Prospective Evaluation of Three Rapid Diagnostic Tests for Diagnosis of Human Leptospirosis.

Background: Diagnosis of leptospirosis by the microscopic agglutination test (MAT) or by culture is confined to specialized laboratories. Although ELISA techniques are more common, they still require laboratory facilities. Rapid Diagnostic Tests (RDTs) can be used for easy point-of-care diagnosis. This study aims to evaluate the diagnostic performance of the RDTs LeptoTek Dri Dot, LeptoTek Lateral Flow, and Leptocheck-WB, prospectively. Methodology: During 2001 to 2012, one or two of the RDTs at the same time have been applied prior to routine diagnostics (MAT, ELISA and culture) on serum specimens from participants sent in for leptospirosis diagnosis. The case definition was based on MAT, ELISA and culture results. Participants not fulfilling the case definition were considered not to have leptospirosis. The diagnostic accuracy was determined based on the 1^st submitted sample and paired samples, either in an overall analysis or stratified according to days post onset of illness. Results: The overall sensitivity and specificity for the LeptoTek Dri Dot was 75% respectively 96%, for the LeptoTek Lateral Flow 78% respectively 95%, and for the Leptocheck-WB 78% respectively 98%. Based on the 1^st submitted sample the sensitivity was low (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB), but substantially increased when the results of paired samples were combined, although accompanied by a lower specificity (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB). Conclusions: All three tests present antibody tests contributing to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. Since the overall sensitivity of the tested RDTs did not exceed 80%, one should be cautious to rely only on an RDT result, and confirmation by reference tests is strongly recommended. Author Summary: Leptospirosis is one of the world's most spread zoonoses causing acute fever. The illness can rapidly develop into a severe, potentially fatal, form with a high mortality rate. Laboratory tests are needed to confirm the diagnosis. Culturing leptospires from patient material can take months to grow. Therefore, most used laboratory tests are based on detection of antibodies against leptospires. The microscopic agglutination test is considered the reference standard but is only performed at specialized laboratories. In this study, we measured the diagnostic accuracy of three rapid diagnostic tests (RDTs) by doing a prospective evaluation during 11 years. These tests produce results within 15 minutes. The overall sensitivities (77%) and specificities (96%) were similar for the RDTs. Evaluating the first submitted specimen resulted in lower sensitivities (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB). When paired specimens were evaluated, the sensitivity increased although the specificity decreased (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB). Based on these results confirmation by reference tests is still strongly recommended, although the RDTs contribute to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. [ABSTRACT FROM AUTHOR]