Typhoid fever

Etiology

Salmonella typhi

Incubation period 

10 to 14 days

Clinical features 

Fever - Step ladder remittent fever

Rashes - Maculopapular rash seen on chest, trunk. Also called as Rose spots. Rose spots fade on pressure

Nausea, Vomiting

Abdominal pain, Diarrhea 

Important signs -

Hepatospleenomegaly

Relative bradycardia 

What do you mean by relative bradycardia?

The pulse is slower than it is expected at that height of temperature. This is called as relative bradycardia.

Complications -

1. Gastrointestinal bleeding

2. Intestinal perforation 

When typhoid fever is complicated with intestinal perforation, guarding and rigidity of abdomen is present

Transmission

Ingestion of contaminated water and food

Typhoid fever is more common in area of overcrowding and poor sanitation

Carriers

Untreated patients become carriers

Carriers are of 2 types -

1. Urinary -

2. Fecal - More common

Temporary carriers shed S. typhi for 3 months

Chronic carriers shed S. typhi for more than 1 year

Lab diagnosis 

A. CULTURE

1. Blood culture 

Done in first week of illnesss

2. Bone marrow culture

Done in first week of illness

Done when blood culture turns out to be negative

3. Duodenal aspirate culture 

Also done in first week of illness

Done when both blood and bone marrow cultures turn out to be negative

Blood culture is of 2 types

1. Conventional: Brain heart infusion broth/agar is used

 2. Automated blood culture systems: BACTEC or BacT/ALERT

8 - 10 ml blood is used for blood culture

From positive blood culture broth, subcultures are made on blood and MacConkey agar

Blood agar - Non hemolytic colonies are seen

MacConkey agar - Non lactose fermenting colonies are seen

4. Stool culture 

Done in 3–4 weeks of illness

Stool culture is useful for detection of carriers

Enrichment broth such as Selenite F broth, tetrathionate broth are used

Selective media

MacConkey agar - NLF colonies

DCA (Deoxycholate citrate agar) - NLF colonies with black centres

XLD (Xylose lysine deoxycholate) agar - Red colonies with black centre

Wilson Blair’s media - Black coloured colonies with metallic sheen

5. Urine culture 

Done in 3–4 weeks of illness

MacConkey agar is used for urine culture

B. Motility test

Motile bacilli seen

C. Biochemical tests

Catalase positive and oxidase negative

ICUT: 

Indole –ve

Citrate –ve

Urease –ve

TSI:

K/A

Gas + except in S. Typhi, S. typhi is anaerogenic

H2S production-

S. Typhi - A small speck of H2S is seen

S. Paratyphi A - No H2S is seen

S. ParatyphiB - Abundant H2S is seen

Slide agglutination test:

Done to confirm the serotype

D. Widal test

The Widal test is a serological test for enteric fever which detects antibodies against O (surface) and H (flagellar) antigens

Done in 2–3 weeks of illness

Antibodies are detected against TO, TH, AH, BH antigens

S. Typhi infection:

↑TO and TH antibodies

S. Paratyphi A infection:

↑TO and AH antibodies

S. Paratyphi B infection:

↑TO and BH antibodies.

Result and interpretation

When O antibodies react with O Ag they  produce granular chalky clumps

When H antibodies react with H Ag they produce cottony woolly clumps

E. Antigen detection 

Antigen detection is done in serum and urine by ELISA

F. Molecular methods

PCR detects flagellin gene, iro B and fliC gene

G. Antimicrobial susceptibility testing

Done by either disk diffusion method on Mueller Hinton agar or by Vitek 

H. Detection of carriers

1. By urine culture which detects urinary carriers and by bile and stool culture which detects fecal carriers

2. Detection of Vi antibodies - Tube agglutination test is used by Bhatnagar strains (S. typhi suspension carrying Vi antigen)

Treatment 

Third generation cephalosporins: Ceftriaxone is the drug of choice for empirical treatment.

Dose - 1–2 g/day IV, for 10–14 days

Azithromycin: Alternative drug for empirical therapy. 

Dose - 1g/day orally for 5 days

Fluoroquinolones [e.g. ciprofloxacin]: It should not be given empirically because of frequent drug resistance

Dose - 500 mg twice a day oral for 5 days.

Drugs that were used in the past were: Chloramphenicol, Amoxicillin and Cotrimoxazole

Treatment of carriers 

Ampicillin or amoxicillin plus probenecid - Given for 6 weeks

Vaccines for Typhoid Fever

1. Vi antigen capsular polysaccharide vaccine

Composed of purified Vi capsular polysaccharide antigen 

Derived from S. Typhi strain Ty2

Route of administration - IM or subcutaneously

2. Vi-rEPA: Vi antigen is conjugated with recombinant Pseudomonas aeruginosa Exotoxin A

3. Typhoral

Oral live attenuated S. Typhi Ty21a vaccine

Typhoral is a stable live attenuated mutant of S. Typhi strain Ty21a

Mnemonic 1 

STaIR Case

ST- Step ladder pyrexia

I - Intestinal perforation

R - Rose spots, Relative bradycardia

C - Carrier state can happen in untreated cases

Mnemonic 2 

BASU 1234

This Mnemonic can be used to remember the types of culture done for Typhoid

Blood culture - Done in 1st week of of illness

Antibody detection (Widal test) - Done in 2nd week of illness

Stool and urine culture - Done in 3 to 4 week of illness

Mnemonic 3

ACE

A - Azithromycin 

C - Ceftriaxone 

E - Empirical treatment 

Ceftriaxone and Azithromycin are used for empirical treatment of typhoid fever