The need for evidence-based strategies and tools for onchocerciasis elimination in Africa.

In a recent article we discussed the feasibility of onchocerciasis elimination in Africa by 2025. We expressed concern that elimination may be impeded by failure to build on the lessons learned in the African onchocerciasis control programmes and the introduction of strategies and tools from the Americas. Richards et al. and Cupp et al. wrote to refute our concern and described recent achievements with stopping treatment in some areas.In this response, we discuss their arguments which did not convince us. We point out several scientific flaws in the American conceptual framework of elimination which has led to longer periods of treatment than necessary, and in the use of an arbitrary threshold for stopping treatment. We show that recent achievements fall significantly short of what would be needed to achieve onchocerciasis elimination by 2025.We conclude our response by advocating for a more objective and inclusive debate on strategies and tools for onchocerciasis elimination.

Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on lessons learnt from the African control programmes.

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.

Wolbachia endosymbiont levels in severe and mild strains of Onchocerca volvulus.

Epidemiological, clinical and genetic data have all suggested that the filarial parasite Onchocerca volvulus, the causative agent of onchocerciasis (or river blindness) exists as two strains in West Africa. The severe strain induces severe ocular disease in a large proportion of the infected population, while the mild strain induces little ocular disease. Although DNA probes based upon a non-coding repeat sequence family can distinguish the two strains, the underlying basis for this difference in pathogenicity is not understood. Recently, several studies have implicated products produced by the Wolbachia endosymbiotic bacterium of O. volvulus in the pathogenesis of onchocerciasis. This suggested the hypothesis that differences in the Wolbachia endosymbiont population might be responsible for the pathogenic differences noted in the two strains. To test this hypothesis, quantitative PCR assays were used to measure the amount of Wolbachia DNA per nuclear genome in a collection of well characterized samples of mild and severe strain O. volvulus. The median ratio of Wolbachia DNA to nuclear DNA was significantly greater in severe strain parasites than in mild strain parasites. These data support the hypothesis that the pathogenic differences seen in severe and mild strain O. volvulus may be a function of their relative Wolbachia burden and provide additional support to the hypothesis that Wolbachia products may play a central role in the pathogenesis of ocular onchocerciasis.

Final report of the Conference on the eradicability of Onchocerciasis.

Sixty-four experts from a variety of disciplines attended a Conference on the Eradicability of Onchocerciasis at The Carter Center, in Atlanta GA, held January 22-24, 2002. The Conference, which was organized by The Carter Center and the World Health Organization, with funding from the Bill & Melinda Gates Foundation, addressed the question: "Is onchocerciasis (River Blindness) eradicable with current knowledge and tools?" Former US President Jimmy Carter attended part of the final plenary proceedings on January 24.The Conference consisted of a series of presentations by invited expert speakers (Appendix C) and further deliberations in four workgroups (Appendix D) followed by plenary discussion of major conclusions. The presentations underlined epidemiological and entomological differences between onchocerciasis in Africa and the Americas. Whilst onchocerciasis in Africa covers extensive areas and is associated with striking human and fly population migrations and remarkably efficient black fly vectors, in the Americas onchocerciasis is found in limited foci. Human and fly population migration are not major problems in the Americas, where most black fly species are inefficient, though some efficient black flies are also found there. Vector control has been effectively applied in the Onchocerciasis Control Program in West Africa (OCP) with remarkable results, interrupting transmission in most parts of the original Program area. The use of ivermectin has given variable results: while ivermectin treatment has been effective in all endemic areas in controlling onchocerciasis as a public health problem, its potential for interrupting transmission is more promising in hypo- and mesoendemic areas. The African Program for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, applies ivermectin, its principal control tool, to communities in high-risk areas as determined by rapid epidemiological mapping of onchocerciasis (REMO) and Geographic Information Systems (GIS). In the Americas, through support of the Onchocerciasis Elimination Program in the Americas (OEPA), a strategy of bi-annual ivermectin treatment of at least 85% of the eligible populations in all endemic communities is showing very good results and promises to be effective in eliminating onchocerciasis in the region.The Conference concluded that onchocerciasis is not eradicable using current tools due to the major barriers to eradication in Africa. However, the Conference also concluded that in most if not all the Americas, and possibly Yemen and some sites in Africa, transmission of onchocerciasis can be eliminated using current tools. The Conference recommended that where interruption of transmission is feasible and cost effective, programs should aim for that goal using all appropriate and available interventions so that the Onchocerca volvulus can eventually be eliminated and interventions halted. Although interruption of transmission of onchocerciasis cannot currently be achieved in most of Africa, the Conference recommended that efforts be made to preserve areas in West Africa made free of onchocerciasis transmission through the Onchocerciasis Control Program over the past 25 years. In the remaining hyper and mesoendemic foci in Africa, continued annual distribution of ivermectin will keep onchocerciasis controlled to a point where it is no longer a public health problem or constraint to economic development.