Typhoid
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"typhoid fever"[MeSH Terms] AND treatment
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Typhoid Fever (Enteric Fever)
Causative Organism
Typhoid fever is caused by Salmonella enterica serotype Typhi (S. typhi). A clinically similar illness, paratyphoid fever, is caused by S. paratyphi A, B, and C, as well as occasionally S. Typhimurium. Together they are referred to as enteric fever.
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Humans are the sole natural reservoir for S. typhi and S. paratyphi
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The disease affects up to 30 million individuals worldwide annually
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Children and adolescents are most affected in endemic areas; S. paratyphi predominates in travelers to lower-resource countries
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Robbins & Kumar Basic Pathology, p. 529
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Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 2197
Transmission & Pathogenesis
Transmission is fecal-oral - contaminated food or water, or contact with carriers. Dose-related: higher inoculum = more severe disease. Incubation: 1-3 weeks.
Pathogenesis steps:
- Ingested organisms reach the small intestine
- S. typhi is taken up by M cells overlying Peyer's patches in the terminal ileum
- Engulfed by mononuclear cells in underlying lymphoid tissue
- Peyer's patches enlarge into plateau-like elevations up to 8 cm; mucosal shedding creates oval ulcers oriented along the long axis of the ileum
- S. typhi (unlike non-typhoidal Salmonella) disseminates via lymphatic and blood vessels
- Causes reactive hyperplasia of draining lymph nodes with bacteria-containing phagocytes
- Red pulp of the spleen expands due to phagocyte hyperplasia
- Typhoid nodules - small foci of parenchymal necrosis with macrophage aggregates - appear in the liver, bone marrow, and lymph nodes
- Gallbladder colonization may occur, especially with gallstones, leading to a chronic carrier state
- Robbins & Kumar Basic Pathology, pp. 529-531
Clinical Features
Classic Presentation
| Week | Features |
|---|---|
| Week 1 | Fever (stepwise rise), headache, malaise, dry cough, relative bradycardia |
| Week 2 | High sustained fever, abdominal distension/pain, splenomegaly, rose spots |
| Week 3 | Complications possible - perforation, haemorrhage, encephalopathy |
| Week 4 | Gradual defervescence (untreated) |
Key clinical signs:
- Relative bradycardia (Faget sign) - pulse-temperature dissociation; classic but may be absent
- Rose spots - pale red (salmon-colored) maculopapular rash on trunk; seen mainly in fair-skinned patients
- Splenomegaly - develops with disease progression
- Constipation in ~30% (diarrhea is actually less common acutely)
- Leukopenia and elevated liver enzymes
Complications
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GI: Small bowel perforation (life-threatening), haemorrhage
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Neurological: Encephalopathy, meningitis, psychosis, ataxia, seizures, deafness
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Cardiovascular: Myocarditis, mycotic aneurysm
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Others: Disseminated intravascular coagulation (DIC), pneumonia, septic arthritis, cholecystitis, renal failure
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Untreated mortality: 10-20%, mostly in young children
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Tintinalli's Emergency Medicine, p. 3383
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Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 2197
Diagnosis
| Method | Notes |
|---|---|
| Blood culture | Most practical; positive in ~90% during febrile phase (first week) |
| Bone marrow culture | Most sensitive (gold standard); remains positive even after antibiotic treatment |
| Stool/urine culture | Best in 2nd week of illness |
| Widal test | Measures agglutinating antibodies; unreliable due to cross-reactions and low specificity |
| Rapid antigen testing | Available; useful in resource-limited settings |
- Tintinalli's Emergency Medicine, p. 3385
Treatment
Antibiotic Therapy
| Setting | First-line | Alternative |
|---|---|---|
| Uncomplicated (susceptible strains) | Ciprofloxacin 500 mg BD × 7-10 days OR Ofloxacin 400 mg BD × 7-10 days | Ceftriaxone 2 g IV daily × 10-14 days |
| Fluoroquinolone resistance (S/SE Asia) | Ceftriaxone 2 g IV daily × 10-14 days | Azithromycin 1 g daily × 5 days |
| Chloramphenicol, ampicillin, TMP-SMX | Unreliable due to widespread resistance | - |
Important: Fluoroquinolone resistance is increasing globally, particularly in travelers returning from South and Southeast Asia, associated with nalidixic acid-resistant strains. A 2026 systematic review on AMR in India (PMID 41990105) confirms escalating antimicrobial resistance in S. Typhi isolates.
Severe Disease
- Add dexamethasone for typhoid meningitis/encephalitis or septic shock
- IV fluid resuscitation
- Blood transfusion if significant GI losses
Surgical
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Bowel perforation requires emergency surgery (peritoneal lavage + closure/resection)
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Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 2197
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Tintinalli's Emergency Medicine, p. 3387
Vaccination
Two vaccines are available:
| Vaccine | Type | Age | Schedule | Efficacy | Booster |
|---|---|---|---|---|---|
| Ty21a (Vivotif) | Live attenuated oral | ≥6 years | 1 capsule every other day × 4 doses | ~50% at 2.5-3 years | Every 5 years |
| ViCPS (Typhim Vi) | Capsular polysaccharide injectable | ≥2 years | Single IM dose | ~55% at 2.5-3 years | Every 2 years |
| Typhoid conjugate vaccine (TCV) | Vi-conjugated | ≥6 months | Single IM dose | Higher, more durable | - |
Important points:
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Vaccines do NOT protect against S. paratyphi
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Food and water precautions remain essential even in vaccinated travelers
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Ty21a must be taken 1 week before travel; avoid antibiotics during course
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A recent 2025 meta-analysis (PMID 41125003) confirms real-world effectiveness of typhoid conjugate vaccines in children and adolescents
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Goldman-Cecil Medicine, p. 1835-1837
Chronic Carrier State
- ~1-4% of patients become chronic carriers, excreting S. typhi in stool for >1 year
- Associated with gallbladder colonization and gallstones
- Treatment: prolonged ciprofloxacin (4 weeks) ± cholecystectomy if gallstones present
Key Differentials
| Condition | Differentiating Feature |
|---|---|
| Malaria | Must be excluded first in any febrile traveler |
| Brucellosis | Animal exposure, undulant fever |
| Leptospirosis | Water/animal exposure, conjunctival suffusion, jaundice |
| Infectious mononucleosis | Pharyngitis, lymphadenopathy, heterophile antibodies |
| Viral hepatitis | Jaundice, liver function derangement |
Typhoid is commonly the cause of febrile illness lasting >10 days once malaria is excluded in a returning traveler.
Sources: Goldman-Cecil Medicine (International Ed.) | Sleisenger & Fordtran's GI and Liver Disease | Tintinalli's Emergency Medicine | Robbins & Kumar Basic Pathology
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