The Ecology, Emergence and Pandemic Potential of Nipah virus in Bangladesh

描述（由申请人提供）：尼帕病毒（NiV）是一种致命的人畜共患副粘病毒，以果蝠（翼蝠属）为宿主。它于1999年通过家养猪宿主在马来西亚出现，导致脑炎暴发，病死率为40%。自那时以来，在孟加拉国和印度发生了7次经确认的NiV疫情。该病毒已达到出现的晚期阶段，具有从蝙蝠直接传播给人、感染呼吸道途径的能力、多达五个人传人周期以及增加的病死率（71%）。我们认为，孟加拉国的人口密度和社会行为、新冠病毒生物学、果蝠中的新冠病毒生态学以及蝙蝠、牲畜和人类之间的相互作用增加了新冠病毒爆发和大流行的可能性。我们将在孟加拉国进行为期5年的实地调查，收集蝙蝠生态学、病毒学、人口学和社会行为方面的数据。我们将使用我们的结果来参数化蝙蝠，牲畜和人类内部和之间的NiV动力学的数学模型。我们将研究哪些因素导致持续的人与人之间的爆发，并评估NiV出现大流行的可能性。我们将检验4个假设：1)蝙蝠对人类的NiV溢出风险是果蝠种群生物学的一个因素，特别是它们的同步繁殖模式。我们将研究菌落聚集、生育动态和其他相互作用如何影响病毒流行增加的可能性，以及爆发的开始。2)孟加拉国以人类为主导的环境中蝙蝠的行为增加了它们与牲畜和人的接触，并导致了NiV出现的更高级阶段。我们将增强我们先前开发的矩阵模型，并将其与基于卫星和无线电遥测的蝙蝠群落之间迁移率的测量参数化。我们将对NiV分离株进行测序，并检查与外溢暴发有关的蝙蝠株多样性。3)人类社会行为、高人口密度和特定的病毒特征加强了孟加拉国的NiV传播，这些因素促进了人与人之间的传播。我们将使用疫情数据来检验特定的人类行为和NiV感染是否以及以下哪一项促进了人与人之间的传播：1)呼吸道脱落的异质性导致一些个体充当超级传播者；2)患者与亲属密切身体接触；3)孟加拉国NiV感染呼吸道的倾向。4)孟加拉国的新冠病毒对区域和流行病传播构成威胁。我们将使用我们的模型来估计未来新冠病毒在孟加拉国不同条件下的传播以及通过国际旅行传播到其他国家的情况。公共卫生相关性：尼帕病毒在孟加拉国反复出现，导致70%的感染者在人际传播链中死亡。我们的工作将研究这种病毒出现的原因，并帮助在孟加拉国建立尼帕病毒的早期预警系统。它还将使我们更好地了解这种病原体和其他病原体成为大流行的可能性。

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.