What is the recommended diagnostic workup for a patient from an endemic area with suspected enteric fever, considering their medical history and potential exposure to contaminated food or water?

Diagnostic Workup for Enteric Fever

Blood cultures should be obtained immediately as the primary diagnostic test for suspected enteric fever, with bone marrow culture reserved for cases where antibiotics have already been administered or blood cultures remain negative despite high clinical suspicion. 1, 2

Primary Diagnostic Testing

Blood Culture (Gold Standard)

• Obtain 2-3 blood cultures of 20 mL each in adults before initiating antimicrobial therapy to maximize detection, as the median magnitude of bacteremia in enteric fever is low at 0.3 colony-forming units/mL 2
• Blood culture has approximately 50% sensitivity compared to bone marrow culture 3, 2
• Highest yield occurs within the first week of symptoms 2
• Critical pitfall: Blood cultures must be collected BEFORE antibiotics are given, as prior antimicrobial administration significantly reduces sensitivity 2

Bone Marrow Culture (Highest Sensitivity)

• Particularly valuable if antimicrobial agents have been administered or when blood cultures are negative despite high clinical suspicion 1, 3, 2
• Higher sensitivity than blood culture but more invasive 3, 2
• Should be considered when blood cultures are negative and clinical suspicion remains high 2

Additional Culture Sites (Supplementary)

• Stool, duodenal fluid, and urine cultures may be beneficial to detect enteric fever, though these are weaker recommendations 1, 2
• These specimens provide additional diagnostic yield but should not replace blood culture as the primary test 2

Molecular and Multiplex Testing

Panel-Based Molecular Diagnostics

• Culture-independent testing including panel-based multiplex molecular diagnostics from stool and blood specimens should be performed when there is clinical suspicion of enteric fever 1
• Important caveat: These assays detect DNA and not necessarily viable organisms, so clinical context must be considered when interpreting results 1, 2
• Nucleic acid amplification tests lack sensitivity for detection of S. Typhi in blood but may be useful for rapid detection in research settings 2

Culture Confirmation Requirement

• All specimens that test positive by culture-independent methods must be cultured in clinical or public health laboratories to ensure outbreak detection and enable antimicrobial susceptibility testing 1, 2
• Isolate submission is required under public health reporting rules for surveillance and outbreak investigation 2

Tests to AVOID

Serologic Testing

• Serologic tests including the Widal test should NOT be used to diagnose enteric fever due to poor performance characteristics 1, 3, 2
• The Widal test has insufficient sensitivity (64-80%) and specificity (82-100% depending on cutoff values) 4
• Rapid diagnostic tests (RDTs) including TUBEX, Typhidot, and Test-It Typhoid have moderate diagnostic accuracy but are not recommended as primary diagnostic tools 5

Clinical Indications for Testing

When to Obtain Blood Cultures

Blood cultures should be obtained from: 1

• Infants <3 months of age with diarrhea
• People of any age with signs of septicemia or when enteric fever is suspected
• People with systemic manifestations of infection
• Immunocompromised individuals
• Travelers from enteric fever-endemic areas (especially South Asia) with febrile illness of unknown etiology 1, 3

Clinical Features Suggesting Enteric Fever

• Persistent fever with relative bradycardia and normal to low WBC count in returning travelers from endemic areas 3
• Leukopenia with relative lymphocytosis and monocyte predominance 3
• Thrombocytopenia may be present 3
• Important distinction: Diarrhea is uncommon in enteric fever, unlike other infectious diarrheas 1

Supportive Laboratory Findings

Complete Blood Count

• Leukopenia with relative lymphocytosis is typical 3
• Monocyte predominance suggests intracellular pathogen such as Salmonella 3
• Thrombocytopenia may be present 3
• CBC alone is insufficient for diagnosis due to non-specific nature 3

Specimen Collection Guidelines

Optimal Specimen Type

• Diarrheal stool sample (takes the shape of the container) is optimal for laboratory diagnosis 1
• If timely diarrheal stool cannot be collected, a rectal swab may be used for bacterial detection 1
• Fresh stool is preferred for identification of pathogens 1

Public Health Considerations

Reporting and Surveillance

• Specimens from people involved in an outbreak of enteric disease should be tested per public health department guidance 1
• Practitioners should collaborate with local public health authorities to adhere to policies regarding return to settings where transmission is a consideration 1
• Follow-up testing using culture-dependent methods for Salmonella Typhi or Paratyphi is recommended in certain situations by local health authorities following cessation of diarrhea 1

Key Clinical Pearls

• Monocytosis is more suggestive of enteric fever than viral infection 3
• Blood culture sensitivity is only 50%, so negative cultures do not rule out disease if clinical suspicion is high 3, 2
• Consider bone marrow culture if blood cultures are negative and clinical suspicion remains high, especially if antibiotics were given 3, 2
• The rising rates of multidrug-resistant and extensively drug-resistant (XDR) Salmonella strains necessitate culture confirmation for antimicrobial susceptibility testing 6, 7