Typhoid — Symptoms, Causes & Treatment | MyMedicPlus

Typhoid fever (enteric fever) is a systemic bacterial infection caused by Salmonella enterica serotype Typhi, transmitted via the fecal-oral route through consumption of contaminated food or water. It predominantly affects children and young adults in South and Southeast Asia, sub-Saharan Africa, and Latin America. Approximately 9 million cases and 110,000 deaths occur annually. Following ingestion, S. Typhi penetrates the intestinal mucosa, is taken up by macrophages in Peyer's patches, and enters the systemic circulation (bacteraemia), disseminating to the liver, spleen, gallbladder, and bone marrow. The gallbladder acts as a long-term reservoir — S. Typhi can persist and be shed chronically in bile, forming the basis of the 'chronic carrier' state (2-5% of cases, including the historical 'Typhoid Mary'). The global burden is concentrated in areas with inadequate sanitation and limited access to safe water: South Asia (70% of cases — India, Pakistan, Bangladesh), sub-Saharan Africa, and Southeast Asia. Children aged 2-15 are disproportionately affected. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains emerging from Pakistan since 2016 are a major global public health threat, with resistance to ampicillin, chloramphenicol, co-trimoxazole, fluoroquinolones, and third-generation cephalosporins, leaving azithromycin and carbapenems as key treatment options.

Typhoid is caused by ingestion of food or water contaminated with Salmonella enterica serotype Typhi — a human-specific pathogen with no animal reservoir (unlike non-typhoidal Salmonella). The infectious dose is 10,000 to 1,000,000 organisms. Risk factors: travel to endemic areas (especially the Indian subcontinent — India, Pakistan, Bangladesh account for 70% of global cases), consumption of street food, raw vegetables, or untreated water in endemic countries, poor sanitation infrastructure and open defaecation practices, household contact with a typhoid carrier (2-5% of infected individuals become chronic biliary carriers excreting S. Typhi in stool for more than 1 year — associated with gallstones and modestly increased risk of gallbladder carcinoma). Immunocompromise (HIV infection, sickle cell disease, or functional asplenia) substantially increases susceptibility and risk of invasive complications. Unlike most Salmonella serotypes, S. Typhi transmission is exclusively human-to-human via the faecal-oral route. Waterborne transmission from contaminated municipal water supplies is responsible for large community outbreaks. The 2016 XDR typhoid outbreak originating in Hyderabad, Pakistan, spread internationally through travellers and highlights the global threat of antimicrobial-resistant typhoid.

Incubation period is typically 7-14 days (range 3-60 days). Week 1: stepwise rising fever reaching 39-40°C by day 7, relative bradycardia (Faget's sign — the characteristic pulse-temperature dissociation where heart rate is inappropriately slow for the degree of fever, distinguishing typhoid from other bacterial infections), severe frontal headache, malaise, anorexia, dry cough, and constipation (more common than diarrhoea in adults in the early phase). Week 2: sustained high fever (plateau at 39-40°C), hepatosplenomegaly (70-80% of patients — tender, soft), rose spots (2-4 mm salmon-pink blanching macular papules on the trunk and upper abdomen, visible in 20-30% of fair-skinned patients but rarely seen in darker-skinned individuals; caused by bacterial emboli within dermal capillaries), abdominal distension and tenderness, and relative bradycardia. Week 3 in untreated disease ('typhoid state'): high sustained fever, extreme toxaemia, delirium and altered consciousness ('muttering delirium'), and 'pea soup' diarrhoea — intestinal complications (perforation and haemorrhage) peak during this week. Children and infants often present atypically with vomiting, diarrhoea, febrile seizures, and irritability rather than the classic stepladder fever pattern described in adults. Patients returning from endemic areas who develop a fever with frontal headache, constipation, and relative bradycardia should be investigated urgently for typhoid.

