What is the role of C-Reactive Protein (CRP) in diagnosing and managing typhoid fever?

Role of CRP in Diagnosing and Managing Typhoid Fever

C-reactive protein (CRP) can be valuable in diagnosing typhoid fever with moderate sensitivity and specificity, serving as a useful adjunct to clinical evaluation, though it should not be used alone for definitive diagnosis. 1, 2

Diagnostic Value of CRP in Typhoid Fever

Clinical Utility

• CRP levels typically rise 12-24 hours after infection onset, reaching peak values after 48 hours 2
• Normal CRP levels are below 5 mg/L, with typical cutoff for abnormal being 10 mg/L 2
• In suspected typhoid fever, elevated CRP (often >30 mg/L) can support the diagnosis when combined with clinical features 1
• CRP testing is widely available with results obtainable within minutes (point-of-care) or within an hour (laboratory-based) 1

Clinical Correlation

• CRP elevation correlates with the systemic inflammatory response in typhoid fever
• Studies have shown that CRP is consistently elevated in typhoid fever patients 3
• CRP levels should be interpreted alongside clinical features of typhoid fever:
  • Fever (present in 100% of cases)
  • Gastrointestinal symptoms (84%)
  • Headache (58%)
  • Dry cough (26%) 3

Limitations of CRP in Typhoid Diagnosis

• CRP is a non-specific marker of inflammation and can be elevated in many infectious and non-infectious conditions 2
• CRP has only moderate sensitivity and specificity for diagnosing bacterial infections 1
• CRP levels can be affected by:
  • Neutropenia
  • Immunodeficiency
  • Use of nonsteroidal anti-inflammatory drugs 1
• CRP should not be used as the sole diagnostic marker for typhoid fever

Comparison with Procalcitonin (PCT)

• PCT has slightly better diagnostic accuracy than CRP for bacterial infections:
  • PCT: SROC 0.85, sensitivity 80%, specificity 77%
  • CRP: SROC 0.73, sensitivity 80%, specificity 61% 1, 2
• However, PCT is not routinely recommended for diagnosing typhoid fever specifically 1
• PCT rises faster (4 hours after bacterial exposure) and clears more quickly as inflammation resolves compared to CRP 2

Role in Management and Monitoring

• CRP can be useful for monitoring treatment response in typhoid fever
• Declining CRP levels may indicate effective antibiotic therapy 3
• Persistently elevated or rising CRP despite treatment may suggest:
  • Antibiotic resistance
  • Development of complications
  • Need for alternative antibiotic therapy 4, 3

Clinical Application Algorithm

1. Initial Presentation:

   • Measure CRP in patients with suspected typhoid fever (fever, GI symptoms, recent travel to endemic areas)
   • CRP >30 mg/L along with typical clinical features increases likelihood of typhoid fever 1

2. Diagnostic Integration:

   • Combine CRP results with:
     • Clinical symptoms and signs
     • Travel history (particularly to Indian subcontinent)
     • Blood cultures (gold standard)
     • Widal test (where available) 3

3. Treatment Monitoring:

   • Serial CRP measurements to assess treatment response
   • Declining CRP suggests effective therapy
   • Persistent elevation may indicate treatment failure or complications 3

Practical Considerations

• CRP testing is more widely available and less expensive than PCT in many settings
• CRP results should always be interpreted in clinical context, not in isolation
• In resource-limited settings, CRP may be more accessible than blood cultures for initial assessment
• CRP can help differentiate typhoid fever from viral infections when combined with clinical features 1, 2

Pitfalls and Caveats

• Do not rely solely on CRP for typhoid fever diagnosis; blood culture remains the gold standard
• CRP elevation is non-specific and can occur in many conditions
• Normal CRP does not rule out early typhoid fever (may take 12-24 hours to rise)
• CRP should complement, not replace, thorough clinical assessment and appropriate microbiological testing 1, 3