Emerging Infectious Diseases Research Center - East and Central Africa

项目总结 自2012年第一例人感染中东呼吸综合征冠状病毒(MERS-CoV)以来 经证实，世界卫生组织报告称，2220人感染，近800人死亡 覆盖中东、欧洲、亚洲和美国的27个国家和地区。尽管单峰骆驼 都是已知的病毒宿主，但对与之相关的机制和因素的了解有限 骆驼传人，这仍然是人类感染的主要机制。人类暴发疫情 中东和亚洲记录的MERS冠状病毒病例数量继续增长；然而 到目前为止，在东非国家还没有记录的人类疾病病例，在这些国家中 世界上最大的单峰骆驼被发现。尽管有证据表明MERS冠状病毒在骆驼中的流行感染 在这一地区。东非没有人类疾病可能是因为病毒的可塑性导致了 传播效率低和/或毒力减弱，或疾病监测和报告不力 居住在该地区偏远干旱土地上的边缘化骆驼游牧民族。我们会 通过在一个封闭的天真社区内进行整合的纵向队列研究来检验这些假设 牧民和他们的骆驼种群在马尔萨比特县维持着MERS冠状病毒的传播， 肯尼亚，为了确定病毒在骆驼中的维持和传播，人畜共患病 向人类传播，以及人类感染的严重性。以确定正在循环的MERS冠状病毒是否 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 通过每两周从211头骆驼的婴儿队列(出生1岁)收集样本来感染东非病毒，随后是 病毒的培养和分离，以进行与已知分支病毒的基因分型和表型比较 调查薄弱的监测和难以获得医疗保健的组合是否导致 在没有疾病的情况下，我们将对573名骆驼饲养员进行为期一年的跟踪调查，通过每周两次的访问 电话和免费号码，以便集中检查和测试MERS冠状病毒 疾病。此外，我们将在以下地点识别、测试和跟踪&gt；4500名住院和门诊呼吸系统疾病患者 在马尔萨比特县转诊医院工作3年。为了评估病毒对人类构成的风险，我们将确定 骆驼体内的病毒排出水平，并与人畜共患传播的发生率和骆驼的类型有关 接触者会增加传播风险。这些研究将确定在东非传播的病毒类型， 增加对MERS冠状病毒的可塑性及其对人畜共患传播和疾病影响的认识。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进展， 我们将通过以下方式确定病毒对处于新出现的毒力病毒前线的社区构成的风险 他们的职业和生活方式的优点，为改善监测和适当的发展铺平了道路 防控策略。

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.