What is the preferred test, IgM or IgG, for diagnosing acute Leptospirosis?

Leptospirosis Serology: IgM Testing is Preferred for Acute Diagnosis

For diagnosing acute leptospirosis, IgM antibody testing is the preferred serological test, as it becomes positive early in the disease course (typically 6-10 days after symptom onset) and provides diagnostic information when treatment decisions are most critical. 1, 2

Timing and Diagnostic Performance of IgM vs IgG

IgM Antibodies (Preferred for Acute Diagnosis)

• IgM antibodies appear 6-10 days after symptom onset and are detectable in the first week of illness, making them ideal for early diagnosis 1, 3
• IgM ELISA demonstrates high sensitivity (89.6-100%) and specificity (90.6-98%) for acute leptospirosis when tested during the first week of symptoms 4, 5, 6
• IgM titers >1:320 are diagnostic of leptospirosis, while titers of 1:80 to 1:160 are consistent with early infection 3
• The IgM immunoblot test shows 88.2% sensitivity within 1-3 days after symptom onset, far superior to other early diagnostic methods 7

IgG Antibodies (Limited Role in Acute Diagnosis)

• IgG antibodies require paired acute and convalescent sera (taken 3-6 weeks apart) to demonstrate a fourfold rise in titer for diagnostic confirmation 8, 3
• A single IgG result is not useful for acute diagnosis because antibodies may persist for months to years after infection, making it impossible to distinguish acute from past infection 3
• IgG testing is primarily reserved for retrospective confirmation rather than guiding immediate treatment decisions 8

Clinical Application Algorithm

When to Order IgM Testing

1. Order IgM serology immediately in patients with:

   • Fever with exposure history to contaminated water or animals within 2-20 days 2
   • Characteristic clinical features: severe myalgias (especially calves), headache, conjunctival suffusion 2, 3
   • Systemic manifestations: jaundice, hemorrhage, renal dysfunction 2, 3

2. Optimal timing for IgM testing:

   • First sample should be obtained as soon as leptospirosis is suspected, ideally after day 5-7 of illness when sensitivity is highest 4
   • Do not delay antibiotic treatment while waiting for serological results, as each hour of delay increases mortality 1, 2

When to Order Convalescent Serology

• Obtain convalescent serology (both IgM and MAT) >10 days after symptom onset for definitive confirmation 1, 2
• A fourfold or greater increase in titer between acute and convalescent specimens confirms diagnosis 3

Important Caveats and Pitfalls

Limitations of IgM Testing

• IgM antibodies may persist for >1 year in some cases, potentially causing false-positive results in patients with prior infection 9
• IgM can be negative in the first 5-7 days of illness, so a negative result early in the disease course does not exclude leptospirosis 4, 6
• False-positive IgM results occur in approximately 4-10% of patients with other febrile illnesses 4, 5

Why IgG Alone is Inadequate

• Single IgG measurements cannot distinguish between acute infection, past infection, or baseline antibodies from previous exposure 3
• IgG requires paired sera 3-6 weeks apart, which is impractical for acute management decisions 8
• Only 2 of 70 patients showed a 4-fold rise in IgG in one study, demonstrating poor sensitivity for acute diagnosis 9

Critical Clinical Considerations

• Treatment with doxycycline or penicillin must be initiated immediately upon clinical suspicion, without waiting for serological confirmation 1, 2
• Blood cultures should be obtained before antibiotics if this causes no significant delay (<45 minutes), ideally within the first 5 days of illness 2
• Faine's clinical criteria have 88.9% sensitivity and 98.6% negative predictive value, making them useful for screening when combined with IgM testing 9

Recommended Testing Strategy

The optimal approach combines immediate clinical assessment with IgM serology:

1. Start antibiotics immediately based on clinical suspicion (exposure history + compatible symptoms) 1, 2
2. Order IgM ELISA as the primary serological test for acute diagnosis 2, 4
3. Obtain blood cultures before antibiotics if no significant delay 2
4. Order convalescent serology (IgM and MAT) >10 days after symptom onset for confirmation 1, 2
5. Do not order isolated IgG testing for acute diagnosis 3