How does onchocerciasis-related skin and eye disease in Africa depend on cumulative exposure to infection and mass treatment?

Background Onchocerciasis (river-blindness) in Africa is targeted for elimination through mass drug administration (MDA) with ivermectin. Onchocerciasis may cause various types of skin and eye disease. Predicting the impact of MDA on onchocercal morbidity is useful for future policy development. Here, we introduce a new disease module within the established ONCHOSIM model to predict trends over time in prevalence of onchocercal morbidity. Methods We developed novel generic model concepts for development of symptoms due to cumulative exposure to dead microfilariae, accommodating both reversible (acute) and irreversible (chronic) symptoms. The model was calibrated to reproduce pre-control age patterns and associations between prevalences of infection, eye disease, and various types of skin disease as observed in a large set of population-based studies. We then used the new disease module to predict the impact of MDA on morbidity prevalence over a 30-year time frame for various scenarios. Results ONCHOSIM reproduced observed age-patterns in disease and community-level associations between infection and disease reasonably well. For highly endemic settings with 30 years of annual MDA at 60% coverage, the model predicted a 70% to 89% reduction in prevalence of chronic morbidity. This relative decline was similar with higher MDA coverage and only somewhat higher for settings with lower pre-control endemicity. The decline in prevalence was lowest for mild depigmentation and visual impairment. The prevalence of acute clinical manifestations (severe itch, reactive skin disease) declined by 95% to 100% after 30 years of annual MDA, regardless of pre-control endemicity. Conclusion We present generic model concepts for predicting trends in acute and chronic symptoms due to history of exposure to parasitic worm infections, and apply this to onchocerciasis. Our predictions suggest that onchocercal morbidity, in particular chronic manifestations, will remain a public health concern in many epidemiological settings in Africa, even after 30 years of MDA. Author summary Onchocerciasis, also known as river blindness, is the second most common infectious cause of blindness worldwide, but also leads to serious skin conditions. Large-scale interventions are ongoing to control and eliminate the disease in Africa, yet the impact of these interventions on onchocercal morbidity is largely unknown. Here, we predict the trends in a wide spectrum of skin and eye disease due to onchocerciasis after up to 30 years of annual mass drug administration (MDA) with ivermectin. To this end, we have developed a novel disease framework within the established ONCHOSIM model. We show that annual MDA will rapidly reduce the prevalence of acute clinical conditions, whereas the prevalence of chronic clinical manifestations will decline much more slowly. The new disease framework was validated with several data sources and reproduced morbidity trends adequately, making the framework applicable for more refined disease prevalence predictions by taking account of treatment history in Africa. Such predictions are essential for accurate estimates of disability-adjusted life years lost due to onchocerciasis by 2025.