Typhoid fever


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Typhoid, also known as Typhoid fever or Typhoid Disease , is a common worldwide
bacterial disease, transmitted by the ingestion of food or water contaminated with the
feces of an infected person, which contain the bacterium Salmonella enterica, serovar
Typhi(fig.1). The bacteria then perforate through the
intestinal wall and are phagocytosed by macrophages.
The organism is a Gram-negative short bacillus that is
motile due to its peritrichous flagella(fig.1). The
bacterium grows best at 37°C / 98.6°F – human body

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Typhoid fever

  1. 1. 0 | P a g e
  2. 2. 1 | P a g eSECTION I • Typhoid DiseaseCHAPTER 1Introduction ................................................................................................................................. 2CHAPTER 2History and Distribution ............................................................................................................... 4CHAPTER 3Symptoms and Transmission and Pathogenesis ........................................................................ 8CHAPTER 4Diagnosis and Treatment .......................................................................................................... 14CHAPTER 5Resistance and Prevention ......................................................................................................... 16CHAPTER 6Genetic and Complication ........................................................................................................ 19__________________________________________________________SECTION I I • Salmonella speciesCHAPTER 7Salmonella and Nomenclature .................................................................................................. 22CHAPTER 8Antigenic Structure ....................................................................................................................24CHAPTER 9Habitats ......................................................................................................................................26CHAPTER 10Isolation and Identification ........................................................................................................27CHAPTER 11Salmonella infection .................................................................................................................. 30CHAPTER 12Conclusion and recommendation ...............................................................................................33CHAPTER 13Typhoid Fever Questions and Answers .....................................................................................35Contend
  3. 3. 2 | P a g eIntroductionTyphoid, also known as Typhoid fever or Typhoid Disease , is a common worldwidebacterial disease, transmitted by the ingestion of food or water contaminated with thefeces of an infected person, which contain the bacterium Salmonella enterica, serovarTyphi(fig.1). The bacteria then perforate through theintestinal wall and are phagocytosed by macrophages.The organism is a Gram-negative short bacillus that ismotile due to its peritrichous flagella(fig.1). Thebacterium grows best at 37°C / 98.6°F – human bodytemperature.as well as by certain non-typhoid salmonella (NTS),particularly Paratyphoid strains A, B, C. Thesewaterborne gram negative aerobes are associatedwith poor sanitation and fecal contamination of waterand food supplies. The syndrome needs to be distinguished from that caused by manyother organisms. Today there are as many as 16-30 million cases per year, almostexclusively in the developing world, with a mortality rate of 10%. Recent developmentsin the mapping of the Salmonella genome haveprovided insights into its pathogenicity and howantibiotic resistance and human immunitydevelop. Typhoid fever is important surgicallybecause abdominal complications such asintestinal perforation(fig.2), bleeding, cholecystitisand pancreatitis represent the most seriouscomplications of the illness. Typhoid perforationof the ileum is one of the most common causesof bowel perforation in the developing world.This fever received various names, such as gastric fever, abdominal typhus(fig.2), infantileremittant fever, slow fever, nervous fever, pythogenic fever, etc. The name of "typhoid"comes from the neuropsychiatric symptoms common to typhoid and typhus (fromGreek τῦϕος, "stupor").(Fig 1. Salmonella spp.)(Fig 2. Human abdomin.)
  4. 4. 3 | P a g eTyphoid fever is very contagious. An infected person can pass the bacteria out of theirbody in their faeces when they have a bowel movement or, less commonly, when theyurinate. If someone else eats food or drinks water that has been contaminated with asmall amount of infected faeces or urine, they can contract typhoid fever.Typhoid fever is an infection caused by bacteria that can spread throughout the body.Without prompt treatment, it can cause serious complications and can be fatal. Thisdisease is characterised by high fever, abdominal pain with or without diarrhoea,enlarged spleen and rose coloured spots confined to chest & abdomen. It can infect theblood (septicaemia) which has a fatality rate of 10 - 20 % if untreated & 1% in treatedpersons. The risk of infection is generallylow, approximately 1 in 30,000 fortravellers to developing countriesspending 4 weeks. Risk is 10 timeshigher in parts of India, Africa, Asia andSouth America(fig.3). Typhoid is generallya milder illness in children under 5. Riskis increased by failing to observehygiene cook it, peel it or forget it.The fever also known as enteric fever, is a potentially fatal multisystemic illness. Theprotean manifestations of typhoid fever make this disease a true diagnostic challenge.The classic presentation includes fever, malaise, diffuse abdominal pain,and constipation. Untreated, typhoid fever is a grueling illness that may progressto delirium, obtundation, intestinal hemorrhage, bowel perforation, and death withinone month of onset. Survivors may be left with long-term or permanentneuropsychiatric complications.Salmonella typhi has been a major human pathogen for thousands of years, thriving inconditions of poor sanitation, crowding, and social chaos. The name S typhi is derivedfrom the ancient Greek typhos, an ethereal smoke or cloud that was believed to causedisease and madness. In the advanced stages of typhoid fever, the patients level ofconsciousness is truly clouded. Although antibiotics have markedly reduced thefrequency of typhoid fever in the developed world, it remains endemic in developingcountries.(Fig 3. Distribution of thyphoid disease.)
  5. 5. 4 | P a g eHistoryTyphoid fever was not well understood in the ancient world, probably because itssymptoms are not primarily diarrheal, but rather systemic and non-specific. It was onlyin the mid-19th century that physicians began to distinguish it from typhus and malaria.Sir William Osler’s clinical description remains unsurpassed. Typhoid fever wasfrequently associated with military campaigns and was a significant cause of death inthe American Civil War and Boer War where deaths from typhoid exceeded those fromcombat. With recognition that fecal contamination of food and water supplies was themain mode of transmission of the illness and measures taken to prevent these , typhoidfever has been restricted, in industrialized countries, to localized epidemics andinfections in travelers returning from endemic areas.Mary Mallon ("Typhoid Mary") in ahospital bed (foreground)(fig.4). Shewas forcibly quarantined as acarrier of typhoid fever in 1907 forthree years and then again from1915 until her death in 1938.Some historians believe that theEnglish colony of Jamestown,Virginia, died out from typhoid.Typhoid fever killed more than6000 settlers between 1607 and1624. During the American Civil War,81,360 Union soldiers died of typhoid or dysentery. In the late 19th century, the typhoidfever mortality rate in Chicago averaged 65 per 100,000 people a year. The worst yearwas 1891, when the typhoid death rate was 174 per 100,000 people. The mostnotorious carrier of typhoid fever was Mary Mallon, also known as Typhoid Mary. In1907, she became the first American carrier to be identified and traced.(Fig 4. Typhoid Mary in a hospital bed.)
