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.