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Background Onchocerciasis (“river blindness”) can cause severe morbidity, including vision loss and various skin manifestations, and is targeted for elimination using ivermectin mass drug administration (MDA). We calculated the number of people with Onchocerca volvulus infection and onchocercal skin and eye disease as well as disability-adjusted life years (DALYs) lost from 1990 through to 2030 in areas formerly covered by the African Programme for Onchocerciasis Control. Methods Per MDA implementation unit, we collated data on the pre-control distribution of microfilariae (mf) prevalence and the history of control. Next, we predicted trends in infection and morbidity over time using the ONCHOSIM simulation model. DALY estimates were calculated using disability weights from the Global Burden of Disease Study. Results In 1990, prior to MDA implementation, the total population at risk was 79.8 million with 26.0 million (32.5%) mf-positive individuals, of whom 17.5 million (21.9%) had some form of onchocercal skin or eye disease (2.5 million DALYs lost). By 2030, the total population was predicted to increase to 236.1 million, while the number of mf-positive cases (about 6.8 million, 2.9%), people with skin or eye morbidity (4.2 million, 1.8%), and DALYs lost (0.7 million) were predicted to decline. Conclusions MDA has had a remarkable impact on the onchocerciasis burden in countries previously under the APOC mandate. In the few countries where we predict continued transmission between now and 2030, intensified MDA could be combined with local vector control efforts, or the introduction of new drugs for mopping up residual cases of infection and morbidity.

Background Oral ivermectin is a safe broad spectrum anthelminthic used for treating several neglected tropical diseases (NTDs). Currently, ivermectin use is contraindicated in children weighing less than 15 kg, restricting access to this drug for the treatment of NTDs. Here we provide an updated systematic review of the literature and we conducted an individual-level patient data (IPD) meta-analysis describing the safety of ivermectin in children weighing less than 15 kg. Methodology/Principal findings A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for IPD guidelines by searching MEDLINE via PubMed, Web of Science, Ovid Embase, LILACS, Cochrane Database of Systematic Reviews, TOXLINE for all clinical trials, case series, case reports, and database entries for reports on the use of ivermectin in children weighing less than 15 kg that were published between 1 January 1980 to 25 October 2019. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017056515. A total of 3,730 publications were identified, 97 were selected for potential inclusion, but only 17 sources describing 15 studies met the minimum criteria which consisted of known weights of children less than 15 kg linked to possible adverse events, and provided comprehensive IPD. A total of 1,088 children weighing less than 15 kg were administered oral ivermectin for one of the following indications: scabies, mass drug administration for scabies control, crusted scabies, cutaneous larva migrans, myiasis, pthiriasis, strongyloidiasis, trichuriasis, and parasitic disease of unknown origin. Overall a total of 1.4% (15/1,088) of children experienced 18 adverse events all of which were mild and self-limiting. No serious adverse events were reported. Conclusions/Significance Existing limited data suggest that oral ivermectin in children weighing less than 15 kilograms is safe. Data from well-designed clinical trials are needed to provide further assurance., Author summary Oral ivermectin is a safe and efficacious drug for the treatment of neglected tropical diseases. To date, ivermectin is not indicated in children weighing less than 15 kg because there have been insufficient safety data to support a change of recommendation. A PRISMA-level systematic review was conducted, and 97 potential sources were identified. All lead investigators were contacted to share individual patient data if they could provide the minimum criteria. These were the known weights of the children less than 15 kg in whom there were possible adverse events. A total of 17 investigators replied, sharing individual-level patient data (IPD) from 15 studies, which represent a database of 1,088 children weighing less than 15 kg treated with oral ivermectin. Overall 18 adverse events were reported in 1.4% (15/1,088) of children, all of which were mild and self-limiting. No serious adverse events were recorded. These data suggest that ivermectin is safe for use in children weighing less than 15 kilograms. Further data from well-designed clinical trials are needed to assess the safety of oral ivermectin at escalating doses in children weighing less than 15 kg.

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.