Kuesel Annette C
UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, 20 Avenue Appia, 1211 Geneva, Switzerland.
Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):272-286. doi: 10.1016/j.ijpddr.2016.04.002. Epub 2016 May 19.
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.
盘尾丝虫病是一种由丝虫线虫盘尾丝虫引起的寄生虫病，通过媒介传播。超过99%的感染风险人群生活在非洲。1974年在西非启动了盘尾丝虫病防治工作，最初是进行病媒控制，后来补充了伊维菌素群体药物给药；1995年在其他非洲流行国家开展了年度伊维菌素社区定向治疗（CDTI）。这显著降低了感染率。随着塞内加尔和马里病灶通过年度CDTI消除盘尾丝虫病的概念验证，这使得目标是到2020年在选定的非洲国家消除盘尾丝虫病，到2025年在80%的非洲国家消除该病。实现这些目标面临的挑战包括：一些流行国家因冲突导致控制项目延迟或中断；跨境病灶；可能出现对伊维菌素敏感性低的寄生虫菌株；以及另一种通过寄生虫媒介传播的疾病——罗阿丝虫病的共同流行，这减缓或阻碍了CDTI的实施。其中一些挑战可以通过对盘尾丝虫比伊维菌素有更高疗效的新药或药物组合来解决。本文回顾了从新化合物发现到其具备大规模使用资格的过程，以及监管机构为被忽视热带病药物开发提供的支持。还回顾了盘尾丝虫病新药或治疗方案在获得监管批准和具备大规模使用资格道路上的研究现状。这项研究包括伊维菌素和阿苯达唑的新方案及组合、针对盘尾丝虫内共生菌沃尔巴克氏体的抗生素、氟苯达唑、莫西菌素和埃莫昔肽，以及新化合物的发现。
