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

Abstract

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.

The burden of skin disease and eye disease due to onchocerciasis in countries formerly under the African Programme for Onchocerciasis Control mandate for 1990, 2020, and 2030

“…We used the mathematical model ONCHOSIM [2,[8][9][10] to predict the prevalence of infection and morbidity over time, taking account of the pre-control distribution of infection levels, bioclimate (forest vs. savanna parasite strain), and history of control (MDA, vector control) of each APOC project. Development of morbidity was modelled using a new version of ONCHOSIM that captures the dynamic association between infection, treatment, and morbidity [7]. DALYs lost due to onchocerciasis were quantified by calculating the number of years lived with disability (YLDs) and years of life lost (YLL) due to blindness-related excess mortality.…”

“…We predict the prevalence of O. volvulus infection and clinical manifestations per APOC project from 1990 through to 2030, using a newly developed version of the mathematical model ONCHOSIM that captures the dynamic association between infection, treatment, and morbidity [7]. A brief description of ONCHOSIM and its generic morbidity module is provided in S1 Text, sections 3.1 and 3.2.…”

“…Disease manifestations were modelled using a newly developed disease module within ONCHOSIM that, for the first time, could simultaneously simulate reversible and irreversible clinical manifestations, as well as single-and multi-stage disease, taking into account the impact of excess mortality due to blindness on the trends for prevalence of all these conditions. Model outcomes were externally validated against longitudinal trends in morbidity prevalence, community-level patterns in prevalence of infection and disease manifestations, agestratified pre-control morbidity prevalence data from savanna communities, and data on the concurrence of clinical manifestations, and it was shown that the model could reasonably well reproduce the morbidity patterns in the field [7]. Also, it is important to note that our analysis builds on estimates of the pre-control distribution of infection levels based on REMO (rapid epidemiological mapping of onchocerciasis) data, which are the most comprehensive and accurate data available, and the basis of the current map of onchocerciasis in the 20 APOC countries.…”

“…We include a wide spectrum of onchocercal skin (OSD) and eye disease (OED): severe itch, reactive skin disease, skin depigmentation (leopard skin), skin atrophy, hanging groin, subcutaneous onchocercal nodules, and vision loss (visual impairment and blindness). We predict trends over time in the prevalence of infection, OSD, and OED based on data on the pre-control distribution of infection and the history of MDA, and a newly developed version of the mathematical model ONCHOSIM that captures the dynamic association between infection, treatment, and morbidity [7]…”

Onchocerciasis: Current knowledge and future goals

“…Human Onchocerciasis is a vector-borne disease, a parasitic infection caused by filarial worms and transmitted by repeated bites of infected blackflies. Because the vectors -blackflies of the genus Simulium -are insects that breed as larvae in fast-flowing rivers and streams and bite humans near these sites, the disease is also known as "river blindness" (1).…”