How do you diagnose leptospiral meningitis?

Diagnosis of Leptospiral Meningitis

Diagnose leptospiral meningitis through CSF analysis showing lymphocytic pleocytosis (typically 5-1,000 cells/μL with lymphocyte predominance) combined with PCR testing of CSF and serum, while obtaining blood cultures within the first 5 days of illness—but do not delay treatment while awaiting laboratory confirmation. 1, 2, 3, 4

Clinical Suspicion and Risk Assessment

Suspect leptospiral meningitis in patients presenting with the characteristic biphasic illness pattern: an initial bacteremic phase lasting 4-7 days with high fever, severe myalgias, and headache, followed by an immune phase with meningeal signs. 2, 3, 5

Key clinical features that should immediately raise suspicion:

• Conjunctival suffusion (a distinctive finding that differentiates leptospirosis from other causes of aseptic meningitis) 2, 3, 5
• History of exposure to fresh water, particularly in tropical areas or endemic regions 6
• Occupational or recreational water exposure, especially after floods 2, 3
• Contact with animal urine (direct or indirect) 3, 6

Cerebrospinal Fluid Analysis

Perform lumbar puncture and collect at least 22 mL of CSF for comprehensive testing. 7

CSF Findings Characteristic of Leptospiral Meningitis:

• Mildly elevated leukocyte count: median 206 cells/mm³ (range 6-2,072), typically 5-1,000 cells/μL 7, 6
• Lymphocytic predominance: median 95% lymphocytes (though neutrophils may predominate early) 7, 6
• Clear appearance (not turbid or purulent) 7
• Normal or mildly raised opening pressure 7
• Normal to mildly elevated protein 7, 6

Laboratory Diagnostic Testing

Primary Diagnostic Tests (in order of priority):

1. PCR Testing (Most Sensitive Early Diagnostic Tool)

• Perform PCR on CSF samples—this is the most powerful tool for diagnosing leptospiral meningitis, with sensitivity of 89.5% and specificity of 98-100% 1, 7, 4
• PCR can detect Leptospira DNA from day 3-26 after illness onset 4
• PCR has critical additive value: 58.97% of CSF samples may be positive by PCR alone when other tests are negative 4
• PCR is particularly valuable when antibiotics have been given before lumbar puncture 7, 4
• Also perform PCR on blood samples (EDTA tube) 1

2. Blood Cultures (Time-Sensitive)

• Obtain blood cultures within the first 5 days of illness, before antibiotic administration 2, 3
• Blood cultures are only useful during the bacteremic phase (first 4-7 days) 2, 5
• Culture sensitivity is low overall but may be positive during early illness 4, 8

3. Serologic Testing

• Microscopic Agglutination Test (MAT) remains the reference standard for confirmed diagnosis 1, 3, 8
• Critical limitation: Serologic testing shows earliest positives at 6-10 days after symptom onset, which is too late for early treatment decisions 2
• Confirmed case requires: Fourfold or greater increase in Leptospira agglutination titer between acute and convalescent-phase serum specimens (obtain convalescent sample 2-3 weeks after acute) 1, 3
• Probable case: Single Leptospira agglutination titer ≥200 in one or more serum specimens 3
• Test both CSF and serum: Anti-leptospiral antibodies were found in 33.33% of CSF samples in one study 4

4. Rapid Immunochromatographic Testing (Leptocheck)

• Can provide rapid diagnosis with 97.63% consistency with MAT 8
• May be positive earlier than MAT at first patient testing 8
• Useful for emergency cases with less specialized laboratory staff 8
• Should be confirmed with MAT 8

Diagnostic Algorithm by Disease Phase:

Early Phase (Days 1-5):

• Blood cultures (before antibiotics)
• PCR on blood and CSF
• Rapid immunochromatographic test
• MAT (acute sample—will likely be negative initially)

Late Phase (After Day 5-10):

• PCR on CSF (remains sensitive)
• MAT on serum and CSF
• Urine culture (after first week of illness) 1
• Convalescent serum for MAT (2-3 weeks after acute sample)

Critical Diagnostic Pitfalls to Avoid

Do not delay treatment while awaiting laboratory confirmation—treatment should begin immediately upon clinical suspicion given the non-specific nature of initial investigations and potential for rapid progression to severe disease. 2, 3

Do not rely solely on culture—all CSF cultures may be negative even in confirmed cases, making PCR and serology essential. 4

Do not assume MAT negativity rules out leptospirosis in the first week—serologic tests are not sensitive early in illness. 2, 4

Do not overlook the exposure history—ignoring occupational or recreational water exposure is a critical error in endemic areas. 2, 6

Do not assume mild symptoms will remain mild—even with treatment, patients can progress to severe disease with organ failure. 2

Diagnostic Classification

Confirmed Case:

• Isolation of Leptospira from clinical specimen, OR
• Fourfold or greater increase in Leptospira agglutination titer between acute and convalescent specimens, OR
• Demonstration of Leptospira in clinical specimen by immunofluorescence 3

Probable Case:

• Clinically compatible case with Leptospira agglutination titer ≥200 in one or more serum specimens 3