ENTERIC FEVER
• Genus Salmonella causes three types of infections
• Enteric fever (Typhoidal Salmonella – humans
only)
S.typhi causes typhoid fever
S.paratyphi A & B causes paratyphoid fever
• Enterocolitis (Non Typhoidal Salmonella –
animals,mammals,birds,reptiles and insects )
S.typhimurium
S.entiritidis
S.thompson
S.newport
S.dublin
• Septicemias
S.cholerasuis
S.enteritidis causes osteomyelitis in sickle cell anemia
3
MORPHOLOGY
• Gram negative, motile (except S.gallinarum
pullorum which is nonmotile)
• Non- sporing , non capsulated, size 2-4 x 0.6
microns.
• Peritrichous flagellae
• Posses fimbriae
ANTIGENIC STRUCTURE
Salmonella posses
following antigens
Flagellar antigen “H”
Somatic “O” antigen
Surface “Vi” antigen
PATHOGENICITY
VIRULENCE AFCTORS -
Endotoxin
Invasins
Factors that resist phagocytosis
(superoxide dismutase, defensins)
Factors in ressitance to pH ( acid
tolerence response gene, virulent
antigen/Vi)
PATHOGENICITY
Common species affecting man -S.typhi,
S.paratyphi A & B
Mode of infection:- oral route due to contaminated
food and water
All virulent strains survive gastric acidity, penetrates
mucosa and submucosa. Two types of invasion
Mucosal penetration- acute inflammation &
ulceration
Mucosal infiltration- activation of adenyl cyclase
which lead to fluid & electrolyte accumulation
ENTERIC FEVER
• Bretonneau in 1826 made a detailed study of the
disease.
• The name typhoid was given by Louis in 1829
Bile is good medium for culture so abundantly in gall
bladder
Discharged continuosly into the intestine involves
Peyer’s patches
Inflamed, undergo necrosis and slough-typhoid ulcer
Two complications- intestinal perforation &
haemorrhage
PATHOGENICITY
• Infective dose : 1000 to 100000 bacilli
• Risk factors: Stomach acidity, prior H.pylori
infection,GUT surgery,IBD, antibiotic therapy.
• M cells of intestinal epithelium , BME (bacteria
mediated endocytosis)
• Resist intracellular killing after reaching the
macrophages
ENTERIC FEVER
Reaches the GUT
attaches to microvilli of ileal mucosa
Penetrate lamina propria & submucosa
Phagocytosed by polymorphs & macrophages
resists intracellular killing (measure of virulence)
Enter the mesentric lymphnodes
transient bacteremia
Seeded, bone marrow, lymph nodes, lungs and kidneys
where further multiplication takes place
SIGNS & SYMPTOMS
7-14 days
Mild undifferentiated pyrexia to rapidly fatal disease
Gradual, with head ache, malaise, anorexia, coated
tongue and abdominal discomfort with diarrhea
/constipation
Step -ladder pyrexia
Hepatomegaly
Rose spots on skin that fade on pressure
COMPLICATIONS
Intestinal perforation
Hemorrhage
Circulatory collapse
Bronchitis
/bronchopneumonia
Psychoses
Deafness
Meningitis
LABORATORY DIAGNOSIS
• ISOLATION OF BACTERIA
• DEMONSTRATION OF ANTOBODIES
• ANTIGEN DEMONSTRATION IN BLOOD
AND URINE
ISOLATION OF BACTERIA
Specimens collected:- blood, feaces, urine, bone
marrow,duodenal aspirate,CSF,pus,sputum.
Methods :-
1)Blood culture- 90% positive in first week
75% in second week
60% in third week
25% in thereafter
2)Clot culture
3)Feacal culture
4)Urine culture
Blood Clot culture Feacal Urine
culture culture culture
5-10 ml blood 5 ml of blood In patients Irregular
in 50-100ml of allowed to with
bile broth clot antibiotics
Positive in
Incubate Incubate second& third
week
Subculture on Subculture on Directly on
Mac Conkey, Mac Conkey, enrichment
DCA,Wilson DCA,Wilson broth like
&Blair &Blair seleniteF
medium medium broth&tetrath
oinate
Biochemical Biochemical broth/media
reactions reactions Isolate
identified by
Isolate Isolate Isolate slide
identified by identified by identified by agglutination
slide slide slide
agglutination agglutination agglutination
BLOOD CULTURE METHODS
BIPHASIC MEDIUM/CASTANEDA’S MEDIU
BILE BROTH / BRAIN HEART INFUSION BROTH
CULTURAL CHARACTERS
• Aerobic, facultative anaerobic, grow readily,
temperature requirement is 15 to 41oC (37oC)
• pH- 6 to 8
MEDIA REQUIRED
Grows on ordinary media
Nutrient agar :- 2-3 mm, grey colonies, moist,
circular , convex
Blood agar :- Grey colonies
MacConkey:- Pale colourless / yellow colonies,1-3
mm
MAC CONKEY
Special media
Deoxycholate citrate agar:- colourless, smooth , shiny
colonies
Hektoen enteric agar:- blue green with black center.
