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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10033642
• 关键词: Africa; Animal Model; Animals; Antibodies; Area; Asia; Australia; Bangladesh; Behavior; Behavioral; Behavioral Genetics; Biological Assay; Characteristics; Chiroptera; Clinical; Communities; Consumption; Country; Demography; Disease Outbreaks; Domestic Animals; Encephalitis; Epidemic; Event; Exposure to; Frequencies; Fruit; Genetic; Genetic Variation; Genotype; Genus Pteropus; Geographic Locations; Geography; Goals; Hamsters; Harvest; Health Priorities; Henipavirus; Herd Immunity; Human; Immigration; Immunoglobulin G; India; Infection; International; Lead; Livestock; Location; Malaysia; Measures; Mesocricetus auratus; Modeling; Nipah Virus; Outcome; Paramyxovirus; Pathogenicity; Pattern; Persons; Phenotype; Philippines; Phoenix dactylifera; Population; Populations at Risk; Prevalence; Questionnaires; Recrudescences; Reporting; Risk; Route; Serological; Seroprevalences; Site; Testing; Time; Vaccines; Viral; Virulent; Virus; Virus Shedding; World Health Organization; Zoonoses; exposed human population; field study; genetic strain; global health; high risk population; human model; in vivo; infection rate; laboratory experiment; mathematical model; mortality; multidisciplinary; pandemic disease; pathogen; transmission process; virus genetics

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的帕托马病毒，由非洲和亚洲的旧世界水果蝙蝠进行，这是造成的 人类的严重致命脑炎，可以在孟加拉国的人身上传播 人们每年发生爆发，这是原始约会棕榈树液传播的主要途径。 在孟加拉国西部收获和消耗式棕榈树液，该地区被称为 “尼帕腰带” 在孟加拉国中，孟加拉国尚未发现孟加拉国的爆发。 溢出的溢出造成了一个重大的风险，即更多的致病性和可传染性菌株将出现并引导 大型流行病。 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 NIV的循环菌株影响了Nipah Belt之外的爆发。 对蝙蝠和体内实验感染的多部位纵向感染研究的研究 仓鼠比较各种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ATS行为决定因素 在孟加拉国的尼帕腰带外。 孟加拉国在Nippah腰带以外的社区。 Luminex血清学分析以筛选针对NIV的IgG抗体的风险种群，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病毒的时间动力学 Nipahh Belt。 表征局部蝙蝠人口统计学，衡量随着时间的流逝的血清阳性变化； 通过BSL 4中的实验性蝙蝠感染菌株之间的脱落模式和遗传变化 实验室，我们将确定是否具有针对NIV抗体的蝙蝠是否 并脱离病毒。 与西部蝙蝠相比 这可能会影响人畜共患传播。 3）比较从安德（Ande）和 使用动物模型在尼帕带外部。 NIV遗传变异的临床谱。 孟加拉国。 在BSL 4条件下，在叙利亚仓鼠模型中从翼展中分离出来的流浪。