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Section 9 : Communicable Diseases167   Principles of Infectious Diseases Epidemiology                 RajVir Bhalwar      ...
be transmitted to a human being either directly, or indirectly               Principles of Infectious Diseases    167     ...
Nosocomial Infection : This is an infection contracted while in       to another human so as to further propagate the spec...
provided conditions are favourable (e.g. cholera vibrio, polio       Host Factorsvirus, Hepatitis A, etc. can survive in w...
Incubation Period : Incubation period is the time period between                       Frequency of Disease : As has been ...
within a very close distance so as to be able to directly come         survive environmental adversaries like drying or he...
pertaining to the life cycle of the agent. In addition, for          The “human reservoir” of infectious agents can occur ...
Study Exercises                                                    8.	 Case Fatality Ratio (CFR) is a reasonably good meas...
modern sense, therefore, immunity has been defined as the               with the same antigen, which provokes its producti...
Acquired (Adaptive) immunity : This Box - 1                                                                               ...
molecules per second for four to five days. The other B cells                   process weeds out only those T cells with ...
Local Immunity : Local immunity is believed to be produced by                                               immunization, ...
be elicited. Any subsequent immune response to an antigen          Table - 2 : Immunizing Agentsis called a secondary resp...
Passive Immunisation : Passive immunization may be                             Storage of Vaccinesadministered using human...
Human resources section9-textbook_on_public_health_and_community_medicine
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  1. 1. 10095752550
  2. 2. 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
  3. 3. 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 methods.host 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 •
  4. 4. 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 •
  5. 5. 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 •
  6. 6. 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 •
  7. 7. 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 •
  8. 8. 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 disease.in 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 agent.to 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 •
  9. 9. 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 •
  10. 10. 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 •
  11. 11. 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 •
  12. 12. 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 •
  13. 13. 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 •
  14. 14. 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 •
  15. 15. 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 •

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