Enteric Fever (Typhoid Fever)

Definition

Etiology & Pathogenesis

• Causative organisms: S. Typhi and S. Paratyphi — humans are the only known reservoir
• Transmission: fecal-oral via contaminated food/water; rarely from chronic carriers, healthcare settings, or sexual contact
• Organism invades gut epithelium → penetrates Peyer's patches → lymphatic spread → systemic dissemination via mononuclear phagocytes

Epidemiology

• 9.2–21 million typhoid cases/year; 5 million paratyphoid cases; 110,000–280,000 deaths annually
• Highest burden: Indian subcontinent (India, Pakistan, Bangladesh, Nepal), Eastern Mediterranean, Africa — can exceed 1,000 cases/100,000 children in some urban areas
• Correlates with mixing of drinking water and sewage; more common in urban poor areas and young children/adolescents
• In developed nations, most cases are travel-associated (78%), particularly from Indian subcontinent

Estimated national typhoid fever incidence worldwide

Drug Resistance (Critical)

Clinical Course

Week-by-Week Progression

Key Physical Signs

• Rose spots: Faint salmon-colored, blanching maculopapular rash on trunk/chest; seen in ~30% (difficult to detect in dark-skinned patients)
• Relative bradycardia (pulse-temperature dissociation): up to 50%
• Hepatosplenomegaly: ~50% of patients
• Coated tongue: 51–56%

"Rose spots" — the rash of enteric fever due to S. Typhi or S. Paratyphi

Complications (~27% of hospitalized patients)

• GI bleeding (6%) and intestinal perforation (1%) — from necrosis of ileocecal Peyer's patches; life-threatening, require surgery
• Neurologic: meningitis, Guillain-Barré, neuritis, "muttering delirium" / coma vigil (2–40%)
• Hemophagocytic syndrome, DIC, pancreatitis, hepatitis, myocarditis, endocarditis, orchitis, pneumonia
• Relapse: 10% within 2–3 weeks of fever resolution
• Chronic carriage: 2–5% shed S. Typhi >1 year (more common in women, biliary disease); associated with increased gallbladder cancer risk

Diagnosis

• Gold standard: Culture isolation of S. Typhi / Paratyphi
  • Blood culture: positive in 40–80% (best in first 2 weeks)
  • Bone marrow culture: most sensitive (~90%), even after antibiotics started
  • Stool/urine culture: positive mainly in week 2–3
  • Rose spot biopsy culture also possible
• CBC: Leukopenia/neutropenia in 15–25%; leukocytosis may occur in children or with perforation
• Liver enzymes: Moderately elevated
• Widal test: Agglutination titers to O and H antigens — low specificity, poor positive predictive value; not recommended as sole test
• Rapid antigen tests: Various formats available, but none yet replace culture

Treatment

• Steroids (dexamethasone) + antibiotics for severe disease with altered consciousness/shock
• Surgical intervention for perforation

Prevention

• Safe water, sanitation, hand hygiene
• Vaccines:
  • Vi polysaccharide vaccine (ViCPS): IM, >2 years, ~55–72% effective
  • Ty21a (oral live attenuated): >6 years, 4-dose series
  • Typhoid Conjugate Vaccine (TCV): Vi antigen conjugated to tetanus toxoid; superior immunogenicity, approved from 6 months; 2025 Cochrane review confirms TCVs are highly effective and recommended for endemic regions (PMID: 40326553)
• Vaccines do not protect against S. Paratyphi

Chronic Carrier State

• 2–5% become chronic carriers (>1 year shedding)
• Organisms survive in gallbladder biofilms on gallstones
• Treatment: Prolonged antibiotic course (ciprofloxacin or ampicillin × 4–6 weeks); cholecystectomy may be needed
• Carriers are notifiable in most jurisdictions and excluded from food handling