EPIDEMIOLOGY OF NOVEL HUMAN ASTROVIRUSES

描述（由申请人提供）：人类腹泻是全球感染性死亡的第三大原因，每年造成约200万人死亡。在大多数腹泻病因学研究中，平均约40%的病例不能归因于任何已知的微生物病原体。已确定的病毒病因包括轮状病毒、诺如病毒、萨波病毒、肠道腺病毒和星状病毒。直到最近，人类星状病毒被认为仅限于8种密切相关的血清型（以下称为“经典”人类星状病毒），据估计，大约10%的腹泻病例是由这些病毒引起的。在过去的两年中，在腹泻患者的粪便中发现了两种新的星状病毒。这些病毒，星状病毒MLB1 （MLB1）和星状病毒MLB2 (MLB2)，与经典的人类星状病毒以及所有其他已知的星状病毒高度不同。MLB1和MLB2具有80%的氨基酸同源性。迄今为止，MLB1和MLB2都在北美和印度被发现；此外，在澳大利亚和非洲也发现了MLB1病毒，这表明这些病毒具有全球分布。这两种病毒定义了星状病毒的一个新分支，其流行病学和在人类腹泻或其他疾病中的潜在作用在以前的研究中完全被忽视。这笔拨款的重点是开始解决以下问题：“新发现的星状病毒MLB1和MLB2是否导致了40%的不明原因腹泻的一部分？”为此，这项R21拨款旨在确定这两种新型病毒的流行病学和血清流行病学。具体而言，在Aim 1中，MLB1和MLB2与腹泻的潜在关联将通过对印度Vellore纵向出生队列的病例对照分析来确定。在目标2中，将分析来自北美和印度的年龄分层血清收集，以确定MLB1和MLB2的血清患病率。

DESCRIPTION (provided by applicant): Human diarrhea is the 3rd leading cause of infectious deaths worldwide causing approximately 2,000,000 fatalities per year. In most studies of diarrhea etiologies, on average about 40% of cases cannot be attributed to any known microbial agent. Among the established viral causes are rotaviruses, noroviruses, sapoviruses, enteric adenoviruses and astroviruses. Until very recently, human astroviruses were thought to be limited to 8 closely related serotypes (hereafter referred to as "classic" human astroviruses), which are estimated to be responsible for approximately 10% of diarrhea cases. In the past two years, two novel astroviruses have been discovered in the stool of patients with diarrhea. These viruses, astrovirus MLB1 (MLB1) and astrovirus MLB2 (MLB2), are highly divergent from the classic human astroviruses as well as all other known astroviruses. MLB1 and MLB2 share about 80% amino acid identity to each other. To date, both MLB1 and MLB2 have been detected in North America and India; in addition, MLB1 has also been described in Australia and Africa demonstrating that these viruses have a worldwide distribution. These two viruses define a novel clade of astroviruses, whose epidemiology and potential role in human diarrhea or other diseases has been completely overlooked in prior studies. The focus of this grant is to begin to address the question "Are the newly discovered astroviruses MLB1 and MLB2 responsible for some fraction of the 40% of unexplained diarrhea?" Towards this end, this R21 grant aims to define the epidemiology and seroepidemiology of these two novel viruses. Specifically, in Aim 1 the potential association of MLB1 and MLB2 with diarrhea will be determined by case-control analysis of a longitudinal birth cohort from Vellore, India. In Aim 2, age-stratified serum collections from both North America and India will be analyzed to define the seroprevalence of MLB1 and MLB2. PUBLIC HEALTH RELEVANCE: Two new species of astroviruses have been recently discovered in patients with diarrhea. The goal of this project is to begin to understand whether these viruses might be responsible for causing the diarrhea. The first step is to see if there is any correlation between presence of the virus and diarrhea symptoms.