Study of Nipah virus dynamics and genetics in its bat reservoir and of human exposure to NiV across Bangladesh to understand patterns of human outbreaks

研究蝙蝠储存库中的尼帕病毒动力学和遗传学，以及孟加拉国各地人类接触尼帕病毒的情况，以了解人类爆发的模式

基本信息

批准号：
10033642
负责人：
Jonathan H Epstein
金额：
$ 58.09万
依托单位：
ECOHEALTH ALLIANCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-06-30
项目状态：
未结题

项目摘要

Project Summary Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap. Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the “Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims: 1) To compare NiV exposure and its behavioral determinants among human populations inside and outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if Nipah exposure has occurred and how behavioral risk varies by locality. 2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern), characterize local bat demography, measure changes in seroprevalence over time; determine viral shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4 lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected and shed virus. This will answer a critical question about transmission dynamics and allow us to test the hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats, which may influence zoonotic transmission. 3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.

项目摘要 Nipah病毒是一种人畜共患性帕拉马病毒，由旧世界果蝙蝠在非洲和亚洲携带，这引起了人类严重致命的脑炎，可以从人到人传播。在孟加拉国，哪里人们每年发生爆发，传播的主要途径是消耗原始的日期棕榈树液。在孟加拉国西部收获和最密集地收获和消耗枣棕榈树液，该地区被称为然而，“尼帕腰带”，日期的棕榈树液消费，NIV及其蝙蝠水库，Pteropus Medius 通过孟加拉国。目前尚不清楚为什么在孟加拉国东部未发现爆发。神秘 NIV的Spilover产生了一个重大的风险，即更多的致病性和可传染性菌株将出现和铅大型流行病。这个多学科项目将确定是否发生了NIV爆发孟加拉国东部以及人类行为，蝙蝠的感染模式以及遗传变异如何 NIV的循环菌株会影响Nipah带外的爆发。这个项目结合了人类的曝光在蝙蝠和体内实验感染中对蝙蝠和体内实验感染的多部位纵向感染研究的研究仓鼠比较潜水员菌株之间的临床结果以达到以下特定目的： 1）比较内部人群中的NIV暴露及其行为决定者在孟加拉国的尼帕腰带外面。我们将检验以下假设：孟加拉国在尼帕腰带外的社区中。我们将使用行为问卷和多重问卷 Luminex血清学评估以筛选针对NIV的IgG抗体的高风险种群，并确定是否是否尼帕（Nipah）的暴露发生了，行为风险如何随地方而变化。 2）比较pteropus蝙蝠菌落内外的Nipah病毒临时动力学尼帕腰带。我们将在六个位置（西部3个，东部3）中进行纵向蝙蝠NIV现场研究，表征局部蝙蝠删除术，衡量随着时间的流逝的血清阳性变化；确定病毒菌株之间的脱落模式和遗传变异。通过BSL 4中的实验蝙蝠感染实验室，我们将确定是否可以重新感染具有针对NIV抗体的蝙蝠（以前的暴露）和脱落病毒。这将回答有关传输动态的关键问题，并允许我们测试与西部蝙蝠相比这可能会影响人畜共患传播。 3）比较从蝙蝠和使用动物模型在尼帕带外面。马来西亚型NIV和孟加拉国类型不同人的临床特征。 NIV遗传变异可能是东部人类感染率降低孟加拉国。为了检验这一假设，我们将比较潜水员NIV的传播和致病性在BSL 4条件下，在叙利亚仓鼠模型中从pteropus medius中分离出来的菌株。