Workup for Typhoid Fever
Diagnostic Investigations
Blood cultures are the cornerstone of typhoid diagnosis and must be obtained before starting antibiotics. Collect 2-3 specimens of 20 mL each, which have a sensitivity of 40-80%, with highest yield in the first week of illness 1, 2.
Essential Laboratory Tests
- Blood cultures: Obtain multiple large-volume specimens (20 mL each) before initiating empiric therapy, as sensitivity is highest early in disease 1, 2
- Bone marrow culture: Consider if blood cultures are negative, as this has superior sensitivity (35-65% vs blood culture) 1, 3
- Complete blood count: Look specifically for lymphopenia and thrombocytopenia, which are common findings 1
- Comprehensive metabolic panel: Obtain baseline urea, electrolytes, and liver function tests, as hepatic involvement occurs frequently 1
- Malaria testing: Mandatory in all febrile travelers from tropical areas—perform both thick/thin smears and rapid diagnostic test to exclude malaria 1
Key Clinical Features to Document
- Fever pattern: Present in 97-100% of cases, typically with gradual onset over 3-7 days after a 7-18 day incubation period 2, 4
- Relative bradycardia: Febrile temperatures with inappropriately slow heart rate is a classic finding 5
- Associated symptoms: Headache, vomiting, malaise, and myalgia are common presenting features 2, 4
- Travel history: Critical to determine geographic origin, as >70% of isolates from Asia are fluoroquinolone-resistant 1, 3
Common Diagnostic Pitfalls
Clinical diagnosis alone is highly unreliable—one study showed only 51.5% of clinically diagnosed cases were bacteriologically confirmed. 6 This underscores why culture confirmation is essential before committing to prolonged antibiotic therapy.
Differential Considerations
- Hepatic involvement: Jaundice occurs in 12.2% of typhoid cases and can be confused with viral hepatitis, malaria, or amebic liver disease 7
- Eosinopenia: This finding, along with relative bradycardia and slow defervescence, helps distinguish typhoid from other tropical fevers 5
- Systemic manifestations: Hepatosplenomegaly occurs in 87% of icteric cases and should prompt consideration of typhoid 7
Public Health Requirements
Typhoid fever is a nationally notifiable disease and must be reported immediately to local/state health departments. Submit isolates to public health laboratories for antimicrobial susceptibility testing and molecular typing 8, 2. This enables outbreak detection and guides empiric therapy recommendations based on regional resistance patterns.
Monitoring During Workup
- Serial neurologic examinations: Perform regularly to detect encephalopathy, which develops in 10-15% of patients 2
- Daily clinical assessment: Monitor for signs of complications, particularly in the second week of untreated illness when life-threatening complications typically arise 4
- Infection control: Implement contact precautions with gloves and gowns, plus hand hygiene with soap and water (not alcohol alone) 2