pails etc. is wasteful pictures, spoils grain and entails a risk of fire.and useless. FormaldehydeLiquids The gas is generated popularly by pouring liquid formalin overCoal Tar Derivatives : These are obtained by its fractional crystals of potassium permanganate placed in a deep pan. Aboutdistillation and are most widely used of all the liquid 300 ml of formalin and 150 gm of potassium permanganate aredisinfectants. This group includes the aniline dyes, the phenols required for 1000 cft of space. The room is to be kept closed forand the cresols. 6 to 12 hours to allow disinfection.Cresol : It is a dark brown, oily, readily emulsifiable liquid. AerosolsLiquor cresoli fortis, known in the Armed Forces as ‘disinfecting Aerosols are mists released into the air by a special atomizerfluid black’ or simply as cresol, is the most convenient and to disinfect the air in enclosed places. Their action is believedthe most useful general disinfectant. It turns white on dilution to be either due to collision with and absorption by organismswith water and is extremely stable. Liquor cresoli fortis has or condensation of vapour on bacteria - carrying particles,a RW coefficient of 12, but cresol commercially supplied may quickly destroying their bacterial content. The ideal aerosolhave a 10 RW. All containers are marked with the RW of the should be non - irritating to the mucosa, non - toxic even aftercontained cresol so that, by increasing or decreasing the prolonged exposure, invisible, inodorous, non - corrosive, nonamount of dilution with water a final disinfectant liquid of - inflammable, highly bactericidal in low concentrations, andknown strength can be made. For general use, like scrubbing capable of penetrating organisms in dried secretions suchbedsteads the dilution of 1 per cent of RW 10 cresol is enough. as saliva. The most effective and irritating particles have aIn this dilution it is not dangerously toxic if swallowed, is only diameter of less than 1 micron and act at dilution ranging 1mildly irritating to the skin, and possesses high germicidal in 100 million to 500 million volume of air. Aerosol has anpower. For disinfecting bedpans, sputum or excreta a dilution advantage over ultra violet rays in the disinfection of air inof 2.5% of RW 10 cresol is needed. Even in this dilution cresol enclosed places due to their penetration to the remote cornersdoes not destroy fabrics. Although it is rapidly fatal to micro - of rooms. Aerosols so far tried for killing bacteria suspended inorganisms when it comes in contact with them, its penetration the air, fall into three groups viz. hypochlorites, resorcinols andinto a mass of sputum or faeces is not good. Therefore, as a glycols. Insecticide aerosols are effective against insects only.measure of greater safety, a 5 per cent emulsion is used for They contain Freon gas, Pyrethrum and DDT in solutions.disinfecting sputum of tuberculosis cases and faeces of some General Recommendationsexcremental disease cases. Cresol is of great value in thedisinfection of the receptacle after the contained infective To summarize, disinfection of the following must always bematerial has been disposed of. considered in all cases of infectious illness : (a) The patient’s excreta and discharges, linen, utensils andIzal : This is saponified cresol, officially known as ‘disinfecting other articles used by the patient.fluid white (Izal)’. This correct nomenclature should always (b) The quarters occupied by the patient before removal tobe used. It is used in 3 per cent strength for disinfecting hospital and their contents.mouthpieces of telephones and microphones, of RT sets and PA (c) The vehicle in which the patient is conveyed to hospital.sets and the face pieces of respirators. It should not be used for (d) On recovery of the patient, the ward/ room in which theany other purpose. patient was treated and its contents.Dettol : This is chloroxylenol. It is non - irritating but inactivated (e) In the case of carriers or contacts disinfection shouldby organic matter. It is active against streptococci but has no be carried out at the discretion of the officer in medicaleffect on some gram - negative bacteria. charge. • 1006 •
  • Details of Procedures to be followed (v) Latrine Seats : Scrub with 2.5 per cent cresol, which should(a) Concurrent Disinfection : It should always be considered then be allowed to dry on the extremely important. Concurrent disinfection of various Summaryinfective materials in appropriate cases should be carried outas follows : The fields of preventive medicine and public health share the goals of promoting general health, preventing specific diseases.(i) Sputum should be received directly into sputum cups The amenability of a disease to prevention and control depends containing 2.5 per cent cresol and afterwards burnt. upon the knowledge of aetiological agent, the natural history(ii) Nasal, aural and eye discharges should be received directly or course of the disease and the incubation period. The disease into small pieces of linen, cotton or cotton wool, and process is a dynamic one and is initiated by a disturbance immediately burnt. Vaginal or urethral discharges and of the balance between man and environment. The natural those from open sores should also be similarly received on history of disease can be seen as having three stages the pre pads left in situ under dressings and burnt after removal pathogenesis phase (pre disease phase), the pathogenesis at frequent intervals. Handkerchiefs should be soaked in phase (the latent and symptomatic disease stage) and the post 2.5 percent cresol solution before washing with soap and pathogenesis phase. The objective in the pre - pathogenic phase ironing. is to achieve primary prevention. In the pathogenic phase,(iii) Contents of bed pans and urine bottles used by patients secondary prevention aims at early case detection & treatment. suffering from gastro - intestinal diseases as well as In the post - pathogenic phase, disability limitation helps their vomits should be thoroughly mixed with an equal early rehabilitation of the patients. Control Measures aim at quantity of 2. 5 per cent cresol and allowed to stand for 2 exterminating the causative agent in its reservoir at the source hours before throwing down the sluice or water closet or of its production, its destruction soon after exit and before it incinerated. Bed pans and bottles should subsequently be starts its spread by interrupting its path of transmission. The steeped in 2. 5 per cent cresol for15 min to half an hour practical measure of control broadly fall under three main and then washed. heads; these are : Control of Reservoir and Source of Infection(iv) Bed linen, blankets etc. which have been soiled with comprising of Quarantine, Surveillance, Disinfection etc.; infectious discharges, exudates or excreta should be steeped Blocking the channels of Transmission, which may be achieved in 2.5 percent cresol for half an hour before removal from by general environmental control, specific control measures the ward. Special bedding and clothing marked with ‘I’ such as safe water supply, sanitary disposal of sewage etc., are reserved for use of patients suffering from infectious Disinfection means destruction outside the body, of specific diseases. microorganisms, which cause communicable diseases. It(b) Terminal Disinfection : It is complementary to the must always be considered in all cases of infectious illness.concurrent disinfection. All clothing, mattresses, bedding, Disinfection Procedures involves Concurrent Disinfection,linen, personal wear and similar articles within the specified Terminal Disinfection and Prophylactic Disinfection. Theareas for local or complete disinfection as indicated are packed various Disinfecting agents can be classified as Natural Agents,in sacks, or sheets soaked in 2. 5 per cent cresol and removed to Physical Agents and Chemical Agents.the disinfection center for steam disinfection. After disinfecting,the articles of clothing and linen are washed with soap, dried Study Exercisesin the sun and ironed. The floor, the walls and wall - skirting, Long Question : (1) Discuss Natural History of Disease andbedsteads, shelves and any other metal or wooden article, Levels of Prevention and Control of diseases. (2) Classify andother than those which are removed for steam disinfection, are discuss various disinfecting agentsdisinfected in situ by scrubbing or spraying with 2.5 per cent Short Notes : (1) Control Measures used in infectious diseasescresol. After a suitable period of contact with the disinfectant, (2) Chemoprophylaxis (3) Terminal Disinfection (4) Physicalthese may be washed. Agents of Disinfection (5) Rideal - Walker phenol coefficient(c) Some Special Disinfections test(i) Vehicle or Aircraft : Spray or swab with 5 per cent formalin MCQsor 2. 5 per cent cresol followed by washing in hot water with 1. The objective of Prevention and Control measures in thesoda. pre - pathogenic phase is to achieve (a) Primary prevention(ii) Crockery and Cutlery : Steep for half an hour in 2. 5 per (b) Secondary prevention (c) Tertiary prevention (d) Nonecent cresol followed by washing in hot water with soda. of the above(iii) Toys, Book and Papers : If of small value, they may be 2. Broad categories of Disinfecting Agents are all except (a)burnt. If valuable, spray or swab with 5 per cent formalin Natural Agents (b) Physical Agents (c) Chemical Agents (d)followed by exposure to the air for two to three days. Gaseous Agents(iv) Shaving Brushes : Thoroughly wash in 5 per cent soap 3. The temperature of the air in the oven should be maintainedsolution containing one per cent soda ash at 50°C. Allow to at (a) 160°C for at least one hour (b) 170°C for at least onestand in one per cent soda ash at 50°C for half an hour. Soak hour (c) 180°C for at least one hour (d) 190°C for at leastfor half an hour in 10 percent formalin solution at 50°C. Allow one hourto dry in the shade, bristles downwards. • 1007 •
  • 4. Steam introduced at pressure in excess of atmospheric 3. Clark DW, MacMahon B. Preventive and Community Medicine. Little, Brown pressure is known as (a) Current Steam (b) Unconfined and Cmpany, Boston. 2nd Ed, 1981. Steam (c) Saturated steam (d) Confined steam 4. Benneson AS. Control of Communicable Diseases Manual. Official Publication5. Contents of bed pans used by patients suffering from gastro of American Public Health Association, Washington, USA. 16th Ed 1995 : pages i to xxv; 533 - 545. - intestinal diseases should be thoroughly mixed with an 5. Evans AS. Epidemiological concepts (chapter 1). In : Evans AS, Brachman PS equal quantity of ____ per cent cresol and allowed to stand (eds) : Bacterial Infections of Humans : Epidemiology and Control. Plenum for ______ hours before throwing (a) 0.5% for 1hr (b) 0.5%, Publishing Co, New York, USA. 3rd Ed 1998. 2hr (c) 2.5%, 1hr (d) 2.5%, 2hr 6. Evans AS. Epidemiological concepts and methods (chapter I). In : Evans AS Kaslow PA (eds) : Viral Infections of Humans - Epidemiology and Control.Answers : (1) a; (2) d;(3) a; (4) d; (5) c. Plenum Publishing Co, New York, USA. 3rd Ed 1997. 7. Bres P Public Health Actions in Emergencies caused by Epidemics - A practical .References guide. World Health Organisation, Geneva. 1st Ed 1986 : 281 - 284.1. Nelson KE, Williams CM, Graham NMH. Infectious Disease Epidemiology - 8. Pavri K. Standard Biosafety Guidelines. Indian Council of Medical Research, Theory and Practice. Aspen Publishers Inc, Maryland, USA. 1st Ed, 2001. New Delhi, 1991.2. Leavell HR, Clark D. Preventive Medicine for the Doctor in his Community, 9. Robert J, Kim F; Global strategies for control of communicable diseases; In McGraw Hill, New York USA. 1st Ed 1965. Oxford textbook of public health; Detels R, McEven J, Beaglehole R, Tanaka H editors; 4th ed. Oxford University Press, Oxford 2002; 1839 - 61. ●● Acute Diarrhoeal Syndrome Public Health Laboratory : 170 Microbiological Procedures ●● Acute Haemorrhagic Fever Syndrome ●● Acute Jaundice Syndrome ●● Acute Neurological Syndrome Aniruddha Hazra, LS Vaz & Nandita Hazra ●● Acute Respiratory Syndrome ●● Acute Dermatological SyndromeOutbreaks of communicable diseases are public health ●● Acute Ophthalmological Syndromeemergencies which result in increased morbidity and mortality ●● Acute “Systemic” Syndromeand place acute demands on the health system. A surveillance Some of the diseases or pathogens which cause outbreaks arenetwork, including available laboratory support and aimed at enumerated in Table - 1. The list is not exhaustive as manya simplified syndromic surveillance of priority communicable illnesses are restricted geographically or may present withdisease syndromes is important for early detection, control unexpected clinical features.and prevention of outbreaks. Laboratory support is an integralcomponent of any disease surveillance system as well as Planning for Clinical Specimen Collectionoutbreak investigation system (1, 2). Proper collection of an appropriate clinical specimen is the first step in obtaining an accurate laboratory diagnosis of anSyndromic Approach to Investigation of infectious disease. The important considerations for specimenOutbreaks collection and handling are :The underlying principle of the “Syndromic Approach” to ●● Based on the preliminary information on the syndromecommunicable disease surveillance and field investigation of responsible for the outbreak, decide on the possiblean outbreak is that the case definition is based on a syndrome differential diagnosis for further investigations.and not on a specific disease e.g. acute diarrhoeal syndrome. ●● The quantity and nature of the supplies required in theSyndromic surveillance may be the ideal type of public health field such as containers, reagents, rapid kits, transportsurveillance to detect outbreaks whether they are intentional or media etc. and the level of expertise of the personnelnaturally occurring events. These systems monitor for disease required in the field must be considered before setting outby tracking symptom complexes that are representative of most to investigate the outbreak.diseases. The system looks for significant increases in the ●● Keep outbreak investigation kit always ready with thefrequency of a given syndrome against a baseline and provides team (see Table - 2).timely notification of any increase (3). Syndromic surveillance ●● Specimens obtained in the acute phase of the disease,is already being practiced in India e.g. Acute Flaccid Paralysis preferably prior to administration of antimicrobial drugs,Surveillance. are more likely to yield the infective pathogen. ●● Once in the field, ensure proper collection, storage andDisease Syndromes according to Clinical Criteria transport of the specimen in leak - proof containers labeledFor the purposes of routine disease surveillance as well as field properly and accompanied by complete patient informationinvestigation of priority communicable diseases, the syndromes in standard formats.based on clinical criteria are as given below (2) : ●● Universal safety precautions require that workers should • 1008 •
  • Table - 1 : Diseases and pathogens encountered in outbreak investigations Syndrome Diseases / Pathogens Possible Diseases/ Pathogens : (a) Watery Diarrhoea : Cholera, Viral gastroenteritis (Norwalk - like and Rotavirus), Enterotoxigenic E.coli, Giardiasis, Cryptosporidium Acute Diarrhoeal Syndrome (b) Dysentery : Shigellosis, Salmonellosis, Enterohaemorrhagic E. coli, Amoebic dysentery, Campylobacteriosis, Clostridium difficile Other Causes : Ebola and other haemorrhagic fevers* Acute Haemorrhagic Possible Diseases / Pathogens : Dengue haemorrhagic fever and shock syndrome, Malaria, Fever Syndrome Relapsing fever Other Causes : Yellow fever, other arboviral haemorrhagic fevers Acute Jaundice Syndrome Possible Diseases / Pathogens : Hepatitis A to E, Leptospirosis Other Causes : Yellow fever Acute Neurological Syndrome Possible Diseases / Pathogens : Poliomyelitis or Guillain Barré syndrome, Japanese encephalitis, Meningococcal meningitis, Leptospirosis, Malaria Other Causes : Rabies and other lyssaviruses, Tick - borne encephalitis viruses, Trypanosomiasis Acute Respiratory Syndrome Possible Diseases / Pathogens : Influenza, Diphtheria, Streptococcal pharyngitis, Bacterial pneumonias including : Pneumococcal pneumonia, Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma, Respiratory anthrax, Pertussis, Pneumonic plague, Legionellosis Other Causes : Hantavirus pulmonary syndrome, Respiratory Syncytial Virus (RSV), Q fever, SARS Acute Dermatological Possible Diseases / Pathogens : Chickenpox, Measles, Rubella, Typhus, Cutaneous anthrax Syndrome Other Causes : Monkeypox, Parvovirus B19 Acute Ophthalmological Possible Diseases / Pathogens : Epidemic adenoviral keratoconjunctivitis, Haemorrhagic Syndrome conjunctivitis (adeno - or enteroviral), Trachoma (Chlamydia trachomatis) Acute “Systemic” Syndrome Possible Diseases / Pathogens : Dengue fever and other Arboviral fevers, Viral Hepatitis, Typhoid fever, Malaria, Leptospirosis, Brucellosis, Anthrax, Bubonic Plague, Typhus Other Causes : Hantaviral disease, Lassa fever, Lyme disease, , Relapsing fever, Rift Valley fever, Yellow fever, Borreliosis * NOTE : Ebola and other haemorrhagic fevers may initially present as bloody diarrhoea. If such aetiology is suspected, refer to “Acute Haemorrhagic Fever Syndrome” for appropriate specimen collection guidelines. Source : Adapted from (2) handle all clinical specimens as if they were infectious. of communicable disease. Venous blood is to be collected for●● Ensure that appropriate bio - safety and waste management identification of the pathogen in culture and serum for PCR, measures are followed. specific antibodies, antigens, or toxins and viral pathogens.●● Inform the receiving laboratory about the tentative date For specific antibodies, paired sera are required to be collected. and time of arrival of the specimen. Finger prick method is to be used for slides for microscopy●● The aim should be to reduce the time to confirmation so or for absorption onto special filter paper discs for analysis. that timely public health actions can be taken. Only, a few Whenever possible, blood specimens for culture should be initial cases need confirmation. Rest with similar clinical taken before antibiotics are administered to the patient. manifestations should be treated as confirmed. Handling and transportCollection & Transportation of Clinical Specimens ●● Blood culture bottles and blood sample tubes should beThe appropriate clinical specimens that should be collected in transported upright and secured in a screw cap containervarious disease syndromes for the laboratory confirmation of or in a rack in a transport box. Cushion or suspend bottlesthe pathogen responsible for the outbreak are summarized in during transport over rough terrain to prevent lysis of redTable - 3. cells. They should have enough absorbent paper aroundThe general guidelines for collection and transportation of them to soak up all the liquid in case of a spill. If theclinical specimens are given in the successive paragraphs. specimen will reach the laboratory within 24 hours, most bacterial pathogens can be recovered from blood culturesBlood Specimen Collection : Blood and separated serum are transported at ambient temperature.the most common specimens taken to investigate outbreaks • 1009 •
  • Table - 2 : Proposed Components of the Outbreak Investigation Kit Generic Outbreak Investigation KitDisposable storage vials (5ml & 10 ml) Rubber bandsDisposable sample collection vials Ziploc plastic bagsVacuutainer (plain and EDTA) Absorbent material (tissue paper, cotton wool, newspaper)Cryovials Filter paperSyringes and needles disposable (5ml & 10 ml) Vaccine carrier with ice - packsTuberculin syringes and needles Dry ice packsLancets Glass marking penSlides, cover slips and slide holding box Specimen labelsTourniquet Adhesive tapeGloves ScissorsMasks (triple layer surgical mask) Scalpel/ bladeDisposable caps SpatulaGoggles ForcepsDisposable gowns Loop holderSwabs & gauze pads Parafilm (small rolls)Povidone iodine 10% Leak proof screw capped containersIsopropyl alcohol 70% Pasteur pipettes/ pipettes and pipette aids (rubber teats)Band - aid Sodium hypochlorite concentrate (4%)Spirit lamp/ gas lighter Hand disinfectantMatch - box Stationary (writing pads, pens, pencils, erasers, sharpeners etc.)Test tube rack CalculatorCentrifuge tubes Torch with spare batteries/ rechargeable batteriesPuncture proof discarding bags (disposable) OT test kitThermometers Water sampling kitsTongue depressors (disposable) Distilled water (100ml)CSF collection kit Normal saline in dropper bottleStool culture bottle Magnifying glassThroat swabs Patient register bookBlood culture bottles Laboratory request formsViral transport medium (VTM) Epidemiological survey formatsCary Blair medium/ Stuart’s transport medium Epidemiological reporting formatsRapid diagnostic kits (e.g. H2S method kit for water testing, latex agglutination Outbreak investigation guide/ modulefor meningitis, card test for dengue etc.) wherever possibleSharps disposal boxes Laptop Computer with caseSelected Entomological & Vector Dissection EquipmentAspirator and flashlight for indoor/ outdoor mosquito collection WHO susceptibility kit for adult & larvae with reagentsKit for outdoor mosquito collection Bioassay kitLadle bottles for keeping larvae, strainer, dropper, trays and funnel net for Charts/ synoptic keys for identification of vectorswellsWhite bed sheet to spread on floor Pyrethrum spray with flit gunDissecting microscope Staining equipment & materialDissection needle Filter paperPetridishes Mosquito netSlides, coverslips Physiological salineNote : Any other item, as per the requirements of the outbreak.Source : Adapted from (1, 2, 4, 5) • 1010 •
  • Table - 3 : Clinical Specimens needed and Laboratory Tests to be Performed in Various Disease Syndromes Laboratory Tests To Be Done Syndrome Specimens Required Field / Peripheral Lab Zonal/ Referral LabAcute Diarrhoeal ●● Freshly passed ●● Hanging drop / Earlier tests, plusSyndrome* stool Iodine & wet mount ●● Faecal leukocytes*(including ●● Rectal swab of stool specimen ●● Toxin detection test for cholerasuspected food- ●● Faecal swab ●● Parasite : Macro- toxin (if kit available)borne outbreaks) ●● Environmental and microscopic ●● MPN test for bacteriological sampling especially examination examination of water water for available ●● OT test for available ●● Stool culture for enteropathogens; chlorine and chlorine in water sensitivity testing, if available bacteriological ●● Rapid H2S test for ●● Serotyping examination bacteriological ●● Referral of samples for further If food-borne outbreak examination of water characterization and testing, if required is suspected: Refrigerate all remaining food items for further testing if necessary.Acute ●● Blood ●● Peripheral smear for Earlier tests, plusHaemorrhagic ●● Blood smear malarial parasite ●● Viral : Culture; Antigen detection;Fever Syndrome ●● Serum ●● Total leukocyte count Antibody levels (IgM/ IgG) ●● Post - mortem ●● Differential ●● Parasitic : Demonstration of pathogen tissue specimens leukocyte count ●● Yellow fever : post-mortem liver biopsy (e.g. skin ●● Platelet count ●● Referral of samples for further biopsy and/ or ●● Rapid diagnostic characterization and testing, if required liver biopsy) tests for diagnosis of dengue feverAcute Jaundice ●● Blood ●● OT test for available Earlier tests, plusSyndrome ●● Serum chlorine in water ●● MPN test for bacteriological ●● Urine ●● Rapid H2S test for examination of water ●● Environmental bacteriological ●● Urine microscopy sampling especially examination of water ●● Rapid tests for detection of water for available ●● Dark ground antibodies to Leptospira chlorine and microscopy of ●● Blood for Leptospira : Culture; Serotyping bacteriological peripheral blood ●● Yellow fever : post-mortem liver biopsy examination for leptospirosis ●● Viral : Culture; Antigen detection; ●● Rapid test kit for Antibody levels (IgM/ IgG) diagnosis of viral ●● Referral of samples for further hepatitis (HbsAg characterization and testing, if required antigen detection and anti-HCV)Acute ●● Vesicular fluid ●● Giemsa stain for Earlier tests, plusDermatological ●● Crust Tzanck smears ●● Electron microscopy of vesicle fluidSyndrome ●● Serum (scrapings of floor ●● Bacterial or Viral : Culture; Antibody ●● Lesion swab of vesicles) levels (IgM/ IgG); Immunofluorescence (vesicular exudate) ●● Tzanck smears (vesicle floor scrapings)Acute ●● Conjunctival swab ●● Giemsa stain for HP Earlier tests, plusOphthalmological and smear bodies (C.trachomatis) ●● Chlamydial : Microscopic examination,Syndrome ●● Throat swab Culture, Antigen detection ●● Serum ●● Viral : Antigen detection Antibody levels (IgM/ IgG) • 1011 •
  • Table - 3 (Contd..) Laboratory Tests To Be Done Syndrome Specimens Required Field / Peripheral Lab Zonal/ Referral LabAcute Neurological ●● CSF ●● Gram stain of CSF Earlier tests, plusSyndrome ●● Blood & CSF cytology ●● MPN test for bacteriological ●● Serum ●● India ink mount examination of water ●● Stool of CSF ●● Latex agglutination tests for detection of ●● Urine ●● Dark ground capsular antigen in CSF (if kit available) ●● Throat swab microscopy of ●● Rapid tests for detection of ●● Post - mortem peripheral blood antibodies to Leptospira tissue in suspected for leptospira ●● CSF for bacterial culture (if rabies (e.g. corneal ●● OT test for available facilities available) impressions, chlorine in water ●● Blood for bacterial culture brain tissue, skin ●● Rapid H2S test for ●● ELISA for JE virus biopsy from neck) bacteriological ●● Poliomyelitis : Stool culture, Antigen ●● Environmental examination of water detection, Intratypic differentiation sampling especially ●● Rabies: Demonstration of Negri bodies water for available by Seller’s stain in post-mortem tissue, chlorine and virus isolation, fluorescent antibody test bacteriological ●● Referral of samples for further ●● examination characterization and testing, if requiredAcute Respiratory ●● Throat swab ●● Gram stain of throat Earlier tests, plusSyndrome ●● Per-nasal swab / swab and sputum* ●● Bacterial culture (and antimicrobial nasopharyngeal ●● Albert’s stain of susceptibility, wherever applicable) swab (for throat swab* from throat swab, sputum, blood suspected ●● Inoculation of blood ●● Toxin detection tests for bacteria pertussis) culture bottles and ●● Viral : Culture; Antigen detection; ●● Sputum swabs in appropriate Antibody levels (IgM/ IgG) ●● Bronchoalveolar transport media ●● Serotyping lavage/ tracheal * For diphtheria & ●● Referral of samples for further aspirate other organisms characterization and testing, if required ●● Blood for culture ●● Serum ●● Urine (for Legionella)Acute “Systemic” ●● Blood smears (thick ●● Peripheral smear for Earlier tests, plusSyndrome and thin) malarial parasite ●● Widal test ●● Blood Serum ●● Rapid diagnostic tests ●● Weil-Felix reaction ●● Bubo aspirate for diagnosis of malaria, ●● Stool culture for enteropathogens ●● Post-mortem tissue dengue fever and typhoid ●● Blood culture and sensitivity specimens (e.g. liver (Typhidot test) ●● Viral : Culture; Antigen detection; Antibody levels biopsy) ●● Platelet count (IgM/ IgG) ●● CSF (if meningeal ●● Total leukocyte count ●● Serotyping signs present) ●● Differential leukocyte ●● Yellow fever: post-mortem liver biopsy ●● Urine count ●● MPN test for bacteriological examination of water ●● Stool ●● Gram stain (bacteria) ●● Referral of samples for further characterization ●● Clotted blood (5 or 10 ●● Bubo aspirate: stab deeply and testing, if required ml) into Cary Blair transport ●● Tracheal or lung medium aspirate ●● OT test for available chlorine in water ●● Rapid H2S test for bacteriological examination of water • 1012 •
  • ●● If serum will be required for testing, separation from blood never be refrigerated as many of the relevant pathogens do should take place as soon as possible, preferably within not survive at low temperatures. 24 hours at ambient temperature and ideally as soon as ●● CSF specimens for virology do not need transport medium. clot formation occurs. If the specimen will not reach a They may be transported at 4 - 8°C for up to 48 hours or laboratory for processing within 24 hours, serum should at - 70°C for longer periods. be separated from blood prior to transportation. Sera may Eye Specimen Collection : Conjunctival and corneal swabs be stored at 4 - 8°C for up to 10 days. If testing is delayed and smears are the usual specimens collected. Strict aseptic for a long period, serum samples may be frozen. technique is essential when collecting and processing these●● If separation on site is not possible, or is inadvisable for specimens. safety reasons, the blood sample should be stored at 4 - 8°C Method of collection of conjunctival swabs : Clean the skin and protected from excessive vibration while transporting. around the eye with a mild antiseptic. Moisten a swab in Unseparated blood samples should not be frozen. sterile saline and roll over the conjunctiva in a circular manner.Method of Preparation of Blood Films : Blood films should Insert the swab into a sterile screw - cap tube containing thebe made by trained personnel. If this is not possible, they can appropriate transport media for bacteria e.g. Stuart’s transportbe spread from heparinized or EDTA blood specimens sent to media.the laboratory. Handling and transportSteps for making thick films for microscopy ●● Specimens for detection of bacterial pathogens are●● Label the slide with patient identification number and transported at ambient temperature in appropriate bacterial name. transport medium.●● Disinfect and prick site with a lancet. ●● Specimens for viral detection are transported at 4 - 8°C in●● Touch one or more large drops of blood onto the centre virus transport medium. of the slide making sure that the slide does not touch the ●● Microscopic slides are air dried and transported at ambient skin. temperature in a slide box.●● Spread the blood in a circle about 1 cm in diameter Faecal Specimen Collection : Stool specimens are most useful using the corner of another glass slide or with a needle. for microbiological diagnosis if collected soon after onset of Thickness of the film should be such that it is possible to diarrhoea (for viruses < 48 hours and for bacteria < 4 days), read newsprint through it. and preferably before the initiation of antibiotic therapy. If●● Air dry the film in a horizontal position. Do not dry the film required, two or three specimens may be collected on separate by heating over a flame or other heat source. days. Stool is the preferred specimen for culture of bacterial,Steps for making thin films for microscopy viral, and parasitic diarrhoeal pathogens. Rectal swabs showing●● Label the slide with patient identification number and faeces may also be used from infants. In general, rectal swabs name. are not recommended for the diagnosis of viruses.●● Touch another drop of blood to the glass slide about 2 cm Method for collecting a stool specimen from one end making sure that the slide does not touch ●● Collect freshly passed stool, 5ml liquid or 5g solid (pea - the skin. size), in a container●● Place the slide horizontally on a flat surface. ●● Label the container.●● Hold the side of a second clean glass slide (the spreader) on to the center of the specimen slide and move it back Method of collecting a rectal swab from an infant until it touches the drop and the blood spreads along its ●● Moisten a swab in sterile saline base. ●● Insert that swab tip just past the anal sphincter and rotate●● At an angle of about 45°, move the spreader firmly and gently steadily across the specimen slide and air dry the film ●● Withdraw the swab and examine to ensure that the cotton quickly. Do not dry over a flame or other heat source. top is stained with faeces●● Fix the dried film by dipping the glass slide in methanol or ●● Place the swab in sterile tube/ container containing the other fixative for a few seconds and air dry. appropriate bacterial or viral transport mediumHandling and Transport : Air dried and/ or fixed films are ●● Break off the top part of the stick without touching thetransported at ambient temperature, preferably within 24 tube and tighten the screw cap firmlyhours of specimen collection. They must not be refrigerated. ●● Label the vial with patient’s name type of specimen andThick and thin films are usually kept in separate slide boxes. date of collection. Handling and transportCerebrospinal Fluid (CSF) Specimen Collection : Thespecimen must be taken by a physician or a person experienced ●● Stool specimens should be transported at 4 - 8°C. Bacterialin the procedure. Standard lumbar puncture tray is needed. CSF yields may fall significantly if specimens are not processedis used in the diagnosis of viral, bacterial, parasitic, and fungal within 1 - 2 days of collection. Shigella are particularlymeningitis. sensitive to elevated temperatures. If the laboratory is at a distance, samples should be transported in Cary BlairHandling and transport medium in cases of diarrhoea. In cases of suspected cholera●● CSF specimens for bacteriology are transported at ambient samples should be transported in Alkaline peptone water temperature, generally without transport media. They must or Thiosulphate Citrate Bile salt Sucrose Agar. (TCBSA). • 1013 •
  • ●● Specimens to be examined for parasites should be mixed overgrowth by commensal oral flora. For transit periods up to with 10% formalin or Polyvinyl Alcohol; three parts stool 24 hours, transport bacterial specimens at ambient temperature to one part preservative. Transport at ambient temperature and viruses at 4 - 8°C, in appropriate media. in containers sealed in plastic bags. Collecting Specimens of Skin Lesions : For mostBedside Microscopy : In cases of suspected cholera “darting dermatological conditions, diagnosis may be established onmotility” can be demonstrated if a slide and microscope are the basis of physical examination and clinical history withoutavailable. A hanging drop preparation of the sample is ideal for the collection of diagnostic specimens.making this diagnosis. Method of collectionMethod of preparation of Hanging Drop 1. Vesicular or vesiculo - pustular rash (for diagnosis of●● Take a clean glass slide & make a thin ring of plasticine viral infections) (good quality) and apply it over the slide. ●● Pierce roof of fluid - containing vesicle with sterile lancet.●● Thickness of the ring should not be more than 1mm, so ●● Swab fluid with two sterile swabs. Try to get a good amount that there is no difficulty in focusing the slide with 40X of fluid onto the swab. high power objective. ●● Take a clean labeled microscope slide and make a smear●● Take a clean coverslip & put on small drop of liquid culture with one swab in the central area of the slide. Make two over the coverslip with the help of a small sized inoculating slides if possible. The slides should be left to dry in air. loop (about 1mm diameter). ●● Place the second swab directly into virus transport●● Put the slide containing plasticine ring over the coverslip medium. containing the drop of liquid culture without touching the 2. Crusting stage drop and then invert the slide so that the drop hangs.●● Put the condenser low and focus the slide in low power ●● Gently ease off crust with a lancet or scalpel and a pair of (10X objective) and try to focus the edge of the drop. disposable forceps.●● Examine next in high power i.e. 40X objective for checking ●● Take 5 - 10 crusts; place them in a plastic screw - cap vial. the motility against the stationary background. Make sure the lid is tightly closed. ●● If cutaneous anthrax is suspected, the vesicular fluid underRespiratory Tract Specimen Collection : Preferably, specimens the eschar is a better diagnostic specimen than a piece ofshould be taken within the first 3 days after onset of symptoms the eschar.for most respiratory infections. Specimens are collected fromthe upper or lower respiratory tract, depending on the site of 3. Aspiration of abscessesinfection. Upper respiratory tract pathogens (viral and bacterial) ●● Aspiration of abscesses should only be performed byare found in throat or nasopharyngeal specimens. Lower experienced personnelrespiratory tract pathogens are found in sputum specimens. ●● Disinfect the skin overlying the abscess/bubo with 70% isopropyl alcoholMethod of collecting a throat swab : Hold the tongue down ●● Aspirate the fluid from the abscess with a sterile needle andwith the depressor. Use a strong light source to locate areas syringe. Only enough fluid to perform the diagnostic testsof inflammation and exudate in the posterior pharynx and is required to be sent even though all may be aspirated.the tonsillar region of the throat behind the uvula. Rub the ●● Transfer the aspirate aseptically into a sterile tube witharea back and forth with a Dacron or calcium alginate swab. transport medium.Withdraw the swab without touching cheeks, teeth or gums andinsert into a screw - cap tube containing transport medium. Handling and transport : Specimens for bacteriological analysis should be transported in Stuart’s or Amies transport medium.Method of collecting per - nasal and post - nasal swabs (for Swabs for suspected viral pathogens should be transportedsuspected pertussis) in virus transport medium. If processing takes longer than 2●● Seat the patient comfortably, tilt the head back and insert hours, bacteriology specimens can be maintained at ambient the nasal speculum. temperature for 24 hours. Specimens for virus isolation may●● Insert a flexible calcium alginate/ Dacron swab through be refrigerated at 4 - 8°C, and transported to the laboratory as the speculum parallel to the floor of nose without pointing rapidly as possible. upwards. Alternately, bend the wire and insert it into the Urine Specimen Collection : Give the patient clear instructions throat and move the swab upwards into the nasopharyngeal to pass urine for a few seconds, and then to hold the cup in the space. urine stream for a few seconds to catch a midstream clean catch●● Rotate the swab on the nasopharyngeal membrane a few urine sample. This should decrease the risk of contamination times, remove it carefully and insert it into a screw - cap from organisms living in the urethra. tube containing transport medium.Method of collecting sputum : Instruct patient to take a deep Handling and transport : Transport to the laboratory withinbreath and cough up sputum directly into a wide - mouth 2 to 3 hours of collection. If this is not possible, do not freeze,sterile container. Avoid saliva or postnasal discharge. Minimum but keep the specimen refrigerated at 4 to 8°C. Keeping thevolume should be about 1 ml. specimen refrigerated will decrease the risk of overgrowth of contaminating organisms.Handling and transport : All respiratory specimens exceptsputum are transported in appropriate bacterial/ viral media. Post - mortem Specimen Collection : Strict precautions,Transport as quickly as possible to the laboratory to reduce including respiratory protection from aerosolized particles, must be taken when carrying out post - mortem specimen • 1014 •
  • collection in communicable disease outbreaks. Collect the requests to each relevant laboratory as a ‘line listing’.specimens as soon as possible, since viral titres decline whilebacteria multiply rapidly after death. Thorough post - mortem Transport of Clinical Specimens Using theexaminations may only be accomplished by experienced medical Triple Packaging Systempersonnel. Prior experience and training is also advised even The specimen should be transported in a basic triple packagingfor the minimal collection of specimens from cadavers. system (see Fig.1) to ensure biosafety, transient temperatureHandling and transport and quality of the specimen (2, 8). EPI vaccine carriers or●● Fixed specimens can be stored and transported at ambient other commercially made containers may be used as a tertiary temperature. container to transport specimens. Vaccine Carriers that have●● Tissue specimens for isolation of bacterial pathogens can been used for specimen transport must never be reused for be transported at ambient temperature in transport media carrying vaccines. Gloves should be worn at all times when for up to 24 hours. handling the specimen.●● Transport tissue specimens for isolation of viral pathogens Triple Packaging System for Transport of Clinical in viral transport medium or sterile saline at 4 - 8°C for 24 Specimens - 48 hours. For longer periods, freeze and store at - 70°C. See Fig. - 1, legend for the figure as follows :●● If rabies is suspected and brain samples are collected, freeze unfixed specimens immediately after collection. Formalin - Fig. - 1 : Triple packaging system for transport of clinical fixed samples are also useful and may be transported at specimen ambient temperature.Labeling and Identification of SpecimensAdequate labeling ensures that the laboratory results can belinked to the correct patient. Each patient should be assigneda unique identification number. This unique identificationnumber and the patient name should be present on specimens,epidemiological data forms, and the laboratory transmittalforms. Glass slides for microscopy must be labeled individually,using glass - marking pencil. This should not interfere with thestaining process.Label on specimen : The label may be a piece of paper attachedto the specimen container. Alternatively, the information maybe written directly on the specimen container with the followingessential details : Patient Name _____________ Identification No. ___________ Specimen Type _________ Date & Time of Collection ______Note : Do not attach the label to the top of the specimencontainer.Laboratory Investigation FormA laboratory request form must be completed for each specimenand contain information to interpret the necessary tests. Thismay include : a Primary container b Secondary container (sealed plastic bag holding primary●● Patient information : Age (or date of birth), sex, complete container) address c Sealed plastic bag holding case investigation form●● Clinical information : Date of onset of symptoms, clinical d Absorbent material such as cotton wool and immunization history, risk factors or contact history e Four ice packs. Place ice packs at the bottom of the box where relevant, antimicrobial drugs taken prior to specimen and along the sides. Then place an ice pack on top of the collection etc. specimen. If the specimen should remain cold, but not●● Laboratory information : Acute or convalescent specimen, frozen, wrap the specimen in paper or cardboard to prevent other specimens from the same patient. direct contact with ice packs.For a large number of patients, it may be practical to submit the Points to Remember During Transport of Clinical Specimens ●● Avoid repeated thawing and freezing of specimens. ●● Freeze the specimen only if transport is assured at -20ºC. ●● Store and transport all specimens at 2 - 8ºC, except CSF obtained from suspected cases of pyogenic meningitis. • 1015 •
  • f Insulating material Staining For Malarial Parasiteg Tertiary container (outer carton of double - ply corrugated ●● Prepare thick and thin smear from malaria case on a glass cardboard or plastic) slide.h Address labels on tertiary container ●● Dehaemoglobinize the thick smear by placing the film in ai Diagnostic specimen label on tertiary container vertical position in a glass jar containing distilled water forCommon Staining Techniques Used in Field 5 minutes. When film becomes white, take it out and dry in upright position.Investigations of Disease Outbreaks ●● Fix the thin smear in methanol for 15 minutes.Gram Staining : This is the most extensively used differential ●● Dilute the Geimsa’s stain solution, one part with 9 parts ofstain that divides bacteria into two major groups. Those which boric buffer pH 7.2.retain crystal violet dye after treatment with iodine and alcohol ●● Immerse the smears in this stain for 1 hour.appear purple or bluish purple and are designated as Gram ●● Wash the smear in buffer solution.positive. Those bacteria which lose the crystal violet show the ●● Blot dry.colour of the counter stain employed. The commonly - used ●● Examine the slide under oil immersion of microscope.counter stain is safranin which gives a pink/ red colour to Observation : Examine thin film first. If no parasite is foundbacteria and these organisms are labeled as Gram negative. then only examine thick film. If parasite are seen in the thickSmear prepared from throat swab, nasal swab, ear discharge, film but the identity is not clear, thin film should be re -pleural fluid, CSF, urethral discharge, sputum, centrifuged examined more thoroughly so as to determine the nature ofdeposit of urine, bacterial culture, vaginal discharge etc. can be infection.stained by this method. Thin film examinationReagents ●● Area of the film examined should be along the upper and●● Crystal violet (primary stain) lower margins of tail end film as parasites are concentrated●● Gram’s iodine (mordant) over there.●● Acetone Iodine/ Acetone alcohol (decolouriser) ●● A minimum of 100 fields should be examined in about 8●● Safranin solution (counterstain) - 10 minutes.Staining procedure The following stages of the parasite can be observed in a●● Make a thin smear on a clean glass slide, dry it in air and peripheral blood thin smear : fix by passing through flame of a burner. ●● Ring, trophozoite, schizont and the gametocytes in case of●● Cover the smear with crystal violet, keep for one minute. Plasmodium vivax.●● Wash the slide with water, then cover with Gram iodine ●● The infected erythrocytes are usually enlarged in P. vivax. and let it stand for one minute. ●● However, in case of P. falciparum infection, it is mainly the●● Wash the slide with water. ring stages which are seen and occasionally schizonts and●● Decolour with acetone / alcohol, rocking the slide gently for trophozoites. During the late stages of the disease even 10 - 15 seconds till the violet colour comes off the slide. crescent shaped gametocytes can be seen in the peripheral●● Wash with water immediately. blood.●● Counterstain with safranin. Let the counterstain stand for Observations on thick smear 30 seconds. ●● Only elements seen are leucocytes and malarial parasites.●● Wash with water, blot dry and examine under the oil ●● Morphology of malarial parasites is distorted. immersion lens of a microscope. ●● Species of parasites cannot be identified.Albert’s Staining : Albert’s staining is most common staining Appearance in thick filmtechnique used for examining the specimens, suspected to have ●● Trophozoites appear as streaks of blue cytoplasm withCorynebacterium diphtheriae; which are gram positive rods of detached nuclear dots. The ring forms are rarely seen.varying length and often containing volutin (polyphosphate) ●● Schizonts and gametocytes, however, retain their normalgranules which appears purple black against the light green appearance and are seen if present in the smear (thecytoplasm of the bacillus. The appropriate specimens are throat pigments are seen more clearly).swab/ nasal swab smear or bacterial culture from suspectedcases of diphtheria. C. diphtheriae appear as bacilli with dark Negative (India Ink) Staining : Negative staining is sometimesgreen protoplasm and purple black granules, other bacteria will a very useful technique for demonstrating the capsulatedstain light green. organisms like Meningococcus/ Pneumococcus/ Cryptococcus, the causative agents of meningitis. After the staining procedureProcedure for staining the background will appear dark. The bacterial cells will be●● Make a smear, dry in air, and fix by heat. stained purple. The capsule (if present) will appear clear against●● Cover slide with Albert’s stain-I & leave for 4 - 6 minutes. the dark background.●● Wash in water and blot dry. Procedure●● Cover the slide with Albert’s stain-II and allow to act for 1-2 minutes. ●● Using a Pasteur pipette, put a drop of CSF sediment●● Wash, blot dry and examine under oil immersion lens of (obtained after centrifuging the CSF at 2000 - 3000 rpm microscope. for 10 - 15 min) or any other appropriate specimen on a clean glass slide. • 1016 •
  • Table 4 : Priority communicable diseases and their laboratory diagnosis Disease Sample Laboratory Test Result Chickenpox Vesicle scrapings Tzanck smear of scrapings from Multinucleated giant cells & intranuclear inclusion bodies. base of vesicles Electron microscopy (EM) Herpes virus particles in fluid. Antigen or nucleic acid detection Varicella-zoster virus detected. Culture Human fibroblasts cell line used. Confirmed by Immunofluorescence using Monoclonal Ab on cell line (time consuming). Immunofluorescence (IF) Viral antigens detected. More labour intensive but more sensitive than EM. Blood /Nasal / throat swabs Virus isolation Culture by inoculating into human amnion, fibroblast, HeLa cells, Vero cells. Serum Immunofluorescence and capture Detection of Varicella Zoster Virus (VZV)-specific IgM. RIA or EIA Throat gargle fluid ELISA & PCR Detection of Varicella Zoster Virus antigen/ nucleic acid. Measles Throat and Nasopharyngeal (NP) Giemsa-stained smears Multinucleated giant cells. secretions Viral isolation Measles virus is present in acute stage in throat and nasopharyngeal secretions. It is also excreted in urine intermittently for at least 7 days after rash onset. At least one• 1017 • specimen for virus isolation, along with blood for serology is required. Serum Immunofluorescence Viral antigens detected (more labour intensive). Serological tests (ELISA) Capture ELISA for measles IgM (reference gold standard test). Measles specific IgM antibodies detected using IgM capture ELISA. A single blood specimen collected 3 to 28 days after rash onset is usually satisfactory for IgM serology. Indirect ELISA for measles IgM. For IgG serology, the first (acute) sample is obtained as soon as possible after appearance of rash and no later than 7 days afterwards. The second (convalescent) sample is collected 10 to 20 days after the first sample. Both paired sera tested simultaneously.
