CME to hospital staff

1. Enteric Fever
Dr. Sachin Nepali
MBBS

2. Enteric Fever
• Typhoid and paratyphoid
• Route of transmission: Faeco-oral route
• Causative agent:
– Salmonella enterica, serovar typhi
– Salmonella paratyphi A,B
• Gram –ve bacilli, non lactose fermenting

3. Pathogenesis
• On reaching small intestine the organism
penetrates the mucosa and infects lymphoid
follicles and subsequently the draining lymph
nodes and liver and spleen
• It multiplies in the reticuloendothelial system
• After 7-14 days spills into bloodstream and is
widely desseminated especially to liver, spleen,
bone marrow, gall bladder and peyers patches of
the terminal ileum

4. • These swells at first, thenulcerate and usually
heal.
• After clinical recovery, about 5% of patients
become chronic carriers; the bacilli may live in
the gallbladder for months or years and pass
intermittently in the stool and less commonly
in urine

5. Clinical features

6. Physical signs
• Coated tongue
• Tumid abdomen
• Hepatosplenomegaly

7. Clinical case definitions
• Confirmed enteric fever:
 Fever ≥ 38 ̊C for at least 3 days with a lab confirmed positive
culture typhi
• Probable enteric fever:
 Fever ≥ 38 ̊C for at least 3 days with a positive serodiagnosis or
antigen detection test but without typhi isolation
• Chronic carrier state:
 Excretion of typhi in stools/urine for longer than 1 year after
onset of acute enteric fever.

8. Complications

9. Relapse
• 5-15% of treated cases
• Higher with beta-lactams (Ceftriaxone,
cefixime) as compared to quinolones and
azithromycin

10. Investigtions
• CBC:
– Mild anaemia,
– low to normal TLC,
– Neutrophilia, Eosinopenia, thrombocytopenia
– [Anaemia & thrombocytopenia in advanced cases]
• CRP/ESR may be elevated
• LFT:
– ALP, Transaminases, bilirubin may be increased

11. • Urinalysis: look for proteinuria, pyuria, casts
• Blood culture
• Bone marrow culture
• Stool culture
• Rose spot culture
• Duodenal aspirate culture
• Nested PCR
• Serology

12. • USG: to detect hepatosplenomegaly
• X-Ray abdomen: if bowel perforation
suspected
• CT/MRI: For liver/bone abscesses

13. Gold Standard
• Blood culture is the gold standard for
diagnosis
• Bile broth media
• BACTEC media

14. • Bone marrow culture have higher yield as
compared to peripheral blood cultures as
Salmonella is a pathogen of RES and should be
done in later stages of illness.
• Done in who have been treated previously, have a
long history of illness and had a negative blood
culture
• Remains positive even after administration of
antibiotics
• Expensive and invasive
• Thus reserved for hospitalized and severely sick
patients

15. • Rose spot culture: Punch biopsy can be
cultured
• Duodenal aspirate culture: Not affected by
antibiotics and by duration of illness
• Nested PCR: 100% sensitivity, can detect even
one bacterium in a given sample within a few
hours, not affected by duration of illness and
antibiotics therapy

16. Specific tests
• Widal tests
• Typhidot
• IDL tubex test
• IgM dipstick test

17. Widal Test
• A/c to WHO it should be done within 1 weeks of
onset of fever
• Detects IgM & IgG antibodies to O and H antigens
• Anti O titres are both IgM & IgG that rise and
decline early(require 6-8 days to appear)
• Anti H are primarily IgG that rise and decline late
in course of diseases (require 10-12 days)

18. • Diagnosis is made if
 titres > 1:80 for anti-O
 titres > 1:160 for anti-H
• False positive in Malaria, Typhus, Bacteremia,
Cirrhosis
• Low sensitivity and specificity

19. Typhidot
• Positive in 1st week of illness
• Prefered over widal
• Sensitivity is 95%, Specificity is 75%
• Cost effectiveness
• Detects IgM & IgG antibodies to a specific 50
kD outer membrane protein antigen of S.
typhi

20. IDL Tubex Test
• Rapid test which takes 2 min to perform
• Can detect IgM O9 antibodies
• Not useful for diagnosis of current infections

21. Treatment
• Most can be managed at home on oral
antibiotics
• Children with persisting vomiting, poor oral
intake, severe diarrhoea or abdominal
distension require hospital admission

22. Antimicrobials
• Resistance to Chloramphenicol was first noted
soon after its first use in 1940
• Simultaneously resistant to all drugs that were
used as 1st line treatment
o Chloramphenicol
o Cotrimoxazole (Trimethoprim+Sulphamethoxazole)
o Ampicillin

23. • The fluoroquinolones remain the drugs of
choice (e.g. ciprofloxacin 500 mg 12-hourly).
• Extended-spectrum cephalosporins,
ceftriaxone and cefotaxime, are useful
alternatives but have a slightly increased
treatment failure rate.
• Azithromycin (500 mg once daily) has been
shown to be an alternative where
fluoroquinoline resistance is present but has
not been validated in severe disease.

24. Empirical therapy
• Uncomplicated:
– Cefixime 20mg/kg/day
– Azithromycin (10-20 mg/kg/day)
• Severe illness:
– Ceftriaxone, Cefotaxim (100mg/kg/day)
– Aztreonam, Chloramphenicol, Cotrim in higher
dose if h/o allergy to penicillins/cephalosporins

25. Duration of treatment
• Parenteral antibiotics continued until
defervescence has occured or oral intake has
improved or complications has resolved
• Then therapy can be switched to oral cefixime
or other oral drugs to complete total duration
of 14 days
Azithromycin, Amoxicillin, Cotrimoxazole, Cefopodoxime

26. • Treatment should be continued for 14 days.
Pyrexia may persist for up to 5 days after the start
of specific therapy.
• Even with effective chemotherapy there is still a
danger of complications, recrudescence of the
disease and the development of a carrier state.
• The chronic carrier should be treated for 4 weeks
with ciprofloxacin; cholecystectomy may be
necessary in some cases.

27. Therapy for relapse

28. Prevention
• Improved sanitation and living conditions
• Food hygiene
• Water hygiene
• Immunizations

29. Vaccination
• WHO recommends immunization for
– children aged over 2 years in endemic zones,
– individuals travelling to endemic zones,
– people who are in close contact with chronic
carriers,
– laboratory staffs who handles sample containing
S. typhi

30. Vaccines
• Vi polysaccharide:
– Single dose sc/im
– Protection begins from 7 days of infection and
maximum at 28 days
– Revaccination recommended every 3 years for
travellers
– Approved for persons aged over 2 years

31. Ty 21a oral vaccines
• Available in enteric coated capsule or liquid
• Should be taken in 3 doses with 2 days interval on an empty
stomach
• Gives protection from 10-14 days from 3rd dose
• Travellers should be vaccinated annually
• Antibiotics should be avoided for 7 days before and after
immunization
• Approved for use in children aged minimum 5 years

32. References
• Davidson Principle & Practice of Medicine
• OP Ghai, Essential Paediatrics 7th Edition
• Daily Rounds App
• Uptodate
• Medscape

33. THANK - YOU