Paediatrics chapters
Typhoid fever in children
Enteric fever in children: Salmonella Typhi and Paratyphi, how it spreads, the week-by-week illness, complications such as perforation and bleeding, why blood culture beats the Widal test, drug resistance including XDR typhoid, carriers and vaccines.
- Typhoid is a systemic Salmonella Typhi infection spread by faecal-oral route through food and water; the organism invades Peyer's patches, enters the blood and seeds the liver, spleen, marrow and gallbladder.
- A child has prolonged high fever, headache, abdominal pain, a coated tongue, toxic look, soft splenomegaly and sometimes rose spots; infants may just have diarrhoea or sepsis; perforation and bleeding occur mostly after the second week.
- Blood culture (first week) and bone marrow culture (most sensitive) confirm it; the Widal test is unreliable; treat according to sensitivity, as MDR and XDR strains are common in Pakistan.
On this page
Overview
Typhoid (enteric) fever is a systemic bacterial infection caused by Salmonella Typhi (and, as paratyphoid, by S. Paratyphi A, B and C). It is one of the commonest causes of prolonged fever (PUO) in Pakistani children. It is spread by contaminated food and water, causes weeks of fever and toxicity, and can kill through intestinal perforation or haemorrhage. Rising antibiotic resistance, including extensively drug-resistant (XDR) strains, makes culture-guided treatment and prevention essential.
Aetiology
- Salmonella Typhi: a gram-negative bacillus; infects only humans.
- Paratyphoid fever: S. Paratyphi A, B (S. schottmuelleri) and C (S. hirschfeldii); usually milder.
- Three antigens:
| Antigen | Nature | Exam link |
|---|---|---|
| O | Somatic cell-wall lipopolysaccharide | Widal O titre; endotoxin causes fever |
| H | Flagellar | Widal H titre; reflects past infection or vaccination |
| Vi | Capsular polysaccharide (virulence) | Vi vaccine; Vi antibody in carriers |
- The organism survives drying and cooling, so it lasts in sewage, water, food and ice.
Epidemiology
- Faecal-oral spread: water, milk, food (including raw vegetables and undercooked eggs) contaminated by a case or a carrier.
- The usual source of a home-acquired case is a chronic carrier.
- A large inoculum is needed to cause disease (Akbar gives a range of thousands to millions of organisms).
- All ages and both sexes are affected; most cases are in school-age children and young adults. Akbar notes attack rates are high in under-5s.
- Occurs in all seasons. Previous infection gives only partial protection.
Pathogenesis
- Organisms that survive stomach acid enter the small intestine and penetrate the mucosa into the Peyer's patches of the terminal ileum and mesenteric nodes.
- They multiply inside macrophages and spread via lymphatics to the blood (primary bacteraemia), seeding the liver, spleen, bone marrow and gallbladder.
- After the incubation period, a secondary bacteraemia produces the illness. Endotoxin and cytokines cause the fever and toxicity.
- Bacteria multiply in the gallbladder and re-enter the gut in bile, so stool cultures turn positive later.
- Peyer's patches swell, necrose and ulcerate. These ulcers can bleed or perforate, usually in the third week.
- Cell-mediated immunity is the main defence.
Clinical features
Incubation: usually 7-14 days (range 3-30), shorter with a larger dose.
Week by week
| Week | Main features |
|---|---|
| 1st | Fever rising in a step-ladder pattern, chills, headache, malaise, anorexia, myalgia, abdominal pain, cough; constipation more often than diarrhoea in older children |
| 2nd | Sustained high fever, toxic, apathetic look, coated (furred) tongue, rose spots, soft splenomegaly and hepatomegaly, abdominal distension and tenderness, diarrhoea ("pea-soup") or constipation, delirium or stupor |
| 3rd | Complications: intestinal haemorrhage and perforation, shock, toxic encephalopathy |
| 4th and later | Slow recovery, weight loss; relapse, carrier state |
Key signs
- Rose spots: pink, slightly raised macules a few millimetres across, on the upper abdomen and lower chest, appearing in crops around days 7-10 in about 25%, blanching on pressure and fading in 2-3 days. They contain bacterial emboli and may grow Salmonella.
- Relative bradycardia (pulse slow for the fever): classic in adults but often absent in children.
- Soft, tender spleen palpable in the second week.
- Chest crackles may suggest pneumonia.
Age differences
- Infants: may present as mild gastroenteritis or severe sepsis: vomiting, diarrhoea, distension, high fever, febrile fits, jaundice, hepatosplenomegaly.
