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Enteric Fever

Dr. Priyamadhaba Behera

References
WHO Document, 5th edition OTPH, 18th edition Harrison
principle of medicine, Articles however applicable
1
Epidemiology
• Etiologic agents of enteric fever
– S. typhi and S. paratyphi serotypes A, B, and C
– No known hosts other than humans

• Estimated 22 million cases, with 200,000 deaths annually
• Incidence
Rate

Location

Cases per 1 Lakh opulation per Yr.

Highest

South central and Southeast Asia

>100

Medium

Rest of Asia, Africa, Latin America
and Oceania (excluding Australia
and New Zealand)

10–100

Low

Other parts of the world

<10
Epidemiology
Epidemiology
• Multidrug-resistant (MDR) strains of S. Typhi emerged
in 1989 in China and southeast Asia
• Resistance to chloramphenicol, ampicillin and
trimethoprim antibiotics long used to treat enteric
fever
• Increased use of fluoroquinolones to treat MDR
enteric fever in 1990s, reduced susceptibility to
ciprofloxacin [MIC, 0.125–1 g/ml] have emerged in
the Indian subcontinent, southern Asia
• Resistance - first-generation Quinolone nalidixic acid
detects most but not all strains with reduced
susceptibility to ciprofloxacin
Disease Outbreak Reported
• 17 June 2003 (Haiti)
– As of 30 May, 200 cases and 40 deaths, reported by WHO regional
office for the Americas (PAHO) and the MoH, Haiti
– Epidemic started in April in villages in the Grand Bois area, bordering
the Dominican Republic

• 15 December 2004 (Kinshasa)
– Total of 13400 cases were reported
– Between 1st October and 10th December 2004, 615 severe cases with
peritonitis, with or without perforation, including 134 deaths (case
fatality rate, 21.8%) have occurred

• 19 January 2005
– From 27 September 2004 - 11 January 2005, WHO reported total of
42564 cases and 214 deaths (case fatality ratio, 0.5%), and 696 severe
cases of intestinal perforation in Kinshasa

• Very poor sanitary conditions and a lack of drinking water
have been reported in all these areas
Mode of transmission

• Most commonly, food-borne or waterborne
• Faecal contamination by ill or asymptomatic chronic
carriers
• Health care workers -exposure to infected patients or
during
processing of clinical specimens and cultures
• Sexual transmission between male partners has been
described
Role of asymptomatic carrier in typhoid

George Soper

Dr. Sara Josephine Baker
Risk factors
•
•
•
•

Contaminated water or ice
Flooding
Contaminated food and drinks
Raw fruits and vegetables grown in fields fertilized
with sewage
• Lack of hand washing and toilet access
• Evidence of prior helicobacter pylori infection
Risk factors
Severe disease ( 10–15% of patients)
• Host factors (immunosuppression, antacid therapy,
previous exposure, and vaccination)
• Strain virulence and inoculums
• Choice of antibiotic therapy
Incubation period
• 3 - 21 days (average 10-14 days)
Symptoms
•Enteric fever is a misnomer
•Hallmark features of this
disease—fever and abdominal
pain—are variable
•Fever >75% of cases,
abdominal pain is reported in
only 30–40%
Symptoms
•
•
•
•
•
•
•
•

Sytemic symptoms
Headache (80%)
Chills (35–45%)
Cough (30%)
Sweating (20–25%)
Myalgias (20%)
Malaise (10%)
Arthralgia (2–4%)
Symptoms
Gastrointestinal symptoms
• Anorexia (55%)
• Abdominal pain (30–40%)
• Nausea (18–24%)
• Vomiting (18%)
• Diarrhea (22–28%)
• Constipation (13–16%)
2nd week
Signs
•Relative bradycardia
•Coated tongue (51–56%)
•Splenomegaly (5–6%)
•Abdominal tenderness (4–5%)
• Rose spots (30%)

