How is the diagnosis of leptospirosis made in adults with symptoms such as fever, headache, and muscle aches, and a history of exposure to contaminated water or soil?

Diagnosis of Leptospirosis

The diagnosis of leptospirosis requires laboratory confirmation through either isolation of Leptospira from clinical specimens, a fourfold or greater increase in agglutination titers between acute and convalescent sera, or demonstration of Leptospira by immunofluorescence, though treatment must begin immediately on clinical suspicion without waiting for these results. 1

Clinical Suspicion and Initial Assessment

The diagnosis begins with recognizing the characteristic clinical presentation and exposure history:

• Biphasic illness pattern: Initial bacteremic phase lasting 4-7 days with high fever (≥39°C), severe diffuse myalgias (especially calves), headache, and chills 2, 1, 3
• Conjunctival suffusion: This distinctive finding should immediately raise suspicion and is highly suggestive of leptospirosis 2, 1, 3
• Exposure history: Recent contact with contaminated water (floods, recreational water sports), occupational exposure to animals, or contact with rats, dogs, cattle, or other animals 3
• Additional clinical features: Jaundice, renal insufficiency, hemorrhage, or meningitis indicate severe disease (Weil's disease) 1, 3

Laboratory Confirmation Methods

Definitive Diagnostic Criteria

Confirmed diagnosis requires one of the following 1:

• Isolation of Leptospira from clinical specimens (blood, urine, CSF)
• Fourfold or greater increase in Leptospira agglutination titer between acute and convalescent-phase serum specimens
• Demonstration of Leptospira in clinical specimens by immunofluorescence

Probable diagnosis is established by 1:

• Clinically compatible case with single Leptospira agglutination titer ≥200 (or ≥1:320 for IgM) in one or more serum specimens 1, 3

Timing-Dependent Testing Strategy

Early phase (days 1-5): 2, 3, 4

• Blood cultures are most useful if obtained within first 5 days before antibiotic administration
• PCR/nucleic acid amplification testing can detect Leptospira early but requires 1-2 hours and is unavailable in most developing countries 3, 4
• Serologic testing is typically negative during this period

Later phase (days 6-10 and beyond): 2, 3

• Serologic testing becomes positive at 6-10 days after symptom onset
• IgM titers of 1:80 to 1:160 suggest early infection; titers >1:320 are highly suggestive 3
• Convalescent serology (>10 days after symptom onset) confirms diagnosis with fourfold titer rise 3

Supportive Laboratory Findings

Additional laboratory abnormalities that support the diagnosis include 3:

• Leukocytosis with neutrophilia
• Elevated erythrocyte sedimentation rate (ESR)
• Proteinuria and hematuria on urinalysis
• Elevated bilirubin with mild transaminase elevation (disproportionate pattern)
• Alterations in renal function tests
• Anemia if significant hemorrhage present

Clinical Scoring Systems

Modified Faine's criteria can be used to establish presumptive diagnosis, combining epidemiological, clinical, and laboratory features with moderate sensitivity (81.81%) and specificity (72.91%), and importantly a high negative predictive value (94.59%) to help exclude leptospirosis 5, 6

Critical Diagnostic Pitfalls

• Never delay treatment while awaiting laboratory confirmation: Serologic testing is too late for early treatment decisions (earliest positives at 6-10 days), and each hour of delay increases mortality 2, 4, 7
• Blood cultures are only useful in first 5 days: Must be obtained before antibiotics and within the narrow bacteremic window 2, 3
• Single titers have limited utility: A fourfold rise between acute and convalescent specimens is required for confirmation, though treatment cannot wait for this 1, 3
• Misdiagnosis as viral hepatitis: Patients with fever and jaundice may be incorrectly diagnosed, missing the critical early treatment window 3
• Non-specific presentation: The diverse clinical manifestations make clinical diagnosis difficult without considering exposure history 8, 7

Algorithmic Diagnostic Approach

1. Assess exposure history: Water contact, flooding, occupational/recreational exposure, animal contact 3
2. Identify characteristic clinical features: Fever, severe myalgias, conjunctival suffusion, biphasic pattern 2, 1
3. Obtain blood cultures immediately if within first 5 days and before antibiotics (causes <45 minutes delay) 3
4. Send acute phase serology (IgM), recognizing it will likely be negative early 3
5. Begin treatment immediately without waiting for results if clinical suspicion is high 2, 1
6. Obtain convalescent serology at 10-14 days for confirmation 3