Modelling the impact of mass drug administration with ivermectin or moxidectin on human onchocerciasis when there is sub-optimal response of parasites to treatment

Onchocerciasis is a disease caused by the filarial nematode parasite Onchocerca volvulus and is transmitted by blackflies after they ingest larval offspring, microfilariae, found in the skin of infected people. The elimination of transmission within endemic communities in sub-Saharan Africa, the Americas, and Yemen depends on mass drug administration of ivermectin (MDAi) at high treatment coverage until the prevalence of the parasite in people or in blackflies reaches below a threshold value. In Africa, there are a number of communities where worms that are less susceptible to the effects of ivermectin, i.e., that are sub-optimally responding (SOR), appear to be contributing to the persistence of onchocerciasis despite high-coverage MDAi. We have incorporated this variation in an epidemiological model to explore how the presence of SOR worms impacts the prevalence of people with skin microfilariae, fitting the model to epidemiological data from a community in Ghana, Asubende, where SOR has been detected. Incorporating a cumulative effect of ivermectin into the model fits the data better than if no cumulative effect is assumed. Simulations indicate that elimination is possible under biannual MDAi even if SOR worms are present in the starting population unless the baseline prevalence is hyperendemic. In a hyperendemic region, elimination is predicted if there is no SOR, but when SOR worms are included in the model, elimination is not reached even after twenty years of biannual MDAi with a treatment coverage of 80%. Biannual MDAi increases the proportion of reproducing female worms that would be characterized as SOR compared to annual MDAi. However, when using mass drug administration with moxidectin (MDAm), elimination becomes possible with fewer rounds of MDA even if there are worms that suboptimally respond to moxidectin. Our results support concerns raised in the research community that SOR to ivermectin in O. volvulus could result in persistent transmission despite high-coverage, biannual MDAi, but that MDAm could pose a solution, should safety and efficacy trials support its distribution.