Typhoid Fever in Children

Enteric fever is a systemic febrile illness caused by Salmonella enterica serotype Typhi (and, less commonly, Paratyphi A, B, C). In children it is a high-volume problem in the Indian subcontinent, where faeco-oral transmission, contaminated water, and emerging drug resistance make it a recurring exam favourite — blood culture, Widal interpretation, Faget's sign, ceftriaxone, and intestinal perforation are the load-bearing facts.

Definition & classification

Enteric fever is the umbrella term for the prolonged febrile illness caused by typhoidal Salmonellae. It must be distinguished from non-typhoidal Salmonella (NTS) gastroenteritis, which is usually a self-limiting diarrhoeal illness.

Term	Organism	Note
Typhoid fever	S. enterica serotype Typhi	Most severe, classic enteric fever
Paratyphoid fever	S. Paratyphi A, B, C	Milder, A now rising in India
Non-typhoidal salmonellosis	S. Typhimurium, Enteritidis	Gastroenteritis, bacteraemia in immunocompromised

The organism is a Gram-negative, motile (peritrichous flagella), non-lactose-fermenting, H₂S-producing bacillus of the Enterobacteriaceae family. Key antigens: O (somatic lipopolysaccharide), H (flagellar), and Vi (capsular virulence antigen — basis of the Vi polysaccharide vaccine and the typhoid carrier state).

High-yield: Humans are the only reservoir for S. Typhi. There is no animal host — hence theoretical eradicability through sanitation and vaccination.

Etiology & pathophysiology

Transmission is faeco-oral via the classic 5 F's: Food, Fingers, Faeces, Flies, Fomites. The infective dose is relatively high (10⁵–10⁹ organisms), so contaminated water and food (and chronic carriers handling food) drive most outbreaks.

Pathogenic sequence (flow):

Ingestion → survives gastric acid → invades Peyer's patches of terminal ileum via M cells → engulfed by macrophages but survives intracellularly (Vi antigen resists complement/phagocytosis) → primary bacteraemia (asymptomatic) → seeds reticuloendothelial system (liver, spleen, bone marrow, gallbladder) → multiplies → secondary bacteraemia = onset of clinical fever (after incubation 7–14 days) → re-seeding of gut Peyer's patches → hyperplasia, necrosis, ulceration → risk of perforation/haemorrhage in week 3.

The gallbladder is the key site of persistence; gallstones favour chronic carriage. Mononuclear cell infiltration (not neutrophils) explains the leukopenia/normal count typically seen.

High-yield: The week of illness maps to the pathology — week 1 bacteraemia (positive blood culture, rising fever), week 2 rash + toxaemia, week 3 complications (perforation, haemorrhage), week 4 convalescence.

Clinical features in children

The classic adult "stepladder" fever is less common in children, who often present with high continuous fever and nonspecific toxaemia. Younger children and infants can have an atypical, milder, or diarrhoea-predominant picture, sometimes mimicking sepsis.

• Fever: the dominant feature — high-grade, prolonged (>1 week), with relative bradycardia.
• Gastrointestinal: abdominal pain, anorexia; constipation classically in adults but diarrhoea ("pea-soup" stools) more common in children and infants.
• Coated tongue, foul breath.
• Hepatosplenomegaly (very common in children — more so than adults).
• Rose spots: 2–4 mm blanching, salmon-pink maculopapules on trunk/abdomen, appearing in the 2nd week (caused by bacterial emboli to dermal vessels); often missed in dark skin.
• Toxic look / apathy / "coma vigil", and in severe cases the typhoid state with delirium ("typhos" = cloud/stupor).
• Faget's sign (relative bradycardia): pulse rate lower than expected for the height of fever.

High-yield: Faget's sign = temperature–pulse dissociation. Also seen in brucellosis, legionella, drug fever, and yellow fever — but classically asked for typhoid.

Stepladder fever pattern

Where present, fever rises in a stepwise fashion over the first week, plateaus at a high level in the second week, and remits by lysis in the fourth week if untreated.

Diagnosis & investigation of choice

Test	Best timing	Sensitivity / note
Blood culture	Week 1 (highest yield)	Gold standard / definitive; ~40–80% positive, declines with prior antibiotics
Bone marrow culture	Any week, even after antibiotics	Most sensitive (~90%); not done routinely
Stool / urine culture	Week 2–3 onwards	Useful later; reflects gut shedding
Widal test	After day 7 (paired sera)	Serology; many false +/−
Typhidot (IgM/IgG)	Early, from day 4–5	Detects 50 kDa OMP antigen; rapid

High-yield: Blood culture is the gold standard for diagnosis; bone marrow culture is the most sensitive and stays positive despite prior antibiotic use. Memorise both — exams contrast them.