  • Disease Sample Laboratory Test Result Rubella Blood (within 2-3 days of onset of Virus isolation Viral culture is labour intensive. symptoms); Nasopharyngeal washings / throat garglings Serum Serological tests (ELISA) IgM & IgG antibodies (IgM alone indicates current acute infection & IgG indicates past infection or vaccination). Rubella- specific antibodies are detectable in the IgM fraction within two days after onset of the rash, or even earlier. The titre of rubella specific IgM antibodies remains higher than those in the IgG fraction for about five days after the appearance of the rash. Immunofluorescence for Rubella The test is useful from about one to two days before the rash, specific IgM antibodies prior to the appearance of a detectable level of HI antibody, to about four weeks afterwards. Influenza Nasopharyngeal aspirate/ washings Immunofluorescence (Direct Demonstration of viral antigen. using saline; lower nasal swab/ Fluorescent Antibody Staining) nasopharyngeal swab/ throat swab; Reverse transcriptase PCR Detection of nucleic-acid sequences. bronchoalveolar lavage Serum (Acute phase serum and Haemagglutination inhibition Rise in antibody titres in paired (acute and convalescent) serum convalescent phase serum) samples. Nasopharyngeal aspirate, washings Viral culture Virus identification by immunofluorescence of cell cultures or using saline, lower nasal swab/ Haemagglutination-Inhibition (HI) assay of cell culture medium nasopharyngeal swab/ throat swab; (supernatant).• 1018 • sputum; bronchoalveolar lavage Diphtheria Throat swabs Albert’s stain Corynebacterium diphtheriae appears as green rods containing green-black volutin granules. The rods may be arranged in rows or in V-formation or joined at angles, giving the appearance of Chinese characters. Culture of throat swab/ swab Bacilli showing cuneiform (Chinese letter) arrangement on Gram from membrane at any other site stain with metachromatic granules (seen in smears stained with (inoculated on Loeffler’s serum methylene blue or Albert’s stain). slope) M e n i n g o c o c c a l CSF Gram stain Meningococci appear as gram-negative intracellular diplococci disease (inside polymorphs). Ag detection by Latex Agglutination/ Demonstration of meningococcal antigen. Immunofluorescence Molecular Diagnosis by PCR Detection of meningococcal DNA sequences. Blood Culture Isolation of meningococci.
  • Disease Sample Laboratory Test Result Avian Influenza Nasopharyngeal aspirate; Immunofluorescence; Enzyme Rapid antigen detection. Nasopharyngeal swabs; Nasal immunoassay (for influenza A washings; Throat swab nucleoprotein) Serum (Acute phase serum and Serology IgM & IgG antibodies (IgM alone indicates current acute infection convalescent phase serum) & IgG indicates past infection or vaccination). Virus culture Virus identification by immunofluorescence of cell cultures or Haemagglutination-Inhibition (HI) assay of cell culture medium (supernatant). Polymerase chain reaction and Real- Detection of nucleic-acid sequences. time PCR assays. SARS (new strain Throat and nasal swabs; rectal swab; Reverse transcription PCR for viral Detection of nucleic-acid sequences. of corona virus) nasopharyngeal aspirate; throat RNA washings and urine Serum (paired samples) ELISA; Indirect Demonstrates rising antibody titres. Immunofluorescence Viral isolation Vero E6 cell monolayers examined daily for diffuse, refractile, rounding cytopathic effects characteristic of SARS-CoV confirmed on staining by the indirect immunofluorescence technique and RT-PCR. Hepatitis A Serum Antibody detection: ELISA Anti HAV IgM & IgG antibodies (IgM alone for current/acute• 1019 • infection & IgG for past infection). Hepatitis B Serum ( Acute & Chronic phase sera) Serological demonstration of viral HBsAg in blood; anti-HBc IgM indicates recent infection; anti HBc markers IgG indicates remote infection;HBeAg denotes high infectivity. Blood in sterile container (serum) Viral loads by Real time PCR & HBV Molecular analyses to detect HBV DNA are rarely required and DNA by PCR should be performed only in a well-defined clinical context. Hepatitis C Serum ELISA Antibody detection. Serum Viral loads by Real time PCR & HCV HCV RNA in blood detected. Molecular analyses to detect HCV RNA by PCR RNA are rarely required and should be performed only in a well- defined clinical context. Hepatitis E Serum ELISA Anti HEV IgG & IGM antibodies (IgM in the bile & faeces during incubation period). Whole blood in EDTA/ Serum HEV RNA by PCR Molecular analyses to detect HEV RNA are rarely required and should be performed only in a well-defined clinical context.
  • Disease Sample Laboratory Test Result Leptospirosis Serum Detection of group specific anti Specific IgM antibody detection confirms recent infection. Leptospiral IgG & IGM antibody by latex agglutination test and a sensitive test such as ELISA Detection of species specific anti Live Leptospira strains seen to be immobilized and agglutinated Leptospiral IgG & IGM antibody by patient’s serum. using Microscopic Agglutination Test (MAT) is the Gold Standard CSF/ Urine/ Body fluid (freshly passed Dark ground illumination Motile leptospira. urine sample alkalinized to pH 9 with Sodium bicarbonate) Blood in EDTA; Urine (alkalinized) Culture in EMJH medium. Isolation Motile leptospira seen in dark ground illumination. facility available at Leptospira Surveillance Centres Cholera Faeces (rice water) OR Rectal swab Hanging Drop preparation -darting Demonstration of Vibrio cholerae. moistened with transport medium OR motility Lubricated catheter to pass sample Dark ground illumination or phase Demonstration of immobilization by antiserum (may be directly into screw capped container contrast observed under a simple microscope too using a hanging drop OR Strips of blotting paper soaked in preparation) stool and sent in plastic envelopes OR Bedside inoculation onto media Isolation of cholera vibrios (in a Non lactose fermenting colonies; catalase and oxidase positive• 1020 • stool specimen or sample by rectal with a positive cholera red reaction. Serogrouping into O1 and swab) after enrichment for 6 hours. non O1, biotyping into Classical and El Tor strains and serotyping Venkatraman liquid medium(Holding into Ogawa, Inaba and Hikojima can be done at centres where medium) or Cary - Blair medium facility exists. Strains may be dispatched to a higher centre for (Transport medium); Alkaline confirmation. peptone water or Monsur’s media (Enrichment media)
  • Disease Sample Laboratory Test Result Typhoid Blood for culture Blood culture ( highest positivity if Pale non-lactose fermenting colonies of Salmonella. Organisms sent in first week of fever) are motile, indole & urease negative, ferment glucose and mannitol but not lactose. Strains may be biochemically differentiated on the basis of H2S and acid with/without gas production. Serum (in first week) Widal Test Baseline titres. Serum (in second week and thereafter) Widal Test Demonstration of O & H agglutinins in a paired sera Significant one time titres: - O agglutinins >100 H agglutinins >200 OR Four fold rise in titres in paired sera Faeces Stool enrichment with Selenite F Black colonies with metallic sheen on Wilson Blair media. or Tetrathionate broth followed by faeces culture on a selective medium like Wilson Blair media or DCA. Urine Urine culture ( 2nd & 3rd week) Salmonella shed intermittently so requires repeated sampling. FOOD POISONING Salmonella Faeces & food specimens Gram staining Salmonella are gram-negative organisms. Culture Isolation of salmonella from food macerated in sterile saline. Botulism Faeces & food specimens Gram staining of food samples Gram positive sporing bacilli. Isolation from faeces & food Food is macerated in sterile saline and filtrate is inoculated• 1021 • specimens into mice/ guinea pigs intraperitoneally after protection with polyvalent antitoxin. Serum, autopsied liver tissue Toxin detection Retrospective diagnosis by demonstration in patient’s serum. Cl. perfringens Faeces & food specimens Isolation on selective media Heat resistant Cl. perfringens Type A isolated. B.cereus Faeces & food specimens Isolation on selective media (MYPA Isolation of B.cereus which produces lecithinase & ferments - Mannitol egg Yolk Phenol red glucose but not mannitol. Polymyxin Agar media) Enteropathogenic Faeces Plated on Blood agar & MacConkey Tested for agglutination by polyvalent & monovalent EPEC O E coli (EPEC) media antisera Enterotoxigenic Faeces In Vivo test (ligated rabbit ileal Demonstration of enterotoxins. E coli (ETEC) loop) In Vitro test (Tissue culture test, Serological test) Genetic test (DNA Probe)
  • Disease Sample Laboratory Test Result MALARIA P. falciparum Blood Smear (Thick smear and thin Blood Smear for Malaria parasite Detection of malaria parasite & characteristic morphological P. vivax smear) changes in the RBCs to detect the plasmodium species. The P. malariae thick smear after dehaemoglobinisation is used for screening for P. ovale malaria parasite and thin smear for speciation. Blood in double oxalate, EDTA Quantitative buffy coat Detection of malaria parasite, both ring form (trophozoite) and vacutainer; finger prick blood directly gametocytes using the fluorescent microscope. collected in the QBC capillary tube Whole blood in EDTA; blood from finger Rapid diagnostic tests(RDT) or PfHRP2 or pLDH detection using monoclonal antibody against prick Immunochromatographic tests one of these antigens. PfHRP2 persists to be positive even after therapy unlike pLDH. Both these tests should be supplemented with microscopy. Serum Serology for antibody detection by This does not necessarily detect current infection. ELISA Whole blood Polymerase Chain Reaction for Detection of relevant gene sequence. detection of gene or Multiplex PCR for all four species Dengue (4 Acute phase serum; plasma; Buffy Virus Culture Isolation of dengue virus. serotypes DEN coat (leucocytes) washed to remove 1,2,3,4) antibodies; CSF; autopsy tissue from• 1022 • fatal cases especially liver, spleen, lymph node. Serum (three serial serum samples Serological Tests like Dengue IgM Early dengue-IgM in 3-5 days of onset of infection, later a rise during acute, convalescent phase & &IgG ELISA Dengue IgM &IgG Rapid in IgG is seen. Test should be repeated at least once after 2-3 late convalescent phase, respectively) strip Test(ICT) days if negative at first. Autopsy tissue or serum Viral antigen detection Demonstration of dengue virus antigen in autopsy tissue or serum samples by Direct fluorescence or viral nucleic acid detection using Immunohistochemistry (IHC). Whole blood Platelet count Thrombocytopenia (platelets less than or equal to 100,000/ mm3). Haematocrit Evidence of plasma leakage documented >20% increase of PCV for age and sex.
  • Disease Sample Laboratory Test Result Japanese CSF, autopsied brain in saline, whole Virus isolation can be performed Viral culture. Encephalitis blood (collected in initial 2-3 days) using Vero, LLCMK2 and PS cells Group B Autopsy tissue in saline or serum Viral antigen detection Demonstration of JE virus antigen in autopsied brain tissue by Arbovirus samples fluorescence antibody test. (flavivirus) Serum PCR-based tests Nucleic acid detection. Serological testing using IgM-capture Detects specific IgM. ELISA or using Haemagglutination Inhibition Tests (performed at specialized centres) Trachoma Conjunctival scrapings Giemsa-stained C. trachomatis inclusion bodies or Halberstaedter Prowazek C. trachomatis (HP) bodies seen. Culture : Clinical specimens are Confirmed by demonstration of cytopathic effects in cell lines. inoculated onto McCoy cells, HeLa cell lines (Tissue culture) Poliomyelitis Stool or nasopharyngeal washings Viral isolation in cell lines Demonstration of cytopathic effects in cell line. Serum Serology Neutralizing antibodies. Cerebrospinal fluid (CSF) Cell count in cytology and Increased number of white blood cells (10 to 200 cells/mm3, biochemistry primarily lymphocytes) and a mildly elevated protein from 40 to 50 mg/100 ml.• 1023 • Plague Whole blood; sputum; aspirates from Confirmed by Gram stain/ culture Gram stain shows bipolar staining Gram negative bacilli. Culture buboes, body fluids or tissues of Y. pestis confirmed by specific phage lysis of lawn cultures. Serum (Acute phase serum and Passive haemagglutination testing Four-fold change in antibody titre to the F1 antigen in paired convalescent phase serum) of paired serum samples serum specimens, confirmed by F1 antigen haemagglutination inhibition test. Note : Blood should be collected in a sterile container for serology. If serum needs to be transported across a long distance, it should be centrifuged and separated into a sterile container and sent on ice (4ºC), preferably with a human courier. Any material for culture should be sent in saline and not in formalin. 24-hour samples are not acceptable for culture. Tissue sent for culture or antigen detection tests should not be allowed to dry and may be placed into a sterile container with some saline in it. A second sample for serology (paired sera) is a must for evidence of rising titres.
  • ●● Add another smaller drop of Indian Ink (about 1/3rd the Study Exercises size of CSF drop) on the slide. Mix the two drops thoroughly Short Notes : (1) Syndromic surveillance (2) Laboratory using a match stick. diagnosis of Acute Jaundice Syndrome (3) Preparation of●● Put a coverslip on the resultant mixture. peripheral blood smear for diagnosis of malaria (4) Hanging●● Examine the preparation under the microscope first using drop preparation (5) Triple packaging system for transport of 40x objective and then 100x objective to look for the clinical specimens characteristic encapsulated cells. MCQsInterpretation of Laboratory Tests 1. The underlying principle of “Syndromic Approach” toThe interpretation of laboratory tests for some priority communicable disease surveillance is that the casecommunicable diseases are listed in Table - 4. definition is based on (a) a specific disease (b) a group of diseases (c) a syndrome (d) None of the aboveSummary 2. The possible pathogens in Acute Diarrhoeal Syndrome areOutbreaks of communicable diseases are public health all except (a) Vibrio cholerae (b) Rotavirus (c) Leptospiraemergencies which result in increased morbidity and mortality. (d) CryptosporidiumA surveillance network, including available laboratory support 3. Albert’s staining is used for the demonstration ofaimed at a simplified syndromic surveillance of priority metachromatic granuels in (a) Plasmodium falciparum (b)communicable disease syndromes is important for early Corynebacterium diphtheriae (c) Chlamydia trachomatisdetection, control and prevention of outbreaks. The underlying (d) Clostridium difficileprinciple of the “Syndromic Approach” to communicable disease 4. Serum should be separated from blood prior tosurveillance and field investigation of an outbreak is that the transportation if the time taken to reach the laboratorycase definition is based on a syndrome and not on a specific is (a) > 6hours (b) > 12 hours (c) > 18 hours (d) > 24disease. When investigating outbreaks, it is important to keep hoursan open mind about possible causes, and ensure that adequate Answers : 1(c); 2 (c); 3 (b); 4 (d).clinical samples are taken to eliminate any uncertainty. Propercollection of an appropriate clinical specimen is the first step Referencesin obtaining an accurate laboratory diagnosis of an infectious 1. World Health Organization. Prevention of epidemics. WHO Country office, New Delhi, India, 2006.disease. The specimen should be transported in a basic triple 2. World Health Organization. Guidelines for the collection of clinical specimenspackaging system to ensure biosafety, transient temperature during field investigation of outbreaks. WHO, Geneva, 2000. Publication No.and quality of the specimen. WHO/CDS/CSR/EDC/2000.4. 3. University of South Florida. Syndromic Surveillance. (cited 2008 Sep 25).The effective control of a communicable disease outbreak Available at upon early detection and reporting of suspect cases, 4. National Institute of Communicable Diseases. Manual of laboratoryadequate knowledge regarding collection of appropriate clinical techniques for district public health laboratories. NICD, Delhi, 2004. 5. National Institute of Communicable Diseases. Check - list for central rapidspecimens, their transportation under optimum conditions and response team for disease outbreak investigation including avian influenza.specific diagnostic tests to facilitate rapid confirmation of the NICD, Delhi, 2008.causative agent responsible for the disease outbreak. 6. World Health Organization. Manual of basic techniques for a health laboratory, 2nd ed. WHO, Geneva, 2003 : 199 - 201. 7. National Institute of Communicable Diseases. Laboratory support in disaster situations. Monthly Newsletter of National Institute of Communicable Diseases, New Delhi, India, CD Alert 2005 March; Vol.9 : No.3. 8. The African Field Epidemiology Network. Outbreak investigation laboratory guidelines. AFENET, 2007. • 1024 •
  • personal protection and vector control to community - based 171 Malaria bioenvironmental interventions (1, 2). Epidemiology Rajesh Vaidya Global : Malaria is endemic in over 105 countries and is responsible for over 300 - 500 million clinical cases and overMalaria is the most important parasitic disease of man. It is a million deaths annually. Out of around 3000 deaths a day,defined as an acute and chronic disease caused by obligate over 90% are in Sub Saharan Africa. Out of the 11 countries ofintracellular protozoa of the genus Plasmodium. Four species the South East Asian Region (SEAR) of WHO, 10 are malariaof Plasmodium are capable of infecting humans : Plasmodium endemic. Maldives has no endogenous transmission sincemalariae (Laveran, 1881), Plasmodium vivax (Grassi and Feletti, 1984. SEAR accounts for 30% of global morbidity and 8% of1890), Plasmodium falciparum (Welch, 1897) and Plasmodium global mortality due to malaria. An estimated 82.8% of theovale (Stephens, 1922). The parasites are transmitted to humans total population here is at risk of malaria. Out of the totalby female Anopheles mosquitoes. The illness that ensues is population, 41.5% are at moderate to high risk, 41.7% are athighly variable but is generally characterized by paroxysms of low risk while the remaining 16.8% are considered free fromfever and chills, anaemia and splenomegaly (1). Approximately the risk of malaria.5% of the world population is infected by malarial parasites India : Malaria transmission occurs in almost all areas ofand the disease is responsible for nearly one million deaths India except areas above 1800 meters, above mean sea level.annually world wide. Although drugs against malaria have 95% of the Indian population lives in malaria risk prone areas.been available for many years, widespread drug resistant Malaria in India is unevenly distributed. In most parts of Indiastrains of parasite and insecticide resistant strains of mosquito about 90% malaria is unstable with relatively low incidencevectors have made its treatment and control difficult. but with a risk of increase in cases in epidemic form every 7 toHistory 10 yrs. This depends on the immune status of the population and the breeding potential of the mosquitoes, rainfall beingFew diseases have had a greater impact on human social and the leading cause of malaria epidemic as it increases vectoreconomic development than malaria. Fossil mosquitoes have density. In North - East India, efficient malaria transmissionbeen found in geologic strata 30 million years old. Malaria was is maintained during most months of the year. Intermediatelinked with poisonous vapours of swamps or stagnant water level of stability is maintained in the plains of India in theon the ground since time immemorial. The disease was finally forests and forest fringes, predominantly tribal settlementsnamed by the Italians in the 18th century malaria (from the in eight states (Andhra Pradesh, Gujarat, Jharkhand, MP ,Italian mala “bad” and aria “air”). The first references to periodic Chattisgarh, Maharashtra, Orissa and Rajasthan). The reportedfevers can be found in early Hindu and Chinese writings. In the incidence is between 2 and 2. 5 million cases annually withfifth century B.C., the Greek physician Hippocrates described some fluctuations every year for last over two decades. 44.3%the clinical manifestations and some of the complications of of these are due to Plasmodium falciparum.malaria. Agent : The causative organisms of the disease malaria areThe first major breakthrough in understanding the etiology of protozoa of the genus Plasmodium, family Plasmodiidae,the disease was in 1880, when Laveran, a French army surgeon suborder Haemosporidiidae, order Coccidia. There are 120 orin Algeria, described exflagellated gametocytes of Plasmodium so species of Plasmodium which are recognized taxonomicallyfalciparum in a fresh blood film from a patient with malaria. by the presence of two types of asexual division : schizogony,Even after that, transmission remained a mystery until in the vertebrate host; and sporogony, in the insect vector.the 1880s. It was only in 1897, that Ronald Ross, a British Within the vertebrate host, schizogony is found both withinarmy surgeon in India, conclusively established the major erythrocytes (erythrocytic schizogony) and in other tissuesfeatures of the life cycle of plasmodia by a careful series of (exo - erythrocytic schizogony). However diseases in humansexperiments in naturally infected sparrows. During the 20th is caused by four parasites which have, in the recent past, beencentury, progress was made in vector control technology and in described as follows (3) :the development of potent synthetic antimalarial compounds.One of the major landmarks was in 1955 when, encouraged by ●● Plasmodium vivax : Benign Tertian, Simple Tertian,the high potency, low toxicity, ease of administration and low Tertiancost of DDT and other residual insectides, the World Health ●● Plasmodium malariae : QuartanOrganization (WHO) launched a worldwide program of malaria ●● Plasmodium falciparum : Malignant Tertian (MT),eradication. This program was hindered by the development Subtertian, Aestivo - Autumnal, Tropical, Perniciousof DDT resistance in the mosquito populations and by the ●● Plasmodium ovale : Ovale Tertian.development of chloroquine resistance in some strains of The cyclopropagative life cycle of the Plasmodium occurs in twoPlasmodium falciparum. Soon it was realized by the world stages (Fig - 1). The sexual stage starts with the ‘gametogony’that “Malaria” was here to stay and subsequently in 1978, the in the human host and progresses through ‘sporogony’ in theWorld Health Assembly changed its focus from eradication to mosquito. The asexual stage starts with injection of sporozoitesmalaria control based on the assessment of localized control by the infective mosquito into the human host and progressespotential. This ranged from reducing morbidity and mortality through three phases of ‘schizogony’. The broad outline ofwith chemotherapy to comprehensive campaigns stressing events occurring during the two stages is as follows (4). • 1025 •
  • Fig. - 1 : Life Cycle of malaria (Plasmodium vivax) (5)Sexual Cycle in Mosquito (Sporogony) Asexual Cycle in man (Schizogony)The vector female anopheline mosquito ingests male and Pre - erythrocytic Phase : Sporozoites injected by infectivefemale gametocytes from a malarial subject. In the mosquito’s mosquito into human body circulate for approximately 30stomach the male gametocyte becomes rounded, its chromatin minutes and thereafter leave the peripheral blood. Fullysplits into 5 to 8 particles, which get arranged along its edge. matured, pigmentless schizonts, containing cryptozoites areCytoplasm around each chromatin particle elongates into a seen in the parenchymal liver cells. The cycle lasts approximately‘flagellum’ and together with chromatin separates from the 8 days in Plasmodium vivax, 6 days in Plasmodium falciparummain mass as a ‘microgamete’. Female gametocyte extrudes and 9 days in Plasmodium ovale. On full maturity of the pre -polar bodies and becomes a ‘macrogamete’ ready to be fertilized. erythrocytic schizonts, the liver cells rupture and cryptozoitesSyngamy of microgamete and macrogamete forms ‘zygote’. enter the erythrocytes.This becomes an elongated, motile ‘ookinete’. Penetrating the Erythrocytic Phase : The earliest intracorpuscular form ofstomach wall, this comes to lie under its external basement parasite is the ‘trophozoite’ which has a fine ring of cytoplasmmembrane, becomes rounded & develops into ‘oocyst’. As the with a small chromatin dot. It grows in the parasitised RBCoocyst matures, it increases in diameter and rapidly undergoes that becomes pale and, in some species, enlarged or distorted.division and subdivision to form a large number of haploid The haemoglobin changes into haemozoin pigment and is seensporozoites (varying from new hundreds to thousands). Finally, in the cytoplasm of the parasite as black or brown granules.the oocysts rupture, releasing the elongated sporozoites into Fully developed trophozoite fills the RBC and undergoesthe body cavity, majority of which find their way into the segmentation. The chromatin divides into a number of particlessalivary glands. Sporozoites injected in human host through which migrate towards the periphery. The cytoplasm aroundthe mosquito bite start schizogony. each particle separates off forming merozoites; the pigment concentrates in the centre of the RBC. This is called ‘rosette’ or ‘schizont’. The parasitised RBC eventually ruptures releasing • 1026 •
  • merozoites which enter other RBCs repeating the asexual cycle. in order to infect a mosquito, the blood of a human carrier mustEach asexual cycle is completed in 48 hours in Plasmodium contain at least 12 gametocytes per mm3 and the number offalciparum, Plasmodium vivax and Plasmodium ovale and in female gametocytes must be more than the male gametocytes.72 hours in Plasmodium malariae. Period of Communicability : The human case of malariaGametogony : After a few cycles of erythrocytic schizogony, becomes infective to mosquito when mature, viable gametocytesmale and female gametocytes appear in the blood. The female develop in the blood of the patient in sufficient density.macrogametocyte has a dense and deeply staining cytoplasm Host : All ages are equally affected. Children are usuallyand a small compact nucleus, while the male microgametocyte effective carriers of gametocytes. Gender does not affect thehas a less dense and faintly staining cytoplasm and a relatively incidence or severity of malaria infection and disease per se,large and diffuse nucleus. The gametocyte of Plasmodium vivax but because they are often related to frequency of exposure (viais large and round filling the enlarged RBC, the gametocyte occupation, social behaviour, and migration). Racial immunityof Plasmodium falciparum is sausage or crescent shaped. against one or more species of malaria parasite has beenGametocytes remain within the corpuscles until taken up by observed in certain parts of the world. Negroes with sickle cellthe mosquito or their final disintegration. trait have been found to be relatively immune to PlasmodiumPersistent Tissue Phase (Exoerythrocytic phase) : After the falciparum infection. Individuals lacking the Duffy a and bestablishment of blood infection the initial tissue phase (pre blood group determinants (Duffy - negative blood type) are- erythrocytic phase) disappears completely in Plasmodium resistant to infection with Plasmodium vivax. Economic Statusfalciparum, whereas in Plasmodium vivax, Plasmodium is inversely related to incidence of malaria mainly because ofovale and Plasmodium malariae it continues in the form of a poor housing. Ill ventilated and poorly lighted houses providepersistent tissue phase in the liver. These exoerythrocytic forms ideal resting places for mosquitoes.never arise from the merozoites of erythrocytic schizogamy and Acquired Immunity : In general, populations in endemicare now considered responsible for relapses of vivax, ovale and areas continuously exposed to infected mosquitoes developquartan malaria. immunity to malaria illness and, to a lesser degree, to malariaMost of the severe morbidity and mortality in malaria is infection. Clinical manifestations, asexual parasitemia, and thecaused by Plasmodium falciparum. When compared with the production of gametocytes are all reduced by acquired immunity.three other species infecting humans, the incubation period is In areas with high falciparum transmission, newborns will beshortest, the exoerythrocytic schizonts release 2.5 to 20 times protected during the first few months of life presumably byas many merozoites, and the duration of untreated infections maternal antibodies transferred to them through the the least. By contrast, Plasmodium malariae has the longest As these antibodies decrease with time, these young childrenduration of untreated infection and sometimes is almost a become vulnerable to disease and death by malaria. If theycommensal infection in adults. Certain characteristics of the survive to an older age (2 to 5 years) they will have reached afour species are given in Table - 1 (6). protective semi - immune status.Reservoir and Source : For human plasmodia the only reservoir Environment : Optimal conditions for malaria transmissionis a malaria case. In some parts of Africa, Chimpanzees may act occur when the temperature is between 20°C and 30°C and theas reservoir of Plasmodium malariae. The source of infection mean relative humidity is at least 60%. Sporogony does notis a malaria case with adequate number of mature viable occur at temperatures below 16°C or at temperatures highergametocytes circulating in the blood. It has been estimated that than 33°C. Water temperatures regulate the duration of the Table 1 : Selected characteristics of four species of Human Malaria P. falciparum P. vivax P. ovale P. malariae Exocrythrocytic cycle (days) 5-7 6-8 9 12 - 16 Erythrocytic cycle (hr) 48 42 - 48 49 - 50 72 Usual incubation period in days (range) 13 (12 - 17) 17 (16 - 18) 28 (18 - 40) 12 (9 - 14) or longer or longer or longer Earliest appearance of gametocytes (days) 10 3 7 ? Secondary exoerythrocytic cycle none present present none Average merozoites per tissue schizont 40,000 10,000 15,000 2000 Size of tissue schizont 60 µm 45 µm 70 µm 45 µm Duration of untreated infection (yr) 1-2 1-4 1-4 3 - 50 Average parasitemia (per mm) 20,000 or greater 10,000 9000 6000 Minimum duration (and range) of 9 (9 - 22) 8 (8 - 16) 12 (12 - 14) 16 (16 - 35) sporogony cycle in mosquito in days Usual periodicity of febrile attacks (hr) none 48 48 72 • 1027 •
  • aquatic breeding cycle of the mosquito vector. A high relative the country.humidity increases mosquito longevity and therefore increases Density : For effective transmission of malaria in a locality,the probability that an infected mosquito will survive long the mosquito vector must attain and maintain a certainenough to become infective. Malaria infections and malaria density. This is called critical density and it varies from oneillness are often more common during rainy seasons because mosquito to another and also under different environmentalthe number of breeding sites is increased and because female conditions. Anopheles culicifacies needs a very high density foranophelines survive longer when the humidity is high. However, transmission of malaria.too much rainfall can be deleterious to vector larvae and Longevity : A mosquito must live for at least 10 days after anpupae by washing them away, thus decreasing transmission; infective blood meal, to complete the development of malariaand prolonged droughts may be associated with increased parasites.transmission if they reduce the size and flow rates of largerivers sufficiently to produce suitable breeding sites. Tropism : Some mosquitoes like Anopheles fluviatilis prefer human blood and are called anthropophilic. Others likeThe proximity of human habitation to breeding sites directly Anopheles culicifacies preferably feed on animal blood and areinfluences vector - human contact and, therefore, transmission. called zoophilic. This preferential feeding habit is called tropism.The stability of breeding sites is influenced by water supply, It has obvious bearing on the transmission of malaria.soil, vegetation, etc. Irrigation schemes, dams, and other man- made changes can alter the pattern of malaria transmission Biting Behaviour : Some vector mosquitoes bite at or soon(6). after dusk, others either during late night or early hours of the morning. However, some species may be active at two differentVectors : There are 56 species of anopheline mosquitoes in periods during the same night.India but only six are regarded as primary vectors and anotherthree or four as secondary or local vectors. As per the global Resting Habits : A female mosquito rests either indoorsclassification, India is covered by 3 out of the 12 epidemiological (endophilic) or outdoors (exophilic) after a blood meal forzones. The present distribution of malaria vectors in these maturation of its eggs. Knowledge of these habits is necessaryzones is given below (7) : for organizing antiadult measures. The common resting places are either human dwellings, cattle sheds or mixed dwellings.Northern and Peninsular India Flight Range : The range of flight and dispersion varies from(a) Main Vectors : Anopheles culicifacies, Anopheles stephensi, one vector to another. Knowledge of this is important forAnopheles fluviatilis. planning control measures. Some have a short flight range(b) Local Vectors : Anopheles sundaicus, Anopheles annularis e.g. Anopheles dirus, Anopheles annularis and Anophelesand Anopheles varuna. fluviatilis. The species with flight range upto Two km distanceEastern India are Anopheles culicifacies and Anopheles stephensi. AnophelesMain Vectors : Anopheles dirus, Anopheles sundaicus, sundaicus may fly upto 8 or 10 km.Anopheles philippinensis, Anopheles minimus, Anopheles Mode of Transmission : The most prevalent mode ofmaculatus. transmission of malaria is through the bite of the infectedAndaman and Nicobar Islands female anopheles mosquito. The mosquito is infective only if the sporozoites are present in its salivary glands. However,(a) Main Vectors : Anopheles sundaicus Malaria can also be transmitted by intravenous or intramuscular(b) New Vectors : Anopheles dirus, Anopheles maculatus and injection of infected blood or plasma in an otherwise healthyAnopheles tesselatus. person. The parasite can stay alive for nearly two weeks at -A number of characteristics of vector mosquitoes play an 4°C in bottled blood. Rarely transmission can also occur fromimportant role in the epidemiology of malaria (8, 9). These infected mother to the newborn.include breeding habits, vectorial capacity, density, longevity, Epidemiologic Terminology (10)tropism, biting behaviour, and flight range. A number of descriptive terms are used to describe the malariaBreeding Habits : The breeding habits of mosquitoes show a situation in a given area. Stable endemic Malaria is said tolot of variation. Hence, vector mosquitoes tend to be confined to be present when natural transmission occurs over many yearscertain geographical areas only. Anopheles fluviatilis breeds in and there is a predictable incidence of illness and prevalenceslow moving water, seepages and terraced rice fields. Anopheles of infection. Transmission is generally high and epidemicssundaicus prefers to breed in brackish waters. The main urban are unlikely. Unstable malaria describes the situation wherevector Anopheles stephensi commonly breeds in wells, cisterns malaria occurs in settings where transmission rates vary fromand over head tanks. Tanks, pools, burrow pits and ditches year to year and collective immunity is low. Epidemics are moreare the preferred breeding spots for Anopheles annularis and likely in this setting. Autochthonous (indigenous) malaria isAnopheles philippinensis while Anopheles dirus is usually malaria contracted locally. Secondary cases are those derivedfound breeding in forest pools, streams and slit trenches. from imported cases and are referred to as introduced malaria.Vectorial Capacity : Why only certain species and not others The term induced malaria is used for malaria infections acquiredact as vectors is not exactly known. A complexity of factors by blood transfusion, shared needles, intentional inoculation,determines the vectorial status of a mosquito. Certain new or laboratory accidents.species are emerging as secondary vectors in different parts of A number of parameters are commonly used to classify • 1028 •
  • malaria in an area. Malaria incidence is the number of new sweats, headaches, nausea, vomiting, body aches and generalinfections or cases detected per time unit (e.g. annually) per malaise. Physical findings may include elevated temperature,unit of population (e.g. per 1000). Malaria prevalence is the perspiration, weakness, enlarged spleen etc. In Plasmodiumtotal number of cases or infections at one point in time, per falciparum malaria, additional findings may include mildunit of population. When the measure used is microscopically jaundice, enlargement of the liver and increased respiratoryproven parasitemia, malaria prevalence and parasite rate are rate.synonymous. Severe Malaria : Severe malaria occurs when PlasmodiumAnnual Parasite Incidence : Number of new parasitologically falciparum infections are complicated by serious organ failuresconfirmed cases per 1000 population per year. This tool of or abnormalities in the patient’s blood or metabolism. Theevaluation has been introduced under the National Programme, manifestations of severe malaria include cerebral malaria,which measures not prevalence but the incidence of malaria and with abnormal behaviour, impairment of consciousness,based on this, areas are divided into high & low risk zones. seizures, coma, or other neurologic abnormalities, severeInfant Conversion Rate : Fraction of parasitologically negative anaemia due to hemolysis, hemoglobinuria, pulmonaryinfants becoming positive per time unit. edema or Acute Respiratory Distress Syndrome (ARDS), which may occur even after the parasite counts have decreased inSpleen Rate : Proportion of individuals in a stated age range response to treatment, abnormalities in blood coagulation andwith enlarged spleens. The degree of endemic malaria is thrombocytopenia, cardiovascular collapse and shock.determined by examination of a statistically significant sampleof a population and is assessed and classified as follows : Relapse : In cases of Plasmodium vivax and Plasmodium ovale infections, recurrent attacks could be due to re - activation ofHypoendemic : Spleen rate or parasite rate of 0 to 10% in hypnozoites in the liver. This can occur any time after 30 to180children between the ages of 2 and 9. days of the primary attack. The relapses have the characteristicMesoendemic : Spleen rate or parasite rate of 11 to 50% in symptoms of malaria. Splenomegaly may be a prominentchildren between the ages of 2 and 9. feature in these patients. Such long - term relapses commonlyHyperendemic : Spleen rate or parasite rate consistently over occur in patients who have either not taken primaquine or50% in children between the ages of 2 and 9. Adult spleen rate taken incomplete also high. Recrudescence : In Plasmodium falciparum and PlasmodiumHoloendemic : Spleen rate or parasite rate consistently over malariae infections, the parasites can remain in the blood for75% in children between the ages of 2 and 9. Adult spleen rate months or even years and cause recurrent symptoms fromis low and the transmission index is high. time to time. In falciparum malaria, such recrudescence canPathophysiology occur within 28 days of the primary attack and may indicate partial resistance to chloroquine. However, treating every caseA detailed description of pathophysiology is beyond the scope of of recurrent Plasmodium falciparum as resistant malaria isthis chapter. However in short, the pathophysiology of malaria unjustified. One should consider the possibility of re - infectionresults from destruction of erythrocytes, the liberation of in most of these cases.parasite and erythrocyte (Cytokines, Nitric Oxide etc) materialinto the circulation, and the host reaction to these events. DiagnosisP falciparum malaria differs from the other three human Peripheral smear examination for malarial parasite is the goldspecies of malaria parasite because infected erythrocytes also - standard in confirming the diagnosis of malaria. Thick andsequester in the microcirculation of vital organs, interfering thin smears prepared from the peripheral blood are used forwith micro circulatory flow and host tissue metabolism, which the purpose. The thick smear of correct thickness is the oneresults in severe organ damage. through which newsprint is barely visible. Thick smears areClinical Features used to detect infection and to estimate parasite concentration. Thin film examination is the gold standard in diagnosis ofUncomplicated Malaria : The classical (but rarely observed) malarial infection.malaria attack lasts 6 - 10 hours. It consists of three typicalstages. In the Cold Stage, there is a general sensation of cold The QBC Test, developed by Becton and Dickenson Inc., is a newfollowed by rigors. The temperature rises to 40ºC and stays method for identifying the malarial parasite in the peripheralfor nearly one hour. At this time parasites are demonstrable blood. It involves staining of the centrifuged and compressedin the blood. This stage is followed by the Hot Stage which is red cell layer with acridine orange and its examination undercharacterized by fever, headaches and vomiting. The skin feels UV light source. It is faster and and dry .This lasts from 2 to 6 hours. The last stage is the The other tests include Para Sight F test, OptiMal Assay,Sweating Stage. The patient sweats profusely and temperature the Immuno Chromatographic Test (ICT Malaria P test), .f.returns to normal. This stage lasts from 2 - 4 hours. Polymerase Chain Reaction, detection of antibodies by RadioClassically, the attacks occur every second day with the “tertian” Immuno Assay, Immunofluorescence or Enzyme Immuno Assayparasites (Plasmodium falciparum, Plasmodium vivax, and (11, 12).Plasmodium ovale) and every third day with the “quartan” Rapid Diagnosis of Malaria (Dipstick Test) : Theparasite (Plasmodium malariae). More commonly, the patient immunochromatographic tests for the detection of malariapresents with a combination of symptoms of fever, chills, antigens, developed in the past decade, have opened a new and • 1029 •
  • exciting avenue in malaria diagnosis. However, their role in (clinically/microscopically confirmed), parenteral artemisininthe management and control of malaria appears to be limited or quinine is the drug of choice, irrespective of chloroquineat present. Immunochromatographic tests are based on the resistance status of the area.capture of the parasite antigens from the peripheral blood using ●● Quinine salt : 10mg /kg body weight 8 hourly in 5% dextroseeither monoclonal or polyclonal antibodies against the parasite saline is preferred. Patients should be switched over to oralantigen targets. Currently, immunochromatographic tests can quinine as early as possible and oral dose is 10 mg/kg bodytarget the Histidine - Rich Protein 2 of Plasmodium falciparum, weight eight hourly not exceeding 2gm in a day in anya pan - malarial Plasmodium aldolase, and the parasite specific case. Minimum total duration for quinine therapy shouldlactate dehydrogenase. Pf LDH is cleared rapidly from blood, be for 7 days including both parental and oral doses.the test becomes negative within days of treatment, but P/HRP2 ●● Injectable form of artemisinine derivatives may be used foris cleared very slowly from the blood, and may remain positive the management of severe and complicated malaria (Forfor up to one month after the acute infection, particularly if the adults and non - pregnant only). Artesunate : 2.4 mg/kgparasitaemia was high. This is a disadvantage in areas where bw IM/IV followed by 1.2 mg/kg body weight after 12 hourstransmission is high, and infections frequent. These RDTs are then 1.2 mg/kg body weight once daily for total durationkit based, much faster, need only little training and diagnostic of 5 days.sensitivity similar to trained microscopists (13, 14). Prevention and Control MeasuresTreatment The malaria prevention and control measures aimed at breakingWHO recommends that all malaria endemic countries should the ‘man - mosquito - man’ cycle of transmission include ahave their own national anti - malaria drug policy and defines it number of methods which are complementary to each ‘An antimalarial treatment policy is a set of recommendations None of the measures will be successful if applied alone in anyand regulations concerning the availability and rational use of given environment. At the same time use of all of them togetherantimalarial drugs in a country. It should be the part of the may not be feasible for technical or administrative reasons.national essential drug policy and the national malaria control Local environmental conditions, resources and feasibilitypolicy and in line with the overall national health policy’. will have to be studied before optimum measures may beIndia’s first national anti - malaria drug policy was drafted implemented (16, 17). The various measures are described inin 1982. Thereafter the policy has been reviewed periodically greater detail in section of Entomology.based on sensitivity studies and current National Drug Policy Personal Protective Measures : Individual personal protectionon Malaria has been revised in 2007. The main purpose of the against mosquito bites is achieved by use of mosquito nets,national anti - malaria drug policy is to provide a framework repellents and protective clothing. The feeding and restingfor the safe and effective treatment of uncomplicated and habits of the vectors and the cultural practices and sleepingsevere malaria as well as prevention of malaria in travellers habits of people are important determinants of the efficacy ofand vulnerable groups, such as pregnant women and young personal protective measures.children. Detailed discussion of treatment of malaria is beyond The use of mosquito net is the most effective personal protectivethe scope of this chapter. The main treatment guidelines based measure. Net should be put up before dusk and tucked allon national anti - malaria drug policy are as follows (15) : round under the bedding. For making the mosquito netsMicroscopically positive Plasmodium falciparum/ Plasmodium more effective, the nets are now being treated/medicated withvivax cases : synthetic pyrethroids like deltamethrin, cyfluthrin etc. These●● Plasmodium falciparum cases should be treated with nets can be used by pregnant women & small children. These chloroquine in therapeutic dose of 25 mg/kg body weight nets are also effective against sand flies. over three days and single dose of Primaquine 0.75 mg/kg Commercially available repellants such as Odomos, Mosfree bw on the first day only. have been found to be very effective when applied on clothing●● Plasmodium vivax cases should be treated with chloroquine or on exposed parts of the body. The wearing of long trousers in full therapeutic dose of 25 mg/kg body weight over three and shirts with rolled down sleeves after dusk should be days. Primaquine can be given in dose of 0.25mg/kg bw encouraged in all epidemic areas. Screening of houses and daily for 14 days. barracks as a measure is effective only when all doors, windowsWhen diagnosis by microscopy or Rapid Diagnostic Kits (RDK) and ventilators in the building are screened by wire mesh ofis not possible, cases showing signs and symptoms of malaria proper gauge and size (1.2 to 1.5mm).without any other obvious causes should be considered Anti - larval Measures : Larval control is the only effectiveas “clinical malaria” and treated with chloroquine in full method of radical mosquito control. In urban areas, thistherapeutic dose of 25 mg/kg body weight over three days in method complements the adult mosquito control. Anti - larvallow risk area while in high risk area single dose of Primaquine work is carried out by preventing breeding and destruction0.75 mg/kg bw should also be given on the first day. of larvae and pupae. For long term and permanent mosquitoPlasmodium falciparum in chloroquine resistant areas is control, greater emphasis should be placed on the prevention oftreated with 4mg/kg body weight of artesunate daily for 3 days breeding during non - transmission season than on larvicidalalong with 25mg/ kg body weight of sulphadoxine/sulphalene (chemical & biological) measures during breeding season.+ 1.25 mg per kg bw of pyrimethamine on the first day. Anti - Adult Measures : The principle of malaria control byIn severe and complicated malaria of Plasmodium falciparum intercepting its transmission, by shortening the life span of the • 1030 •
