Enteric Fever
Dr. Sachin Nepali
MBBS
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
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
• 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
Clinical features
Physical signs
• Coated tongue
• Tumid abdomen
• Hepatosplenomegaly
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.
Complications
Relapse
• 5-15% of treated cases
• Higher with beta-lactams (Ceftriaxone,
cefixime) as compared to quinolones and
azithromycin
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
• Urinalysis: look for proteinuria, pyuria, casts
• Blood culture
• Bone marrow culture
• Stool culture
• Rose spot culture
• Duodenal aspirate culture
• Nested PCR
• Serology
• USG: to detect hepatosplenomegaly
• X-Ray abdomen: if bowel perforation
suspected
• CT/MRI: For liver/bone abscesses
Gold Standard
• Blood culture is the gold standard for
diagnosis
• Bile broth media
• BACTEC media
• 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
• 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
Specific tests
• Widal tests
• Typhidot
• IDL tubex test
• IgM dipstick test
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)
• 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
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
IDL Tubex Test
• Rapid test which takes 2 min to perform
• Can detect IgM O9 antibodies
• Not useful for diagnosis of current infections
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
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
• 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.
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
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
• 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.
Therapy for relapse
Prevention
• Improved sanitation and living conditions
• Food hygiene
• Water hygiene
• Immunizations
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
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
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
References
• Davidson Principle & Practice of Medicine
• OP Ghai, Essential Paediatrics 7th Edition
• Daily Rounds App
• Uptodate
• Medscape
THANK - YOU

Enteric fever

  • 1.
  • 2.
    Enteric Fever • Typhoidand 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 reachingsmall 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 swellsat 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.
  • 6.
    Physical signs • Coatedtongue • 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.
  • 9.
    Relapse • 5-15% oftreated cases • Higher with beta-lactams (Ceftriaxone, cefixime) as compared to quinolones and azithromycin
  • 10.
    Investigtions • CBC: – Mildanaemia, – 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: lookfor proteinuria, pyuria, casts • Blood culture • Bone marrow culture • Stool culture • Rose spot culture • Duodenal aspirate culture • Nested PCR • Serology
  • 12.
    • USG: todetect hepatosplenomegaly • X-Ray abdomen: if bowel perforation suspected • CT/MRI: For liver/bone abscesses
  • 13.
    Gold Standard • Bloodculture is the gold standard for diagnosis • Bile broth media • BACTEC media
  • 14.
    • Bone marrowculture 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 spotculture: 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 • Widaltests • Typhidot • IDL tubex test • IgM dipstick test
  • 17.
    Widal Test • A/cto 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 ismade 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 in1st 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 canbe managed at home on oral antibiotics • Children with persisting vomiting, poor oral intake, severe diarrhoea or abdominal distension require hospital admission
  • 22.
    Antimicrobials • Resistance toChloramphenicol 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 fluoroquinolonesremain 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 shouldbe 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.
  • 28.
    Prevention • Improved sanitationand living conditions • Food hygiene • Water hygiene • Immunizations
  • 29.
    Vaccination • WHO recommendsimmunization 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 oralvaccines • 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.

Editor's Notes

  • #6  Fever starts as a low grade fever and then shows stepwise increase peaking to as high as 103-104 ̊ F by the end of the first week. This differentiates it from viral fever where the peak is usually at the onset of fever.
  • #11 Anaemia & thrombocytopenia in advanced cases is strongly suggestive of enteric fever
  • #14  In 1st week sensitivity is 90% In 4th week sensitivity is 40% After antibiotics sensitivity is 20-40%
  • #18 O(Somatic antigen) of typhi & paratyphi A, B H(Flagellar antigen) of S. enterica var typhi and Paratyphi A,B
  • #20  These detects IgM antibodies against typhoid and have not proven to be superior to the Widal test
  • #25 If nalidixic acid resistance and resistance to other drugs (Chloramphenicol, Cotrimoxazole, Amoxicillin), then options are Cefixime & Azithromycin If local resistance pattern is unknown then it is good to use Cefixime or Azithromycin