Widal test interpretation

The Widal test measures agglutinating antibodies to O and H antigens. It is a slide/tube agglutination test and is plagued by cross-reactivity, prior vaccination, and endemic background titres.

Antibody	Significance	Behaviour
Anti-O (IgM)	Acute, recent infection	Rises early, falls fast
Anti-H (IgG)	Past infection / vaccination	Rises later, persists long

• A single titre of O ≥ 1:160 and H ≥ 1:160 is suggestive in an endemic area (some texts cite 1:80 cut-offs; thresholds vary by lab/region).
• The most reliable evidence is a four-fold rise in titre between acute and convalescent (paired) sera taken 7–10 days apart.
• False positives: other Salmonella, malaria, dengue, chronic liver disease, prior vaccination, rheumatologic disease, endemic background.
• False negatives: early disease (<7 days), prior antibiotics, carriers, immunosuppression.

High-yield: A rising (four-fold) Widal titre on paired sera is far more meaningful than any single value; O antibody (IgM) indicates current infection, H antibody (IgG) indicates past/vaccinated. Widal cannot be used in the first week.

Supporting labs: leukopenia or normal WBC with relative lymphocytosis, eosinopenia, mild thrombocytopenia, and raised transaminases. (Leucocytosis should raise suspicion of perforation/another diagnosis.) Newer Typhidot-M (IgM) detects the outer membrane protein early and is more useful than Widal in week 1.

Management & drug of choice

Empirical therapy in India is shaped by resistance. Multidrug-resistant (MDR) typhoid = resistance to the older first-line trio: chloramphenicol, ampicillin, and cotrimoxazole. Subsequently, nalidixic-acid-resistant strains (predicting fluoroquinolone failure) and, more recently, XDR typhoid (resistant to first-line drugs + fluoroquinolones + third-gen cephalosporins) emerged, especially from Pakistan (Sindh, 2016 outbreak).

Setting / severity	Drug of choice	Notes
Uncomplicated, OPD	Oral cefixime or azithromycin	Azithromycin good for FQ-resistant strains
Complicated / hospitalised	IV ceftriaxone	Current empirical first-line in children in India
XDR typhoid	Azithromycin ± carbapenem (meropenem)	Reserve agents
Susceptible / historical	Chloramphenicol, amoxicillin, cotrimoxazole	Now largely abandoned due to resistance

Stepwise approach:

1. Assess severity → toxic, abdominal signs, GI bleed, altered sensorium → admit.
2. Start IV ceftriaxone (≈ 75–100 mg/kg/day) for complicated/inpatient cases; oral cefixime/azithromycin for mild OPD cases.
3. Supportive care → hydration, antipyretics (paracetamol, avoid aspirin in children), nutrition.
4. Severe toxaemia/encephalopathy/shock → adjunctive dexamethasone (high-dose) reduces mortality.
5. Monitor for defervescence (may take 5–7 days) and watch week-3 complications.
6. Treat relapse (5–10%) with a repeat course; address the chronic carrier.

High-yield: Ceftriaxone is the empirical drug of choice for hospitalised/complicated paediatric typhoid in India; azithromycin is preferred for uncomplicated FQ-resistant and many XDR cases. High-dose dexamethasone improves survival in severe typhoid with shock/encephalopathy.

Fluoroquinolones (ciprofloxacin/ofloxacin) were once first-line but are now compromised by nalidixic-acid resistance; they are generally avoided as empirical paediatric therapy. Chronic carriers (excreting >1 year, often with gallstones) are treated with prolonged ciprofloxacin or high-dose amoxicillin; cholecystectomy if refractory.

Complications

Most occur in week 3, when ileal ulcers are deepest.

• Intestinal perforation — the most feared surgical complication; classically terminal ileum, presents with worsening abdominal pain, guarding, rising pulse, and falling fever masked by toxaemia; needs urgent surgery.
• Intestinal haemorrhage — from eroded Peyer's patch vessels; melaena/haematochezia.
• Typhoid encephalopathy — delirium, the "typhoid state", coma vigil.
• Myocarditis (a cause of death), shock.
• Hepatitis, cholecystitis, and the chronic gallbladder carrier state.
• Relapse (~5–10%) typically 1–3 weeks after defervescence, usually milder.
• Others: pneumonia, osteomyelitis (notably in sickle cell disease — Salmonella osteomyelitis), nephritis, DIC, secondary haemophagocytic lymphohistiocytosis.

High-yield: Intestinal perforation and haemorrhage are the classic week-3 lethal complications. In a sickle-cell child, Salmonella is the classic cause of osteomyelitis (vs S. aureus in the general population) — a recurring two-mark question.