Blood culture: the gold standard for definitive diagnosis — sensitivity 40-80% in the first week (highest yield, when bacteraemia is most intense), falling to 20-30% after week 2 or once antibiotics are started. Collect at least 10 mL of blood into aerobic culture bottles. Results require 5-7 days of laboratory incubation. Bone marrow culture: 90% sensitivity even after 4-5 days of antibiotic treatment (bone marrow clears bacteraemia more slowly) — the test of choice when blood cultures are negative despite high clinical suspicion. Widal test (tube agglutination test detecting IgM/IgG antibodies to S. Typhi O and H antigens): widely used in resource-limited settings due to low cost, but has poor specificity (cross-reactivity with other Salmonella species, malaria, dengue, liver disease, and prior typhoid vaccination causing false positives) and poor sensitivity in early disease or partially treated cases — single Widal titres are not diagnostic and should not be used in isolation. NAAT/PCR from blood (targeting IS200 or fliC genes): higher sensitivity than blood culture with results in hours — available in reference laboratories and increasingly in high-burden endemic settings. Full blood count (CBC): leucopenia (WBC 3,000-5,000 cells/mm3) is a characteristic feature distinguishing typhoid from most bacterial infections that cause leucocytosis; relative lymphocytosis and eosinopenia are also typical; thrombocytopenia occurs in severe disease. Liver function tests: elevated transaminases (2-3x upper limit of normal — 'typhoid hepatitis') in 50% of patients. Stool and urine cultures: positive in later weeks, useful for detecting carriers. Susceptibility testing (antibiogram): essential given increasing MDR and XDR strains — nalidixic acid disk susceptibility predicts fluoroquinolone resistance.

Antibiotic therapy — choice guided by susceptibility testing: Azithromycin 1 g daily (500 mg/day in children 20 mg/kg/day) for 5-7 days: the preferred oral agent for uncomplicated typhoid, particularly drug-resistant (MDR/XDR) strains — excellent intracellular penetration, concentrated in macrophages where S. Typhi resides, clinical cure rates exceeding 90%, and very low rates of azithromycin resistance to date. Ciprofloxacin 500 mg twice daily for 7-10 days: effective only for confirmed fluoroquinolone-susceptible strains — fluoroquinolone resistance (detected by nalidixic acid disk susceptibility as surrogate marker) now exceeds 70% in strains from South Asia; use is not appropriate without susceptibility confirmation. Cefixime 15-20 mg/kg/day in two divided doses for 7-10 days: oral third-generation cephalosporin, effective for MDR (non-XDR) typhoid. Severe or complicated typhoid (hospitalised, toxic, unable to take orally): IV ceftriaxone 2-3 g daily (60 mg/kg/day in children) for 10-14 days — globally the most commonly used parenteral agent. IV meropenem or piperacillin-tazobactam: reserved for confirmed XDR typhoid requiring parenteral treatment. Chloramphenicol, ampicillin, and co-trimoxazole: now largely ineffective due to plasmid-mediated resistance widespread since the 1990s. Adjunctive dexamethasone: 3 mg/kg IV loading dose then 1 mg/kg every 6 hours for 48 hours — improves survival in severe typhoid with neurological manifestations or shock (NEJM landmark trial). Supportive care: paracetamol for fever control (avoid NSAIDs — risk of gastrointestinal haemorrhage), oral rehydration therapy or IV fluids (Ringer's lactate), nutritional support, and careful monitoring for complications. Intestinal perforation: emergency surgical management — laparotomy, bowel repair or resection, peritoneal lavage, and parenteral antibiotics (ceftriaxone plus metronidazole); 30-40% mortality even with prompt surgery in resource-limited settings. Chronic carriage: ciprofloxacin 750 mg twice daily for 28 days eradicates carriage in approximately 80% of cases; cholecystectomy if gallstones are present and antibiotics fail.

