In a patient with an acute febrile illness and exposure risk for leptospirosis, should the leptospira IgM test be repeated after an initial negative result?

Should Leptospira IgM Be Repeated?

Yes, Leptospira IgM testing should be repeated if the initial test is negative and clinical suspicion remains high, with convalescent serology obtained more than 10 days after symptom onset to confirm or exclude the diagnosis. 1, 2

Rationale for Repeat Testing

The timing of antibody development in leptospirosis creates a diagnostic window where early testing may yield false-negative results:

• IgM antibodies may not be detectable in the first few days of illness, particularly when infection was acquired very late or when the immune response is delayed 3, 1
• A fourfold or greater increase in Leptospira agglutination titer between acute and convalescent-phase serum specimens is required for confirmed diagnosis 3, 2
• Convalescent serology with microscopic agglutination test (MAT) should be repeated >10 days after symptom onset to capture seroconversion 1

Diagnostic Performance in Early Disease

The sensitivity of serologic testing varies dramatically by disease stage:

• Single acute phase MAT has only 83.3% sensitivity during early infection 4
• IgM ELISA sensitivity is 88.2% in the first 3 days after symptom onset, compared to only 2.0% for MAT 5
• Using both acute and convalescent samples increases MAT sensitivity to 98.2% 4
• IgM ELISA can detect antibodies before MAT titers reach 1:50, making it more sensitive for early diagnosis 6

When to Repeat Testing

Initial Negative Result with High Clinical Suspicion

Repeat IgM testing 2-4 weeks after initial presentation if:

• Patient has characteristic exposure history (flood water, contaminated fresh water, occupational animal contact) within 2-20 days 1
• Clinical features suggest leptospirosis: biphasic fever pattern, severe myalgias (especially calves), conjunctival suffusion, jaundice 3, 1
• Initial testing was performed within the first 3-5 days of symptom onset when antibodies may not yet be detectable 1, 2

Convalescent Phase Confirmation

Obtain convalescent serology at >10 days after symptom onset to:

• Demonstrate fourfold or greater increase in titer (confirms diagnosis) 3, 2
• Achieve diagnostic titers of ≥1:320 (highly suggestive) or ≥1:200 (probable case) 3, 2
• Rule out false-negative acute phase results 4

Critical Clinical Caveat

Do not delay antibiotic treatment while waiting for serologic confirmation, as each hour of delay increases mortality in severe disease 1. Treatment should be initiated immediately upon clinical suspicion:

• Doxycycline 100 mg orally twice daily for 7 days for mild-to-moderate disease 1
• Ceftriaxone 2g IV daily for 7 days for severe disease 1
• Serology is often negative in the first week, so negative results should not prevent empiric treatment 1

Practical Testing Algorithm

1. Obtain initial IgM ELISA and blood cultures (if within first 5 days) at presentation 1, 2
2. Start antibiotics immediately if clinical suspicion is moderate-to-high, regardless of initial test results 1
3. Repeat IgM testing at 10-14 days if initial test was negative but suspicion remains 1, 2
4. Obtain convalescent MAT to demonstrate fourfold titer rise for definitive diagnosis 3, 2

Common Pitfalls to Avoid

• Not recognizing that IgM can persist for months to years after acute infection (67% of patients show persisting IgM at 3-48 months), though at lower levels than acute infection 6
• Mistaking leptospirosis for viral hepatitis in patients with fever and jaundice—conjunctival suffusion is the distinguishing clinical feature 1, 2
• Discontinuing antibiotics early despite clinical improvement—complete the full 7-day course 1
• Using urine for culture, which is not suitable for leptospira isolation 1