Ecology of MERS-CoV in camels, humans, and wildlife in Ethiopia

人畜共患疾病是存在于动物体内并可传播给人类的疾病。目前，人畜共患病约占全球所有新发感染的75%。然而，引发人畜共患疾病出现和传播的因素仍然知之甚少，部分原因是它们涉及多物种、复杂的种间和种内关系，以及许多相互作用的环境、行为、社会和经济因素。中东呼吸综合征-冠状病毒（MERS-CoV）就是一个很好的例子。中东呼吸综合征冠状病毒于2012年首次在人类中被发现，并导致36%的感染者死亡，但人们对导致其出现的原因知之甚少。例如，已查明若干人间病例与从非洲进口的骆驼有过接触；研究还在非洲野生动物中发现了中东呼吸综合征冠状病毒；虽然骆驼是已知的中东呼吸综合征冠状病毒宿主，但尚不清楚是否还有其他宿主或中间宿主，也不清楚中东呼吸综合征冠状病毒溢出发生的频率和条件。该项目将调查中东呼吸综合征冠状病毒的自然生态与更广泛的社会、经济和环境变化的关系；与骆驼有密切接触的潜在野生动物蓄水池；以及对消费、放牧和交易骆驼及骆驼产品的人类的潜在溢出效应。这项工作对应对疾病威胁的国家安全具有直接重要性；中东呼吸综合征冠状病毒目前在世界卫生组织迫切需要加速研究的优先疾病名单上。为了了解中东呼吸综合征冠状病毒何时以及在何种条件下出现并从动物传播给人类，研究人员提出了以下问题：(1)骆驼经济的社会、文化和行为特征如何塑造病毒生态？(2)哪些种内和种间相互作用增加了MERS-CoV的出现和传播？(3)哪些气候和环境变量与传播有关？研究人员将对野生和家养（骆驼）水库进行实地研究，在两年多的时间里，在四个地点从目标野生动物（有蹄类和高脂类）中收集大约800个样本。他们将在整个骆驼价值链上开展社会行为研究，并纵向跟踪单个骆驼，以确定同一个体何时转化为中东呼吸综合征冠状病毒阳性状态。他们将进行实验室分析并进行病毒测序。研究人员将使用“似是而非的参数集方法”（MPPS）将这些数据整合到数学模型中，该模型将确定哪些机制情景与观察到的MERS-CoV在骆驼和人类中的模式一致。这种广泛包容的方法扩展了对人畜共患疾病出现的传统研究。传播模式将适用于与畜牧生产有关的其他人畜共患疾病，并将有助于确定减少疾病出现和传播的干预措施。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Zoonotic diseases are diseases that exist in animals and can be transmitted to humans. Zoonoses currently account for approximately 75 percent of all emerging infections worldwide. However, the factors that trigger zoonotic disease emergence and spread remain poorly understood, in part because they involve multiple species, complex inter-species and intra-species relationships, and many interacting environmental, behavioral, social, and economic factors. Middle Eastern Respiratory Syndrome-Coronavirus (MERS-CoV) presents a case in point. MERS-CoV was first identified in human beings in 2012 and has killed 36 percent of those infected, but little is known about what has led to its emergence. For example, several human cases have been traced to contact with camels imported from Africa; studies also have detected MERS-CoV in African wildlife; and while camels are a known reservoir host for MERS-CoV, it is not known if there are additional reservoirs or intermediate hosts, or how frequently and under what conditions MERS-CoV spillover occurs. This project will investigate the natural ecology of MERS-CoV in relation to broader social, economic, and environmental changes; its potential wildlife reservoirs in close contact with camels; and the potential for spillover to humans who consume, herd, and trade camels and camel products. This work is of direct importance to national security with respect to disease threats; MERS-CoV is currently on the World Health Organization's priority shortlist of diseases in urgent need of accelerated research. To understand when and under what conditions MERS-CoV emerges and spreads from animals to humans, the researchers ask, (1) How do social, cultural and behavioral characteristics of camel economics shape virus ecologies? (2) Which intra- and inter-species interactions increase MERS-CoV emergence and transmission? and (3) What climatic and environmental variables are associated with transmission? Researchers will conduct field studies of wild and domestic (camel) reservoirs, collecting roughly 800 samples from targeted wildlife (ungulates and eulipotyphlads) over two years at four locations. They will carry out socio-behavioral studies across the camel value chain and follow individual camels longitudinally to determine when the same individuals seroconvert to MERS-CoV positive status. They will conduct laboratory analyses and do viral sequencing. The researchers will integrate the data into mathematical models using the 'Method of Plausible Parameter Sets' (MPPS), which will determine which mechanistic scenarios are consistent with observed patterns of MERS-CoV in camels and humans. This broadly inclusive approach expands upon traditional studies of zoonotic disease emergence. The transmission models will be applicable to other zoonotic diseases linked to livestock production and will help to identify interventions to reduce disease emergence and transmission.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.