Uncertainty Surrounding Projections of the Long-Term Impact of Ivermectin Treatment on Human Onchocerciasis

Background: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30–35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment. Methodology/Principal Findings: We modify a deterministic age- and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus–Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution. Conclusions/Significance: There is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities. Author Summary: Studies in Mali, Nigeria, and Senegal suggest that, in some settings, it is possible to eliminate onchocerciasis after 15–17 years of ivermectin distribution. Computer models have been used to estimate the required duration of ivermectin distribution to reach elimination. Some models assume that annual ivermectin treatment reduces the fertility of the causing parasite, Onchocerca volvulus, by 30–35% each time the drug is taken. Other analyses suggest that ivermectin may not have such an effect. We explore how assumptions regarding: a) treatment effects on microfilarial production by female worms (fertility), b) proportion of people who receive the drug (coverage), c) proportion of people who adhere to treatment (compliance), and d) whether people are treated once or twice per year (frequency) affect temporal projections of infection load and prevalence in highly endemic African savannah settings. We find that if treatment does not affect parasite fertility cumulatively, elimination of onchocerciasis in highly endemic areas of Africa may not be feasible with annual ivermectin distribution alone. If two areas have equal coverage but dissimilar compliance, they may experience very different infection load, prevalence and persistence trends. Projections such as these are crucial to help onchocerciasis control programmes to plan elimination strategies effectively.