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Zika virus in the human genital tract and implications for transmission

人类生殖道中的寨卡病毒及其传播影响

基本信息

批准号：
9428419
负责人：
Sylvia Irene Becker-Dreps
金额：
$ 17.14万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-15 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9428419
关键词：
2 year old Accident and Emergency department Acute Address Aedes Algorithms Arbovirus Infections Arboviruses Biological Blood Blood specimen Body Fluids Brazil Case Study Cell Culture System Cell Culture Techniques Central America Cities Clinical Cohort Studies Collaborations Communicable Diseases Community Hospitals Competence Conjunctivitis Culicidae Data Dengue Diagnosis Diagnostic Epidemic Epidemiology Exanthema Exhibits Fever Flavivirus Future Goals Hospital Referrals Household Human Human Milk Immunology Incidence Individual Infection International Intervention Interview Latin America Light Liquid substance Microcephaly Neonatal Nicaragua Nicaraguan North Carolina Participant Pathogenesis Patients Pattern Persons Phylogenetic Analysis Physicians Population Pregnancy Prevalence Prevention Public Hospitals Questionnaires Reporting Research Research Infrastructure Research Personnel Risk Factors Saliva Sampling Sampling Studies Scientist Seasonal Variations Seminal fluid Seroprevalences Serum Sexual Partners Sexual Transmission Sexual transmission of Zika Sexually Transmitted Diseases Site South America Specimen Technology Teratogens Time Universities Urine Vagina Vector-transmitted infectious disease Vero Cells Viral Load result Viremia Virus Virus Shedding World Health Organization ZIKV infection Zika Virus adverse outcome analytical tool base burden of illness care seeking cervicovaginal chikungunya cohort congenital infection disease transmission experience indexing member next generation sequencing novel prevent programs public health emergency reproductive tract sample collection transmission process vaginal fluid vector vector control viral transmission virology

项目摘要

ABSTRACT Zika virus (ZIKV) has spread rapidly throughout South and Central America since it was first reported in Brazil in early 2015. A temporally-related increase in the incidence of microcephaly a few months after the peak of the epidemic in Brazil prompted the World Health Organization to declare a ZIKV public health emergency of international concern. To slow the spread of ZIKV and prevent its severe consequences, a better understanding of modes of transmission is urgently needed. ZIKV, like many arboviruses, is transmitted by mosquitos, but several case reports suggest that it can be sexually transmitted, which is particularly concerning during pregnancy given the virus’s potential teratogenicity. The investigators propose to characterize the epidemiology of Zika virus as it emerges in a ZIKV-naïve population in León, Nicaragua via a cohort study of patients presenting to the city’s public hospital’s emergency department with fever, rash, and/or conjunctivitis. All participants will be interviewed with a questionnaire to determine risk factors for vector-borne and sexual acquisition of ZIKV. Each participant will provide blood, urine, and saliva to be screened for ZIKV, and those diagnosed with acute ZIKV will be followed for 6-12 months, providing serial biological specimens (blood, urine, saliva, semen, cervicovaginal fluid, and breast milk as applicable) to assess duration of shedding in various body compartments and assess potential for sexual transmission of ZIKV. Genital tract samples containing detectable virus will be used to inoculate cell cultures to evaluate viability of ZIKV in semen, cervicovaginal fluid, and breast milk. Next generation sequencing will be employed to determine if ZIKV isolates in the genital tract are replicating independently or contain quasispecies not found in the blood. NGS technology will also be applied to samples from household members including sexual partners of index cases to evaluate phylogenetic relationships between ZIKV strains transmitted by mosquito compared to those possibly transmitted through sexual contact. The University of North Carolina (UNC) and the University of Nicaragua (UNAN-León) have a longstanding and productive research collaboration and are ideally poised to study the emerging ZIKV epidemic. Nicaragua is an ideal site to execute this study because of the high incidence of arboviral infections, the robust research infrastructure at the proposed site, and the strong collaboration between UNC and UNAN- León. This unique collaboration affords us the ability to exchange research and analytic tools to better understand the epidemiology and pathogenesis of ZIKV as it emerges in a naïve population in Nicaragua. This research will generate novel data that are fundamental to the advancement of prevention and control interventions, particularly interventions that go beyond typical vector control programs to prevent sexual transmission and avert potentially catastrophic congenital infection. The study will add to existing research infrastructure to develop capacity for future studies on ZIKV transmission with the ultimate goal of reducing the burden of disease and preventing the adverse outcomes associated with the infection.

摘要寨卡病毒（ZIKV）自巴西首次报告以来，已在整个南美洲和中美洲迅速传播在2015年初。在高峰期后几个月，巴西的疫情促使世界卫生组织宣布ZIKV进入公共卫生紧急状态，国际关注。为了减缓ZIKV的传播并防止其严重后果，迫切需要了解传播方式。ZIKV，像许多虫媒病毒一样，是通过蚊子，但一些病例报告表明，它可以通过性传播，这是特别令人担忧的考虑到病毒的潜在致畸性研究人员建议将寨卡病毒在尼加拉瓜莱昂的ZIKV初治人群中出现时的流行病学，因发烧、皮疹和/或结膜炎而到该市公立医院急诊科就诊的患者。所有参与者都将接受问卷调查，以确定病媒传播和性传播的风险因素。收购ZIKV。每个参与者将提供血液、尿液和唾液以进行ZIKV筛查，并且那些被诊断患有急性ZIKV的患者将被随访6-12个月，提供连续的生物样本（血液，尿液，唾液、精液、宫颈阴道液和母乳（如适用）），以评估各种患者的脱落持续时间。身体隔室和评估ZIKV性传播的可能性。生殖道样本含有可检测的病毒将用于培养细胞培养物，以评估ZIKV在精液、宫颈阴道、子宫颈和子宫颈中的活力。液体和母乳。将采用下一代测序来确定生殖器中的ZIKV分离株是否存在。道是独立复制或包含准种没有发现在血液中。NGS技术也将成为应用于家庭成员的样本，包括索引病例的性伴侣，以评估系统发育蚊子传播的ZIKV毒株与可能通过蚊子传播的ZIKV毒株之间的关系性接触北卡罗来纳州大学和尼加拉瓜大学（UNAN-León）有一个长期和富有成效的研究合作，并准备研究新兴的ZIKV 疫情尼加拉瓜是进行这项研究的理想地点，因为虫媒病毒感染的发病率很高，拟议地点强大的研究基础设施，以及UNAN和UNAN之间的强有力合作- 莱昂这种独特的合作使我们能够交换研究和分析工具，了解ZIKV的流行病学和发病机制，因为它出现在尼加拉瓜的一个天真的人口。这研究将产生新的数据，这些数据对预防和控制的进展至关重要干预措施，特别是超越典型病媒控制方案的干预措施，传播和避免潜在的灾难性先天性感染。这项研究将增加现有的研究基础设施，以发展未来研究ZIKV传输的能力，最终目标是减少疾病负担和预防与感染相关的不良后果。