Integrating Multiple Biomarkers to Increase Sensitivity for the Detection of Onchocerca volvulus Infection

Serological assessment of IgG4 responses to a combination of biomarkers for onchocerciasis enables enhanced case detection (at individual and community level), a current and urgent need towards elimination of the disease as a global health problem. Abstract Background Serological assessments for human onchocerciasis are based on IgG4 reactivity against the OV-16 antigen, with sensitivities of 60-80%. We have previously identified 7 novel proteins that could improve serodiagnosis. Methods IgG4 responses to these 7 proteins were assessed by luciferase immunoprecipitation (LIPS) and enzyme-linked immunosorbent (ELISA) immunoassays. Results OVOC10469 and OVOC3261 were identified as the most promising candidates by IgG4-based immunoassays with sensitivities of 53% for rOVOC10469 and 78% for rOVOC3261 while specificity for each was >99%. These 2 antigens in combination with OV-16 increased the sensitivity for patent infections to 94%. The kinetics of appearance of these IgG4 responses based on experimentally infected non-human primates indicated that they were microfilarial- driven. Further, the IgG4 responses to both OVOC10469 and OVOC3261 (as well as to OV-16) drop significantly (p