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Research for new drugs for elimination of onchocerciasis in Africa.

ABSTRACT: Onchocerciasis is a parasitic, vector borne disease caused by the filarial nematode Onchocerca volvulus. More than 99% of the population at risk of infection live in Africa. Onchocerciasis control was initiated in West Africa in 1974 with vector control, later complemented by ivermectin mass drug administration and in the other African endemic countries in 1995 with annual community directed treatment with ivermectin (CDTI.) This has significantly reduced infection prevalence. Together with proof-of-concept for onchocerciasis elimination with annual CDTI from foci in Senegal and Mali, this has resulted in targeting onchocerciasis elimination in selected African countries by 2020 and in 80% of African countries by 2025. The challenges for meeting these targets include the number of endemic countries where conflict has delayed or interrupted control programmes, cross-border foci, potential emergence of parasite strains with low susceptibility to ivermectin and co-endemicity of loiasis, another parasitic vector borne disease, which slows down or prohibits CDTI implementation. Some of these challenges could be addressed with new drugs or drug combinations with a higher effect on Onchocerca volvulus than ivermectin. This paper reviews the path from discovery of new compounds to their qualification for large scale use and the support regulatory authorities provide for development of drugs for neglected tropical diseases. The status of research for new drugs or treatment regimens for onchocerciasis along the path to regulatory approval and qualification for large scale use is reviewed. This research includes new regimens and combinations of ivermectin and albendazole, antibiotics targeting the O. volvulus endosymbiont Wolbachia, flubendazole, moxidectin and emodepside and discovery of new compounds.

SUBMITTER: Kuesel AC

PROVIDER: S-EPMC5196484 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Research for new drugs for elimination of onchocerciasis in Africa.

Kuesel Annette C AC

International journal for parasitology. Drugs and drug resistance 20160519 3

Onchocerciasis is a parasitic, vector borne disease caused by the filarial nematode Onchocerca volvulus. More than 99% of the population at risk of infection live in Africa. Onchocerciasis control was initiated in West Africa in 1974 with vector control, later complemented by ivermectin mass drug administration and in the other African endemic countries in 1995 with annual community directed treatment with ivermectin (CDTI.) This has significantly reduced infection prevalence. Together with proo ...[more]

PMID: 27693536

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Project description:Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

Project description:BackgroundOnchocerciasis (river blindness) is a parasitic disease transmitted by blackflies. Symptoms include severe itching, skin lesions, and vision impairment including blindness. More than 99% of all cases are concentrated in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly decreased morbidity, and the treatment goal is shifting from control to elimination in Africa.MethodsWe estimated financial resources and societal opportunity costs associated with scaling up community-directed treatment with ivermectin and implementing surveillance and response systems in endemic African regions for alternative treatment goals--control, elimination, and eradication. We used a micro-costing approach that allows adjustment for time-variant resource utilization and for the heterogeneity in the demographic, epidemiological, and political situation.ResultsThe elimination and eradication scenarios, which include scaling up treatments to hypo-endemic and operationally challenging areas at the latest by 2021 and implementing intensive surveillance, would allow savings of $1.5 billion and $1.6 billion over 2013-2045 as compared to the control scenario. Although the elimination and eradication scenarios would require higher surveillance costs ($215 million and $242 million) than the control scenario ($47 million), intensive surveillance would enable treatments to be safely stopped earlier, thereby saving unnecessary costs for prolonged treatments as in the control scenario lacking such surveillance and response systems.ConclusionsThe elimination and eradication of onchocerciasis are predicted to allow substantial cost-savings in the long run. To realize cost-savings, policymakers should keep empowering community volunteers, and pharmaceutical companies would need to continue drug donation. To sustain high surveillance costs required for elimination and eradication, endemic countries would need to enhance their domestic funding capacity. Societal and political will would be critical to sustaining all of these efforts in the long term.