  • vector species to a period shorter than the extrinsic incubation Malaria Vaccine : Despite considerable effort and expense, aperiod of the parasite, has come to be established. This principle generally available and highly effective malaria vaccine has tillhas been successfully employed by the application of residual date not been developed. An ideal malaria vaccine is one thatinsecticides to the resting places of mosquitoes, viz. the inside would prevent the infection at the first instance and if this is notof all the walls of habitations, this is known as Indoor residual possible, should decrease the intensity of infection and shouldspraying. Other methods of adult mosquitoes control include be successful in preventing malaria transmission. The path ofSpace Sprays, Genetic Control etc. vaccine development has proved long and strewn with pitfalls,Vector Engineering : Avoidance of man - made mosquitogenic but there has been progress. Research is now concentrated onconditions is of primary importance. A positive aspect of all stages of the parasite life cycle : the sporozoite, the livermosquito breeding prevention should be kept in view and stage, the asexual blood stage, and the gametocyte.deliberately incorporated in the planning and execution of Summaryall engineering constructions and town planning schemes.Drainage in water supply projects may lead to mosquitogenic Malaria is the most important parasitic disease of man. It isconditions. Besides these, indiscriminate digging, disposal defined as an acute and chronic disease caused by obligateof discarded tins, containers and water collections, overhead intracellular protozoa of the genus Plasmodium. Approximatelystorage tanks and septic tanks without covers are potential 5% of the world population is infected by malarial parasitesmosquito breeding places in urban areas. Clean edging and and the disease is responsible for nearly one million deathswater deweeding, channelling, filling or draining, exposing to annually world wide. The causative organisms of the diseasesunlight, shading or covering are the usual methods adopted. malaria are protozoa of the genus Plasmodium, familyUnderground drainage constitutes the best method of bio - Plasmodiidae, suborder Haemosporidiidae, order method for control of mosquito breeding (17). However diseases in humans is caused by four parasites namely Plasmodium vivax, Plasmodium malariae, PlasmodiumEnvironmental Management : Environmental management falciparum and Plasmodium ovale. Most of the severe morbidityapproaches to vector control aim at modifying the environment and mortality in malaria is caused by Plasmodium deprive the target vector population of its requirements for The cyclopropagative life cycle of the Plasmodium occurs inbreeding, resting and feeding purposes. This reduces human two stages the sexual stage and the asexual stage. For human- vector contact and renders conditions less conducive for plasmodia, the only reservoir is a malaria case. All ages aredisease transmission. These include periodic flushing in equally affected. Optimal conditions for malaria transmissionstreams by means of small dams with siphons and sluice gates occur when the temperature is between 20°C and 30°C and theand changing the salinity of breeding habitats (17). mean relative humidity is at least 60%. There are 56 speciesChemoprophylaxis : Chemoprophylaxis is a valuable of anopheline mosquitoes in India but only six are regardedsupplementary measure under high risk situations, but as primary vectors. The most prevalent mode of transmissionnot a substitute for other control measures. Early colonists of malaria is through the bite of the infected female anophelesdevised many indigenous methods of taking quinine regularly mosquito. Clinical Features can be divided into Uncomplicated(including ‘Indian tonic water’), which were generally neither Malaria and Severe Malaria. Severe malaria occurs whenpleasant nor fully effective. Quinine (a poor prophylactic) Plasmodium falciparum infections are complicated by seriouswas relied upon by armies and colonists until after the Great organ failures or abnormalities in the patient’s blood orWar. But it was only after the introduction of chloroquine, the metabolism. Peripheral smear examination for malarialantimalarial biguanides and subsequently pyrimethamine that parasite is the gold - standard in confirming the diagnosisfinally brought safe and effective antimalarial prophylaxis into of malaria. However immunochromatographic tests for theexistence. In the current age of increasing drug resistance, many detection of malaria antigens, have been developed in the pastprophylactic drugs can no longer be relied upon, particularly in decade for Rapid Diagnosis of Malaria. Treatment is based onareas of multiple drug resistance such as South - East Asia and National Drug Policy on Malaria 2007. The malaria preventionSouth America. Therefore recommendations for each region and control measures aimed at breaking the ‘man - mosquito -vary depending upon the drug sensitivity studies. In India the man’ cycle of transmission include a number of methods whichcurrent recommendations on Chemoprophylaxis as per National are complementary to each other; these are Personal ProtectiveDrug Policy on Malaria (2007) is as follows (15) : Measures, Anti - larval Measures, Anti - adult Measures,●● In chloroquine sensitive areas - chloroquine 10 mg/kg body Environmental Management, Chemoprophylaxis and Malaria weight and followed by a weekly dose of 5 mg/kg body Vaccine. weight . This is to continue till 1 month after delivery in case of pregnancy and in travellers till one month after Study Exercises return from endemic area. The terminating dose should be Long Questions : (1) Discuss the epidemiology, diagnosis radical treatment for P. vivax i.e. 25 mg/kg body weight over and treatment of Malaria (2) Discuss in detail Prevention and 3 days along with 0.25 mg/kg body weight of primaquine control measures against malaria. for 14 days. Short Notes : (1) Spleen rate (2) Characteristics of●● In chloroquine resistant areas - chloroquine 5 mg/kg body vector mosquitoes in transmission of malaria (3) Life weight weekly supplemented with proguanil 200mg daily. cycle of the Plasmodium (4) Rapid Diagnosis of Malaria●● Chemoprophylaxis with chloroquine is not recommended (5) Chemoprophylaxis of malaria. beyond 3 years because of its cumulative toxicity. • 1031 •
  • MCQs Answers : (1) c; (2)a; (3) c; (4) b; (5) b;(6) c; (7) a; (8) a;1. Malignant tertian malaria is caused by (a) Plasmodium (9) b; (10) c. vivax (b) Plasmodium malariae (c) Plasmodium falciparum (d) Plasmodium ovale References 1. Gilles HM; Historical Outline; In Essential Malariology; Gilles HM, Warell DA2. The cyclopropagative life cycle of the Plasmodium occurs editors; 4th ed. Arnold, London, 2002; 1 - 8. in _____________ stages (a) Two stages (b) Three stages 2. Bruce - Chwatt LJ. History of malaria from prehistory to eradication. In (c) Four stages (d) Five stages Wernsdorfer WH & McGregor I (eds) Malaria; and Practice of Malariology. Edinburgh : Churchill ; - one, 1988 : 1 - 59.3. Most of the severe morbidity and mortality in malaria is 3. Robert ES, Gilles HM; The malarial parasites; In Essential Malariology; caused by (a) Plasmodium vivax (b) Plasmodium malariae Gilles HM, Warell DA editors; 4th ed. Arnold, London, 2002; 1 - 8. (c) Plasmodium falciparum (d) Plasmodium ovale 4. Garnham PCC. Malaria Parasites and other Haemosporidia; Blackwell, 1966.4. In order to infect a mosquito, the blood of a human carrier 5. Melvin DM, et al; Common Blood and Tissue Parasites of Man. Life Cycle must contain at least ____________ no. of gametocytes per Charts. Atlanta, Georgia, Centers for Disease Control, 1979. mm3 (a) 10 (b) 12 (c) 14 (d) 16 6. Terrie ET, Strickland GT. Malaria : In Hunter’s Tropical Medicine and emerging5. Main Vector of malaria in Andaman and Nicobar Islands is and Infecticiuos Diseases : Strickland GT, Editor; 8th ed. WB Saunders Pennsylvania 2000; 615 - 643. (a) Anopheles dirus (b) Anopheles sundaicus (c) Anopheles 7. Bina Das, Raj Gopal, Akiyama. Pictorial key to the species of Indian maculatus (d) Anopheles stephensi Anopheline mosquitoes. Zoology (Journal of Pure and Applied Zoology) 19906. A Hyperendemic area is defined as one in which (a) Spleen : 2 (3) : 133 - 159. 8. Rao TR. The Anophelines of India. Revised Ed 1983. Malaria Research Centre rate or parasite rate consistently over 10% in children (Indian Council of Medical Research), Govt of India, Delhi. between the ages of 2 and 9 years (b) Spleen rate or parasite 9. Gillies MT. Anopheline mosquitoes : vector behaviour and bionomics. In rate consistently over 30% in children between the ages of Wernsdorfer WH & McGregor 1 (eds) Malaria : Principles and Practice of 2 and 9 years (c) Spleen rate or parasite rate consistently Malariology. Edinburgh : Churchill34; Livingstone, 1988 : 453 - 485. 10. Molineaux L, Muir DA, Spencer HC & Werndorfer WH. The epidemiology of over 50% in children between the ages of 2 and 9 years malaria and its measurement. In Wernsdorfer WH & McGregor I (eds) Malaria (d) Spleen rate or parasite rate consistently over 75% in : Principles and Practice of Malariology. Edinburgh : Churchill Livingstone, children between the ages of 2 and 9 years 1988 : 999 - 1090. 11. Castelli F, Carosi G. Diagnosis of malaria infection. In Handbook of malaria7. Rapid Diagnostic test of Malaria based on detection of infection in the tropics. Carosi G, Castelli F, eds. Health Cooperation Papers antibodies against Histidine - Rich protein 2 is used for No. 15. Bologna, Associazione Italians, 1997, 53 - 71. diagnosis of (a) Plasmodium falciparum (b) Plasmodium 12. Cheesbrough M. District laboratory practice in tropical countries. Part 1. Tropical Health Technology, 1998. vivax (c) Plasmodium ovale (d) All of the above 13. Proux S, Hkirijareon L, Ngamngonkiri C, McConnell S & Nosten F. Paracheck -8. Gold - standard in confirming the diagnosis of malaria Pf : a new, inexpensive and reliable rapid test for P falciparum malaria. Trop . is (a) Peripheral smear examination (b) Immuno Med Int Health 2001; 6 : 99 - 101. chromatographic test (c) Polymerase Chain Reaction 14. Mayxay M, Pukrittayakamee 5, Chotivanich K, Looareesuwan S & White NJ. Persistence of Plasmodium falciparum HRP - 2 in successfully treated acute (d) Radio immuno assay falciparurn malaria. Trans R Soc Trop Med Hyg 2001; 95 : 179 - 382.9. Drug of choice in severe and complicated malaria of 15. Malaria Drug Policy (2007); Directorate of National Vector Borne Disease Plasmodium falciparum (a) Artesunate (b) Quinine 16. Control Programme publication; Directorate General of Health Services (c) Chloroquine (d) None of the above Ministry of Health and Family Welfare; Delhi 2007. 17. Rozendaal JA. Vector control : Methods for use by individuals and10. In severe and complicated malaria recommended dose of communities. 1st Ed 1997. WHO, Geneva. Quinine is (a) 2.5mg /kg body weight 8 hourly (b) 5mg /kg 18. World Health Organisation. Vector control for malaria and other mosquito body weight 8 hourly (c) 10mg /kg body weight 8 hourly borne diseases. Tech Rep Ser No 857.WHO, Geneva, 1995. (d) 15mg /kg body weight 8 hourly to man by the bite of infective mosquitoes. The three species 172 Lymphatic Filariasis are Wuchereria bancrofti, Brugia malayi and Brugia timori. Wuchereria bancrofti is the most widespread among these three Rajesh Vaidya species (2). Several mosquito species are known to transmit the infection. However, Culex quinquefasciatus and Mansonia annulifera are the two most important vectors in India. InLymphatic Filariasis is widely known as Elephantiasis. More tropical and subtropical areas the prevalence of infection isthan a billion people in more than 80 countries are at risk of continuing to increase. The major reason for this increase is thesuffering from the disease. India accounts for one - third of rapid and unplanned growth of cities which greatly enhancesthe people infected with the disease (1). Filariasis is caused by breeding of the mosquitoes that transmit the disease. Thisthree species of nematode worms belonging to the super family painful and profoundly disfiguring disease is usually acquiredFilarioidea and family Onchocercidae which are transmitted • 1032 •
  • in childhood, but manifests its most disfiguring forms in adults filarial infection. These include the states of Jammu & Kashmir,(3, 4). The disease due to lymphatic filariasis is characterized Himachal Pradesh, Punjab, Haryana, Chandigarh, Rajasthan,by disfigurement of the limbs (elephantiasis) and genitalia Delhi, Uttaranchal Sikkim, Arunachal Pradesh, Nagaland,(hydrocele and other anatomical changes in the male genitalia). Meghalaya, Mizoram, Manipur and Tripura (7). Almost all theConsequently, it often has adverse economic and psychosexual cases in India are caused by Wuchereria bancrofti (94%) whileeffects as well as medical consequences (5). Lymphatic filariasis the remaining 6% are attributed to Brugia malayi (7).is one of the six infectious diseases considered eradicable by Over 400 million people live in filariasis endemic areas in India.WHO with the available tools (6). Three fourths of those at risk live in rural areas. An estimatedIn 1863, Demarquay first described the microfilariae that are 49 million individuals in India are infected. Of these, overthe larvae which live in the blood stream. Microfilariae were twenty million people suffer from chronic forms of filariasisfound in urine by Wucherer in 1868. Patrick Manson was the while another 28 million are thought to be microfilaria carriersfirst to speculate in 1878 that filariasis may be transmitted (11 - 13).by mosquitoes (2). The disease has been known in India since Agent : The three species of nematodes causing lymphaticancient times. It finds mention in “Susruta Samhita” which filariasis, Wuchereria bancrofti, Brugia malayi and Brugiadates back to the 6th century B.C. Madhavakara described the timori are threadlike in appearance. They have five stages insigns and symptoms of the disease in his treatise ‘Madhava their life cycle. Unlike other vector borne diseases, the infectiveNidhana’ in 7th century A. D. In 1709, Clarke called elephantoid stage of the parasite is not injected into the human body by thelegs in Cochin as ‘Malabar legs’ (7). mosquito vector. The Infective third - stage larvae are depositedEpidemiology on skin by the vector and penetrate on their own or throughGlobal : According to the World Health Organization, about the opening created by mosquito bites within minutes to reach1.25 billion people are at risk of suffering from lymphatic the lymphatic system. They then proceed to shed their cuticlefilariasis. As on 31 Dec 2006, 83 countries are considered and develop a new surface as they moult into the fourth stageendemic for filaria. The highest proportion of cases is in the larvae (10). These fourth - stage larvae migrate to centralWHO South - East Asia Region with 64% followed by the WHO lymphatic vessels and develop into sexually mature adult maleAfrican Region with 32%. The WHO European Region remains or female worms over a period of approximately 9 months. Thefree of lymphatic filariasis transmission (8). Approximately one adult worms are significantly larger than larval stages, withthird of those at risk live in India, another one third in Africa male worms being 20 - 40 mm in length and female worms 40and the remainder in other parts of Asia, the Pacific and the to 100 mm in length. The adults reside mostly in the afferentAmericas. The most highly - endemic countries are Bangladesh, lymphatics. The preferred sites for the adult worms seem to theDemocratic Republic of Congo, India, Indonesia, Madagascar, lymphatics of the lower extremities, upper extremities and theNigeria and the Philippines (9). The total number of persons genitalia.infected worldwide is estimated to be 120 million, one third of The mean reproductive life span of adult worms is approximatelywhom have serious disfigurement and incapacitation (1). Almost 5 years. Following copulation female worms discharge25 million men suffer from genital disease, most commonly large numbers (10,000 per day) of microfilariae measuringhydrocoele, while an estimated 15 million people, mostly 150 x 7 μm into the blood stream via the lymphatics. Thewomen suffer from lymphoedema of the leg (elephantiasis). number of microfilariae in the peripheral blood is variable.Among the three parasitic worms responsible for the disease, There is usually a surge in their numbers during the night.Wuchereria bancrofti is the most prevalent particularly in hot These microfilariae are ingested by the mosquito vectors duringand humid climates of Asia, Africa, the Americas and the feeding. The microfilariae exsheath in the mosquito stomachPacific. Brugia malayi is found in Southern India, South East to become first stage larvae. They penetrate the stomach wallAsia and South and Central China. Brugia timori has only been and move to the thoracic muscles of the mosquito where theyfound in parts of Indonesia (2). More than half of all cases of moult twice to develop into the infective third stage larvae. TheLymphatic filariasis live in South East Asia. Of the estimated infective forms then move to the mouth parts of the mosquito700 million people living in endemic areas in the region, about and the cycle repeats. The extrinsic incubation period is usually60 million are estimated to be infected or suffering from the two weeks (2, 3, 13).disease (10). Vector : A wide range of mosquitoes can transmit the parasite,India : One - third of the people infected with the disease live depending on the geographic area. The primary vectors forin India (1). The disease has been described as being second Filaria are the night biting Culex and Anopheles mosquitoes.only to malaria as a major public health problem. The disease Culex quinquefasciatus is the principal vector in urban areasis endemic to most parts of the country. Indigenous cases in South East Asia. In rural areas of both Asia and Africa,have been reported from about 250 districts in 20 states / Anopheles species are the important vectors particularlyunion territories. Local transmission is known to occur in Anopheles gambiae and Anopheles funestes (2). Aedes andAndhra Pradesh, Assam, Bihar, Chhattisgarh, Goa, Jharkhand, Mansonia are also responsible for transmitting the infection inKarnataka, Gujarat, Kerala, Madhya Pradesh, Maharashtra, the parts of Asia and the Pacific region (3).Orissa, Tamil Nadu, Uttar Pradesh, West Bengal, Pondicherry, In India, the most important vector for lymphatic filariasis isAndaman & Nicobar Islands, Daman & Diu, Dadra & Nagar Culex quinquefasciatus. It is the vector for Wuchereria bancrofti.Haveli and Lakshadweep. The North Western and North Eastern It is a ubiquitous mosquito and is present all over the of India appear to be free from indigenously acquired • 1033 •
  • Culex breeds in polluted water. Important breeding sites are arthritis. Occult filariasis in which the classical features of thewet pit latrines, septic tanks, drains, disused wells and paddy disease are absent and microfilaria can not be demonstrated infields. Mansonia annulifera and Mansonia uniformis are the blood, can present as tropical pulmonary eosinophillia. Aboutvectors for Brugia malayi in India. Mansonia lay eggs on the 40% of patients have renal involvement with proteinuria andunder surface of the leaves of plants (7). haematuria (2, 4, 5, 14).Filarial nematodes are poorly transmitted by the vectors. A Diagnosisvery small proportion; usually less than 1% of mosquitoes Diagnosis in symptomatic patients living in endemic areas isare infective even in endemic areas (14). Repeated mosquito based on appropriate history and typical clinical findings. Inbites over several months result in lymphatic filariasis. People patients above 15 years of age the appearance of lymphedemaexposed to intense transmission for a long period are at the of the extremities or disease of the male genitalia is most likelygreatest risk for infection. Visitors to endemic areas from non due to filarial infection.endemic areas for short periods rarely develop disease (2, 15). A definitive diagnosis can be made only by detection ofHost Factors : Varied patterns of infection and disease are the parasites. The standard method for diagnosing activeseen in different endemic areas. Infection is usually acquired infection is the identification of microfilariae in a bloodin childhood (16). The prevalence of infection rises with age smear by microscopic examination. The microfilariae exhibitfrom 5 years to 30 years beyond which it stabilizes. Prevalence nocturnal periodicity with surges of circulating microfilariaemay decline somewhat among the elderly. Signs of disease at night. Blood collection should be done at night to coincidestart becoming apparent during late adolescence and rise with the appearance of the microfilariae. A small dose ofsteadily with age (2). Both sexes are equally susceptible. Minor Diethylcarbamazine (DEC) can increase microfilaraemia duringdifferences, however, are shown by various groups. It has been the day as it causes the microfilariae to be expelled from thepostulated that females in the reproductive age group may be pulmonary vascular bed. A thick smear should be made andmore resistant to infection than males because of hormonal stained with Giemsa or Haemtoxylin and Eosin. Microfilariaefactors (17). are sometimes detected in chylous urine, hydrocoele fluidLymphatic filariasis is primarily a disease of the poor as it occurs and ascites fluid (19). An alternative to microscopic detectionmostly in rural areas or urban slums. The increase in lymphatic of microfilariae is provided by serologic techniques for thefilariasis over the past few years has been attributed to the diagnosis of lymphatic filariasis. Patients with active filarialexpansion of slum areas and poverty, particularly in India and infection are found to have elevated levels of antifilarial IgG4Africa. As many filariasis patients are physically incapacitated, in the blood and these can be detected using routine assaysit has a significant economic impact. Lymphatic filariasis also (19).exerts a heavy social burden. Among men, genital damage may The difficulty in detection of microfilariae led to thebe a severe handicap leading to physical limitations and social development of simple immunochromatographic tests. Thesestigmatization. Enlargement of a leg or arm, the genitals, vulva are very sensitive, very specific and simple “card tests” to detectand breasts may result in severe stigmatization of women (1). circulating parasite antigens without the need for laboratoryEnvironment : Environmental conditions that enhance vector facilities. They use only finger - prick blood droplets takenbreeding and survival increase infection rates. The optimum anytime of the day (1, 20). Adult worms are difficult to detect.conditions for the breeding of the vectors and the development Sonographic examination of the scrotum or breast using highof parasites in them are temperature between 15°C and 35°C and frequency ultrasound may result in the identification of adultrelative humidity above 60%. The density of C quinquefasciatus worms within dilated lymphatics (2, 5).is at its minimum during the monsoon, but due to favourable Treatmentatmospheric conditions, somehow the maximum infectivityrate in the mosquitoes occurs during this period. India presents Diethylcarbamazine (DEC) is the drug used most widely forareas of widely variable endemicity because of its large size treatment of lymphatic filariasis. It exerts no direct lethaland variable climates from region to region (18). action on the adult worms but changes them in a manner which makes their removal by the host’s immune system possible (2).Clinical Features It is considered safe and effective against all filarial infections.The incubation period is very variable stretching from 8 to 16 The dose is 9 - 12 mg / kg orally in three divided doses formonths or even longer. The adult worms induce an immunological 14 or 21 days. The full dose must be reached slowly, startingreaction. A wide variety of clinical manifestations can be seen with 50 mg daily to avoid side effects. For treatment of tropicalin lymphatic filariasis. A large proportion of infected persons eosinophillia, a 21 day treatment regimen must be followed.remain asymptomatic despite the presence of microfilariae. The This course may be repeated twice at intervals of 4 - 6 weeks.manifestations result from either acute inflammation or chronic Ivermectin has also been found effective in a single oral doselymphatic obstruction. Clinical manifestations range from those of 200 - 400 μg / kg body weight. Two drug regimens have alsowithout apparent clinical disease to those with lymphedema been found effective. The combination that may be used includeand severe disfigurement of the limbs and genitalia. Fever 400 mg albendazole with 6mg / kg DEC or 400 mg albendazolemay or may not be present in both the acute and chronic with 150 μg / kg ivermectin once a year. Symptomatic treatmentforms. The various presentations can include lymphangitis such as analgesics, antipyretics and antihistaminics may beand adenitis, funiculitis and hydrocoele, abscess formation, required. Surgical procedures to correct elephantiasis must belymphadoema and elephantiasis, chyluria and monoarticular preceded by drug therapy. • 1034 •
  • In filariasis endemic areas, the primary goal of community and simple “card tests” to detect circulating parasite antigenstreatment is to eliminate microfilariae from the blood of without the need for laboratory facilities. Diethylcarbamazineinfected individuals so that transmission of the infection by (DEC) is the drug used most widely for treatment of lymphaticthe mosquito can be interrupted. Recent studies have shown filariasis. Other drugs used are Albendazole and Ivermectin.that single doses of Diethylcarbamazine (DEC) have the same The use of single doses of two drugs administered togetherlong - term effect in decreasing microfilaraemia as the 12 (albendazole with DEC or ivermectin) is 99% effective inday regimens of DEC. The use of single doses of two drugs removing microfilariae from the blood. Control of the diseaseadministered together (Albendazole with DEC or Ivermectin) is can be achieved by active disease surveillance, vector control,99% effective in removing microfilariae from the blood (1). personal protection and mass treatment of communities inPrevention and Control endemic areas are the corner stone of lymphatic filariasis control. The WHO strategy of the Global Programme to EliminateActive disease surveillance, vector control, personal protection Lymphatic Filariasis aims to stop the spread of infection andand mass treatment of communities in endemic areas are morbidity control. To interrupt transmission, districts in whichthe corner stone of lymphatic filariasis control. The success lymphatic filariasis is endemic must be identified and thenof control measures depends on the level of co - operation mass treatment programmes implemented to treat the entireby the public. The importance of health education cannot at - risk overemphasized. Vector control and personal protectivemeasure are dealt with in detail in the chapter on Entomology. Study ExercisesThe WHO strategy of the Global Programme to Eliminate Long question : Discuss the epidemiology, prevention andLymphatic Filariasis aims to stop the spread of infection and control of Lymphatic Filariasis.morbidity control. To interrupt transmission, districts in which Short Notes : (1) Clinical Spectrum of Filariasis (2) Treatmentlymphatic filariasis is endemic must be identified and then of Lymphatic Filariasis and mass treatment regimen.mass treatment programmes implemented to treat the entire MCQat - risk population. 1. Most prevalent parasitic worm in India (a) WuchereriaMass Treatment involves once - yearly administration of bancrofti (b) Brugia malayi (c) Brugia timori (d) None ofsingle doses of two drugs given together, albendazole plus the aboveeither diethylcarbamazine (DEC) or ivermectin. An alternative 2. Brugia timori has only been found in parts of (a) Southcommunity - wide regimen with equal effectiveness is the India (b) Indonesia (c) China (d) Bangladeshuse of common table / cooking salt fortified with DEC in the 3. The most important vector for lymphatic filariasis in Indiaendemic region for a period of one year (1). This programme is (a) Culex quinquefasciatus (b) Culex tritaeniorhyncusin operation on a national level in India (7, 22 24). (c) Mansonia annulifera (d) Mansonia uniformis Summary 4. Drug most widely used for treatment of lymphatic filariasis (a) Diethylcarbamazine (DEC) (b) Ivermectin (c)Lymphatic Filariasis is widely known as Elephantiasis. Albendazole (d) None of the aboveAccording to the World Health Organization as on 31 Dec 5. Dose of Diethylcarbamazine (DEC) (a) 1 - 3mg / kg orally2006, 83 countries are considered endemic for filaria. The in three divided doses (b) 3 - 6 mg/ kg orally in threemost highly - endemic countries are Bangladesh, Democratic divided doses (c) 6 - 9 mg / kg orally in three divided dosesRepublic of Congo, India, Indonesia, Madagascar, Nigeria and (d) 9 - 12 mg / kg orally in three divided dosesthe Philippines. One - third of the people infected with thedisease live in India. Almost all the cases in India are caused Answers : (1) a; (2) b; (3) a; (4) a; (5) Wuchereria bancrofti (99.4%) while the remaining 6% are Referencesattributed to Brugia malayi. The three species of nematodes 1. World Health Organization. Lymphatic Filariasis. Fact sheet No 102.causing lymphatic filariasis : Wuchereria bancrofti, Brugia Revised Sep 2000. http : // Accessed on 15 Mar 08.malayi and Brugia timori are threadlike in appearance. In 2. cMahon JE and Simonsen PE. Filariases. In Gordon Cook (Ed).Manson’s MIndia, the most important vector for lymphatic filariasis is Culex Tropical Diseases. 20th Edition. WB Saunders. London 1996.1321 - 1368.quinquefasciatus. It is the vector for Wuchereria bancrofti. 3. DC Atlanta.Lymphatic Filariasis. Epidemiology and Risk Factors. CMansonia annulifera and Mansonia uniformis are the vectors http : // lymphatic_ filar.htm. Accessed on 15 Mar 2008.for Brugia malayi in India. The prevalence of infection rises 4. orld Health Organization.Lymphatic Filariasis. http : // Wwith age from 5 years to 30 years beyond which it stabilizes. lymphatic _filariasis/en/. Accessed on 15 mar 2008.Lymphatic filariasis is primarily a disease of the poor as it 5. azura James W. and Nutman Thomas B. Filariasis In Guerrant RL, Walker DH Koccurs mostly in rural areas or urban slums. The incubation and Weller PF. (Editors) Tropical Infectious Diseases : Principles, Pathogens & Practice. 2nd Edition. Elsevier Churchill Liningstone.2005period is very variable stretching from 8 to 16 months or 6. orld Health Organization. WHO SEARO. Lymphatic Filariasis : The Disease Weven longer. Clinical manifestations range from those without and its Treatment. clinical disease to those with lymphedema and severe 10613.htm. Accessed on 15 Mar 2008. 7. roblem and Elimination of Lymphatic Filariasis in India. National Vector Pdisfigurement of the limbs and genitalia. A definitive diagnosis Borne Diseases Control Programme. Directorate General of Health Services.can be made only by detection of the parasites. The standard Ministry of Health and Family Welfare. Governemt of India. New Delhi. httpmethod for diagnosing active infection is the identification of : // Accessed on 15 Mar 2008 8. orld Health Organization. Geneva. Global programme to eliminate Wmicrofilariae in a blood smear by microscopic examination. lymphatic filariasis. Weekly epidemiological record. No. 42, 2007, 82,Immunochromatographic tests are very sensitive, very specific 361380. • 1035 •
  • 9. orld Health Organization. Lymphatic Filariasis. The disease and its W 16. Shenoy RK, Suma TK., Kumaraswami V, Rahmah N, Dhananjayan G, Padma Epide miology. http : // S, Abhilash G, and Ramesh C. Preliminary findings from a cross - sectional Accessed on 15 Mar 2008. study on lymphatic filariasis in children, in an area of India endemic for10. orld Health Organization. WHO SEARO. Lymphatic Filariasis : Burden of W Brugia malayi infection. Annals of Tropical Medicine and Parasitology Lymphatic Filariasis in South - East Asia Region http : // 2007.101(3) : 205 - 213. en/Section10/ Section2096_10583.htm. Accessed on 15 Mar 2008. 17. rabin L. Sex Differentials in Susceptibility to Lymphatic Filariasis and B11. CMR Bulletin. Prospect of Elimination of Lymphatic Filariasis in India. Vol I Implications for Maternal Child Immunity. Epidemiol Infect 1990; 105 : 335 32. No 5 & 6. May Jun 2002. 353.12. ani SP and Dhanda V. Natural History and Dynamics of Progression of P 18. as PK, Ramaiaha D, Augustin DJ and Kumar A. Towards Elimination of D Filarisis. In Sushil Kumar etal (Editors). Tropical Disease : Molecular Biology Lymphatic Flariasis in India. Trends in Parasitology. Volume 17, Issue 10, and Control Strategies. Publication and Information Centre. Council of 2001, 457 - 460. Scientific and Industrial Research. 1994. 19. DC Atlanta. Division of parasitic diseases. Lab identification of parasites C13. orld Health Organization. Lymphatic Filariasis : The Disease and its W of public health concern. http : // geninfo_ Control. Fifth Report of the WHO Expert Committee on Filarisis Technical diagnosis _diseases.htm. Accessed on 15 Mar 2008. Report Series No 821. 1992. 20. ahmah N, Makoto I, Eisaku K, Rohana AR, Balachandran R, Rohela M, R14. ‘Gove David I. Tissue Nematodes. In Mandell GL, Bennet JE and Dolin R Taniawati S and Mirani W. Multicentre evaluations of two new rapid IgG4 (Editors) Mandell, Douglas, and Bennett’s Principles and Practice of tests (WB rapid and panLF rapid) for detection of lymphatic filariasis. Filaria Infectious Disease. 6th Edition. Elsevier Churchill Livingstone. Philadelphia Journal 2007, 6 : 9 2005 .3267 3272. 21. Nandha B, Sadanandane C, Jambulingam P and Das PK. Delivery strategy of15. enters for Disease Control and Prevention. Lymphatic Filariasis fact sheet C mass annual single dose DEC administration to eliminate lymphatic filariasis http : // in the urban areas of Pondicherry, South India : 5 years of experience. Filaria lymphatic filar.htm. Accessed on 15 Mar 2008. Journal 2007, 6 : 7 22. Ramaih KD and Das PK. Mass drug administration to eliminate lymphatic filariasis in India. Trends Parasitol. 2004 Nov;20(11) : 499 - 502. Leishmaniasis world wide. The true incidence and prevalence 173 Leishmaniasis are uncertain because of the large number of undiagnosed cases, the lack of screening, and underreporting (7 - 9). Every year, an estimated one and a half to two million children and adults Rajesh Vaidya develop symptomatic disease and the incidence of infection is substantial when sub - clinical infections are included. TheLeishmaniasis encompasses a varied collection of diseases number of new cases of Cutaneous Leishmaniasis each year inranging in severity from a spontaneously healing skin ulcer to the world is estimated to be about 1.5 million while the numberoverwhelming visceral disease (1). The disease is named after of new cases of Visceral Leishmaniasis is estimated to be aboutLeishman, who first identified the organisms in smears taken 5,00,000. An estimated 12 million people are presently infectedfrom a man who had died of “Dum Dum” fever in 1901 (2). worldwide. Leishmaniasis is associated with about 2.4 millionAn estimated two million cases of all forms of Leishmaniasis disability - adjusted life years and around 7,00,000 deathstaken together occur worldwide every year (3, 4). The disease per year (7 - 9). Since 1993, the geographical distribution ofis caused by 21 species of the genus Leishmania which are Leishmaniasis has expanded significantly.pathogenic to humans and transmitted by the bite of 30 species The disease is endemic in three countries of the WHO Southof the phlebotomine sandfly (3, 4). There are four main types East Asia Region, Bangladesh, India and Nepal. Approximatelyof the disease : Cutaneous, Diffuse cutaneous, Mucocutaneous 200 million people in the Region are “at risk” from the disease.and Visceral Leishmaniasis which is commonly called Kala The disease is reported in 45 districts in Bangladesh, 52 inAzar (3). Leishmania species are members of the family India and 12 in Nepal. Of the estimated 5,00,000 people inTrypanosomatidae, order Kinetoplastida. They reside as the world infected each year, nearly 1,00,000 are estimated tointracellular amastigotes within macrophages in mammals and occur in the Region (10).as extracellular promastigotes in the gut of their insect vectors,phlebotomine sand flies (5). Leishmaniasis has also emerged India : India is one of the world’s largest foci of Visceralas an AIDS - associated opportunistic infection (6). Leishmaniasis, accounting for 50% of the total burden of this disease. Leishmaniasis is endemic in eastern States of India.Epidemiology A total of 52 districts in the country are considered endemicGlobal : Leishmaniasis is endemic in 88 countries on five for the disease. An estimated 165.4 million population is atcontinents. More than 90% of Cutaneous Leishmaniasis cases risk of Kala Azar in four states. In India, about 1,00,000 casesoccur in Iran, Afghanistan, Syria, Saudi Arabia, Brazil and of Visceral Leishmaniasis are estimated to occur annually. OfPeru. More than 90% of Visceral Leishmaniasis cases occur these, the State of Bihar accounts for more than 90 per cent ofin Bangladesh, Brazil, India and Sudan. The World Health the cases. Cutaneous Leishmaniasis usually occurs in the dry,Organization estimates that 350 million people are at risk of north eastern states of India, bordering Pakistan extending from • 1036 •
  • Amritsar to Kutch and Gujrat plains. Cases of Anthroponotic more often than females probably due to greater exposure.Cutaneous Leishmaniasis has been reported from Bikaner city Population movement is important in spreading infection(10, 11). between endemic and non endemic regions. The disease usuallyAgent : The disease is caused by 21 protozoan species of the strikes the poorest of the poor (10, 16, 17). It is common ingenus Leishmania (order Kinetoplastida). The amastigote forms various farming practices, forestry, mining and fishing whoare obligate intracellular parasites while the promastigotes are have greater risk of being bitten by sand - flies. Recovery fromextracellular in the arthropod vectors. Kala - Azar gives a lasting immunity.These human pathogens include the Leishmania donovani Environment : The disease is mostly confined to the plains.complex with three species ( Leishmania donovani, Leishmania It does not occur in altitudes over 2000 feet. Prevalenceinfantum and Leishmania chagasi). The Leishmania mexicana usually shows a rise during and after rains. The diseases arecomplex has three main species which are Leishmania mexicana, largely confined to rural areas and those urban areas whereLeishmania amazonensis and Leishmania venezuelensis. opportunities for breeding of sand flies exist. Overcrowding,The other major pathogenic species are Leishmania tropica, poor ventilation and accumulation of organic matter inLeishmania major and Leishmania aethiopica. The different the environment facilitates transmission. Developmentalspecies are morphologically indistinguishable, but they can be projects like forest cleaning, and cultivation projects, largedifferentiated by isoenzyme analysis, molecular methods, or water resources schemes, and colonization and resettlementmonoclonal antibodies. In India, Leishmania donovani is the programmes are bringing human beings into areas of highonly parasite causing this disease. vector and reservoir concentration (5, 18).The life cycle is relatively simple. Amastigotes are oval or Transmission : The disease is transmitted by the bite ofround in shape and approximately 2 to 3 μm in diameter. infected female sandflies. Rarely other modes of transmissionThey have a large, eccentrically located nucleus, a specialized might result in infection. Visceral Leishmaniasis can be directlymitochondrial structure, the kinetoplast, which contains a initiated by amastigotes via blood (shared needles, transfusion,substantial amount of extranuclear DNA and a flagellar pocket transplacental spread) or organ transplantation. Cutaneousand flagellum, which lie within the confines of the cell. They infection can develop after inadvertent needlestick injury if themultiply by simple binary division. In the gut of the sand needle or syringe contains infected material (6, 12 14).fly, leishmania live and multiply as extracellular, flagellated Clinical Features : The outcome of leishmanial infection ispromastigotes that vary morphologically from short, stumpy dependent on a series of complex and only partially understoodforms to elongated ones ranging from 10 to 15 μm in length interactions between Leishmania species - specific virulenceand 2 to 3 μm in diameter. A single flagellum extends from factors and the genetically determined cell - mediated immunethe anterior pole. After development in the sand fly gut, which responses of their mammalian hosts. The incubation in man istakes approximately 1 or 2 weeks depending on the Leishmania extremely variable. It usually ranges from 3 to 8 months butspecies, infectious metacyclic promastigotes migrate to the can be as short as 10 days to as long as two years.proboscis (5, 12, 13). Leishmaniasis has several diverse clinical manifestations :Vector : Leishmania species are transmitted by female sand ulcerative skin lesions, destructive mucosal inflammation,flies of the genus Lutzomyia in the Americas and Phlebotomus and disseminated visceral infection (Kala Azar). Epidemiology,in other parts of the world. Depending on the species, sand immunopathology, and outcome are similarly diverse, sinceflies live in forested areas, rodent burrows, or debris in peri infection occurs in multiple endemic regions, in both children- domestic habitats. Sandflies breed in cracks and crevices in and adults, and is caused by nearly two - dozen distinctthe soil and buildings, tree holes, caves. They are weak fliers, Leishmania species. Nevertheless, all forms of this protozoalbut they can be carried considerable distances by the wind. infection share three pathogenetic features : resident tissueSand flies probe with their proboscis to form a venous pool, macrophages are targeted and support intracellular parasitefrom which they obtain blood by capillary action (5, 14, 15). A replication; the host immunoinflammatory response regulatestotal of about 30 species in Phlebotomus genus (old world) and expression and outcome of disease; and persistent tissueLutzomyia genus (new world) have been identified as vectors. infection is characteristic (6, 12, 13). Each of the three majorSandflies are active in the evening and night - time hours. clinical syndromes can present with a wide spectrum ofIn India, Phlebotomus argentipes is a proven vector of Kala findings. Each of these syndromes is associated with moreAzar. Cutaneous Leishmaniasis is transmitted by Phlebotomus than one Leishmania species, and any given species is capablepapatasi and Phlebotomus sergenti. of producing more than one syndrome. Variations are common,Host : Most leishmaniases are zoonotic and humans become particularly among people who are concurrently infected withinfected only when accidentally exposed to the natural HIV or other immunosuppressive illness (5, 12, 13).transmission cycle. The animal host may be wild animals, such Cutaneous Leishmaniasis : The typical lesion of Cutaneousas rodents, and domestic animals, such as dogs. However, in Leishmaniasis (5, 12) develops at the site where promastigotesthe anthroponotic forms humans are the sole reservoir host. are injected by the vector. Promastigotes are taken up byIndian Kala - Azar is anthroponotic with humans being the mononuclear phagocytes. They transform to amastigotes andonly known reservoir of infection. multiply within the macrophages. A papule is formed at theInfection can occur in all age groups and both genders. In site of inoculation. The papule enlarges and then ulcerates.India peak age of infection is 5 to 9 years. Males are affected Multiple lesions may be present in the same patient. Depending • 1037 •
  • on the location, Old World Cutaneous Leishmaniasis is known the name Kala - Azar, which means “black fever” in Sanskrit.locally as Oriental sore, Bouton d’Orient, Bouton de Crete, The late stages of disease are characterized by malnutrition,Bouton d’Alep, Bouton de Briska, Aleppo evil, Baghdad boil, severe wasting, and progressive debilitation. Stunting mayand Delhi boil. be seen in children. Death often occurs due to a secondaryThere can be marked variation in the appearance of the lesions. bacterial infection, such as pneumonia, septicemia, dysentery,The classic wet lesion of Leishmania major and Leishmania or tuberculosis, or with measles or other viral infection.braziliensis is “pizza - like” with a raised outer border, Laboratory findings include anaemia, neutropenia,granulating base, and overlying white, purulent exudate. thrombocytopenia and pronounced hypergammaglobulinemia.Infection by Leishmania tropica produces dry lesions in the The anaemia is usually normocytic, normochromic, unless thereMiddle East and India. The ulcer tends to be smaller and is concomitant iron deficiency. Leukopenia can be profoundcovered with a crust. Contiguous mucosal involvement may be with white blood cell counts below 1000/mL. The globulin levelseen in some patients. Some leishmanial lesions are papular can reach 9 or 10 g/dl.or nodular, without ulceration. Cutaneous lesions persist for Post - Kala - Azar Dermal Leishmaniasis : Some patients ofmonths, and in some cases years, before they heal, leaving Visceral Leishmaniasis in India and Africa develop skin lesionsflat, atrophic scars as evidence of disease. Once a lesion has following treatment, ranging from hyperpigmented macules toresolved, the person is usually left with immunity against frank nodules. Skin lesions typically appear in India 1 or 2the infecting Leishmania species. Cutaneous Leishmaniasis years after treatment and may persist for as long as 20 years.should be considered in the differential diagnosis of subacute Persistence of lesions beyond one year is associated with highor chronic skin lesions in people who have lived, worked, or anti - leishmanial antibody titers and negative leishmanialtraveled in endemic areas. skin test responses. Anti - leishmanial treatment is indicatedMucosal Leishmaniasis (Espundia) : A small proportion of in Indian post - Kala Azar dermal Leishmaniasis. In a fewpeople infected with Leishmania braziliensis develop mucosal instances in India, Visceral Leishmaniasis has recurred inlesions in the nose, mouth, pharynx, or larynx months to years patients with post - Kala - Azar dermal Leishmaniasis. Theafter resolution of the primary skin lesion. The condition is differential diagnosis includes leprosy (5, 12, 13).known as Espundia in Latin America. Mucosal Leishmaniasis HIV - Visceral Leishmaniasis Co - infection : Leishmania withoften begins with nasal stuffiness and inflammation. Ulceration HIV co - infection is has emerged as a serious new disease andof the nasal mucosa and septum follows. The lips, cheeks, is increasingly frequently being reported. Immunocompromisedsoft palate, pharynx and larynx may eventually be involved, individuals progress to full blown Visceral Leishmaniasis farresulting in substantial disfigurement. Mucosal involvement more often than immunocompetent people who get also observed with other Leishmania species, although AIDS and Visceral Leishmaniasis are mutually reinforcing.the pathophysiology may be somewhat different. Destructive Visceral Leishmaniasis quickly accelerates the onset of AIDSinvolvement of the nose and mouth has been reported with and shortens the life expectancy of HIV - infected people.Leishmania tropica in Saudi Arabia. Mucosal involvement has Similarly AIDS increases the risk of Visceral Leishmaniasisbeen reported rarely in immunocompetent people and more by 100 - 1000 times in endemic areas. This combination offrequently in those who are immunosuppressed with neoplasms HIV and Leishmaniasis produces cumulative deficiency of theor AIDS. (5, 12). immune response since Leishmania parasites and HIV destroyVisceral Leishmaniasis : The majority of infections of Visceral the same cells, exponentially increasing disease severity andLeishmaniasis are sub clinical. Only a minority of those consequences. Visceral Leishmaniasis is considered a majorinfected develop full - blown Visceral Leishmaniasis, or Kala contributor to a fatal outcome HIV in co - infected patients.- Azar. The disease is characterized by fever, weight loss, and Another implication of this combination is that Leishmaniasishepatosplenomegaly. can be transmitted directly person to person through theMalnutrition is known to suppress cell - mediated immune sharing of needles, as is often the case among intravenousresponses and may contribute to progression to symptomatic drug users (13, 19).Visceral Leishmaniasis. The incubation period is typically Diagnosisweeks to several months, but it may be as short as 10 days or Cases of Leishmaniasis should be confirmed by demonstrationas long as several years. The onset of Visceral Leishmaniasis of the parasite, which is straightforward if parasites are plentifulis usually insidious, but it can be abrupt, with high fever. Full as in Visceral Leishmaniasis but can be difficult otherwise.- blown, progressive Visceral Leishmaniasis, or Kala - Azar, isassociated with fever, abdominal enlargement, weakness, loss Parasite Identification : The diagnosis of Leishmaniasis isof appetite, and weight loss. The clinical findings are similar most often confirmed by identifying leishmania amastigotes inwith disease due to Leishmania donovani and Leishmania Wright - Giemsa - stained touch preparations or tissue sectionsinfantum / chagasi. Symptoms may be present for weeks to or by isolating the parasite in culture. Amastigotes are seenmonths before patients come to medical attention in rural, in macrophages in tissue sections, but they may appear to beendemic areas. The fever pattern may be intermittent, remittent extracellular in touch preparations. Leishmania can be grownor rarely continuous. The spleen is firm, non - tender, and over as promastigotes in NNN medium, Schneider’s insect medium,time becomes massively enlarged. There is hepatomegaly with and other tissue culture media. The cultures are incubated atthe enlarged liver having a sharp edge and smooth consistency.Some patients in India develop hyperpigmentation leading to • 1038 •