Key differentials

Feature	Typhoid	Malaria	Dengue	TB / disseminated
Fever pattern	Continuous, stepladder	Periodic with chills/rigors	Saddle-back, retro-orbital pain	Evening rise, chronic
Pulse	Relative bradycardia	Tachycardia	Variable	Variable
Key clue	Rose spots, splenomegaly	Periodicity, smear +	Thrombocytopenia, plasma leak	Weight loss, contact
Diagnosis	Blood culture	Peripheral smear/RDT	NS1/IgM	AFB, CBNAAT

Other mimics in a child with prolonged fever: brucellosis (also causes Faget's sign), infective endocarditis, rickettsial (scrub typhus) infection, leptospirosis, abdominal/miliary TB, Kawasaki disease, and occult abscess/UTI. The combination of prolonged fever + hepatosplenomegaly + relative bradycardia + leukopenia in an endemic setting should prompt blood culture for enteric fever.

Typhoid vaccines & prevention (India)

Vaccine	Type	Age	Route / schedule	Notes
Typhoid conjugate vaccine (TCV)	Vi-polysaccharide–protein conjugate (Vi-TT)	From 6 months	Single IM dose; booster per programme	WHO-prequalified; T-cell dependent → immunogenic in infants, durable
Vi polysaccharide (ViCPS)	Pure polysaccharide	≥ 2 years	Single IM/SC; revaccinate every 3 years	T-independent, poor in <2 y, no memory
Ty21a	Live oral attenuated	≥ 6 years	Oral capsules, alternate days × 3–4 doses	Contraindicated in immunocompromised/pregnancy; not with antibiotics

High-yield: TCV (typhoid conjugate vaccine) is now the preferred vaccine because it works from 6 months of age, gives a booster response, and confers longer protection. The old Vi polysaccharide vaccine is for ≥2 years and needs revaccination every 3 years. Ty21a is live oral, given ≥6 years, and contraindicated in immunosuppression.

General prevention: safe water, sanitation, hand hygiene, food safety, identifying and treating carriers, and not allowing carriers to handle food (the historical "Typhoid Mary" — Mary Mallon, an asymptomatic gallbladder carrier cook).

Recently asked / exam angle

• Investigation of choice: "Definitive diagnosis of enteric fever?" → Blood culture (gold standard); "most sensitive even after antibiotics?" → Bone marrow culture.
• Widal: which antibody indicates recent/acute infection? → O antibody (IgM); significance of paired four-fold rise.
• Faget's sign / temperature-pulse dissociation identification.
• Drug of choice in hospitalised child → ceftriaxone; XDR typhoid → azithromycin/meropenem.
• MDR typhoid definition (resistance to chloramphenicol + ampicillin + cotrimoxazole).
• Week-3 complication (intestinal perforation site = terminal ileum).
• Vaccine that can be given from 6 months → TCV; Ty21a route and contraindications.
• Salmonella osteomyelitis in sickle cell disease.
• Pathology buzzword: Peyer's patch hyperplasia/ulceration, rose spots mechanism.
• Adjunctive dexamethasone in severe typhoid with shock/encephalopathy reduces mortality.

Mnemonics:

• Transmission 5 F's — Food, Fingers, Faeces, Flies, Fomites.
• "Typhoid FACES" — Faget's sign, Abdominal pain, Coated tongue, Enlarged spleen/liver, Stepladder fever + rose Spots.
• Widal — O = Ongoing (IgM, acute); H = History/Had it before (IgG, past/vaccine).

Rapid revision

1. S. Typhi — Gram-negative, motile, H₂S-producing; humans are the only reservoir.
2. Incubation 7–14 days; transmitted faeco-orally (5 F's), infective dose high.
3. Pathology: invades Peyer's patches → macrophage survival (Vi antigen) → bacteraemia → week-3 ileal ulceration.
4. Faget's sign = relative bradycardia (temperature–pulse dissociation).
5. Rose spots = 2nd-week salmon maculopapules from bacterial dermal emboli.
6. Children: diarrhoea and hepatosplenomegaly more common than constipation.
7. Blood culture = gold standard (week 1); bone marrow culture = most sensitive, unaffected by antibiotics.
8. Widal: O antibody = acute (IgM); H antibody = past/vaccine (IgG); rely on four-fold rise in paired sera; cut-off ~1:160 endemic; useless in week 1.
9. Labs: leukopenia/eosinopenia; leucocytosis suggests perforation.
10. Ceftriaxone = first-line for complicated/admitted children; azithromycin for FQ-resistant/XDR; chloramphenicol/ampicillin/cotrimoxazole resistance defines MDR.
11. Week-3 complications: intestinal perforation (terminal ileum) and haemorrhage, myocarditis, encephalopathy; Salmonella osteomyelitis in sickle cell.
12. TCV usable from 6 months (preferred); Vi polysaccharide ≥2 y, revaccinate every 3 y; Ty21a live oral ≥6 y, contraindicated in immunosuppression; chronic carrier hides in gallbladder (treat ± cholecystectomy).