  6. 6. 5 | P a g eShe was a cook in New York. She is closely associated with fifty-three cases and threedeaths. Public health authorities told Mary to give up working as a cook or have her gallbladder removed. Mary quit her job but returned later under a false name. She wasdetained and quarantined after another typhoid outbreak. She died of pneumonia after26 years in quarantine.In 1880 Karl Joseph Eberth(fig.5)described abacillus that he suspected was the cause oftyphoid. In 1884 pathologist GeorgTheodor August Gaffky (1850–1918)confirmed Eberths findings, and theorganism was given names such as Eberthsbacillus, Eberthella typhi and Gaffky-Eberthbacillus. Today the bacillus that causestyphoid fever goes by the scientific nameof Salmonella enterica , serovar Typhi.Almroth Edward Wright developed aneffective inactivated whole-cell typhoidvaccine that was introduced in 1896. In1909, Frederick F. Russell, a U.S.Army physician, developed an Americantyphoid vaccine and two years later hisvaccination program became the first inwhich an entire army was immunized. Iteliminated typhoid as a significant cause ofmorbidity and mortality in the U.S. military.Most developed countries saw declining rates of typhoid fever throughout the first halfof the 20th century due to vaccinations and advances in public sanitation and hygiene.Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality.Today, the incidence of typhoid fever in developed countries is around 5 cases per1,000,000 people per year. An outbreak in the Democratic Republic of Congo in 2004–05recorded more than 42,000 cases and 214 deaths. Typhoid fever was also knownas suette milliaire in nineteenth-century France.(Fig 5. Carl Joseph Eberth.)
  7. 7. 6 | P a g eDistributionIn contrast to that seen in the rich countries, typhoid fever remains an important causeof illness in the developing world where annual incidences in Papua New Guinea andIndonesia may reach 1200/100,000 population. A recent epidemiologic study showedthat south-east and south-central Asia are the regions of highest endemicity with ratesgreater than 100/100,000 cases per year; the rest of Asia, Africa, Latin America(fig.6), theCaribbean and Oceania (except Australia and New Zealand) are the next highest withincidence rates of 10-100/100,000 and Europe, North America and the rest of thedeveloped world have low rates of disease. Typhoid fever represents the 4th mostcommon cause of death in Pakistan(fig.6).The majority of patients, 60-90%, are treated as outpatients and, therefore, hospitalbased studies will underestimate true incidence. Two hospital based case-controlstudies from Vietnam found that risk of infection was related to recent contact with aninfected person, lack of education and drinking untreated water. S. paratyphi A, whichnormally causes about 15-20% of cases of typhoid fever in Asia, increasingly is becominga pathogen in India and China, possibly due to vaccination against S. typhi.(Fig 6. Geografical distribution of Typhoid fever.)
  8. 8. 7 | P a g eRecent epidemiologic studies also show the rise of multi-drug resistant (MDR)organisms. In a study of 1100 hospitalized children in Pakistan, the mortality rate of1.6% was found to be related to younger age and MDR infection. Traditionally the agerange considered to be at greatest risk was 5-25 years(fig.7). However this has beenquestioned in a study from a private laboratory in Bangladesh, which found that the57% of S. typhi isolates were inchildren less than 5 years of ageand 27% less than 2 years. Thishas significant implications forvaccination policies.High-risk countriesThe countries with the highestrates of typhoid fever are: Bangladesh China India Indonesia Laos Nepal Pakistan VietnamWorldwide, typhoid fever affects about six million people with more than 6,00,000deaths a year. Almost 80% of cases and deaths occur in Asia, and most others in Africaand Latin America. Among Asian countries, India probably has a large number of thesecases. In Indian statistics typhoid fever is endemic in India. Health surveys conducted bythe Central Ministry of Health in the community development areas indicated amorbidity rate varying from 102 to 2219 per 1,00,000 population in different parts ofthe country. A limited study in an urban slum showed 1% of children up to 17 years ofage suffer from typhoid fever every year.(Fig 7. Distribution of Typhoid and paratyphoid fever.)