  • 24 to 26°C to approximate sand fly temperatures. market for human Leishmaniasis vaccines. Leishmaniasis is aSerology : Antileishmanial antibody titers are typically present considered a local/regional problem and not a global one (24).in high titer in people with Visceral Leishmaniasis and at low A number of candidate vaccines are undergoing clinical trails.titer or undetectable in those with Cutaneous Leishmaniasis. Killed parasites as vaccines produced encouraging results inThey can be measured by a number of assays. Enzyme - Linked Brazil in the 1970s. Trials have tested autoclaved LeishmaniaImmunosorbent Assay (ELISA), indirect immunofluorescent major plus BCG versus adjuvant (BCG) alone. In Ecuador, twotests, and agglutination assays have all been used (20). doses of a killed multi - leishmania species cocktail plus BCG reduced Cutaneous Leishmaniasis incidence by 73% the firstSkin Test : The intradermal leishmanin (Montenegro) skin test year (13,25).is positive in the majority of people who have asymptomatic,self resolving Leishmania donovani and Leishmania infantum/ Summarychagasi infections and in people with Cutaneous or Mucosal Leishmaniasis encompasses a varied collection of diseasesLeishmaniasis. The skin test is negative in people with ranging in severity from a spontaneously healing skinprogressive Visceral Leishmaniasis or Diffuse Cutaneous ulcer to overwhelming visceral disease. Leishmaniasis isLeishmaniasis, but it becomes positive in the majority of people endemic in 88 countries on five continents. The World Healthwho are successfully treated for Visceral Leishmaniasis. Organization estimates that 350 million people are at risk ofTreatment Leishmaniasis world wide. Leishmaniasis each year in theThe drug of choice for the treatment of Visceral Leishmaniasis world is estimated to be about 1.5 million while the number ofis Sodium stibogluconate, a pentavalent antimonial compound new cases of Visceral Leishmaniasis is estimated to be aboutexcept in regions that are considered Sodium stibogluconate 5,00,000. India is one of the world’s largest foci of Visceralunresponsive. The dose is 20 mg Sb/kg/day IV or IM daily for Leishmaniasis, accounting for 50% of the total burden of this20 - 30 days. However, resistance is on the rise and resistance disease. The disease is caused by 21 protozoan species of thelevels as high as 43% have been reported from Bihar where genus Leishmania (order Kinetoplastida). The amstigote formsVisceral Leishmaniasis is endemic. Patients resistant to are obligate intracellular parasites while the promastigotes arestibogluconate should be treated with alternative agents, such extracellular in the arthropod vectors. Leishmania species areas liposomal amphotericin (0.5 - 3 mg/kg) on alternate days transmitted by female sand flies of the genus Lutzomyia in theor pentamidine (2 - 4 mg/kg) on alternate days for 15 doses. Americas and Phlebotomus in other parts of the world. In India,Amphotericin B deoxycholate is the drug of choice in India, Phlebotomus argentipes is a proven vector of Kala - Azar. Thewhereas the lipid formulation liposomal amphotericin is used disease is transmitted by the bite of infected female Europe (2). The dose of Amphotericin B used in India is 1mg/ The incubation in man is extremely variable. It usually rangeskg IV infusion daily or alternate day for 15 - 20 infusions. The from 3 to 8 months but can be as short as 10 days to as longdose can be increased in patients with incomplete response as two years. There are three main types of the disease :with 30 injections. Miltefosine, the first effective oral treatment Cutaneous, Diffuse Mucocutaneous and Visceral Leishmaniasisfor Visceral Leishmaniasis, including for antimony - resistant which is commonly called Kala Azar. Immunocompromisedinfection has been approved for self - administered outpatient individuals progress to full blown Visceral Leishmania withtherapy (13, 21, 22). The drug is to be used in a dose of 100 mg HIV co - infection is has emerged as a serious new disease anddaily for four weeks. Supportive treatment includes rest, high is increasingly frequently being reported. AIDS and Visceral- calorie diet, blood transfusions, and treatment of secondary Leishmaniasis are mutually reinforcing. Cases of Leishmaniasisinfections. should be confirmed by demonstration of the parasite by identifying leishmania amastigotes in Wright - Giemsa -Prevention and Control stained touch preparations or tissue sections or by isolatingLeishmaniasis can be prevented by interrupting sand fly the parasite in culture. The drug of choice for the treatmenttransmission or by removing or treating reservoirs of infection. of Visceral Leishmaniasis is Sodium stibogluconate. However,(18, 23). The short - term visitor to an endemic area should resistance is on the rise and these patients should be treateduse personal protective measures to avoid sand fly bites. Sand with alternative agents, such as liposomal amphotericin (0.5flies tend to bite from dusk to dawn. The application of DEET - 3 mg/kg) on alternate days or pentamidine (2 - 4 mg/kg) on(diethyltoluamide) - containing insect repellents to exposed alternate days for 15 and under pant and shirt cuffs, the use of fine - meshscreens or insect nets, and the application of insecticide Study Exercises(usually permethrin or other pyrethroids) to clothing and bed Long Question : Discuss the epidemiology, treatment,nets - decrease the risk of transmission of Leishmaniasis. prevention and control of Kala - AzarFurther details on vector control are given in the chapter on Short Notes : (1) Life cycle of Leishmania parasite (2) VisceralEntomology. Leishmaniasis (3) HIV - Visceral Leishmaniasis Co - infectionVaccine (4) Treatment of Visceral LeishmaniasisThere is experimental evidence to indicate that Leishmaniasis MCQsshould be vaccine preventable. However, there is currently 1. The disease is endemic in following three countries of theno vaccine against any form of Leishmaniasis for general WHO South East Asia Region except (a) Bangladesh (b)human use. One major factor may be the lack of a conceived India (c) Nepal (d) Sri lanka • 1039 •
  • 2. The disease is reported in _________ no of districts in India 11. National Vector Borne Diseases Control Programme. Kala Azar. Directorate General of Health Services, Ministry of Health & Family Welfare. http : // (a) 51(b) 52(c) 53(d) 54 www. nvbdcp. gov. in /Kala - Azar. html.Accessed on 15 Mar 2008.3. State which accounts for more than 90 per cent of the 12. Dedet JP and Pratlong F. Protozoan Infections. Leishmaniasis. In Gordon cases in India (a) Uttar Pradesh (b) Bihar (c) Assam (d) Cook and Zumla A (Editors). Manson’s Tropical Diseases. 21st Edition. Saunders.Elsvier Science 2003. Madhya Pradesh 13. Murray W Henry, Berman D Jonathan, Davies R Clive and Saravia G Nancy.4. Leishmania donovani complex comprises of all except Advances in leishmaniasis The Lancet 2005; 366 : 1561 - 1577. (a) Leishmania infantum (b) Leishmania chagasi 14. Kalra NL, Bang YH. Manual on entomology in visceral leishmaniasis, World (c) Leishmania venezuelensis (d) Leishmania donovani Health Organization;1988. Document SEA/VBC/35.New Delhi. 15. Swaminath CS, Short HE, Anderson LAP Transmission of Indian Kala - Azar .5. Cutaneous Leishmaniasis is also known as all the following to man by the bite ofP argentipes. Indian J Med Res 1942; 30 : 473 - 7. . except (a) Oriental sore (b) Aleppo evil (c) Delhi boil 16. Kala - Azar incidence in Bihar (1985 - 1991) published by Office of the (d) Espundia Chief Malaria Officer, Bihar Directorate of Health Services & Development of Health, M. E.&FamilyWelfare Govt. of Bihar, Patna, 1991.Answers : (1) d; (2) b; (3) b; (4) c; (5) d. 17. Sanyal RK. Some observations on epidemiology of current outbreak of Kala - Azar in Bihar. JCommunDis 1979; 11 : 170 - 82.References 18. Bhattacharya SK, Sur D, Sinha PK, and Karbwang J. Editorial. Elimination1. Roberts LJ, Handman E and Foote SJ. Clinical review. Science, medicine, and of leishmaniasis (Kala - Azar) from the Indian subcontinent is technically the future Leishmaniasis. BMJ 2000;321 : 801 - 804. feasible & operationally achievable. Indian J Med Res 123, March 2006 :2. Vidyashankar C and Agarawal R. Leishmaniasis. Emedicine article. Last 195 - 196 revised Aug 2007. http : //www. emedicine. com/ped/topic1292. htm. 19. World Health Organization. The leishmaniases and Leishmania/HIV co - Accessed on 18 Mar 2008. infections. Factsheet No 116.World Health Organization. Geneva 2000.3. World Health Organization. Division of Control of Tropical Diseases. 20. Sunder S, Reed SG, Singh VP Kumar PCK, Murray HW. Rapid accurate field , Leishmaniasis control home page www. who. int/health - topics/ diagnosis of Indian visceral leishmaniasis. Lancet 1998; 351 : 563 - 5. leishmaniasis. htm.Accessed on 18 Mar 2008. 21. Sunder S, Jha TK, Thakur CP Engel J, Sindermann H, Fischer C, et al. Oral ,4. World Health Organization. Manual on control of leishmaniasis. WHO Tech miltefosine for Indian visceral leishmaniasis.NEngl J Med 2002; 347 : 1739 Rep Ser No 797.990 - 46.5. Jeronimo B Selma M, Queiroz Sousa De Anastacio and Pearson D Richard. 22. Bhattacharya SK, Jha TK, Sunder S, Thakur CP Engel J, Sindermann H, et al. , Leishmaniasis. In Guerrant RL, Walker DH and Weller PF (Editors) Tropical Efficacy and tolerability of miltefosine for childhood visceral leishmaniasis Infectious Diseases : Principles, Pathogens & Practice. 2nd Edition. Elsevier in India.Clin Infect Dis 2004; 38 : 217 - 21 Churchill Livingstone. 2005 : 1095 - 1113. 23. Kishore K, Kumar V, Kesari S, Dinesh DS, KumarAJ, Das Pand Bhattacharya6. Herwaldt BL. Leishmaniasis. The Lancet 1999; 354 : 1191 - 1199 SK. Vector control in leishmaniasis. Indian J Med Res 123, March 2006 :7. World Health Organization. Zoonoses and veterinary public health. 467 - 472. Leishmaniasis. http : //www. who. int/zoonoses/diseases/leishmaniasis/en/. 24. Ali K, Sima R, Davoudi N, Maboudi F and Modabber F. Leishmaniasis vaccine Accessed on 15 Mar 2008. candidates for development : A global overview. Indian Journal of Medical8. World Health Organization. Leishmaniasis. The Disease and its Epidemiology. Research, Mar 2006. http : //www. who. int/leishmaniasis/disease_epidemiology/en/index. html. 25. Dumonteil Eric, McMahon - Pratt Diane and Price L Virginia. UNDP/World Accessed on 15 Mar 2008. Bank/WHO Special Programme for Research & Training in Tropical Diseases9. World Health Organization. Leishmaniasis. Magnitude of the problem. http (TDR). Report of the Fourth TDR/IDRI Meeting on Second - Generation : //www. who. int/leishmaniasis/burden/magnitude/ burden_magnitude /en/ Vaccines against Leishmaniasis, 2001. index. Html Accessed on 18 Mar 2008.10. World Health Organization. SEARO. Kala Azar Status in SEA Region. CurrentDisease Burden. http : //www. searo. who. int/en/Section10/ Section2163_11668. htm.Accessed on 15 Mar 2008. regions of the world. The global prevalence of Dengue has grown Dengue & Dengue Haemorrhagic 174 Fever dramatically in recent decades. The World Health Organization reports that the disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Rajesh Vaidya South - East Asia and the Western Pacific. South - East Asia and the Western Pacific are most seriously affected. WHO currently estimates there may be 50 million cases of Dengue infectionDengue is a vector borne viral disease which occurs in tropical worldwide every year. 2.5 billion people live in Dengue endemicand sub - tropical regions around the world, predominantly in countries and are at risk of acquiring the infection (4, 5).urban and semi - urban areas. Dengue fever (DF) is the mostrapidly spreading vector borne viral disease and is a major Epidemiologyinternational public health concern (1, 2). The disease is caused Global Situation : The geographical extent of the disease hasby the four serotypes of the Dengue virus which are arboviruses risen significantly in the recent past. It has spread to newof the genus flaviviruses. The principal vector for the disease is areas and reemerged in areas where it appeared to have beenthe mosquito Aedes aegypti. The disease can present in several controlled. Tropical areas in South - East Asia, Africa, Westernforms, from asymptomatic illness to life threatening diseases Pacific and the Mediterranean are most seriously affected. Priorlike Dengue Haemorrhagic Fever (DHF) and Dengue Shock to 1970 only nine countries had experienced DHF epidemic, aSyndrome (DSS). number that had increased by more than four times by 1995.The virus is widely distributed in the tropical and subtropical During 1998 over 1.2 million cases with 3, 442 deaths were • 1040 •
  • reported to WHO which is the largest for any single year. WHO overhead uncovered or partially covered water tanks, discardedcurrently estimates there may be 50 million cases of Dengue buckets, tyres, utensils and large containers used for collectinginfection worldwide every year with around 24,000 deaths (5). rain water which are not emptied and cleaned periodically.The rapid rise in the geographical extent of the disease has The mosquitoes rest indoors on various objects, in closets andbeen attributed to the enhanced geographic distribution of the other dark places. Outside, they rest where it is cool and shady.four Dengue viruses and of their mosquito vectors, particularly Aedes mosquito can fly upto a limited distance of 400 metersthe predominantly urban Aedes aegypti. A rapid rise in urban but can spread over vast distances mechanically in variouspopulation particularly urban slums has contributed to the rise types of vehicles used by man. Aedes aegypti is primarily a dayin the number of cases (3, 5). The WHO expects the spread time biter (4, 6, 12, 13).of the disease to continue because of increasing urbanisation, Environmental Factors : The outbreaks of DF/DHF are mostincreasing population movement, and proliferation of man - likely to occur in post - monsoon period when the breeding ofmade larval habitats of the mosquito vector. the mosquitoes is highest. High temperature and high humidity1.3 billion people living in South - East Asia are at risk of during these seasons prolongs the life span of the vector. TheDengue fever. In 2003 only eight countries in South - East spread of Dengue has resulted from several factors includingAsia Region reported Dengue cases. By 2006, ten out of the 11 human behaviour, climate and movement of humans. Usuallycountries which form part of the WHO South - East Asia region urban areas, having high population density, poor sanitationwere reporting the disease. Bhutan reported the first Dengue and large number of desert coolers, flower vases, constructionoutbreak in 2004. An outbreak, with a high case fatality rate sites, overhead tanks etc which promote mosquito breeding,(3.55%) was first reported in Timor - Leste in 2005. Nepal are at high risk. Dengue fever/DHF can also occur in rural areasreported Dengue cases for the first time in Nov 2006 (6 - 8). where the environment is friendly for mosquito breeding likeIndian Situation : Large parts of India are endemic for Dengue storage water for cattle feeding and drinking, cement cisternsFever. The disease is reported from most parts of the country and underground cemented water sumps (4, 6, 8).except those at high altitudes. The first major outbreak in India Transmission : The infection is transmitted by the bite of anwas reported during 1963 in Kolkata. The next major outbreak infected female mosquito Aedes aegypti. Mosquitoes acquireof Dengue / Dengue Haemorrhagic Fever was reported in Delhi the virus while feeding on the blood of an infected person.and neighboring states in 1996. Following this outbreak, the After an extrinsic incubation period of 8 to 10 days, an infectedreporting of Dengue fever was made mandatory to ensure early mosquito can transmit the virus for the rest of its life. Transpreventive measures in case of outbreak. Out of 18 endemic - ovarian transmission of the Dengue virus in mosquitoesstates, the most affected states are Delhi, West Bengal, Kerala, maintains the virus in nature. Humans are the main host ofTamil Nadu, Karnataka, Maharashtra, Rajasthan, Gujarat the virus, although studies have shown that in some parts ofand Haryana (9). Data for the last 10 years reveals that the the world monkeys may become infected. The virus circulateslargest number of cases and deaths due to Dengue/DHF were in the blood of infected humans for two to seven days (4, 6,reported in 1996 while the next increase was in 2003. 12, 317 12, 13).cases with 184 deaths were reported to the National Vector Clinical PresentationBorne Diseases Control Programme in India in 2006 (9). Delhirecorded several outbreaks of Dengue fever between 1967and The incubation period of Dengue fever is usually 5 - 6 days,2006. The outbreak in 2006 was estimated to have resulted in but may vary from 3 to 10 days. Infection with Dengue10, 344 cases and 162 deaths (10, 11). virus can result in four different clinical syndromes. They are undifferentiated fever, the Classic Dengue fever, DengueAgent Factors : DF / DHF is caused by Dengue virus which Haemorrhagic fever (DHF) and Dengue Shock syndrome (DSS)belongs to genus Flavivirus family Flaviviridae and includes (14 - 16).serotypes 1, 2, 3 and 4 (Den - 1, Den - 2, Den - 3 and Den -4). The Dengue virus is composed of single - stranded RNA. Undifferentiated Fever : This is the most common manifestationEach serotype provides specific lifetime immunity and short of Dengue infection. Almost 90% of those infected remain either- term cross - immunity. All serotypes can cause severe and asymptomatic or only mildly symptomatic. The patient hasfatal disease. There are genetic variations within the serotypes. fever, headache, body ache and may develop a mild rash.Some genetic variants within each serotype appear to be more Classic Dengue Fever : This is characterized by abrupt onset ofvirulent or have greater epidemic potential. When a person has high fever, severe headache, severe muscle and joint pain (Breakhad classic Dengue, a second infection later by another serotype Bone Fever), rash and other haemorrhagic manifestations.increases the likelihood of suffering from DHF as explained Dengue Haemorrhagic Fever : DHF is a potentially deadlyby the immune enhancement mechanism (1, 2, 4). Infection complication that is characterized by high fever, accompaniedwith one serotype provides life - long homologous immunity by headache, anorexia, vomiting and abdominal pain. Petechiaebut does not provide protection against other serotypes, and on the extremities, face, and trunk are the manifestations ofinstead may exacerbate subsequent infection (4, 6, 7). haemorrahage. Bleeding from nose, gums and gastrointestinalVector : Aedes aegypti is the main vector of Dengue transmission tract may be found. In moderate cases, spontaneousin India. Another important vector is the Aedes albopictus. The mucocutaneous bleeding, nasal bleeding and GI bleeding usuallymosquito is a peri - domestic and domestic breeder. Mosquito occurs. In severe cases, the patient’s condition may suddenlybreeding can occur in any water - storage containers, such as deteriorate after a few days of fever. Any case with fever, ordesert coolers, flower vases, coconut shells, construction sites, recent history of acute fever, haemorrhagic manifestations, low • 1041 •
  • platelet count (100,000/mm or less), and objective evidence of Serological diagnosis is based on detection of IgM antibodies.“leaky capillaries” in the form of elevated haematocrit (20% or IgM antibodies against Dengue virus appear around 5 daysmore over baseline), low albumin, or pleural or other effusions after onset of symptoms and are detectable for one to threemeets the case definition for DHF. months after the illness. The tests employed are IgM captureDengue Shock Syndrome : Patients may rapidly develop varying ELISA test and Rapid IgM strip test. IgM capture ELISA test kitdegree of circulatory disturbances and go into a critical state of is available from NIV Pune and commercial sources and Rapidshock. Patients with DHF who develop evidence of circulatory IgM Strip Test kit is available commercially.failure manifested indirectly by rapid and weak pulse, narrow Treatmentpulse pressure (< 20 mm Hg) or hypotension for age, cold, The basics of management of cases of Dengue fever are fluids,clammy skin and altered mental status meet the criteria for DSS. rest, antipyretics (avoid aspirin and non - steroidal anti -Frank shock is direct evidence of circulatory failure. Prolonged inflammatory drugs) and close monitoring of blood pressure,shock is often complicated by metabolic acidosis and severe haematocrit, platelet count and level of consciousness.bleeding. Case fatality rates can exceed 20% in such patients. A Liberal fluids intake including home available fluids likemajor cause of deaths due to DHF is leakage of plasma in the rice water, kanji, fruit juices, plain water or ORS solution arepleural and abdominal cavities leading to hypovolaemic shock. recommended for patient with excessive sweating, nausea,Encephalitic signs associated with intracranial haemorrhage, vomiting or diarrhoea to prevent dehydration (1, 3). Monitoringmetabolic and electrolyte disturbances, and hepatic failure may must be continued after defervescence. If the level of hydrationoccur. falls intravenous fluids, guided by serial haemtocrits, bloodDifferential Diagnosis pressure, and urine output must be given. The volume of fluidDifferential diagnosis must include all other arboviral fevers, needed is similar to the treatment of diarrhoea with mild tomeasles, rubella and other systemic febrile illnesses, especially moderate isotonic dehydration.those accompanied by rash (6). The presence of marked Management of DHF : Patients of DHF need regular assessmentthrombocytopenia with concurrent haemoconcentration by serial haematocrit levels. Urine output should be monitoreddifferentiates DHF / DSS from other syndromes such as closely in areas where serial haematocrit estimation is notendotoxic shock from bacterial or meningococcaemia. possible. A rise in haematrocrit of 20% or more or singleAlarming Signs haematocrit value of more than 40%, platelets count of 50,000/ cmm or less and spontaneous haemorrhage are all danger(a) Minute spots on the skin suggesting bleeding within the signs. skin.(b) Nose bleeds and gum bleeds, haemetemesis. Management of DSS : DSS patients present with shock.(c) Abdominal pain and/or passage of black tarry stool. Volume replacement is the most important treatment measure(d) Refusal to food or drink. and immediate administration of intravenous fluids to(e) Abnormal behaviour or drowsiness. expand plasma volume is essential. Close observation with(f) Difficulty in breathing or cold hands and feet, reduced good nursing care is imperative. Blood transfusion should amount of urine being passed. be given in case with significant haemorrhage. Fresh frozen plasma or concentrated platelet transfusion may be givenDiagnosis when disseminated intravascular coagulation causes massivePatients suspected to be suffering from Dengue fever must bleeding. Readers may refer to standard texts for details onundergo repeated clinical laboratory tests : Complete Blood management of patients (3, 4, 14 - 17)Counts including WBC, platelets, haematocrit, Liver functiontests, and urine analysis for microscopic haemturia. These Prevention and Controlblood tests may indicate a diagnosis of Dengue fever and DHF Vector Control : Vector control and personal protective measures/ DSS. Thrombocytopenia (100,000 cells or less per mm) and are the mainstay of prevention of Dengue infections. Bothhaemoconcentration as evidenced by a greater than 20% rise aspects are dealt with in detail in the chapter on average haematrocrit for age and sex are the haemtological Surveillance : Epidemiological surveillance of the disease ascriteria for diagnosis. well as the vector form an important part of control measures.Laboratory tests essential for confirmatory diagnosis of The disease surveillance should include fever surveillance,Dengue infection include isolation of the virus, demonstration diagnosis based on standard case definitions, and reporting ofof a rising titre of specific serum Dengue antibodies, and DF/DHF cases to state health authorities. Vector surveillancedemonstration of a specific viral antigen or RNA in the tissue includes both larval and adult vector surveillance (18). Aor serum. Virus isolation can be done by inoculation of clinical number of indices have been described and are currently usedmaterial in tissue culture, mosquitoes or suckling mice and to monitor the vector population :further detection is performed using fluorescent antibody test House index : Percentage of houses positive for larvae of Aedesor haemagglutination inhibition test. Viral antigen can be aegypti. House index of more than 10% indicates high risk ofdemonstrated by doing direct fluorescent antibody test using transmissionspecific monoclonal antibodies for Dengue virus. Viral RNA or Breteau index : Number of positive containers for Aedesgenomic sequence can also be detected in autopsy specimen, aegypti per 100 houses. An index of more than 50 indicatesserum, CSF or culture supernatant by doing Polymerase Chain high risk of transmission while index below five indicates lowReaction (PCR) and gene sequencing. risk of transmission. • 1042 •
  • Notification : Dengue is a cross border disease. With massive 3. Dengue virus has how many serotypes (a) 2 (b) 4 (c) 6air travel, outbreaks can rapidly cross international borders. (d) 8.Outbreaks must, therefore, be notified at the earliest to both 4. IgM antibodies against Dengue virus appear around _____the national as well as international health authorities. days after onset of symptoms (a) 3 (b) 5 (c) 7 (d) 9Vaccine : No effective vaccine is available for Dengue. Research 5. House index of more than ___ % &/or Breteau index ofinto Dengue vaccines has focused on the use of live attenuated more than ___ indicates high risk of transmission (a) 5or inactivated vaccines, infectious clone derived vaccines, and & / or 40 respectively b)10 &/ or 50 respectively (c) 15 &/nucleic acid vaccine (19). or 60 respectively (d)20 &/ or 70 respectively Answer : (1) d; (2) b; (3) b; (4) b; (5) b.SummaryDengue is a vector borne viral disease which occurs in tropical References 1. orld Health Organization. Special Programme for Research and Training in Wand sub - tropical regions around the world. Dengue fever is Tropical Diseases. Report of the Scientific Working Group on Dengue, 2006.the most rapidly spreading vector borne viral disease and is Geneva. October 2006.a major international public health concern. WHO currently 2. DC Atlanta. Dengue Fever. http : //www. cdc. gov/ncidod/dvbid/dengue/ C index. htm Accessed on 15 Mar 2008.estimates there may be 50 million cases of Dengue infection 3. engue Haemorrhagic Fever : Diagnosis, Treatment, Prevention and Control. Dworldwide every year. 2.5 billion people live in Dengue endemic 2nd edition. World Health Organization. 1997.countries and are at risk of acquiring the infection. Large parts 4. Nimmanntya, Dengue Fever. In Cook Gordon, Zumla Alimudin editors. S Manson’s Tropical diseases; 21st edn. Saunders, Elsvier Science, 2003 : 765of India are endemic for Dengue Fever. The first major outbreak - India was reported during 1963 in Kolkata. Indian data 5. orld Health Organization. Dengue and dengue haemorrhagic fever. Fact Wfor the last 10 years reveals that the largest number of cases Sheet No : 117.http : //www. who. int/mediacentre/factsheets/fs117/en/.and deaths due to Dengue/DHF were reported in 1996 while Accessed on 15 Mar 2008. 6. ark K. Park’s Textbook of Preventive and Social Medicine. 19th Edition. Pthe next increase was in 2003. DF / DHF is caused by Dengue Publisher : Banarsidas Bhanot, Jabalpur, India. 2007.virus which belongs to genus Flavivirus family Flaviviridae 7. orld Health organization. Regional Office for South - East Asia. Situation Wand includes serotypes 1, 2, 3 and 4. All serotypes can cause of Dengue/Dengue Haemorrhagic Fever in the South - East Asia Region. 1998.severe and fatal disease. Aedes aegypti is the main vector of 8. orld Health Organization. SEARO. Situation update of dengue in the SEA WDengue transmission in India. Another important vector is the Region, 2007.New Delhi 2007.http : //www. searo. who. int/en/Section10 /Aedes albopictus. The infection is transmitted by the bite of an Section332.htm. Accessed on 15 Mar 2008.infected female mosquito Aedes aegypti. The incubation period 9. ational Vector Borne Diseases Control Proigramme. Status Note on Dengue N Fever / Dengue Haemorrhagic Fever. Ministry of Health and Family Welfare.of Dengue fever is usually 5 - 6 days, but may vary from 3 Government of India. www. nvbdcp. gov. in/Doc/DenStatusNote. pdf. Accessedto 10 days. Clinical Presentation comprises of Undifferentiated on 18 Mar 2008.Fever, Classic Dengue Fever, Dengue Haemorrhagic Fever 10. ingh B. Dengue outbreak in 2006 : Failure of public health system? Indian S J Community Med 2007;32 : 99 - 100.and Dengue Shock Syndrome. Complete Blood Counts, Liver 11. aul SM, Sharma RS, Sharma SN, Panigrahi N, Phukan PK, Lal S. Preventing Kfunction tests, and urine analysis for microscopic haemturia dengue/dengue haemorrhagic fever outbreaks in the National Capitalindicate a diagnosis of Dengue fever and DHF / DSS. Territory of Delhi - the role of entomological surveillance. JCommunDis 1998;30 : 187 - 92.Confirmatory diagnosis of Dengue is done by isolation of the 12. DC Atlanta. Division of vector borne & infectious diseases. Dengue and Cvirus, demonstration of a rising titre of specific serum Dengue Dengue Haemorrhagic Fever : Information for Health Care Practitioners. httpantibodies, and demonstration of a specific viral antigen or : //www. cdc. gov/ncidod/dvbid/dengue/dengue - hcp. htm. Accessed on 15 Mar 2008.RNA in the tissue or serum. The basics of management of cases 13. ational Vector Borne Diseases Control Programme. Dengue / Dengue Nof Dengue fever are fluids, rest, antipyretics. In DSS volume Haemorrhagic Fever. Directorate General of Health Services, Ministry ofreplacement is the most important treatment measure and Health & Family Welfare. http : //mohfw. nic. in/NVBDCP%20WEBSITE/ dengueall. html. Accessed on 15 Mar 2008.immediate administration of intravenous fluids to expand 14. heodre F Tsia, David W Vaughn& Tom Soloman, Dengue. In Mandell Gerald Tplasma volume is essential. Prevention and Control comprise L, Bennet John E, Dolin R, editors. Mandell Douglas & Benett’s Principlesof Vector Control, epidemiological surveillance of the disease & Practices of Infectious Diseases, 6th edn. Elsevier Churchill Livingstone,as well as the vector and notification at the earliest to both the 2005 : 1926 - 1950. 15. larence J Petres, Dengue. In Kasper Dennis L, Braunwald Eugene, Cnational as well as international health authorities. FauciAnthony S et al editors Harrison’s Principles of Internal Medicine, 16th edition. Mc Graw Hill, Medical Publishing Division, 2005 : 1164 - 1173.Study exercises 16. hepherd Suzanne Moore. Dengue Fever. http : //www. emedicine. com/MED/ SLong Question : Discuss the epidemiology, treatment, topic528.htm. Accessed on 15 Mar 2008. 17. ational Vector Borne Diseases Control Programme. Do’s And Don’ts for Nprevention and control of Dengue. Managing Dengue Fever/Dengue Haemorrhagic Fever Cases. DirectorateShort Notes : (1) Spectrum of clinical presentation of Dengue General of Health Services, Ministry of Health & Family Welfare.(2) Enlist Alarming sign’s in Dengue Fever (3) Indices of vector 18. orld Health organization. SEARO. Prevention and Control of Dengue/ W Dengue Haemorrhagic Fever : Comprehensive Guidelines. WHO Regionalpopulation Publication. SEARO No 29. Division of vector borne and infectious diseases. Centres for Disease Control.MCQs 19. Future Outlook. http : //www. cdc. gov/ncidod/dvbid/dengue/index.1. Prior to 1970 only _______countries had experienced DHF htm#future. Accessed on 15 Mar 2008. epidemic (a) 3 (b) 5 (c) 7 (d) 92. In which city was the first major outbreak in India during 1963 reported ? (a) Mumbai (b) Kolkata (c) Delhi (d) Chennai • 1043 •
  • 2, 58, 998 from Maharashtra. In some areas attack rates have 175 Chikungunya reached up to 45% (1). Agent : The Chikungunya virus is an arbovirus belonging to Rajesh Vaidya the group alphaviruses of the family Togaviridae. It is believed that there are two distinct lineages of the Chikungunya virus, one containing Western African and the second comprisingChikungunya fever is an arboviral illness characterized by all Southern and East African strains. The virus originated insevere, persistent joint pains, fever and rash. The disease Africa and was subsequently introduced into Asia (12).resembles dengue fever and is spread by the bite of infectedmosquitoes. It is rarely life - threatening. However, widespread Vector : Chikungunya is transmitted by mosquitoes, includingoccurrence of the disease causes substantial morbidity and many Aedes species which bite during daylight hours. In someeconomic loss. Chikungunya virus disease has occurred parts of the world Culex species are important vectors. Insporadically in India and Southeast Asia for at least 200 India, the two important vectors are Aedes aegypti and Aedesyears. Epidemics with symptoms resembling Chikungunya albopictus, both of which also transmit dengue virus (13).fever have been recorded as early as 1824 in India (1). Transmission : There appear to be two distinct transmissionOver the last 40 years, several widespread epidemics have cycles for Chikungunya virus. A sylvatic cycle between wildoccurred in many cities of India and Southeast Asia affecting primates and arboreal Aedes mosquitoes, similar to that ofthousands of people (2, 3). Occasionally, epidemics of Dengue sylvatic Yellow fever virus in the same region has been seenand Chikungunya have occurred simultaneously in the same in Africa. Urban Chikungunya outbreaks are associated withcommunity, making clinical differentiation of the two diseases Aedes aegypti transmission in a human - mosquito - humandifficult. Unlike Dengue which has become endemic in many cycle. Urban outbreaks are sporadic in occurrence but explosiveparts of Asia, Chikungunya virus disappears and reappears in nature. Till recently it was believed that there is no directat irregular intervals. The name Chikungunya originates from person - to - person transmission. However, vertical maternalSwahili, and means “that which bends up, ” which refers to foetal transmission of the virus has been documented in anthe characteristic posture assumed by patients suffering severe outbreak at La Reunion Island (14). The virus has been isolatedjoint pains. Chikungunya virus was first isolated during a 1952 from monkeys in Africa (15). There is a risk for travellers inepidemic in Tanzania (2, 3). areas where Chikungunya is endemic and in areas affected byEpidemiology epidemics (16, 17).Global : The Chikungunya virus is probably maintained in Clinical Featuresnature by transmission between jungle primates (4). The The Incubation period is usually 2 - 3 days with a range ofdisease displays a striking epidemiological profile with major 1 - 12 days (3). The onset is with fever, chills, headache,epidemics appearing and disappearing cyclically, usually with photophobia, backache, nausea, vomiting, arthralgia, andan inter - epidemic period of 7 - 8 years and sometimes as long rash. The acute illness usually lasts about 3 to 5 days but canas 20 years (1). Currently, Chikungunya is a major arboviral be very severe. Most patients recover completely within 5 todisease in urban parts of Africa and Asia. The known geographic 7 days. More than three fourths of the patients complain ofdistribution of the virus includes large parts of Sub - Saharan severe arthralgia. One or more joints may be involved, withAfrica, Southeast Asia including Indonesia, Philippines, and swelling and redness. Another characteristic feature is theIndia, as well as islands in the South - West Indian Ocean (2, rash which is maculopapular and mainly involves the trunk.3). Other affected regions include Mauritius and Seychelles In some cases the joint pains may persist for weeks, months orin the Indian Ocean. Imported cases have been reported by even longer. Chikungunya may also be asymptomatic (2, 5, 18 -European countries like France, Germany, Italy, Norway and 21). Children may suffer from febrile convulsions. Infrequently,Switzerland (5 - 7). haemorrhagic manifestations (petechiae, purpura, epistaxis)India : The virus was first isolated in India from Kolkata in also have been reported.1963 (8). In the mid sixties outbreaks resembling Chikungunya Diagnosiswere reported from various parts of India including Vellore, Any illness with the classical triad of fever, rash, andKolkata and parts of Maharashtra (1). The last outbreak of joint pains in endemic areas must give rise to suspicion ofChikungunya virus infection was reported in 1971. There has Chikungunya. The definitive diagnosis can only be reached bybeen no active or passive surveillance of Chikungunya and serology or isolation of the virus. Alphaviruses can usually betherefore, it appeared that the virus had disappeared from recovered from blood taken during the first few days of illness.the country (9). Since 2005, however, there have been several Seroconversion can be shown in acute and convalescent serumreports of outbreaks from widespread parts of the country and samples drawn two weeks apart. Virus - specific IgM antibodiesthe re - emergence of the virus has been confirmed (10 - 12). In can be detected by capture ELISA in patients recovering fromthe present outbreak, 151 districts of eight states of India have Chikungunya infection and they decline within 3 - 6 months.reported Chikungunya fever as of Oct 2006. The affected states Haemagglutination inhibition antibodies appear as the viraemiaare Andhra Pradesh, Andaman & Nicobar Islands, Tamil Nadu, declines. Patients usually become positive by the 5th to 7thKarnataka, Maharashtra, Gujarat, Madhya Pradesh, Kerala day of illness. RT - PCR can be used for molecular diagnosis atand Delhi. More than 1.25 million cases have been reported specialized centre (12, 20).from the country with 7, 52, 245 cases from Karnataka and • 1044 •
  • Differential Diagnosis Study ExercisesChikungunya infection is often mistaken for dengue, which Long Question : Discuss the epidemiology, treatment,has a similar distribution in Asia and Africa. It may also be prevention and control of Chikungunya.confused with West Nile virus infection. Short Note : Control measures for Chikungunya.Treatment ReferencesTreatment is symptomatic and includes antipyretic and anti 1. World Health Organization. Regional Office for SE Asia. Chikungunya Fever,- inflammatory drugs. Aspirin should be avoided because of a re - emerging Disease in Asia. http : //www. searo. who. int/en/Section10/ Section2246. htm. Accessed on 15 Mar 2008.reports of mild haemorrhagic manifestations. Movement and 2. Peters Sherif CJ. and Zakioverview R. Overview of Viral Haemorrhagicmild exercise tend to improve stiffness and morning arthralgia, Fevers. In Guerrant RL, Walker DH and Weller PF (Editors) Tropical Infectiousbut heavy exercise should be avoided as it may exacerbate Diseases : Principles, Pathogens & Practice. 2nd Edn. Elsevier Churchill Livingstone. 2005.rheumatic symptoms. Although the joint symptoms may 3. Chikungunya Fever. CD Alert. Vol 10 No. 2. February 2006. Monthly Newsletterpersist for months, Chikungunya is generally an acute, self - of National Institute of Communicable Diseases, Directorate General oflimited infection with no deaths reported. Patients should be Health Services, Ministry of Health & Family Welfare. Government of India. 4. Markoff L. Alphaviruses. In Mandell GL, Bennet JE and Dolin R (Editors)nursed under mosquito nets during the viraemic stage to avoid Mandell, Douglas, and Bennett’s Principles and Practice of Infectioustransmission of the disease (2, 5, 21). Disease. 6th Edition. Elsevier Churchill Livingstone. Philadelphia 2005. 1913 - 1919.Prevention and Control 5. Powers AM, Brault AC, Shirako Y, Strauss EG, Kang W, Strauss JH, et al.There is no vaccine against this arboviral disease. No specific Evolutionary relationships and systematics of the alphaviruses. J Virol. 2001;75 : 10118 - 31.treatment is available. Prevention is entirely dependent upon 6. Carey DE. Chikungunya and dengue : a case of mistaken identity. J Hist Medtaking steps to avoid mosquito bites and elimination of Allied Sci. 1971;26 : 243 - 62.mosquito breeding sites. Control measures consist of vector 7. Krastinova E, Quatresous I, Tarantola A. Imported cases of Chikungunyacontrol activities as outlined for dengue earlier. Details about in metropolitan France : update to June 06. Eurosurveillance. 2006;11 : E060824. 1.vector control and personal protective measures are given in 8. Shah KV, Gibbs CJ Jr, Banerjee G. Virological investigation of the epidemic ofthe Chapter on Entomology. haemorrhagic fever in Calcutta : isolation of three strains of Chikungunya virus. Indian J Med Res 1964; 52 : 676 - 83.Summary 9. Pavri K. Disappearance of Chikungunya virus from India and South East Asia. Trans R Soc Trop Med Hyg 1986;80 : 491.Chikungunya fever is an arboviral illness characterized by severe, 10. Chikungunya and Dengue in the south west Indian Ocean. Epidemic andpersistent joint pains, fever and rash. The name Chikungunya Pandemic Alert and Response (EPR). http : //www. who. int/csr/don/2006originates from Swahili, and means “that which bends up, ” 11. Ravi V. Re - emergence of Chikungunya virus in India. Indian Journal of Medical Microbiology. 2006; 24 (2) : 83 - 84.which refers to the characteristic posture assumed by patients 12. Chhabra M, Mittal V, Bhattacharya D, Rana UVS, Lal S. Chikungunya fever :suffering severe joint pains. The disease appears and disappears A re - emerging viral infection. Indian Journal of Medical Microbiology. 08;cyclically, usually with an inter - epidemic period of 7 - 8 years. 26(1) : 5 - 12.The known geographic distribution of the virus includes large 13. Reiter P Fontenille D, Paupy C. Aedes albopictus as an epidemic vector of , Chikungunya virus : another emerging problem? Lancet Infect Dis. 2006;6parts of Sub - Saharan Africa, Southeast Asia including India. : 463 - 4.Chikungunya is transmitted by mosquitoes, including many 14. Robillard PY, Boumahni B, Gerardin P Michault A, Fourmaintraux A, ,Aedes species. In India, the two important vectors are Aedes Shuffenceker I, et al. Vertical maternal fetal transmission of the Chikungunya virus. Presse Med 2006;35 : 785 - 8aegypti and Aedes albopictus, Urban Chikungunya outbreaks 15. Rao TR, Paul SD, Singh KR. Experimental studies on the mechanicalare associated with Aedes aegypti transmission in a human - transmission of Chikungunya virus by Aedes aegypti. Mosquito News.mosquito - human cycle. The Incubation period is usually 2 - 3 1968;28 : 406 - 8. 16. Lanciotti Robert S., Kosoy Olga L., Laven Janeen J. Et al. Chikungunya Virusdays with a range of 1 - 12 days (3). The onset is with fever, in US Travellers Returning from India, 2006. Emerging Infectious Diseases.chills, headache, photophobia, backache, nausea, vomiting, Vol. 13, Number 5 - May 2007arthralgia, and rash. Most patients recover completely within 17. Centers for Disease Control and Prevention. Chikungunya fever diagnosed5 to 7 days. More than three fourths of the patients complain among international travellers—United States, 2005 - 2006.MMWR Morb Mortal Wkly Rep. 2006;55 : 1040 - 2.of severe arthralgia. Any illness with the classical triad of 18. WHO Country Office for India. Chikungunya. Clinical Features and Casefever, rash, and joint pains in endemic areas must give rise to Definition. http : //www. WHO India. org/LinkFiles/Chikungunya_Fever_cds -suspicion of Chikungunya. The definitive diagnosis can only chikunguniya - clinical_features. pdf. Accessed on 15 Mar 2003 19. WHO Country Office for India. Situation of Chikungunya Fever in thebe reached by serology or isolation of the virus. Treatment is World. http : //www. Who India. org/LinkFiles/Chikungunya_Fever_cds -symptomatic and includes antipyretic and anti - inflammatory chikunguniya - world. pdf. Accessed on 15 Mar 2008.drugs. There is no vaccine against this arboviral disease. No 20. National Vector Borne Diseases Control Programme. Directorate General of Health Services. Ministry of Health and FamilyWelfare. Governemt ofspecific treatment is available. Prevention is entirely dependent India. New Delhi.WHO Country Office for India. Laboratory Diagnosis ofupon taking steps to avoid mosquito bites and elimination of Chikungunyamosquito breeding sites. 21. NVBDCP WHO Country Office for India. Clinical Management of Chikungunya. . http : //www. whoindia. org/LinkFiles/Chikungunya_Fever_cds - chikunguniya - management. pdf. Accessed on 15 Mar 2008. • 1045 •
