Typhoid fever is a systemic bacterial infection caused by Salmonella enterica serovar Typhi, transmitted through food or water contaminated with the feces of an infected person or chronic carrier. WHO estimates 9-13 million cases and 110,000-160,000 deaths globally each year, with South Asia carrying over 70% of the burden.
Typhoid fever (ICD-10: A01.0) is an acute systemic illness caused by the human-restricted gram-negative bacillus Salmonella enterica serovar Typhi, transmitted via the fecal-oral route through contaminated food and water. The bacterium is ingested, survives gastric acidity, invades small intestinal Peyer patches via M cells, and is taken up by macrophages within which it replicates and disseminates through the reticuloendothelial system to the liver, spleen, bone marrow, and gallbladder. After an incubation of 7-21 days (typically 8-14), illness begins with a stepwise daily rise in fever (Wunderlich pattern), followed by sustained fever with relative bradycardia, hepatosplenomegaly, rose spots, and absolute eosinopenia. Without treatment, complications emerge in week 3 — intestinal perforation, intestinal hemorrhage, encephalopathy ("typhoid state"), myocarditis, and shock — and mortality reaches 10-30%.
The key symptoms of Typhoid Fever are: Stepwise rising fever each day during the first week, eventually reaching 39-40°C, with daily afternoon spikes and minimal morning relief., Relative bradycardia (pulse-temperature dissociation) — the heart rate is lower than expected for the fever (a 1°C rise typically raises pulse 10 bpm; in typhoid, the rise is half that)., Severe headache, particularly frontal, and generalized malaise from the first day of fever., Abdominal pain and tenderness, sometimes diffuse, sometimes localized to the right lower quadrant, in week 2-3., Constipation early (more common in adults) or diarrhea later (more common in children) — both can occur, classically described as "pea-soup" stool., Hepatosplenomegaly developing in week 2 — palpable in 30-60% of cases., Rose spots — sparse 2-4 mm pink, blanching macules on the trunk in week 2, present in 30% of light-skinned patients and harder to see on darker skin..
Diagnosis combines clinical suspicion based on travel and exposure history with microbiologic confirmation. Blood culture is the gold standard during the first week of illness, with sensitivity 70-90% in the first week, falling to 30-40% by week 3. Bone marrow culture (sensitivity 90-95%) outperforms blood culture, especially in patients who have received antibiotics, but is invasive and reserved for diagnostic difficulty. Stool and urine cultures are positive in 30-50% of cases, more often in week 2-4. Multiple cultures (3+ samples) increase yield. Serologic tests (Widal test) have limited sensitivity and specificity, particularly in endemic regions where baseline titers are elevated; the WHO no longer recommends Widal as the primary diagnostic test, although it remains in use in many countries due to cost. Rapid diagnostic tests (Typhidot, Tubex) detect IgM antibodies and provide faster results but have variable sensitivity. Newer LAMP and PCR-based assays are emerging in research settings. Complete blood count typically shows leukopenia or normal WBC with absolute eosinopenia (a useful clue when present), normocytic anemia, and thrombocytopenia. C-reactive protein and ferritin are elevated. Transaminases are mildly raised. Differential diagnoses include malaria (always test in returned travelers), dengue, rickettsial infections, leptospirosis, viral hepatitis, miliary tuberculosis, brucellosis, amoebic liver abscess, and infectious mononucleosis. Any returned traveler with fever for more than 5 days warrants blood cultures and travel-targeted differential workup. Public health reporting is mandatory in all US states because of carrier state and outbreak implications. Susceptibility testing is essential — empiric therapy must reflect local resistance patterns, with MDR and XDR strains requiring azithromycin or carbapenem coverage.
With appropriate antibiotic therapy, mortality is under 1% in healthy adults and 1-3% in children. Untreated typhoid carries 10-30% mortality, almost all from week-3 complications: intestinal perforation, hemorrhage, encephalopathy, and shock. Defervescence typically occurs within 3-5 days of effective antibiotics; persistent fever beyond 7 days suggests resistance, complication, or alternative diagnosis. Relapse occurs in 5-15% of cases within 1-3 weeks of initial cure, more common after short antibiotic courses and with chloramphenicol historically. Chronic carrier state develops in 1-5% of treated patients, more common in women, older adults, and patients with cholelithiasis (~25% carrier rate in this subset). Carriers shed S. Typhi for over a year and remain a source of community transmission. Intestinal perforation carries 10-40% mortality in resource-limited settings, falling to 5-15% in centers experienced with prompt surgical management. Long-term sequelae are rare after uncomplicated disease. The dominant prognostic factors are time from symptom onset to effective antibiotics, presence of complications at presentation, age, comorbidities, and whether the strain is susceptible to first-line empiric therapy. The introduction of typhoid conjugate vaccines (Typbar TCV) in endemic countries has shown 80-90% efficacy in trials and is expected to reduce population-level mortality substantially.
Infectious disease consultation is recommended for any confirmed typhoid case in a non-endemic country, suspected MDR or XDR infection, severe or complicated disease, treatment failure, chronic carrier management, and pregnancy. In endemic countries, primary care and pediatrics manage most uncomplicated cases; surgical and ID input is added for complications.
Find specialists →Fever defervesces within 3-5 days of effective antibiotic therapy. Appetite returns over 7-14 days. Hepatosplenomegaly resolves over 2-4 weeks. Full energy returns over 4-6 weeks. Stool shedding continues for an average of 6-8 weeks in treated cases; chronic carriers shed for over a year. Follow-up stool cultures at 4-6 weeks document clearance for food handlers and healthcare workers. Relapse, if it occurs, peaks 1-3 weeks after antibiotic completion and warrants repeat blood cultures.
Strict bed rest during the febrile phase. Gradually return to normal activity over 2-4 weeks after defervescence. Avoid heavy lifting and strenuous exercise for 4 weeks because of perforation risk in the inflamed terminal ileum.
Choose a clinician with current knowledge of regional resistance patterns and access to blood culture and susceptibility testing. In travel medicine, a specialist familiar with the CDC Yellow Book and WHO travel advisories provides optimal pre-travel vaccination and post-travel evaluation. Endemic-area patients benefit from continuity care that can address chronic carrier evaluation if recurrence occurs.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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