Infectious Diseases: Typhoid Fever

TYPHOID FEVER
- 2300 serotypes; S.typh/paratyphi-enteric fever only in human. Non-typhoidal Salmonella –GIT of mammals, reptiles, birds.
- Typhoid: is a systemic disease characterized by fever and abdominal pain caused by dissemination of S. typhi or S. paratyphi.
ETIOLOGYGm –ive bacilli, family Enterobacteriaceae, facultatively anaerobic, motile-peritrichous flagella .
- Salmonella has three major antigenic determinants: the somatic O antigen [lipopolysaccharide (LPS) cell-wall components], the surface Vi antigen (restricted to S. typhi and S. paratyphi C), and the flagellar H antigen.
PATHOGENESIS (ID50) of S. typhi, 103 - 106 CFU, Host defenses- most important is the acidity of the stomach & integrity of SI epithelium.
- ↑ risk - age1 year, antacid ingestion, or achlorhydric disease,inflammatory bowel disease, history of gastrointestinal surgery.
- Contaminated food or water→ to colonize the small intestines→ cross the intestinal barrier→ phagocytosis by macrophages →dissemination throughout the reticuloendothelial system(liver, spleen, lymph nodes, and bone marrow. During this initial incubation stage, patients are relatively asymptomatic.
EPIDEMIOLOGY S. typhi and S. paratyphino known hosts except humans, the fecal-oral transmission via ingestion of contaminated food or water.
- Children 1 year of age appear to be most susceptible to initial infection and to the development of severe disease.
- Endemic in developing regions, many S. typhi strains contain plasmids encoding resistance to chloramphenicol, ampicillin, and trimethoprim
CLINICAL COURSE Incubation period - 3 -21 days.
- Symptoms: prolonged fever, headache, anorexia, cough, weakness, sore throat, dizziness, and muscle pains with either diarrhea or constipation; 20-30%with abdominal pain. Neuropsychiatric symptoms described as a "muttering delirium" or "coma vigil," with picking at bedclothes or imaginary objects.
- Signs: rash("rosespots"), hepato-splenomegaly, epistaxis, and relative bradycardia.
- Late complications,at 3-4th week - intestinal perforation and/or gastrointestinal hemorrhage. These complications can develop despite clinical improvement and presumably result from necrosis at the initial site of Salmonella infiltration in the Peyer's patches of the small intestine.
- Rare complications: pancreatitis, hepatic and splenic abscesses, endocarditis, pericarditis, orchitis, hepatitis, meningitis, nephritis, myocarditis, pneumonia, arthritis, osteomyelitis, and parotitis.
- Relapse rate~10% in immunocompetent hosts (with complete Rx).
- Chronic carriers:1 to 5% & is higher among women and among persons with gallstones, Ca-gallbladder & GI malignancies.
DIAGNOSIS
- TLC – N or ↓ed, rarely ↑.
- "Gold standard" is-culture positive for S. typhi or S. paratyphi --
- 1st week : blood culture, 2nd week bone marrow culture, 3rd week stool culture.
- Other Cultures : urine, rose spots, gastric/intestinal secretions (by a noninvasive duodenal string test)
- If blood, bone marrow, and intestinal secretions are all cultured, the yield of a positive culture is 90%
- Widal test : high rates of false-positivity and false-negativity
- TREATMENT
- 3rd gen CS: Ceftriaxone (1 to 2 g intravenously or intramuscularly) for 10 to 14 days; 5- to 7-day course of ceftriaxone +Cefixime 200BD for 7days
- Quinolones : Ciproflox – 500mg BD / Oflox – 200 -400mg BD for 10-14 days
- In cases of typhoid fever + alt. sensorium - Dexamethasone treatment should be considered
- Rx of Chronic carriers:Amox / Cotrimoxazole / Quinolone for 6 weeks (~80% effective). However, in cases of anatomic abnormality - requires surgical correction of the abnormalities.
PREVENTION AND CONTROL
- Good facilities for sewage disposal and water treatment
- Avoid uncooked food
- Consider vaccination
- Three vaccine are available:
- a heat-killed, phenol-extracted, whole-cell vaccine (two parenteral doses) - minimum age: 6 yrs
- Ty21a, L attenuated typhi vaccine (four oral doses); minimum age: 2 yrs
- ViCPS, consisting of purified Vi polysaccharide from the bacterial capsule (one parenteral dose) minimum age: 6 months
- All three vaccines have similar efficacy for the first year, the heat-killed whole-cell vaccine maintains its efficacy for 5 years, while Ty21a (4Yr) and ViCPS (2Yr).
- However, the whole-cell vaccine is associated with a much higher incidence of side effects than the other two vaccines