What is the recommended blood test for diagnosing typhoid fever?

Blood Tests for Typhoid Fever Diagnosis

Blood culture is the recommended primary diagnostic test for typhoid fever, with a sensitivity of 40-80%, and should be collected before antimicrobial administration. 1

Primary Diagnostic Methods

Blood Culture

• Gold standard for clinical practice
• Sensitivity: 40-80%
• Should be collected before antibiotics are administered
• For adults: Two to three 20-mL blood cultures are recommended
• For children: Lower volumes may be sufficient due to higher bacteremia levels 2, 1

Bone Marrow Culture

• Highest sensitivity (considered gold standard)
• Particularly valuable if antibiotics have been administered
• More invasive but more reliable than blood culture
• 1 mL of bone marrow culture provides similar sensitivity to 15 mL of blood culture 1

Additional Cultures

• Stool culture (sensitivity 35-65%)
• Duodenal fluid culture
• Urine culture
• These can be beneficial as supplementary tests to blood culture 2

Culture-Independent Methods

Molecular Diagnostics

• Nucleic acid amplification tests (NAATs) and PCR show higher sensitivity (84.5%) compared to blood culture (61.8%)
• Useful for rapid detection when available 1

Serologic Tests

Important Caution: The Infectious Diseases Society of America (IDSA) strongly recommends against relying solely on serologic tests, particularly the Widal test, due to poor performance characteristics 2, 1.

Serologic tests available include:

• Typhidot test: Detects IgG and IgM antibodies with reported sensitivity of 100% and specificity of 80% in some studies 3
• TUBEX test: One-step test detecting anti-Salmonella O9 antibodies, showing improved accuracy over Widal test in research settings 4

Laboratory Findings Supporting Diagnosis

• Normal or low white blood cell count (<10.0 x 10³/mm³) is strongly associated with typhoid fever 5
• Leucopenia due to absolute neutropenia with relative lymphocytosis is highly suggestive of typhoid fever 5
• Monocyte predominance may suggest Salmonella infection 2

Diagnostic Algorithm

1. First line: Collect blood cultures (before antibiotics if possible)
2. If blood cultures are negative or unavailable: Consider bone marrow culture
3. Supplementary tests: Stool, duodenal fluid, and urine cultures
4. If molecular testing is available: PCR-based methods can be used for rapid detection
5. Monitor: Complete blood count with differential (looking for normal/low WBC count with relative lymphocytosis)

Common Pitfalls to Avoid

• Relying solely on the Widal test for diagnosis (poor sensitivity and specificity) 1, 6, 7
• Failing to collect blood cultures before starting antibiotics (reduces sensitivity) 1
• Not considering typhoid fever in febrile travelers returning from endemic areas 1
• Overlooking typhoid fever in patients with fever but without diarrhea 1
• Using inadequate blood volume for cultures (reduces sensitivity) 2

Special Considerations

• In resource-limited settings where blood culture is not available, serologic tests may be used with caution, understanding their limitations
• Multiple blood cultures increase the yield of positive results
• The sensitivity of blood culture decreases with prior antibiotic use and duration of illness

Blood culture remains the cornerstone of typhoid fever diagnosis in clinical practice, despite its limitations in sensitivity. When available, bone marrow culture provides the highest diagnostic yield, especially in patients who have already received antibiotics.