Enteric fever

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American veterinary scientist, Daniel E. Salmon , discovered the first strain of salmonella from the intestine of a pig. This strain was called Salmonella choleraesuis , It is still used to describe the genus and species of this common human pathogen.

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In 1880s , the typhoid bacillus was first discovered by Eberth in spleen sections and mesenteric lymph nodes from a patient who died from typhoid. Robert Koch confirmed a related finding and succeeded in cultivating the bacterium in 1881. Serodiagnosis of typhoid was thus made possible by 1896. Wright and his team prepared heat killed vaccine from S.typhi in 1896

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General Characteristics Gram-negative motile rod, do not ferment lactose, intracellular Facultative, Oxidase-negative, Fermentative - acid and gas (H 2 S) Resistant to freezing and to certain chemicals – Brilliant green and sodium desoxycholate inhibit Coliforms but not Salmonella This is used to isolate these pathogens from fecal material (selective media)

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Antigenic structure - Flagellar (H) antigens Somatic (O) antigens – group specific Capsular (Vi) antigen - specialized K antigen which appears to be associated with virulence, specifically with Salmonella typhi

Flagella :


H antigen:

H antigen Flagellar heat labile protein Strongly immunogenic Antibody  Rapid high titre 2 phases phase 1 specific for species Phase 2 nonspecific or group phase S.typhi  Phase 1 only

O antigen:

O antigen Somatic Phospholipid- protein-polysaccharide Less immunogenic Classify into a number of groups

Vi antigen:

Vi antigen Surface polysaccharide enveloping O antigen Act as virulane factor – inhibit phagocytosis Poorly immunogenic Poor prognosis if total absence of Vi antibody in proven cases of Typhoid S.typhi strains typed based on specific Vi bacteriophage


Classification Kauffmann-White classification Agglutination test with absorbed sera to determine content of “O” antigens and phase 1 and phase 2 flagellar antigens in unknown samples S. paratyphi A = O-2 H a (group A) S. typhimurium = O-4 H i 1,2 (group B) S. paratyphi B = O-4 H b 1,2 (group B) S. typhi = O-9 group D

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Disease – S.typhi Animal source- S.gallinarium Discoverer- S.schottmulleri Patient- S.thompson Place- S.poona

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Current Classification Scheme Based on DNA hybridization studies, one species with 7 subspecies have been designated for the Salmonella - Arizona group Of the 2000 strains recognized, human infection are caused mainly by 5 serotypes, typhi, paratyphi, typhimurium, choleraesuis enteritidis.

Salmonella enterica sub sp enterica serotype typhi:

Salmonella enterica sub sp enterica serotype typhi Species Salmonella enterica Sub species enterica salamae arizonae diarizonae houtinae bongori indica SalmonellaTyphi

Isolation, Diagnosis, & Prevention:

Isolation, Diagnosis, & Prevention Specimens - blood cultures, stools, urine, serum etc. - Must be taken repeatedly Media inoculation - enrichment broths (selenite F, tetrathionate) used to stimulate the growth of pathogens, followed by isolation on selective & differential media MacConkey’s, HE, XLD, SS agar, DCA Wilson Blair

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Wilson and Blair bismuth sulphite medium jet black colony with a metallic sheen


Identification Biochemical tests followed by serology to identify serogroup of Salmonellae isolates G L S M I M V C H 2 S S.Typhi ┴ - - ┴ - + - + + S paratyphi A + - - + - + - + - S paratyphi B + - - + - + - + ++ S typhimurium + - - + - + - + ++

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S. paratyphi A = O-2 S. typhimurium = O-4 & H i S. paratyphi B = O-4 S. typhi = O-9 National Salmonella reference centre Central research institute Kasauli Salmonella of animal origin Indian veterinary research institute IzatNagar

Enteric Fevers (Typhoid & Paratyphoid):

Enteric Fevers (Typhoid & Paratyphoid) Etiologic agents - S. typhi , S. paratyphi A & S. schottmulleri disseminated from GI tract to blood stream and organs with development of splenomegaly, hepatitis, focal liver necrosis, gallbladder inflammation & inflammation of other sites Symptoms - headache, chills, malaise, anorexia, constipation, and a high plateau-like fever following a 3 to 21 day incubation

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Typhos in Greek means ,smoke and typhus fever got its name from smoke that was believed to cause it. Typhoid means typhus-like and thus the name given to this disease. The term Typhoid was given by Louis 1829 to distinguish it from typhus fever. It is a disease of poor environmental sanitation and hence occurs in parts of the world where water supply is unsafe and sanitation is substandard.