Project description:BACKGROUND:Onchocerciasis (river blindness), caused by the filarial worm species Onchocerca volvulus, is a serious vector-borne neglected tropical disease (NTD) of public health and socioeconomic concern. It is transmitted through the bite of black flies of the genus Simulium, and manifested in dermal and ocular lesions. Ninety-nine percent of the total global risk and burden of onchocerciasis is in Africa. This scoping review examines the key challenges related to the elimination of onchocerciasis by 2020-2025 in Africa, and proposes recommendations to overcome the challenges and accelerate disease elimination. To find relevant articles published in peer-reviewed journals, a search of PubMed and Google Scholar databases was carried out. MAIN TEXT:Rigorous regional interventions carried out to control and eliminate onchocerciasis in the past four decades in Africa have been effective in bringing the disease burden under control; it is currently not a public health problem in most endemic areas. Notably, transmission of the parasite is interrupted in some hyperendemic localities. Recently, there has been a policy shift from control to complete disease elimination by 2020 in selected countries and by 2025 in the majority of endemic African countries. The WHO has published guidelines for stopping mass drug administration (MDA) and verifying the interruption of transmission and elimination of human onchocerciasis. Therefore, countries have revised their plans, established a goal of disease elimination in line with an evidence based decision to stop MDA and verify elimination, and incorporated it into their NTDs national master plans. Nevertheless, challenges remain pertaining to the elimination of onchocerciasis in Africa. The challenge we review in this paper are: incomplete elimination mapping of all transmission zones, co-endemicity of onchocerciasis and loiasis, possible emergence of ivermectin resistance, uncoordinated cross-border elimination efforts, conflict and civil unrest, suboptimal program implementation, and technical and financial challenges. This paper also proposes recommendations to overcome the challenges and accelerate disease elimination. These are: a need for complete disease elimination mapping, a need for collaborative elimination activities between national programs, a need for a different drug distribution approach in conflict-affected areas, a need for routine monitoring and evaluation of MDA programs, a need for implementing alternative treatment strategies (ATSs) in areas with elimination anticipated beyond 2025, and a need for strong partnerships and continued funding. CONCLUSIONS:National programs need to regularly monitor and evaluate the performance and progress of their interventions, while envisaging the complete elimination of onchocerciasis from their territory. Factors hindering the targeted goal of interruption of parasite transmission need to be identified and remedial actions should be taken. If possible and appropriate, ATSs need to be implemented to accelerate disease elimination by 2025.

Project description:BACKGROUND:Onchocerciasis is found predominantly in Africa where large scale vector control started in 1974. Registration and donation of ivermectin by Merck & Co in 1987 enabled mass treatment with ivermectin in all endemic countries in Africa and the Americas. Although elimination of onchocerciasis with ivermectin was considered feasible only in the Americas, recently it has been shown possible in Africa too, necessitating fundamental changes in technical and operational approaches and procedures. MAIN BODY:The American programme(OEPA) operating in onchocerciasis epidemiological settings similar to the mild end of the complex epidemiology of onchocerciasis in Africa, has succeeded in eliminating onchocerciasis from 4 of its 6 endemic countries. This was achieved through biannual mass treatment with ivermectin of 85% of the eligible population, and monitoring and evaluation using serological tests in children and entomological tests. The first African programme(OCP) had a head start of nearly two decades. It employed vector control and accumulated lots of knowledge on the dynamics of onchocerciasis elimination over a wide range of epidemiological settings in the vast expanse of its core area. OCP made extensive use of modelling and operationalised elimination indicators for entomological evaluation and epidemiological evaluation using skin snip procedures. The successor African programme(APOC) employed mainly ivermectin treatment. Initially its objective was to control onchocerciasis as a public health problem but that objective was later expanded to include the elimination of onchocerciasis where feasible. Building on the experience with onchocerciasis elimination of the OCP, APOC has leveraged OCP's vast modelling experience and has developed operational procedures and indicators for evaluating progress towards elimination and stopping ivermectin mass treatment of onchocerciasis in the complex African setting. CONCLUSIONS:Following the closure of APOC in 2015, implementation of onchocerciasis elimination in Africa appears to overlook all the experience that has been accumulated by the African programmes. It is employing predominantly American processes that were developed in a dissimilar setting from the complex African onchocerciasis setting. This is impeding progress towards decisions to stop intervention in many areas that have reached the elimination point. This article summarizes lessons learned in Africa and their importance for achieving elimination in Africa by 2025.

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Research for new drugs for elimination of onchocerciasis in Africa.

Publications

Research for new drugs for elimination of onchocerciasis in Africa.

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