Rotavirus vaccination in South Africa: safety and factors influencing the immune response to oral enteric vaccine

项目摘要 米歇尔·格鲁姆博士是呼吸道和脑膜病原体研究所的高级研究人员 南非克里斯哈尼巴拉格瓦纳斯学术医院的单位。她有一个本科生 医学学位和硕士学位，流行病学和生物统计学从大学 威特沃特斯兰德她最近提交了博士论文，评估了 非洲儿童口服轮状病毒疫苗。她在几个同行中发表了文章- 审查国际期刊，并在当地和国际会议上发表论文。她继续 增长和生产力是她致力于肠道疾病和疫苗事业的证据 在南非进行研究。 她希望在现有的儿童轮状病毒疫苗组合的基础上， 研究包括其他重要的肠道病原体和腹泻风险群体，例如 老年人和艾滋病毒感染者。需要进行研究，以描述 不同年龄组的腹泻，并评估预防腹泻的干预措施，特别是疫苗， 南非的疾病有了专门的研究时间，她可以扩大她在关键领域的知识， 如疫苗免疫学、实验室检测方法、统计分析、基金撰写和报告 skills.与肠道疫苗领域研究人员的科学互动将确定潜在的 在非洲和更远的地方合作。与经验丰富的导师团队一起， 合作者在南非和美国，她将获得必要的技能，建立 作为一个独立的研究人员，她的总体长期目标是建立一个专门的肠道 南非约翰内斯堡的疫苗部门。 腹泻病仍然是5岁以下儿童发病和死亡的主要原因， 特别是在低收入和中等收入国家。接种轮状病毒疫苗有可能 提供一个具有成本效益的公共卫生影响，并大大减少肠道疾病的负担， 但这种疫苗在发展中国家的效果不如在高收入国家。 了解疫苗效力较低背后的原因至关重要，因为即使是很小的改进， 有效性可能导致由以下原因引起的死亡和住院人数大幅减少 轮状病毒这项研究的目的是描述住院治疗的病因 5岁以下儿童，特别是检测到一种以上肠道病原体的感染， 了解口服肠道疫苗的安全性和影响免疫应答的因素， 非洲背景虽然这些数据只会在南非产生，但调查结果可能是 适用于非洲各地的儿童。 拟议的研究计划将建立在以前的工作，并旨在评估季节性的影响， 母体轮状病毒特异性抗体，肠道合并感染和免疫遗传多态性 对轮状病毒疫苗的反应和/或因轮状病毒胃肠炎住院的风险。结果 可以为政策决策提供信息，并指导未来与使用和 开发轮状病毒疫苗以及目前正在开发的其他肠道疫苗。全球 目前的数据表明，轮状病毒疫苗可能与肠套叠的小风险有关， 小儿肠梗阻的病因传染性病原体的鉴定和 与肠套叠相关的炎症标志物将提供对潜在问题的深入了解 这不仅对轮状病毒疫苗， 可能用于其它减毒活肠疫苗候选物。

Project summary Dr Michelle Groome is a senior research officer at the Respiratory and Meningeal Pathogens Research Unit based at the Chris Hani Baragwanath Academic Hospital, South Africa. She has an undergraduate medical degree and a Masters in Science degree in Epidemiology and Biostatistics from the University of the Witwatersrand. She has recently submitted her PhD thesis, assessing the impact and effectiveness of the oral rotavirus vaccine among children in an African setting. She has published in several peer- reviewed international journals and presented at local and international conferences. Her continued growth and productivity is evidence of her commitment to a career in diarrhoeal diseases and vaccine research in South Africa. She would like to build on her existing rotavirus vaccine portfolio in children as well as expand her research to include other important enteric pathogens and groups at risk for diarrhoea, for example the elderly and HIV-infected adults. Research is needed to describe the epidemiology and aetiology of diarrhoea in different age groups and to assess interventions, especially vaccines, to prevent diarrhoeal disease in South Africa. With dedicated research time she can expand her knowledge in key areas such as vaccine immunology, laboratory testing methods, statistical analysis, grant writing and presentation skills. Scientific interactions with fellow researchers in the enteric vaccine field will identify potential collaborators in Africa and further afield. Together with an experienced team of mentors and collaborators both in South Africa and the Unites States, she will acquire the skills necessary to establish herself as an independent researcher with the overall long-term goal of establishing a dedicated enteric vaccines unit in Johannesburg, South Africa. Diarrhoeal disease remains a leading cause of morbidity and mortality in children <5 years of age, especially in low- and middle-income countries. Vaccination against rotavirus has the potential to provide a cost- effective public health impact and substantially reduce the burden of diarrhoeal disease, but the vaccine does not perform as well in developing countries as in high-income countries. Understanding the reasons behind the lower vaccine efficacy is critical as even small improvements in efficacy could lead to substantial decreases in the number of deaths and hospitalisations caused by rotavirus. The goals of the proposed research are to describe the aetiology of diarrhoeal hospitalisations in children <5 years of age, especially infections with more than one diarrhoeal pathogen detected, and to understand safety and factors influencing the immune response to an oral enteric vaccine in an African setting. Although these data will only be generated in South Africa, the findings could be applicable to children across Africa. The proposed research plan will build on previous work, and aims to assess the effect of seasonality, maternal rotavirus-specific antibodies, enteric co-infections and genetic polymorphisms on the immune response to the rotavirus vaccine and/or risk of hospitalisation for rotavirus gastroenteritis. Results could inform policy decisions as well as guide the future research agenda pertaining to use and development of rotavirus vaccines as well as other enteric vaccines currently under development. Global data currently suggests that rotavirus vaccines may be associated with a small risk of intussusception, a cause of intestinal obstruction in young children. Identification of infectious pathogens and inflammatory markers associated with intussusception will provide insight into the underlying aetiology of this condition, which has important implications not just for rotavirus vaccines but also possibly for other live-attenuated enteric vaccine candidates.