TYPHOID FEVER Typhoid fever is the most serious salmonella infection with significant morbidity & mortality. Caused by Salmonella typhi & paratyphi. Incubation period is 1-2 weeks. Bloody diarrhea & petechial hemorrhages on chest or abdomen (rose spots) may develop later in course of illness

Host-Parasite Relationships:

Host-Parasite Relationships Fecal-oral transmission via contaminated food or water Sources - milk & other dairy products, raw eggs, dried or frozen eggs, meats, meat products, poultry, roast beef, corned beef, shellfish and undercooked whitefish, animal dyes, dried coconut Origin - many animals are naturally infected with various Salmonellae (especially poultry)

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These can be found in tissues, eggs, and excreta Household pets - turtles, dogs, & cats can also transmit these bacteria Human carriers, especially food handlers Typhoid Mary

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Host Factors very important in intestinal infections Gastric pH, luminar wall sheath, intestinal mobility Local immune factors, normal flora Intrinsic characteristics of pathogens Salmonellae = 10 5 organisms to cause infect.


Pathogenicity Acute enterocolitis - 8 hour to 3 day incubation followed by symptoms of headache, low grade fever, abdominal discomfort, and diarrhoea; nausea and vomiting at times S. typhimurium S. heidelberg S. agona S. newport

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Septicemias - from GI tract to bloodstream High fever with/without focal infections (osteomyelitis, abscesses, arthritis, endocarditis) Usually caused by S. choleraesuis primarily and S. typhimurium , occasionally Debilitated hosts – sickle cell disease exceedingly susceptible - osteomyelitis Compromised hosts - peripheral vascular grafts (femoral arterial bypass)

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Mode of transmission : The disease is transmitted by faeco - oral route or urine – oral routes – either directly through hands soiled with faeces or urine of cases or carriers or indirectly by ingestion of contaminated water, milk, food, or through flies. Contaminated ice, ice-creams, and milk products are a rich source of infection.

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Salmonella typhi infect the body via the Peyer's patches of the small intestine. The bacteria migrates to mesenteric lymph nodes and arrive via the blood in the liver and spleen during the first exposure. multiple replication in the above locations,

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the bacteria Migrates back into the Peyer's patches of the small intestine for the secondary exposure consequently the clinical symptoms Inflammation in the small intestine leads to ulcers and necrosis.


CLINICAL PICTURE Symptoms begin with sudden onset of high-grade fever, headache & dry cough. Fever is swinging or may show step ladder pattern & patient initially feel well & mobile. Abdominal pain & toxicity follow soon & by the end of 1st week spleen is palpable & pink, discrete, skin rash appears over the trunk. Constipation is more common than diarrhea which is usually greenish in color (pea soup).

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First week : The disease classically presents with step-ladder fashion rise in temperature (40 - 41°C) over 4 to 5 days, accompanied by headache, vague abdominal pain, and constipation. Second week: B etween the 7 th -10 th day of illness, mild hepato-splenomegally occurs in majority of patients. Relative bradycardia may occur and rose-spots may be seen. Third week: The patient will appear in the "typhoid state" which is a state of prolonged apathy, toxaemia, delirium, disorientation and/or coma. Diarrhoea will then become apparent. If left untreated by this time, there is a high risk (5-10%) of intestinal hemorrhage and perforation. Rare complications : Typhoid hepatitis,Emphyema, Osteomyelitis, and Psychosis . 2-5% patients may become Gall-bladder carriers

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Abdominal tenderness & hepatomegaly occur in 50% of patients The pulse is relatively slow in relation to fever (Paget sign). The tongue is coated with free margins & halitosis may be present. The sweat of some patients smell like yeast

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The 3rd week of illness is the usual time for complications in the untreated patients. Local gut as well as systemic complications may occur. Serious infections may progress rapidly to drowsiness & coma which is usually fatal (coma vigil). Mortality is unlikely after the 4th week & patients may become carrier if not treated.


