Question
Pathogenesis and lab diagnosis of typhoid fever.
Answer
Pathogenesis Typhoid (enteric) fever is caused by Salmonella enterica serovar Typhi. Ingested bacilli survive gastric acidity and invade ileal mucosa via M cells overlying Peyer’s patches; taken up by macrophages, in which the facultative intracellular organism survives and multiplies, it spreads to mesenteric lymph nodes and then via the thoracic duct into blood (primary bacteraemia, usually asymptomatic). The organism seeds the reticuloendothelial system (liver, spleen, bone marrow, gallbladder), multiplies during the incubation period, and re-enters the blood (secondary bacteraemia), producing the clinical illness — sustained fever, relative bradycardia, coated tongue, and hepatosplenomegaly. Peyer’s patch hyperplasia can progress to necrosis and ulceration over the terminal ileum, risking haemorrhage/perforation; the gallbladder may harbour the organism chronically, producing the carrier state.
Laboratory diagnosis
- Blood culture — best yield in the first week (bacteraemic phase); bile broth is used to neutralise antibacterial serum activity.
- Bone marrow culture — most sensitive at any stage of illness, even after antibiotics have begun.
- Stool and urine culture — become positive from the second/third week as the organism localizes to the gut and gallbladder/kidney.
- Widal test — detects rising titres of O and H agglutinating antibody in paired (acute and convalescent) sera; limited by cross-reactions and background titres in endemic populations, so a single titre is only suggestive.
- Newer methods — Typhidot/IgM dot-EIA for rapid diagnosis, and PCR where available.