Modelling exposure heterogeneity and density dependence in onchocerciasis using a novel individual-based transmission model, EPIONCHO-IBM: Implications for elimination and data needs

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Abstract
Density dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin. Density dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d’Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model. This is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improving model predictions during MDA. We discuss possible ways in which such data may be collected as well as the importance of better understanding the effects of immunological responses on establishing parasites prior to and during ivermectin treatment. Onchocerciasis, caused by the helminth parasite Onchocerca volvulus, is transmitted via the bites of Simulium blackflies. The World Health Organization has proposed onchocerciasis elimination in African countries by 2020/2025. Processes regulating parasite abundance in the lifecycle of helminths are known to influence the endemic prevalence in mathematical models. For example, when transmission intensity is low, a high proportion of incoming parasites may establish within a human host, whilst the opposite may be true when transmission intensity is high, possibly due to immunological processes. These processes may interact with exposure as some people are bitten more than others and receive more parasites. Therefore, regulatory processes that depend on parasite density and inter-individual variation in exposure play a central role in the ability of transmission to bounce back following mass drug administration. The former, because they may increase the success of parasite establishment as treatment progresses; the latter, because a few highly infected individuals may maintain transmission. We developed an individual-based model for onchocerciasis transmission and show that the interaction between these two processes impacts treatment outcomes. We highlight the need to obtain data on exposure to vector bites and to understand how immunological processes potentially regulating parasite establishment change under treatment.

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