LOCAL COMPLICATIONS Intestinal hemorrhage Intestinal perforation Paralytic ileus Zenker degeneration of abdominal muscles


SYSTEMIC COMPLICATIONS Arteritis & arterial emboli Cholecystitis Endocarditis Hepatic & splenic abscesses Meningitis Osteomyelitis & septic arthritis Pneumonia or empyema Urinary tract infection

Lab diagnosis:

Lab diagnosis First week Clot culture Blood culture Faecal culture Carriers On antibiotic Repeated sample Bile broth Mac Conckeys agar NLF Colonies Wilson and Blair bismuth sulphite medium jet black colony with a metallic sheen  S typhi Green colony  S.para A

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Second week Widal test Faecal culture Urine culture Blood culture (75 %) Widal test O agglutination Dryers tube Disc like pattern 1/100 or more H agglutination Felix tube Loose cotton wooly clumps 1/200 or more

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Third week Blood culture (60%) Urine culture (25%)


Treatment Antibiotic therapy - Chloramphenicol, Ciprofloxacin, & Ampicillin are drugs of choice for enteric fevers and septicemias Trimethoprim/Sulfamethoxazole for resistant strains Contraindicated for acute enterocolitis Ampicillin & Ciprofloxacin effective for intestinal carriers, but biliary carriers require cholecystectomy as well

Carrier State:

Carrier State After recovery or subclinical infection - may harbor pathogens for 1 week to several months About 3% of typhoid fever survivors become permanent carriers organism. survive in gallbladder, intestines, and sometimes in urinary tract

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Carriers may be temporary or chronic. Temporary (convalescent or incubatory) carriers usually excrete bacilli up to 6-8 weeks . By the end of one year, 3-4 per cent of cases continue to excrete typhoid bacilli. Persons who excrete the bacilli for more than a year after a clinical attack are called chronic carriers.

Control & Prevention:

Control & Prevention Sanitary measures Thorough cooking of poultry, eggs, meat, etc. Identification of carriers Vaccination during travel to foreign countries

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World largest outbreak of typhoid in SANGLI on December 1975 to February 1976 . This disease is endemic in India

Specific protection:

Specific protection THREE TYPES OF VACCINES Injectable Typhoid vaccine ( TYPHIM –Vi,TYPHIVAX) 2. The live oral vaccine (TYPHORAL) 3. TAB vaccine In immunised there will be antibodies to S.typhi S.paratyphi A and B where as in infection only against infecting species

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Injectable Typhim -Vi This single-dose injectable typhoid vaccine, from the bacterial capsule of S. typhi strain of Ty21a. This vaccine is recommended for use in children over 2 years of age. Sub-cutaneous or intramuscular injection Efficacy : 64% -72%

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Typhoral This is a live-attenuated-bacteria vaccine manufactured from the Ty21 a strain of S. typhi . The efficacy rate of the oral typhoid vaccine ranges from 50-80% Not recommended for use in children younger than 6 years of age. The course consists of one capsule orally, taken an hour before food with a glass of water or milk ( 1stday,3 rd day &5 th day) No antibiotic should be taken during this period Immunity starts 2-3 weeks after administration and lasts for 3 years A booster dose after 3 years

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Indications for Vaccination Travelers going to endemic areas who will be staying for a prolonged period of time, Persons with intimate exposure to a documented S. typhi carrier 3. Microbiology laboratory technologists who work frequently with S. typhi 4.Immigrants 5. Military personnel

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SIDE EFFECTS . Injectable Typhim -Vi The most common adverse reactions are injection site pain, erythema, and induration, which almost always resolve within 48 hours of vaccination. Occasional fever, flu-like episodes, headache, tremor, abdominal pains, vomiting, diarrhea, and cervical pains have been reported. Typhoral Nausea, abdominal pain and cramps, vomiting, fever, headache, and rash or urticaria may occur in some instances but are rare.


TREATMENT Medical care include rehydration, antipyretics & antibiotics. Drugs of choice are Chloramphenicol Ampicillin, Cotrimoxazole, Ciprofloxacin & Ceftriaxone Ampicillin kills bacilli hiding in the bile & hence prevents or reduce the carrier state. Chronic resistant carrier state may necessitate cholecystectomy. Surgical care may also be needed in patients with intestinal complications.


PROGNOSIS With early diagnosis and prompt treatment most patients with typhoid fever will recover in due time. Fever & toxicity subsides within 72 hours of antibiotic treatment. Mortality is > 50% in untreated severe typhoid fever particularly in children & elderly. Recrudescence is rare but chronic carrier state is reported in 10% of patients.


SALMONELLOSIS Salmonella typically produces 3 distinct syndromes: food poisoning, typhoid fever & asymptomatic carrier state. Salmonella gastroenteritis manifest as vomiting & diarrhea within 6-48 hours after ingestion of food or drink contaminated with bacteria. It is self-limiting, treatment is by water & salts replacement. Antibiotics are not usually needed.


MORTALITY & MORBIDITY Infection with nontyphoidal salmonella produces self-limiting gastroenteritis and food poisoning. it is associated with significant mortality & morbidity in tropical countries (10-30%). Dehydration is the most common complication of typhoid fever, but serious intestinal & extra-intestinal complications may occur.

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