The effects of Mansonella perstans infections on concomitant mycobacterial infections and BCG vaccination efficacy in Ghana, Cameroon, and Benin

永久曼氏杆菌(Mansonella perstans，M.perstans)是撒哈拉以南非洲最流行的寄生虫之一，在流行地区估计有1亿感染者。儿童和青少年很早就被这种线虫感染。尽管曼氏杆菌病本身可能因其无症状或轻微的临床表现而与公共卫生问题不太相关，但永久分枝杆菌可以调节或阻碍对伴随感染(联合感染)的免疫力。来自加纳的初步研究表明，患有布鲁里溃疡病(BUD)的儿童合并感染了永久分枝杆菌。由于在这些永久分枝杆菌分离株中检测到了必要的沃尔巴克氏菌内共生体，因此合并感染的人对抗生素治疗敏感。这些观察结果构成了由来自加纳、贝宁、喀麦隆和德国(杜塞尔多夫和波恩)的五个伙伴机构开展的拟议的流行病学、临床和免疫学研究的基础。我们提出的问题是，与永久分枝杆菌混合感染引起的免疫极化是否影响：1)对分枝杆菌疾病(即芽孢杆菌、结核病)的易感性；2)芽孢杆菌/结核的病程和恢复；以及3)儿童接种卡介苗的效果。多西环素对感染永生化支原体的健康青少年的驱虫作用将被用来确定混合感染对抗分枝杆菌免疫的影响。最后，我们的目标是通过建立和实施基于PCR和血清学的方法来提高诊断水平。在这方面，一个关键因素将是建立一种永久分枝杆菌的动物模型，以识别成虫的特定抗原。该项目的预期结果可能对Perstans流行国家的公共卫生政治产生重要影响。将作出重大努力，促进非洲和德国伙伴之间的互动，包括技术转让和能力建设。这将改善撒哈拉以南非洲不同文化和语言背景的研究人员之间正在进行的合作，并为今后的合作提供便利。

Mansonella perstans (M. perstans) is one of the most prevalent parasites in sub-Saharan Africa with estimated 100 million infected individuals in endemic regions. Children and adolescents are infected early by this nematode species. Although Mansonellosis itself may be less relevant for public health issues because of its asymptomatic or mild clinical picture, M. perstans can modulate or impede immunity against concomitant infections (co-infections). Initial studies from Ghana indicate co-infections of M. perstans in children with Buruli ulcer disease (BUD). Since essential Wolbachia endosymbionts were detected in these M. perstans isolates, co-infected individuals are susceptible to antibiotic treatment. These observations form the basis for the proposed epidemiological, clinical, and immunological studies performed by five partner institutions from Ghana, Benin, Cameroon, and Germany (Düsseldorf and Bonn). We address the questions whether immune polarization due to co-infection with M. perstans affects i) susceptibility to mycobacterial diseases (i.e. BUD, Tuberculosis (TB), ii) disease course and recovery of BUD/TB, and iii) BCG vaccination efficacy in children. Doxycycline-mediated deworming of M. perstans infected healthy adolescents will be applied to determine the influence co-infections on anti-mycobacterial immunity. Finally, we aim to improve diagnosis by establishing and implementing PCR-based and serological methods. In this regard a crucial factor will be establishment of an M. perstans animal model to identify specific antigens of adult worms. The expected results of this project may have crucial implications for public health politics in M. perstans endemic countries. Major efforts will be undertaken to catalyze interactions between African and German partners including technology transfer and capacity building. This will improve ongoing and facilitate future collaborations between researchers with different cultural and linguistic background from sub-Saharan Africa.