Dengue virus infected patients can generate false positives in the 'gold standard' Leptospira spp. microscopic agglutination test (MAT) and IgG- and IgM- antibody specific immunofluorescence and protein (Western) immunoblot assays due to cross-reactions with their outer surface membrane proteins: Public health concern.

BACKGROUND: The dengue viruses (DENVs) and Leptospira spp. both cause large numbers of human infections and fatalities within their widely overlapping distributions, thereby requiring differential diagnoses for appropriate patient therapies.

METHODS: Many paired acute (S1) and convalescent (S2) phase patients' sera were tested as potential on-going DENV infections by their IgM and/or IgG antibody reactions and DENV isolations and serotype determinations. The sera from these DENV-confirmed cases were further tested for their abilities to cross-react with the Leptospira spp. of different serovars in the 'gold standard' microscopic agglutination test (MAT), immunofluorescence assays (IFAs), IgM-ELISA and protein (Western) immunoblot assays, as well as Leptospira spp. isolation and PCR tests.

RESULTS: In this study, 35 % of these patients' sera were confirmed as on-going DENV infections by their dramatically (>> 4-fold S1 to S2) increased anti-DENV IgM and/or IgG antibody ELISA titres. Of those, 8.6 % also displayed high S2 and/or ≥ 4-fold increased S1 to S2 serum titres using the Leptospira spp. MAT due to their IgM and/or IgG cross-reactions with their 68-72, 38-42 and 18-22 kDa outer surface membrane proteins (OSMPs) identified by SDS-PAGE and protein (Western) blotting after Triton X-114 detergent phase-separations. DENV-1, -2 or -3 serotypes, but not Leptospira spp., were isolated and their sera were negative using a Leptospira spp.-specific PCR and commercial anti-Leptospira spp. IgM-specific ELISA.

CONCLUSIONS: This is the first report of false-positive anti-Leptospira spp. IgM and/or IgG antibody reactions resulting from on-going primary or secondary DENV infections which may: a) account for some 'DENV-Leptospira spp. co-infections' being erroneously reported and b) lead to inappropriate antibiotic therapies, rather than appropriate early supportive therapy for 'severe dengue' cases in their widely co-endemic pan-global regions.