  • - reactive, neutralizing epitopes. The virus contains several 176 Japanese Encephalitis structural and non - structural polypeptides, which are encoded by a single long open reading frame (7). The virus has two sub types, Nakayam and Jagar - 01 (2). The major genotypes of this Rajesh Vaidya virus have different geographical distribution, but all belong to the same serotype and are similar in terms of virulence andJapanese Encephalitis (JE) is an arboviral disease spread by host preference (3).Culicine mosquitoes. The disease presents periodically in Vector : Anthropophilic culicine mosquitoes transfer the virusepidemic form in areas such as northern India, parts of central to humans from animal amplifying hosts, principally domesticand southern India. An overwhelming majority of the infections pigs and wading birds. The virus is transmitted chiefly byare asymptomatic. However, among symptomatic individuals the bites of mosquitoes of the Culex vishnui complex; withcase fatality rates may be higher than 20%. The public health individual vector species differing in specific geographic areas.importance of this vaccine preventable disease lies in the In India and many endemic areas in Asia, Culex tritaeniorhyncusfact that most infections occur among children and that a is the principal vector. This species feeds outdoors beginning atsizeable proportion of the survivors are left with permanent dusk and during evening hours until dawn. It breeds in waterneurological and/or psychiatric sequelae (1). The incidence of pools, marshes, flooded rice fields, and small stable collectionsJapanese encephalitis has shown an increasing trend in recent of water around cultivated fields. This vector has a wide hosttimes and the disease is fast becoming a major public health range, including domestic animals, birds, and humans. Inproblem in India (2). temperate zones, the vectors are present in greatest numbersEpidemiology from June through September and are inactive during winterGlobal : Japanese encephalitis infections occur throughout the months (8).temperate and tropical zones of Asia. The annual incidence of Host Factors : Pigs and aquatic birds (mainly herons andJapanese encephalitis disease varies considerably from one egrets of the Ardeidae family) are the natural hosts for thecountry to the other as well as within affected countries, ranging virus. Pigs are considered amplifying hosts since they allowfrom less than 10 to more than 100 per 100,000 population. manifold virus multiplication without suffering from diseaseNearly 3 billion people or close to half the global population live and maintain prolonged viraemia (6). Viraemic adult pigsin Japanese encephalitis endemic regions. Over 50,000 cases remain asymptomatic, but pregnant sows may abort or deliverare reported worldwide every year with 10,000 deaths (3). The still births. Humans are dead end accidental hosts.disease periodically becomes hyperendemic in areas such as Among humans, the virus has no specific age or sex predilection.northern India, parts of central and southern India, southern In areas where the virus has been recently introduced, all ageNepal, and northern Vietnam (3). Other countries reporting large groups are affected equally. In endemic areas, however, mostnumber of cases of Japanese encephalitis include Philippines, people are infected below the age of 15 years. In hyper - endemicThailand, Cambodia, Myanmar, and Sri Lanka. Though named areas, half of all Japanese encephalitis cases occur before theJapanese encephalitis, the disease is now rare in Japan, due to age of four years, and almost all before 10 years of age. Onlyextensive vaccination and adequate vector control. one out of 250 to 500 JE viral infections lead to symptomaticIndia : In India Japanese encephalitis was first reported in 1955 disease. Those endemic regions where childhood JE vaccinationfrom Vellore in Tamil Nadu (4). Currently this disease is reported has been widely implemented have experienced a shift in thefrom 26 states in India. Of these, only 15 states are reporting age distribution of cases towards older children and adults (3).JE regularly. The total population at risk is estimated to be In India, Japanese encephalitis is considered to be largely a160 million (5). A disturbing feature of Japanese encephalitis paediatric problem. Young children below 10 years of age arereporting in India has been the occurrence of several large more likely to die, and if they survive, are more likely to haveoutbreaks from different parts of the country. The first major residual neurological sequelae (2).outbreak of JE was reported from West Bengal in 1973 in two Environmental Factors : Environmental factors related todistricts followed by another outbreak in 1976. Subsequently transmission of JE are related principally to temperature andoutbreaks have been reported from the states of Bihar, Uttar humidity conditions conducive to breeding and survival ofPradesh, Assam, Manipur, Andhra Pradesh, Karnataka, Madhya the vector. In tropical and subtropical areas, transmissionPradesh, Maharashtra, Tamil Nadu, Haryana, Kerala, West intensifies in the rainy season. In temperate locations,Bengal, Orissa and union territories of Goa and Pondicherry transmission usually starts in April and may last until October.(2). In the recent past the reported annual incidence in India In irrigated areas, transmission may occur even in the dryhas ranged between 1,765 and 3,428 and deaths between 466 season (3). Habitats supporting the transmission cycle ofand 707 (6). JE virus are principally in rural, agricultural locations. InAgent : Japanese encephalitis virus belongs to the family many areas of Asia, appropriate ecologic conditions for virusFlaviviridae, which are single - stranded RNA viruses. Like other transmission occur near and even within urban centres (8). Inflaviviruses, the Japanese encephalitis virus is an enveloped, many Asian countries, major outbreaks of JE occur at intervalsplus sense virus. It is antigenically related to several other of 2 - 15 years (3).flaviviruses including dengue virus, St. Louis encephalitisvirus, Murray Valley virus and West Nile virus (2). The envelope Clinical Featuresglycoprotein of the JE virus contains specific as well as cross The incubation period of Japanese encephalitis ranges from • 1046 •
  • 4 to 14 days (3). The virus initially multiplies at the site of Probable : A suspected case with presumptive laboratorythe bite and in the draining lymph nodes. Subsequently, results: Detection of an acute phase anti - viral antibodyviremia develops, leading to inflammatory changes in the response through IgM in serum/ elevated and stable JE antibodyheart, lungs, liver, and reticuloendothelial system. Most titres in serum through ELISA/HI/Neutralizing assay.infections are cleared before the virus can invade the central Confirmed : A suspect case with confirmed laboratory result:nervous system (CNS). However, neurologic invasion can JE IgM in CSF or 4 fold or greater rise in paired sera (acutedevelop leading to involvement of large areas of the brain, and convalescent) through IgM/IgG ELISA, HI, Neutralizationincluding the thalamus, basal ganglia, brain stem, cerebellum, test or detection of virus, antigen or genome in tissue, blood orhippocampus, and cerebral cortex (9). Most infected persons other body fluid by immuno - chemistry, immunoflourescencedevelop mild symptoms or no symptoms at all. Symptoms soon or PCR.after exposure appear 6 - 8 days after the bite of an infectedmosquito. The disease is characterized by sudden onset of Treatmentfever, chills, body ache and mental confusion. Severe cases There is no specific anti - viral medicine available againstmay progress to coma. In children, gastrointestinal pain and JE virus. The cases are managed symptomatically. Clinicalvomiting may be the dominant initial symptoms. Irritability, management of JE is supportive and in the acute phase isvomiting and diarrhoea or an acute convulsion may be the directed at maintaining fluid and electrolyte balance andearliest objective signs of illness in an infant or child. JE may control of convulsions, if present. However, treating raisedpresent as a mild disease, leading to an uneventful recovery, intracranial pressure and convulsions have been reported toor may rapidly progress to severe encephalitis with mental decrease the mortality and morbidity significantly (10).disturbances, general or focal neurological abnormalities and Prevention and Controlcoma. Vector control and vaccination are the two primary strategiesOut of the approximately 50,000 cases of JE that are estimated for control of Japanese Encephalitis. In countries such asto occur each year, about 10,000 end fatally, and about 15,000 Japan and Korea the incidence of JE has decreased over severalof the survivors are left with neurological and/or psychiatric decades, primarily as a result of extensive use of JE vaccines.sequelae, requiring rehabilitation and continued care (2, 3). Improved socioeconomic conditions, changed life styles andApproximately 33 - 50% of patients who survive have major control measures such as centralized pig production and the useneurologic sequelae at one year, including seizure disorders; of insecticides may also have contributed to this developmentmotor or cranial nerve paresis, or movement disorders. Nearly (3). Details on vector control are available in the chapter on75% of symptomatic patients with JE who are evaluated five Entomology.years after the disease score lower than uninfected subjects on Vaccines : Three types of vaccines are currently in use againststandardized tests (9). Japanese encephalitis. The mouse brain - derived, purified andDiagnosis inactivated vaccine, which is based on either the Nakayama orJE is clinically indistinguishable from other forms of viral Beijing strains of the JE virus and is produced in several Asianencephalitis. History of exposure to mosquitoes in an endemic countries including India. Another inactivated vaccine is thearea or during an epidemic may be elicited. A CBC count often cell culture - derived, vaccine based on the viral Beijing P - 3shows nonspecific modest leukocytosis in the first week of strain. A live attenuated vaccine widely used in China is the cellillness. A mild anaemia also may be present. Some studies culture - derived vaccine based on the SA 14 - 14 - 2 strain ofhave reported thrombocytopenia in children with Japanese the JE virus (3).encephalitis (9). Neutrophils predominate in early CSF The mouse brain - derived JE vaccine is used in India. It issamples but a lymphocytic pleocytosis is typical. CSF protein is produced by the Central Research Institute, Kasauli. Threemoderately elevated in about 50% of cases (2). doses are required to produce primary immunization. TwoConfirmation of a suspected case of Japanese encephalitis is doses of 1 ml (0.5 ml for children below three years) aremainly based on serology using IgM - capture ELISA which administered sub - cutaneously within a gap of 7 - 14 daysdetects specific IgM in the cerebrospinal fluid or in the blood followed by third dose any time after one month and before oneof almost all patients within 7 days of onset of disease. Other year of the second dose. A booster is required after 3 years (6).methods include conventional antibody assays on paired sera Several other Asian countries have adopted a similar schedulefor the demonstration of a significant rise in total JE - specific of two primary doses four weeks apart, followed by a boosterantibody, as well as a dot - blot IgM assay, suitable for use in after one year. In some countries, subsequent boosters arethe field (3). recommended, usually at about 3 - year intervals up to the age of 10 to 15 years (3). For travellers aged more than oneCase Definitions for JE Diagnosis and Reporting (6) year visiting rural areas of endemic countries, the establishedClinical Suspect : Febrile illness of variable severity associated practice is to administer 3 primary doses at days 0, 7 and 28 orwith neurological symptoms ranging from headache to two primary doses preferably four weeks apart.meningitis or encephalitis. Symptoms can include headache, The mouse brain - derived JE vaccine is been considered safe.fever, meningeal signs, stupor, disorientation, coma, tremors, Local reactions such as tenderness and swelling occur inparalysis (generalized), hypertonia, loss of coordination (Patient about 20% of vaccinees. Mild systemic symptoms, includingwith fever, altered sensorium lasting more than 6 hours, no headache, myalgia, gastrointestinal symptoms and fever mayskin rash & other known causes of encephalitis excluded). • 1047 •
  • also occur. Being a killed vaccine, only contraindication to the Japanese Encephalitis. Three types of vaccines are currently inuse of this vaccine is a history of hypersensitivity reactions to use against Japanese encephalitis. The mouse brain - derived,a previous dose. Pregnant women should be vaccinated only purified and inactivated vaccine, which is based on either thewhen at high risk of exposure to the infection. The vaccine can Nakayama or Beijing strains of the JE virus. A live attenuatedbe given to HIV infected individuals (3). The biggest limitation vaccine widely used in China is the cell culture - derived vaccineof the mouse derived killed vaccine is that rapid large scale based on the SA 14 - 14 - 2 strain of the JE virus. The Worldproduction of the vaccine is not feasible. Health Organization recommends that JE immunization shouldThe live attenuated vaccine was licensed in China in 1989. be integrated into the EPI programmes in all areas where JEExtensive use of this and other vaccines has significantly constitutes a public health problem.contributed to reducing the burden of JE in China. The vaccine Study Exerciseshas recently been licensed for use in India. It is administered in Long Question : Discuss the epidemiology, treatment,two doses at an interval of one year. prevention and control of Japanese encephalitis.WHO Position on JE Vaccines : The World Health Organization Short Notes : (1) Case definitions for JE, Diagnosis andrecommends that JE immunization should be integrated into Reporting (2) Vaccines for Japanese Encephalitisthe EPI programmes in all areas where JE constitutes a publichealth problem. The most effective immunization strategy in JE MCQs :- endemic settings is one time catch - up campaigns including 1. Currently this disease is reported from ____ no. of states inchild health weeks or multi - antigen campaigns in the locally - India (a) 23 (b) 24 (c) 25 (d) 26defined primary target population, followed by incorporation of 2. Japanese encephalitis virus is (a) Single - stranded RNAthe JE vaccine into the routine immunization programme (3). Virus (b)Double - stranded RNA Virus (c) Single - stranded DNA Virus (d)Double - stranded DNA VirusSummary 3. In India principal vector for JE is (a) Culex quinquefasciatusJapanese encephalitis is an arboviral disease spread by culicine (b) Culex tritaeniorhyncus (c) Aedes vittatus (d) Aedesmosquitoes. The public health importance of this vaccine niveuspreventable disease lies in the fact that most infections occur 4. Natural host for the virus are (a) Humans (b) Cattleamong children and that a sizeable proportion of the survivors (c) Pigs (d) Monkeysare left with permanent neurological and/or psychiatric sequelae. 5. Cell culture - derived vaccine is based on the _________Nearly 3 billion people or close to half the global population strain of the JE virus (a) SA 14 - 14 - 1 (b) SA 15 - 15 - 1live in Japanese encephalitis endemic regions. Over 50,000 (c) SA 14 - 14 - 2 (d) SA 15 - 15 - 2cases are reported worldwide every year with 10000 deaths. Answers : (1) d; (2) a; (3) b; (4) c; (5) c.In India Japanese encephalitis was first reported in 1955 fromVellore in Tamil Nadu. Currently this disease is reported from References 1. World Health Organization.Weekly Epidemiological Record. 1998, 73, 33726 states in India. Japanese encephalitis virus belongs to the - Flaviviridae, which are single - stranded RNA viruses. 2. Kabilan L, Rajendran R, Arunachalam N, Ramesh S, Srinivasan S, PhilipAnthropophilic culicine mosquitoes transfer the virus to humans Samuel P Dash AP Japanese encephalitis in India : An overview. Indian J , .from animal amplifying hosts, principally domestic pigs and Pediatr 2004; 71 : 609 - 15. 3. World Health Organization. Weekly Epidemiological Record. No. 34/35,wading birds. The virus is transmitted chiefly by the bites of 2006, 81, 325 - 340. http : //www. who. int/wer.mosquitoes of the Culex vishnui complex. In India and many 4. Namachivayam V, Umayal K. Proceedings of National Conference on Japaneseendemic areas in Asia, Culex tritaeniorhyncus is the principal Encephalitis 1982; 30 - 33.vector. Pigs and aquatic birds are the natural hosts for the virus. 5. National Institute of Health and Family Welfare. National Japanese Encephalitis Control Programme. http : //www. nihfw. org/index. asp.Humans are dead end accidental hosts. In hyper - endemic Accessed on 12 Mar 2008.areas, half of all Japanese encephalitis cases occur before the 6. Directorate General of Health Services. Ministry of Health and Family Welfare.age of four years, and almost all before 10 years of age. Only 1 Government of India. National Vector Borne Diseases Control Programme. http : //mohfw. nic. in/NVBDCP%20WEBSITE/home. htm. Accessed on 12 Marin 250 to 500 JE viral infections result in symptomatic disease. 2008.The incubation period of Japanese encephalitis ranges from 4 - 7. Sumeyoshi H, Mori C, Fuka I et al. Complete nucleotide sequence of the14 days. The disease is characterized by sudden onset of fever, Japanese encephalitis virus genome RNA. Virology 1987; 161 : 497 - 510 8. National Institute of Communicable Diseases, Directorate General of Healthchills, body ache and mental confusion. Severe cases may Services, Ministry of Health and Family Welfare (GOI). http : //nicd. org/progress to coma. JE is clinically indistinguishable from other factsheet_je. asp. Accessed on 12 Mar 2008.forms of viral encephalitis. Confirmation of a suspected case of 9. Kallen Alexander J. Japanese Encephalitis. http : //www. emedicine. com/ med/TOPIC3158. HTM. Accessed on 14 Mar 2008.Japanese encephalitis is mainly based on serology using IgM. 10. Tiroumourougane SV, Raghava P Srinivasan S, Badrinath. Management ,There is no specific anti - viral medicine available against JE parameters affecting the outcome of Japanese encephalitis. J Trop Pediatrvirus. The cases are managed symptomatically. Vector control 2003; 49(3) : 153 - 156and vaccination are the two primary strategies for control of • 1048 •
  • Spotted fever group; Typhus group; Scrub typhus (or Orientia 177 Rickettsial Diseases group); and others (1, 6). Epidemiology Rajesh Vaidya Global : The geographic as well as temporal distribution of rickettsial diseases is largely determined by their vectors. LouseRickettsial diseases occur in all parts of the world and are a borne rickettsial diseases are reported from across the world.significant cause of morbidity and mortality (1). The occurrence Common flea species like the dog, cat, and rat flea are alsoof rickettsial diseases often goes unrecognized because of global in distribution. As a consequence, rickettsial diseasesdifficulties in arriving at a definitive diagnosis. Lately, however, transmitted by them are also reported from all parts of theRickettsiae are being recognized as emerging or re - emerging world. Ticks are more restricted in their distribution. Tick bornepathogens in many places of the world making them the cause diseases are, therefore, more localized in their distribution.of some of the oldest and most recently recognized infectious The geographic distribution of rickettsial agents is describeddiseases (2, 3). New genetic tools have led to the discovery of in Table - 1.many new rickettsial diseases over the past 20 years (4). Of the India : Rickettsioses are reported from many parts of India.14 currently recognized rickettsioses, six have been described A large number of studies have documented outbreaks ofwithin the last 12 years (5). Although rickettsiae require living rickettsial diseases, particularly Scrub typhus among Indiancells for growth, they are true bacteria as they have metabolic Armed Forces personnel from different parts of the countryenzymes and cell walls, and are susceptible to antibiotics. Most (7 - 13). Occurrence of Rickettsioses, including scrub typhusrickettsial infections result in zoonotic diseases which are as well as spotted fevers have been reported from Himachalmaintained in nature through a complex interaction between Pradesh, Maharashtra, Assam, West Bengal, Kerala and Tamilmammalian reservoirs and invertebrate factors (ticks, mites, Nadu (2, 14 - 19).fleas, and lice). An important feature of rickettsial infections Agent : Rickettsiae are a diverse collection of organismsis that some invertebrate vectors can also serve as reservoirs. with several differences. The common threads that hold theHumans are usually accidental hosts and play little role in rickettsiae into a group are their epidemiology and their obligatenatural disease transmission. intracellular lifestyle. The classification of rickettsia has seenDifferent authors have grouped Rickettsial diseases in several a significant reorganization in the recent past particularlyways. Rickettsial diseases are usually divided into four groups: Table - 1 : Epidemiologic Features of Rickettsial Diseases (20) Animal Disease Group Disease Agent Vector Geographical Distribution Reservoir Human Mountainous regions of Africa, Asia, body louse Epidemic Rickettsia and Central and South America. (Pediculus Humans typhus prowazekii India - J&K, Himachal, Uttarakhand, humanus W Bengal, Arunachal Pradesh. corporis), Rat flea Typhus Group Murine Rickettsia (Xenopsylla Rats, mice Worldwide typhus typhi cheopis) Tick (Ixodes sp Indian Tick Rickettsia Boophilus sp Dogs, Africa, India, Europe, East, Typhus conorii Haemophysalis rodents Mediterranean, India - Uttaranchal sp) Rickettsial Rickettsia Russia, South Africa, Korea, Mite House mice pox akari Turkey, Balkan countries Spotted Fever Rocky Rickettsia Tick Rodents Mexico, Central and South America Group Mountain rickettsii spotted fever Orientia Scrub Orientia Mite (L Rodents Asia and Australia typhus tsutsugamushi deliense) India - J&K, Himachal, Uttarakhand, W Bengal, Arunachal Pradesh Others Q fever Coxiella Inhalation Goats, Worldwide burnetii of infectious sheep, aerosols; tick cattle, cats • 1049 •
  • due to technological advances in molecular genetics. The Diagnosisorder Rickettsiales has two families Rickettsiacese and Confirmation of diagnosis is done most often by serology.Anaplasmataceae. The family Rickettsiacese has two genera : Titres of specific antibodies rise to diagnostic levels usually byRickettsia and Orientia. The family Anaplasmataceae has five the second week of illness (1). Indirect Fluorescent Antibodygenera. At least 26 agents from the order Rickettsiales have (IFA) and ELISA tests are available for serology. The Weil - Felixbeen recognized as human pathogens (1). Rickettsia are small test, which uses the OX and K strains of Proteus mirabilis, is(0.3 X 2 μm) aerobic, obligate intracellular parasites. They are still the most widely used diagnostic test in India. However, thePleomorphic, usually coccobacillary. They appear blue with test is not very sensitive. PCR is also being increasingly used toGiemsa’s stain and their growth is enhanced in the presence confirm the diagnosis (4).of sulphonamides. TreatmentHost : Groups at risk for exposure to agents of rickettsialdiseases are travellers, wood cutters, farmers and armed forces Tetracyclines are the antibiotic of choice against rickettsialpersonnel as their occupational or recreational activities bring infections. Doxycycline is the most commonly prescribed drug.them in contact with habitats that support the vectors or animal Chloramphenicol should be used for infections in pregnantreservoir species associated with these pathogens (21). women but caution should be exercised in the third trimester because of the risk of “gray baby syndrome”. ChloramphenicolTransmission : Rickettsiae are transmitted to humans by the is not considered effective against Ehrlichioses. The clinicalbite of infected ticks and mites and by the contamination of the features, diagnosis and treatment of common rickettsialbite or other skin wounds with the faeces of infected lice and diseases is given in Table - 2.fleas. The rickettsiae present in the dried excreta of insects mayalso enter through the conjunctivae or even through inhalation. Prevention and ControlIn ticks and mites transovarial and trans - stadial transmission The essential method of prevention is avoidance of potentiallyof rickettsia frequently occurs. After entering the body rickettsia vector infected areas and the use of personal protectivespread through the bloodstream to infect vascular endothelium measures. The use of insect repellents such as DEET and DEPAin the skin, brain, lungs, heart, kidneys, liver, gastrointestinal in combination with appropriate clothing such as long sleevestract and other organs. and anklets may be useful in avoiding contact with vectors.Clinical Features Scrub TyphusMost rickettsial diseases are characterized by the classical triad Scrub typhus is caused by Orientia tsutsugamushi andof fever, headache, and rash. Hepatosplenomegaly and myalgia transmitted by the bite of infected larvae of the miteare often accompanying features. Rash is absent in Q fever and Leptotrombidium deliense. It is a zoonoses with humans beingin several of the newly recognized rickettsial infections. About accidental, dead end hosts. Scrub typhus was first describedhalf the patients infected by a tick or mite bite develop a typical by Hashimoto from Japan (22). It is reported most often fromeschar at the bite site. Southeast Asia and Japan and is the most commonly reported Table 2 : Clinical Features and Treatment of Rickettsial Diseases Incubation Weil Felix Disease Clinical Features Treatment period Reaction Epidemic typhus 6 - 15 days Headache, chills, fever, prostration, OX - 19 Doxycycline 100mg BD for 7 - 10 confusion, photophobia, vomiting, days or till person is afebrile. rash (generally starting on trunk) Chloramphenicol 60 - 75mg/ kg/day in 4 divided doses for pregnant women Murine typhus 8 - 16 days As above, generally less severe OX - 19 Same as above Indian Tick 5 - 10 days Fever, eschar, regional adenopathy, OX - 19 Same as above Typhus maculopapular rash on extremities or OX - 2 Alternative - Ciprofloxacin Rocky Mountain 2 - 14 - days Headache, fever, abdominal pain, OX - 19 Same as above spotted fever macular rash progressing into opular or OX - 2 or petechial (starting on extremities) Scrub typhus 6 - 21 days Fever, headache, sweating, OX - K Doxycycline 100mg BD. conjunctival injection, adenopathy, Rifampicin 600 - 900mg/day, eschar, rash, respiratory distress Azithromycin and Ciprofloxacin are other alternatives Q fever 3 - 30 days Fever, headache, chills, sweating, None Doxycycline. pneumonia, hepatitis, endocarditis Rifampicin, Ciprofloxacin are other alternatives • 1050 •
  • rickettsial infection in India. Globally over one billion people incubation period ranging from 6 to 21 days (usually 10 - 12are at risk for scrub typhus and an estimated one million cases days), patients usually present with fever and headache. Otheroccur annually (22). symptoms and signs include myalgia, chills, cough, adenopathy,Epidemiology and diarrhoea. The patient is often labeled as “fever of unknown origin” because of the non specific symptoms. In about half theThe disease is largely limited to Southeastern and Eastern Asia, patients, a skin ulcer may develop after the onset of fever atNorthern Australia, India, Pakistan, Ceylon and other islands the site of the mite bite. The ulcer is approximately 1 cm inin the region. In India, it is present in whole of the Shivalak diameter and fills with fluid, eventually rupturing and formingranges from Kashmir to Assam, Eastern and Western Ghats a black eschar. A macular rash may appear on the body on 5thand the Vindhyachal and Satpura ranges in the central part to 7th day and last for a few hours to a few days. Complicationsof India. The distribution of the disease corresponds with the such as pneumonitis, myocarditis, encephalitis and peripheraldistribution of Leptotrombidium deliense and Leptotrombidium circulatory failure may occur. Deaths usually occur as a resultakamushi. The vector mite is now known to be present in of late presentation or a delayed diagnosis (22).diverse ecological niches such as equatorial rain forests, semi -deserts and Alpine subarctic terrains in the Himalayan regions. DiagnosisEndemic foci are usually associated with specific habitats such A high index of suspicion in occupational settings like theas abandoned plantations, gardens or rice fields, overgrown armed forces can aid timely clinical diagnosis. The diagnosisforest clearings, shrubby fringes of fields and forests, river can be confirmed by Weil - Felix (WF), Fluorescent Antibodybanks and grassy fields. These ecological patches which attract (FA), Complement Fixation (CF) or Microscopic Agglutinationthe natural host of mite vectors are called “mite islands”. (MA) test. Initial laboratory diagnosis may be difficult sinceWithin the mite islands there may be a limited area of intensive antibody levels may be low during early infection. Mosttransmission of rickettsiae called “Typhus Island”. Outbreaks serological tests become positive only in the second week ofof scrub typhus have been repeatedly been reported in India illness. PCR has now become one of the important diagnosticboth among civilians and personnel of the Armed Forces (8 - techniques for scrub typhus. A nested PCR on the eschar13, 16, 17, 19). provides a rapid diagnostic test for scrub typhus in the early,Agent : Orientia tsutsugamushi is the agent of scrub typhus in acute stage (24). Ready to use ELISA kits are also availableIndia. It differs from other rickettsiae in its antigenic structure. commercially.At least eight serotypes are recognized. Infection with one Most of these tests may not be available in remote areas wherestrain does not produce immunity against infection by others. most cases occur. The Weil - Felix test (WF) using Proteus OXKVector : The infection is transmitted through the larval mites strain is still the most commonly used test, though it lacksor “chiggers” belonging to the family Trombiculidae, genus sensitivity. Only half the patients will have positive Weil - Felixand subgenus Leptotrombidium. More than 150 species test during second week of illness. A four fold rise in titre orhave been described but only a few are known to be of a single reading of at least is 1:80 are considered significantimportance to man. About 204 trombiculid mite species have (22).been described from India so far. The important mite species Treatmentare Leptotrombidium deliense, Leptotrombidium akamushi, Tetracyclines are the antibiotic of choice. The dosage isLeptotrombidium scutellare and Leptotrombidium pallidum. Tetracycline, 500 mg four times a days or doxycycline 200 mgTransovarian transmission of rickettsiae occurs in mites for once (or 100 mg BD) a day for 7 to 14 days. Alternatives includeseveral generations. Only the larval stage takes a blood meal. Chloramphenicol 500 mg four times a day or Rifampicin, 900Host : A number of small rodents particularly wild rats of mg per day for seven days. Early treatment results in bettersubgenus Rattus are the natural hosts for scrub typhus (22) outcomes and faster resolution (22, 23).The rodents and acarine hosts do not succumb to the disease. Prevention and ControlThus the field rodents and the vector mites act as a reservoirand between the two the infection perpetuates in nature. The Avoidance of exposure to the vector and personal protectivemigration of infested or infected rodents leads to establishment measures are the mainstay of prevention of scrub typhus.of new foci of disease. Outdoor camp sites should be selected carefully to avoid mites. Camp sites should be cleared of vegetation and treated withTransmission : The infection is transmitted to man through the insecticide (Malathion / Fenthion) before occupation. Antibite of infective mite larvae, which feeds on lymph and tissue rodent measures like denying shelter and food to rodents byfluid rather than blood. Rather than biting or piercing the skin, proper storage of food, hygienic disposal of refuse and keepingmite larvae prefer to insert their mouthparts down hair follicles the area cleared of all junk, and rubble must be followed.or pores. A large numbers of the Orientia tsutsugamushi are Application of repellants to all clothing is the most importantpresent in the salivary glands of the larvae and these are single preventive measure (25, 26).injected into its host when it feeds (23). Human infection takesplace when man accidentally picks up an infective larval mite Epidemic Typhuswhile walking, sitting, or lying on the infested ground. Epidemic typhus is the classical form of rickettsial disease.Clinical Features About 30 million cases including three million deaths occurredScrub typhus has a broad clinical spectrum varying from mild in the Soviet Union & Eastern Europe during 1918 - 1922.or inapparent infection to organ failure and death. After an During World War II, typhus struck heavily in concentration • 1051 •
  • camps in Eastern Europe and North America. endemic country (27, 28). The recurrence is presumed to beThe disease is caused by Rickettsia prowazekii and transmitted precipitated by stress or a waning immune system. The illnessby the human louse Pediculus humanus corporis. The infection is similar to louse borne typhus but is usually milder. Weil -is transmitted by the entry of the infectious faeces, the gut Felix reaction may be negative in very low titre.contents, or the body fluid of the louse through abrasion on Endemic (Murine) Typhusthe skin which may result from simultaneous scratching. Therickettsiae present in the dried excreta of insects may also enter It is an acute febrile illness caused by Rickettsia typhi andthrough the conjunctivae or even through inhalation. Once transmitted to humans by the rat flea Xenopsylla cheopis.infected, the lice remain infective throughout their remaining The mode of transmission is by contamination of the brokenlife. skin by rickettsia - laden faeces, and dried flea faeces gaining entry through conjunctivae or the upper respiratory tract byEpidemic typhus is characterized by sub - acute onset, with aerosol. Complement fixing antibodies against murine typhusfever interposed by rigors, accompanied by headache, nausea, have recently been detected in paired sera from local casesgiddiness, vomiting and flushed dry skin. On the third day, the of fever of unknown origin by workers of NIV, Pune. Similartemperature rapidly rises up to 40° C, face and eyes become studies elsewhere indicate that murine typhus is endemic insuffused, headache and bodyache become severe, and the practically every town of India especially where rats abound.peculiar stuporose, drunken, confused and delirious state, Control measures should be directed against rodents and ratsimilar to that found in enteric fever is seen. The patient has fleas. There is no specific vaccine. Epidemic typhus vaccinea foul smell and heavily coated tongue. The spleen is enlarged does not protect against murine typhus. However followingand haematuria and albuminuria occur. Blood pressure falls. attack by one disease, there is some cross - protection againstTemperature remains high for 12 - 14 days. Rash occurs on 5th the other disease.or 6th day. The case fatality varies widely and is influencedby the nutritional state and age of patient. In healthy, well fed Q Feveryoung adults the case fatality is less than 5 percent. Diagnosis It is an acute infectious disease caused by Coxiella confirmed by Microscopic Agglutination (MA), Complement The disease has world - wide distribution. During World WarFixation (CF) and Fluorescent Antibody (FA) tests. II it was a cause of major epidemics in Europe (Balkan grippe).Man has no natural immunity; one clinical attack confers high Apart from two case reports, studies on human Q fever in Indiaimmunity but not life long and a second attack may occur. All have been mainly limited to sero epidemiological surveys inages and sexes are susceptible. The immunity is type specific; several parts of the country. Isolation of and demonstration oftherefore, an attack does not confer immunity against other its antibodies from human milk have also been reported.rickettsial diseases. Cases are infectious to the louse during the Small mammals and possibly some birds are the permanentlast two or three days of the incubation period, and throughout reservoirs of infection with some Ixodid and Argasid ticksthe febrile period, for a total of about 12 to 13 days. Doxycycline acting as vectors. From the wild animals the infection spreadsor chloramphenicol (for pregnant women) are the drug of choice to cattle, sheep and goats. The mode of transmission forfor treatment. humans is by inhalation of infected dust, by handling infectedA high standard of personal hygiene to prevent louse infestation, materials and possibly by drinking contaminated raw milk.avoidance of contact with those likely to be infected with the The incubation period of Q fever ranges from 15 to 26 daysdisease and infested with louse and preventive immunization with an average of approximately 19 days. The disease isare the important preventive measures. Treatment of louse characterized by fever, malaise, myalgia, headache, weakness,infested individuals can be carried out by application of dust of anorexia, loss of weight and interstitial pneumonitis. Case10% DDT, 1% malathion or 1% indane powder to the person as fatality is low but convalescence is prolonged. Complicationswell as his clothing. Treatment can also be done with phenothrin such as hepatitis, endocarditis, thrombosis, heamorrhagesdust 0. 3 - 0. 4%. Other lotions or shampoo formulations can and meningitis may follow. The diagnosis is confirmed by CFalso be applied for better results like permethrin lotion (1. 0%) tests. Radiological findings resemble those of primary atypicalor deltamethrin lotion (0. 03%). pneumonia. Human cases of Q fever should be treated withA formalin inactivated epidemic typhus vaccine prepared from tetracyclines or chloramphenicol.rickettsia grown in embryonated eggs was used to protect The disease can be prevented by avoiding exposure to infectedtroops during World War II. It is given in 2 subcutaneous aerosols. Milk from infected cattle must be boiled or pasteurized.injections of 1 ml each at an interval of 10 to 14 days. Booster Persons at risk such as dairy workers, butchers, wool sorters,doses are recommended every 6 months. A recent advancement farmers, cowherds and laboratory workers can be protected byis the development of a vaccine consisting of live attenuated immunization with specific vaccines such as those preparedstrain ‘E’ rickettsial organisms. It has been tried extensively from phase I rickettsiae.and appears to be effective when tested under field conditions.It is not yet available for general use. SummaryBrill - Zinsser Disease Rickettsial diseases occur in all parts of the world and are aIt is a recrudescent episode of epidemic typhus which occurs significant cause of morbidity and mortality. Most rickettsialyears after the initial attack, in persons who have recovered infections result in zoonotic diseases. Humans are usuallyfrom the epidemic disease acquired while residing in the accidental hosts and play little role in natural disease • 1052 •
  • transmission. Rickettsial diseases are usually divided into four 3. Parola P Paddock CD and Raoult D. Tick - Borne Rickettsioses Around The , World : Emerging Diseases Challenging Old Concepts. Clinical Microbiologygroups : Spotted fever group; Typhus group; Scrub typhus (or Reviews 2005; 18 (4) : 719 - 756.Orientia group); and others. The geographic as well as temporal 4. Raoult D. Introduction to Rickettsioses and Ehrlichoses. In Mandell GL,distribution of rickettsial diseases is largely determined Bennet JE and Dolin R (Editors) Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease. 6th Edition. Elsevier Churchill their vectors. Rickettsia are small (0.3 X 2 μm) aerobic, Philadelphia 2005. 2284 - 2287.obligate intracellular parasites. Groups at risk for exposure 5. Raoult D and Roux Ve´Ronique. Rickettsioses as Paradigms of New orto agents of rickettsial diseases are travellers, wood cutters Emerging Infectious Diseases. Clinical Microbiology Reviews; Vol. 10, No. 4 : Oct. 1997 : 694 - their occupational or recreational activities bring them in 6. Rathore MH and Maraqua N. Rickettsial Infection. Emedicine Article.http : //contact with habitats that support the vectors. Rickettsiae are Accessed on 24 Oct 2008.transmitted to humans by the bite of infected ticks and mites 7. Bhalwar R, Tilak R, Rao MKK and Tilak VW. Surveillance of Scrub Typhus inand by the contamination of the bite or other skin wounds with the Fringe Areas Around Pune : Potential for Transmission Does Exist. MJAFI 2003;59 : 117 - 120.the faeces of infected lice and fleas. Most rickettsial diseases 8. Aggarwal SK. Report on outbreak of scrub typhus in IMA Dehradun by SHOare characterized by the classical triad of fever, headache, and Dehradun (Unpublished Report), 1992 : 1 - 15.rash. Confirmation of diagnosis is done most often by serology. 9. Prasad BNBM, Das MR, and Kasthuri AS. Scrub Typhus - Not a BygoneThe Weil - Felix test, which uses the OX and K strains of Proteus Disease. JAPI 1997; 45 : 188 - 190. 10. Singh P Singh R, and Dhand VP Resurgence of Scrub Typhus. MJAFI 1992; , .mirabilis, is still the most widely used diagnostic test in India. 48 : 84 - 87.Tetracyclines are the antibiotic of choice against rickettsial 11. Chauhan SS, Ohri VC, Kumar N, and Dhingra A. Scrub Typhus : Twoinfections. The essential method of prevention is avoidance Interesting Cases. MJAFI. 1993; 49 : 277 - 278.of potentially vector infected areas and the use of personal 12. Mehta SR, Dham SK, Jetley V, and Shahane AG. Scrub Typhus - A Report of Six Cases. MJAFI 1993;49 : 279 - 281.protective measures. 13. Rajagopal R, Khati C, Vasdev V, and Trehan A. Scrub Typhus : A Case Report. Indian J Dermatol Venereol Leprol 2003; 69 : 413 - 415.Study Exercises 14. Padbidri VS and Gupta NP Rickettsiosis In India : A review. J Indian Med .Long Question : Discuss the epidemiology, treatment, Assoc 1978; 71 : 104 - 107. 15. Mathai E, Lloyd G, Cherian T, et al. Serological Evidence for the Continuedprevention and control of Rickettsial diseases. Presence of Human Rickettsioses in Southern India. Ann Trop Med ParasitShort Notes : (1) Classification of Rickettsial diseases (2) Scrub 2001;95 : 395 - 398. 16. Batra HV. Spotted Fevers & Typhus Fever in Tamil Nadu. Indian J Med Res;Typhus (3) Epidemic Typhus 26, August 2007 : 101 - 103.MCQs 17. Mahajan SK, Rolain JM, Kashyap R, Bakshi D, Sharma V, Parasher BS, et al. Scrub Typhus in Himalayas. Emerg Infect Dis 2006; 12 : 1590 - 1592.1. Limited area of intensive transmission of rickettsiae called 18. Sundhindra BK, Vijaykumar S, Kutti AK, Tholpadi SR, Rajan AS, Mathai E, et as (a) Typhus Island (b) Mite islands (c) Rickettsiae Island al. Rickettsial Spotted Fever in Kerala. Natl Med J India 2004; 17 : 51 - 52. (d) None of the above 19. Kamarasu K, Malathi M, Rajagopal V, Subramani K, Jagadeeshramasamy D,2. Agent for Indian Tick Typhus is (a) Rickettsia typhi and Mathai E. Serological Evidence for Wide Distribution of Spotted Fevers and Typhus Fever in Tamil Nadu. Indian J Med Res 2007; 126 : 128 - 30. (b) Rickettsia conorii (c) Rickettsia akari (d) Rickettsia 20. Centres for Disease Control and Prevention. Traveller’s Health : Yellow Book. prowazekii Prevention of Specific Infectious Diseases. 2008. Rickettsial Infections http3. Most commonly reported rickettsial infection in India is (a) : // - Rickettsial.aspx. Accessed on 27 Oct 2008. Scrub typhus (b) Indian Tick Typhus (c) Epidemic typhus 21. Jensenius M, Fournier PE and Raoult D. Tick - Borne Rickettsioses in (d) Rickettsial pox International Travellers. Int J Infect Dis. 2004; 8(3) : 139 - 46.4. Epidemic Typhus is transmitted by (a) Tick (b) Mite 22. Mahajan SK. Scrub Typhus. JAPI. 2005 ; 53(November)  : 954 - 958. (c) Human louse (d) Rat flea 23. Devine J. A Review of Scrub Typhus Management in 2000 - 2001 and Implications for Soldiers. Journal of Rural and Remote Environmental5. The infection is transmitted to man through the bite of Health 2003; 2 : 14 - 20. which form of infective mite (a) Larvae (b) Pupa (c) Male 24. Lee SH, Kim DM, Cho YS, Yoon SH and Shim SK. Usefulness of Eschar PCR for adult (d) Female adult Diagnosis of Scrub Typhus. J Clin Microbiol. Mar 2006; 44(3) : 1169 - 71 25. Rozendaal JA. Vector control : Methods for Use by Individuals andAnswers : (1) a; (2) b; (3) a; (4) c; (5) a. Communities. 1st Ed 1997. World Health Organization (WHO), Geneva. 26. Sehgal S and Bhatia R. Manual on Zoonoses. National Institute ofReferences Communicable Diseases (Govt of India, Min of Health and Family welfare).1. Guerra MA and Swerdlow DL. Rickettsial Infections. In Wallace RB and New Delhi 1981. Kohatsu N. Eds. Maxcy Rosenau Last Public Health and Preventive Medicine. 27. Brill NE. An Acute Infectious Disease of Unknown Origin. A Clinical Study 15th Edition. 2008. The McGraw - Hill Comapanies.New York. 362 - 368. Based on 221 Cases. AmJ Med Sci 1910; 139 : 484 - 502.2. Mahajan SK, Kashyap R, Sankhyan N, Sharma V, Rolain JM, Prasher BS 28. Zinsser H. Varieties of the Typhus Vaccine and the Epidemiology of the and Raoult D. Spotted Fever Group Rickettsioses in Himachal Pradesh. JAPI. American Form of European Typhus Fever (Brill’s Disease). AmJ Hyg 1934 December 2007; 55 : 868 - 870. ; 20 : 513 - 32. • 1053 •
  • mosquitoes may be domestic (breeding close to and around 178 Yellow Fever houses), wild (breeding in the jungle) or semi - domestic types. In South America Haemogoggus spegazzinii is the principal vector for forest transmission. In Africa, the principal vectors Rajesh Vaidya for forest transmission are the Aedes africanus and Aedes simpsoni. In both the continents, the principal urban vectorYellow fever was the first viral haemorrhagic fever to be is the Aedes aegypti. Female mosquitoes become infected bydescribed. It is a mosquito - borne infection endemic to feeding on an infected host usually during the first to third dayAfrica and South America. Its presentation is widely variable of fever. The extrinsic incubation period in the mosquitoes canranging from a minimal flulike illness to a fulminant disease vary from 4 to 18 days depending on the ambient temperaturecharacterized by haemorrhage, hepatic failure, renal failure (6). During subsequent blood meals, the virus is transmittedand death. The Yellow Fever virus is an arbovirus, of the family to a new vertebrate host. In addition, Yellow fever virus canFlaviviridae (1). Despite being currently restricted to parts of be transmitted transovarially, allowing viral survival in theAfrica and South America, Yellow fever has the potential to absence of adult mosquitoes. The principal urban vector Aedescause large outbreaks in other areas due to the presence of aegypti, is an inefficient vector of the Yellow fever virus.suitable vectors and climatic conditions (2). Yellow fever has However, the anthropophilic nature of the vector and the highbeen cited in historic texts dating back to 400 years ago. The densities of the mosquito in urban areas make it an excellent“yellow” in the name originates from the jaundice that occurs vector for human - to - human transmission (5, 7).in seriously ill patients. Although an effective vaccine has Host : Primates are the only vertebrate hosts for Yellow fever.been available for 60 years, the number of people infected Humans and monkeys are the principal hosts. The reservoirover the last two decades has increased and the World Health of urban Yellow fever is sub - clinical human cases. For ruralOrganization considers Yellow fever to be a serious public health Yellow fever the most important animal reservoir is the monkey.issue again (3). The virus is transmitted by several species of In endemic areas almost 30% monkeys may be infected. Monkeymosquitoes. The Aedes is the most important vector while is the only reservoir for jungle Yellow fever (2, 5).Haemogogus species are responsible for the transmission inSouth America. Mosquito - borne transmission of Yellow fever Transmission : Three transmission cycles can be distinguishedwas first suggested by Carlos Finlay in 1881. In 1900, Walter in Africa - The sylvatic (in jungle areas, mainly affecting theReed observed that the infectious agent was transmitted by wild monkeys), intermediate (primarily affecting both man andmeans of a mosquito bite. Extensive mosquito control measures monkeys) and urban (mainly affecting human beings in highand widespread vaccination led to the elimination of Yellow population density areas). In South America, only the sylvaticfever in the early 20th century from most areas of the world and urban Yellow fever cycles of transmission are seen. In allexcept parts of Africa, South America and the Caribbean. three cycles, Yellow fever virus is transmitted between primates by diurnally active tree hole-breeding mosquitoes. In all of theseEpidemiology cycles, endemic & epidemic disease patterns can occur (4).Global : Yellow fever is currently confined almost entirely to The normal low risk to travellers increases with travel to jungleSouth and Central America and Africa. The virus is constantly areas in endemic countries and in or near cities during urbanpresent with low levels of infection in these areas. Periodically outbreaks. Areas where Yellow fever virus is present far exceedthis viral presence amplifies into regular epidemics. Over 500 those officially reported. The risk of exposure to infection canmillion people live in 33 endemic countries in Africa and are be reduced by taking measures to prevent mosquito bites (4, 5,considered to be at risk of suffering from Yellow fever. All these 7). The mosquito vectors of Yellow fever are mostly day biters.countries lie within a band from 15°N to 10°S of the equator. In Although reported cases of human disease are the principalSouth America, Yellow fever is endemic in nine countries and indicator of disease risk, some countries may have no reportedin several Caribbean islands. The countries considered to be at cases, either because of a high level of vaccine coverage againsthigh risk are Bolivia, Brazil, Colombia, Ecuador and Peru. A Yellow fever in the population or because poor surveillancesmall number of imported cases also occur in countries free of resulted in no cases being reported. However, the risk of YellowYellow fever. Yellow fever has never been reported from Asia. fever may still persist as the virus, the vector or the animalHowever, WHO considers this region to be at risk because the reservoirs are still present (8 - 10).appropriate primates and vectors are present (3). The globalincidence of Yellow fever fluctuates with the occurrence of large Incubation Period : The intrinsic incubation period in humanepidemics in Africa. The World Health Organization estimates beings is between two and six days. The extrinsic incubationthat there are 2,00,000 cases of Yellow fever every year with period in a mosquito varies from four to 18 days (average 1230,000 estimated deaths. However, due to underreporting, only days), with the temperature and humidity. Once the mosquitoa small percentage of these cases are identified (3). becomes infective, it remains so for the rest of its life (2).Agent : The viral pathogen is a Flavivirus belonging to the Period of Communicability : The case is infective to the vectorfamily Togaviridae. It is a small (40 to 60 nm), single stranded mosquito during the later part of the incubation period andpositive sense, enveloped RNA virus. The envelope consists of a first three clinical days. An infected individual, therefore, canlipid bilayer containing an envelope glycoprotein and a matrix spread infection for about four to six days, starting two to threeprotein (4, 5). days after exposure to the infection. It is to prevent the entry of such individuals in India that rigorous rules and regulationsVectors : The virus is transmitted by several different species are enforced (2).of the Aedes and Haemogogus (only in South America). These • 1054 •
