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 尼帕病毒是一种人畜共患副粘病毒，由非洲和亚洲的旧大陆果蝠携带， 严重的，致命的脑炎，可以在人与人之间传播。在孟加拉国， 每年在人群中爆发，主要传播途径是食用生椰枣汁。 椰枣树汁的收获和消费最集中在孟加拉国西部，该地区被称为 “尼帕带”，然而，椰枣汁消费，NiV，和它的蝙蝠水库，中狐蝠，是存在的 在孟加拉国各地。目前还不清楚为什么孟加拉国东部没有发现疫情。神秘 NiV的溢出产生了更大的风险，即更多的致病性和传播性菌株将出现并导致 大规模流行病。这一多学科项目将确定是否有NiV疫情发生， 孟加拉国东部以及人类行为、蝙蝠感染模式和 尼帕病毒的流行株影响尼帕病毒带以外的爆发。这个项目结合了人类接触 蝙蝠多部位纵向感染研究和蝙蝠体内实验感染研究， 仓鼠比较不同菌株的临床结果，以实现以下特定目标： 1)为了比较NiV暴露及其行为决定因素， 在孟加拉国的尼帕带外。我们将检验NiV溢出发生在 孟加拉国尼帕带以外的社区。我们会用行为调查问卷和多功能 Luminex血清学检测，用于筛查针对NiV的IgG抗体的高风险人群，并确定 尼帕暴露已经发生，行为风险如何因地区而异。 2)为了比较Nipah病毒在Pteropus蝙蝠群内外的时间动态， 尼帕腰带。我们将在六个地点（西部3个，东部3个）进行纵向蝙蝠NiV实地研究， 描述当地蝙蝠的人口统计学特征，测量血清阳性率随时间的变化;确定病毒 脱落模式和品系间的遗传变异。通过实验蝙蝠感染在一个BSL 4 实验室，我们将确定是否蝙蝠与抗体对NiV（以前的接触）可能会再次感染 并散播病毒这将回答一个关于传动动态的关键问题，并允许我们测试 假设东方蝙蝠和西方蝙蝠的病毒脱落频率不同， 这可能会影响人畜共患病的传播。 3)比较不同蝙蝠尼帕病毒分离株的致病性和传播性， 在尼帕病毒带外，使用动物模型。马来西亚型NiV和孟加拉型NiV具有不同的 人类的临床特征NiV基因变异可能是东部地区人类感染率较低的原因。 孟加拉国.为了验证这一假设，我们将比较不同NiV的传播性和致病性， 在BSL 4条件下，在叙利亚仓鼠模型中从中狐蝠分离的菌株。