  9. 9. 8 | P a g eSymptomsClassically, the course of untreated typhoid fever is divided into four individual stages,each lasting approximately one week.In the first week, there is a slowly rising temperature with relativebradycardia, malaise,headache, and cough (fig.8). A bloody nose (epistaxis) . There is leukopenia, a decrease inthe number of circulating white blood cells with eosinopenia and relative lymphocytosis,a positive reaction and blood cultures are positive for Salmonella typhi or paratyphi. Theclassic Widal test is negative in the first week.In the second week of the infection, the patient lies prostrate with high fever in plateauaround 40 °C (104 °F) and bradycardia (sphygmothermic dissociation), classically witha dicrotic pulse wave. Delirium is frequent, frequently calm, but sometimes agitated.This delirium gives to typhoid the nickname of"nervous fever". Rose spots appear on thelower chest and abdomen in around a third ofpatients. There are rhonchi in lung bases. Theabdomen is distended and painful in the rightlower quadrant where borborygmi can beheard. Diarrhea can occur in this stage: six toeight stools in a day, green with a characteristicsmell, comparable to pea soup. However,constipation is also frequent. The spleen andliver are enlarged (hepatosplenomegaly) andtender, and there is elevation of livertransaminases. The Widal reaction is stronglypositive with (antiO) and (antiH) antibodies.Blood cultures are sometimes still positive atthis stage. (The major symptom of this fever isthat the fever usually rises in the afternoon upto the first and second week.)(Fig 8. Typhoid fever sickness )
  10. 10. 9 | P a g eIn the third week of typhoid fever, a number of complications can occur: Intestinal hemorrhage due to bleeding in congested Peyers patches; this can be veryserious but is usually not fatal. Intestinal perforation in the distal ileum: this is a very serious complication and isfrequently fatal. It may occur without alarming symptoms until septicaemia ordiffuse peritonitis sets in. Encephalitis Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), withpicking at bedclothes or imaginary objects. Metastatic abscesses, cholecystitis, endocarditis and osteitisThe fever is still very high and oscillates very little over 24 hours. Dehydration ensuesand the patient is delirious (typhoid state). By the end of third week the fever hasstarted reducing this (defervescence). This carries on into the fourth and final week.In the fourth week the fever reduces and comes down gradually by the end of fourthweek. And the symptoms decrease. But the Typhoid fevers danger doesnt end whensymptoms disappear, even if your symptoms seem to go away, you may still be carryingSalmonella Typhi. If so, the illness could return, or you could pass the disease to otherpeople. In fact, if you work at a job where you handle food or care for small children,you may be barred legally from going back to work until a doctor has determined thatyou no longer carry any typhoid bacteria. If you are being treated for typhoid fever, it isimportant to do the following: Keep taking the prescribed antibiotics for as long as the doctor has asked you to takethem. Wash your hands carefully with soap and water after using the bathroom, and do notprepare or serve food for other people. This will lower the chance that you will passthe infection on to someone else. Have your doctor perform a series of stool cultures to ensure that no SalmonellaTyphi bacteria remain in your body.
  11. 11. 10 | P a g eGeneral symptoms of Typhoid fever : The patient feels weak, cold and tired. Headache, backache, diarrhea, constipation, loss of appetite are other symptoms(fig9). Temperature rises and remains high for about 10-14 days. Body temperaturetypically rises in the evening and drops in the morning(fig.9). Skin eruptions appear, tongue becomes dry and gets white patches in the center,which causes oily taste in mouth and inflamed bones(fig.9).(Fig 9. Symptoms of Typhoid fever.)
  12. 12. 11 | P a g eTransmissionThe bacteria which causes typhoid fever may be spread through poor hygiene habitsand public sanitation conditions, and sometimes also by flying insects feeding on feces.Public education campaigns encouraging people to wash their hands after defecatingand before handling food are an important component in controlling spread of thedisease. Causes of Typhoid Fever are: Poor sanitation, contaminated water and infected milk are some of the main factorsresponsible for typhoid. Flies contaminate the food with germs. People carrying the germs can also spreadthe disease if they prepare or serve food. Wrong dietary habits and faulty lifestyle lead to accumulation of toxic waste in thebody and promotes typhoid fever. Typhoid is common in people who eat more meat and meat products.Spread of Typhoid fever:Salmonella Typhi lives only in humans.Persons with typhoid fever carry the bacteriain their bloodstream and intestinal tract. Inaddition, a small number of persons, calledcarriers, recover from typhoid fever butcontinue to carry the bacteria. Both illpersons and carriers shed SalmonellaTyphi intheir feces (stool). You can get typhoid feverif you eat food or drink beverages that havebeen handled by a person who is sheddingSalmonella Typhi or if sewage contaminatedwith Salmonella Typhi bacteria gets into thewater you use for drinking or washing food.Once Salmonella Typhi bacteria are eaten ordrunk, they multiply and spread into thebloodstream. The body reacts with fever andother signs and symptoms(fig.10). (Fig 10. transmission of Typhoid fever.)
  13. 13. 12 | P a g eSalmonella typhi has no nonhuman vectors. The following are modes of transmission: Oral transmission via food or beverages handled by an individual who chronicallysheds the bacteria through stool or, less commonly, urine Hand-to-mouth transmission after using a contaminated toilet and neglectinghand hygiene Oral transmission via sewage-contaminated water or shellfish (especially in thedeveloping world)A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms,but capable of infecting others. According to the CDC approximately 5% of people whocontract typhoid continue to carry the disease after they recover. The most famousasymptomatic carrier was Mary Mallon (commonly known as "Typhoid Mary"), a youngcook who was responsible for infecting at least 53 people with typhoid, three of whomdied from the disease. Mallon was the first apparently perfectly healthy person knownto be responsible for an "epidemic".Many carriers of typhoid were locked into an isolation ward never to be released toprevent further typhoid cases. These people often deteriorated mentally, driven mad bythe conditions they lived in. Typhoid fever is more common in areas of the world wherehandwashing is less frequent and water is likely to be contaminated with sewage.
  14. 14. 13 | P a g ePathogenesisMuch of the genetic and cellular studies on the pathophysiology of invasive Salmonellainfection have been carried out in the murine model using S. typhimurium, which causesinvasive disease in mice but not in humans. As opposed to the Salmonella spp.associated with human diarrheal illness, S. typhi and those strains that cause typhoidfever are able to achieve cellular invasion.The pathophysiology of typhoid fever is a complex process which proceeds throughseveral stages. during which bacteria invade macrophages and spread throughout thereticuloendothelial system. The first week of symptomatic disease is characterized byprogressive elevation of the temperature followed by bacteremia. First ingestedbacteria must survive the acidic environment of the stomach. ncomitant Helicobacterpylori infection may express itself via the hypochlorhydria associated with chronicH.pylori infection. Invading organisms pass through the intestinal epithelial cells andcome into contact with phagocytic cells in the Peyer’s patches of the intestinal wall.However the macrophages do not kill the bacteria. Thence, bacterial replication isprimarily intracellular. Salmonella avoids encapsulation in lysosomes by divertingnormal cellular mechanisms. Bacteria inject effector proteins into the cells of the innateimmune system though a type III protein secretion system (TTSS) which stimulate bothpro and anti-inflammatory responses. Over the asymptomatic incubation period of 7-14days the bacteria proliferate and spread through the blood stream to other cells in thereticuloendothelial system in the liver, spleen, bone marrow and gall bladder. Asreplication inside phagocytic cells continues, bacteria are shed into the blood stream insustained but low concentrations and the clinical syndrome of fever, headache andabdominal pain begins. The gallbladder is felt to be a significant site for ongoingexposure of intestinal epithelial cells to the pathogen. The inflammatory response tothis process of repeated exposure is felt to give rise to the necrosis which is a prominentfeature of the disease. This occurs in areas of greatest macrophage concentration suchas the Peyer’s patches and explains why intestinal bleeding and perforation are themost frequent complications. Elsewhere typhoid nodules, foci of macrophages andlymphocytes proliferate. As the infection progresses the typical changes of sepsisaccumulate in the heart, brain and kidneys. If not interrupted this process may lead tocirculatory failure and death from overwhelming sepsis.
