What are the Indian Academy of Pediatrics (IAP) recommendations for evaluating and managing a child with suspected or confirmed typhoid fever?

IAP Guidelines for Typhoid Fever in Children

First-Line Treatment Recommendation

Azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days is the preferred first-line treatment for children with typhoid fever, particularly given fluoroquinolone resistance exceeding 70% in South Asia. 1, 2

Diagnostic Approach

Blood Culture Collection

• Obtain blood cultures before starting antibiotics whenever possible, as they provide the highest diagnostic yield (40-80% sensitivity) within the first week of symptom onset 1, 3
• If the child is clinically unstable or has sepsis features, start empiric treatment immediately after collecting cultures 1, 3

Avoid the Widal Test

• Do not use the Widal test for diagnosis due to poor performance characteristics: specificity of only 68.44% and positive predictive value of just 5.7% 3
• Blood cultures remain the gold standard for diagnosis 3

Treatment Algorithm by Clinical Severity

Uncomplicated Typhoid Fever (Oral Therapy)

• Azithromycin: 20 mg/kg/day (maximum 1g/day) orally for 7 days 1, 2
• This regimen demonstrates superior outcomes with lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter with azithromycin compared to fluoroquinolones 1, 2
• Relapse risk is dramatically lower (OR 0.09) compared to ceftriaxone 1, 2

Severe Cases Requiring IV Therapy

• Ceftriaxone: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1, 2
• Ceftriaxone has demonstrated superior outcomes compared to cefotaxime in multidrug-resistant typhoid 4
• Mean time to defervescence with ceftriaxone is approximately 6-7 days 5, 4

Critical Pitfalls to Avoid

Never Use Ciprofloxacin Empirically

• Do not use ciprofloxacin empirically for cases from South or Southeast Asia where resistance approaches 96% in some regions 1, 2, 3
• Fluoroquinolone resistance exceeds 70% in isolates from South Asia 1, 2
• Fluoroquinolone-resistant typhoid treated with fluoroquinolones results in significantly prolonged illness (76.4 hours vs 41.2 hours for susceptible strains) 1

Avoid Cefixime as First-Line

• Cefixime has documented treatment failure rates of 4-37.6% in clinical practice 1
• If cefixime must be used, a mandatory test-of-cure at 1 week is required due to high failure rates 1
• Despite susceptibility, clinical non-response occurs in approximately 10% of patients treated with cefixime 5

Complete the Full Course

• Never discontinue antibiotics prematurely, even if fever resolves early 1, 2, 3
• Complete the full 7-day course (or 14 days per some guidelines) to prevent relapse, which occurs in 10-15% of inadequately treated cases 1, 2, 3

Expected Clinical Response and Monitoring

Fever Clearance Timeline

• Expect fever clearance within 4-5 days of appropriate antibiotic therapy 1, 2, 3
• Mean duration of defervescence is approximately 6.4 days with ceftriaxone 5
• If fever persists beyond 5 days, consider resistance or alternative diagnosis 1

Common Adverse Effects

• Monitor for azithromycin adverse effects: nausea, vomiting, abdominal pain, and diarrhea 1, 2
• Watch for potential drug interactions with azithromycin, particularly QT-prolonging medications 1, 2

Complications to Watch For

Intestinal Perforation

• Occurs in 10-15% of patients when illness duration exceeds 2 weeks 1, 2, 3
• Requires immediate surgical intervention with simple excision and closure, successful in up to 88.2% of cases 1, 2

Other Serious Complications

• Gastrointestinal bleeding, typhoid encephalopathy, and other life-threatening complications occur in 10-15% of patients 3
• These typically arise in the second week of untreated illness 3

Age-Specific Considerations

Typhoid in Children Under 5 Years

• Contrary to older beliefs, children under 5 years have the highest incidence of typhoid (27.3 per 1000 person-years) compared to older age groups 6
• 44% of culture-positive typhoid cases occur in children under 5 years 6
• Morbidity in children under 5 is similar to older patients in terms of duration of fever, signs and symptoms, and need for hospital admission 6

Prevention Strategies

Vaccination Recommendations

• Typhoid vaccination is recommended for children traveling to endemic areas (Latin America, Asia, Africa) 7, 1, 2
• Ty21a oral vaccine (for children ≥10 years): one enteric-coated capsule on alternate days for a total of four capsules, taken with cool liquid ≤37°C, one hour before meals; booster every 5 years 7, 1
• Parenteral inactivated vaccine (for children ≥10 years): 0.5 mL subcutaneously in two doses spaced ≥4 weeks apart; booster every 3 years 7, 1

Important Vaccination Limitations

• Vaccination provides only 50-80% protection and does not protect against Salmonella Paratyphi 1, 2, 3
• Only monovalent Salmonella Typhi preparations should be used; combination typhoid-paratyphoid vaccines increase adverse reactions without proven benefit 7, 1
• Hand hygiene and food/water safety precautions remain essential and cannot be replaced by vaccination alone 1, 2

Geographic and Resistance Considerations

South Asian Cases

• Over 70% of S. typhi isolates from South Asia are fluoroquinolone-resistant 1
• Multidrug-resistant (MDR) strains (resistant to chloramphenicol, ampicillin, tetracycline, and trimethoprim-sulfamethoxazole) account for 92.3% of isolates in some Indian studies 8
• All strains remain uniformly susceptible to gentamicin, amikacin, and third-generation cephalosporins 8

Treatment Adjustments Based on Travel History

• Always consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 1, 2
• Ciprofloxacin remains an alternative only if the patient traveled from sub-Saharan Africa 3