Typhoid Fever (Salmonella Typhi)

Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi, an exclusively human pathogen with no animal reservoir. Transmission occurs via the fecal-oral route through ingestion of contaminated food, water, or fomites, with chronic asymptomatic carriers (especially in gallbladder—Mary Mallon 'Typhoid Mary' phenomenon) serving as important reservoirs. The infectious dose ranges from 10⁵ to 10⁹ organisms; gastric acid is a key barrier (low pH protective).

Pathogenesis involves bacterial invasion through M cells overlying Peyer's patches in distal ileum, intracellular survival within macrophages, dissemination via mesenteric lymph nodes to liver, spleen, gallbladder, and bone marrow, with secondary bacteremia leading to systemic symptoms. Incubation period is typically 7-14 days. Classic clinical course progresses through four weeks: first week (rising stepwise fever, headache, malaise, abdominal pain, constipation), second week (sustained high fever, relative bradycardia, rose spots in 30%, hepatosplenomegaly), third week (peak severity with potential intestinal perforation, encephalopathy, intestinal hemorrhage), fourth week (resolution or convalescence).

Diagnosis: blood culture is most sensitive in first week (60-80%), bone marrow culture is gold standard (>95% sensitivity even after antibiotics), stool/urine culture more useful in later weeks. Widal test has limited utility due to cross-reactivity. Treatment: ceftriaxone 2 g IV daily × 10-14 days, azithromycin 1 g daily × 5-7 days, or fluoroquinolones (where susceptible)—but resistance is common. XDR S. Typhi (resistant to chloramphenicol, ampicillin, TMP-SMX, fluoroquinolones, and third-generation cephalosporins) requires meropenem or azithromycin. Complications: intestinal perforation (1-3%, surgical emergency), GI bleeding, typhoid encephalopathy, myocarditis, hepatitis, chronic carriage (1-5%, requires prolonged antibiotics or cholecystectomy if gallstones). Vaccines: Ty21a (oral live attenuated, 4 doses, 5-year duration) and Vi capsular polysaccharide (single injection, 2-3 year duration) and newer Vi-conjugate (TCV) for children >6 months, longer duration.