What is the approach to evaluate and manage undifferentiated fever in India?

Approach to Evaluation and Management of Undifferentiated Fever in India

The evaluation of undifferentiated fever in India should prioritize rapid testing for malaria, dengue, enteric fever, and scrub typhus, as these constitute the majority of cases, with empiric treatment guided by local epidemiology and clinical presentation. 1

Epidemiology and Common Causes

In India, the most common causes of acute undifferentiated febrile illness (AUFI) include:

• Dengue (30-38%)
• Enteric fever (16-17%)
• Scrub typhus (10-14%)
• Bacterial sepsis (8-10%)
• Malaria (7-17%)
• Leptospirosis (0.1-7%)
• Chikungunya (6%)
• Viral hepatitis A and E (1-2%)
• Undiagnosed cases (8-11%)

Mixed infections occur in approximately 2% of cases 1, 2.

Diagnostic Algorithm

Step 1: Initial Assessment (Day 1)

• Detailed travel history: Recent travel to endemic areas
• Exposure history: Animal contact, insect bites, water exposure
• Clinical examination: Focus on rash, eschar (for scrub typhus), hepatosplenomegaly, lymphadenopathy, jaundice
• Essential laboratory tests:
  • Complete blood count (look for thrombocytopenia, leukopenia or leukocytosis)
  • Peripheral blood smear for malaria
  • Rapid diagnostic tests for malaria and dengue NS1 antigen
  • Blood cultures (before antibiotics)
  • Liver function tests
  • Renal function tests
  • Urinalysis

Step 2: Additional Testing (Days 1-3)

• Serological tests:
  • Dengue IgM/IgG
  • Scrub typhus IgM ELISA
  • Leptospira IgM ELISA
  • Chikungunya IgM ELISA
  • Widal test (for enteric fever)
• Imaging:
  • Chest radiograph for all patients with fever 3
  • Ultrasound abdomen if hepatosplenomegaly, jaundice or abdominal symptoms present

Step 3: Advanced Testing (if diagnosis remains unclear)

• PCR-based tests for malaria, dengue, scrub typhus if available
• CT scan of thorax/abdomen if post-surgical or no clear diagnosis after initial workup 3
• Consider bone marrow examination in prolonged fever with pancytopenia

Management Approach

1. Empiric Treatment Decision

When clinical evaluation suggests infection as the cause of fever, empiric antimicrobial therapy should be initiated as soon as possible after cultures are obtained, especially if the patient is seriously ill or deteriorating. 3

2. Empiric Treatment Algorithm

For patients with suspected enteric fever:

• First-line: Azithromycin 1g on day 1, followed by 500mg daily for 5-7 days
• Alternative: Ceftriaxone 2g IV daily for 10-14 days (note increasing resistance up to 11.6% reported in Mumbai) 4

For patients with suspected scrub typhus:

• Doxycycline 100mg twice daily for 7 days

For patients with suspected malaria:

• Artemisinin-based combination therapy for P. falciparum
• Chloroquine plus primaquine for P. vivax (after G6PD testing)

For patients with suspected leptospirosis:

• Doxycycline 100mg twice daily for 7 days
• Alternative: Ceftriaxone 1g IV daily for 7 days

For undifferentiated severe illness with shock/organ dysfunction:

• Broad-spectrum antibiotics covering Gram-negative organisms including:
  • Ceftriaxone 2g IV daily plus
  • Doxycycline 100mg twice daily

3. Supportive Care

• Antipyretics for symptomatic relief (paracetamol preferred over NSAIDs for dengue) 5
• Adequate hydration
• Monitoring for complications (bleeding, shock, organ dysfunction)

Special Considerations

Critically Ill Patients

• Obtain cultures before starting antimicrobials
• Start empiric antimicrobial therapy within 1 hour if sepsis is suspected 3
• Consider broader antimicrobial coverage if clinically unstable

Diagnostic Pitfalls to Avoid

1. Relying on single diagnostic tests: Due to high overlap between case definitions and cross-reactivity, multiple diagnostic methods should be employed 2
2. Overlooking non-infectious causes: Consider drug fever, thromboembolism, malignancy, and autoimmune conditions 5
3. Delaying antimicrobial therapy when infection is strongly suspected in critically ill patients 3
4. Overtreatment of fever without addressing underlying cause 5
5. Using unreliable temperature measurement methods such as axillary or tympanic readings 5

Follow-up Recommendations

• Daily clinical reassessment
• Repeat blood counts every 48-72 hours
• Obtain convalescent serology samples after 2-3 weeks for definitive diagnosis
• Adjust antibiotics based on culture results and clinical response

By following this systematic approach to undifferentiated fever in India, clinicians can efficiently diagnose and manage these common but potentially serious conditions while minimizing unnecessary testing and inappropriate antibiotic use.