  15. 15. 14 | P a g eDiagnosisDiagnosis is made by any blood, bone marrow or stool cultures and with the Widaltest (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria,dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generallyundertaken while awaiting the results of Widal test and cultures of the blood and stool.The Widal test is time consuming and often, when a diagnosis is reached, it is too late tostart an antibiotic regimen. The term "enteric fever" is a collective term that refers totyphoid and paratyphoid.Exams and Tests A complete blood count (CBC) will show a high number of white blood cells. A blood culture during the first week of the fever can show S. typhi bacteria. Other tests that can help diagnose this condition include: ELISA urine test to look for the bacteria that cause Typhoid fever Fluorescent antibody study to look for substances that are specific to Typhoidbacteria Platelet count (platelet count will be low) Stool culture
  16. 16. 15 | P a g eTreatmentYou will probably be given an antibiotic to treat the disease. Three commonly prescribedantibiotics are ampicillin, trimethoprim-sulfamethoxazole, and ciprofloxacin (Cipro).Persons given antibiotics usually begin to feel better within 2 to 3 days, and deathsrarely occur. However, persons who do not get treatment may continue to have feverfor weeks or months, and as many as 20% may die from complications of the infection.Medical TreatmentWhere resistance is uncommon, the treatment of choice is a fluoroquinolone suchas ciprofloxacin otherwise; a third-generation cephalosporin such asceftriaxoneor cefotaxime is the first choice. Cefixime is a suitable oral alternative.Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin,chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin (Amoxil) and ciprofloxacin(Cipro), have been commonly used to treat typhoid fever in developed countries.Prompt treatment of the disease with antibiotics reduces the case-fatality rate toapproximately 1%.When untreated, typhoid fever persists for three weeks to a month. Death occurs inbetween 10% and 30% of untreated casesIn some communities, however, case-fatalityrates may reach as high as 47%.The rediscovery of oral rehydration therapy in the 1960s provided a simple way toprevent many of the deaths of diarrheal diseases in general.Surgical TreatmentSurgery is usually indicated in cases of intestinal perforation. Most surgeons prefersimple closure of the perforation with drainage of the peritoneum. Small-bowelresection is indicated for patients with multiple perforations.If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladdershould be resected. Cholecystectomy is not always successful in eradicating the carrierstate because of persisting hepatic infection.
  17. 17. 16 | P a g eResistanceResistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole andstreptomycin is now common, and these agents have not been used as first linetreatment now for almost 20 years. Typhoid that is resistant to these agents is knownas multidrug-resistant typhoid (MDR typhoid). Ciprofloxacin resistance is an increasingproblem, especially in the Indian subcontinent and Southeast Asia. Many centres aretherefore moving away from using ciprofloxacin as the first line for treating suspectedtyphoid originating in South America, India, Pakistan, Bangladesh, Thailand or Vietnam.For these patients, the recommended first line treatment is ceftriaxone. It has alsobeen suggested that azithromycin is better at treating typhoid in resistant populationsthan both fluoroquinolone drugs and ceftriaxone. Azithromycin significantly reducesrelapse rates compared with ceftriaxone. There is a separate problem with laboratorytesting for reduced susceptibility to ciprofloxacin: current recommendations are thatisolates should be tested simultaneously against ciprofloxacin (CIP) and againstnalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should bereported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP butnot to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, ananalysis of 271 isolates showed that around 18% of isolates with a reducedsusceptibility to ciprofloxacin (MIC 0.125–1.0 mg/l) would not be picked up by thismethod. It is not certain how this problem can be solved, because most laboratoriesaround the world (including the West) are dependent on disk testing and cannot testfor MICs. Two basic actions can protect you from typhoid fever:1. Avoid risky foods and drinks.2. Get vaccinated against typhoid fever.It may surprise you, but watching what you eat and drink when you travel is asimportant as being vaccinated. This is because the vaccines are not completely effective.Avoiding risky foods will also help protect you from other illnesses, including travelersdiarrhea, cholera, dysentery, and hepatitis A.
  18. 18. 17 | P a g ePreventionInfected or asymptomatic carrier humans represent the reservoir for S. typhi. Thereforeidentification and treatment of these individuals represents one strategy forinterruption of transmission.Food and water sanitationThere is no doubt that lack of clean drinking water and unsanitary conditions for theproduction and preparation of food represent the main reasons for the ongoingendemicity of typhoid fever in the developing world. Poor water quality, sanitation andhygiene account for some 1.7 million deaths a year world-wide mainly throughinfectious diarrhea. Nine out of 10 such deaths are in children. Poverty, uncontrolledurbanization and inadequate infrastructure all contribute to the contamination of watersupplies. Filtration and chlorination together are effective methods of interrupting thetransmission of water-borne diseases.VaccineThe other approach to the control and eradication of typhoid fever has been throughvaccination. Acquired immunity to S. typhi infection is both humoral and cellular but isincomplete, allowing for subsequent infections and restricting the efficacy of vaccines.Older, parenteral whole-cell vaccines resulted in significant local and systemic reactions.Two new vaccines are in current use: a parenteral capsule polysaccharide vaccine basedon the Vi antigen and an oral live attenuated vaccine containing strain Ty21a. The first,while resulting in local pain in 86% of children, requires 1 injection with a booster in 3years and confers protection within 7-10 days of inoculation. On the other hand theTy21a vaccine requires several doses, is only moderately immunogenic and its efficacy isreduced by simultaneous anti-malarial therapy, (although a report from Gabon showedthat simultaneous anti-malarial prophylaxis with atovaquone/proguanil does not havethis effect. A systematic review for the Cochrane Database showed these two vaccineshad significantly reduced efficacy (efficacy rates approx.50%) in comparison to the olderwhole-cell vaccines, but fewer side effects. Current vaccines do not afford protectionagainst Paratyphoid strains. The search for better vaccines continues.
