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.

摘要 人类杯状病毒现在是儿童病毒性胃肠炎的主要原因，因为 轮状病毒疫苗。虽然关于诺沃克病毒的流行病学和免疫学的大量数据正在涌现， 这是一种广为人知的杯状病毒，但对于一种基本上不为人所知且未被研究的杯状病毒则没有类似的数据。 重要的是，萨普病毒作为一种重要的儿童胃肠道病原体正在得到认可。数据来自 最近发表的研究表明，在五岁以下的儿童中，萨普病毒的流行率可能高达12%至24% 患有胃肠炎的年龄。此外，最近对多点Mal-Ed队列样本的重新分析 发现，在所有婴儿肠道病原体中，沙门氏菌病毒引起腹泻的可归因率最高。 鉴于沙普病毒在胃肠炎儿童中的重要性，迫切需要数据来指导控制 和预防策略。对于这一提议，我们将调查免疫的自然历史，发展， 萨普病毒在400名尼加拉瓜儿童中的传播动态从出生到3岁 几年前。广泛的问卷调查数据、生物标本(即粪便、血清、唾液和母乳)， 地理坐标和环境样本将在基线上定期收集(每周或 每月)，在36个月的随访中。由于人源病毒株是不可培养的，我们的团队也将 开发针对常见萨巴病毒基因型别的新型病毒样颗粒(VLP)，以检测抗萨普病毒IgA 采集样本中的免疫球蛋白抗体浓度。此外，尖端实验室技术将被 结合流行病学资料调查#年儿童萨巴病毒感染病程 这群人、他们的家庭和他们的社区。尼加拉瓜提供了进行这项研究的理想地点 由于SAP病毒的高发病率，SAV的自然历史、免疫学和传播动力学 5岁以下儿童的胃肠炎，拟议地点强大的研究基础设施，以及长期的- 北卡罗来纳大学(UNC)和尼加拉瓜大学(UNAN)之间的常设合作。 除了利用这一预先存在的合作，我们还与杯状病毒专家Jan Vinjé博士合作，他 将为这项研究提供内容方面的专业知识，并将在他位于 疾病控制和预防中心。我们还与美国国立卫生研究院资助的 正在对秘鲁儿童病毒性胃肠炎进行平行研究的研究人员，那里的 诺沃克病毒的发病率很高，但不是萨普病毒。总之，这一独特的合作使我们能够 交流研究和分析工具，以更好地了解病毒的流行病学和免疫学 幼儿的胃肠道病原体。具体地说，这项新的研究提案将产生新的数据， 对于推进控制和预防干预措施，包括未来的萨巴病毒疫苗来说，是至关重要的 发展。