Collaborative Research: Microparasite-Macroparasite Interactions: Dynamics of Co-infection and Implications for Disease Control

摘要多种寄生虫感染宿主在大多数自然种群中是常态而不是例外，然而寄生虫动力学的研究主要集中在单个寄生虫与单个宿主的相互作用上。免疫学的基本原理表明，寄生虫（细菌，病毒，原生动物）和大型寄生虫（蠕虫）共同感染宿主对疾病动态有重要影响。例如，接触大型寄生虫可能会增加宿主对重要的微寄生虫病的易感性和进展，如人类艾滋病、结核病和疟疾。本研究的中心目标是调查微寄生虫-大寄生虫相互作用的后果，在三个不同层次的生物组织的疾病模式：个人，种群和物种。为了实现这一目标，非洲布法罗（Syncerus caffer）共感染牛结核病（BTB，牛分枝杆菌）和胃肠道线虫将被用作模型系统，以调查个人水平的感染模式和寄生虫种群动态。具体而言，结合实地和圈养研究和数学建模将被用来评估模式的感染和免疫力在这些自由放养的动物，了解线虫治疗对BTB传播的影响，并检查BTB对线虫的相互影响。从这个系统扩大，一个全面的数据库的寄生虫和病原体感染野生哺乳动物和人类，然后将被用来调查蠕虫的影响分布的微寄生虫病在人群和物种。结合起来，这些分析将揭示如何在宿主内的免疫相互作用之间的micoparasites和macroparasites形状模式的疾病在自然宿主种群和物种。这项研究的更广泛的影响包括多个研究生，本科生和准专业人员的培训;研究结果的生态和经济上重要的野生动物疾病的管理应用;和公共卫生界的积极合作，以了解使用蠕虫控制的效用作为一种工具，打击人体微寄生虫病。

Abstract Infection of hosts by multiple parasite species is the norm rather than the exception in most natural populations, yet studies of parasite dynamics largely focus on single parasites interacting with single hosts. Fundamental principles of immunology suggest that co-infection of hosts by microparasites (bacteria, viruses, protozoa) and macroparasites (helminths) should have important effects on disease dynamics. For example, exposure to macroparasites may increase host susceptibility to and progression of important microparasitic diseases such as AIDS, tuberculosis and malaria in humans. The central goal of this study is to investigate the consequences of microparasite-macroparasite interactions for patterns of disease at three distinct levels of biological organization: individuals, populations and species. To achieve this goal, African buffalo (Syncerus caffer) co-infected with bovine tuberculosis (BTB, Mycobacterium bovis) and gastrointestinal nematodes will be used as a model system to investigate individual-level patterns of infection and parasite population dynamics. Specifically, a combination of field and captive studies and mathematical modeling will be used to assess patterns of infection and immunity in these free-ranging animals, understand the effects of nematode treatment on BTB transmission, and examine the reciprocal effects of BTB on nematodes. Scaling up from this system, a comprehensive database of parasites and pathogens infecting wild mammals and humans will then be used to investigate the effect of helminths on the distribution of microparasitic diseases across populations and species. In combination, these analyses will reveal how within-host immunological interactions between micoparasites and macroparasites shape patterns of disease in natural host populations and among species. Broader impacts of this study include training of multiple graduate students, undergraduate students and paraprofessionals; application of study results to the management of an ecologically and economically important wildlife disease; and active collaboration with the public health community to understand the utility of using helminth control as a tool for combating microparasitic diseases in humans.