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.

Highlights

  • Four life stages of Onchocerca volvulus live in humans: the infective (L3) larvae injected by the vector undergo two moultings to develop via L4 larvae into juvenile adults (L5) and mature to reproductively competent adults within around 1 year (Duke, 1991; Basanez and Ricardez-Esquinca, 2001)

  • Around 0.56 Million people were estimated to live in the 13 small endemic foci in 6 countries in Central and South America (Center for Disease Control (CDC), 2013) and around 0.3 Million in Yemen (Mackenzie et al, 2012) Onchocerciasis control started in 1974 with the Onchocerciasis Control Programme in West Africa (OCP) which conducted large scale larviciding of vector breeding sites in the West African Savannah

  • Ivermectin is suitable for mass drug administration (MDA) because it has an excellent safety profile: adverse reactions are due to the efficacy of the drug, i.e. the immunological reaction of the body to the death of the microfilariae which includes inflammatory components (Mackenzie et al, 2003)

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Summary

Introduction

Systematic and evidence based clinical research in onchocerciasis Dr Awadzi was instrumental in development of the methods for assessing the efficacy and safety of anti-onchocercal drugs, providing training and collaboration for many young scientists and physicians. He evaluated most drug candidates for onchocerciasis proposed before and after the development of ivermectin. Four life stages of Onchocerca volvulus live in humans: the infective (L3) larvae injected by the vector undergo two moultings to develop via L4 larvae into juvenile adults (L5) and mature to reproductively competent adults (macrofilariae) within around 1 year (Duke, 1991; Basanez and Ricardez-Esquinca, 2001).

Onchocerciasis control programmes
Ivermectin - the ’standard of control’
Moving towards onchocerciasis elimination in Africa
Challenges for elimination of onchocerciasis in Africa
The path from discovery to qualification of drugs for human use
Research for new drugs for onchocerciasis control and elimination
Drugs approved for human use for other indications
Findings
Discovery of new compounds
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