Effect of Community Wide Deworming on Hookworm Modulated Immune Responses to Bystander Antigens and Vaccines in Southern India

项目总结 在这一新兴的全球领袖奖申请中，西塔拉·阿贾姆普尔博士计划研究 全社区钩虫驱虫调节对旁观者抗原和疫苗的免疫应答 在印度南部。这项研究将建立在正在进行的基于社区的整群随机试验的基础上 (Deworm3研究)。这项研究对印度的两个公共卫生问题具有潜在的影响：社区- 广泛驱虫和改善幼儿对疫苗接种的反应。这样做的长期目标是 申请是在印度建立一个关于蠕虫和寄生虫感染的独立研究计划。 这与K43奖项启动和支持独立研究事业的目标是一致的。 在LMIC与公共卫生优先事项保持一致的领域。 阿贾姆普尔博士计划在流行病学和实验室研究方面积累先前的经验 在杰出导师的指导下学习。本奖项提供的受保护时间将 让她在免疫分析和Flow方面的实验室实践培训有广泛的基础 疫苗学的细胞学和实验室方面。她还将接受研究设计、量化方面的培训 传染病流行病学的研究方法，统计分析，包括回归分析和 荟萃分析。她将与她的导师一起进行系统的审查，以进一步开发手稿和数据 在顶级期刊上发表文章的视觉化技能。她计划在定性研究方法和 实施科学，以了解干预策略的有效性，如应用于被忽视的寄生虫 并将研究成果转化为政策变化。 以前的工作已经描述了抗蠕虫疗法在逆转免疫调节中的作用。 钩虫感染对其他细菌或病毒病原体和疫苗保护性反应的影响 回应。在印度，一个出色的现场和跟进Deworm3研究队列的工作人员的组合 已发现钩虫感染占主导地位的人口；以及强大的研究设施， 来自基督教医学院、Vellore和NIH的该领域著名领导者的指导，提供了 全面剖析社区驱虫的免疫学效应的巨大机会 并确定这些影响是否在驱虫后时期持续。 具体指标包括研究全社区驱虫对1)免疫动态平衡的影响 成人对无关但常见的旁观者抗原(结核分枝杆菌)的免疫反应 3)儿童对白喉、百日咳、乙型流感嗜血杆菌的疫苗反应。研究持续时间 为期5年，最初的磨合期是从钩虫那里招募和测试样本- 感染和未感染的成年人。此外，在产后时期(6岁以下)招募的一批儿童 将跟踪至3岁，以评估对疫苗的纵向免疫反应。

PROJECT SUMMARY In this Emerging Global Leader Award application, Dr. Sitara Ajjampur plans to study the effect of community-wide deworming on hookworm modulated immune responses to bystander antigens and vaccines in Southern India. This research will be built onto an ongoing community-based cluster randomized trial (Deworm3 study). This study has potential ramifications for 2 public health concerns in India: community- wide deworming and improving response to vaccination in young children. The long-term goal of this application is to establish an independent research program on helminth and parasitic infections in India. This is in keeping with the objective of the K43 award to launch and support independent research careers in LMIC in fields that align with public health priorities. Dr Ajjampur plans to build on prior experience in the conduct of epidemiological and laboratory-based studies with guidance from highly eminent mentors. The protected time made available on this award, will allow her to have a broad-based focus with hands-on laboratory training in immunoassays as well as flow cytometry and laboratory aspects of vaccinology. She will also have training in study design, quantitative research methods in infectious disease epidemiology, statistical analysis including regression analysis and meta-analysis. She will work with her mentors on systematic reviews to further develop manuscript and data visualization skills to publish in top-tier journals. She plans to train in qualitative research methods and implementation science to understand the efficacy of intervention strategies, as applied to neglected parasitic infections and translate research findings to policy change. Previous work has described the role of anti-helminthic therapy in reversing the immunomodulatory effects of hookworm infection on protective responses to other bacterial or viral pathogens as well as vaccine responses. In India, a combination of an excellent field site and staff following up the Deworm3 study cohort population where a predominance of hookworm infection has been found; and a strong research facility with mentorship from eminent leader in the field, from Christian Medical College, Vellore and the NIH, provides a tremendous opportunity to comprehensively dissect the immunological effects of community-wide deworming in these populations and determine whether these effects are sustained in the post-deworming period. Specific indicators will include studying the effect of community-wide deworming on 1) immune homeostasis in adults 2) immune response to unrelated but common bystander antigens (M. tuberculosis) in adults and 3) vaccine response to Diphtheria, Pertussis and Haemophilus influenzae b in children. The study duration will be 5 years with an initial run-in period followed by recruitment and testing samples from hookworm- infected and uninfected adults. In addition, a cohort of children recruited in the post-natal period (under 6 weeks) will be followed up to the age of 3 years to assess the longitudinal immune response to vaccines .