What is the approach to diagnose leptospirosis?

Diagnosing Leptospirosis

The diagnosis of leptospirosis requires a combination of clinical suspicion based on exposure history, characteristic symptoms, and laboratory confirmation through serological testing or culture. 1

Clinical Presentation

Leptospirosis presents with a wide spectrum of clinical manifestations, ranging from mild flu-like illness to severe disease (Weil's disease):

• Initial phase (bacteremic phase):

  • Fever (almost invariable)
  • Headache
  • Chills and rigors
  • Myalgia (especially of calves)
  • Conjunctival suffusion (highly suggestive)
  • Flu-like symptoms lasting 4-7 days

• Immune phase (1-3 days after initial phase):

  • Return of fever
  • Potential progression to severe disease with:
    • Jaundice
    • Renal failure
    • Hemorrhage
    • Meningitis
    • Myocarditis/pericarditis

Risk Factors to Identify

• Exposure to urine of infected animals (particularly rats, but also dogs, cattle, other domestic/wild animals)
• Contact with contaminated water:
  • Recreational water activities (swimming, rafting, kayaking)
  • Occupational exposure
  • Flooding
• Travel to endemic areas, especially tropical/subtropical regions

Laboratory Diagnosis

Initial Non-Specific Tests

• Urinalysis: may show proteinuria and hematuria
• Complete blood count: polymorphonuclear leukocytosis, thrombocytopenia (in 65.5% of cases) 2
• Chemistry: elevated bilirubin with mild transaminase elevation, evidence of renal failure
• Coagulation studies: often normal despite bleeding (due to capillary fragility)

Specific Diagnostic Tests

1. Serological Testing (most common method) 1:

   • IgM ELISA: earliest positives appear 6-10 days after symptom onset
   • Microscopic Agglutination Test (MAT):
     • Single titer ≥1:320 is suggestive of leptospirosis
     • Titer of 1:80-1:160 may indicate early infection or cross-reaction
     • Fourfold or greater increase between acute and convalescent specimens (≥2 weeks apart)

2. Culture 1:

   • Blood or CSF cultures within first 5 days of onset (before antibiotics)
   • Blood cultures should be kept at room temperature
   • Note: isolation can take months and doesn't contribute to early diagnosis 3

3. Molecular Testing 3:

   • PCR assays can confirm diagnosis in early phase before antibody detection
   • Not widely available in resource-limited settings

4. Direct Visualization:

   • Darkfield microscopy is unreliable and not recommended 3
   • Immunofluorescence to demonstrate Leptospira in clinical specimens 1

Diagnostic Algorithm

1. Suspect leptospirosis if:

   • Compatible clinical presentation (fever, headache, myalgia, conjunctival suffusion)
   • Epidemiological risk factors (water exposure, animal contact)
   • No other obvious diagnosis

2. Initial laboratory workup:

   • Complete blood count, liver function tests, renal function tests
   • Urinalysis
   • Blood cultures (if within first 5 days)

3. Specific testing:

   • Acute serology (IgM ELISA and MAT)
   • Convalescent serology >10 days after symptom onset
   • PCR if available and in early disease

4. Case classification 1:

   • Probable case: Clinically compatible with supportive serologic findings (Leptospira agglutination titer ≥200)
   • Confirmed case: Clinically compatible plus one of:
     • Isolation of Leptospira from clinical specimen
     • Fourfold or greater increase in agglutination titer between acute and convalescent sera
     • Demonstration of Leptospira by immunofluorescence

Important Caveats and Pitfalls

• Antibodies are absent during the acute phase, potentially leading to false-negative serological results 3
• Clinical presentation is highly variable and may mimic other diseases (influenza, dengue, viral hepatitis, meningitis) 3
• Treatment should begin upon clinical suspicion, without waiting for laboratory confirmation 1
• Jaundice and cardiac damage are independent predictors of progression to severe disease 2
• Urine is not a suitable sample for isolation of leptospira 1
• Paired serum samples (acute and convalescent) are often necessary for definitive diagnosis

Early diagnosis and treatment are crucial for preventing progression to severe disease with potentially life-threatening complications such as renal failure, pulmonary hemorrhage, and myocarditis.