Modelling anti-Ov16 Seroprevalence for the Control and Elimination of Onchocerciasis

The World Health Organization aims to verify the elimination of onchocerciasis transmission in one-third of endemic countries by 2030, principally through mass drug administration (MDA) of ivermectin. Serological assays that detect IgG4 antibodies against the Onchocerca volvulus Ov16 antigen are central to decision-making regarding start- and stop-MDA, post-treatment surveillance and post-elimination surveillance. Transmission models have a crucial role to play in understanding anti-Ov16 IgG4 seroprevalence dynamics, but uncertainty associated with the parasite stage(s) that stimulate(s) seroconversion and the duration of antibody persistence have hitherto hindered progress. Using the individual-based stochastic transmission model, EPIONCHO-IBM, we tested several hypotheses on the timing of anti-Ov16 IgG4 seroconversion and seroreversion. We fitted the model to data from treatment-naïve communities in Gabon and validated its predictions using data collected in Togo after 39 years of onchocerciasis interventions. The model best reproduced observed patterns when anti-Ov16 IgG4 seroconversion was elicited by near-patent/patent infection, marked by the production of O. volvulus microfilariae by a mating worm pair. The duration of antibody persistence remains uncertain. These findings support the use of mechanistic transmission models to refine serological thresholds for initiating and safely stopping MDA, and to aid interpretation of serological signals in post-treatment and post-elimination surveillance.