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

摘要 人类杯状病毒现在是儿童病毒性胃肠炎的主要原因， 轮状病毒疫苗虽然关于诺如病毒的流行病学和免疫学的大量数据正在出现， 一种众所周知的杯状病毒，对于一种基本上未知和未研究的杯状病毒，sapovirus，不存在类似的数据。 重要的是，沙波病毒作为一种重要的儿童胃肠道病原体正在得到认可。数据从 最近发表的研究表明，在5岁以下儿童中， 年，患有肠胃炎。此外，最近对多中心MAL-ED队列样本的重新分析 发现在婴儿的所有肠道病原体中，沙波病毒引起腹泻的比例最高。 考虑到沙波病毒在胃肠炎患儿中的重要性，迫切需要数据来指导控制 和预防战略。对于这个建议，我们将调查自然史，免疫力的发展， 在一个400名从出生到三岁的巴布亚新几内亚儿童的队列中， 岁的广泛的调查问卷数据、生物标本（即，粪便、血清、唾液和母乳）， 将在基线和定期（每周或 在36个月的随访期间，每月一次。因为人类的痘病毒株是不可培养的，我们的团队也将 开发新的病毒样颗粒（VLP）用于常见的sapovirus基因型，以测量抗sapovirus伊加 和IgG抗体浓度。此外，尖端的实验室技术将在 结合流行病学资料，调查1999年至2002年儿童中的沙波病毒感染过程。 这群人，他们的家庭，他们的社区。尼加拉瓜是进行这项研究的理想地点， 由于sapovirus的高发病率， 五岁以下儿童的肠胃炎，拟议地点强大的研究基础设施，以及长期- 北卡罗来纳州大学（北卡罗来纳大学）和尼加拉瓜大学（尼加拉瓜大学）之间的长期合作。 除了利用这种预先存在的合作，我们还与杯状病毒专家Jan Vinje博士合作， 他将为这项研究提供内容方面的专业知识，并将在他的实验室进行一些实验室分析。 疾病控制和预防中心。我们还与NIH资助的 研究人员正在秘鲁进行一项儿童病毒性胃肠炎的平行研究， 诺如病毒的发病率很高，但沙波病毒的发病率不高。这种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 小儿胃肠道病原体。具体来说，这项新的研究提案将产生新的数据， 是推进控制和预防干预措施的基础，包括未来的沙波病毒疫苗 发展

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.