What is the diagnostic test for typhoid fever?

Diagnostic Testing for Typhoid Fever

Primary Recommendation

Blood culture is the gold standard diagnostic test for typhoid fever and should be performed in all patients with clinical suspicion of enteric fever, with bone marrow culture reserved for cases where antibiotics have already been administered or when blood cultures remain negative despite high clinical suspicion. 1

Recommended Diagnostic Approach

First-Line Testing

• Blood culture remains the primary diagnostic modality with approximately 50% sensitivity compared to bone marrow culture, and should be obtained before antimicrobial administration 1
• Collect 2-3 blood cultures of 20 mL each in adults to maximize detection, as the median magnitude of bacteremia in enteric fever is low at 0.3 colony-forming units/mL 1
• Culture-independent multiplex molecular diagnostics from blood and stool specimens should be performed when there is clinical suspicion of enteric fever 1
• Obtain cultures within the first week of symptoms when blood culture yield is highest 2

Additional Diagnostic Specimens

• Bone marrow culture has higher sensitivity than blood culture and is particularly valuable if antimicrobial agents have been administered 1
• Cultures of stool, duodenal fluid, and urine may be beneficial to detect enteric fever, though these are considered weak recommendations 1
• Larger blood volumes are needed in adults due to low-level bacteremia, while lower volumes may suffice in children who have higher magnitudes of bacteremia 1

Tests That Should NOT Be Used

Serologic Testing

• Serologic tests including the Widal test should NOT be used to diagnose enteric fever due to poor performance characteristics 1
• The Widal test has low sensitivity (71.4%), low specificity (68.4%), and very poor positive predictive value (5.7%), making it unreliable for diagnosis 3
• False positives occur due to cross-reactions with other Salmonella species, previous typhoid vaccination, prior infection, or other febrile illnesses 4
• The CDC explicitly states that serologic evidence alone is not sufficient for diagnosis and that isolation of Salmonella typhi from clinical specimens is required for confirmation 4

Molecular Testing Limitations

• Nucleic acid amplification tests lack sensitivity for detection of S. Typhi in blood but may be useful for rapid detection in research settings 1
• Panel-based multiplex molecular diagnostics detect DNA and not necessarily viable organisms, so clinical context must be considered when interpreting results 1

Critical Clinical Pearls

Specimen Collection Timing

• Blood cultures should be collected prior to antimicrobial administration to maximize sensitivity 1
• Continuously monitored blood culture systems may shorten time to detection and improve sensitivity compared with manual methods 1

When Culture is Negative

• Consider bone marrow culture if blood cultures are negative and clinical suspicion remains high, especially if antibiotics were given 1
• Blood cultures may remain negative in 87.5-95% of cases, so negative cultures do not rule out typhoid fever 4

Public Health Requirements

• All specimens testing positive by culture-independent methods should be cultured in clinical or public health laboratories to ensure outbreak detection and enable antimicrobial susceptibility testing 1
• Isolate submission is required under public health reporting rules for surveillance and outbreak investigation 1

Common Pitfalls to Avoid

• Do not rely on Widal test alone for diagnosis despite its widespread use in endemic areas 4, 3
• Do not interpret elevated Widal titers in endemic areas as diagnostic, as background antibody levels may be elevated 4
• Do not delay blood culture collection while waiting for fever to spike—cultures may be drawn simultaneously 1
• Do not use multiple specimens for C. difficile testing, as a single diarrheal stool specimen is sufficient and multiple specimens do not increase yield 1