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

描述（由申请人提供）：候选人：莱昂博士已经完成了他的第一年作为一个初级教师在埃默里大学休伯特全球卫生部。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独立的翻译研究者。他的长期研究目标是确定有效的干预措施，以优化人群对轮状病毒（RV）和诺如病毒（NoV）等引起腹泻的肠道病毒的天然和疫苗获得性免疫力，从而保护儿童免受腹泻。工作环境：Dr. Dr. Martorell和Usha Ramakrishnan，两位由NIH资助的全球营养流行病学领导人将指导Leon博士。背景技术背景：新推出的RV疫苗可能对预防儿童腹泻产生重大影响，这是全球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又可以保护儿童免受腹泻的侵害。这项为期五年的K 01研究计划将通过流行病学和统计建模方法测试该模型，以量化营养，免疫能力和RV疫苗接种对儿科腹泻的综合影响。具体目的：1）了解免疫能力和营养如何影响小儿腹泻。2)确定营养影响免疫力的机制。3)量化严重营养不良和免疫能力对RV感染和RV疫苗接种后腹泻的影响。培训：Leon博士将通过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。他将在埃默里大学接受目标1-2的培训，通过课程和研究来自墨西哥国家公共卫生研究所正在进行的队列研究的临床标本和数据，超过800对墨西哥母婴。他还将获得指导的前瞻性队列研究的设计和执行的现场经验。他将在玻利维亚的轮状病毒监测疫苗项目中接受目标3的培训，招募并收集200多名婴儿接种轮状病毒疫苗后一年的数据和标本。相关性：模型来测试这些固定的和可变的风险因素的综合影响，可以提供急需的和及时的科学证据，为儿童腹泻干预和全球轮状病毒疫苗接种政策。我们的目标，在这个五年的指导K 01提案，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小儿腹泻的综合影响。营养、宿主易感性和暴露、免疫能力和轮状病毒疫苗对小儿腹泻影响的有用预测模型将为公共卫生小儿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.