Investigating seasonal drivers of viral zoonoses from Madagascar fruit bats

来自动物宿主的人畜共患病原体约占新发病原体的60-75%， 人类感染性疾病，其中不成比例的数量发生在资源贫乏的地区， 在这些国家，相应的卫生危机造成的经济和社会负担最大。蝙蝠有 近年来，由于它们作为许多植物的假定储库宿主的作用而备受关注。 高知名度的烈性人畜共患病，包括埃博拉病毒和马布格丝状病毒、亨德拉病毒和尼帕病毒 亨尼帕病毒和SARS冠状病毒，所有这些病毒都表现出传播高峰， 蝙蝠和从蝙蝠到溢出宿主（包括人类）-在资源贫乏的旱季， 系统有问题。众所周知，季节性强迫在推动流行病周期方面发挥着重要作用， 人类和野生动物的传染病，尽管季节性的机械驱动因素可以 有时很难识别。在蝙蝠系统中，研究者们假设， 可能是由于每年同步出生的婴儿脉冲式地增加到易受免疫接种影响的群体中， 而其他人则认为蝙蝠可能会将这些病毒作为持久性病毒 在他们的生命周期中，他们会受到感染，并经历周期性的病毒脱落。一个真正 了解这些动态将是至关重要的预测和预防下一个蝙蝠人兽共患病， 这是我们为马达加斯加等发展中国家开展工作的一个重要公共卫生目标。到 日期，纵向数据的一个足够精细的规模不存在区分之间的建议 假设我们的项目汇集了来自巴斯德研究所的分子生物学家的多元化团队， 马达加斯加和杜克-NUS，流行病学建模从普林斯顿大学，和外地生态学家从 哈佛应对这些挑战。在我们研究的目标1中，我们引入了新的Luminex检测方法， 鉴定马达加斯加蝙蝠和人类血清样本中的亨尼帕病毒、丝状病毒、冠状病毒和狂犬病毒抗体。 在目标2中，我们建立了机械传播模型，探索季节性的假设， 蝙蝠系统中感染动力学的驱动因素，在目标3中，我们将这些目标统一在一个纵向模型中- 指导实地研究，并进行相应的血清学和分子分析，以生成数据 需要进行有效的模型比较和评估。我们的工作解决了一些关键问题， 对进化生物学和公共卫生都感兴趣，同时建立科学的 发展中国家的能力。

Zoonotic pathogens derived from an animal reservoir account for some 60-75% of emerging infectious diseases in humans, a disproportionate number of which take place in resource poor countries where the economic and social burden of corresponding health crises is greatest. Bats have received much attention in recent years for their role as the putative reservoir hosts for a number of high profile, virulent zoonoses, including Ebola and Marbug filoviruses, Hendra and Nipah henipaviruses, and SARS coronavirus, all of which demonstrate peaks in transmission—both between bats and from bats to spillover hosts (including humans)—during the resource-poor dry season for the system in question. Seasonal forcings are known to play an important role in driving epidemic cycles in infectious diseases for both humans and wildlife, though the mechanistic drivers of seasonality can sometimes be difficult to identify. In bat systems, researchers have posited that dynamical patterns could result from pulsed additions of annual, synchronous births to the pool susceptible to immunizing viruses, while others have suggested that bats might instead maintain these viruses as persistent infections across the duration of their lifespans and undergo periodic bouts of viral shedding. A true understanding of these dynamics will be essential to predicting and preventing the next bat zoonosis, a critical public health aim for developing world countries, like Madagascar, where we base our work. To date, longitudinal data of a fine enough scale do not exist to distinguish among the proposed hypotheses. Our project brings together a diverse team of molecular biologists from Institut Pasteur de Madagascar and Duke-NUS, epidemiological modelers from Princeton, and field ecologists from Harvard to address these challenges. In Aim 1 of our research, we introduce novel Luminex assays to identify henipaviruses, filoviruses, coronaviruses, and lyssaviruses antibodies in both bat and human serum samples in Madagascar. In Aim 2, we build mechanistic transmission models exploring the proposed hypotheses of seasonal drivers of infection dynamics in bat systems, and in Aim 3, we unite these goals in a longitudinal model- guided field study, with corresponding serological and molecular analyses, which will generate the data needed to enable effective model comparison and evaluation. Our work addresses questions of critical interest to both evolutionary biology and public health, while simultaneously building scientific capacities in the developing world.