  • Clinical Features Immune Response : More than 95% of vaccinated peopleThe disease presents in two phases. Some infections may be develop neutralizing antibodies within 10 to 14 days ofcompletely asymptomatic. Usually the first “acute” phase is immunization. The International Health Regulations stipulatecharacterized by fever, muscle pain, headache, loss of appetite, that the vaccination certificate for Yellow fever is valid for 10nausea and vomiting. The high fever may be paradoxically days after administration of 17D vaccine, corresponding toassociated with a slow pulse. After three to four days most the time at which the majority of vaccinees are demonstrablypatients improve and their symptoms disappear. About 15% immune. Immunity following 17D vaccination is remarkablyof patients enter a “toxic phase” within 24 hours. The patient durable and may be lifelong.rapidly develops jaundice and has abdominal pain with Dose, Route of Administration and Preparations : A 17Dvomiting. Bleeding can occur from the mouth, nose, eyes and/ vaccine dose contains approximately 105 PFU in 0. 5 mL and isor stomach. Blood may appear in the vomit and faeces. Kidney given subcutaneously, usually in the upper arm. Because therefunction deteriorates. About half of the patients in the “toxic is no preservative in the vaccine and because the vaccine rapidlyphase” die within 10 - 14 days. The remaining recover without loses potency after reconstitution, it must be refrigerated at thesignificant organ damage. Yellow fever is difficult to recognize, point of use and held on ice and used soon after reconstitution.especially during the early stages. It can easily be confused Reconstituted vaccines must be discarded within 4 hours. Thewith malaria, typhoid, rickettsial diseases, haemorrhagic viral vaccine is supplied in single and multiple - dose containers.fevers, dengue fever, leptospirosis and viral hepatitis (3). Vaccine Failure : Rarely, healthy people fail to developDiagnosis neutralizing antibodies following 17D vaccination. This is not an absolute refractoriness; people who fail to develop antibodyBaseline investigations must be carried out in suspected after their first vaccination may develop antibody uponcase. Leukopenia with relative neutropenia can occur. revaccination (2, 4, 7).Thrombocytopenia can occur as part of a consumptivecoagulopathy. Patients are also likely to have an elevated Precautions and Contraindications : Tolerance of theprothrombin time and prolonged clotting times. Renal damage, vaccine is generally good. Less than 5% of vaccine recipientsif present, results in grossly elevated serum creatinine levels have mild reactions, including myalgia and headache.and markedly elevated levels of urinary protein. In severe cases Contraindications include true allergy to the constituents,liver function tests are grossly deranged. Specific laboratory cellular immunodeficiency and symptomatic HIV infection.diagnosis relies on serology or on detection of the virus and Many industrialized countries administer Yellow fever vaccineviral antigens. Rapid detection methods include the detection to persons with symptomatic HIV infection provided that theof Yellow fever antigen by monoclonal enzyme immunoassay CD4 count is at least 200 cells/mm3 (11, 12). Asymptomaticin serum specimens & detection of viral genome sequences HIV - positive individuals may have a reduced response to thein tissue or blood using polymerase chain reaction (PCR). vaccine. There is a theoretical risk of harm to the foetus if theSerologic studies include the Immunoglobulin - M (IgM) vaccine is given during pregnancy, but this must be weighedantibody - capture enzyme - linked immunosorbent assay (MAC against the risk to the mother of remaining unvaccinated and- ELISA) used to detect the specific presence of IgM for Yellow travelling to a high - risk zone. There have been recent reportsfever. IgM appears 7 - 10 days following infection. A four - fold of a small number of cases of serious disease, including deaths,rise in haemgglutination inhibition, complement fixation, or following Yellow fever vaccination; most of these reactionsneutralization of antibodies in acute and convalescent phases occurred in elderly persons (12, 13 - 15).is also diagnostic of Yellow fever. The Yellow fever virus can be The risk to unvaccinated individuals who visit countries whereisolated from viral culture with the intracerebral inoculation of there may be Yellow fever transmission is far greater than thesuckling mice or inoculation of mosquito cell cultures (1). risk of a vaccine - related adverse event and it remains importantTreatment for all travellers at risk to be vaccinated. Nonetheless, Yellow fever vaccination should not be prescribed for individuals whoAs there is no specific treatment for Yellow fever, supportive are not at risk of exposure to infection (16 - 18). Yellow fevercare is critical. Dehydration and fever must be corrected with vaccination should be encouraged as a key prevention strategy,oral rehydration salts and anti - pyretics. Any superimposed but it is important to screen travel itineraries, particularly ofbacterial infection should be treated with appropriate older travellers and carefully evaluate the potential risk ofantibiotics. Intensive supportive care may improve the outcome systemic illness after Yellow fever vaccination (2, 7, 10, 11).for seriously ill patients. Mandatory Vaccination : Mandatory vaccination againstPrevention and Control Yellow fever is carried out to prevent the importation of YellowVector control and vaccination are the cornerstones of Yellow fever virus into vulnerable countries. These are countries wherefever control. Vector control is considered in detail in the Yellow fever does not occur but where the mosquito vectorChapter on Entomology. and non - human primate hosts are present. Importation ofYellow Fever Vaccine : During the 1930s, both wild - type the virus by an infected traveller could potentially lead to theYellow fever virus strains, Asibi and French, were attenuated to establishment of infection in mosquitoes and primates, with aderive live vaccines known as 17D and the French neurotropic consequent risk of infection for the local population. In suchvaccine, respectively (2). Currently, 17D is the only strain cases, vaccination is an entry requirement for all travellersof Yellow fever virus used for vaccination. 17D vaccines are arriving from countries, including airport transit, where there isheterogenous mixtures of multiple virus subpopulations (10). a risk of Yellow fever transmission. If Yellow fever vaccination • 1055 •
  • is contraindicated for medical reasons, a medical certificate Yellow fever does not occur but where the mosquito vector andis required for exemption (19). The international Yellow fever non - human primate hosts are present.vaccination certificate becomes valid 10 days after vaccinationand remains valid for a period of 10 years. Travellers should be Study Exercisesaware that the absence of a requirement for vaccination does Long Question : Discuss the epidemiology, treatment,not imply that there is no risk of exposure to Yellow fever in prevention and control of Yellow fever.the country. Short Notes : (1) Transmission cycles of Yellow FeverPrevention of Entry of Disease in India : In India, Aedes (2) Yellow fever Vaccine (3) Importance of Yellow fever vaccineaegypti is wide spread and the people possess no immunity in International Travel.against Yellow fever. Yellow fever has not so far entered India MCQsdue to the stringent regulations and their rigid enforcement. It 1. All the following are countries considered to be at highis, however, interesting to note that Yellow fever never entered risk for yellow fever except (a) Brazil (b) ColombiaIndia even before these regulations were introduced. May be, (c) Hong Kong (d) Peruthis was due to the slow mode of voyage from the African coast 2. Principal urban vector of Yellow fever is (a) Aedes aegyptito India. Due to faster means of travel the danger of its entry (b) Aedes africanus (c) Aedes simpsoni (d) Aedes vittatushas increased. The details on International Health Regulations 3. In South America _______ is the principal vector forare given in a separate chapter. forest transmission (a) Aedes simpsoni (b) Haemogoggus spegazzinii (c) Aedes vittatus (d) Aedes niveus Summary 4. Strain of Yellow fever virus used for vaccination (a)16 DYellow fever was the first viral haemorrhagic fever to be (b)17 D (c)18 D (d)19 Ddescribed. The “yellow” in the name originates from the jaundice 5. The international Yellow fever vaccination certificate becomes valid ________ days after vaccination (a)10 (b)15that occurs in seriously ill patients. Yellow fever is currently (c)20 (d)25confined almost entirely to South and Central America andAfrica. All these countries lie within a band from 15°N to 10°S Answers : (1) c; (2) a (3) b; (4) b; (5) a.of the equator. WHO considers Asian region to be at risk because Referencesthe appropriate primates and vectors are present. The viral 1. Shoff WH, Hinfey PB and Behrman AJ. Emedicine Article. Yellow Fever.pathogen is a Flavivirus belonging to the family Togaviridae. In Updated Nov 2006. http : //www. emedicine. com/MED/topic2432. htm Accessed on 8 Mar 2008.South America Haemogoggus spegazzinii is the principal vector 2. Marfin AA, Barwick Eidex R, Monath TP Yellow Fever. In : Guerrant RL, Walker .for forest transmission. In Africa, the principal vectors for forest DH, Weller PF, eds. Tropical Infectious Diseases : Principles, Pathogens, & Practice. 2nd ed. Philadelphia : Elsevier; 2005.transmission are the Aedes africanus and Aedes simpsoni. In 3. World Health Organization. Yellow Fever. Fact Sheet No 100. Revised Decboth the continents, the principal urban vector is the Aedes 2001. http : //www. who. int/mediacentre/factsheets/fs100/en/. Accessed onaegypti. Humans and monkeys are the principal hosts. The 18 Mar 2008. 4. Division of Vector - Borne Infectious Diseases. Centers for Disease Controlreservoir of urban Yellow fever is sub - clinical human cases. and Prevention. Atlanta. http : //www. cdc. gov/ncidod/dvbid/yellowfever/For rural Yellow fever the most important animal reservoir is index. html. Accessed on 15 Mar 2008.the monkey. Three transmission cycles can be distinguished in 5. Ananthanarayan R, Paniker CK. Paramyxoviruses. In : Text Book of Microbiology. 4th ed. Hyderabad : Orient Longman Ltd. 1995.Africa. The sylvatic, intermediate and urban cycle. The intrinsic 6. Simpson DIH. Arbovirus Infections. In Gordon Cook (Ed). Manson’s Tropicalincubation period in human beings is between two and six Diseases. 20th Edition.WBSaunders. London 1996. 615 - 654.days. The extrinsic incubation period in a mosquito varies 7. Centres for Disease Control and Prevention. Prevention of Specific Infectious Diseases. CDC Health Information for International Travel 2008. Chapter 4.from four to 18 days (average 12 days). The case is infective Traveller’ Health : Yellow Book. http : //wwwn. cdc. gov/travel/yellowBookCh4to the vector mosquito during the later part of the incubation - YellowFever. aspx. Accessed on 15 Mar 2008. 8. WHO.Weekly epidemiological record. No. 43, 2006, 81, 409 - 416.period and first three clinical days. The disease presents in two 9. WHO.Weekly epidemiological record. No. 33, 2006, 81, 317 - 324.phases first “acute” phase is characterized by fever, muscle 10. World Health Organisation. International Health Regulations 2005.pain, headache, loss of appetite, nausea and vomiting. About 11. Monath TP Yellow Fever. In : Plotkin S, Orenstein WA, eds. Vaccines. 3rd ed. .15% of patients enter a “toxic phase” within 24 hours. The Philadelphia : WBSaunders; 1999. p. 815 - 80. 12. CDC. Fatal Yellow Fever in a Traveller Returning From Amazonas, Brazil,patient rapidly develops jaundice and has abdominal pain with 2002. MMWRMorb Mortal Wkly Rep. 2002;51 : 324 - 5.vomiting. About half of the patients in the “toxic phase” die 13. Barros ML, Boecken G. Jungle Yellow Fever in the Central Amazon. Lancet.within 10 - 14 days. Complications include Kidney, liver and 1996;348 : 969 - 70. 14. Monath TP Cetron MS. Prevention of Yellow Fever in Persons Traveling to the ,myocardial damage. Specific laboratory diagnosis relies on Tropics. Clin Infect Dis. 2002;34 : 1369 - 78.serology or on detection of the virus and viral antigens. There 15. CDC. Fatal Yellow Fever in a Traveller Returning From Venezuela, no specific treatment for Yellow fever, supportive care is MMWR Morb Mortal Wkly Rep. 2000;49 : 303 - 5. 16. Chan RC, Penney DJ, Little D, Carter IW, Roberts JA, Rawlinson WD. Hepatitiscritical. Vector control and vaccination are the cornerstones of and Death Following Vaccination with 17D - 204 Yellow Fever Vaccine.Yellow fever control. Currently, 17D is the only strain of Yellow Lancet. 2001;358 : 121 - 2.fever virus used for vaccination. More than 95% of vaccinated 17. Barwick R. History of thymoma and yellow fever vaccination. Lancet. 2004;364 : 936.people develop neutralizing antibodies within 10 to 14 days 18. Doblas A, Domingo C, Bae HG, Bohorquez CL, de OF, Niedrig M, et al. Yellowof immunization. The international Yellow fever vaccination fever vaccine - associated viscerotropic disease and death in Spain. J Clin Virol. 2006;36 : 156 - 8.certificate becomes valid 10 days after vaccination and remains 19. Cetron MS, Marfin AA, Julian KG, Gubler DJ, Sharp DJ, Barwick RS, et al.valid for a period of 10 years. Mandatory vaccination against Yellow fever vaccine. Recommendations of the Advisory Committee onYellow fever is carried out to prevent the importation of Yellow Immunization Practices (ACIP), 2002.MMWRRecomm. Rep. 2002;51 (RR - 17) : 1 - 11.fever virus into vulnerable countries. These are countries where • 1056 •
  • hyperendemic for HAV infection with very high infection rates 179 Viral Hepatitis in the first few years of life and most of the population acquiring antibodies to HAV by 10 yrs of age. Seroprevalence was of anti- HAV was lower (54.5%) in the higher socio-economic group Rajesh Vaidya as compared to the lower socio-economic group (85%) (7-9). However recent studies suggest that seroprevalence of anti-The word “Jaundice” comes from old french “Jaunice” or HAV vary in different parts of country with some parts showing“Yalnice”. “Icterus” is a greek word for yellow. Some brightly a gradual shift in the epidemiology of hepatitis A with morecoloured birds belong to the family “Icteradae”. Pliny believed cases occurring in adult population (10).that if a jaundiced patient looked at the icterus or golden oriole, Agent : The HAV is a member of the Picornavirus family. Itthe patient recovered but the bird died. Epidemic jaundice was is an icosahedral virus 27 to 32 nm in diameter. The particledescribed by Hippocrates in 400 BC. Outbreaks among armies is non-enveloped and has single stranded, positive sense RNAhave been documented in Europe in the 17th and 18th centuries (3). Four human genotypes of the virus have been identified.(1). The distinction between ‘infectious’ and ‘serum’ hepatitis However, they are closely related anti-genically and infectionwas first made by Krugman (2). with one genotype results in immunity against the otherThe term hepatitis indicates an inflammation of the liver strains. There is only one serotype. HAV is relatively resistantdue to any cause. Infection by a number of viruses can cause to destruction.inflammation of the liver. However, the term ‘Viral Hepatitis’ is Host : HAV infection, usually, is common in children and theused only for disease caused by hepatotrophic viruses. There risk of developing symptomatic illness following HAV infectionare five viruses which are taxonomically diverse but share is directly correlated to age. In children below six years ofthe common characteristic of replicating primarily in the liver. age, HAV infection is usually asymptomatic, with only 10%These viruses are the Hepatitis A Virus (HAV), Hepatitis B Virus developing jaundice. Among older children and adults, infection(HBV), Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), and usually causes clinical disease, with jaundice occurring in moreHepatitis E Virus (HEV). These five viruses are further divided than 70% of cases. However any age group can be affected, ifinto two groups. The hepatitis A and E viruses are primarily susceptible. For practical purposes, the world can be dividedtransmitted by the faeco-oral route and result in acute but self into areas of low, intermediate and high disease endemicity. Inlimited infection. The hepatitis B, C & D viruses are transmitted areas of low endemicity disease occurs mainly in adolescentsby the parenteral route and can cause both acute and chronic and adults in high-risk groups (e.g. homosexual men, injecting-infection. Some newer agents have been identified as causes of drug users), persons travelling to countries of intermediateviral hepatitis but they are not well characterized so far. and high HAV endemicity. In areas of intermediate endemicityOther viruses like Cytomegalovirus, Epstein Barr virus, person to person in the general community via faeco-oral routeYellow Fever virus & Rubella virus can also cause hepatitis. is predominant, most cases occur in late childhood and earlyIn immunocompromised individuals, herpes simplex virus, adulthood. In areas of high disease endemicity lifetime risk ofvaricella virus and adenovirus also result in hepatic dysfunction. infection is greater than 90%, most infections occur in earlyHowever, as the site of primary infection is not the liver in these childhood and are asymptomatic (4).cases, they are not listed as causes of viral hepatitis. Modes of Transmission : Person-to-person transmission by theHepatitis A faeco-oral route is the predominant mode of HAV transmission.The Hepatitis A Virus (HAV) is the commonest cause of viral The other less common mode of transmission include blood-hepatitis worldwide (1). borne transmission, sexual transmission in homosexuals and in some rare cases vertical intrauterine transmission has alsoEpidemiology been demonstrated (11). Secondary attack rates are as high asGlobal : Endemicity of HAV infection is closely related 30% among household sanitary and living condition and other indicators of Incubation Period : Incubation period ranges from 15 to 50development, various sero-epidemiological studies show that days with median of about 28 days(12).prevalence of anti-HAV antibodies in the general population Period of Infectivity : 2 weeks before to 1 week after onset ofvaries from 15% to close to 100% in different parts of the world. jaundice. Highest concentration of virus is excreted in faeces 2An estimated 1.5 million clinical cases of hepatitis A occur weeks prior to onset of clinical illness, which rapidly declinesworld-wide each year (4). In areas of low endemicity such as with appearance of jaundice (13).United States, Canada, western Europe, Australia, and otherdeveloped countries, hepatitis A usually occurs as single cases Clinical Features(5). However HAV is also known to have potential to cause The clinical course of acute hepatitis A is indistinguishable fromlarge outbreaks, one of the worst known outbreaks was seen other types of acute viral hepatitis. Symptoms typically includein 1988 in Shanghai, China, when over 3,00,000 young adults fever, malaise, anorexia, nausea and abdominal discomfort,became ill when shellfish contaminated with HAV were sold followed by dark urine and jaundice. The severity of diseasein the marketplace and subsequently prepared in a traditional and mortality increases in older age groups. The convalescencemanner at temperatures that did not kill the virus (6). following hepatitis A may be slow, and is characterized byIndia : In India, limited epidemiological data are available fatigue, nausea and lack of appetite. Complications of hepatitis Aon HAV infection. A few reports suggested that India was include relapsing hepatitis, cholestatic hepatitis and fulminant • 1057 •
  • hepatitis. Fulminant hepatitis occurs in approximately 0.01% WHO recommends that in highly endemic countries where HAVof clinical infections and is characterized by rapid deterioration is almost universal before the age of 10 years and is usually ain liver function and a very high fatality rate. Chronic infection minor public health problem, large-scale immunization effortswith HAV does not occur. against this disease should not be undertaken. In developedDiagnosis countries with low endemicity of hepatitis A and with high rates of disease in specific high-risk populations (injection-drugSince Hepatitis A is clinically indistinguishable from other users, homosexual men, persons travelling to high-risk areas,forms of hepatitis, diagnosis requires serologic detection of and certain ethnic or religious groups), vaccination shouldIgM in single acute-phase serum sample. IgM anti-HAV is be given to this high risk population. Recommendations forusually detectable from 5 days prior to the onset of symptoms hepatitis A vaccination in outbreak situations should dependand declines to undetectable levels within six months after on the epidemiology of hepatitis A in the community, and theinfection. IgG anti-HAV is used to detect previous infection as it feasibility of rapidly implementing a widespread vaccinationusually persists for lifelong after infection. PCR can be used to programme. Hepatitis A vaccination in small, self-containeddetect virus in faeces, blood etc. Other biochemical parameters communities has been found to be very successful in controlinclude elevated levels of serum bilirubin and elevated hepatic of the outbreak (15).enzymes (AST, ALT) (14). Passive Immunization : Passive immunization with IG thatTreatment contain anti-HAV are more than 85% effective in preventingTreatment primarily comprises of symptomatic management symptomatic HAV infection if given before, or within two weekswith complete bed rest and low protein diet as no specific of exposure. With the availability of hepatitis A vaccines, IGantiviral therapy is currently available. is primarily recommended for postexposure prophylaxis forPrevention and Control unvaccinated persons who are exposed to HAV. A single IM dose of IG (0.02 mL/kg) should be administered as soon as possible,As almost all HAV infections are spread by the faeco - oral but not more than two weeks after the last exposure, toroute, good personal hygiene, high quality standards for public unvaccinated household contacts, to persons who have sharedwater supplies and proper disposal of sanitary waste are the illegal drugs with a person with hepatitis A, and to childrenmainstay of prevention and control of infective hepatitis. Some and staff exposed in day care or certain other institutionalof the important measures are as follows : settings.●● Water supply should be safeguarded against faecal contamination. Even chlorination may sometimes not kill Hepatitis E the virus, unless water is very efficiently chlorinated and Hepatitis E virus (HEV) was first identified in India in 1955 a half an hour contact period is ensured. Water should be but it was only after development of specific serological test for preferably boiled during an outbreak. acute HAV which resulted in the retrospective determination●● Sanitation should be kept at a very high level. Methods that large outbreaks of hepatitis with faeco-oral mode of of proper disposal of human wastes and strict anti-fly transmission were not hepatitis A, but enterically transmitted measures should be reinforced. Non-A Non-B virus (NANB or E-NANB). Hepatitis E was●● Personal hygiene must be maintained at an extremely recognized as a distinct human disease in early 1990’s (16). high level. Particularly cooks and housewives must be persuaded to wash their hands with soap and water after Epidemiology defaecation and before handling or consuming food. Global : The highest rates of infection occur in regions where●● Complete inactivation of HAV in food can be done by low standards of sanitation promote the transmission of the heating at 85°C for at least one minute. virus. Hepatitis E is endemic in many parts of the world andActive Immunization : Several inactivated or live attenuated always where HAV infection is highly endemic. Epidemics ofvaccines against hepatitis A have been developed, but only hepatitis E have been reported in Central and South-East Asia,four inactivated hepatitis A vaccines are currently available North and West Africa, and in Mexico, especially where faecalinternationally. All four vaccines are all highly immunogenic. contamination of drinking water is common (19).Nearly 100% of adults will develop protective levels of antibody India : HEV is responsible for the majority of epidemic andwithin one month after a single dose of vaccine. Similar results sporadic hepatitis in adults. Epidemics of Hepatitis E haveare obtained with children and adolescents in both developing been reported from across the country, one of the largestand developed countries. These vaccines are given parenterally such epidemic occured in Delhi during the winter of 1955-56,(IM), as a two-dose series, 6-18 months apart. The dose of infecting over 30,000 persons within six weeks (17).vaccine, vaccination schedule, paediatric and adult formulation Agent : HEV is a 27-34 nm non-enveloped icosahedral virusvaries from manufacturer to manufacturer. Currently no vaccine with a single-stranded, positive-sense RNA genome. Theia available for children less then 1 yr. surface of the viron shows indentation and spikes (17). InA combination vaccine containing inactivated hepatitis A and morphology it resembles Calcivirus like Norwalk virus hencerecombinant hepatitis B vaccines has been licensed since 1996 was wrongly classified into the family Caliciviridae, but nowfor use in children aged one year or older in several countries. has been reclassified to an separate genus of “Hepatitis E likeThe combination vaccine is given as a three-dose series, using viruses” (18).a 0, 1, 6 month schedule. • 1058 •
  • Host : The zoonotic origin of HEV is suspected, as monkeys, route, good personal hygiene, high quality standards for publicrats, cattle, sheep, goats, ducks and pigs are susceptible to water supplies and proper disposal of sanitary waste is the keyinfection with humans being an end or inadvertent target. for prevention of HEV infection. At present, no commerciallyThe reservoir of Hepatitis E is unknown. Although asymptomatic available vaccines exist for the prevention of hepatitis E.infections occur among children, seroprevalence studies in However, several studies for the development of an effectivehigh endemic areas have not identified high rates of infection vaccine against hepatitis E are in this age group. Various studies have shown high attack Hepatitis Brate among young adults (20). Hepatitis E has been found tohave intriguing relationship with pregnancy. Pregnant women HBV is one of the oldest known hepatitis viruses. Even afterparticularly those in the second and the third trimester, are the advent of an effective vaccine it still continues to be a majormore frequently affected during HEV outbreak. In addition, public health problem with more then 2 billion people infectedamong pregnant women, especially those infected in the third worldwide.trimester, the disease is more severe with high mortality (20- Epidemiology40%) (21). Global : The prevalence of HBV infection varies greatlyModes of Transmission : HEV is transmitted via the faeco-oral worldwide. There are more then 2 billion people infectedroute. Hepatitis E is a waterborne disease, and contaminated worldwide, and 350 million suffering from chronic HBV infection.water or food supplies have been implicated in major outbreaks. HBV infections result in 5,00,000 to 1.2 million deaths perConsumption of faecally contaminated drinking water has year caused by chronic hepatitis, cirrhosis, and hepatocellulargiven rise to epidemics, and the ingestion of raw or uncooked carcinoma. More than one-third of the population has beenshellfish has been the source of sporadic cases in endemic areas. infected with HBV, and it is estimated that there are 80 millionHepatitis E has been found to be transmitted from infected HBV carriers (about 6% of the world population) (27).mothers to their babies with significant perinatal morbidity India : On meta-analysis, the point prevalence of hepatitis Band mortality (22). However Person-to-person transmission is was found to be 2.1 per cent with a chronic carrier rate of 1.7uncommon with low secondary attack rates ranging from 0.7 per cent (28). Hepatocellular carcinoma is rare in India andto 2.2%. There is no evidence for sexual transmission or for constitutes only 1.6 per cent of all cancers. The estimatedtransmission by transfusion. annual deaths attributable to hepatocellular carcinoma due toIncubation Period and Period of Infectivity : The incubation hepatitis B was found to be approximately 5000 (29). Howeverperiod following exposure to HEV ranges from 3 to 8 weeks, certain studies have found higher carrier state ranging fromwith a mean of 40 days. The period of communicability is 11% in healthcare worker to 5% in general population (30).unknown. There are no chronic infections reported (23). Agent : The Hepatitis B Virus (HBV) is a double-stranded,Clinical Features enveloped virus of the Hepadnaviridae family. With a genomeClinical signs and symptoms are indistinguishable from of only 3200 base pairs, HBV is one of the smallest DNAHepatitis A. Typical signs and symptoms of hepatitis include viruses known. The complete HBV viron (Dane Particle) isjaundice (yellow discoloration of the skin and sclera of the 42nm in diameter and is composed of outer lipoprotein coateyes, dark urine and pale stools), anorexia (loss of appetite), containing the Hepatitis B Surface Antigen (HBsAg) and 27nman enlarged, tender liver (hepatomegaly), abdominal pain and nucleocapsid core, the Hepatitis B Core Antigen (HBcAg) (17).tenderness, nausea and vomiting, and fever. Most persons with HbsAg circulates independently in the blood and has fourHepatitis E have self limited disease except in pregnant women possible subtypes (adw, adr, ayw and ayr). Antibodies to thein whom high degree of fatality is observed. Infants acquiring “a” antigen confer immunity to all subtypes (25). A thirdinfection via vertical transmission have increased risk of antigen HBeAg is a soluble protein, which can be detected infulminant hepatitis (24). Chronic liver disease is not known to serum of patients with acute HBV infection. It acts as a markeroccur with HEV infection. of viral replication. There are eight genotypes of hepatitis B Virus (A to H).Diagnosis Genotypes have different geographic distributions like genotypeHepatitis E are not clinically distinguishable from other types A is pandemic whereas genotype B and C are present in Asia,of acute viral hepatitis, diagnosis is made by blood tests which D in Southern Europe and US, E in Africa, F in the US, G in USdetect elevated antibody levels of specific antibodies to hepatitis and France and H in Central and South America (26)E in the body or HEV RNA can be detected in faeces or serum by Host : There is a direct relationship between the age of theReverse Transcriptase Polymerase Chain Reaction (RT-PCR). patient and the likelihood to develop symptomatic infectionTreatment which includes acute (clinically apparent) hepatitis B, chronicHEV infections are usually self-limited and available therapy is HBV infection, cirrhosis and HCC. Acute hepatitis B occurs incapable of altering the course of acute infection. Hospitalization approximately 1% of perinatal, 10% of early childhood (1-5is required for fulminant hepatitis and should be considered for years old) and 30% of late (>5 years old) HBV infections.infected pregnant women. Fulminant hepatitis develops in 0.1-0.6% of acute hepatitisPrevention and Control cases; mortality from fulminant hepatitis B is approximately 70%. However, there is an inverse relationship with age andAs almost all HEV infections are spread by the faeco-oral probability of developing chronic infection. About 90% of infants • 1059 •
  • infected during the first year of life and 30% to 50% of children sickness-like syndrome may develop during the prodromalinfected between 1 to 4 years of age develop chronic infection. phase that is characterized by artharalgias or arthritis, rash,Whereas only 2-6% of adults develop chronic infection (31). and angioedema. In patients with icteric hepatitis (30% or moreCertain occupational categories have been identified as of infected adults), jaundice usually develops within 1-2 weeksassociated with an excess risk of hepatitis B, C & D infection. after onset of illness, dark urine and clay-colored stools mayThe categories include dentists, nurses, laboratory technicians appear 1-5 days before the onset of clinical jaundice (25). Liverand the work areas include haemodialysis units, blood banks enzyme elevations usually occur prior to onset of jaundice.and surgical intensive care units. In most cases it is a self limiting disease and clinical signs and symptoms of acute hepatitis B usually resolve within 1-3Modes of Transmission : Humans are the only reservoir of months.HBV. The virus is highly contagious and is transmitted bypercutaneous and permucosal exposure to infected blood and Diagnosisother body fluids (i.e. semen and vaginal fluid). The virus is Acute hepatitis is indistinguishable from other hepatitis byfound in highest concentrations in blood and serous exudates biochemical parameters which include elevated levels of serumfollowed by lower concenterations in various body secretions bilirubin and elevated hepatic enzymes (AST, ALT). Diagnosissuch as saliva, semen and vaginal fluid. Common modes of can be made on the basis of serological antigen and antibodytransmission include mother-to-infant, unsafe injection markers of HBV infection. HBsAg, IgM anti-HBc, and HBeAgpractices, blood transfusions and sexual contact. can all be detected in serum as early as 1-2 months afterPerinatal Transmission : Perinatal HBV transmission is one exposure to HBV, but IgM anti-HBc is the only reliable markerof the most efficient modes of infection. Most perinatal HBV of acute infection, as the others can also be detected in personsinfections occur among infants of pregnant women with chronic with chronic HBV infection. IgM anti-HBc usually becomesHBV infection. Risk of transmission from pregnant women who undetectable within 6-9 months after acute infection, and HBsAgacquire infection during the third trimester is approximately and HBeAg are usually cleared within six months following60%. Perinatal transmission occurs most often at the time onset of illness in those who recover from the acute infection.of birth, with in utero transmission rarely accounting for Anti-HBs and anti-HBe develop during the convalescent phase,infections transmitted from mother to infant. Although HBV with anti-HBs being a protective antibody that neutralizes thecan be detected in breast milk, there is no evidence that HBV is virus. Presence of anti-HBs following acute infection indicatestransmitted by breast-feeding (32-33). recovery and immunity from reinfection. And anti-HBs can also be detected in persons who have received hepatitis B vaccine.Sexual Transmission : Presence of HBV in semen and vaginal Detection of anti-HBs is not routinely performed duringfluid favours transmission of virus by sexual contact, which diagnostic testing of persons with clinical illness but mayis one of the common modes of acquiring the infection. Both be used in certain instances to determine a person’s immuneheterosexual and homosexual intercourse may transmit HBV. status following vaccination. In persons who develop chronicThe sexually promiscuous, particularly male homosexuals, are HBV infection, HBsAg and total anti-HBc remain detectable,at very high risk of infection with hepatitis B. generally for life. Although all persons with detectable HBsAgPercutaneous Transmission : The risk of acquiring HBV should be considered infectious, but its presence along withinfection through needle stick injury exposure to HBsAg positive HBeAg and HBV DNA, is more indicative of infectivity (35). Inblood is approximately 30-60%. This poses a significant risk to addition Polymerase Chain Reaction (PCR) can be used to detecthealth care workers and IV drug abusers. HBV DNA.In highly endemic areas (>8% of the population HBsAg-positive), TreatmentHBV is most commonly spread from mother to child at birth,or from person to person in early childhood. In countries with In most cases treatment is supportive as the infection is selflow HBV endemicity (<2% of the population HBsAg-positive), limiting. Patient is advised to avoid most drugs and bed rest tillsexual transmission and the use of contaminated needles, jaundice is completely resolved. Patients with fulminant viralespecially among injecting drug users, are the major routes of hepatitis require ICU care with absolute bed rest, low proteininfection (34). diet, enemas to cleanse the bowel and oral neomycin (1 - 1.5g every six hours). Patients with chronic active Hepatitis B mayIncubation Period and Period of Infectivity : The incubation be given specific anti viral therapy in the form of:period ranges from 30 to 180 days with median of 75 days. (a) Interferon α: 5 million units / day or 10 million units thricePeriod of Infectivity may extend from appearance of HBV in a week for 16 weeks ORblood (30-60 days following infection) to several months (b) Lamivudine: 100 mg OD orally for one year ORor until disappearance of HBsAg and appearance of surface (c) Adefovir: 10 mg OD orally for 48 weeksantibody. Prevention and ControlClinical Features General prophylactic measures for HBV prevention include theAs mentioned earlier, the chances of development of following:symptomatic illness is directly related to age. In patients who ●● Safe sexual practicesdevelop symptomatic infection, the clinical onset of hepatitis ●● Use of CondomsB is usually insidious, with malaise, weakness, and anorexia ●● Safe hygiene practices (not sharing shaving blades)being the most common findings. In 5-10% of patients, a serum • 1060 •
  • ●● Safe blood transfusion and injections WHO position on hepatitis B vaccine : WHO has called for●● Health care personnel to practice proper “Universal safety all countries to add hepatitis B vaccine into their national precautions” and correct disinfection procedures immunization programmes in 1991. As of March 2004, more●● Biomedical waste management as per laid down than 160 countries had followed the WHO recommendation guidelines and had added hepatitis B vaccine as an integral part of theirActive Immunization : More than three decades of experience national infant immunization programmes. The need for catch-have shown that hepatitis B vaccination is safe and cost up vaccination of older age groups, including adolescents andeffective way of preventing HBV infection. Currently Two types adults, is determined by the baseline epidemiology of HBVof hepatitis B vaccines are available: plasma derived vaccines infection in the country. In countries of high endemicity, large-and recombinant vaccines are available world wide. The two scale routine vaccination of infants rapidly reduces infectionvaccines show no differences in terms of reactogenicity, efficacy and transmission of HBV. In this situation, catchup vaccinationor duration of protection. Plasma-derived vaccines are prepared of older children and adults has relatively little impact becausefrom purified HBsAg obtained from the plasma of persons most of them will have already been infected. In countries ofwith chronic HBV infection and inactivated using formalin. intermediate or low hepatitis B endemicity, catch-up strategiesAluminium phosphate or aluminium hydroxide is added to targeted at adolescents could be considered as a supplementthe vaccine as adjuvant and for multi-dose vials; thiomersal is to routine infant vaccination. Possible additional target groupsused as a preservative. The recombinant hepatitis B vaccines for catch-up vaccination include persons with risk factors for(RDNA - Yeast derived vaccine) use HBsAg synthesized in yeast acquiring HBV infection, such as health care workers who mayor mammalian cells. be exposed to blood or blood products, dialysis patients, personsDoses and Schedule : The recommended dose varies by interned in prisons, injecting drug users, household and sexualproduct and with the age of the recipient. In most cases, infants contacts of persons with chronic HBV infection, and personsand adolescents receive 50% of the adult dose. The vaccine is with multiple sexual partners. Catch-up vaccination shouldadministered by intramuscular injection in the anterolateral be considered only if the continuity of the infant vaccinationaspect of the thigh (infants and children aged <2 years) or in programme can be ensured (34).the deltoid muscle (older children and adults). Administration Hepatitis Cin the buttock is not recommended. In case of adults schedule Hepatitis C is a viral infection of the liver which was initiallyis 0, 1 & 6 months. In case of infants and children there are referred to as parenterally transmitted “non A, non B hepatitis”multiple options for incorporating the hepatitis B vaccine until identification of the causative agent in 1989. HCV is oneinto national immunization programmes (36). The choice of of the major cause of acute hepatitis and chronic liver disease,schedule depends on the local epidemiological situation and including cirrhosis and liver cancer and despite extensive globalprogrammatic considerations. The minimum recommended efforts there is still no vaccine available to prevent HCV.interval between the doses is four weeks.Immunogenicity and clinical efficacy : The protective efficacy Epidemiologyof hepatitis B vaccination is directly related to the induction Global : It is estimated that about 180 million people or 3%of anti-HBs antibodies. An antibody titre of >10 mIU per ml of the world’s population, are infected with hepatitis C virusmeasured 1-3 months after the administration of the last dose (HCV), 130 million of whom are chronic HCV carriers at riskof the primary vaccination series is considered a reliable marker of developing liver cirrhosis and/or liver cancer. It is estimatedof immediate and long-term protection against infection. The that three to four million persons are newly infected each year,complete vaccine series induces protective antibody levels in 70% of whom will develop chronic hepatitis (40).>95% of infants, children and young adults. After the age of India : Hepatitis C virus (HCV) which accounts for one-fourth40 years, protection following the primary vaccination series of all cases of chronic liver disease in India. It is estimateddrops below 90%. However despite the loss of anti-HBs over that there are 12.5 million HCV carriers in our country (41).time, booster doses are not recommended (37,38). Seroprevelance studies among blood donors in India, havePassive Immunization : Post exposure prophylaxis using HBIG shown a rate varying from 0.48% in Vellore (42) to 1.85% inis indicated in the following situation : New Delhi (43).(i) For newborn infants whose mothers are HBsAg-positive Agent : HCV is an enveloped virus with an icosahedral capsid(ii) Following percutaneous or mucous membrane exposure to that contains a 9.6 kb-long, single-stranded, positive sense HBsAg-positive blood or body fluids genomic RNA. It has been classified into genus Hepacivirus(iii) Following sexual exposure to an HBsAg-positive person in the family Flaviviridae. The single translated polyprotein(iv) To protect patients from recurrent HBV infection following contains structural proteins including the core and two envelope liver transplantation proteins and three nonstructural proteins. Two regions of oneHBIG as early as possible (ideally with 6 to 48 hrs). of the envelope proteins called the hypervariable regions haveImmunoglobulin (16 % solution) should be given at 0.02 to extremely high rate of mutation. It is postulated that this rapid0.12 ml per kg of body weight intramuscularly in two doses evolution of genetic variation facilitates viral persistence in30 days apart. As a rule, HBIG should be used as an adjunct to most infected persons. There are 6 HCV genotypes and morehepatitis B vaccine. than 100 subtypes (39). • 1061 •
