What are the definitive diagnostics and treatment options for Leptospirosis?

Definitive Diagnostics for Leptospirosis

The definitive diagnosis of leptospirosis relies on a combination of serology (microscopic agglutination test as the gold standard), PCR for early detection, and blood culture during the first week of illness. 1, 2

Diagnostic Approach by Timing

Early Phase (First 5-7 Days of Illness)

PCR is the most valuable diagnostic tool during the acute septicemic phase, as it can detect leptospiral DNA before antibody development and provides results within 1-2 hours. 1, 2, 3

• Blood/serum PCR targeting the lipL32 gene should be performed first, with sensitivity of approximately 52% and specificity of 79% compared to MAT. 4, 5
• Urine PCR is actually superior to serum PCR in early disease (before day 8), detecting leptospires in approximately 90% of cases even when serum is negative. 6
• Blood cultures should be obtained within the first 5 days before antibiotic administration, though culture requires specialized expertise and takes weeks for results. 1, 2

After First Week (Convalescent Phase)

Serology becomes the primary diagnostic method after 7-10 days of illness. 1

• Microscopic Agglutination Test (MAT) is the gold standard for confirmation. 2, 5

  • IgM titers >1:320 are suggestive of leptospirosis. 1
  • IgM titers of 1:80 to 1:160 indicate early infection. 1
  • Convalescent serology (>10 days after symptom onset) with fourfold rise in titer confirms diagnosis. 1

• IgM ELISA provides 59% detection rate in acute phase, increasing to 80% when combined with PCR. 5

Specimen Collection Strategy

For maximum diagnostic yield, collect multiple specimen types simultaneously:

• Blood/serum: Optimal during first 5 days for both PCR and culture. 1, 3
• Urine: Can be positive even before day 8 and remains positive longer than blood; superior for early PCR diagnosis. 6
• Cerebrospinal fluid: When meningeal signs present; real-time reverse-transcription PCR may improve detection. 2

Critical Diagnostic Pitfalls to Avoid

• Do not wait for serological confirmation before starting treatment in suspected severe cases, as each hour of delay increases mortality. 1
• Do not rely on rapid leptocheck tests alone (only 44% detection rate); combine with PCR for 71% detection. 5
• Avoid heparin, sodium polyanetholesulfonate, and saponin anticoagulants for blood collection as they inhibit PCR; use EDTA or citrate instead. 4
• Do not assume negative serology rules out leptospirosis in early disease; PCR can detect 50% of cases that are seronegative. 5, 3

Supporting Laboratory Findings

While not definitive, these findings support the diagnosis: 1

• Proteinuria and hematuria on urinalysis
• Leukocytosis with polymorphonuclear predominance
• Elevated bilirubin with mild transaminase elevation (distinguishes from viral hepatitis)
• Elevated creatinine indicating renal dysfunction
• Anemia if significant hemorrhage present

Optimal Diagnostic Algorithm

For suspected leptospirosis presenting within 7 days:

1. Obtain blood for PCR (lipL32 target) and culture immediately
2. Collect urine for PCR (often more sensitive than blood in early disease)
3. Send acute phase serology (IgM ELISA or MAT)
4. Start antibiotics immediately without waiting for results if severe disease suspected

For suspected leptospirosis presenting after 7 days:

1. Obtain serology (MAT preferred, IgM ELISA acceptable)
2. Plan convalescent serology in 10-14 days to demonstrate rising titers
3. Urine PCR may still be positive even weeks after infection