Overview
Systemic bacterial infection caused by Salmonella Typhi, transmitted via contaminated food and water. A major travel health risk in South Asia with ~11 million cases annually.
Symptoms
Symptoms | Frequency | Severity | Onset |
|---|---|---|---|
| Fever | 99% | Moderate | Early |
| Headache | 80% | Mild | Early |
| Malaise | 75% | Mild | Early |
| Chills | 55% | Mild | Early |
| Fatigue | 65% | Mild | Early |
| Loss of appetite | 70% | Mild | Early |
| Myalgia | 60% | Mild | Early |
| Bradycardia | 40% | Mild | Peak |
| Hepatomegaly | 55% | Mild | Peak |
| High fever | 97% | Severe | Peak |
| Maculopapular rash | 20% | Mild | Peak |
| Splenomegaly | 40% | Mild | Peak |
| Abdominal pain | 50% | Mild | Peak |
| Bloating | 30% | Mild | Peak |
| Constipation | 35% | Mild | Peak |
| Dehydration | 30% | Moderate | Peak |
| Diarrhea | 40% | Mild | Peak |
| Nausea | 25% | Mild | Peak |
| Vomiting | 20% | Mild | Peak |
| Dark urine | 15% | Mild | Peak |
| Confusion | 15% | Severe | Late |
| Weight loss | 30% | Moderate | Late |
| Bloody stool | 4% | Severe | Late |
Transmission
Overview
Bacterial infection spread through contaminated food and water.
Overview
Typhoid fever is a life-threatening systemic infection caused by Salmonella enterica serovar Typhi, a gram-negative bacterium exclusive to humans. Transmission is fecal-oral — via contaminated water, food prepared by carriers, or direct contact. The bacterium invades intestinal epithelium, spreads to reticuloendothelial organs (liver, spleen, bone marrow, lymph nodes), and causes sustained bacteremia. Without treatment, case fatality is 10–30%; with appropriate antibiotics, <1%. Paratyphoid fever (S. Paratyphi A, B, C) causes a clinically similar but generally milder illness.
Emergency Signs
Seek emergency medical care immediately if:
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Sustained high fever (>39°C) not responding to antipyretics
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Sudden severe abdominal pain (possible intestinal perforation — surgical emergency)
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Bloody or black tarry stools (intestinal hemorrhage)
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Confusion, delirium, or altered consciousness
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Signs of shock: rapid pulse, low blood pressure, cold clammy skin
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Persistent vomiting with inability to maintain hydration
Detailed Symptoms
Most common signs and symptoms
Incubation: 6–30 days (typically 8–14). Classic presentation follows a stepwise pattern:
Week 1:
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Gradual onset of sustained fever rising in a "staircase" pattern to 39–40°C
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Frontal headache, malaise, and myalgia
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Relative bradycardia (pulse-temperature dissociation — Faget sign)
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Dry cough in ~30% of patients
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Constipation (more common than diarrhea in adults initially)
Week 2:
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Sustained high fever (40–41°C)
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Rose spots: faint salmon-colored maculopapular lesions on trunk (seen in 5–30%, more visible on light skin)
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Abdominal distension and tenderness
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Hepatosplenomegaly
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Diarrhea ("pea soup" stools) may develop
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Confusion or delirium in severe cases ("typhoid state")
Week 3 (untreated):
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Progressive weakness and weight loss
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Risk of intestinal hemorrhage or perforation peaks
-
Complications may become life-threatening
Week 4+: Gradual defervescence if patient survives. 1–5% become chronic carriers (gallbladder colonization).
Knowing the symptoms is the first step to a quick response.
Course of Disease
Typhoid fever can progress from mild to severe forms, potentially leading to intestinal perforation and death.
Diagnosis
How this disease is identified
Definitive diagnosis requires isolation of S. Typhi:
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Blood culture: Gold standard; positive in 40–80% during week 1 (sensitivity decreases with antibiotic use). Collect before antibiotics.
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Bone marrow culture: Most sensitive (80–95%); positive even after antibiotic exposure. Reserved for difficult cases.
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Stool/urine culture: Positive from week 2 onward; useful for carrier detection
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Widal test: Detects anti-O and anti-H agglutinins; widely available but poor sensitivity/specificity — NOT recommended as sole diagnostic
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Typhidot/TUBEX (IgM rapid tests): Sensitivity 60–85%; useful in resource-limited settings for presumptive diagnosis
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CBC: Leukopenia (not leukocytosis) is typical; thrombocytopenia in severe cases; elevated LFTs
Drug susceptibility testing is essential — multidrug-resistant (MDR) and extensively drug-resistant (XDR) typhoid is a growing global threat.
