Effect of Nutrition, Immunity, and Vaccines on Pediatric Enteric Infections

描述（由申请人提供）：候选人：Leon博士在埃默里大学休伯特全球卫生系完成了他的第一年初级教员工作。他计划在免疫学、流行病学和统计建模等多学科领域成为一名成功的独立翻译研究者。他的长期研究目标是确定有效的干预措施，以优化人群对腹泻诱导肠道病毒（如轮状病毒（RV）和诺如病毒（NoV））的自然和疫苗获得性免疫力，从而保护儿童免受腹泻的侵害。环境:Drs。雷纳尔多·马托雷尔和乌沙·拉马克里什南是两位由美国国立卫生研究院资助的全球营养流行病学领域的知名领导者，他们将指导莱昂博士。背景：新引入的RV疫苗可能对预防儿童腹泻有重大影响，腹泻是世界范围内发病率和死亡率的主要原因。我们假设，儿童营养，与其他易感性（如母亲的影响，如母乳喂养）和暴露（如社会人口）因素，直接调节免疫能力，包括RV疫苗获得性免疫能力。足够的免疫能力，反过来，保护儿童免受腹泻。这项为期五年的K01研究计划将通过流行病学和统计建模方法来检验该模型，以量化营养、免疫能力和RV疫苗接种对儿童腹泻的综合影响。具体目的：1)了解免疫能力和营养对儿童腹泻的影响。2)确定营养影响免疫能力的机制。3)量化接种RV疫苗后严重营养不良和免疫能力对RV感染和腹泻的影响。培训：Leon博士将以流行病学和统计建模方面的指导培训来补充他强大的实验室免疫学背景。他将在埃默里大学（Emory University）的第1-2项目接受培训，通过课程学习和研究临床标本以及来自墨西哥国立卫生研究院（Instituto Nacional de Salud Publica）正在进行的一项队列研究的数据，该研究涉及800多对墨西哥母婴。他还将在前瞻性队列研究的设计和执行方面获得指导的现场经验。他将在玻利维亚轮状病毒监测疫苗规划的第三个目标中接受培训，在接种RV疫苗后的一年内，从200多名婴儿中招募和收集数据和标本。相关性：测试这些固定的和可改变的危险因素的综合效应的模型可以为儿科腹泻干预和全球轮状病毒疫苗接种政策提供急需和及时的科学证据。在这项为期五年的K01建议中，我们的目标是使用先进的流行病学和统计建模方法来量化营养、免疫能力和轮状病毒疫苗对儿童腹泻的综合影响。营养、宿主易感性和暴露、免疫能力和轮状病毒疫苗对儿童腹泻影响的有用预测模型将为公共卫生儿童腹泻干预和全球轮状病毒疫苗接种政策提供信息。

DESCRIPTION (provided by applicant): CANDIDATE: Dr. Leon has completed his first year as a junior faculty at the Hubert Department of Global Health at Emory University. He plans a successful career as an independent translational investigator in the multidisciplinary fields of immunology, epidemiology and statistical modeling. His long-term research goal is to identify effective interventions to optimize a population's natural and vaccine-acquired immunity to diarrhea-inducing enteric viruses like rotavirus (RV) and norovirus (NoV) and thereby protect children from diarrhea. ENVIRONMENT: Drs. Reynaldo Martorell and Usha Ramakrishnan, two established, NIH-funded leaders in global nutritional epidemiology will mentor Dr. Leon. BACKGROUND: Newly introduced RV vaccines could have a significant impact on preventing childhood diarrhea, a leading cause of morbidity and mortality worldwide. We postulate that child nutrition, with other susceptibility (e.g. maternal influences like breastfeeding) and exposure (e.g. socio-demographic) factors, directly modulate immune-competence, including RV vaccine-acquired immune-competence. Adequate immune-competence, in turn, protects a child from diarrhea. This five-year mentored K01 research proposal will test this model through epidemiologic and statistical modeling approaches to quantify the combined effects of nutrition, immune-competence, and RV vaccination on pediatric diarrhea. SPECIFIC AIMS: 1) To understand how immune-competence and nutrition influence pediatric diarrhea. 2) To identify the mechanisms through which nutrition affects immunecompetence. 3) To quantify the influence of severe malnutrition and immune-competence on RV infection and diarrhea after RV vaccination. TRAINING: Dr. Leon will complement his strong laboratory immunology background with mentored training in epidemiologic and statistical modeling. He will be trained, in Aim 1-2, at Emory University, through coursework and by studying clinical specimens and data from an ongoing cohort study, at the Instituto Nacional de Salud Publica in Mexico, of over 800 Mexican mothers-infant pairs. He will also acquire mentored field experience in the design and execution of prospective cohort studies. He will be trained, in Aim 3, at the Rotavirus Surveillance Vaccine Program in Bolivia, by recruiting and collecting data and specimens from over 200 infants for one year after RV vaccination. RELEVANCE: Models to test the combined effect of these fixed and modifiable risk factors could provide much needed and timely scientific evidence for pediatric diarrhea interventions and global rotavirus vaccination policy. Our goal, in this five-year mentored K01 proposal, is to use advanced epidemiologic and statistical modeling approaches to quantify the combined effects of nutrition, immune-competence, and the rotavirus vaccine on pediatric diarrhea. The useful predictive models of the effect of nutrition, host susceptibility and exposure, immune-competence, and rotavirus vaccine on pediatric diarrhea would inform public health pediatric diarrhea interventions and global rotavirus vaccination policy.