Enteric fever(typhoid fever)

Enteric fever

1. Enteric fever(Typhoid Fever) John Stephen

2. Area to be covered DEFINITION EPIDEMIOLOGY ETIOLOGY PATHOGENESIS CLINICAL FEATURE DIAGNOSIS COMPLICATION TREATMENT PREVENTION

3. Definition Typhoid fever is a systemic infectious disease, caused by bacteria Salmonella typhi, characterized by slowly progressive fever as high as 40 °C, malaise involvement of lymphoid tissues and spleen It is transmitted through the ingestion of food or drink contaminated by the faeces or urine of infected people. A similar but generally less severe illness known as paratyphoid is due to infection with S. paratyphi A, B or C. Man is the only natural host for S. typhi , which is transmitted in contaminated food or water. The incubation period is 10–14 days but can be longer.

4. Epidemiology Typhoid and paratyphoid fevers are endemic in our country as well as many parts of the world like South-East, Far East Asia, Central and South America and Middle East Africa.

5. Etiology The Enteric fevers are caused by bacteria of the genus Salmonellae i.e. Salmonella typhi causes typhoid in humans who are the only source and reservoir.

6. Pathogenesis All Salmonella infections begin with ingestion of organisms, most commonly in contaminated food or water. The infectious dose is 10 3 –10 6 colony-forming units. Conditions that decrease either stomach acidity (an age of <1 year, antacid ingestion, or achlorhydric disease) or intestinal integrity (inflammatory bowel disease, prior gastrointestinal surgery, or alteration of the intestinal flora antibiotic administration) increase susceptibility to Salmonella infection.

7. Once S. typhi and S. paratyphi reach the small intestine, they penetrate the mucus layer of the gut and traverse the intestinal layer through phagocytic microfold (M) cells that reside within Peyer’s patches. Salmonellae can trigger the formation of membrane ruffles in normally nonphagocytic epithelial cells. These ruffles reach out and enclose adherent bacteria within large vesicles by a process referred to as bacteria-mediated endocytosis (BME). BME is dependent on the direct delivery of Salmonella proteins into the cytoplasm of epithelial cells by a specialized bacterial secretion system ( type III secretion ). These bacterial proteins mediate alterations in the actin cytoskeleton that are required for Salmonella uptake.

8. After crossing the epithelial layer of the small intestine, S. typhi and S. paratyphi , which cause enteric (typhoid) fever, are phagocytosed by macrophages. These salmonellae survive the antimicrobial environment of the macrophage by sensing environmental signals that trigger alterations in regulatory systems of the phagocytosed bacteria. For example, PhoP / PhoQ (the best-characterized regulatory system) triggers the expression of outer-membrane proteins and mediates modifications in LPS so that the altered bacterial surface can resist microbicidal activities and potentially alter host cell signaling. In addition, salmonellae encode a second type III secretion system that directly delivers bacterial proteins across the phagosome membrane into the macrophage cytoplasm. This secretion system functions to remodel the Salmonella -containing vacuole, promoting bacterial survival and replication.

9. Once phagocytosed, typhoidal salmonellae disseminate throughout the body in macrophages via the lymphatics and colonize reticuloendothelial tissues (liver, spleen, lymph nodes, and bone marrow). Patients have relatively few or no signs and symptoms during this initial incubation stage. Signs and symptoms, including fever and abdominal pain, probably result from secretion of cytokines by macrophages and epithelial cells in response to bacterial products that are recognized by innate immune receptors when a critical number of organisms have replicated. Over time, the development of hepatosplenomegaly is likely to be related to the recruitment of mononuclear cells and the development of a specific acquired cell-mediated immune response to S. typhi colonization. The recruitment of additional mononuclear cells and lymphocytes to Peyer’s patches during the several weeks after initial colonization/ infection can result in marked enlargement and necrosis of the Peyer’s patches, which may be mediated by bacterial products that promote cell death as well as the inflammatory response.

10. Clinical features Fever that starts low and increase dairly , often to us high us 39.4 c or 40 Headache Weakness and fatigue Dry cough Loss of appetite Abdominal pain Diarrhea (22-28%) constipation (13–16%) hepatosplenomegaly, lymphadenopathy and a scanty maculopapular rash (‘rose spots’). Coated Tongue Epistaxis and relative bradycardia Neurological manifestation occurs in 2 to 40% these includes Meningitis,neuritis , Guillain Barre syndrome, Delirium and Coma

11. Diagnosis The gold standard of diagnosis is culture of blood, stool, urine or bone marrow aspirates. • Blood cultures may be positive during the first week and for a variable period after this. • Stool and urine cultures are positive after the first week • The Widal test becomes positive by the end of first week, and a rising titre shown by two tests performed 4-5 days apart may indicate active typhoid • The test has limited sensitivity (i.e. does not correctly detect most cases) and specificity (i.e. a negative test does not rule out infection in most cases) • Helpful laboratory test include:- o WBC count: low (leukopenia) with a relative lymphocytosis ( more common among children, during the first 10 days of illness, and in cases complicated by intestinal perforation or secondary infection) o Stool: in 100% of cases, occult blood is present in the stool • Exclude malaria then refer patient to hospital where the above investigations can be done to confirm the diagnosis

12. Complication Bowel perforation • intestinal Hemorrhage • Peritonitis • Cholecystitis • Hepatitis • Meningitis lobar pneumonia osteomyelitis Orchitis Glomerulonephritis, Pyelonephritis Pericarditis,myocarditis , endrocarditis Hemolytic Uremic Syndrome (HUS)

13. Treatment Pharmacological Treatment A: Ciprofloxacin (PO) 500mg 12 hourly for 10 days OR B: Azithromycin (PO) Adult 500mg 24hrly for 7 days Chloramphenicol, cotrimoxazole and amoxicillin may all still be effective in some cases, but quinolones (e.g. ciprofloxacin 500 mg twice daily) are now the treatment of choice, although increased resistance to these agents is being seen: in such cases azithromycin may be effective. The patient’s temperature may remain elevated for several days after starting antibiotics and this alone is not a sign of treatment failure.

14. Prevention General prevention is as for faeco -oral diseases: cook food thoroughly, boil water, and wash hands before preparing food, after preparing food and before eating. • It is important to identify carriers who work as food handlers as they are especially likely to transmit the infection (although searching for carriers is impracticable in endemic areas). • In some countries, vaccines are currently in use (VI capsular polysaccharide antigen vaccine and live attenuated oral vaccine). • It is not part of immunization program of Tanzania. • Early diagnosis and treatment of cases is important