  19. 19. 18 | P a g eThe use of vaccines for travelers to endemic areas has been recommended for sometime; even if the travel is for short periods. Malaria remains the most common febriledisease of returning travelers to Italy requiring hospital admission.Mass vaccination campaigns have been used to lower the risk of disease in India andThailand, but their use in the rest of the developing world is otherwise limited. A reportfrom the ongoing epidemic in Tajikistan advocated mass vaccination. A recent reportfrom an urban slum community in Delhi, India showed the high costs of typhoid feverand recommended more widespread vaccination. The current Vi and Ty21a vaccines arenot licensed for use in children less than 2 years, in whom its efficacy is unproven, andtherefore are deemed unsuitable for expanded immunization programs which targetinfants in their first year of life. They are also costly. All these factors have restrictedmass vaccination for typhoid in endemic countries.The World Health Organization appears to advocate mass vaccination in endemic areas.(50;51) However this is seldom implemented. The Diseases of the Most Impoverished(DOMI) project is undertaking a randomized cluster vaccination program in Asia whichshould help to clarify the effects of mass typhoid vaccination.
  20. 20. 19 | P a g eGeneticsIn 2001 the entire genome of a MDR isolate of S. typhi was sequenced. This showed thatSalmonella share more than 70-80% of genes with other enteric bacteria, like E. coli.Another feature of S. typhi genome is the presence of over 200 inactivated genes whichare felt to be related to the adaptation of the bacteria to the human host and possiblyits ability to invade human tissue. Drug resistance is encoded in a transmissible plasmid.The development of additional horizontal genes in the salmonella pathogenicity islands(SPI) represented the separation of the E. Coli and Salmonella lineages and allows forthe targeting of intestinal epithelial cells by Salmonella.
  21. 21. 20 | P a g eComplicationsComplications occur in 10-15% of patients, particularly those who have been ill for morethan 2 weeks. Gastrointestinal hemorrhage, perforation and encephalopathy are themost important. GI hemorrhage is most common but usually resolves withoutsurgery. Severe typhoid may be defined as occurring in those patients with hypotensiondespite rehydration and mental confusion or altered state of consciousness. Thesepatients may benefit from high dose dexamethasone therapy (3mg/kg followed by 8doses of 1mg/kg q6h) with a marked reduction in mortality. This is one of the fewinstances where high dose steroids are of value in sepsis.PerforationThe surgeon is typically consulted in typhoid fever when perforation is suspected. It maypresent suddenly as an acute abdomen or more commonly as worsening in an alreadysick patient with increasing abdominal signs, rising pulse and falling blood pressure. Thepresence of free air on abdominal xrays is pathognomonic.These are very sick patients who require vigorous resuscitation and the addition ofmetronidazole to combat gram-negative anaerobes and gentamycin for aerobes.Conservative therapy has been abandoned with improved mortality rates. Mortalityincreased when time to presentation is delayed and also with delayed time to surgeryafter perforation. Mortality rates vary from 14% in Nigeria to 34% in Cote d’Ivoire. Singleperforations are most common (70%) and in the terminal ileum, but multipleperforations may occur.At operation the entire small bowel and proximal colon should be carefully examined forperforation. Debate exists as to the various methods of closure from simple suture, towedge resection and closure to segmental resection and primary anastomosis. It is notclear to me that any conclusion can be drawn from the evidence. Obviously multipleperforations lend themselves to segmental resection.Other complicationsNumerous other complications are seen with typhoid fever. see Table 163-1 The mostimportant surgical ones being: hepatic or splenic abscess, splenic rupture andpancreatitis. Encephalomyelitis, osteomyelitis, glomerulonephritis and renal failure mayall occur. Myocarditis is a common cause of circulatory collapse.
  22. 22. 21 | P a g eSalmonellaIs a Gram-negative facultative rod-shaped bacterium in the same proteobacterial familyas Escherichia coli, the family Enterobacteriaceae, trivially known as "enteric"bacteria. Salmonella is nearly as well-studied as E. coli from a structural, biochemicaland molecular point of view, and as poorly understood as E. coli from an ecological pointof view. Salmonellae live in the intestinal tracts of warm and cold blooded animals.Some species are ubiquitous. Other species are specifically adapted to a particular host.In humans, Salmonella are the cause of two diseases called salmonellosis: entericfever (typhoid), resulting from bacterial invasion of the bloodstream, and acutegastroenteritis, resulting from a foodborne infection/intoxication.(Fig 11. bacillus shape salmonella)
  23. 23. 22 | P a g eenterica Isalamae IIarizonae IIIadiarizonae IIIbhoutenae IVbongori Vindica VISalmonella NomenclatureThe genus Salmonella is a member of the family Enterobacteriaceae, It is composed ofbacteria related to each other both phenotypically and genotypically. Salmonella DNAbase composition is 50-52 mol% G+C, similar to that of Escherichia,Shigella, and Citrobacter. The bacteria of the genus Salmonella are also related to eachother by DNA sequence. The genera with DNA most closely relatedto Salmonella are Escherichia, Shigella, and Citrobacter. Similar relationships were foundby numerical taxonomy and 16S ssRNA analysis. And has been controversial since theoriginal taxonomy of the genus was not based on DNA relatedness, rather names weregiven according to clinical considerations, e.g., Salmonella typhi, Salmonella cholerae-suis, Salmonella abortus-ovis, and so on. When serological analysis was adopted into theKauffmann-White scheme in 1946, a Salmonella species was defined as "a group ofrelated fermentation phage-type" with the result that each Salmonella serovar wasconsidered as a species. Since the host-specificity suggested by some of these earliernames does not exist (e.g., S. typhi-murium, S. cholerae-suis are in fact ubiquitous),names derived from the geographical origin of the first isolated strain of the newlydiscovered serovars were next chosen, e.g., S. london, S. panama, S. stanleyville.Susequently it was found that all Salmonella serovarsform a single DNA hybridization group, i.e., a singlespecies composed of seven subspecies, andthenomenclature had to be adapted. To avoidconfusion with the familiar names of serovars, thespecies name Salmonella enterica was proposed withthe following names for the subspecies:Since this formal Latin nomenclature may not be clearly understood by physicians andepidemiologists, who are the most familiar with the names given to the most commonserovars, the common serovars names are kept for subspecies I strains, which representmore than 99.5% of the Salmonella strains isolated from humans and other warm-blooded animals. The vernacular terminology seems preferred in medical practice,e.g., Salmonella ser. Typhimurium (not italicized) or shorter Salmonella (or S.)Typhimurium.