End of the first week and resolves
without a trace after 2–5 days
Two or three crops of lesions
Salmonella can be cultured from punch
biopsies of these lesions
Faintness of rash makes difficult to
detect in highly pigmented patients
Investigations
• Definitive diagnosis of enteric fever by isolation of S.
Typhi or S. Paratyphi from blood, bone marrow,
other sterile sites, rose spots, stool, or intestinal
secretions
• Serologic tests- widal test
 ƒTiming of test is important
 ƒSingle test is usually of not much value
 ƒBaseline titre of the population must be known
before attaching significance to the titres (≥100 for O
and ≥200 for H)
 Treated with antibiotics may not show any rise
 False positive reactions
 Anamnestic response ƒƒ
Investigations
• None of these tests is sufficiently sensitive or specific
to replace culture-based methods for the diagnosis
• PCR and DNA probe assays to detect S. typhi in blood
have been identified but have not yet been
developed for clinical use
Treatment
Control
• Health education about personal hygiene, especially
regarding hand-washing after toilet use and before
food preparation
• Provision of a safe water supply
• Proper sanitation systems
• Excluding disease carriers from food handling
Control
• Possible to eliminate enteric fever since they
survive only in human hosts and spread by
contaminated food and water
• High prevalence of the disease in developing
countries that lack adequate sewage disposal and
water treatment, goal is currently unrealistic
• Travelers to developing countries should be
advised to monitor their food and water intake
carefully and to consider vaccination
Typhoid vaccines
Two typhoid vaccines are commercially available .
Currently, there is no licensed vaccine for paratyphoid
fever
Ty21a
– Oral live attenuated S. Typhi vaccine
– Days 1, 3, 5, and 7, with a booster every 5 years
– Minimal age for vaccination is 6 years
Typhoid vaccines
Vi CPS
• Parenteral vaccine consisting of purified vi
polysaccharide from the bacterial capsule
• Given in 1 dose, with a booster every 2 years
• Minimal age for vaccination is 2 years
Meta-analysis of vaccine trials comparing whole-cell
vaccine, ty21a, and vi CPS in populations in endemic
areas indicates
• All three vaccines are similarly effective for the first year
• 3-year cumulative efficacy of the whole-cell vaccine
(73%) exceeds both ty21a (51%) and vi CPS (55%)
Typhoid vaccines
• Typhoid vaccine is not required for international travel,
but recommended for travellers to moderate to high
risk areas (Asia, Africa, the Caribbean, and Central and
South America)
• Typhoid vaccine should be considered even for persons
planning <2 weeks of travel to high-risk areas
• laboratory workers who deal with S. typhi and
household contacts of known S. typhi carriers
• Immunization is not recommended for adults residing
in typhoid-endemic areas or for the management of
persons who may have been exposed in a commonsource outbreak