- Older children: the classic picture above.
Think of typhoid in any child with fever for more than a week, headache and abdominal symptoms, a toxic look and a soft spleen, especially if white cells are low.
Complications
Most complications occur after the second week, especially if treatment is late.
| Complication | Key facts |
|---|---|
| Intestinal perforation | Akbar 0.5-3%; usually the distal ileum; sudden abdominal pain, vomiting, peritonitis, absent bowel sounds, gas under the diaphragm on X-ray. Often comes after a few days of treatment when the child seems better. Nelson notes it is commoner in adults than children |
| Intestinal haemorrhage | Akbar 1-10%; a sudden fall in temperature and blood pressure with rising pulse, then melaena |
| Toxic encephalopathy | Delirium, coma, raised pressure, ataxia, chorea, psychosis, deafness, neuritis |
| Other | Myocarditis (arrhythmia, shock), hepatitis, cholecystitis, pneumonia, pyelonephritis, meningitis, osteomyelitis and septic arthritis (especially with sickle cell disease), bone marrow suppression |
| Relapse | Recurrence about 2 weeks after stopping antibiotics; usually milder |
| Chronic carriage | Excretion beyond 1 year |
A child improving on treatment who suddenly develops abdominal pain and a fall in temperature may have perforated or bled; it is not simply recovery.
Investigations
Culture: the gold standard
| Sample | Best time | Yield |
|---|---|---|
| Blood culture | First week (first 2 weeks) | Akbar 40-60%; falls later and after antibiotics |
| Bone marrow culture | Any stage, even after antibiotics | Most sensitive (85-90%), but invasive |
| Stool culture | From the second or third week | Also detects carriers |
| Urine culture | Later weeks | Lower yield |
"BASU": Blood (week 1), Antibodies/Widal (week 2), Stool (week 3), Urine (week 4); bone marrow at any time.
Widal test
- Measures agglutinating antibodies to O and H antigens. O antibodies appear around days 6-8, H around days 10-12 (Park).
- Akbar: an O titre above 1:160 is suggestive; a rising titre over 7-10 days helps more. H titres reflect past infection or vaccination.
- Unreliable: false positives in endemic areas (previous exposure, cross-reacting Salmonella and other gut bacteria, malaria) and false negatives (early disease, prior antibiotics; Park: up to 30% of culture-proven cases).
A single positive Widal in Pakistan does not prove typhoid, and a negative one does not exclude it. Blood culture is the investigation of choice.
Bone marrow culture is the most sensitive test and stays positive even after antibiotics have been started.
Other tests
- Rapid serological tests: Typhidot (IgM and IgG against a 50 kD S. Typhi antigen) and Tubex (IgM to O9) (Park).
- PCR for S. Typhi in blood: quick and sensitive (Akbar).
- Blood count: leucopenia despite high fever is typical, but young children often have leucocytosis; normocytic anaemia; thrombocytopenia.
- Raised liver enzymes; abdominal X-ray if perforation is suspected.
Differential diagnosis
Malaria, tuberculosis (including miliary), urinary infection, septicaemia, brucellosis, amoebic liver abscess, viral hepatitis, infectious mononucleosis, endocarditis, leukaemia and lymphoma.
Treatment
Principles
- Choose the antibiotic by culture and sensitivity and local resistance.
- Resistance in Pakistan:
| Type | Resistant to |
|---|---|
| MDR (multidrug-resistant) | The old first-line drugs: chloramphenicol, ampicillin/amoxicillin, co-trimoxazole |
| Quinolone-resistant | Fluoroquinolones (ciprofloxacin, ofloxacin) |
| XDR (extensively drug-resistant) | The MDR drugs plus fluoroquinolones and third-generation cephalosporins (ceftriaxone, cefixime); first reported from Sindh |
Antibiotic options (from Akbar's table)
| Situation | Drugs |
|---|---|
| Fully sensitive | Chloramphenicol, amoxicillin or a fluoroquinolone |
| MDR | Fluoroquinolone, cefixime or azithromycin; ceftriaxone or cefotaxime if severe |
| Quinolone-resistant | Azithromycin, cefixime, or ceftriaxone/cefotaxime if severe |
| Severe typhoid | IV ceftriaxone or cefotaxime; fluoroquinolone if sensitive |
- Most children become afebrile within about a week of effective treatment; total treatment is usually 10-14 days (shorter for azithromycin). Doses vary between sources; follow the current national guideline.
