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

人畜共患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病例的75%。然而，引发人畜共患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个物种，复杂的物种间和物种内关系，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。MERS-CoV于2012年首次在人类身上发现，已导致36%的感染者死亡，但人们对它的出现原因知之甚少。例如，已追踪到几个人感染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MERS-CoV；虽然骆驼是MERS-CoV的已知宿主，但尚不清楚是否有更多的宿主或中间宿主，也不知道MERS-CoV溢出发生的频率和条件。该项目将调查与更广泛的社会、经济和环境变化有关的MERS-CoV的自然生态；与骆驼密切接触的潜在野生动物水库；以及溢出到消费、放牧和贸易骆驼和骆驼产品的人类的可能性。这项工作对疾病威胁方面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被列入世界卫生组织迫切需要加快研究的疾病的优先候选名单。为了了解MERS-CoV何时以及在什么条件下出现并从动物传播到人类，研究人员问：(1)骆驼经济学的社会、文化和行为特征如何塑造病毒生态？(2)哪些物种内和物种间的相互作用增加了MERS-CoV的出现和传播？以及(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，在四个地点的两年时间里从目标野生动物(有蹄类和真骆驼)收集大约800个样本。他们将在骆驼价值链上进行社会行为研究，并纵向跟踪单个骆驼，以确定相同的个体何时血清转换为MERS-CoV阳性状态。他们将进行实验室分析和病毒测序。研究人员将使用“貌似合理的参数集方法”(MPPS)将数据整合到数学模型中，这将确定哪些机械场景与在骆驼和人类身上观察到的MERS-CoV模式一致。这一广泛包容的方法扩展了对人畜共患病出现的传统研究。传播模型将适用于与畜牧业生产相关的其他人畜共患病，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NSF的法定使命，并通过使用基金会的智力优势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.