Treatment
Available treatment methods
Antibiotic therapy (definitive treatment):
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Uncomplicated (drug-susceptible): Fluoroquinolones — ciprofloxacin 500 mg BID × 7–14 days (first-line where susceptible); azithromycin 1 g day 1 then 500 mg × 5–7 days (WHO preferred for uncomplicated)
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MDR typhoid: Azithromycin or cephalosporins (ceftriaxone 2 g IV daily × 10–14 days)
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XDR typhoid (ceftriaxone-resistant): Azithromycin + carbapenems (meropenem); prevalent in Pakistan (Punjab/Sindh — ongoing XDR outbreak since 2016)
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Severe/complicated: Ceftriaxone 2 g IV daily + dexamethasone 3 mg/kg then 1 mg/kg q6h × 48h (reduces mortality in severe typhoid with delirium per Hoffman 1984 study)
Supportive care:
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Oral or IV rehydration
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Antipyretics (avoid aspirin — bleeding risk)
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Surgical consultation for suspected intestinal perforation
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Follow-up stool cultures to confirm clearance and detect carriers
Most cases are effectively treated with early diagnosis.
Prevention Details
How to protect yourself
Vaccination:
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Vi polysaccharide (injectable — Typhim Vi): Single IM dose ≥2 weeks before travel; ~55–72% efficacy; revaccinate every 3 years if ongoing exposure. Age ≥2 years.
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Ty21a (oral — Vivotif): 4 capsules on alternate days; ~50–67% efficacy; revaccinate every 5 years. Avoid with concurrent antibiotics/antimalarials (mefloquine). Requires refrigeration.
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Typhoid conjugate vaccine (TCV — Typbar-TCV): WHO-prequalified 2018; single dose from 6 months; ~82% efficacy (TyVAC trial). Recommended by WHO for routine immunization in endemic countries.
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Vaccination does NOT replace food/water precautions — efficacy is 50–80%, not absolute.
Food and water hygiene:
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"Boil it, cook it, peel it, or forget it"
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Avoid street food, raw salads, unpasteurized dairy, ice in drinks
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Drink bottled/boiled water; use water purification tablets as backup
Preparation is the best protection.
Travel Advice
Risk to travelers:
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Very high risk: India (especially subcontinental), Pakistan (XDR), Bangladesh, Nepal
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High risk: Indonesia, Philippines, Sub-Saharan Africa, Egypt
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Vaccinate before ALL travel to South Asia — even short business trips carry risk
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Typhoid vaccine provides only 50–80% protection — food/water hygiene is ESSENTIAL alongside vaccination
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Carry oral rehydration salts and consider azithromycin as standby treatment (pre-discuss with travel clinic)
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If visiting Pakistan: be aware of XDR typhoid — azithromycin is the only reliable oral option
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Travelers who develop sustained fever (>38°C for >3 days) after returning from South Asia should report travel history and request blood cultures
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Post-travel: seek medical evaluation for fever within 60 days of return from endemic areas
How common is it?
Statistics and geographic data
WHO estimates 11–21 million cases and 128,000–161,000 deaths annually (2019 GBD data). Highest incidence in South and Southeast Asia:
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South Asia: India, Pakistan, Bangladesh, Nepal — incidence >100/100,000 per year; XDR typhoid spreading in Pakistan since 2016
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Sub-Saharan Africa: Growing recognition of high burden; TCV introduction underway
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SE Asia: Indonesia, Philippines, Vietnam — moderate incidence
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Latin America: Declining due to improved sanitation but focal outbreaks persist
Travel-associated typhoid: ~500 cases/year in the US (70% from South Asia); ~300/year in UK. Attack rate in travelers to South Asia: 3–30 per 100,000 trips. India accounts for >60% of travel-associated typhoid globally. Antimicrobial resistance is the primary clinical challenge — XDR strains (resistant to chloramphenicol, ampicillin, co-trimoxazole, fluoroquinolones, AND ceftriaxone) now dominant in parts of Pakistan.
Risk Factors
Who is most at risk
Traveling to endemic areas, consuming contaminated food or water, poor hygiene practices.
Complications Details
Potential complications
Untreated typhoid has 10–30% case fatality. Major complications:
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Intestinal hemorrhage: Occurs in 1–4% during weeks 2–3
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presents as melena or frank hematochezia
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may cause hemorrhagic shock
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Intestinal perforation: 1–3% of cases
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typically ileal
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requires emergency surgery
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mortality 30–60% even with treatment
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Hepatitis/hepatic abscess: Elevated transaminases in ~50%
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frank hepatitis in 5%
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Myocarditis: Rare but potentially fatal
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presents as tachycardia, hypotension, ECG changes
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Encephalopathy (typhoid psychosis): Delirium, confusion, obtundation
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associated with high mortality
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Osteomyelitis: More common in sickle cell disease patients
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Chronic carriage: 1–5% excrete S. Typhi for >1 year (gallbladder colonization)
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major public health concern — treatable with prolonged antibiotics ± cholecystectomy
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Relapse: 5–20% of treated patients relapse 2–3 weeks after defervescence
Recovery & Outlook
Expected outcomes and recovery
Prognosis is good with appropriate antibiotic treatment. Untreated cases can be fatal.
