Natural history, immunity, and transmission patterns of sapovirus in a Nicaraguan birth cohort

尼加拉瓜出生队列中沙波病毒的自然史、免疫和传播模式

• 批准号: 9759754
• 负责人: Sylvia Irene Becker-Dreps
• 金额: $ 77.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-27 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759754
• 关键词: 3 year old; 5 year old; Animals; Antibodies; Antibody titer measurement; Biological; Biological Assay; Birth; Breast Feeding; Calicivirus; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical; Cohort Studies; Collaborations; Communities; Data; Detection; Development; Diarrhea; Diet; Disease; Environment; Environmental Exposure; Epidemiology; Epitopes; Family Characteristics; Feces; Funding; Future; Gastroenteritis; Genetic; Genotype; Geographic Information Systems; Geography; Goals; Hospitalization; Household; Human; Human Milk; Immunity; Immunoglobulin A; Immunoglobulin G; Immunologics; Immunology; Incidence; Infant; Infection; Intervention; Laboratories; Life; Longitudinal cohort; Maternal antibody; Measures; Methods; Morbidity - disease rate; Natural History; Newborn Infant; Nicaragua; Nicaraguan; Norovirus; North Carolina; Nutritional status; Pattern; Peru; Peruvian; Population; Population Attributable Risks; Prevalence; Prevention; Prevention strategy; Preventive Intervention; Publishing; Questionnaires; Research; Research Infrastructure; Research Personnel; Research Proposals; Risk Factors; Rotavirus Vaccines; Saliva; Sampling; Sanitation; Sapovirus; Serological; Serum; Site; Source; Specimen; Techniques; Technology; United States National Institutes of Health; Universities; Viral; Viral Gastroenteritis; Virus-like particle; Water; acquired immunity; analytical tool; base; burden of illness; co-infection; cohort; disorder risk; early childhood; enteric pathogen; epidemiologic data; epidemiology study; follow-up; gastrointestinal; member; next generation sequencing; novel; pathogen; protective effect; research study; tool; transmission process; vaccine development

Abstract Human caliciviruses are now the leading cause of viral gastroenteritis in children following introduction of rotavirus vaccines. While a great deal of data are emerging on the epidemiology and immunology of norovirus, a well-known calicivirus, similar data do not exist for sapovirus, a largely unknown and unstudied calicivirus. Importantly, sapovirus is gaining recognition as an important gastrointestinal pathogen in children. Data from recently published studies indicate sapovirus prevalence can range as high as 12 to 24% in children under five years of age with gastroenteritis. Furthermore, a recent re-analysis of the multi-site MAL-ED cohort samples found that sapovirus had the highest attributable fraction for diarrhea among all enteropathogens in infants. Given the importance of sapovirus among children with gastroenteritis, data are urgently needed to guide control and prevention strategies. For this proposal, we will investigate the natural history, development of immunity, and transmission dynamics of sapovirus in a cohort of 400 Nicaraguan children followed from birth until three years of age. Extensive questionnaire data, biological specimens (i.e., stool, serum, saliva, and breast milk), geographic coordinates, and environmental samples will be collected at baseline and regularly (weekly or monthly) during 36 months of follow-up. Because human sapovirus strains are unculturable, our team will also develop new virus-like particles (VLPs) for common sapovirus genotypes in order to measure anti-sapovirus IgA and IgG antibody concentrations in collected samples. In addition, cutting-edge laboratory techniques will be used in combination with epidemiologic data to investigate the course of sapovirus infections among children in the cohort, their households, and their communities. Nicaragua provides an ideal site to execute this study of the natural history, immunology, and transmission dynamics of sapovirus, because of the high incidence of sapovirus gastroenteritis in children under 5 years, the robust research infrastructure at the proposed site, and a long- standing collaboration between the University of North Carolina (UNC) and the University of Nicaragua (UNAN). In addition to leveraging this pre-existing collaboration, we have joined with calicivirus expert, Dr. Jan Vinjé, who will provide content expertise for the study and will carry out some of the laboratory analyses in his lab at the Centers for Disease Control and Prevention. We are also forming a new collaboration with NIH-funded investigators who are conducting a parallel research study of childhood viral gastroenteritis in Peru, where the incidence of norovirus, but not sapovirus, is high. Together, this unique collaboration affords us the ability to exchange research and analytic tools to better understand the epidemiology and immunology of viral gastroenteric pathogens in young children. Specifically, this new research proposal will generate novel data that are fundamental for the advancement of control and prevention interventions, including future sapovirus vaccine development.

抽象的 现在，人类的蜡膜病毒是在引入后儿童病毒胃肠道的主要原因 轮状病毒疫苗。 Sapovirus是一个众所周知的彩色病毒，它是一个较大的未知和未研究的彩色病毒。 重要的是，Sapovirus正在成为儿童中出色的病原体识别。 最近发表的研究表明，在不足的儿童中，肉毒囊病毒的范围高达12％至24％ 胃肠炎的年龄。 发现Sapovirus在婴儿中所有肠道病中的腹泻的属性最高。 鉴于胃炎儿童中囊病毒病毒的症状，迫切需要数据以指导控制 和措施策略。 和Sapovirus的传播动力学在400名尼加拉瓜儿童的队列中从出生到三个 年龄。广泛的问卷数据，生物标本（即 地理坐标和环境样本将定期（每周或或 每月）随访36个月。 为常见的囊病毒基因型开发新的类似病毒样颗粒（VLP），以测量抗Sapvirus IgA 和收集样品中的IgG抗体浓度。 与流行病学数据结合使用，以研究儿童中囊病毒感染的过程 队列，他们的家庭及其社区。 由于SAPVIRUS的发病率很高，自然病史，免疫学和传播动力学 5岁以下儿童的胃肠炎，支撑部位的稳健研究基础设施以及长期 北卡罗来纳大学（UNC）和尼加拉瓜大学（UNAN）之间的长期合作。 除了利用这种兴奋的合作外，我们还与彩色病毒专家JanVinjé博士一起加入了 将为研究提供内容专业知识，并将在其实验室中的一些实验室分析 疾病控制和预防中心。 正在研究秘鲁儿童病毒病毒胃炎的平行研究的研究者。 诺如病毒的发病率，但不是Sapovirus，这种独特的合作使我们有能力 交换研究和分析工具，以更好地了解病毒的流行病学和免疫学 特别是幼儿的胃肠病原体。 对于国际控制和预防干预的进步至关重要，包括未来的囊病毒疫苗疫苗 发展。