Is elimination of human onchocerciasis possible? Epidemiological, entomological and parasitological studies in a bovine model in Cameroon

我们自1976年以来在喀麦隆研究人类盘尾丝虫病的病原体盘尾丝虫病，由于微丝虫药伊维菌素的大规模分布，盘尾丝虫病已接近消灭。我们在咬人媒介中仍然发现的少数感染幼虫是否足以维持寄生虫的地方性，应在三个不同的地理区域进行研究：在阿达马瓦高原，传播似乎已因动物预防而中断；在北部苏丹稀树草原，传播速度仍接近阈值水平；在巴门达附近的梅切姆山谷，尚无数据。对人和牛的模拟蝇捕获应提供正在进行的传播以及牛和动物丝虫病媒中所占比例的数据，这些数据是动物预防的指标。人类盘尾丝虫病能否最终被根除，基本上取决于盘尾丝虫病的种群动态和生殖生物学，由于无法在人类宿主中进行研究，我们对盘尾丝虫病知之甚少。相反，我们关注的是牛的同系物，盘尾丝虫，我们在一群暴露于自然传播的zebu牛中研究：-这些蠕虫如何调节它们在脊椎动物宿主中的种群密度？-哪些因素决定了新幼虫的形成以及成虫的交配和繁殖行为？-盘尾丝虫的种类和品系是如何进化的？在虫体中产生抗药性的速度有多快？牛奥氏丝虫病在本研究区高度流行，为研究提供了良好的工具。在我们的瘤牛群中，从出生开始接触自然传播近三年，我们可以在一个理想的系统中研究蠕虫种群动态。我们期望它们的寄生虫数量在这个项目期间达到平衡，即获得新寄生虫的速度应该等于旧寄生虫的自然死亡率。这从来没有在控制良好的条件下进行纵向研究！在德国马克斯-普朗克研究所（Max-Planck-Institute in tbingen），分子遗传技术被开发出来，可以将单个微丝虫分配给它们的母亲和父亲。这样我们就可以详细研究繁殖行为和种群动态。与此同时，我们重点研究了在中非稀树草原盘尾丝虫物种形成热点地区存在的盘尾丝虫菌株和物种的进化。该项目基于与喀麦隆农村发展研究所（IRAD） 20多年来的成功合作，该研究所旨在研究和控制牛寄生虫。虽然牛丝虫病在兽医方面的重要性不大，但它们的研究是研究人类疾病的桥梁，恩oundere大学和巴门达大学的参与加强了这些机构的研究和教学能力。

Onchocerca volvulus, the causative agent of human onchocerciasis, which we study in Cameroon since 1976, has been brought close to elimination by the mass-distribution of the microfilaricidal drug ivermectin. Whether the few infective larvae that we still find in the man-biting vectors are sufficient to maintain the parasite endemic, shall be studied in three different geographic regions: The Adamawa highland, where transmission seems to be interrupted already due to zooprophylaxix, in the Sudan savanna in the North, where transmission still goes on at a rate close to the threshold level, and in the Metchum valley near Bamenda, from where there are no data yet. Simulium-fly catches on man and cattle shall provide data on the ongoing transmission and the proportion of bovine and animal filariae in the vectors, which are indicators of zooprophylaxis.Whether human onchocerciasis can be finaly eradicated shall basically depend from the population dynamics and reproductive biology of the Onchocerca worms, about which we know very little, because it cannot be studied in the human host. Instead we focus on a bovine homologue, Onchocerca ochengi, which we study in a herd of zebu cattle, exposed to natural transmission:- How do these worms regulate their population density in the vertebrate host?- Which factors govern the establishment of new-coming larvae and the mating and reproduction behaviour of adult worms?- How does the evolution of Onchocerca-species and strains go on, and how quickly resistance may be distributed amongst the worms?The bovine filaria O. ochengi, which is highly prevalent in our study area, provides an excellent research tool. In our herd of Zebu cattle, exposed to natural transmission from birth since almost three years, we can study the worm population dynamics in an ideal system. We expect their parasite population to reach its equilibrium during the period of this project, i.e. the rate of acquisition of new worms should equal the natural death-rate of old parasites. This has never been followed-up by a longitudinal study under well-controlled conditions!At the Max-Planck-Institute in Tübingen, molecular genetic techniques were developed that allow assigning single microfilariae to their mother and father worm. So we can study the reproductive behaviour and population dynamics in great detail. At the same time, we focus on the evolution of Onchocerca strains and species that are present in this hot-spot of Onchocerca speciation in the savanna of Central Africa.This project is based on over 20 years of successful collaboration with the Cameroonian Institute for Research for Rural Development (IRAD), which aims to study and control cattle parasites. Though bovine filariae are not of much veterinary importance, their research forms a bridge to human diseases and the participation of the Ngaoundere and Bamenda universities strengthens the research and teaching capacities of these institutions.