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

摘要 除非我们更好地了解和防止蝙蝠传播的病毒蔓延到中间宿主 对于人类来说，我们在阻止流行病方面的能力将受到严重限制。埃尼帕病毒是由蝙蝠传播的，RNA 通过这条路线传播的病毒。在所有报告的人类埃尼帕病毒感染中，近一半是 与接触生病的家养动物有关，尽管我们对埃尼帕病毒的驱动因素的理解 溢出效应和具体的传播途径仍然受到严重限制。基于关于以下方面的初步数据 BAT，家养动物和人类感染，这项多学科的研究综合了流行病学、生态学、 和人类学，以确定埃尼帕病毒在孟加拉国家养动物中的溢出途径 它们对人类健康构成的风险。我们的第一个目标是确定埃尼帕病毒溢出的驱动因素 孟加拉国法里德布尔的家养动物。我们将使用多重泛埃尼帕病毒检测来确定 中翼蝙蝠和栖息在该栖息地附近的驯养动物通过横断面感染 和前瞻性研究。结合对蝙蝠驯养动物相互作用和天气的深入研究 数据，我们将建立统计模型，以确定这些因素中每个因素的相对贡献。我们的第二个目标 描述哪些埃尼帕病毒正从蝙蝠传播到家养动物。血清学 对孟加拉国动物的研究表明，它们经常感染非尼帕埃尼帕病毒。穿过 对患病家养动物的监测和采样，我们将描述溢出的特定病毒 来自法里德布尔的蝙蝠。我们的第三个目标是确定从驯养的埃尼帕病毒传播的风险 从动物到人类。我们假设，未被检测到的埃尼帕病毒在人类中的溢出是通过 与患病的家养动物接触，并将对人类进行横断面和前瞻性血清调查 他们与法里德布尔的患病动物有密切接触。我们仍然对埃尼帕病毒的溢出一无所知 通过中间宿主-包括溢出的特定病毒、频率和分布 溢出效应和传播途径--后果自负。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 埃尼帕病毒在蝙蝠体内传播。通过了解哪些蜂鸟病毒感染人类，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向公共卫生监测项目提供建议 对孟加拉国各地的案件进行调查。我们对法里德布尔溢出效应的调查也可以扩大- 直到孟加拉国的其他地区和埃尼帕病毒在蝙蝠中传播的国家，这样我们才能真正开始 以了解埃尼帕病毒在全球范围内溢出的规模。

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.