Dr. Priyamadhaba BeheraReferences WHO Document, 5th edition OTPH, 18th edition Harrison principle of medicine, Articles however applicable

1

Enteric Fever

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 daysTwo or three crops of lesionsSalmonella can be cultured from punch

biopsies of these lesionsFaintness 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 Timing of test is important� Single test is usually of not much value� Baseline 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 ��

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 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 common-source outbreak

Typhoid vaccines