Emerging Infectious Diseases Research Center - East and Central Africa

新发传染病研究中心 - 东非和中非

• 批准号: 10464357
• 负责人: M KARIUKI NJENGA
• 金额: $ 66.45万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-13 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464357
• 关键词: Africa; Africa South of the Sahara; African; Agriculture; Air; Animals; Asia; Berlin; Birth; Blood Circulation; Camels; Centers for Disease Control and Prevention (U.S.); Central Africa; Cessation of life; China; Clinical; Clinical Research; Collaborations; Communicable Diseases; Communities; Congo; Coronavirus Infections; Country; County; Democratic Republic of the Congo; Development; Diagnostics Research; Disease; Disease Outbreaks; Disease Surveillance; Dromedaries; Eastern Africa; Ebola; Emerging Communicable Diseases; Environment; Epidemic; Europe; Far East; Food; Frequencies; Genotype; Health; High Prevalence; Hospital Referrals; Human; Incidence; Infant; Infection; Infectious Diseases Research; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Infrastructure; Institutes; International; Kenya; Knowledge; Laboratories; Life Style; Livestock; Longitudinal cohort study; Maintenance; Marburgvirus; Measures; Middle East; Middle East Respiratory Syndrome; Middle East Respiratory Syndrome Coronavirus; Morbidity - disease rate; Nomads; Occupations; Outpatients; Pathogenicity; Phenotype; Physicians; Pilot Projects; Population; Prevention; Public Health; Reagent; Recurrence; Reporting; Research; Rift Valley Fever; Rift Valley fever virus; Risk; Role; Sampling; Scientist; Seroprevalences; Services; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Site; Tanzania; Telephone; Testing; Time; Travel; Tropical Medicine; Uganda; United States; Universities; Veterinarians; Viral; Viral Hemorrhagic Fevers; Viral reservoir; Virulence; Virulent; Virus; Virus Diseases; Virus Shedding; Visit; Washington; World Health Organization; ZIKA; Zoonoses; base; cohort; community living; density; emerging pathogen; experience; field study; follow-up; forest; global health; health care availability; health seeking behavior; human disease; improved; influenza epidemic; mortality; pathogen; physical conditioning; programs; respiratory; response; social culture; translational study; transmission process; vector; viral detection; viral transmission

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.

项目概要 自 2012 年发现首例中东呼吸综合征冠状病毒 (MERS-CoV) 人类病例以来 经证实，世界卫生组织已报告超过 2220 例人类感染病例和近 800 例死亡病例 遍布中东、欧洲、亚洲和美国的 27 个国家。虽然单峰骆驼 是已知的病毒储存库，但对其相关机制和因素的了解有限 骆驼向人类传播，这仍然是人类感染的主要机制。人类爆发 中东和亚洲记录的中东呼吸综合征冠状病毒病例数量继续增加；然而 迄今为止，东非国家还没有记录到人类疾病病例，这些国家的人口比例超过 65% 世界上的单峰骆驼被发现。尽管有证据表明骆驼普遍感染中东呼吸综合征冠状病毒 在该地区。东非没有人类疾病的原因可能是病毒的可塑性导致 传播效率低下和/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地区的边缘化的拥有骆驼的游牧民族。我们将 通过在一个封闭的幼稚社区内进行综合纵向队列研究来检验这些假设 已知在马萨比特县维持中东呼吸综合征冠状病毒循环的牧民及其骆驼种群， 肯尼亚，为了确定病毒在骆驼中的维持和传播，人畜共患 传播给人类以及人类感染的严重程度。确定循环的 MERS-CoV 是否是 在遗传和表型上与中东和亚洲已知的病毒分支不同，我们将分离出 东非病毒，每两周从 211 头骆驼的婴儿组（出生 -1 岁）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是否是造成这种情况的原因 如果没有疾病，我们将对 573 名骆驼饲养员进行为期一年的跟踪，每两周一次、每周一次 拨打电话并拨打免费电话，以便对他们进行中东呼吸综合征冠状病毒检查和测试 疾病。此外，我们还将识别、检测和随访超过 4500 名患有呼吸道疾病的住院和门诊患者。 马萨比特县转诊医院 3 年。为了评估病毒对人类构成的风险，我们将确定 骆驼的病毒脱落水平，并将其与人畜共患传播的发生率以及骆驼的类型联系起来 增加传播风险的接触。这些研究将确定在东非传播的病毒类型， 增加对中东呼吸综合征冠状病毒的可塑性及其对人畜共患传播和疾病的影响的了解。经过 阐明人畜共患传播的频率和机制以及临床人类疾病的进展， 我们将通过以下方式定义该病毒对处于新出现的剧毒病毒前线的社区构成的风险： 凭借他们的职业和生活方式，为改进监测和适当的发展铺平道路 预防和控制策略。