Intestinal perforation (1-3% — the most feared complication; S. Typhi ulcerates Peyer's patches in the terminal ileum, causing sudden severe abdominal pain, board-like abdominal rigidity, and shock; requires emergency laparotomy with bowel repair or resection and peritoneal lavage; 30-40% mortality even with prompt surgery in resource-limited settings). Gastrointestinal haemorrhage (3-5% — from necrosis of ileal lymphoid tissue; management is supportive with blood transfusion; surgical haemostasis is rarely required). Typhoid encephalopathy (confusion, agitation, obtundation, or coma — occurs in 2-40% of severe disease, particularly in malnourished patients and young children; responds to adjunctive dexamethasone in severe cases). Myocarditis (ECG changes, arrhythmias — rarely haemodynamically significant), pneumonia (2-3%), hepatitis (transaminase elevation in up to 50% — usually mild and self-limiting; fulminant hepatic failure is rare), and cholecystitis. Chronic carrier state (2-5% — persistent biliary excretion of S. Typhi for more than 1 year after apparent clinical recovery; associated with gallstones acting as a bacterial nidus; carriers have an increased lifetime risk of gallbladder carcinoma; ciprofloxacin 750 mg twice daily for 28 days eradicates carriage in approximately 80% of cases). Disease relapse (5-10% — occurs 1-3 weeks after completing apparently successful antibiotic therapy; typically milder than the primary illness but requires repeat microbiological confirmation and further antibiotic treatment).

Typhoid conjugate vaccine (TCV — Typbar-TCV): WHO's preferred vaccine, recommended for routine childhood immunisation in all endemic countries; a single dose is effective from age 6 months; TCV (Vi polysaccharide conjugated to tetanus toxoid carrier protein) elicits T-cell mediated immunological memory providing sustained long-term protection superior to unconjugated vaccines; WHO-estimated efficacy 80-90% against culture-confirmed typhoid in endemic settings. Vi polysaccharide vaccine (ViCPS — Typhim Vi): for international travellers aged 2 years and above; generates antibody response only without immunological memory; requires booster dose every 2-3 years; 50-80% efficacy. Oral live attenuated Ty21a vaccine (Vivotif): 4 enteric-coated capsules taken on alternate days (days 1, 3, 5, 7); for travellers aged above 6 years; must not be taken concurrently with antibiotics; requires refrigeration; 50-70% efficacy for 3-5 years. Food and water safety in endemic areas: cook all food thoroughly to above 70°C; avoid raw vegetables, salads, and street food; drink only bottled, boiled, or iodine/chlorine-treated water; use bottled water for brushing teeth; peel all fruits; avoid ice in drinks; wash hands with soap before handling food and after toilet use. Treatment of chronic carriers (ciprofloxacin 750 mg twice daily for 28 days) eradicates carriage in approximately 80% and reduces ongoing community transmission; cholecystectomy for carriers with associated gallstones who fail or cannot tolerate antibiotic eradication.

Seek emergency care immediately (999/911) for: signs of intestinal perforation from typhoid — sudden severe abdominal pain with a rigid board-like abdomen, high fever, and signs of shock (pale, clammy, rapid pulse, low BP) — a surgical emergency with high mortality; or severe typhoid encephalopathy (altered consciousness, extreme confusion, seizures). See a doctor urgently within 24 hours for: return from a high-risk destination (Indian subcontinent, Bangladesh, Southeast Asia, sub-Saharan Africa) with fever persisting more than 3-4 days, even if vaccinated (typhoid vaccination is only 50-80% effective); 'stepladder' fever pattern with relative bradycardia, frontal headache, and constipation; or diarrhoea with high fever following international travel. Typhoid must be confirmed by blood culture before starting antibiotics — antibiotic resistance (particularly to fluoroquinolones and third-generation cephalosporins) is increasing from the Indian subcontinent; susceptibility testing guides definitive therapy. Vaccination before travel to endemic areas significantly reduces risk — discuss with a travel health clinic or GP at least 4 weeks before departure.