Emerging Infectious Diseases Research Center - East and Central Africa

项目摘要 自2012年第一例中东呼吸综合征冠状病毒（MERS-CoV）人间病例以来， 世界卫生组织报告说，已有2220人感染，近800人死亡 遍布中东、欧洲、亚洲和美国的27个国家。尽管单峰骆驼 是已知的病毒储存库，但对与病毒相关的机制和因素的了解有限。 骆驼传染给人，这仍然是人类感染的主要机制。人类疫情 中东和亚洲记录在案的MERS-CoV病例数量继续增长;然而， 迄今为止，在东非国家没有记录在案的人类疾病病例， 尽管有证据表明中东呼吸综合征冠状病毒在骆驼中流行， 本地区东非没有人类疾病可能是由于病毒的可塑性， 传播效率低和/或毒力减弱，或疾病监测和报告不力， 这些人是居住在该地区偏远干旱土地上的边缘化的养骆驼游牧民。我们将 通过在一个封闭的社区内进行综合纵向队列研究来验证这些假设。 牧民和他们的骆驼种群，这是众所周知的维持中东呼吸综合征冠状病毒在马尔萨比特县的传播， 肯尼亚，为了确定病毒在骆驼中的维持和传播， 传播给人类，以及人类感染的严重程度。为了确定MERS冠状病毒是否是 在基因和表型上与中东和亚洲的已知病毒分支不同，我们将分离出 东非病毒，每两周从211头骆驼的婴儿队列（出生-1岁）中收集样本，然后 培养和分离病毒，与已知的进化枝病毒进行基因型和表型比较 调查薄弱的监测和难以获得医疗保健的结合是否是造成 如果没有疾病，我们将随访一年，通过每两周一次的访问，每周一次， 电话，并获得免费电话号码，以便深入检查和测试MERS CoV 疾病此外，我们还将对4500名以上的呼吸道疾病住院和门诊患者进行识别、检测和随访， 马尔萨比特县转诊医院3年。为了评估该病毒对人类构成的风险，我们将确定 骆驼的病毒散毒水平，并将其与人畜共患传染病的发病率和骆驼的类型联系起来。 接触会增加传播风险。这些研究将确定在东非传播的病毒类型， 增加对MERS-CoV可塑性及其对人畜共患病传播和疾病影响的了解。通过 阐明人畜共患病传播的频率和机制，以及向临床人类疾病的发展， 我们将通过以下方式确定病毒对处于新出现的致命病毒前线的社区构成的风险： 由于他们的职业和生活方式，为发展更好的监测和适当的 预防和控制策略。

PROJECT SUMMARY Since 2012 when the first human case of Middle East respiratory syndrome coronavirus (MERS-CoV) was confirmed, the World Health Organization has reported >2220 human infections and almost 800 deaths spread across 27 countries located in the Middle East, Europe, Asia, and the United States. Although dromedary camels are the known reservoir of the virus, there is limited knowledge on the mechanisms and factors associated with camel-to-human transmission, which remains the primary mechanism of human infections. Human outbreaks and the number of documented cases of MERS-CoV continue to grow in the Middle East and Asia; however there have, to date, been no documented cases of human disease in the eastern Africa countries where >65% of the world’s dromedary camels are found. This is despite evidence of prevalent MERS-CoV infection of camels in the region. The absence of human disease in East Africa may be explained by viral plasticity resulting in inefficient transmission and/or weakened virulence, or poor disease surveillance and reporting among the marginalized camel-owning nomadic pastoralist populations that inhabit remote arid lands of the regions. We will test these hypotheses by conducting integrated longitudinal cohort studies within a closed community of naïve pastoralists and their camel population that is known to sustain MERS-CoV circulation in Marsabit County, Kenya, in order to determine the maintenance and transmission of the virus among camels, zoonotic transmission to humans, and severity of human infections. To determine if the circulating MERS-CoV is genetically and phenotypically distinct from known virus clades in the Middle East and Asia, we will isolate the East African virus by collecting samples biweekly from an infant cohort (birth -1 year) of 211 camels, followed by culture and isolation of the virus to performed genotypic and phenotypic comparison with the known clade viruses To investigate whether a combination of weak surveillance and poor access to health care are responsible for absence of disease, we will follow-up for a year, a cohort of 573 camel handlers through biweekly visits, weekly telephone calls, and access to a toll-free number in order to intensively examine and test them for MERS-CoV disease. In addition, we will identify, test, and follow-up >4500 in- and out-patients with respiratory illness at Marsabit County Referral Hospital for 3 years. To assess the risk the virus poses to humans, we will determine the level of viral shedding in camels, and relate this to the incidence of zoonotic transmission, and types of camel contact that increase transmission risk. These studies will identify the type of virus circulating in East Africa, increasing knowledge about plasticity of MERS-CoV and its impact on zoonotic transmission and disease. By elucidating the frequency and mechanisms of zoonotic transmission, and progression to clinical human disease, we will define the risk the virus poses to this community at the frontline of a newly emergent virulent virus by virtue of their occupation and lifestyle, paving the way for development of improved surveillance and appropriate prevention and control strategies.