Dengue virus infected patients can generate false positives in the ‘gold standard’Leptospiraspp. microscopic agglutination test (MAT), immunofluorescence assays (IFAs), and immunoblot assays due to cross-reactive IgG and/or IgM antibodies against their outer surface membrane proteins

Abstract

There are overlapping world distributions of the mosquito-borne dengue viruses (DENVs) and the water-borne bacterial disease leptospirosis which cause large numbers of human infections and fatalities. As such, early differential diagnosis is required to then administer appropriate early leptospirosis antibiotic therapy or DENV patient supportive care, but co-infections have also been reported. In this study, using paired (S1: acute and S2: convalescent phase) patients' serum samples, we report that some DENV infected patients' IgG and/or IgM antibodies cross-reacted with 68-72 and 38-42 KDa outer surface membrane antigens of all Leptospira spp. serovars tested in immunoblot (western blot) assays and paraformaldehyde (cell-membrane impermeable fixative) treated Leptospira spp. in immunofluorescent assays (IFAs), as well as displayed a > 4-fold rise between their S1 and S2 serum samples in the 'gold standard' Leptospira spp. microscopic agglutination test (MAT). While DENV-1, -2 or -3 were isolated from their S1 sera, a) Leptospira spp. could not be isolated from them, b) their S1 sera were all PCR-negative using a Leptospira spp. gene target, and c) their S2 sera were all negative in a commercial anti-Leptospira spp. IgM ELISA. As such, we believe this is the first report of DENVs causing false positive reactions in the 'gold standard' Leptospira spp. MAT and with paraformaldehyde fixed Leptospira spp. serovars in IFAs as well as immunoblot (western blot) assays, and which needs further assessments using more DENV infected patients' serum samples and to identify these 68-72 and 38-42 KDa Leptospira spp. outer surface membrane antigens by proteomic analyses.