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Enteric fever

  • 1. Enteric Fever Dr. Priyamadhaba Behera References WHO Document, 5th edition OTPH, 18th edition Harrison principle of medicine, Articles however applicable 1
  • 2. Epidemiology • Etiologic agents of enteric fever – S. typhi and S. paratyphi serotypes A, B, and C – No known hosts other than humans • Estimated 22 million cases, with 200,000 deaths annually • Incidence Rate Location Cases per 1 Lakh opulation per Yr. Highest South central and Southeast Asia >100 Medium Rest of Asia, Africa, Latin America and Oceania (excluding Australia and New Zealand) 10–100 Low Other parts of the world <10
  • 4. Epidemiology • Multidrug-resistant (MDR) strains of S. Typhi emerged in 1989 in China and southeast Asia • Resistance to chloramphenicol, ampicillin and trimethoprim antibiotics long used to treat enteric fever • Increased use of fluoroquinolones to treat MDR enteric fever in 1990s, reduced susceptibility to ciprofloxacin [MIC, 0.125–1 g/ml] have emerged in the Indian subcontinent, southern Asia • Resistance - first-generation Quinolone nalidixic acid detects most but not all strains with reduced susceptibility to ciprofloxacin
  • 5. Disease Outbreak Reported • 17 June 2003 (Haiti) – As of 30 May, 200 cases and 40 deaths, reported by WHO regional office for the Americas (PAHO) and the MoH, Haiti – Epidemic started in April in villages in the Grand Bois area, bordering the Dominican Republic • 15 December 2004 (Kinshasa) – Total of 13400 cases were reported – Between 1st October and 10th December 2004, 615 severe cases with peritonitis, with or without perforation, including 134 deaths (case fatality rate, 21.8%) have occurred • 19 January 2005 – From 27 September 2004 - 11 January 2005, WHO reported total of 42564 cases and 214 deaths (case fatality ratio, 0.5%), and 696 severe cases of intestinal perforation in Kinshasa • Very poor sanitary conditions and a lack of drinking water have been reported in all these areas
  • 6. Mode of transmission • Most commonly, food-borne or waterborne • Faecal contamination by ill or asymptomatic chronic carriers • Health care workers -exposure to infected patients or during processing of clinical specimens and cultures • Sexual transmission between male partners has been described
  • 7. Role of asymptomatic carrier in typhoid George Soper Dr. Sara Josephine Baker
  • 8. Risk factors • • • • Contaminated water or ice Flooding Contaminated food and drinks Raw fruits and vegetables grown in fields fertilized with sewage • Lack of hand washing and toilet access • Evidence of prior helicobacter pylori infection
  • 9. Risk factors Severe disease ( 10–15% of patients) • Host factors (immunosuppression, antacid therapy, previous exposure, and vaccination) • Strain virulence and inoculums • Choice of antibiotic therapy Incubation period • 3 - 21 days (average 10-14 days)
  • 10. Symptoms •Enteric fever is a misnomer •Hallmark features of this disease—fever and abdominal pain—are variable •Fever >75% of cases, abdominal pain is reported in only 30–40%
  • 11. Symptoms • • • • • • • • Sytemic symptoms Headache (80%) Chills (35–45%) Cough (30%) Sweating (20–25%) Myalgias (20%) Malaise (10%) Arthralgia (2–4%)
  • 12. Symptoms Gastrointestinal symptoms • Anorexia (55%) • Abdominal pain (30–40%) • Nausea (18–24%) • Vomiting (18%) • Diarrhea (22–28%) • Constipation (13–16%) 2nd week
  • 13. Signs •Relative bradycardia •Coated tongue (51–56%) •Splenomegaly (5–6%) •Abdominal tenderness (4–5%) • Rose spots (30%) End of the first week and resolves without a trace after 2–5 days Two or three crops of lesions Salmonella can be cultured from punch biopsies of these lesions Faintness of rash makes difficult to detect in highly pigmented patients
  • 14. Investigations • Definitive diagnosis of enteric fever by isolation of S. Typhi or S. Paratyphi from blood, bone marrow, other sterile sites, rose spots, stool, or intestinal secretions • Serologic tests- widal test  ƒTiming of test is important  ƒSingle test is usually of not much value  ƒBaseline titre of the population must be known before attaching significance to the titres (≥100 for O and ≥200 for H)  Treated with antibiotics may not show any rise  False positive reactions  Anamnestic response ƒƒ
  • 15. Investigations • None of these tests is sufficiently sensitive or specific to replace culture-based methods for the diagnosis • PCR and DNA probe assays to detect S. typhi in blood have been identified but have not yet been developed for clinical use
  • 17. Control • Health education about personal hygiene, especially regarding hand-washing after toilet use and before food preparation • Provision of a safe water supply • Proper sanitation systems • Excluding disease carriers from food handling
  • 18. Control • Possible to eliminate enteric fever since they survive only in human hosts and spread by contaminated food and water • High prevalence of the disease in developing countries that lack adequate sewage disposal and water treatment, goal is currently unrealistic • Travelers to developing countries should be advised to monitor their food and water intake carefully and to consider vaccination
  • 19. Typhoid vaccines Two typhoid vaccines are commercially available . Currently, there is no licensed vaccine for paratyphoid fever Ty21a – Oral live attenuated S. Typhi vaccine – Days 1, 3, 5, and 7, with a booster every 5 years – Minimal age for vaccination is 6 years
  • 20. Typhoid vaccines Vi CPS • Parenteral vaccine consisting of purified vi polysaccharide from the bacterial capsule • Given in 1 dose, with a booster every 2 years • Minimal age for vaccination is 2 years Meta-analysis of vaccine trials comparing whole-cell vaccine, ty21a, and vi CPS in populations in endemic areas indicates • All three vaccines are similarly effective for the first year • 3-year cumulative efficacy of the whole-cell vaccine (73%) exceeds both ty21a (51%) and vi CPS (55%)
  • 21. Typhoid vaccines • Typhoid vaccine is not required for international travel, but recommended for travellers to moderate to high risk areas (Asia, Africa, the Caribbean, and Central and South America) • Typhoid vaccine should be considered even for persons planning <2 weeks of travel to high-risk areas • laboratory workers who deal with S. typhi and household contacts of known S. typhi carriers • Immunization is not recommended for adults residing in typhoid-endemic areas or for the management of persons who may have been exposed in a commonsource outbreak

Editor's Notes

  1. as antibodies begin to arise during end of first week. The titres increase during second, third and fourth week after which it gradually declines. The test may be negative in early part of first week. . 2-A rise in titre between two sera specimens is more meaningful than a single test. If the first sample is taken late in the disease, a rise in titre may not be demonstrable. Instead, there may be a fall in titre 3-The antibody levels of individuals in a population of a given area give the baseline titre. A titre of 100 or more for O antigen is considered significant and a titre in excess of 200 for H antigens is considered significant. Patients already treated with antibiotics may not show any rise in titre, instead there may be fall in titre. Patients treated with antibiotics in the early stages may not give positive results. ƒ Patients who have received vaccines against Salmonella may give false positive reactions. This can be differentiated from true infection by repeating the test after a week. True untreated infection results in rise in titre whereas vaccinated individuals don’t demonstrate any rise in titre ƒ Those individuals, who had suffered from enteric fever in the past, sometimes develop anti-Salmonella antibodies during an unrelated or closely related infection. This is termed anamnestic response and can be differentiated from true infection by lack of any rise in titre on repetition after a week.