  • Host : Since HBV is transmitted parenterally, certain group sensitive and specific immunoassay, such as IgM anti-HCV.of people can classified as high risk this includes recipients A Recombinant Immunoblot Assay (RIBA) that identifiesof blood transfusions, healthcare and laboratory personnel, antibodies which react with individual HCV antigens is oftenhomosexuals, prostitutes, percutaneous drug abuser, infants used as a supplemental test for confirmation of a positive EIAof HCV carrier mothers. result. PCR can be utilized for confirmation of serological resultsModes of Transmission : HCV is transmitted by percutaneous as well as for assessing the effectiveness of antiviral therapy. Aof mucosal exposure to infectious blood and blood derived positive result indicates the presence of active infection and abody fluids. The primary route of transmission is percutaneous potential for spread of the infection and or/the development ofexposure to blood. Sexual and perinatal transmission of HCV chronic liver disease.infection appears to be inefficient, occurring at a frequency Treatmentlower than that observed for HBV and HIV infection (44). Treatment of acute hepatitis is essentially symptomatic andPercutaneous Transmission: Injection drug use is a major similar to other forms of viral hepatitis. For chronic hepatitis Csource of HCV transmission in developed countries. Drug users antiviral drugs such as interferon taken alone or in combinationwho have injected even once or twice in the past should be with ribavirin, can be used. Treatment with interferon alone isconsidered at high risk of infection, since HCV infection is effective in about 10% to 20% of patients. Interferon combinedacquired more rapidly among IDUs than either HBV or HIV with ribavirin, is effective in about 30% to 50% of patients.infection (45). Transfusion of blood or plasma derived products Ribavirin does not appear to be effective when used aloneand transplantation of solid organs from HCV infection donors (47).are highly effective routes for transmitting HCV infection. Prevention and ControlNosocomial transmission of HCV infection due to poor infectioncontrol practices and aseptic techniques is a common means of There is no vaccine against HCV. Research is in progress buttransmission in developing countries. due to high mutability of the HCV genome, possibility of development of vaccine in the foreseeable future seems remote.Other modes of transmission such as social, cultural, and Hence in the absence of a vaccine, all precautions to preventbehavioural practices using percutaneous procedures (e.g. infection must be taken including :ear and body piercing, circumcision, tattooing) can occur if ●● Screening and testing of blood and organ donors.inadequately sterilized equipment is used. HCV is not spread ●● Virus inactivation of plasma derived sneezing, hugging, coughing, food or water, sharing eating ●● Implementation and maintenance of infection controlutensils, or casual contact. practices in health care settings, including appropriateIncubation Period : The incubation period of HCV infection sterilization of medical and dental equipment.before the onset of clinical symptoms ranges from 15 to 150 ●● Promotion of behaviour change among the general publicdays. and health care workers to reduce overuse of injectionsClinical Features and to use safe injection practices; and risk reductionMost persons (60-80%) with newly acquired HCV infection are counselling for persons with high-risk drug and sexualasymptomatic and only 15-30% become jaundiced. The clinical practices (47).illness in persons with acute hepatitis C is similar to that Hepatitis Dobserved in hepatitis of other viral etiologies and the diagnosis HDV is a defective single-stranded RNA virus that requiresof hepatitis C can only be made with appropriate serologic the helper function of HBV to replicate. HDV infection can betesting. The most outstanding feature of HCV infection is acquired either as a co-infection with HBV or as a Superinfectionthat about 80% of newly infected patients progress to develop of persons with chronic HBV infection.chronic infection. Cirrhosis develops in about 10% to 20% ofpersons with chronic infection, and liver cancer develops in 1% Epidemiologyto 5% of persons with chronic infection over a period of 20 to Global : In general, the global pattern of HDV infection30 years. Most patients suffering from liver cancer who do not corresponds to the prevalence of chronic HBV infection;have hepatitis B virus infection have evidence of HCV infection. however, several distinct features of the distribution of HDVThe mechanisms by which HCV infection leads to liver cancer infection have been identified. The highest prevalences of HDVare still unclear (46). infection is found in the Amazon basin, parts of Africa, andDiagnosis Romania where 20% of persons with chronic HBV infection and up to 90% of people with HBV-related chronic liver diseaseDiagnostic tests for HCV are used to prevent infection through have HDV infection. Other countries, including northern Italy,screening of donor blood and plasma, to establish the clinical Spain, Turkey, and Egypt, have a moderate prevalence ofdiagnosis and to make better decisions regarding medical HDV infection among asymptomatic HBV carriers (10%-19%)management of a patient. Diagnostic tests commercially and among patients with chronic HBV-related liver diseaseavailable today are based on Enzyme Immunosorbant Assays (30%-50%). In most of Southeast Asia and China, where the(EIA) for the detection of HCV specific antibodies. EIAs can prevalence of chronic HBV infection is very high but HDVdetect more than 95% of chronically infected patients but can infection is uncommon (49).detect only 50% to 70% of acute infections. This limitationof diagnosis of recent HCV infection is due to the lack of a India : The anti-HDV positivity in acute viral hepatitis patients have been reported to vary from 10.7 to as high as >30 per • 1062 •
  • in various studies conducted across the country. In chronic about 10 times more common in hepatitis D than in other typeshepatitis and cirrhosis groups, anti-HDV antibodies have been of viral hepatitis.found to range from 8-21% and 15-19% patients respectively About 60 to 70% of patients with chronic hepatitis D develop(50). cirrhosis. Progression to cirrhosis usually takes 5 - 10 yrs, butAgent : The hepatitis delta virus (HDV) is a 1.7kb RNA virus it can appear 2 years after onset of infection. A high proportionparticle containing a circular, single-stranded RNA genome. of these patients die of hepatic failure.HDV encodes a single protein, the delta antigen, which is Diagnosisencapsulated with HBsAg, encoded by the hepatitis B virus(HBV). HDV is classified as a satellite virus or subviral agent The diagnosis of acute hepatitis D is made by serologic testsbecause it requires HBsAg as a surface protein to replicate for detecting anti HDV. One of the major drawbacks is that(48). commercially available Radioimmunoassay (RIA) or Enzyme Immunoassay (EIA) kits can only detect Total anti-HDV andHost : Certain group of people are found to be at high risk of may result in under diagnosis of HDV. HD-ag detection incontracting HDV infection these are as follows : serum is only available in research laboratories and not very●● Intravenous drug users using HDV-contaminated injection sensitive. Hence method of choice for the diagnosis of ongoing needles. HDV infection if available, should be RT-PCR, which can detect●● Promiscuous homosexual and heterosexual groups 10 to 100 copies of the HDV genome in infected serum (53). (although HDV infections are less frequent than HBV or HIV infections). Treatment●● People exposed to unscreened blood or blood products such Currently there is no effective antiviral therapy available for haemophiliacs, persons with clotting factor disorders. treatment of acute or chronic type D hepatitis. In some casesModes of Transmission : Transmission is similar to that of giving massive doses of a-interferon (9 million units threeHBV: times a week for 12 months or 5 million units daily for up to 12 months) have yielded remissions, but most of the patients●● Bloodborne and sexual. have remained unaffected.●● Percutaneous (injecting drug use, haemophiliacs).●● Permucosal (sexual). Prevention and Control●● Rare perinatal. Since HDV is dependent on HBV for replication, HBV-HDVIncubation Period : The incubation is period similar to HBV coinfection can be prevented with either pre- or postexposureinfection 30 to 180 days. prophylaxis for HBV. However, no products exist to preventClinical Features HDV superinfection of persons with chronic HBV infection. Thus, prevention of HDV superinfection depends primarily onAn HDV infection absolutely requires an associated HBV education to reduce risk behaviours.infection. The outcome of disease largely depends on whetherthe two viruses infect simultaneously (co-infection), or whether Hepatitis Gthe newly HDV-infected person is a chronically infected HBV In 1995, a new virus that causes hepatitis was cloned. Thecarrier (Superinfection). 3 viruses identified were GBV-A, GBV-B, GBV-C. They wereCo-infection : HBV and HDV (simultaneous infection with together named HGV. Of the three, the third, GBV-C appearsthe two viruses) results in both acute type B and acute type D to affect man and seems to produce a long standing disease.hepatitis. The incubation period depends on the HBV titre of This hepatitis G virus (HGV) or the GB virus C (GBV-C), is a 30-the infecting inoculum. Depending on the relative titres of HBV 60 nm. Enveloped, single stranded RNA virus which belongsand HDV, a single bout or two bouts of hepatitis may be seen. to the flavivirus family. HGV is distinct from hepatitis C virusCo-infections of HBV and HDV are usually acute, self-limited but has a similar genomic organization. The virus has a globalinfections. The chronic form of hepatitis D is seen in less than distribution and is reported to be present in 1-3% in volunteer5% of HBV - HDV coinfected patient (51). blood donors (54). In India, no formal information is availableSuperinfection : HBV and HDV (HDV infection of a chronically on the prevalence of HGV in acute viral hepatitis howeverinfected HBV carrier) causes a generally severe acute hepatitis various studies have reported hepatitis G virus infection inwith short incubation time that leads to chronic type D hepatitis acute viral hepatitis with rates varying from 0 to up to 80% of cases. Superinfection is associated with Incubation period ranges from 30-120 days. HGV can befulminant acute hepatitis and severe chronic active hepatitis, transmitted by blood transfusion, sexual contact or verticaloften progressive to cirrhosis (52). transmission from mother to child. It is often detected inAcute hepatitis D occurs after an incubation period of 3 - 7 patients who received multiple blood transfusion or inweeks, and a pre-icteric phase begins with symptoms of hemodialysis patients and intravenous drug users. The virusfatigue, lethargy, anorexia and nausea, lasting usually 3 to 7 has a global distribution and is reported to be present in 1-3%days. The appearance of jaundice is typical at the onset of the in volunteer blood donors. HGV co-infection is observed in 6%icteric phase. Fatigue and nausea persist, clay-colored stools of chronic HBV infections and in 10% of chronic HCV infections.and dark urine appear, and serum bilirubin levels become HGV has been shown to produce a persistent infection in aabnormal. In patients with acute hepatitis, self-limiting high proportion of persons with or without acute hepatitis orinfection, convalescence begins with the disappearance of hepatitis -related chronic liver disease (55). Since hepatitis Gclinical symptoms. Fulminant viral hepatitis is rare, but still • 1063 •
  • is a blood-borne infection, prevention relies on avoiding any harboured in the_____________possible contact with contaminated blood. Drug users should (4) The virus causes 60-80 per cent of all primary liver cancer,not share needles, syringes, or other equipment. Till date which is one of the three common causes of cancer relatedthere is no vaccine or treatment of HGV, however it has shown death in _______________________high sensitivity to interferon but most cases relapsed after (5) HCV is a ___________with a diameter of 55 nm. It hascompletion of treatment. _______ serotype and multiple genotypes. (6) ______ is the reservoir for all the viruses.Summary (7) Acute hepatitis occurs in approximately ____ of perinatal,Viral hepatitis is defined as an infection of the liver caused by ______of early childhood and about ____ in those above 5hepatotropic virus and is clinically characterized by an acute years of age.or sub acute febrile illness associated with nausea, anorexia, (8) Maximum infectivity for hepatitis A & E is during theabdominal discomfort, dark colored urine, light colored stools ________half of incubation period continuing throughand appearance of jaundice in sclera or skin. The known early acute phase of infection during the first 1-2 weeks orhepatotropic viruses commonly include hepatitis viruses A, longer.B, C, D, E and G. Infections with hepatitis viruses, especially (9) Contacts of HAV may be given normal humanhepatitis virus B and C, have been associated with a wide immunoglobulin (16 % solution) at ____________ml per kgvariety of extra hepatic manifestations. Whether hepatitis G of body weight intramuscularly as soon as possible aftervirus (HGV) is pathogenic in humans remains unclear. HAV exposure to prevent or attenuate clinical illness.has a world wide distribution. The risk of infection is inversely (10) Yeast derived vaccine is as effective in protection but moreproportional to levels of sanitation and personal hygiene. cost effective than the above vaccine. The schedule isIn developing countries with poor environmental hygienic _______ months. Protection is up to _______ years.conditions, nearly all children are infected with HAV before the (11) Needles and syringes used for routine immunization mustage of 9. HBV also has world wide distribution where 66 percent be autoclaved for twenty minutes or boiled for ____ min.of the world’s population is living in areas where there are high Answers : (1) 66%; (2) 17-90%; (3) liver; (4) East and SEAR,levels of infection. More than 2 billion people in the world had the Pacific Basin and Sub-Saharan Africa; (5) Flavivirus;been found to have HDV prevalence rates ranging from 17- one (6) Man; (7) 1%, 10%, 30% (8) later; (9) 0.02 to 0.12;90%. Sexual and perinatal transmissions are also described. (10) 0, 1 & 6, 15; (11) 30HEV is transmitted via the faeco-oral route. HEV appears tobe endemic in some parts of the lesser-developed countries. ReferencesSporadic infections are observed in persons travelling from 1. Curry MP and Chopra S. Acute Viral Hepatitis. In Mandell GL, Bennet JE and Dolin R (Editors). Mandell, Douglas, and Bennett’s Principles and Practice ofwestern countries to these regions. HGV can be transmitted by Infectious Disease. 6th Edition. Elsevier Churchill Livingstone. Philadelphiablood transfusion. HGV co-infection is observed in 6% of chronic 2005. 1426 - 1441.HBV infections and in 10% of chronic HCV infections. However, 2. Krugman S, Giles JP and Hammond J. Infectious Hepatitis: Evidence for Two , Distinct Clinical Epidemiological and Immunological Types of Infection.whether HGV is actually pathogenic in humans remains unclear. JAMA. 1967; 200: 365.Maximum infectivity for hepatitis A & E is during the later half 3. Buffington J, Mast E. Viral Hepatitis. In Wallace RB (editors). Wallace/Maxcy-of incubation period continuing through early acute phase of Rosenau-Last Public Health and Preventive Mecdicine. 15th Edi. Mc Graw Hill. New York 2007. 211-28.infection during the first 1-2 weeks or longer. In hepatitis B, 4. Hepatitis A vaccines, WHO position paper; Weekly epidemiological record;C & D blood remains infective many weeks before the onset No. 5, 2000, 75, 37-44.of symptoms, through the acute clinical course of the disease 5. Steffen R, Kane MA, Shapiro CN, et al. Epidemiology and prevention ofand during the chronic carrier state. As almost all HAV & HEV hepatitis A in travellers. JAMA. 1994;272:885. 6. Halliday ML, Kang Lai-Y, Zhou T, et al. An epidemic of hepatitis A attributableinfections are spread by the faeco - oral route, good personal to the ingestion of raw clams in Shanghai, China. JlnfectDis. 1991;I64:85Zhygiene, high quality standards for public water supplies and 7. Batra Y, Bhatkal B, Ojha B, Kaur K, Saraya A, Panda SK, et al. Vaccinationproper disposal of sanitary waste are the mainstay of prevention against hepatitis A virus may not be required for schoolchildren in northern India: results of a seroepidemiological survey. Bull World Health Organand control of infective hepatitis. Preventive measures for HBV 2002; 80 : 728-31.& HCV infection include active and passive immunization & 8. Jindal M, Rana SS, Gupta RK, Das K, Kar P Serological study of hepatitis .universal precautions in all health care settings. A virus infection amongst the students of a Medical College in Delhi and evaluation of the need of vaccination. Indian J Med Res 2002; 115 : 1-4.Study Exercises 9. Das K, Agarwal A, Andrews R, Frosner GG, Kar P Role of hepatitis and other . hepatotropic virus in aetiology of sporadic acute viral hepatitis : A hospital-Long Question : Discuss the epidemiology, treatment, based study from urban Delhi. Eur J Epidemiol 2000; 16 : 937-40prevention and control of Viral Hepatitis 10. Kar P Is there a change in seroepidemiology of hepatitis A infection in India? . Indian J Med Res 2006; 123 : 727-9.Short Notes : (1) Difference between Hepatitis A & B (2) Active 11. Hadler SC. Global impact of hepatitis A virus infection changing patterns.and Passive Immunization against Hepatitis A & B In: Hollinger FB, Lemon SM, Margolis HS, eds. Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins; 1991.Fill in the blanks 12. Zukerman JN and Zukerman AJ. Viral Heaptitis. In Cook G and Zumla A(1) HBV also has world wide distribution where ____________ (editors). Manson’s Tropical diseases 21st Edition. Saunders, London 2003. 707-725. of the world’s population is living in areas where there are 13. Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890 high levels of infection. 14. Centre for disease control and prevention . Hepatitis Surviellance Report No.(2) HDV prevalence rates ranging from ___________ 59. Atlanta, GA: US Department of Health and Human Services. Centre for(3) 350 million are chronic carriers of the virus, which is disease control and prevention 2004. 15. Centers for Disease Control and Prevention. Prevention of hepatitis A through • 1064 •
  • active or passive immunization. Recommendation of the Advisory Committee 36. Centers for Disease Control. Hepatitis B virus: a comprehensive strategy for on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, eliminating transmission in the United States through universal childhood 1999, 48(RR-12):1-37 vaccination. Recommendations of the Immunization Practices Advisory16. Wong DC, Purcell RH, Sreenivasan MA, et al. Epidemic and endemic hepatitis Committee (ACIP). MMWR. 1991;40:1-19 in India; Evidence for Non-A/ Non-B Hepatitis virus etiology. Lancet. 1980; 37. Fiore AE, Goldstein ST. Hepatitis B virus. In: Long SS, Pickering LK, Prober 2:876. CG, eds. Principles and Practice of ‘Paediatric. Infectious Disease. 2nd ed.17. Paniker CKJ. Viral Hepatitis. In Paniker CKJ (editor). Ananthnarayan and New York: Churchill Livingstone; 2003:1086-97. Panikers Textbook of Microbiology. Orient Longman, Hyderabad. 7th eds 38. Williams IT, Goidstein ST, Tufa J, et al. Long-terra antibody response to 2005; 547-562. hepatitis B vaccination beginning at birth and to subsequent booster18. Bell BP Mast EE. Hepatitis E virus and other newly identified viruses. In: , vaccination. Pediatr Infect Dis J. 2003;22:157-63. Long SS, Pickering LK, Proher CG, eds. Principles and Practice ofPediairic 39. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345;41- infectious Disease, New York: Churchill Livingstone; 2003. 52.19. WHO Fact sheet N°280, Revised January 2005; 40. Kim WR. Global epidemiology and burden of hepatitis C. Microbes ans mediacentre/factsheets/fs280/en. acessed on 05 Jan 09. infection. 2002;4:1219-122520. Aggrawal R, Krawezynski K; Heapatitis E: An overview and recent advances 41. Khaja, M. N. et al., Curr. Sci., 2002, 83, 219-224. in clinical and laboratory research. J Gastroentrol Hepatol 2000; 15:9-20. 42. Issar SK, Ramakrishna BS, Ramakrishna B et al. Prevalence and presentation21. Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI: Incidence and Severity of hepatitis C related chronic liver disease in Southern India. J Trop Med Hyg of Viral Hepatitis in Pregnancy. Am J Med. 1981;70:252-5 1995; 98: 161-5.22. Khuroo MS, Kamili S, Jameel S: Vertical Transmission of Hepatitis E Virus 43. Panigrahi AK, Panda SK, Dixit RK et al. Magnitude of hepatitis C virus Lancet 1995;345(8956): 1025-6. infection in India. Prevalence in healthy blood donors, acute and chronic23. Viral Hepatitis. CD Alert. National Institute of Communicable Disease liver diseases. J Med Virol 1997; 51: 167-74. publication 2007; 11:1; 4-5. 44. Alter MJ, Marjolis HS et al. The natural history of community acquired24. Aggrawal. Hepatitis E and Pregnancy; Ind j Gastroenterology;2007. vol 26. hepatitis C in United States. N Engl J Med. 1992;327;1899.25. Mast E, Mahoney F, Kane M et al Hepatitis B Vaccine. In: Plotkin SA Orenstien 45. Centre for disease control and prevention. Transmission of hepatitis B and W A, eds. Vaccines . Philadelphia: WB Saunders; 2004; 299-337. C viruses in outpatient settings - New York, Oklahoma and Nebraska, 2000-26. Kenrad EN, David LT. Viral Hepatitis. In : Infectious Disease Epidemiology : 2002. MMWR. 2003;52(38):901-906 Theory and Practice. 2nd Ed. Jones and Bartlett Publishers, US, 2007. 46. Alter MJ, Kruzon-Moran, Nainan OV et al. The prevalence of hepatitis C27. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and infection in United States. N Engl J Med. 1999;341;556-562. N Engl J Med. current and emerging prevention and control measures. Journal of Viral 1992;327;1899. Hepatitis2004; 11 (2) : 97 47. WHO Fact sheet N°164 Revised January 2000; Batham A, Narula D, Toteja T, Sreenivas V, Puliyel JM. Systematic review and mediacentre/factsheets/fs280/en. acessed on 08 Jan 09 meta-analysis of data on point prevalence of hepatitis B in India. Indian 48. Polish LB, Gallagher M, Fields HA, et al. Delta hepatitis: molecular biology Pediatr 2007; 44 : 663-75 and clinical and epiderniological features. Clin Microb Rev. 1993;6:211.29. Dhir V, Mohandas KM. Epidemiology of digestive tract cancers in India. IV. 49. Purcell RH and Gerin JL. Hepatitis Delta virus. In: Fields BN, Knipe DM, and Gall bladder and pancreas. Indian J Gastroenterol 1999; 18 : 24-8. Howley PM, eds. Fields Virology, 3rd ed. Philadelphia, Lippincott - Raven,30. Sarin SK, Singal AK (eds). Hepatitis B in India problems and prevention. CBS 1996, 2819-2829 Publishers, New Delhi. 1st Ed 1996. 50. Chakraborty P Kailash U, Jain A et al. Seroprevalence of hepatitis D virus in ,31. McMahon BJ, Alward WLM, Hall DB, et al. Acute hepatitis B virus infection: patients with hepatitis B virus-related liver diseases. Indian J Med Res 122, relation of age to the clinical expression of disease and subsequent Septermber 2005, pp 254-257 development of the carrier state. J Infect Dis. 1985;151:599. 51. Hadziyannis SJ. Review: Hepatitis delta. Journal of Gastroenterology and32. Schweitzer IL, Dunn AEG, Peters RL, et al. Viral hepatitis type B in neonates Hepatology, 1997, 12(4):289-298. and infants. Am J Med. 1973;55:762-3 52. Lai MMC. Hepatitis Delta virus. In: Webster RG and Granoff A, eds.33. Beasley RP Stevens CE, Shiao IS, et al. Evidence against breatfeeding feeding , Encyclopedia of Virology, London, Academic Press Ltd, 1994, 574-580. as a mechanism for vertical transmission of hepatitis B; Lancet. 1975; 53. Monjardino JP and Saldanha JA. Delta hepatitis. The disease and the virus. 2:740-1 British Medical Bulletin, 1990, 46(2):399-407.34. Hepatitis B vaccines. WHO position paper. Weekly epidemiological record; 54. Heringlake, S., Osterkamp, S., Trautwein, C., Tillmann, H. L., Boker, K. and No. 28, 2004, 79, 253-264 Muerthoff, S., Lancet, 1996, 348, 1626-162935. Rehermann B. Immunopathogenesisof acute hepatitis Band hepatitis C. 55. Alter, H. J., Nakatniji, Y., Melpolder, J et al. The incidence of Transfusion Hepatitis annual update 2004. Published online: Associated Hepatitis G virus infection and its relation to liver disease. N. hepatitis acessed on 07 Jan 09. Engl. J. Med., 1997, 336, 741-754. • 1065 •
  • location to location (4). 180 Anthrax Transmission : Anthrax is a zoonosis. Though the bulk of infections occur in herbivores, carnivores are not immune to Rajesh Vaidya the disease. Cases among scavengers and other carnivores have been reported with infection occurring due to eating infected carcasses. The precise manner in which grazingThe word “Anthrax” originates from Greek for black or coal animals become infected is not known. It is speculated thatbecause of the black eschar which is characteristic of the Infection of the herbivorous animals occurs due to ingestion ofcutaneous form of Anthrax infection. It is principally a disease the spores while grazing accompanied by minor trauma in theof herbivores but has the potential to infect all mammals oral mucosa or other parts of the gastrointestinal tract due toand even some birds (1). Anthrax is caused by infection with chewing rough vegetation.the bacterium, Bacillus anthracis. The spores of the bacteriacan survive in the environment for years or decades (2). The Human infections occur as a result of contact with diseaseddisease is endemic in all parts of the world but human cases animals or animal products. The modes of transmissionare not common. Human infection results from direct or include direct Inoculation of spores through breaks in theindirect exposure to infected animals or occupational exposure skin, inhalation of spores and ingestion of contaminatedto infected or contaminated animal products. Anthrax has meat. Human-to-human transmission and laboratory acquiredbeen in the news because of the fact that it is a suitable agent anthrax are extremely rare (6).for germ warfare and its use a weapon of bioterrorism in the Clinical FeaturesUnited States of America (3). Other names for anthrax include Anthrax can present in three different forms depending on the“malignant pustule” and “Wool sorter’s disease”. route through which the infection was acquired. CutaneousEpidemiology anthrax occurs when the spores enter through a skin lesion,Anthrax incidence among humans is dependent on the level gastrointestinal tract anthrax is contracted from ingestion ofof exposure to affected animals. Anthrax continues to be contaminated food, and pulmonary (inhalation) anthrax fromendemic in many parts of the world. The WHO also reports that breathing in airborne anthrax spores. Another form is Anthraxthe disease is enzootic in most parts of Asia and Africa and meningitis.sporadic outbreaks among herbivorous animals are reported Cutaneous Anthrax : This is the commonest form offrom other parts of the world (4). presentation accounting for over 95% of all cases. TheAccurate figures on human anthrax in India are not available. incubation period can be as short as 9 hours to as long as twoHowever sporadic outbreaks continue to occur. The three weeks, but usually ranges from two to six days. Over a periodsouthern states of Tamil Nadu, Andhra Pradesh and Karnataka of approximately ten days the cutaneous lesion which occurshave recorded at least 200 cases of human anthrax since the at the site of entry of the spores, goes through the stages of a1950s. In the recent past, the National Institute of Communicable papule, ring of vesicles, ulceration and formation of a typicalDiseases has investigated two outbreaks of human anthrax black eschar. The cutaneous lesion is non purulent and isone in Mysore and the other in Midnapore (5). Animal anthrax typically painless. After ten days the eschar begins to resolve.remains endemic in India because inadequate vaccination. The resolution of the eschar occurs over six weeks and is not hastened by treatment. Cutaneous anthrax is self limitingAgent : Bacillus anthracis is a large, spore - forming, gram and in over 90% of cases resolution of the eschar takes place- positive bacillus with a diameter of 1.5 µm and a length of without complications. However, a small proportion of cases, if5µm. It can easily be cultured on sheep blood agar growing untreated, develop systemic anthrax (4, 6).typically “medusa head” colonies. Anthrax can be differentiatedfrom other gram - positive bacilli as it is non motile and non Pulmonary Anthrax : Inhalational anthrax usually occurringhaemolytic and typically sensitive to penicillin. The virulence after the inhalation of spores from contaminated animal hidesof the organism depends on the bacterial capsule and the toxin or products. Historical evidence indicates the role of individualcomplex. The capsule is a poly - D - glutamic acid that protects it susceptibility to infection as only a few cases on inhalationalagainst lysis and phagocytosis. There are three anthrax toxins: anthrax occurred among workers exposed occupationally tothe Edema Factor (EF), the Lethal Factor (LF) and a protective high concentration of viable anthrax spores (6). The onset ofantigen (2). Only one strain is known. illness is usually non specific with fever, chills, non-productive cough, myalgia and malaise. After one to three days, the diseaseUnder unfavourable conditions which are not conducive to suddenly becomes hyperacute with dyspnoea, strident cough,growth and multiplication of the bacilli, they form spores. cyanosis and disorientation culminating in death. Death maySporulation requires the presence of free oxygen. The spores are occur within hours of onset of symptoms. Case fatality rateresistant to drying, heat, ultraviolet light, radiation, and most can be over 80% even with aggressive antimicrobial therapydisinfectants. The spores can survive for many years in the (4, 6, 7).soil. Spores are the predominant form in the environment andit is through the uptake of spores that anthrax is contracted. Gastro - intestinal Anthrax : Gastrointestinal anthrax can present in two clinical forms following ingestion of BacillusEnvironment : There is clear evidence that anthrax is a anthracis in contaminated food. The incubation period rangesseasonal disease. The occurrence of anthrax among animals in from two to five days following consumption of contaminatedany one place is related to temperature and rains. However, the meat (8). Intestinal anthrax usually presents with nausea,conditions which predispose to outbreaks differ widely from • 1066 •
  • vomiting, fever, abdominal pain, haematemesis, diarrhoea and Prevention and Controlascites. Overt gastrointestinal tract anthrax cases are often Control of the disease in animals is the key to prevention offatal, because they may remain unrecognized until it is too late anthrax in humans. Vaccination of susceptible animals, correctfor effective treatment. Oropharyngeal anthrax is characterized disposal of carcasses of anthrax cases and proper disinfection,by sore throat, dysphagia, fever, regional lymphadenopathy in decontamination and disposal of contaminated materials willthe neck and toxaemia. These cases are usually milder than the prevent exposure of humans to anthrax spores. In additionclassic gastrointestinal disease and carry a more favourable vaccination of persons at risk and chemoprophylaxis of thoseprognosis. exposed can also be used for prevention.Anthrax Meningitis : Haematogenous spread of the pathogen Annual immunization of livestock herds is required to becan take place from any form of anthrax. Meningitis due to carried out in endemic areas. Decontamination and disinfectionanthrax is a serious development which carries close to 100% of materials and surfaces suspected to be harbouring sporesmortality. The patient shows clinical signs of meningitis. The is difficult because the spores are highly resistant to commonmeningitis of anthrax is haemorrhagic (9). measures. Autoclaving, dry heat, formaldehyde, ethylene oxide,Diagnosis gamma irradiation and sodium hypochlorite solution can all beCutaneous anthrax has the characteristic painless, blackened, used for disinfection. Carcasses of suspected anthrax cases cannecrotic eschar in the late stages of the infection. The early be disposed by incineration or deep burial. Details pertainingforms of the cutaneous lesion need to be differentiated from to decontamination and disposal of contaminated material areother papular lesions that present with lymphadenopathy. A given in reference 4.high index of suspicion is required for a clinical diagnosis of Vaccination : Vaccination among humans should be restrictedgastrointestinal and inhalational anthrax. History of possible to those at risk, particularly those at occupational risk. Liveoccupational exposure or consumption of contaminated meat spore vaccines are used in China and Russia. In Britainmust be sought. and the United States bacteria free aluminium hydroxideConfirmation of diagnosis can be done by serology or precipitated vaccine is licensed. A complex primary schedule ofbacteriological tests. Specific Enzyme - Linked Immunosorbent six vaccinations over an 18 month period is required followedAssays (ELISAs) are available for anthrax antibodies. by annual boosters. Newer vaccines including a plasmid DNADetection indicates past infection or vaccination while a four vaccine and vaccines for intranasal use are under developmentfold rise in titre indicates recent infection (10, 11). Indirect (2, 4, 9).Heamagglutination tests have also been developed (12, 13). Chemoprophylaxis : The United States Army recommendsBlood cultures can also be used to confirm diagnosis. Bacilli Ciprofloxacin or Doxycycline for four weeks for unimmunizedcan also be cultured from ascitic fluid, pleural fluid, and CSF. individuals. A longer duration of chemoprophylaxis is requiredIn cases of systemic anthrax infection blood cultures are for complete clearance of spores from the lungs (18).almost always positive but patients often die before blood Summarycultures are obtained. Cultures from skin lesions are not usefuldiagnostically (14). The word ‘Anthrax’ originates from Greek for black or coal because of the black eschar which is characteristic of theNewer molecular techniques including the Polymerase Chain cutaneous form of Anthrax infection. Anthrax continues to beReaction (PCR) are now available for diagnosis of Anthrax. endemic in many parts of the world. Accurate figures on humanThese rapid methods may are useful because early diagnosis anthrax in India are not available. The three southern states ofis crucial (15, 16). Tamil Nadu, Andhra Pradesh and Karnataka have recorded atTreatment least 200 cases of human anthrax since the 1950s. BacillusPrompt and timely antibiotic therapy is essential results in anthracis is a large, spore - forming, gram - positive bacilluscomplete recovery of cases of anthrax. Bacillus anthracis is with a diameter of 1.5 µm and a length of 5 µm. There are threehighly sensitive to penicillin which is the antibiotic of choice. anthrax toxins : the Edema Factor (EF), the Lethal Factor (LF)The pathogen is also sensitive to several other antibiotics and a protective antigen. Only one strain is known. Spores areincluding Chloramphenicol, Tetracyclines, Fluoroquinolones the predominant form in the environment and it is through theand Erythromycin. In most cases particularly inhalational uptake of spores that anthrax is contracted. Human infectionsand gastrointestinal anthrax, antibiotics must initially be occur as a result of contact with diseased animals or animaladministered intravenously. products. The modes of transmission include direct Inoculation of spores through breaks in the skin, inhalation of sporesDuring the bioterrorism attacks of 2001 in the United States, and ingestion of contaminated meat. Anthrax can present init was found that using two or more antibiotics intravenously three different Cutaneous, Pulmonary and Gastrointestinalimproved survival (9). CDC protocols issued after the Anthrax. Confirmation of diagnosis can be done by serologybioterrorism attacks recommend Ciprofloxacin 400mg BD or bacteriological tests or blood culture. Prompt and timelyor Doxycycline 100mg BD for a total of 60 days. The dose of antibiotic therapy is essential which results in completeCiprofloxacin for children is 10 - 15 mg/Kg BD for 60 days recovery of cases of anthrax. Penicillin is the antibiotic of choice.(17). The treatment remains the same for pregnant women and Control of the disease in animals is the key to prevention ofimmunocompromised individuals. anthrax in humans. Vaccination of susceptible animals, correct disposal of carcasses of anthrax cases and proper disinfection, • 1067 •
  • decontamination and disposal of contaminated materials will 3. Klietmann WF, Ruoff Kl. Bioterrorism : Implications For The Clinical Microbiologist. Clin Microbiol Rev 2001;14 : 364 - 381.prevent exposure of humans to anthrax spores. Vaccination 4. Turnbull PCB. Guidelines for the Surveillance and Control of Anthrax inamong humans should be restricted to those at risk, particularly Humans and Animals. 3rd edition. World Health Organization. Emergingthose at occupational risk. Chemoprophylaxis recommended in and other Communicable Diseases, Surveillance and Control. WHO/EMC/ ZDI/98.6the United States Army is Ciprofloxacin or Doxycycline for four 5. Ganapati M. Human anthrax in India may be linked to vulture decline. BMJweeks for unimmunized individuals. 2001;322 : 320 6. Dixon TC, Meselson M, Guillemin J and Hanna PC. Anthrax. The New EnglandStudy Exercises Journal of Medicine. 1999. 341 : 815 - 826.Long Question : Discuss the epidemiology, treatment, 7. Inglesby TV, O’toole T and Henderson D et al. Anthrax As A Biological Weapon, 2007 : Updated Recommendations For Management. JAMA 2002;prevention and control of Anthrax. 287 : 2236 - 52.Short Notes : (1) Spectrum of clinical presentation of Anthrax 8. LaForce FM. Anthrax. Clin Infect Dis 1994;19 : 1009 - 1014 9. Shadomy SV and Rosentstein NE. Anthrax. In Wallace RB and Kohatsu(2) Prevention and control of Anthrax. N. Eds. Maxcy Rosenau Last Public Health and Preventive Medicine. 15thMCQs Edition. 2008. The McGraw - Hill Comapanies.New York.427 - 431. 10. Harrison LH, Ezzell JW, Abshire TG, Kidd S, Kaufmann AF. Evaluation of1. All are properties of Bacillus anthracis except (a) Gram - serologic tests for diagnosis of anthrax after an outbreak of cutaneous positive (b) Spore - forming (c) Non motile (d) Haemolytic anthrax in Paraguay. J Infect Dis 1989;160 : 706 - 710.2. All are anthrax toxins Except (a) Edema Factor (EF) 11. Turnbull PC, Doganay M, Lindeque PM, Aygen B, McLaughlin J. Serology and anthrax in humans, livestock and Etosha National Park wildlife. Epidemiol (b) Swelling Factor (SF) (c) Lethal Factor (LF) (d) Protective Infect 1992;108 : 299 - 313. antigen 12. Sirisanthana T, Nelson KE, Ezzell JW, Abshire TG. Serological studies of3. Bacillus anthracis is known to have how many strains patients with cutaneous and oral - oropharyngeal anthrax from northern Thailand. Am J Trop Med Hyg 1988;39 : 575 - 581. (a) 1 (EF) (b) 2 (c) 3 (d) 4 13. Johnson - Winegar A. Comparison of enzyme - linked immunosorbent and4. Antibiotic of choice in treatment of Anthrax (a) Penicillin indirect haemgglutination assays for determining anthrax antibodies. J Clin (b) Ciprofloxacin (c) Tetracyclines (d) Chloramphenicol Microbiol 1984;20 : 357 - 3615. Commonest clinical form of presentation of Anthrax is 14. Green BD, Battisti L, Koehler TM, Thorne CB, Ivins BE. Demonstration of a capsule plasmid in Bacillus anthracis. Infect Immun 1985;49 : 291 - 297 (a) Pulmonary Anthrax (b) Gastrointestinal Anthrax 15. Patra G, Sylvestre P Ramisse V, Therasse J, Guesdon JL. Isolation of a specific , (c) Cutaneous Anthrax (d) Anthrax Meningitis chromosomic DNA sequence of Bacillus anthracis and its possible use inAnswers : (1) d; (2) b; (3)a; (4) a; (5) c. diagnosis. FEMS Immunol Med Microbiol 1996;15 : 223 - 231. [ 16. Ramisse V, Patra G, Garrigue H, Guesdon JL, Mock M. Identification andReferences characterization of Bacillus anthracis by multiplex PCR analysis of sequences on plasmids pXO1 and pXO2 and chromosomal DNA. FEMS Microbiol Lett1. WHO Fact Sheet on Anthrax. Fact sheet No. 264 October 2001. Available on 1996;145 : 9 - 16 http : // Accessed on 08 Oct 17. CDC Update : Investigation of Bioterrorism Related Anthrax and Interim 2008. Guidelines for Exposure Management and Antimicrobial Therapy. October2. Lucey D. Bacillus Anthracis (Anthrax). In Mandell GL, Bennet JE and Dolin 2001. MMWR Oct 26, 2001;50 : 909 - 919 R (Editors) Mandell, Douglas, and Bennett’s Principles and Practice of 18. Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against Infectious Disease. 6th Edition. Elsevier Churchill Livingstone. Philadelphia experimental inhalation anthrax. J Infect Dis 1993;167 : 1239 - 1243 2005. 2485 - 2490. spores of Clostridium tetani which are universally present in 181 Tetanus the soil. The disease can occur at any age but is particularly common and serious in newborn babies in the form of neonatal tetanus (3). Tetanus among adolescents and young adults Rajesh Vaidya usually occurs as result of infection through skin injuries.Tetanus is the only non communicable disease that is vaccine Epidemiologypreventable (1). It is an infectious disease caused by infection The widespread use of a safe and effective vaccine has made thewith Clostridium tetani. Under favourable anaerobic conditions, disease rare in the developed world. In developing countries,the pathogen produces tetanospasmin, which is a potent however, tetanus remains a major public health problem.neurotoxin. This toxin blocks inhibitory neurotransmitters in The WHO estimated that the total number of tetanus deathsthe central nervous system and causes the muscular stiffness worldwide in 2002 was 213,000, of which neonatal tetanus wasand spasms typical of generalized tetanus (2). Despite a estimated to cause about 180,000 deaths and maternal tetanusmarked decrease in the occurrence of disease following the about as 15,000 - 30,000 deaths (4). The global incidence ofintroduction of vaccination, the disease continues to be a tetanus is estimated to be one million cases annually or 10 perimportant public health problem in many parts of the world, 100,000 population. Mortality rates can be as high as 28 perparticularly in developing countries. Infection occurs through 100,000 in developing countries as compared to less than 0.1 • 1068 •
  • per 100,000 in North America (5). Clinical FeaturesA large majority of tetanus cases are birth - associated and occur The incubation from the entry of spores to the onset of clinicalin developing countries among newborn babies or in mothers manifestations can vary from 3 to 21 days, but is usuallyfollowing unclean deliveries and poor postnatal hygiene (4). between six and eight days. Usually, the further the injury siteNeonatal tetanus accounts for more than half of all tetanus is from the central nervous system, the longer the incubationcases in developing countries. The WHO aims to eliminate period. The severity of disease is inversely related to thematernal and neonatal tetanus; MNT defined as less than one duration of the incubation period. The shorter the incubationneonatal tetanus case per 1000 live births at district level per period, the higher the chance of death. In neonatal tetanus,year. 47 countries have not been able to eliminate MNT as of the average incubation period is about 7 days with a range ofDecember 2007 (6). In South East Asia, India, Bangladesh, 4 - 14 days (1, 9). Tetanus can classified into four forms basedMyanmar and Indonesia are yet to eliminate MNT. on clinical presentation.Neonatal tetanus is one of the most under reported notifiable Generalized Tetanus : This is the most common form ofdiseases. In 1995, over 5,500 cases of tetanus were reported presentation. The earliest sign of the disease is usually a spasmfrom Uttar Pradesh, Madhya Pradesh, Rajasthan, Orissa, Bihar of the jaw muscles (lockjaw) and a grimace like appearance ofand Assam. the face (Risus Sardonicus). As the symptoms progress, there isAgent : Clostridium tetani are gram positive bacilli that are spasm of the muscles of the abdomen, neck, back and thorax.obligate anaerobes. The organisms are sluggishly motile In severe cases tonic seizures can occur. A characteristicin fresh cultures. On maturity they loose their flagellae and feature is that the patient does not loose consciousness duringdevelop a terminal spore which gives the characteristic the spasms. The spasms can be triggered by external stimuli.drumstick appearance. The vegetative forms produce two Patients may also have elevated temperature, sweating,exotoxins, tetanolysin and tetanospasmin (also called Tetanus hypertension and tachycardia. Spasms may continue for overToxin). The role of tetanolysin in the pathogenesis of tetanus three weeks and complete recovery may take unknown. Tetanospasmin is a neurotoxin and causes the Localized Tetanus : This is a less common form of the disease.clinical manifestations of tetanus. It diffuses from the wounds There is stiffness and rigidity of the muscles around the site ofto local muscles and can also spread systemically through the infection. Recovery is usually spontaneous. Only about 1% ofblood and lymphatics. Weight for weight, tetanospasmin is one cases are fatal. However, at times, localized rigidity may be aof the most potent toxins known. The estimated human lethal prodrome of generalized tetanus.dose is less than 2.5 ng per kg (2). Cephalic Tetanus : This is a rare form of the localized diseaseTetanus spores are extremely stable and can geminate into and is generally associated with lesions on the head or face.vegetative forms even after years. They are highly resistant to Involvement of cranial nerves is a characteristic feature of thisheat and most chemical disinfectants including ethanol, phenol, form of tetanus.and formalin. They can be destroyed by iodine, glutaraldehyde, Neonatal Tetanus : This is the form of generalized tetanusand hydrogen peroxide. Autoclaving at 121°C under 15 psi occurring in neonates. Generalized weakness followed bypressure also destroys the spores (1, 5). Tetanus spores are an inability to suckle are the common manifestations. WHOwidely distributed in nature. They are found in the soil, human considers any neonate with normal ability to suck and cryand animal faeces, and even on human skin. during the first 2 days of life and who, between 3 and 28 daysHost : Tetanus can occur at any age. In developed countries of age, cannot suck normally and becomes stiff or has spasmstetanus is now largely a disease of the elderly. In the United (i.e. jerking of the muscles) as a confirmed case of neonatalStates, the risk of tetanus increases with age (7). In developing tetanus (6).countries, however, a large proportion occur among newborn Diagnosisbabies or in mothers following unclean deliveries and poorpostnatal hygiene. Tetanus in children and adults following Diagnosis of tetanus is usually based on history and clinicalinjuries also constitutes a considerable public health problem. signs and symptoms rather than laboratory findings. ANeonatal tetanus in India is reported more in male children. bedside diagnostic test called the ‘Spatula Test’ with very highThis male preponderance may reflect a male bias for health care specificity and sensitivity has been proposed from India (10).seeking rather than an actual male predilection (8). In India, Isolation of Clostridium tetani from can neither confirm norneonatal tetanus shows distinct seasonal variation with the exclude the diagnosis. The pathogen is often isolated fromlargest number of cases being reported during the monsoons wounds among patients who do not have the disease andand post - monsoon period. even carefully performed anaerobic cultures are negative even from contaminated wounds. The only condition which mimicsTransmission : The ubiquitous nature of tetanus spores makes tetanus closely is strychnine poisoning. Serology also has littleit possible for them to enter the body through any form of value as antibody levels even in the protective range do notinjury. Neonatal tetanus results from unclean deliveries and the rule out disease (1, 5).application of contaminated material on the umbilical stump. Inchildren and adults tetanus can result from both acute wounds Treatmentand chronic infections. Puncture and deep wounds are more Local wound management, supportive therapy particularlylikely to result in tetanus rather than superficial abrasions. airway maintenance and passive immunization are the main • 1069 •