Selective meida:-
Wilson and blair medium:- (brilliant green bismuth
sulphite)
Typhi & paratyphi B - black colonies
Paratyphi A - green colonies
Xylose lysine deoxycholate ( Na deoxycholate - .1 to
.25%):- red coloured colonies with black centers
DEOXYCHOLATE CITRATE AGAR
XYLOSE LYSINE DEOXYCHOLATE
Selective media
Wilson & blair medium Deoxycholate citrate agar
Wilson & blair medium
Culture media – for feacal
sample
Enrichment media
Tetrathionate
broth
Selenite F broth
Colony morphology
Media Organism Colony morphology
Mac Genus Non lactose
Conke Salmonell fermenting
y agar a
Wilson S.typhi Black colonies
&blair Other Green colonies
agar Salmonell
a
Biochemical tests
Genus Salmonella
S.typhi
H2S production , no gas, citrate negative
S.para A
No H2s, gas, citrate negative
S.para B
H2S production ,Citrate positive, gas
Serotyping
• High titre serum of ‘O’ antigen (factor 9/D
group) is used for confirmation of
Salmonella typhi isolate from patient
• By slide agglutination test
DEMONSTRATION OF
ANTIBODIES
Aim:- is to detect the ‘O’ & ‘H’ agglutinins
Principle:- is slide/tube agglutination test –WIDAL TEST
Sample :-is serum
Procedure :- two tubes are used
Conical bottom- Dreyer’s tube -’H’ agglutinins
Round bottom- Felix tube -’O’agglutinins
Serial dilutions of serum made as 1in 20, 1in 40, 1in80
etc
Equal amounts of antigen is added and incubated in
water bath over night
Result – granular clumps in”O”
- loose, cotton woolly in “H”
TUBE WIDAL
H
O
ANTIGENS OF
SALMONELLA
H O antigen Vi
antigen antigen
Flagellar Somatic O antigen, Surface
antigen ,heat labile integral part of polysaccharide
cell wall antigen covers the
(endotoxin) O antigen, heat
Destroyed by labile
boiling /alcohol but Uneffected by
not formaldehyde boiling and alcohol Uneffected by
alcohol
Highly
immunogenic Forms compact,
When mixed with chalky, granular
antisera it forms clumps It poorly
large, loose, fluffy immunogenic not
clumps. used diagnostically
act as virulent
factor in
SLIDE AGGLUTINATION
O & H coloured antigens
INTERPRETATION OF
WIDAL TEST
1)Titers are significant at the end of
first week
2)Rising titers are significant
3)Local titer in Chennai more than 1
in80
4)Anamnestic reactions
5)Antibiotic treatment
6)Carriers and vaccinated persons
Interpretation of widal test
Widal test result Suggestive of
Rise of TO and TH Abs Enteric fever due to S.typhi
Rise of TO and AH Abs Enteric fever due to
S.paratyphi A
Rise of TO and BH Abs Enteric fever due to
S.paratyphi B
Rise of TO Abs only Recent infection with any
serotype
Rise of TH Abs only Convalescent
phase/amanestic reaction
Rise of all TH,TO, AH & BH Post TAB vaccine
Abs
09/05/25
TREATMENT AND DRUG
RESISTANCE
The drug of choice is chloramphenicol
Resistance to this drug is seen first in Mexico and
Kerala in 1972
Then Ampicillins, Amoxycillins are used resistance
was also seen in these in1980
Now we use quinolones like ciprofloxacin,
pefloxacin, third generation cephalosporins
like ceftriaxone, and recently azithromycin.
Carriers of typhoid
• Urinary carriers
• Feacal carriers
• Convalescent carriers
• Temporary carriers
• Chronic carriers – common in
women,infants,old age, biliary tract
abnormalities, urinary tract abnormalities.
• Food handlers and cooks
Detection of carriers
• Culture of stool, bile and urine.
• Detection of Vi antibodies: Titers of 1:10 significant
• Isolation of Salmonella from sewage: by sewer swab
technique, Membrane filtration
Control of carriers
1. Antibiotic therapy (Amp, Amox + probenecid – 6weeks)
2. Early diagnosis
3.Disinfection of Stool, urine soiled chlothes with 5% cresol ,2%
chlorine
4. Follow up examination
5. Sugery Cholecystectomy
09/05/25
EPIDEMIOLOGY
• NOMENCLATURE
• ENDEMIC DISEASE
• CARRIERS- TYPHOID MARY
• BACTERIOPHAGE TYPING
Prophylaxis
Sanitation measures:
1. Safe drinking water
2. Hand a nd food hygiene
3. Health education
Indication of vaccines:
1. Travellers to endemic area
2. Melas and yatras
3. Household contacts
4. School children
5. Endemic population
09/05/25
PROPHYLAXIS
TYPHOID VACCINES
Two types- killed & live
1. Killed-TAB vaccine contains S.typhi 1000 million, S.paratyphiA & B 750
million
Dose -0.5 ml sc at 4to 6 week intervals
2. Live – Typhoral contains S.typhi mutant strains to be taken before food on
1,3,5 days (10 9 baccili)
3. Parentaral Vi capsular polysaccharide vaccine (Vi CPS) 25 microgrmas
IM or SC, given only after 2 yrs of age
Vi-r EPA – Recombinant vaccine
National Salmonella referral
centres
Non – Typhoidal Salmonella
S.Typhimurium, S.Enteriditis, S.Newport, S.Javiana, S. Heidelberg,
S.Choleraesius and S.Dublin
Zoonotic (animal or animal products)
Gastroenteritis (self-limited), Bacteraemia(endovascular or
metastatic localized infections)
Ciprofloxacin – Preemptive treatment
Ceftriaxone - Bacteraemia and invasive infections
09/05/25
