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对盘尾丝虫病患者的免疫流行病学分析揭示了个体和社区层面上微丝蚴载量和伊维菌素摄入之间的关联。

Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels.

机构信息

Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany.

Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana ; Faculty of Allied Health Sciences and School of Medical Sciences of Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

出版信息

PLoS Negl Trop Dis. 2014 Feb 20;8(2):e2679. doi: 10.1371/journal.pntd.0002679. eCollection 2014 Feb.

Abstract

Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes.

摘要

大规模药物驱虫(MDA)计划针对盘尾丝虫使用伊维菌素(IVM),该药针对微丝蚴(MF),即虫体的后代。尽管寄生虫负担很高,但大多数受感染者的反应较低,表现出调节性免疫反应。最近,随着 MDA 计划的实施,出现了一种微丝蚴血症(a-MF)个体,但对其免疫反应知之甚少。在这项免疫流行病学研究中,我们比较了无感染志愿者和 MF(+)或 a-MF 感染者的寄生虫学、病理学和免疫特征。后者来自加纳中部或阿散蒂地区的村庄,研究时,这些村庄分别接受了多达 8 轮或仅 1 轮 MDA。有趣的是,a-MF 患者的结节较少,对所有测试刺激物的 IL-10 反应降低。另一方面,该患者组在体外刺激或血浆中显示出相反的 IL-5 谱,后者的反应减弱与嗜酸性粒细胞和相关因子减少以及中性粒细胞升高有关。此外,具有 MF、IVM 或区域(中部与阿散蒂)等协变量的多元回归分析表明,免疫反应与不同的协变量相关:尽管 O. volvulus 特异性 IL-5 反应主要与 MF 相关,但 IL-10 分泌与个体 IVM 治疗(IIT)次数呈负相关。所有血浆参数(嗜酸性粒细胞阳离子蛋白、IL-5、嗜酸性粒细胞和中性粒细胞)与 MF 高度相关。关于 IL-17 分泌,尽管各组之间对丝虫特异性或旁观者刺激物无差异,但这些反应与区域高度相关。这些数据表明,免疫反应既受 IIT 又受社区内 IVM MDA 轮数的影响。因此,由于 IVM MDA 降低了感染压力,即使社区成员没有定期参加这些计划,也可能影响其免疫状况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1e/3930501/64a66af9140a/pntd.0002679.g001.jpg

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