Typhoid Fever — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Typhoid fever (enteric fever) is a systemic bacterial illness caused by Salmonella enterica serotype Typhi (S. Typhi) — a gram-negative bacillus spread exclusively via the faecal-oral route through contaminated food and water. Paratyphoid fever (caused by S. Paratyphi A, B, or C) is clinically similar but generally milder. The WHO estimates 9-11 million typhoid cases annually worldwide, causing approximately 110,000 deaths. The global burden is concentrated in low- and middle-income countries with inadequate water sanitation and sewage infrastructure — approximately 80% of the world's typhoid burden occurs in South Asia (particularly India, Pakistan, Bangladesh, and Nepal). S. Typhi is uniquely adapted to humans — there is no animal reservoir. Following ingestion, the bacteria penetrate the intestinal epithelium, survive intracellularly in macrophages, spread via lymphatics to the systemic circulation (bacteraemia), and seed the liver, spleen, gallbladder, and bone marrow. The gallbladder is an important site of persistent carriage — chronic carriers (3-5% of those infected) excrete S. Typhi in faeces for over 12 months after acute illness and represent the most important reservoir for ongoing transmission. The emergence of extensively drug-resistant (XDR) typhoid — first documented in Pakistan in 2018 and now spreading — resistant to fluoroquinolones, third-generation cephalosporins, and chloramphenicol poses a serious global health threat.

Typhoid is caused exclusively by Salmonella Typhi (paratyphoid by S. Paratyphi) transmitted via the faecal-oral route — there is no animal reservoir. Transmission routes: contaminated water (most common in endemic areas — sewage contamination of drinking water supplies); contaminated food (raw fruits and vegetables washed in contaminated water; street food; shellfish and seafood from contaminated waters); and direct faecal-oral transmission (poor hand hygiene after using the toilet — person-to-person spread, particularly in overcrowded conditions). Risk factors: travel to endemic regions (South Asia — particularly India, Pakistan, Bangladesh — sub-Saharan Africa, Latin America) — typhoid is a major travel-related infection; consumption of potentially unsafe food and water (ice, raw salads, street food, undercooked shellfish); absence of typhoid vaccination; children aged 5-15 years (highest disease burden in endemic countries); household contact with a known typhoid case or chronic carrier; immunocompromise (HIV, sickle cell disease — increased severity); and achlorhydria (reduced gastric acid — medications such as PPIs or antacids increase susceptibility by reducing gastric acid barrier). The infective dose is low — as few as 100 organisms can cause infection in a susceptible host. Chronic carriers (typically middle-aged women with gallstones who harbour S. Typhi in the gallbladder) are asymptomatic but an important transmission source.

Typhoid has a characteristic stepwise clinical progression over 3-4 weeks if untreated, with an incubation period of 6-30 days (typically 10-14 days). Week 1 — Bacteraemic phase: insidious onset of fever (classically rising in a stepwise 'staircase' pattern each day, peaking at 39-40°C by end of week 1); headache; malaise; myalgia; relative bradycardia (pulse rate not rising proportionately with temperature — Faget sign); dry cough; constipation (more common than diarrhoea in week 1); and abdominal discomfort. Week 2 — Toxic phase: sustained high fever; 'typhoid tongue' (coated centre, red tip and edges); rose spots (2-4 mm salmon-coloured macules on abdomen and chest — appear in 20-30% of patients, more visible in pale-skinned individuals; they blanch on pressure; last 2-3 days); hepatosplenomegaly (palpable in 50%); abdominal distension; and in severe cases, delirium, stupor, and meningism. Weeks 3-4 — Complications or resolution: complications may develop — intestinal haemorrhage (haematochezia, melaena — occurs in 1-5%; complicates the second week as Peyer's patches ulcerate and erode into blood vessels) and intestinal perforation (the most feared complication — peritonitis from Peyer's patch necrosis — occurs in 1-3%; sudden severe abdominal pain, peritonism, and collapse; requires emergency surgery — carries 30-50% mortality if managed conservatively only). Other complications: typhoid encephalopathy ('typhoid state' — obtundation, coma — high mortality), myocarditis, hepatitis, cholecystitis, and haemolytic anaemia (in G6PD deficiency).

Definitive diagnosis requires bacterial isolation (culture), as clinical features overlap with many other febrile illnesses. Blood culture: the gold standard — positive in 60-80% of cases in week 1-2; sensitivity declines with antibiotic use; bone marrow culture is the most sensitive (90%+) and remains positive even after antibiotics, but is invasive. Stool and urine culture: stool culture positivity increases in weeks 2-4 (as intestinal shedding peaks); urine culture positive in approximately 25% in week 3. Bone marrow culture: 90%+ sensitivity — indicated for culture-negative suspected typhoid who has already received antibiotics. Serology (Widal test): widely used in resource-limited settings — measures agglutinating antibodies against S. Typhi O (somatic) and H (flagellar) antigens. Significant titre is generally 1:160 or more for O antigen; however, specificity is poor (cross-reactivity with other Salmonella, malaria, Dengue) and sensitivity is 64-74%. Must be interpreted with local baseline titres. Not recommended as the sole diagnostic test. Typhoid-specific rapid diagnostic tests (Typhidot, TUBEX): detect IgM antibodies to specific S. Typhi antigens — better specificity than Widal in acute illness; sensitivity approximately 70-80%. Full blood count: typically shows leucopaenia (low WBC — contrary to what most bacterial infections cause; WBC below 4 x 10^9/L is a supportive but not diagnostic finding in typhoid); mild anaemia; elevated ESR; elevated liver enzymes (ALT/AST — in 70% — hepatitis); thrombocytopaenia in severe cases. Chest X-ray if perforation or pneumonia suspected.

