Investigating seasonal drivers of viral zoonoses from Madagascar fruit bats

调查马达加斯加果蝠病毒性人畜共患病的季节性驱动因素

• 批准号: 9920107
• 负责人: Philippe DUSSART
• 金额: $ 13.5万
• 依托单位: PASTEUR INSTITUTE FROM MADAGASCAR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-02 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920107
• 关键词: Address; Adopted; Age; Animals; Antibodies; Antibody titer measurement; Attention; Automobile Driving; Autophagocytosis; Biological; Biological Assay; Biology; Birth; Chiroptera; Collaborations; Collection; Communicable Diseases; Communities; Consequentialism; Coronavirus; Country; Data; Ebola; Economics; Educational workshop; Emerging Communicable Diseases; Epidemic; Epidemiology; Evaluation; Event; Excretory function; Expression Profiling; Family; Filovirus; Frankfurt-Marburg Syndrome Virus; Fruit; Future; Genes; Goals; Head; Health; Hendra Virus; Henipavirus; Human; Immune response; Immunize; Immunologics; Infection; Lead; Longevity; Lyssavirus; Madagascar; Medicine; Modeling; Molecular; Molecular Analysis; Pattern; Performance; Periodicity; Pharyngeal structure; Physiologic pulse; Physiological; Plasma; Play; Population; Process; Public Health; Research; Research Personnel; Resources; Risk; Role; SARS coronavirus; Sampling; Scientist; Seasons; Secondary to; Series; Serologic tests; Serological; Seroprevalences; Serum; Severe Acute Respiratory Syndrome; Swab; System; Taxon; Techniques; Technology; Testing; Time; Tissues; Universities; Urine; Variant; Viral; Viral Antibodies; Viremia; Virulent; Virus; Virus Diseases; Virus Shedding; Work; Zoonoses; base; bat-borne; chronic infection; college; cross-species transmission; epidemiological model; field study; interest; novel; pathogen; prevent; professor; skills; social; tool; transmission process; virology

Zoonotic pathogens derived from an animal reservoir account for some 60-75% of emerging infectious diseases in humans, a disproportionate number of which take place in resource poor countries where the economic and social burden of corresponding health crises is greatest. Bats have received much attention in recent years for their role as the putative reservoir hosts for a number of high profile, virulent zoonoses, including Ebola and Marbug filoviruses, Hendra and Nipah henipaviruses, and SARS coronavirus, all of which demonstrate peaks in transmission—both between bats and from bats to spillover hosts (including humans)—during the resource-poor dry season for the system in question. Seasonal forcings are known to play an important role in driving epidemic cycles in infectious diseases for both humans and wildlife, though the mechanistic drivers of seasonality can sometimes be difficult to identify. In bat systems, researchers have posited that dynamical patterns could result from pulsed additions of annual, synchronous births to the pool susceptible to immunizing viruses, while others have suggested that bats might instead maintain these viruses as persistent infections across the duration of their lifespans and undergo periodic bouts of viral shedding. A true understanding of these dynamics will be essential to predicting and preventing the next bat zoonosis, a critical public health aim for developing world countries, like Madagascar, where we base our work. To date, longitudinal data of a fine enough scale do not exist to distinguish among the proposed hypotheses. Our project brings together a diverse team of molecular biologists from Institut Pasteur de Madagascar and Duke-NUS, epidemiological modelers from Princeton, and field ecologists from Harvard to address these challenges. In Aim 1 of our research, we introduce novel Luminex assays to identify henipaviruses, filoviruses, coronaviruses, and lyssaviruses antibodies in both bat and human serum samples in Madagascar. In Aim 2, we build mechanistic transmission models exploring the proposed hypotheses of seasonal drivers of infection dynamics in bat systems, and in Aim 3, we unite these goals in a longitudinal model- guided field study, with corresponding serological and molecular analyses, which will generate the data needed to enable effective model comparison and evaluation. Our work addresses questions of critical interest to both evolutionary biology and public health, while simultaneously building scientific capacities in the developing world.

来自动物宿主的人畜共患病原体约占新发病原体的 60-75% 人类传染病，其中大部分发生在资源匮乏的地区 相应健康危机造成的经济和社会负担最严重的国家。蝙蝠有 近年来，由于它们作为许多假定的储库宿主的作用而受到广泛关注。 引人注目的致命人畜共患病，包括埃博拉病毒和马尔巴格丝状病毒、亨德拉病毒和尼帕病毒 亨尼帕病毒和 SARS 冠状病毒，所有这些病毒都表现出传播高峰——两者都在 蝙蝠以及从蝙蝠到溢出宿主（包括人类）——在资源匮乏的旱季 有问题的系统。众所周知，季节性强迫在推动流行病周期方面发挥着重要作用 人类和野生动物的传染病，尽管季节性的机械驱动因素可以 有时很难识别。在蝙蝠系统中，研究人员假设动态模式 可能是由于每年同步出生的婴儿脉冲式添加到易受免疫影响的池中所致 病毒，而其他人则认为蝙蝠可能会维持这些病毒的持久性 在其整个生命周期中都会受到感染，并经历周期性的病毒脱落。一个真实的 了解这些动态对于预测和预防下一次蝙蝠人畜共患病至关重要 发展中国家的重要公共卫生目标，例如我们工作的基地马达加斯加。到 日期，不存在足够精细的纵向数据来区分拟议的 假设。我们的项目汇集了来自巴斯德研究所的多元化分子生物学家团队 马达加斯加和杜克-新加坡国立大学、普林斯顿大学的流行病学建模师以及来自普林斯顿大学的现场生态学家 哈佛致力于应对这些挑战。在我们研究的目标 1 中，我们引入了新颖的 Luminex 检测方法 在马达加斯加的蝙蝠和人血清样本中鉴定亨尼帕病毒、丝状病毒、冠状病毒和狂犬病病毒抗体。 在目标 2 中，我们建立了机械传播模型，探索所提出的季节性假设 蝙蝠系统中感染动态的驱动因素，在目标 3 中，我们将这些目标统一在一个纵向模型中 - 指导现场研究，以及相应的血清学和分子分析，这将生成数据 需要进行有效的模型比较和评估。我们的工作解决了关键问题 对进化生物学和公共卫生的兴趣，同时建立科学 发展中国家的能力。