DESCRIPTION (provided by applicant): Nipah virus (NiV) is a lethal zoonotic paramyxovirus with fruit bat (Pteropus spp.) reservoir hosts. It emerged in 1999 in Malaysia via domestic pig amplifier hosts, causing an encephalitis outbreak with a 40% case fatality rate. Since this time, 7 recognized outbreaks of NiV have occurred in Bangladesh and India. The virus has achieved an advanced stage of emergence, with direct transmission from bats to people, capacity to infect the respiratory pathway, up to five cycles of human-to-human transmission, and increased (71%) case fatality. We propose that human population density and social behavior in Bangladesh, NiV viral biology, NiV ecology in fruit bats, and interactions between bats, livestock and humans create increased potential for NiV outbreaks and pandemic emergence. We will conduct 5 years of fieldwork in Bangladesh, collecting data on bat ecology, virology, demography and social behavior. We will use our results to parameterize a mathematical model of NiV dynamics within and among bats, livestock and humans. We will examine which factors cause sustained human-to-human outbreaks, and assess NiV's potential for pandemic emergence. We will test 4 hypotheses: 1) That NiV spillover risk from bats to humans is a factor of fruit bat population biology, especially their synchronous breeding patterns. We will examine how colony aggregation, birthing dynamics, and other interactions affect the potential for increased viral prevalence, and initiation of an outbreak. 2) That bat behavior in the human-dominated environment in Bangladesh has increased their contact with livestock and people, and led to a more advanced stage of NiV emergence. We will enhance our previously developed matrix model, and parameterize this with measurements of the migration rate between bat colonies based on satellite and radio telemetry. We will sequence NiV isolates, and examine strain diversity in bats in relation to spillover outbreaks. 3) That NiV transmission in Bangladesh is enhanced by human social behavior, high population density and specific viral traits, and that these factors promote human-to-human transmission. We will use outbreak data to examine whether specific human behaviors and NiV infection and which of the following promote person-toperson transmission: 1) Heterogeneity in respiratory shedding leading to some individuals acting as superspreaders; 2) Close physical contact between sick patients and relatives; 3) The propensity of Bangladesh NiV to infect the respiratory tract. 4) That NiV in Bangladesh presents a threat for regional and pandemic spread. We will use our model to estimate future spread of NiV under different conditions within Bangladesh and to other countries via international travel.

PUBLIC HEALTH RELEVANCE: Nipah virus has emerged repeatedly in Bangladesh causing death in 70% of infected people undergoing chains of person-to-person transmission. Our work will examine why this virus is emerging, and help provide an early warning system for Nipah virus in Bangladesh. It will also give us a better understanding of the likelihood of this and other pathogens becoming pandemic.