Should Lepto (Leptospirosis) IGM (Immunoglobulin M) or PCR (Polymerase Chain Reaction) be ordered to diagnose suspected leptospirosis?

Diagnostic Testing for Suspected Leptospirosis

For suspected leptospirosis, order both PCR and IgM serology on the initial sample, as combining these tests significantly improves early diagnostic sensitivity compared to either test alone.

Timing-Based Testing Strategy

Early Phase (Days 0-7 of symptoms)

• PCR is superior during the first week of illness when leptospires are circulating in blood but antibodies have not yet developed 1, 2, 3
• PCR demonstrates 62% positivity in acute phase samples, detecting leptospires before antibody development in many cases 3
• IgM antibodies typically appear 6-10 days after symptom onset, making serology less sensitive in the first week 4, 5
• PCR detected 50% of cases that were negative by all serological tests in the acute phase 2

Later Phase (Days 8-14 and beyond)

• IgM serology becomes highly sensitive after day 7, with sensitivity reaching 79-100% by days 9-14 6
• PCR sensitivity decreases in later phases (72.7% at days 9-14, dropping to 44.4% after day 15) 6
• IgM titers >1:320 are highly suggestive of leptospirosis, while titers of 1:80-1:160 indicate early infection 4, 7

Combined Testing Approach

The evidence strongly supports ordering both tests simultaneously on the first sample, regardless of symptom duration:

• Combined PCR and serology detected leptospirosis in 56% of suspected cases, compared to 26% by serology alone or 38% by PCR alone 1
• Combined testing in the acute phase achieves 93.1-96.5% sensitivity, far superior to either test individually 6
• When PCR is added to rapid IgM testing, detection rates increase from 44% to 71% 2

Technical Considerations for PCR

• Use multiplex PCR targeting multiple genes (lipL32 and 16S rDNA/rrs) to maximize detection rates 1
• Testing multiple targets increased detection from 29% (lipL32 alone) to 38% (both targets) 1
• PCR has 100% specificity, making it highly reliable when positive 6
• PCR turnaround time is 1-2 hours, allowing rapid diagnosis 7

Critical Clinical Context

Do not delay antibiotic treatment while waiting for test results:

• Start antibiotics immediately upon clinical suspicion with either IV penicillin or doxycycline for 7 days 4, 5
• Each hour of delay in severe disease increases mortality 7, 5
• Treatment initiated after 4 days of symptoms may be less effective 4
• Positive IgM confirms active or recent infection and justifies immediate treatment without additional confirmatory testing 4

Common Pitfalls to Avoid

• Do not rely on IgM alone in the first week - you will miss up to 50% of early cases that PCR would detect 2, 6
• Do not rely on PCR alone after day 7 - sensitivity drops significantly while IgM becomes highly sensitive 6
• Do not order only one test - the biphasic nature of leptospirosis means different tests perform optimally at different disease stages 1
• Do not wait for laboratory confirmation before starting antibiotics in clinically suspected cases 4, 7

Optimal Testing Algorithm

1. On initial presentation (any day of symptoms): Order both PCR and IgM serology simultaneously 1, 6
2. If both tests are negative but clinical suspicion remains high: Obtain convalescent serology at 10-14 days after symptom onset 4, 5
3. Start antibiotics immediately based on clinical suspicion without waiting for results 4, 7, 5