  24. 24. 23 | P a g eAntigenic StructureAs with all Enterobacteriaceae, the genus Salmonella has three kinds of major antigenswith diagnostic or identifying applications: somatic, surface, and flagellar.Somatic (O) or Cell Wall AntigensSomatic antigens are heat stable and alcohol resistant. Cross-absorption studiesindividualize a large number of antigenic factors, 67 of which are used for serologicalidentification. O factors labeled with the same number are closely related, although notalways antigenically identical.Surface (Envelope) AntigensSurface antigens, commonly observed in other genera of enteric bacteria(e.g., Escherichia coli and Klebsiella), may be found in some Salmonella serovars. Surfaceantigens in Salmonella may mask O antigens, and the bacteria will not be agglutinatedwith O antisera. One specific surface antigen is well known: the Vi antigen. The Viantigen occurs in only three Salmonella serovars (out of about 2,200): Typhi, ParatyphiC, and Dublin. Strains of these three serovars may or may not have the Vi antigen.Flagellar (H) AntigensFlagellar antigens are heat-labile proteins. Mixing salmonella cells with flagella-specificantisera gives a characteristic pattern of agglutination (bacteria are loosely attached toeach other by their flagella and can be dissociated by shaking). Also, antiflagellarantibodies can immobilize bacteria with corresponding H antigens.
  25. 25. 24 | P a g eA few Salmonella entericaserovars (e.g., Enteritidis, Typhi) produce flagella which alwayshave the same antigenic specificity. Such an H antigen is then called monophasic.Most Salmonella serovars, however, can alternatively produce flagella with twodifferent H antigenic specificities. The H antigen is then called diphasic. For example,Typhimurium cells can produce flagella with either antigen i or antigen 1,2. If a clone isderived from a bacterial cell with H antigen i, it will consist of bacteria with i flagellarantigen. However, at a frequency of 10-3- 10-5, bacterial cells with 1,2 flagellar antigenpattern will appear in this clone.(Fig 12. Flagellar stain of a Salmonella Typhi)
  26. 26. 25 | P a g eHabitatsThe principal habitat of the salmonellae is the intestinal tract of humans andanimals. Salmonella serovars can be found predominantly in one particular host, can beubiquitous, or can have an unknown habitat. Typhi and Paratyphi A are strictly humanserovars that may cause grave diseases often associated with invasion of thebloodstream. Salmonellosis in these cases is transmitted through fecal contamination ofwater or food. Gallinarum, Abortusovis, and Typhisuis are, respectively, avian, ovine,and porcine Salmonella serovars. Such host-adapted serovars cannot grow on minimalmedium without growth factors (contrary to the ubiquitousSalmonella serovars).Ubiquitous (non-host-adapted) Salmonella serovars (e.g., Typhimurium) cause verydiverse clinical symptoms, from asymptomatic infection to serious typhoid-likesyndromes in infants or certain highly susceptible animals (mice). In human adults,ubiquitous Salmonella organisms are mostly responsible for foodborne toxic infections.The pathogenic role of a number of Salmonella serovars is unknown. This is especiallythe case with serovars from subspecies II to VI. A number of these serovars have beenisolated rarely (some only once) during a systematic search in cold-blooded animals.Salmonella in the Natural EnvironmentSalmonellae are disseminated in the natural environment (water, soil, sometimes plantsused as food) through human or animal excretion. Humans and animals (either wild ordomesticated) can excrete Salmonella either when clinically diseased or after havinghad salmonellosis, if they remain carriers. Salmonella organisms do not seem to multiplysignificantly in the natural environment (out of digestive tracts), but they can surviveseveral weeks in water and several years in soil if conditions of temperature, humidity,and pH are favorable.