  • requirements of management of cases of tetanus. All wounds Summaryshould be cleaned and adequate debridement carried out. Tetanus is the only non communicable disease that is vaccineThe course of the disease, however, is not altered by wound preventable. Despite a marked decrease in the occurrence ofdebridement. Clostridium tetani is sensitive to several disease following the introduction of vaccination, the diseaseantibiotics including Penicillin, Tetracycline and Metronidazole. continues to be an important public health problem in manyAntibiotics may eliminate the organism and consequently parts of the world, particularly in developing countries. Theprevent further production of toxin. Airway maintenance may WHO estimated that the total number tetanus deaths worldwiderequire an endotracheal tube or even a tracheostomy. Sedation is in 2002 were 213,000. The global incidence of tetanus isthe mainstay of symptomatic treatment. Intravenous Diazepam estimated to be one million cases annually or 10 per 100,000or Lorazepam may be required for control of the spasms. population. The WHO aims to eliminate maternal and neonatalImmunization : Passive immunization with Human Tetanus tetanus; MNT defined as less than one neonatal tetanus caseImmunoglobulin (HTIG) is required to neutralize unbound per 1000 live births at district level per year. In South Easttetanus toxin. Doses ranging from 500 units to 3000 - 6000 Asia, India, Bangladesh, Myanmar and Indonesia are yet tounits have been recommended by various experts (11). eliminate MNT. Clostridium tetani are gram positive bacilliIntrathecal HTIG was earlier used for neonatal tetanus, but has that are obligate anaerobes. The vegetative forms produce twonow been shown to be ineffective. As the amount of tetanus exotoxins, tetanolysin and tetanospasmin. The ubiquitoustoxin released during infection is inadequate to produce an nature of tetanus spores makes it possible for them to enter theeffective immune response, all patients of tetanus should also body through any form of injury. The incubation from the entrybe given active immunization. of spores to the onset of clinical manifestations can vary fromPrevention and Control 3 to 21 days, but is usually between six and eight days. TheActive immunization against tetanus is the cornerstone of severity of disease is inversely related to the duration of theprevention and control of tetanus. Mass education campaigns incubation period. The shorter the incubation period, the higherand training of birth attendants to ensure hygienic and safe the chance of death. Tetanus can be classified into four formsdeliveries are also important measures for prevention of based on clinical presentation they are Generalized Tetanus,neonatal tetanus. Localized Tetanus, Cephalic Tetanus and Neonatal Tetanus. Diagnosis of tetanus is usually based on history and clinicalActive Immunization : Tetanus toxin is inactivated by signs and symptoms rather than laboratory findings. A bedsideformaldehyde to form tetanus toxoid. The toxoid has been diagnostic test called the ‘Spatula Test’ has a very high specificityused as a Monovalent Vaccine (TT) to immunize adults, or as a and sensitivity. Local wound management, supportive therapycomponent of combined Diphtheria - Tetanus - Pertussis (DTP) particularly airway maintenance and passive immunizationvaccine or Diphtheria - Tetanus (DT) vaccine for immunization are the main requirements of management of cases of tetanus.of children. Several other combinations like combined Tetanus Passive immunization with Human Tetanus Immunoglobulindiphtheria (Td) vaccine for adults and a Tetanus - diphtheria (HTIG) is required to neutralize unbound tetanus toxin. Active- acellular Pertussis (TdaP) combination are also available. immunization against tetanus is the cornerstone of preventionAdsorption of tetanus toxoid onto aluminium salts increases and control of tetanus.its antigenicity (2). Tetanus toxoid can withstand exposure totemperatures of around 20°C for months and storage at 37°C Study Exercisesfor a few weeks without significant loss of potency. The vaccine Long Question : Discuss the epidemiology, treatment,should be stored at 2 - 8°C. Vaccines that have been frozen prevention and control of Tetanus.should not be used (4). Short Notes : (1) Forms of clinical presentation of TetanusWHO recommends a childhood tetanus immunization schedule (2) Active Immunization against Tetanusof five doses. In India, the primary series of three doses of DTP MCQsare given at six, ten and fourteen weeks followed by a boosterbetween 16 and 24 months of age. Another booster of the DT 1. The global incidence of tetanus is estimated to be (a) 1 pervaccine is given at the school going age, while boosters of TT 100,000 population (b) 10 per 100,000 population (c) 100are given at 10 years and 16 years of age. per 100,000 population (d) None of the above 2. In South East Asia, following country has eliminatedPregnant women with an inadequate or unknown immunization Maternal and Neonatal Tetanus (a) India (b) Bangladeshhistory should always receive 2 doses of tetanus toxoid - (c) Myanmar (d) None of the abovecontaining vaccine : the first dose as early as possible during 3. In neonatal tetanus, the average incubation period is aboutpregnancy and the second dose at least 4 weeks later (4). (a) 4 days (b) 7 days (c) 11 days (d) 15 daysIn cases of injury a dose of tetanus toxoid vaccine may be given 4. This is the most common form of clinical presentationdepending on the severity of the injury and on the reliability of tetanus (a) Localized Tetanus (b) Generalized Tetanusof the history of previous tetanus vaccinations. The vaccine (c) Cephalic Tetanus (d) Neonatal Tetanusshould be given if the last dose was administered more than 10 5. The only condition which mimics tetanus closely isyears ago (or 5 years in the case of severe injuries) (4). (a) Strychnine poisoning (b) Botulism Poisoning (c) Rabies (d) None of the above Answers : (1) b; (2) d; (3) b; (4) b; (5) a. • 1070 •
  • References 2005. 2817 - 2822. 6. World Health Organization. WHO - recommended surveillance standard of1. Kretsinger K, Moran JS and Roper MH. Tetanus, In Wallace RB and Kohatsu neonatal tetanus. http : // N. Eds. Maxcy Rosenau Last Public Health and Preventive Medicine. 15th MNTE initiative/ en/index. html. Accessed on 14 Oct 2008. Edition. 2008. The McGraw - Hill Comapanies.New York.115 - 117. 7. Pascual FB, McGinley EL, Zanardi LR et al. Tetanus Surveillance - United2. Borrow R, Balmer Pand Roper MH. The Immunological Basis of Immunization States, 1998 - 2000. MMWR.2003;52(SS - 3) : 1 - 8. Series. Module 3 Tetanus Update 2006. World Health Organization. Geneva 2007. 1 - 3. 8. Govt of India. New Delhi. CSSM Review. No 4. Apr 933. WHO Tetanus : http : // 9. CDC Altanta. http : // html Accessed on 14 Oct 2008. tetanus.pdf Accessed on 14 Oct 2008.4. WHO Position Paper. Tetanus Vaccine. Weekly Epidemiological Record. No. 10. Apte NM and Karnad DR. Short report : the spatula test : a simple bedside 20, 2006, 81, 197 - 208. test to diagnose tetanus. Am J Trop Med Hyg. 1995; 53(4) : 386 - 7.5. Bleck TP Clostridium tetani (Tetanus) In Mandell GL, Bennet JE and Dolin . 11. Wassilak SGF, Roper MH, Murphy TV and Orenstein WA.Tetanus Toxoid. In R (Editors) Mandell, Douglas, and Bennett’s Principles and Practice of : Plotkin SA, Orenstein WA eds. Vaccines 4th Ed 2004. Philadelphia. WB Infectious Disease. 6th Edition. Elsevier Churchill Livingstone. Philadelphia Saunder and Co 745 - 781. Epidemics of plague occasionally occur when the disease 182 Plague spreads from wild rodents to rats that live in close proximity of human habitation. Rajesh Vaidya Between 1989 and 2003, a total of 15 year period, 38, 310 cases with 2845 deaths were recorded in 25 countries. InPlague is one of the oldest diseases known to man (1). It is these 15 years the highest number of human plague cases wasprimarily a zoonotic disease that exists in nature between small reported in 1991 and the lowest number 1989. Eight countriesmammals, usually wild rodents, and the fleas that they harbour reported human plague almost every year. These countries(2). Plague is endemic in many parts of the world and exits in were the Democratic Republic of the Congo, Madagascar andmany small natural foci. It is widely distributed in the tropics the United Republic of Tanzania in Africa; Peru and the Unitedand subtropics and in warmer areas of temperate countries. States in the Americas, and China, Mongolia and Viet NamThe causative bacteria, Yersinia pestis can also infect humans. in Asia. An increase in the incidence of human plague hasIt is transmitted between animals and humans by the bite of become apparent since the early 1990s, particularly in Africa.infected fleas, direct contact, inhalation and rarely, ingestion Three geographical areas experienced outbreaks of humanof infective materials. Untreated plague can be a very serious plague after silent periods of about 30 - 50 years : India indisease with case fatality rates between 30% and 60% (3). 1994, Indonesia in 1997 and Algeria in 2003 (5 - 7). The totalRecent outbreaks have shown that plague may recur in areas number of human plague cases reported to WHO in 2002 wasthat have long remained silent (1). 1925, of which 177 were fatal. In 2003, nine countries reported 2,118 cases and 182 deaths. 98.7% of those cases and 98. 9% ofPlague has been known as a dreaded killer from times those deaths were reported from Africa. Today the distributionimmemorial. The first pandemic, also called the Justinian of plague coincides with the geographical distribution of itsplague took place in the sixth century and is reputed to have natural foci (3, 5).killed nearly a hundred million victims. The second plaguepandemic is known as the “Black Death” of the fourteenth India : India suffered very large number of deaths during thecentury which caused 50 million deaths. A quarter of the third Plague pandemic. Plague outbreaks continued to occur,population of Europe is said to have been wiped out by this but with decreasing frequency during the first half of the 20thpandemic. The third pandemic began in Hong Kong in 1894. century. This is often attributed to the collateral benefit fromWithin 10 years this pandemic had spread to all the continents. the extensive insecticide spraying done as a part of the NationalThis pandemic resulted in 13 million deaths in India (1, 4). Malaria Programme. India remained plague free for almost 30During the third pandemic, the causal agent, Yersinia pestis years after the last human case was reported from Karnatakawas discovered in 1894. in1966. In August - October 1994 human plague was reported inEpidemiology India. During this outbreak, 876 cases with 54 deaths wereGlobal : The number of cases of human plague reported to the characterized as presumptive plague. Most cases were reportedWorld Health Organization has remained stable in the recent from Maharashtra (596), 151 from Gujarat, 68 from Delhi, 50past. The WHO believes that the number of cases officially from Karnataka, 12 from Madhya Pradesh, and 10 from Uttarnotified is considerably lower than the actual number (5). Pradesh. Almost all the deaths were reported from Gujarat.Plague exists in natural enzootic cycles involving wild rodents Several reasons have been put forth to explain this outbreak.and their fleas in several parts of the world. These natural Rat - fall was first reported from Mamla village in the Beedcycles are usually hidden with no transmission to humans. district of Maharashtra on 5 August 1994. This was followed • 1071 •
  • by reports of flea nuisance. Three weeks later, suspected cases and epizootic (amplification) hosts (1). Enzootic hosts areof bubonic plague were reported from Mamla village followed characterized by relatively mild illness, and low mortality reports from other villages in Beed and other districts. Beed Voles and mice have been suggested as maintenance hosts.has had sylvatic plague in the past. Ecological changes created Epizootic rodents are associated with susceptibility and highby the earthquake in September 1993 and large scale storage mortality. Highly susceptible or epizootic plague hosts includeof foodgrains probably contributed to a gradual growth of the various species of mice, rats, voles, gerbils, ground squirrelsrat population. The resurgence of plague in Surat, Gujarat, and marmots. Rats have historically been a primary carrier ofwas related to a record high rainfall during the September plague (1, 15, 17 - 20).monsoon. Floods in the Tapti river resulted in inundation of Transmission : The most common mode of transmission oflarge areas. Many rodents were found dead when the water Yersinia pestis to humans is by the bite of infectious fleas.floods receded. Based on the clinical picture and the plague Other, less common modes of transmission include directoutbreak in neighbouring Maharashtra the outbreak in Surat contact with infectious body fluids or tissues while handlingwas declared as pneumonic plague on 21 September 1994 (1, 8 an infected animal or inhaling infectious respiratory droplets- 12). In February 2002, an outbreak of pneumonic plague (16 (13). The mode of entry of the organism has marked clinicalcases, 4 deaths) occurred in Hat Koti village, Shimla district, significance.Himachal Pradesh. The outbreak is believed to have startedafter a person acquired the infection in the forest, which then Clinical Featuresspread to others through person - to - person contact (5). Since Infection by Yersinia pestis causes a severe febrile illness2002 there has been no confirmed case of plague in India. characterized by headache, myalgia, malaise, shakingAgent : Yersinia pestis is a gram - negative coccobacillus. Yersinia chills, prostration and gastrointestinal symptoms. The threewas formerly classified in the family Pasteurellaceae, but has commonest clinical presentations of plague are bubonic,been now reclassified as members of the Enterobacteriaceae septicaemic and pneumonic (1, 13, 15). Less common forms offamily. Though there are 11 species in the genus Yersinia, plague include pharyngeal and meningeal plague.only three are considered important human pathogens. The Bubonic Plague : For bubonic plague the mode of entry ofbacteria is small (1.0 to 2.0 mcm x 0.5 mcm), pleomorphic the organism is by a flea bite. The infection spreads via theand is seen as single cells or short chains in direct smears. lymphatics to the regional lymph nodes causing inflammationThey are nonmotile, nonsporulating, non - lactose fermenting and swelling in one or several nodes forming the classic buboes.facultative anaerobes (13 - 15). Buboes may occur in any regional lymph node sites includingVector : Yersinia pestis is most commonly transmitted between inguinal, axillary and supraclavicular. After an incubationanimal reservoirs and to humans through the bites of infected period of two to six days, a patient experiences sudden onset offleas. There are more than 1, 500 flea species, of which about illness characterized by headache, chills, fever, malaise and pain30 are known to be vectors for Yersinia pestis. The major flea in the affected regional lymph nodes. Progression of symptomsvectors include the following (15) : is usually rapid with the regional lymphadenitis becoming tender and painful. With specific treatment in uncomplicated(a) Xenopsylla cheopis (the oriental rat flea; nearly worldwide cases, fever and general clinical symptoms usually resolve over in moderate climates) three to five days.(b) Oropsylla montanus (United States)(c) Nosopsyllus fasciatus (nearly worldwide in temperate Septicaemic Plague : Septicaemic plague occurs when Yersinia climates) pestis invades and continues to multiply in the bloodstream. It(d) Xenopsylla brasiliensis (Africa, India, South America) can occur secondarily to bubonic plague or can develop without(e) Xenopsylla astia (Indonesia and Southeast Asia) detectable lymphadenopathy. The host response may result in a wide spectrum of pathological events including disseminated(f) Xenopsylla vexabilis (Pacific Islands) intravascular coagulopathy, multiple organ failure andTo be an efficient plague vector, the flea must be able to adult respiratory distress syndrome. Complications includeingest the Yersinia pestis with its blood meal. It must also plague pneumonia, plague meningitis and hepatic or spleniclive long enough for the pathogen to multiply in sufficiently abscesses.large numbers. It must be able to transfer the pathogen to an Pneumonic Plague : Pneumonic plague is the least commonanimal or human host in sufficient concentrations to cause an but most dangerous and fatal form of the disease. It caninfection. Xenopsylla cheopis is the most important vector of develop as a secondary complication of septicaemic plague orplague. A high incidence of plague infected Xenopsylla cheopis result from inhalation of infectious droplets. The incubationin a given focus, greatly increases the risk of transmission to period is usually varies from one to three days. There is suddenhumans (1). Pulex irritans, the human flea may be responsible onset of chills, fever, headache, body pains, weakness andfor human to human transmission of Plague (1, 16). chest discomfort. This progresses rapidly to severe pneumoniaHost Factors : More than 200 mammalian species have been accompanied by high fever, dyspnea, and often haemoptysis.known to be naturally infected with Yersinia pestis. However, If specific antibiotic therapy is not begun within 18 - 24 hoursplague is primarily a disease of rodents. The infection is of onset, the patient is unlikely to survive. Pneumonic plaguemaintained in natural foci of the disease in wild rodent must be considered highly contagious, although person - to -colonies through transmission between rodents. The animal person transmission is most likely in cold humid environmentshosts of plague are classified as enzootic (maintenance) hosts coupled with overcrowding. As the transmission occurs through • 1072 •
  • infected droplets (and not airborne droplet nuclei), person - to provides presumptive evidence of plague (1, 15). In the recent- person transmission requires close contact. past rapid diagnosis of plague has become available using theDifferential Diagnosis F1 antigen diagnostic assays based on dipsticks. These tests make a bedside diagnosis available within 15 minutes usingDifferential diagnosis of bubonic plague includes bacterial bubo aspirate, serum and urine specimens (23).lymphadenitis, infectious mononucleosis, lymphaticfilariasis, tick typhus, tularemia and other causes of acute Treatmentlymphadenopathy. Involvement of intra - abdominal lymph When a diagnosis of human plague is suspected, appropriatenodes may mimic appendicitis or acute cholecystitis. Pneumonic specimens for diagnosis should be taken immediately and theplague may be confused with other causes of acute, severe patient should be started on specific antibiotic treatment withoutcommunity - acquired pneumonia, such as pneumococcal, waiting for laboratory confirmation. All patients suspected ofstreptococcal or Haemophilus influenzae pneumonia (1). having bubonic plague should be placed in isolation until 2Diagnosis days after starting antibiotic treatment. Suspect plague patients with evidence of pneumonia should be placed in isolation andPlague is diagnosed clinically based on exposure history and the managed under respiratory droplet precautions.symptoms of the patient. Presence of the classical buboes leadsto suspicion of plague. Septicaemic plague resembles other Streptomycin is the drug of choice. The dose of streptomycin isgram - negative septicemias and is, therefore more difficult to 30 mg/Kg/day (Not more than of 2 g/day) in divided doses givendiagnose on clinical grounds. Pneumonic plague can similarly intramuscularly. Streptomycin must be given for a full coursebe mistaken for other pneumonias. If possible, samples for of 10 days or until 3 days after the temperature has returnedconfirmation of plague should be taken before treatment is to normal. Chloramphenicol is a suitable alternative. The dosebegun. However, treatment should not be delayed by waiting of chloramphenicol is 50 mg/Kg/day administered in dividedfor the laboratory results (15). Collection and transport of doses either parenterally or orally for 10 days. Tetracyclines arespecimens is dealt with in detail in a separate chapter. effective in the primary treatment of patients with uncomplicated plague. An oral loading dose of 15 mg/Kg tetracycline (not toRoutine blood tests show Leucocytosis with a predominance exceed 1 g total) should be followed by 25 - 50 mg/Kg/day (upof neutrophils. Total WBC counts may be as high as 25,000/ to a total of 2 g/day) for 10 days. Tetracyclines may also beml. The degree of leucocytosis is proportional to the severity of used adjunctively with other antibiotics. Fluoroquinolones,illness. Peripheral blood smear may show toxic granulations. such as ciprofloxacin are also effective (1, 15, 21).Thrombocytopenia is common (21). The laboratory diagnosis ofplague is based on bacteriological and/or serological evidence. ProphylaxisDiagnostic specimens for smear and culture include whole Close contacts of cases with pneumonic plague, or personsblood, sputum, aspirates from suspected buboes, pharyngeal suspected to have had direct contact with body fluids or tissuesswabs and cerebrospinal from suspected plague meningitis of a Yersinia pestis - infected mammal, or exposed during acases (1). Smears stained with Gram, Giemsa, Wright, or laboratory accident to known infectious materials shouldWayson stain can provide supportive but not confirmatory receive prophylactic antibiotics if the exposure was in theevidence of a plague infection in the form of bipolar staining previous six days. Tetracycline and chloramphenicol are theGram - negative bacilli. antibiotics of choice for prophylaxis (1).The diagnosis of plague is confirmed by the culture of Yersinia Prevention and Controlpestis from body fluids or tissues. Yersinia pestis grows on Control of transmission is directed at controlling the rodentsolid media as grey - white, translucent colonies, usually reservoirs and flea vectors of the disease. Trying to eliminatetoo small to be seen as individual colonies at 24 hours. After fleas and wild rodents from the natural environment in plagueincubation at 37°C for 48 hours, colonies are about 1 - 2mm in - infected areas are impractical. However, controlling rodentsdiameter. After 48 - 72 hours of incubation colonies are raised and their fleas around places where they are in close proximityand have an irregular appearance. Cultures are definitely of human beings is very important. Environmental sanitationidentified as Yersinia pestis by specific phage lysis (1, 22). and public health education are effective means of achievingPlague can be also be confirmed serologically by a four - fold these ends. Rodent and flea control measures are discussed inor greater change in titre to the Yersinia pestis F1 antigen by detail in the relevant Chapters in the section on Entomology.passive haemagglutination testing of paired serum specimens.The specificity of a positive passive haemagglutination test Surveillance : An effective surveillance system to provide earlycan be confirmed by the F1 antigen haemagglutination - warning can abort epidemics. Effective plague prevention andinhibition test. Some patients of plague seroconvert as early as control programmes require up - to - date information on thefive days after onset of symptoms, most seroconvert between incidence and distribution of the disease. The surveillanceone and two weeks after onset, while a few seroconvert three programme must be designed to collect, analyse, and interpretweeks or more after onset. Less than 5% do not seroconvert. clinical, epidemiological, and epizootiological data on plague.After seroconversion, positive serological titres usually Surveillance should identify cases and epizootics as quickly asdiminish gradually over months to years. Enzyme - Linked possible so that steps can be taken to control disease spread (1).ImmunoSorbent Assays (ELISAs) for detecting IgM and IgG Surveillance must include reporting of human cases, ecologicalantibodies may also be used for diagnosis. Detection of the F1 and environmental observations, and surveillance of rodentantigen in tissues or fluids by direct fluorescent antibody testing populations. Readers may refer to the WHO Plague Manual • 1073 •
  • (1) for details on human and rodent surveillance including pestis vaccines composed of presumably avirulent strainsprecautions to be observed by health care workers. also have been developed. However, none of these vaccines isFlea Indices : The most basic information obtained from flea commercially available, and their safety and efficacy have notand rodent surveys is the number of fleas of different species been adequately tested (13, 25).found on various species of hosts. This raw data can be used Summaryto calculate various indices. The important flea indices in useare (1) : Plague is one of the oldest diseases known to man. The first plague epidemic has been described in the Bible as the outbreak Total number of fleas collected among the Philistines in 1320 BC. The causal agent, Yersinia (regardless of species)Total Flea index = pestis was discovered In1894. Plague exists in natural enzootic Total number of host cycles involving wild rodents and their fleas in several parts species examined of the world. These natural cycles are usually hidden with no Number of fleas of species ‘A collected ’ transmission to humans. Between 1989 and 2003, a total of from host speciesSpecific Flea Index = Number of individuals of 15 year period, 38, 310 cases with 2845 deaths were recorded in 25 countries including India. Yersinia pestis is nonmotile, host species examined nonsporulating, non - lactose fermenting, gram - negative(Multiplication of this index by 100 gives the percentage index). coccobacillus. Yersinia pestis is most commonly transmitted Number of host species between animal reservoirs and to humans through the bites ofPercentage of = infested with flea species infected fleas. There are more than 1, 500 flea species, of which x 100 about 30 are known to be vectors for Yersinia pestis. Plaguehosts infested Total number of host species examined is primarily a disease of rodents. The infection is maintained in natural foci of the disease in wild rodent colonies through transmission between rodents. The most common mode of Number of Flea species collected transmission of Yersinia pestis to humans is by the bite of from burrows (or nest or house) infectious fleas. The three commonest clinical presentationsBurrow (or nest = of host species of plague are bubonic, septicaemic and pneumonic. Plagueor house) index Total number of burrows is diagnosed clinically based on exposure history and the (or nest or house) of host symptoms of the patient. The laboratory diagnosis of plague species examined is based on bacteriological and/or serological evidence. Smears stained with Gram stain can provide supportive but notThe specific flea index is the most widely used of the above confirmatory evidence in the form of bipolar staining Gram -indices. It has been reported that a specific flea index of greater negative bacilli. The diagnosis of plague is confirmed by thethan 1 for Xenopsylla cheopis on rats represents a potentially culture of Yersinia pestis from body fluids or tissues. In thedangerous situation with respect to increased plague risk for recent past rapid diagnosis of plague has become availablehumans. using the F1 antigen diagnostic assays based on dipsticks.Vaccination : Plague vaccines were widely used in the past These tests make a bedside diagnosis available within 15but have not proven effective in the control of plague. Both live minutes using bubo aspirate, serum and urine specimens. Allattenuated and formalin - killed Yersinia pestis vaccines have patients suspected of having bubonic plague should be placedbeen developed. The vaccines are variably immunogenic and in isolation until 2 days after starting antibiotic treatment.moderately to highly reactogenic. They do not protect against Streptomycin is the drug of choice. The dose of streptomycin isprimary pneumonic plague. Vaccination is of little use during 30 mg/Kg/day (Not more than of 2 g/day) in divided doses givenhuman plague outbreaks, since a month or more is required to intramuscularly. Close contacts of cases with pneumonic plaguedevelop a protective immune response. Vaccines are, therefore, should receive prophylactic antibiotics if the exposure was innot recommended for immediate protection in outbreak the previous six days. Tetracycline and chloramphenicol are thesituations. Vaccination is only recommended as a prophylactic antibiotics of choice for prophylaxis. Control of transmission ismeasure for high - risk groups like laboratory personnel who directed at controlling the rodent reservoirs and flea vectors ofare constantly exposed to the risk of contamination (1,16,24). the disease. An effective surveillance system to provide earlyThe killed or inactivated plague vaccine is prepared from warning can abort epidemics. The surveillance programmeYersinia pestis organisms grown in artificial media and then must be designed to collect, analyse, and interpret clinical,inactivated in formaldehyde. It is administered intramuscularly epidemiological, and epizootiological data on plague. Plagueas a series of three primary doses. The initial dose of 1 ml is vaccines were widely used in the past but have not provenfollowed 1 to 3 months later by a 0.2 ml dose. A third primary effective in the control of plague. Vaccines are, therefore, notinjection of 0.2 ml is given 5 to 6 months after the second. Two recommended for immediate protection in outbreak situations.booster doses of 0.2 ml are administered at 6 - month intervals,and additional boosters may be given every 1 to 2 years (15). Study ExercisesAdverse reactions following injection of the first dose of plague Long Question : Discuss the epidemiology, treatment,vaccine generally are mild, but the frequency and severity of prevention and control of Plaguesuch events can increase with repeated doses. Live Yersinia Short Notes : (1) Spectrum of clinical presentations of plague (2) Characteristics of efficient plague vector (3) Flea Indices • 1074 •
  • MCQs 7. World Health Organization. Weekly epidemiological record. Human plague in 1994. 1996, 22 : 165 - 168.1. Yersinia pestis was first discovered in (a) 1893 (b) 1894 (c) 8. Datta KK (Ed). Occurence of Plague in India, Plague : Epidemiology, 1895 (d) 1896 Prevention and Control, Delhi, National Institute of Communicable Diseases,2. Number of species in the genus Yersinia considered 1994 : 7 - 14. 9. Campbell GL. And Hughes JM Plague in India : A New Warning from an Old important human pathogens (a) 1 (b) 3 (c) 5 (d) 7 Nemesis. Annals of Internal Medicine. 1995; 122 (2) : 151 - 153.3. Human flea responsible for human to human transmission 10. Sant MV, Nimbkar YS, Renapurkar DM. Is plague lurking in Maharashtra? A of Plague (a) Pulex irritans (b) Oropsylla montanus survey in Bhir district. Indian J Med Sci. 1972; 26 : 480 - 4. (c) Nosopsyllus fasciatus (d) Xenopsylla vexabilis 11. Centers for Disease Control and Prevention. Update : Human plague—India, 1994.MMWRMorb Mortal Wkly Rep. 1994; 43 : 761 - 2.4. Epizootic hosts are all except (a) Amplification hosts 12. Dennis DT. Plague in India. Editorial. BMJ. 1994;309 : 893 - 894 (b) Maintenance hosts (c) Highly susceptible (d) Have high 13. Gage KL, Dennis DT and Tsai T F. 2001. Prevention of Plague : mortality Recommendations of the Advisory Committee on Immunization Practices5. ___________ Plague is the least common but most (ACIP). Center for Disease Control, Morbidity and MortalityWeekly Report. MMWR, 1996;45(RR - 14) : 1 - 15 dangerous (a) Septicaemic plague (b) Bubonic plague 14. CIDRAP Plague : Current, comprehensive information on pathogenesis, . (c) Pneumonic plague (d) None of the above microbiology, epidemiology, diagnosis, and treatment. http : //id_center.6. Drug of choice for treatment of plague (a) Tetracyclines apic. org/cidrap /content/bt/plague/biofacts/plaguefactsheet. html. Accessed on 15 Mar 2008. (b) Chloramphenicol (c) Ciprofloxacin (d) Streptomycin 15. Perry RD, Fetherston JD. Yersinia pestis - etiologic agent of plague. Clin7. Antibiotics of choice for prophylaxis (a) Tetracyclines Microbiol Rev, 1997;10 : 35 - 66. (b) Rifampicin (c) Ciprofloxacin (d) Streptomycin 16. Houhamdi L, Lepidi H, Drancourt M, et al. Experimental model to evaluate the human body louse as a vector of plague. J Infect Dis 2006 Dec 1;194(11)8. Specific flea index of greater than ______________ for : 1589 - 96 Xenopsylla cheopis on rats represents a potentially 17. Christie, A. B. 1982. Plague : review of ecology. Ecol. Dis. 1 : 111 - 115. dangerous situation (a) 1 (b) 2 (c) 3 (d) 4 18. Poland, J. D., and A. M. Barnes. 1979. Plague, p. 515 - 559. In J. H. Steele (ed), CRC handbook series in zoonoses. Section A. Bacterial, rickettsial, andAnswers : (1) b; (2) b; (3) a; (4) b; (5) c; (6) d; (7) a; (8) a. mycotic diseases, vol. I. CRC Press, Inc., Boca Raton, Fla.References 19. Butler T. Plague. In : Strickland GT, ed. Tropical medicine. Philadelphia, Pa : WB Saunders, 1991 : 408 - 161. Dennis, DT, Gage KL, Gratz N, Poland JD, and Tikhomirov E. (Principal 20. Gage KL. Plague. In : Collier L, Balows A, Sussman M, Hausler WJ, eds. authors). Plague Manual. Epidemiology, Distribution, Surveillance and Topley and Wilson’s microbiology and microbial infections. Ed 9. Vol 3. Control. World Health Organization. Geneva 1999. London : Arnold, 1998 : 885 - 9032. World Health Organization. Epidemic and Pandemic Alert and Response 21. Minnaganti VR and Cunha A. Plague. Emedicine article. Updated 12 May (EPR). Plague. http : //www. who. int/csr/disease/plague/en/ WHO. Accessed 2006. http : //www. emedicine. com/med/topic3381. htm Accessed on 15 Mar 0n 15 Mar 2008. 2008.3. World Health Organization. Plague. Fact sheet No 267. Revised February 22. Quan TJ, Poland JD, Barnes AM, Yersinioses. In Barlows A, Hausler W. (Eds) 2005. http : //www. who. int/mediacentre/factsheets/fs267/en/. Accessed on : Diagnostic procedures for bacterial, mycotic and parasitic infections. 6th 15 Mar 2008. edition.Washington DC, American Public Health Association, 1981, 723 -4. Pollitzer R. Plague, Geneva, World Health Organization, 1954 (Monograph 745. series) 23. Chanteau S, Rahalison L, Ratsitorahina M, Mahafaly, Rasolomaharo M,5. World Health Organization. Weekly epidemiological record. Human plague Boisier P O’Brien T, Aldrich J, Keleher A, Morgan C, Burans J. Early diagnosis , in 2002 and 2003. No. 33, 2004, 79, 301 - 308 of bubonic plague using F1 antigen capture ELISA assay and rapid6. World Health Organization. Weekly epidemiological record. Human plague immunogold dipstick. Int J Med Microbiol. 2000 Jul;290(3) : 279 - 83. in 2001 and 2002. No. 16, 2003, 78, 129 - 136. 24. Centers for Disease Control and Prevention. Prevention of plague. Morbidity and MortalityWeekly Report, 1996;45 : 1 - 15. 25. Meyer KF, Cavanaugh DC, Bartelloni PJ, Marshall JD Jr. Plague immunization. I. Past and present trends. J Infect Dis 1974;129(suppl) : S13 - S18. other animals and humans through close contact with their 183 Rabies saliva (bites, scratches, licks on broken skin, and mucus membranes). Rajesh Vaidya Epidemiology Magnitude of the problem : Rabies is enzootic in animal inThe word ‘Rabies’ has its origin in Sanskrit, “rabhas” means more than100 countries with a population of over 3.3 billion.“to do violence”. The Greek word for rabies, “lyssa” derives Approximately 55,000 people die from rabies each year, the vastfrom the root “lud” which means “violent”. Rabies is an acute majority of these deaths occurring in Asia and Africa. In Africa,viral disease, which causes encephalomyelitis in virtually all there are estimated at 24,000 (or 4 per 1,00,000 population)the warm blooded animals, including man. The causative agent deaths annually. More than 10 million people, mostly inis found in domestic and wild animals and is transmitted to Asia, receive post exposure vaccination against rabies every • 1075 •
  • year (1). In India alone, 20,000 deaths are estimated to occur to infection of some of the adjacent non - nervous tissuesannually, i.e. 2 per 1,00,000 population. Almost 1.8 million like secretory tissues of salivary glands. The virus is widelypeople annually receive post exposure - prophylaxis against disseminated throughout the body at the time of clinical onsetrabies. With the exception of Andaman & Nicobar islands and (4).Lakshadweep islands, human cases of rabies are reported from Clinical Featuresall over the country round the year (2). Prodromal symptoms of rabies are non specific and may last forAgent : The Rabies viruses belong to the genus Lyssavirus 2 to 10 days. Malaise, headache, anorexia may be present alongof the Rhabdoviridae family. Currently, this genus comprises with fever, cough, chills, and sore throat. Some patients mayseven genotypes, type 1 of which represents the classic rabies have gastro - intestinal symptoms like abdominal pain, nauseavirus. This RNA virus is bullet shaped round at one end and and diarrhoea (3). The first rabies specific symptom is pain orflat at the other measuring 100 - 300 nm in length and 75 nm paraesthesia referred to the site of exposure which is present inin diameter. The virus is covered with a lipid envelope having about 50% of cases. Major clinical signs are related to the virusspike like projections. - induced encephalomyeloradiculitis. The acute neurologicalThe rabies virus is highly resistant to cold, and dryness. The period shows objective signs of CNS involvement. Two majorvirus is highly thermolabile with a half life of approximately clinical presentations are observed : furious and paralytic4 hours at 40°C and 35 seconds at 60°C. In brain tissue, it can forms that cannot be correlated with any specific anatomicalsurvive up to 1 - 2 weeks at room temperature (1). The rabies localization of rabies virus in the CNS. In furious rabies therevirus remains stable for several days at 0 - 4°C, indefinitely at is hyperactivity, disorientation, and hallucinations. The patient(-) 70°C and when freeze dried. The virus cannot withstand pH may have periods of agitation alternating with periods of calm.less than 4 or more than 10. It is also susceptible to the action of Attempts at drinking result in spasm of pharynx, larynx, andoxidizing agents, most organic solvents, surface acting agents diaphragm. Similar effects may occur even on seeing water orand quaternary ammonium compounds. Proteolytic enzymes blowing air on the face (Aerophobia). Eventually there may beand UV rays rapidly inactivate the rabies virus. Soaps and abrupt death or paralysis develops. Paralytic rabies is presentdetergents are effective against rabies virus because of their in about 20% of cases from onset. The paralysis is maximal inlipid eliminating property, which destroy the outer covering of bitten extremity, diffuse or symmetric. The final stage of comathe virus (3, 4). almost always begins within 10 days. Death may occur due toHost factors : Although all age groups are susceptible, rabies respiratory arrest soon after onset of coma. In cases the patientis most common in children aged below 15 years, with 30 - 50% survives for a few days complications like raised ICT, cardiacof post - exposure prophylaxis given to children aged 5 - 14 arrhythmias, hypotension, and renal failure may be seen.years, the majority being male (3). Rabies is invariably fatal (3).Transmission : Human infection usually occurs following a Diagnosistransdermal bite or scratch by an infected animal. Transmission A diagnosis of rabies can be made on clinical grounds ifmay also occur when infectious material, usually saliva, comes reliable history of exposure is available or specific signs likeinto direct contact with the victim’s mucosa or with fresh skin hydrophobia or aerophobia are present. There are no laboratorylesions. The virus cannot cross intact skin. Very rarely, rabies tests to diagnose the infection before onset of clinical disease.may occur through inhalation of virus - containing aerosol or Fluorescent Antibody detection in skin biopsy (from neck)via infected organ transplants. In developing countries, dog can be done for confirmation of diagnosis. Post mortem testsbites account for over 90% of cases. Wild animals like jackals, include demonstration of ‘Negri Bodies’ and isolation of, or hyena may also be a source of infection. In developed It is important to distinguish rabies from treatable conditionscountries, rabies due to domestic animal bites is rare. Most to ensure protection of health care workers, prevent rabiescases are due to contact with wild animals such as raccoons or hysteria / psychosis. It is also essential to distinguish rabiesskunks. Bat rabies is reported from Latin American countries from post vaccinial encephalomyelitis caused by the nervelike Brazil, Venezuela and Mexico, Southern United States and tissue vaccine (5, 6, 7).parts of Europe including Germany, Denmark, and Holland. TreatmentIncubation periods for Rabies have been reported from as Rabies is invariably fatal once symptoms develop. Treatmentshort as four days to as long as 19 years. The usual duration discussed later in the chapter focuses on animal exposuresis between 20 to 90 days. 95% cases have incubation period where rabies transmission is a possibility.less than one year. The duration of the incubation period maydepend on the severity of bite, quantity of virus inoculated, Prevention and Controlinnervation of the bitten area and distance from CNS (3). The essential measures required for the control of rabies arePathogenesis eliminating the diseases in domestic animals like dogs and immunoprophylaxis for humans.On entering the human body, the virus then either replicates innon - nervous tissues or directly enters peripheral nerves and Rabies Vaccinestravels by retrograde axoplasmic flow to the central nervous Nerve Tissue Vaccine (NTV) : More than 100 years ago, Louissystem (CNS). The estimated speed of virus migration is 15 Pasteur and his colleagues developed the first crude rabies- 100 mm per day. The virus then moves from the CNS via vaccine for post - exposure prophylaxis based on attenuatedanterograde axoplasmic flow within peripheral nerves, leading virus in desiccated nerve tissue. Although continuously • 1076 •
  • improved over the years, inactivated NTVs produced in the injected into the deltoid muscle (or anterolateral thigh inbrains of sheep or goats (Semple) or suckling mice (Fuenzalida) children aged <2 years) on each of days 0, 3, 7, 14 andare associated with neurological adverse reactions. In about 28.0.3 - 0.8 individuals per 1000 vaccinees, contaminating (b) The 4 - dose regimen (“2 - 1 - 1” or Zagreb regimen) :neuroproteins present in the vaccine cause severe allergic Prescribes 2 doses on day 0 (1 in each of the 2 deltoid/encephalomyelitis. India and Nepal have successfully phased thigh sites) followed by 1 dose on each of days 7 and 21.out production and use of NTVs (1, 3). Intradermal Administration : The high cost of CCVs by theCell Culture Vaccines (CCV) : CCVs consist of virus that has volume required for the standard IM route is prohibitive forbeen inactivated following propagation in cell cultures the widespread use in many areas where dog rabies is endemic. Forhuman diploid cell vaccine was introduced in 1967. The more some CCVs, equal immunogenicity has been demonstrated byrecently developed, and less expensive, purified chick embryo ID using at least 60% less vaccine than by IM vaccination. Sincecell vaccine and purified Vero cell - based vaccines have 1991, WHO has recommended the ID route of administrationcharacteristics comparable to the human diploid cell vaccines. for rabies pre - and post - exposure prophylaxis. Either the 8 -CCVs are based on fixed viruses of genotype 1. site or the 2 - site regimen should be used, as recommended byFactors that should be taken into consideration when deciding the respective vaccine manufacturer (8, 9).whether or not to initiate post exposure prophylaxis include (a) The 8 - site ID regimen : Prescribes on day 0, injections ofthe likelihood of the concerned animal being rabid, category 0.1 ml given at 8 sites (1 in each upper arm, 1 in each lateralof exposure (I - III), clinical features of the animal, as well as thigh, 1 on each side of the suprascapular region, and 1 onits availability for observation and laboratory testing. In most each side of the lower quadrant region of the abdomen) ;situations in developing countries, the vaccination status of on day 7, 1 injection in each upper arm and each lateralthe offending animal should not be taken into consideration to thigh; and on each of days 30 and 90, 1 injection in onewithhold prophylaxis (1, 3). upper arm. The dose on day 90 may be replaced by 2 ID injections on day 30.Rabies Immunoglobulin (RIG) : Rabies immunoglobulin of (b) The 2 - site ID regimen : Prescribes 1 injection of 0.1 ml atboth equine (ERIG) and human (HRIG) is available. RIG should 2 sites on days 0, 3, 7 and administered in all category III exposures and in categoryII exposures involving immunodeficient individuals. Given Previously Vaccinated Individuals : For rabies - exposedits relatively slow clearance, Human Rabies Immunoglobulin patients who have previously undergone complete pre -(HRIG) is the preferred product, particularly in cases of multiple exposure vaccination or post - exposure prophylaxis with asevere exposures. Where HRIG is not available or affordable, CCV, 2 IM or ID doses of such a vaccine administered on dayspurified Equine Immunoglobulin (ERIG) is used. Most of the 0 and 3 are sufficient. RIG is not necessary in such cases. Thenew ERIG preparations are potent, highly purified, safe and same rules apply to people vaccinated against rabies who haveconsiderably less expensive than HRIG. The dose for HRIG is demonstrated VNA titres of at least 0.5 IU/ml.20 IU/kg body weight, and for ERIG is 40 IU/kg body weight. Post - exposure prophylaxis of HIV - infected persons andAs much of the recommended dose of passive immunization HIV/AIDS patients : Several studies of patients with HIV/AIDSproducts as is anatomically feasible should be infiltrated into have reported that those with very low CD4 counts will mountand around the wounds. The remainder should be administered a significantly lower or no detectable neutralizing antibodyby deep intramuscular injection at an injection site distant response to rabies. In such patients and those in whom thefrom the vaccine injection site. In case of multiple wounds, the presence of immunological memory is no longer assured as aRIG should be diluted with normal saline to make sufficient result of other causes, proper and thorough wound treatmentvolume to ensure infiltration at all wound sites. RIG for passive as described above and antisepsis accompanied by localimmunization should not be injected later than seven days after infiltration of a passive immunization product are of utmostthe initiation of post - exposure vaccination. Several studies of importance. Immunocompromised patients with category IIpatients with HIV/AIDS have reported that those with very low exposures should receive rabies immunoglobulin in additionCD4 counts will mount a significantly lower or no detectable to a full post - exposure vaccination series as listed above. Anneutralizing antibody response to rabies. In such patients local infectious disease specialist with expert knowledge of rabiesinfiltration of a passive immunization product are of utmost prevention should be consulted.importance (1, 3). Pre Exposure VaccinationVaccination Pre exposure vaccination should be offered to :Rabies vaccines are required to be used in three situations : (a) People at high risk of exposure such as those working inPost exposure prophylaxis, pre exposure prophylaxis, and rabies diagnostic or research laboratoriesvaccination in those previously vaccinated. (b) Veterinarians, animal handlers (including bat handlers),Post Exposure Prophylaxis animal rehabilitators and wildlife officers (c) People (especially children) living in or traveling to high -Intramuscular administration : The post exposure vaccination risk areasschedule is based on IM doses of 1 ml or 0.5 ml, depending onthe manufacturer. The recommended regimen consists of either Intramuscular Administration : Pre - exposure rabiesa 5 - dose or a 4 - dose schedule. vaccination requires IM doses of 1 ml or 0.5 ml, depending on the vaccine type, given on days 0, 7 and 28 (day 28 preferable,(a) The 5 - dose regimen (Essen regimen) : Prescribes 1 dose • 1077 •
  • but administration may be advanced towards day 21 if time is canine vaccination campaigns have been the most effectivelimited). For adults, the vaccine should always be administered measure for controlling canine rabies. At least 70% of the dogin the deltoid area of the arm; for children aged <2 years, population in each community should be vaccinated in areasthe anterolateral area of the thigh is recommended. Rabies where canine rabies is endemic. Oral vaccination of dogs offersvaccine should not be administered in the gluteal area, where a new approach that may significantly improve dog vaccinationthe induction of an adequate immune response may be less coverage (especially of free - roaming and poorly supervisedreliable. dogs) when applied either exclusively or in combination withIntradermal Administration : ID administration of 0.1