What is the recommended approach for diagnosing and treating Leptospira infection?

Diagnosis and Treatment of Leptospirosis

The diagnosis of leptospirosis requires laboratory confirmation through isolation of Leptospira from clinical specimens, a fourfold increase in agglutination titer between paired serum samples, or demonstration of Leptospira by immunofluorescence. 1

Clinical Presentation

• Leptospirosis presents as a biphasic illness characterized by fever, headache, chills, myalgia, conjunctival suffusion, and less frequently by meningitis, rash, jaundice, or renal insufficiency 1
• The disease can be classified into two main clinical forms: mild to moderate (flu-like symptoms) and severe form (Weil's disease) characterized by hemorrhage, jaundice, and hepato-renal failure 2
• The septicemic or bacteremic phase lasts 4-7 days with high fever (≥39°C), diffuse myalgias (especially in calves), headache, and conjunctival suffusion 2
• Conjunctival suffusion is a suggestive clinical sign that should prompt consideration of leptospirosis 2

Diagnostic Approach

Laboratory Criteria for Diagnosis

• Confirmed diagnosis requires one of the following:
  • Isolation of Leptospira from a clinical specimen 1
  • Fourfold or greater increase in Leptospira agglutination titer between acute and convalescent-phase serum specimens obtained ≥2 weeks apart and studied at the same laboratory 1
  • Demonstration of Leptospira in a clinical specimen by immunofluorescence 1

Recommended Diagnostic Testing

1. Serology:

   • Most common method for confirming diagnosis 2
   • IgM titers >1:320 are suggestive of leptospirosis 2
   • IgM titers of 1:80 to 1:160 are consistent with early infection 2
   • A single Leptospira agglutination titer of ≥200 in one or more serum specimens supports a probable case classification 1
   • Rapid serological tests (Leptocheck WB, Latex agglutination) show good sensitivity (84.8-90.7%) and can be used in resource-limited settings 3

2. Molecular Testing:

   • PCR testing of blood and urine samples offers early diagnosis, especially during the first few days before antibody development 4
   • PCR has shown higher sensitivity (62%) compared to culture (48%) in clinical samples 4
   • Real-time PCR assays can confirm diagnosis in the early phase before antibody detection 5

3. Culture:

   • Blood cultures should be obtained in the first 5 days of illness, before antibiotics 2
   • Isolation of Leptospira is definitive but can take weeks to months 5

4. Other Laboratory Findings:

   • Proteinuria and hematuria in urinalysis 2
   • Leukocytosis with polymorphonuclear cells 2
   • Elevated bilirubin with mild elevation of transaminases 2
   • Alterations in renal function tests 2

Treatment Recommendations

• Treatment for mild to moderate leptospirosis should be started as soon as possible with antibiotics such as penicillin or doxycycline 2
• For severe leptospirosis (Weil's disease), treatment should be initiated immediately without waiting for laboratory confirmation 2
• Early antibiotic therapy is crucial as severe leptospiral infection can run a fulminant course 4

Diagnostic Challenges

• Diagnosis is challenging due to non-specific clinical manifestations that mimic other infectious diseases 6, 7
• Direct observation by darkfield microscopy is unreliable and not recommended 5
• Antibodies are typically absent during the acute phase, limiting early serological diagnosis 5
• Laboratory diagnostic facilities are often unavailable in endemic regions 7

Case Classification

• Probable case: A clinically compatible case with supportive serologic findings (Leptospira agglutination titer ≥200 in one or more serum specimens) 1
• Confirmed case: A clinically compatible case that is laboratory confirmed through isolation, serological conversion, or immunofluorescence 1

Prevention

• Avoid contact with urine from infected animals and contaminated water 2
• Take precautions during water recreational activities, occupational exposure to animals or water, and during floods 2