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的人类盘尾丝虫病的病原体盘尾丝虫，由于大量分发杀微丝蚴药物伊维菌素，已接近消灭。我们在咬人媒介中仍然发现的少数感染性幼虫是否足以维持寄生虫的地方性，将在三个不同的地理区域进行研究：在阿达马瓦高地，由于动物园的松懈，传播似乎已经中断，在北部的苏丹稀树草原，传播仍然以接近阈值的速度进行，在巴门达附近的梅彻姆山谷，从没有数据的地方开始在人和牛身上捕获的蚋可以提供关于传播的数据以及牛和动物丝虫在媒介中的比例，这是动物预防的指标。人类盘尾丝虫病能否最终根除，基本上取决于盘尾丝虫的种群动态和生殖生物学，我们对盘尾丝虫的种群动态和生殖生物学知之甚少，因为它不能在人类宿主中进行研究。相反，我们专注于牛的同源物，Onchocerca ochengi，我们在一群接触自然传播的瘤牛中进行研究： 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建立以及蠕虫的交配和繁殖行为？ 盘尾丝虫属的物种和品系是如何进化的，抗药性在蠕虫中的分布有多快？牛丝虫O. ochengi，这是非常普遍的，在我们的研究领域，提供了一个很好的研究工具。在我们的一群从出生到自然传播近三年的瘤牛中，我们可以在理想的系统中研究蠕虫的种群动态。我们希望在本项目期间，它们的寄生虫种群达到平衡，即新蠕虫的获得率应等于旧寄生虫的自然死亡率。这从来没有在良好控制的条件下进行过纵向研究！在蒂宾根的马克斯-普朗克研究所，分子遗传技术被开发出来，可以将单个微丝蚴分配给它们的母亲和父亲。所以我们可以详细研究它们的繁殖行为和种群动态。与此同时，我们专注于在非洲中部稀树草原上的盘尾丝虫物种形成的热点中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学上不太重要，但其研究构成了人类疾病研究的桥梁，Ngaoundere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.