What are the recommended investigations and treatment for typhoid fever?

Investigation and Treatment of Typhoid Fever

Blood culture is the primary diagnostic method for typhoid fever, with a sensitivity of 40-80%, and should be performed before initiating antibiotics in all suspected cases. 1

Diagnostic Approach

First-line Investigations

• Blood cultures:

  • Collect at least two sets prior to antibiotic therapy (sensitivity up to 80% in typhoid) 2
  • Large-volume blood culture (15 ml) in adults gives similar sensitivity to bone marrow culture 3
  • Culture medium should be a rich nutrient broth containing a lysing agent 4

• Complete blood count:

  • Look for lymphopenia (common in typhoid)
  • Check for thrombocytopenia (seen in typhoid) 2

• Serological tests:

  • Typhidot test: Higher sensitivity (85-97%) and specificity (77-97%) with rapid results 1
  • Widal test: Traditional but less reliable with poor sensitivity (34-72%) and specificity (42-87%) 1

• Molecular testing:

  • PCR-based methods offer higher sensitivity (84.5%) compared to blood culture (61.8%) 1

Additional Investigations

• Stool culture:

  • Use selenite F or selenite mannitol media
  • Culturing 2g rather than 1g increases isolation rate by 10.5% 4

• Liver function tests: To assess hepatic involvement 2

• Renal function tests: To evaluate renal status and guide treatment 2

Treatment Protocol

First-line Treatment

• Ceftriaxone: 2g IV every 24 hours for 10-14 days 1
  • Particularly recommended for patients returning from Asia due to increasing fluoroquinolone resistance
  • Has shown 100% sensitivity in studies 5

Alternative Treatments

• Azithromycin: For uncomplicated cases or step-down therapy when fluoroquinolone resistance is confirmed 1

• Fluoroquinolones (e.g., ciprofloxacin):

  • Should only be used if confirmed sensitive to both ciprofloxacin and nalidixic acid
  • Not recommended for empiric therapy due to increasing resistance patterns 1
  • Ciprofloxacin resistance has been reported in 4.3% of cases 5
  • Ofloxacin may still be effective in some regions 6

Severe Cases

• Steroids: Consider in severe cases 1
• Surgical intervention: Required for intestinal perforation, which carries mortality rates up to 60% 1

Clinical Presentation to Guide Diagnosis

• Insidious onset of sustained fever
• Headache and lethargy
• Malaise and anorexia
• Relative bradycardia
• Abdominal pain
• Hepatosplenomegaly 1

Prevention Strategies

• Vaccination: Available for travelers to endemic areas

  • Oral live-attenuated Ty21a vaccine (efficacy 50-70%)
  • Parenteral polysaccharide capsular Vi vaccine
  • Booster doses required every 5 years for oral vaccine and every 2 years for injected vaccine 1

• Preventive measures:

  • Hand hygiene
  • Consumption of treated water
  • Proper cooking of food
  • Washing fruits and vegetables
  • Adequate refrigeration of food 1

Important Considerations

• Notify local health protection units of suspected or confirmed cases 2
• Warn laboratory staff about potential hazards when processing samples for enteric fever 2
• Implement source isolation precautions for patients with suspected or confirmed enteric fever 2
• Monitor for increasing antimicrobial resistance, particularly to fluoroquinolones in South and Southeast Asia 1

Common Pitfalls to Avoid

• Relying solely on the Widal test for diagnosis
• Failing to collect blood cultures before starting antibiotics
• Using fluoroquinolones empirically without considering regional resistance patterns 1
• Inadequate volume of blood for culture (larger volumes increase sensitivity) 3