BackgroundLeptospirosis is most often diagnosed clinically, and a laboratory test with high diagnostic accuracy is required. MethodsIgM and IgG ELISAs using Leptospira antigens were established and evaluated in relation to the microscopic agglutination test (MAT). Antigen preparation consisted of saprophytic Leptospira biflexa to detect genus-specific antibodies (genus-specific ELISA) and a pool of the five most prevalent Leptospira interrogans serovars in Sri Lanka to detect serovar-specific antibodies (serovar-specific ELISA). IgM and IgG immune responses were studied in severe and mild leptospirosis patients (n = 100 in each group). ResultsThe ELISAs showed high repeatability and reproducibility. The serovar-specific IgM-ELISA showed a sensitivity of 80.2% and specificity of 89%; the genus-specific IgM-ELISA showed a sensitivity of 83.3% and specificity of 91%. The serovar- and genus-specific IgG-ELISAs showed sensitivities of 73.3% and 81.7%, respectively, and specificities of 83.3% and 83.3%, respectively. The commercial IgM-ELISA showed a sensitivity of 79.2% and specificity of 93%. The commercial IgG-ELISA showed a sensitivity of 50% and specificity of 96.7%. IgM levels observed in mild and severe leptospirosis patients were significantly higher than in the healthy control group, with mean absorbance values of 0.770, 0.778, and 0.163, respectively. Severe leptospirosis patients had significantly higher mean anti-leptospiral IgG levels compared to both mild leptospirosis patients and healthy control group subjects (0.643, 0.358, and 0.116, respectively; ANOVA, p < 0.001). The presence of anti-leptospiral IgG above an optical density of 0.643 at 1:100 could predict a high risk of severe disease. ConclusionThe serovar-specific in-house ELISA could be used for the laboratory diagnosis of leptospirosis in endemic settings. The high levels of anti-leptospiral IgG observed suggest its value as a predictor of disease severity.