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

描述(申请人提供)：尼帕病毒(Nipah Virus，NIV)是一种带有果蝠(Pteropus spp.)的致死性人畜共患副粘病毒。水库主人。它于1999年在马来西亚通过国内猪扩增宿主出现，导致脑炎暴发，病死率为40%。自那时以来，孟加拉国和印度已经发生了7起已确认的新城疫疫情。该病毒已达到出现的后期阶段，从蝙蝠直接传播到人，具有感染呼吸道的能力，人与人之间最多传播5个周期，病例死亡率增加(71%)。我们认为，孟加拉国的人口密度和社会行为、新城疫病毒生物学、果蝠的新城疫生态以及蝙蝠、牲畜和人之间的互动增加了新城疫爆发和大流行出现的可能性。我们将在孟加拉国进行为期5年的实地考察，收集蝙蝠生态、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暴发，并评估新城疫出现大流行的可能性。我们将检验4个假说：1)新城疫病毒从蝙蝠向人类的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、分娩动态和其他相互作用如何影响病毒流行率增加和疫情爆发的可能性。2)在孟加拉以人类为主的环境中，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。我们将改进我们以前开发的矩阵模型，并使用基于卫星和无线电遥测的蝙蝠群体之间迁移率的测量来对其进行参数化。我们将对新城疫病毒分离株进行测序，并检查蝙蝠的菌株多样性与溢出疫情的关系。3)孟加拉国的新城疫传播是由于人类的社会行为、高人口密度和特定的病毒特征而加强的，这些因素促进了人与人之间的传播。我们将使用暴发数据来检查特定的人类行为和新城疫病毒感染是否以及以下哪些因素促进人与人之间的传播：1)呼吸道脱落的异质性导致一些人充当超级传播者；2)病人与亲属之间的密切身体接触；3)孟加拉国新城疫病毒感染呼吸道的倾向。4)孟加拉国的新城疫病毒对区域和大流行传播构成威胁。我们将使用我们的模型来估计未来新城疫病毒在孟加拉国境内不同条件下的传播情况，并通过国际旅行传播到其他国家。

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.