Solving Opportunities for Spillover (SOS): Frequency and Mechanisms of Cross-species Transmission of Henipaviruses in Bangladesh

摘要 除非我们更好地理解和防止蝙蝠传播的病毒溢出到中间宿主 和人类，我们阻止流行病的能力将受到严重限制。亨尼帕病毒是蝙蝠传播的，RNA 通过这条途径传播的病毒在所有报告的人类亨尼帕病毒感染中， 与接触生病的家养动物有关，尽管我们对亨尼帕病毒驱动因素的了解 溢出效应和具体的传播途径仍然非常有限。根据初步数据， 蝙蝠，驯养动物和人类感染，这项多学科研究整合了流行病学，生态学， 和人类学，以确定亨尼帕病毒进入孟加拉国家养动物的溢出途径， 它们对人类健康构成的风险。我们的第一个目标是确定亨尼帕病毒溢出的驱动因素， 在孟加拉国的法里德布尔驯养动物。我们将使用多重泛亨尼帕病毒检测， 通过横断面调查， 和前瞻性研究。结合对蝙蝠与驯养动物的相互作用和天气的深入研究 数据，我们将建立统计模型，以确定每个因素的相对贡献。我们的第二个目标 是描述哪些亨尼帕病毒是从蝙蝠传播给家养动物的。血清学 对孟加拉国动物的研究表明，它们经常感染非尼帕亨尼帕病毒。通过 监测和采样生病的家养动物，我们将描述特定的病毒， 从法里德布尔的蝙蝠身上。我们的第三个目标是确定亨尼帕病毒从家养动物传播的风险。 动物到人类我们假设，未被检测到的亨尼帕病毒在人类中的溢出是通过以下途径发生的： 接触患病的家养动物，并将对人类进行横断面和前瞻性血清调查 在法里德布尔与患病动物有密切接触的人。我们仍然对亨尼帕病毒的溢出一无所知 通过中间宿主-包括特定的病毒溢出，频率和分布， 溢出效应和传播途径--我们自己承担风险。从这项研究中获得的知识将是 立即适用于孟加拉国和其他国家的人类和动物健康计划， 亨尼帕病毒在蝙蝠体内传播。通过了解哪些亨尼帕病毒感染人类，以及它们是如何感染的， 我们可以就如何优化检测和流行病学， 调查孟加拉国各地的案件。我们对法里德布尔溢出效应的调查也可以按比例进行- 直到孟加拉国的其他地区和亨尼帕病毒在蝙蝠中传播的国家，这样我们就可以真正开始 来评估亨尼帕病毒在全球蔓延的规模。

Abstract Until and unless we better understand and prevent spillovers of bat-borne viruses into intermediate hosts and humans, we will be severely limited in our ability to stop pandemics. Henipaviruses are bat-borne, RNA viruses that spillover through this route. Nearly half of all reported human henipavirus infections have been associated with contact with sick domesticated animals, though our understanding of drivers of henipavirus spillovers and specific transmission pathways remains severely limited. Building on preliminary data about bat, domesticated animal and human infections, this multidisciplinary study integrates epidemiology, ecology, and anthropology to identify spillover pathways for henipaviruses into domesticated animals in Bangladesh and the risk they pose to human health. Our first aim is to identify drivers of henipavirus spillovers into domesticated animals in Faridpur, Bangladesh. We will use multiplex pan-henipavirus assays to identify infections in Pteropus medius bats and domesticated animals living nearby this roost through cross-sectional and prospective studies. Combined with intensive studies of bat-domesticated animal interactions and weather data, we will build statistical models to identify the relative contribution of each of these factors. Our second aim is to describe which henipaviruses are being transmitted from bats to domesticated animals. Serologic studies of animals in Bangladesh show that they are frequently infected with non-Nipah henipaviruses. Through surveillance for and sampling of sick domesticated animals, we will describe the specific viruses that spillover from bats in Faridpur. Our third aim is to determine the risk of henipavirus transmission from domesticated animals to humans. We hypothesize that undetected henipavirus spillovers in humans are occurring through contact with sick domesticated animals and will conduct cross-sectional and prospective serosurveys of humans who have close contact with sick animals in Faridpur. We remain ignorant about henipavirus spillovers through intermediate hosts – including the specific viruses spilling over, the frequency and distribution of spillovers, and the pathways of transmission – at our own peril. The knowledge gained from this study will be immediately applicable to human and animal health programs in Bangladesh and other countries where henipaviruses circulate in bats. By learning about which henipaviruses infect humans, and how they are infected, we can advise public health surveillance programs on how to optimize detection and epidemiologic investigation of cases across Bangladesh. Our investigations about spillovers in Faridpur can also be scaled- up to other areas of Bangladesh and countries where henipaviruses circulate in bats so that we can truly begin to appreciate the scale of henipavirus spillovers in the global landscape.