Antibiotic treatment is the cornerstone of typhoid management — choice depends on susceptibility patterns which vary significantly by region. Ceftriaxone IV (1-2g once daily for 10-14 days) is the preferred first-line treatment for severe or hospitalised typhoid and in regions with high fluoroquinolone resistance (South Asia — all S. Typhi from Pakistan should be assumed XDR until proven otherwise). Azithromycin oral (500-1000mg daily for 5-7 days) is effective for uncomplicated typhoid from most regions, with good bioavailability, low resistance, and safety in pregnancy; it is now the preferred oral option for travel-associated uncomplicated typhoid in most guidelines. Ciprofloxacin: historically first-line but now limited due to widespread resistance, particularly in South Asia where nalidixic acid resistance (a surrogate marker) is near-universal and clinical failures with ciprofloxacin are common — use only if in vitro sensitivity is confirmed. XDR typhoid (resistant to fluoroquinolones, ampicillin, chloramphenicol, trimethoprim, and third-generation cephalosporins — defined by the Pakistan 2018 clone): only carbapenems (meropenem) and azithromycin retain activity — meropenem 1g TDS IV for 7-14 days. Dexamethasone: IV high-dose corticosteroids (3 mg/kg over 30 minutes, then 1 mg/kg every 6 hours for 8 doses) are indicated for severe typhoid with delirium, obtundation, stupor, coma, or shock — reduces mortality from 55% to 10% in this group. Surgical: intestinal perforation requires emergency laparotomy with primary repair or resection and anastomosis plus broad-spectrum antibiotics covering gram-negatives and anaerobes. Chronic carriers: prolonged oral ciprofloxacin or norfloxacin (4 weeks) clears carriage in 80% of carriers without gallstones; cholecystectomy may be required for carriers with gallstones. Supportive: IV fluids for dehydration; paracetamol for fever (avoid NSAIDs); careful nutrition (soft diet); bed rest.

Intestinal complications are the most feared — occurring in weeks 2-3 of untreated typhoid fever when Peyer's patches in the terminal ileum undergo necrosis. Intestinal perforation occurs in 1-3% of hospitalised typhoid cases, causing sudden onset of diffuse peritonitis with severe abdominal pain, rigidity, and septic shock — surgical emergency with mortality of 10-32% even with surgery. Intestinal haemorrhage from ulceration occurs in approximately 10% of cases — presenting with melaena and haemodynamic compromise requiring transfusion. Typhoid encephalopathy (altered consciousness, confusion, and coma) occurs in severe cases and carries 50% mortality without treatment. Myocarditis and pericarditis complicate 1-5% of cases — arrhythmias and cardiac failure can develop suddenly. Typhoid hepatitis (elevated transaminases in 30-40% of cases) and rarely acute liver failure. Haemolytic anaemia, particularly in patients with G6PD deficiency treated with chloramphenicol. Septicaemic complications include pneumonia, meningitis, osteomyelitis, and metastatic abscesses from bacteraemia. The chronic carrier state develops in approximately 3% of patients (more common in women, elderly, and those with biliary disease) — Salmonella Typhi persists in the gallbladder, acting as a reservoir for community transmission. Multi-drug resistant (MDR) S. Typhi (resistant to ampicillin, chloramphenicol, and trimethoprim) and extensively drug-resistant (XDR) strains are emerging in South Asia, reducing treatment options to ceftriaxone or azithromycin.

Typhoid prevention relies on vaccination for travellers and at-risk populations, combined with improvements in water sanitation and food hygiene. Typhoid vaccines: Vi polysaccharide vaccine (Typherix, Typhim Vi — single IM injection; 50-80% protective efficacy for 2-3 years; licensed for those aged 2 years and above; boosters recommended every 3 years for ongoing exposure). Ty21a oral live attenuated vaccine (Vivotif — 3-4 doses on alternate days; 70% efficacy for 5-7 years; licensed for those aged 6 years and above; avoid antibiotics for 3 days around vaccination). Vi-conjugate typhoid vaccine (Typbar-TCV — single IM injection; 80-85% efficacy; licensed from 6 months; recommended by WHO for mass vaccination campaigns in endemic countries — introduced in national immunisation programmes in Pakistan, Zimbabwe, Nepal). WHO recommended travellers from non-endemic to endemic countries (South Asia, sub-Saharan Africa, Latin America) receive typhoid vaccination at least 2 weeks before travel. Safe food and water precautions for travellers: 'boil it, cook it, peel it, or forget it'; avoid ice in drinks; bottled water for drinking and brushing teeth; avoid street food and raw salads in endemic areas. WASH (Water, Sanitation, and Hygiene) improvements are the ultimate long-term solution. Hand hygiene — especially after using the toilet and before food handling — is the most effective simple preventive measure.

Seek immediate emergency medical care for: sudden severe abdominal pain and rigidity in a patient with known or suspected typhoid (possible intestinal perforation — a surgical emergency); high fever with confusion, delirium, extreme drowsiness, or loss of consciousness ('typhoid state' — requires IV antibiotics and dexamethasone urgently); rectal bleeding or black tarry stools in a febrile patient (intestinal haemorrhage complicating typhoid); and collapse or profound weakness with high fever. See a doctor urgently within 24-48 hours for: fever persisting for more than 5-7 days in a traveller recently returned from South Asia, sub-Saharan Africa, or Latin America — typhoid must be considered; fever with relative bradycardia and rose spots; and any febrile illness in a returned traveller that does not clearly improve. Tell your doctor you have recently travelled and exactly where — this is critical for prompt diagnosis of tropical infections including typhoid and malaria, which must be excluded in any febrile returned traveller. Inform your doctor if you have previously been diagnosed with typhoid and may be a chronic carrier — public health reporting and management of carriers is required.