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

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.