Multibead-based immunoassay provides one-step species-specific serodiagnosis of filarial infections and Strongyloides stercoralis in travelers and immigrants.

Abstract

Previously, antifilarial antibody testing in the evaluation of returned travelers and immigrants to North America has relied on IgG- and IgG4-specific responses to crude filarial extracts (BmA), tests that suffer from significant cross-reactivity with Strongyloides and cannot distinguish among the infecting filarial species. Nevertheless, between 1992 and 2016 we have tested >11000 samples from providers across North America in whom a filarial infection was being considered; close to 20% were able to be definitively diagnosed with a filarial infection (based on IgG4 anti-BmA reactivity) and ∼50% had the diagnosis excluded (based on IgG anti-BmA seronegativity). To create an all-in-one assay for screening travelers and immigrants where infections with filariae or Strongyloides stercoralis are being considered, we configured a multibead-based assay to measure simultaneously the IgG and IgG4 responses to BmA and to the species-specific recombinants Ll-SXP1, Ov-16, OvOC3261, Wb-123, Wb5, Ss-NIE and Ss-IR. By tuning the assays to >98% specificity for the species of interest (using ROC-based cutoffs), we have utilized this new assay to prospectively test samples from 1865 unique patients. Based on a hierarchical algorithm among the 318 (17%) seropositive samples, we were able to provide a species-specific diagnosis (Loa loa [N=99], Wuchereria bancrofti [N=29], Onchocerca volvulus [N=32], and S. stercoralis [N=93]) in 80%. We were able to exclude any of these organisms in 1547 (83%) based on parasite antigen-specific seronegativity. These data provide a new framework for clinically useful parasite-specific serology that helps to direct targeted therapeutic options.