What is the diagnostic test for enteric fever?

Diagnostic Testing for Enteric Fever

Blood culture is the gold standard diagnostic test for enteric fever and should be obtained in all patients with clinical suspicion, ideally collecting 2-3 cultures of 20 mL each before antimicrobial administration. 1

Primary Diagnostic Approach

Blood Culture - First-Line Test

• Blood culture remains the definitive diagnostic test with approximately 50% sensitivity and 100% specificity, and should be performed before starting antibiotics 1
• Collect 2-3 blood cultures of 20 mL each in adults to maximize detection, as the median bacteremia magnitude is low at 0.3 colony-forming units/mL 1
• Obtain cultures within the first week of symptoms when blood culture yield is highest 1
• Blood cultures should be obtained from patients with signs of septicemia, systemic manifestations, or travelers from enteric fever-endemic areas with unexplained febrile illness 2

Bone Marrow Culture - When Blood Culture Fails

• Bone marrow culture has higher sensitivity than blood culture and is particularly valuable if antimicrobial agents have already been administered 2, 1
• Consider bone marrow culture when blood cultures remain negative despite high clinical suspicion 1
• This is especially important in patients who received antibiotics before diagnostic testing 2, 1

Additional Culture Sites

• Cultures of stool, duodenal fluid, and urine may be beneficial to detect enteric fever, though these represent weaker recommendations 2, 1
• These alternative sites can increase diagnostic yield in culture-negative cases 2

Tests to AVOID

Serologic Testing - Do Not Use

• Serologic tests including the Widal test should NOT be used to diagnose enteric fever due to poor performance characteristics 2, 1
• The CDC explicitly states that serologic evidence alone is insufficient for diagnosis and that isolation of Salmonella typhi from clinical specimens is required for confirmation 1
• Despite some research showing rapid IgM tests with high sensitivity 3, guidelines consistently recommend against serologic testing 2, 1

Emerging Diagnostic Technologies

Molecular Testing - Limited Role

• Nucleic acid amplification tests (NAATs) 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, requiring careful clinical interpretation 1

Rapid Diagnostic Tests - Not Guideline Recommended

• While research shows RDTs like TUBEX (78% sensitivity, 87% specificity), Typhidot (84% sensitivity, 79% specificity), and Test-It Typhoid (69% sensitivity, 90% specificity) have moderate accuracy 4, these are not endorsed in current clinical practice guidelines
• RDTs may miss 22-31% of enteric fever cases and produce false positives in 9-23% of non-enteric fever patients 4

Clinical Context and Supportive Findings

Complete Blood Count - Suggestive but Not Diagnostic

• CBC findings are insufficient for diagnosis but may provide supportive evidence 2, 5
• Enteric fever typically shows leukopenia with relative lymphocytosis and monocyte predominance 5
• Thrombocytopenia may be present 5
• Do not rely on CBC alone - blood culture confirmation is mandatory 2, 5

Critical Clinical Pearls

Timing and Specimen Collection

• Always collect blood cultures BEFORE starting antibiotics to maximize sensitivity 1
• First week of illness provides highest blood culture yield 1
• If antibiotics were already given, strongly consider bone marrow culture 2, 1

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 for surveillance and outbreak investigation 1

Common Pitfalls to Avoid

• Do not order serologic tests (Widal test) - they have poor performance and should not guide clinical decisions 2, 1
• Do not rely on single blood culture - collect multiple specimens to increase yield 1
• Do not delay blood culture collection while waiting for other test results 1
• Do not use peripheral white blood cell count alone to establish diagnosis 2