  27. 27. 26 | P a g eIsolation and Identification of SalmonellaA number of plating media have been devised for the isolation of Salmonella. Somemedia are differential and nonselective, i.e., they contain lactose with a pH indicator,but do not contain any inhibitor for non salmonellae (e.g., bromocresol purple lactoseagar). Other media are differential and slightly selective, i.e., in addition to lactose and apH indicator, they contain an inhibitor for nonenterics (e.g., MacConkey agar and eosin-methylene blue agar).The most commonly used media selective for Salmonella are SS agar, bismuth sulfiteagar, Hektoen enteric (HE) medium, brilliant green agar and xylose-lisine-deoxycholate(XLD) agar. All these media contain both selective and differential ingredients and theyare commercially available.(Fig 13. Salmonella sp. after 24 hours growth on XLD agar)
  28. 28. 27 | P a g eMedia used for Salmonella identification are those used for identification ofall Enterobacteriaceae. Most Salmonella strains are motile with peritrichous flagella,however, nonmotile variants may occur occasionally. Most strains grow on nutrient agaras smooth colonies, 2-4 mm in diameter(fig.14). Most strains are prototrophs, notrequiring any growth factors. However, auxotrophic strains do occur, especially in host-adapted serovars such as Typhi and Paratyphi A.(Fig 14. Colonial growth Salmonella ,bacteria grown on a blood agar culture plate)
  29. 29. 28 | P a g eTable 1. Characteristics shared by most Salmonella strains belonging to subspecies IMotile, Gram-negative bacteriaLactose negative; acid and gas from glucose, mannitol, maltose, and sorbitol; no Acid fromadonitol, sucrose, salicin, lactoseONPG test negative (lactose negative)Indole test negativeMethyl red test positiveVoges-Proskauer test negativeCitrate positive (growth on Simmons citrate agar)Lysine decarboxylase positiveUrease negativeOrnithine decarboxylase positiveH2S produced from thiosulfateDo not grow with KCNPhenylalanine and tryptophan deaminase negativeGelatin hydrolysis negative(Fig 15. Colonial growth pattern displayed by Salmonella Typhimurium cultured on a Hektoen enteric agar)
  30. 30. 29 | P a g eSalmonella infectionsFoodborne Salmonella toxic infectionsare caused by ubiquitous Salmonella serovars (e.g., Typhimurium). About 12-24 hoursfollowing ingestion of contaminated food (containing a sufficient numberof Salmonella), symptoms appear (diarrhea, vomiting, fever) and last 2-5 days.Spontaneous cure usually occurs.Salmonella may be associated with all kinds of food. Contamination of meat (cattle, pigs,goats, chicken, etc.) may originate from animal salmonellosis, but most often it resultsfrom contamination of muscles with the intestinal contents during evisceration ofanimals, washing, and transportation of carcasses. Surface contamination of meat isusually of little consequence, as proper cooking will sterilize it (although handling ofcontaminated meat may result in contamination of hands, tables, kitchenware, towels,other foods, etc.). However, when contaminated meat is ground, multiplicationof Salmonella may occur within the ground meat and if cooking is superficial, ingestionof this highly contaminated food may produce a Salmonellainfection. Infection mayfollow ingestion of any food that supports multiplication of Salmonella such as eggs,cream, mayonnaise, creamed foods, etc.), as a large number of ingested salmonellae areneeded to give symptoms. Prevention of Salmonella toxic infection relies on avoidingcontamination (improvement of hygiene), preventing multiplication ofSalmonella infood (constant storage of food at 4°C), and use of pasteurized and sterilized milk andmilk products. Vegetables and fruits may carry Salmonella when contaminated withfertilizers of fecal origin, or when washed with polluted water.The incidence of foodborne Salmonella infection/toxication remains reletavely high indeveloped countries because of commercially prepared food or ingredients for food.Any contamination of commercially prepared food will result in a large-scale infection.In underdeveloped countries, foodborne Salmonella intoxications are less spectacularbecause of the smaller number of individuals simultaneously infected, but also becausethe bacteriological diagnosis of Salmonella toxic infection may not be available.
  31. 31. 30 | P a g eSalmonella Enteritidis InfectionEgg-associated salmonellosis is an important public health problem in the United Statesand several European countries. Salmonella Enteritidis, can be inside perfectly normal-appearing eggs, and if the eggs are eaten raw or undercooked, the bacterium can causeillness. During the 1980s, illness related to contaminated eggs occurred mosy frequentlyin the northeastern United States, but now illness caused by S. Enteritidis is increasing inother parts of the country as well.Unlike eggborne salmonellosis of past decades, the current epidemic is due to intact anddisinfected grade A eggs. Salmonella Enteritidis silently infects the ovaries of healthyappearing hens and contaminates the eggs before the shells are formed. Most typesof Salmonella live in the intestinal tracts of animals and birds and are transmitted tohumans by contaminated foods of animal origin. Stringent procedures for cleaning andinspecting eggs were implemented in the 1970s and have made salmonellosis caused byexternal fecal contamination of egg shells extremely rare. However, unlike eggbornesalmonellosis of past decades, the current epidemic is due to intact and disinfectedgrade A eggs. The reason for this is that Salmonella Enteritidis silently infects the ovariesof hens and contaminates the eggs before the shells are formed.Although most infected hens have been found in the northeastern United States, theinfection also occurs in hens in other areas of the country. In the Northeast,approximately one in 10,000 eggs may be internally contaminated. In other parts of theUnited States, contaminated eggs appear less common. Only a small number of hensseem to be infected at any given time, and an infected hen can lay many normal eggswhile only occasionally laying an egg contaminated with Salmonella Enteritidis.A person infected with the Salmonella Enteritidis usually has fever, abdominal cramps,and diarrhea beginning 12 to 72 hours after consuming a contaminated food orbeverage. The illness usually lasts 4 to 7 days, and most persons recover withoutantibiotic treatment. However, the diarrhea can be severe, and the person may be illenough to require hospitalization. The elderly, infants, and those with impaired immunesystems (including HIV) may have a more severe illness. In these patients, the infectionmay spread from the intestines to the bloodstream, and then to other body sites andcan cause death unless the person is treated promptly with antibiotics.
  32. 32. 31 | P a g eExotoxinsSalmonella strains may produce a thermolabile enterotoxin that bears a limitedrelatedness to cholera toxin both structurally and antigenically. This enterotoxin causeswater secretion in rat ileal loop and is recognized by antibodies against both choleratoxin and the thermolabile enterotoxin (LT) of enterotoxinogenic E. coli, but it does notbind in vitro to ganglioside GM1 (the receptor for E. coli LT and cholera ctx).Additionally, a cytotoxin that inhibits protein synthesis and is immunologically distinctfrom Shiga toxin has been demonstrated. Both of these toxins are presumed to play arole in the diarrheal symptoms of salmonellosis.Antibiotic SusceptibilityDuring the last decade, antibiotic resistance and multiresistance of Salmonella spp. haveincreased a great deal. The cause appears to be the increased and indiscriminate use ofantibiotics in the treatment of humans and animals and the addition of growth-promoting antibiotics to the food of breeding animals. Plasmid-borne antibioticresistance is very frequent among Salmonella strains involved in pediatric epidemics(e.g., Typhimurium, Panama, Wien, Infantis). Resistance to ampicillin, streptomycin,kanamycin, chloramphenicol, tetracycline, and sulfonamides is commonly observed.Colistin resistance has not yet been observed.Until 1972, Typhi strains had remained susceptible to antibiotics, includingchloramphenicol (the antibiotic most commonly used against typhoid) but in 1972, awidespread epidemic in Mexico was caused by a chloramphenicol-resistant strainof S. Typhi. Other chloramphenicol-resistant strains have since been isolated in India,Thailand, and Vietnam. Possible importation or appearance of chloramphenicol-resistance strains in the United States is a real threat. Salmonella strains should besystematically checked for antibiotic resistance to aid in the choice of an efficient drugwhen needed and to detect any change in antibiotic susceptibility of strains (either fromanimal or human source). Indiscriminate distribution and use of antibiotics should bediscouraged.