- Chloramphenicol clears the blood well but has high relapse rates and does not clear carriage.
- XDR typhoid: oral options are very limited (azithromycin is usually the remaining oral drug), and carbapenems are used for severe illness. This is not covered by the textbooks; treatment follows culture sensitivity and the current national guideline (see WHO typhoid, checked 8 Nov 2026).
Supportive care
- Fluids, electrolytes and nutrition; paracetamol and tepid sponging.
- Dexamethasone for severe toxaemia with shock or coma (Akbar: 3 mg/kg, then 1 mg/kg every 6 hours for 48 hours) improves survival.
- Blood transfusion for anaemia or major bleeding; platelets for bleeding with thrombocytopenia.
- Perforation: urgent surgery with broad-spectrum antibiotic cover.
Perforation needs surgery; antibiotics alone are not enough.
Carriers
- Convalescent carriers excrete for weeks to months; chronic carriers excrete for over 1 year.
- About 1-5% of patients become carriers; children are at low risk. Gallbladder disease (stones) predisposes; the gallbladder is the main reservoir.
- Carriers are the key source of new cases. Park describes treatment with prolonged ampicillin or amoxicillin with probenecid, and cholecystectomy with antibiotic cover in resistant cases. Vi antibody is found in most chronic carriers.
- Carriers must not handle food for others.
Prevention
- Safe drinking water, proper sewage disposal, fly control.
- Hand-washing after the toilet and before preparing food; cook food and eggs thoroughly; avoid keeping cooked food warm for long or reheating.
- Treat and supervise carriers.
Vaccines
| Vaccine | Key facts |
|---|---|
| Vi polysaccharide (injection) | From 2 years; one dose; protection from about a week; repeat every 3 years (Park) |
| Ty21a (oral, live) | Capsules on days 1, 3 and 5; licensed from 5 years (Park); avoid antibiotics around the doses |
| Typhoid conjugate vaccine (TCV) | Works from infancy; Pakistan has added it to routine immunisation and used it in XDR outbreak campaigns. Check the current schedule at EPI Pakistan (checked 8 Nov 2026) |
Akbar notes that the older vaccines protect only about 50-80% of recipients, so hygiene remains essential.
Prognosis
- Akbar puts mortality above 10% where diagnosis or treatment is delayed; Park gives about 1% with early treatment, higher in children under 4 years and in untreated cases.
- Relapse in about 7-10% (Akbar), usually milder.
Expect: S. Typhi as a gram-negative bacillus with O, H and Vi antigens; faecal-oral spread and carriers as the source; Peyer's patch ulceration; step-ladder fever, coated tongue, rose spots, soft spleen and relative bradycardia (often absent in children); blood culture in week 1 and bone marrow as most sensitive; limitations of the Widal test; leucopenia; perforation in the distal ileum in the third week, often after treatment starts; haemorrhage signs; dexamethasone in shock or coma; MDR and XDR resistance and choice of azithromycin, ceftriaxone or carbapenem; gallbladder carriage; Vi, Ty21a and conjugate vaccines.
Quick revision
- S. Typhi: gram-negative, humans only; O, H, Vi antigens.
- Faecal-oral; incubation 7-14 days; carriers are the source.
- Week 1 step-ladder fever; week 2 toxic, rose spots, spleen; week 3 complications.
- Blood culture first week; bone marrow most sensitive; stool later.
- Widal: unreliable alone; O over 1:160 or rising titre.
- Perforation: distal ileum, third week, surgery.
- MDR, quinolone-resistant and XDR strains: treat by culture; azithromycin, ceftriaxone, carbapenem per guideline.
- Vi vaccine from 2 years, Ty21a from 5 years, conjugate vaccine from infancy.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics; Park's Preventive and Social Medicine).
FAQ
Which single test is best for diagnosing typhoid in the first week?
Blood culture. Bone marrow culture is even more sensitive and stays positive after antibiotics, but it is invasive.
Why is the Widal test so often misleading?
Many people in endemic areas already have antibodies, other bacteria cross-react, and early or treated cases may not have raised titres yet.
What is XDR typhoid?
A strain resistant to the old first-line drugs, fluoroquinolones and third-generation cephalosporins such as ceftriaxone, leaving few treatment options. Treatment follows culture results and national guidance.
Why does a typhoid patient sometimes worsen suddenly after improving?
Ulcerated Peyer's patches can perforate or bleed in the third week, even after treatment has started, causing peritonitis or shock.