Typhoid (Enteric) Fever — Viva

Q1: Clinical recognition (2 min)

"A 25-year-old returns from Pakistan with a week of fever. What clinical features make you suspect typhoid?"

• Step-ladder fever: rises stepwise each day, with morning remissions, peaking week 2
• Relative bradycardia (Faget sign): pulse slower than the fever would predict
• Rose spots: blanching salmon-pink macules, 2–4 mm, on the trunk — bacterial (septic) emboli
• Coated 'typhoid tongue'; splenomegaly; dull frontal headache; constipation then 'pea-soup' diarrhoea
• Incubation 7–14 days; faecal–oral; only human reservoir; South Asia/Africa
• Confirm with blood culture (gold standard, first week)

Q2: Pathophysiology (2 min)

"Walk me through how Salmonella Typhi produces the fever and the week-3 complications."

• Ingestion (infective dose 10⁵–10⁹; lower with achlorhydria/PPIs); survives gastric acid via acid-tolerance response
• Invades through M cells overlying Peyer's patches of terminal ileum; taken up by macrophages
• Survives and replicates inside macrophages in a Salmonella-containing vacuole (SPI-1 / SPI-2 type III secretion systems); Vi capsular polysaccharide masks O antigen
• First bacteraemia (silent) → mesenteric nodes → portal/systemic blood → liver, spleen, marrow, gallbladder (reticuloendothelial seeding)
• Macrophages release IL-1, IL-6, TNF-α, IFN-γ → step-ladder fever
• Second (symptomatic) bacteraemia coincides with fever; gallbladder re-seeds the gut → Peyer's patch hypertrophy
• Weeks 3–4: Peyer's patches necrose and slough → ulceration → perforation/haemorrhage
• Cell-mediated immunity (Th1, IFN-γ, macrophage activation) governs recovery; humoral antibodies (anti-O, anti-H, anti-Vi) are diagnostic but not protective

Q3: Diagnosis (2 min)

"How would you confirm typhoid fever, and what is the role of the Widal test?"

• Blood culture: gold standard, first week, before antibiotics; ~60–90% sensitivity
• Bone marrow culture: most sensitive (~90%), remains positive after antibiotics
• Stool culture: positive week 2–3 and in chronic carriers (selenite F broth, MacConkey — non-lactose fermenter)
• Widal test: anti-O (IgM, acute) and anti-H; single titre is unreliable in endemic regions (false positives from prior exposure/vaccination/cross-reacting Gram-negatives); a four-fold rise between paired sera 10–14 days apart is supportive; cut-offs are population-specific (anti-O 1:80, anti-H 1:160 in India)
• Rapid IgM tests (Typhidot, Tubex): variable accuracy; never standalone
• FBC: leucopenia with relative lymphocytosis, eosinopenia, mild thrombocytopenia; LFTs mild transaminitis

Q4: Antibiotic resistance and XDR (3 min)

"What is XDR typhoid, and how do you treat uncomplicated and severe disease?"

• XDR S. Typhi: Pakistan-origin clone (first described 2016) resistant to ampicillin, chloramphenicol, co-trimoxazole, fluoroquinolones AND third-generation cephalosporins — susceptible essentially only to azithromycin and carbapenems
• Uncomplicated XDR: oral azithromycin 500–1000 mg once daily × 7 days
• Severe XDR (shock, perforation, obtundation): IV meropenem with azithromycin step-down once improving
• Always tailor to culture and susceptibility; review at 48–72 hours for clinical response
• For quinolone-susceptible strains: ciprofloxacin 500–750 mg BD or ofloxacin 400 mg BD × 7–10 days (but resistance is so common in South Asia that empiric ciprofloxacin is no longer appropriate there)
• For non-XDR quinolone-resistant: ceftriaxone 2–3 g IV OD or cefixime 200 mg BD PO × 7–14 days

Q5: Severe typhoid (2 min)

"Your patient has become delirious and hypotensive. What do you add?"

• Diagnosis: severe typhoid (toxic encephalopathy with shock); untreated mortality 30–50%
• Add the Hoffman dexamethasone regimen: 3 mg/kg IV loading over 30 min, then 1 mg/kg IV every 6 hours for 8 doses (24 h) — reduces mortality to ~10% (Hoffman et al., NEJM 1984)
• Plus: IV fluids (careful — myocarditis risk), oxygen, empirical IV ceftriaxone ± meropenem if XDR, ICU monitoring
• Watch for and treat intestinal perforation (rigid abdomen, free gas → surgery) and haemorrhage (melaena → transfuse)

Q6: Chronic carrier (2 min)

"A cook has had three positive stool cultures for S. Typhi over a year. How do you manage?"

• Diagnosis: chronic carrier (gallbladder colonisation, typically on gallstones; ~2–5% of cases, classically women >40)
• Prolonged ciprofloxacin 750 mg BD × 4–6 weeks (if susceptible) OR high-dose amoxicillin × 6 weeks
• Cholecystectomy if gallstones present (definitive cure; removes the biofilm nidus)
• Exclude from food-handling until three consecutive negative stool cultures
• The historical archetype: 'Typhoid Mary' Mallon — asymptomatic carrier who infected dozens as a cook