  33. 33. 32 | P a g eConclusionsDespite intensive scrutiny and major advances in genetic research and understandingthe details of cellular inflammation, typhoid fever remains a major cause of death anddisease in the developing world. Its eradication awaits the provision of sanitary watersupplies and proper disposal of human sewage. Its eradication would probably beaccelerated by programs of mass vaccination in endemic regions. Appropriate antibiotictherapy may postpone the further development of MDR strains. In the meantime,surgeons will continue to be asked to care for desperately sick typhoid patients withintestinal perforations and other complications.
  34. 34. 33 | P a g eRecommendations1. Typhoid fever should be suspected in young children and infants with fevers ofunknown origins in endemic regions.2. Filtration and chlorination are the two important steps in ensuring a safe watersupply. In urban areas safe drinking water should be made available though pipedsystems or trucked tankers.3. Appropriate food handling is essential: washing hands with soap before preparingand handling food; eating only cooked or still hot food; avoiding raw food, ice.4. Appropriate systems for human waste disposal must be available for the entirecommunity.5. Countries with high rates of typhoid fever should consider mass immunizationprograms using new Vi and Ty21a vaccines for those more than 2 years of age.6. In hospitals where microbiological facilities are available for the culture of salmonellaspp., bone marrow samples, as well as blood and stool should be obtained in patientswhen typhoid fever is suspected.7. Testing should include stools of recovering patients at 3 months or urine in regionswhere schistosomiasis is common, to detect the carrier state.8. The Widal test cannot be used in the diagnosis without assessing backgroundantibody levels in the population. Better serologic tests should be available soon.9. Antibiotic therapy should be based on the sensitivity spectrum of local S. typhistrains. Chloramphenicol, ampicillin or co-trimazole may be adequate agents if strainsare susceptible.10. In regions where MDR strains are known to exist, fluroquinolones are the agents ofchoice.11. In regions where MDR strains exist and where quinolone use has been extensive,testing for relative flouroquinolone resistance with nalidixic acid discs should beundertaken.12.Patients, with “severe typhoid” manifested by hypotension and/or altered state ofconsciousness, should receive short term high dose steroid therapy.13.The treatment of typhoid perforation is aggressive resuscitation using broadspectrum antibiotics against enteric organisms, prompt surgery with examination ofthe entire small bowel and right colon with resection (local or segmental) of all fullthickness ulcers and perforations.
  35. 35. 34 | P a g eTyphoid Fever Questions and AnswersI was diagnosed with viral fever by my local doctor. After 4 days when the fever didnot subside, my doctor asked me to get a blood test done as he is suspecting typhoid.[A] What symptoms are you facing for typhoid fever?[Q] I have Headache and fever, but commonly occurs at night, temperature not morethan 101 degree and irritation in eyes plus tiredness and fatigue.[A] And how many days do you have the fever for?[Q] About 4 days with sputum in chest.[A] How is your appetite? Do you have any appetite?[Q] My appetite seems to be ok; I don’t have a problem there.[A] Do you have constipation?[Q] No constipation.[A] It’s tough to diagnose this remotely. What exactly are you looking for? Do you wantto know some home remedies for typhoid? Do you want to know about typhoidsymptoms?[A] You must most certainly follow your doctor’s advice and get your blood check updone to detect what the problem is – whether its typhoid fever or something else[A] Here are some home remedies I can suggest – but use them only after you haveconsulted your doctor: Take a lot of rest Cold compress if your fever goes over 40C Drink more water; even orange juice will be good as that will give you more energy Stick to easily digestible foods – liquid diet is good if you can tolerate it. Warm eater enema may also be administered for some people during typhoid fever.
  36. 36. 35 | P a g eReferences1- http://en.wikipedia.org/wiki/Typhoid_fever2- http://www.nhs.uk/Conditions/Typhoid-fever/Pages/Introduction.aspx3- http://www.cdc.gov/nczved/divisions/dfbmd/diseases/typhoid_fever/#top4- http://www.tandurust.com/natural-home-remedies/typhoid-fever.html5- http://www.ptolemy.ca/members/archives/2006/typhoid_fever.htm6- http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002308/7- http://www.medicinenet.com/typhoid_fever/article.htm8- http://www.nlm.nih.gov/medlineplus/ency/article/001332.htm9- http://www.who.int/topics/typhoid_fever/en/10- http://www.mayoclinic.com/health/typhoid-fever/DS0053811- http://emedicine.medscape.com/article/231135-overview12- http://www.webmd.com/a-to-z-guides/typhoid-fever?page=213- http://news.softpedia.com/news/Typhoid-Bacterium-Accompanied-Us-Along-Our-Evolution-41046.shtml14- http://textbookofbacteriology.net/themicrobialworld/Salmonella.html15- http://www.onlinemedicinetips.com/disease/t/typhoid/Typhoid-Causes.html16- http://nutrivize.com/blog/general-health/mystery-rash/17- http://www.turbosquid.com/3d-models/max-microbes-micro-organisms/64473518- http://www.rightdiagnosis.com/phil/html/typhoid-fever/2114.html19- http://www.humanillnesses.com/original/T-Ty/Typhoid-Fever.html#b