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

印度南部社区范围内驱虫对钩虫调节旁观者抗原和疫苗免疫反应的影响

• 批准号: 10542779
• 负责人: Sitara Swarna Rao Ajjampur
• 金额: $ 6.99万
• 依托单位: CHRISTIAN MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-28 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10542779
• 关键词: 3 year old; Adult; Adverse event; Affect; Albendazole; Anemia; Anthelmintics; Antigens; Area; Ascaris lumbricoides; Attenuated; Award; Bystander Effect; Cells; Child; Cluster randomized trial; Cognition; Cohort Studies; Communicable Diseases; Communities; Defecation; Diphtheria; Diphtheria Toxoid; Ecuador; Epidemiology; Female of child bearing age; Flow Cytometry; Frequencies; Goals; Haemophilus influenzae; Helminths; Homeostasis; Hookworm Infections; Hookworms; Immune; Immune response; Immunity; Immunoassay; Immunoglobulin G; Immunologics; India; Infant; Infection; Infectious Disease Epidemiology; Influenza B Virus; Interferon Type II; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-4; Interleukin-5; Interruption; Intervention; Iron; Journals; Laboratories; Malaria; Manuscripts; Measures; Mentors; Mentorship; Meta-Analysis; Morbidity - disease rate; Mothers; Mycobacterium tuberculosis; National Institute of Allergy and Infectious Disease; Necator americanus; Nursery Schools; Old World Hookworm; Parasites; Parasitic Diseases; Parasitic infection; Performance; Persons; Pertussis; Peru; Pharmaceutical Preparations; Plasma; Policies; Population; Pregnant Women; Prevalence; Public Health; Publishing; Qualitative Research; Recommendation; Regression Analysis; Regulatory T-Lymphocyte; Research; Research Design; Research Methodology; Role; Running; Sampling; Sanitation; Schistosomiasis; School-Age Population; Schools; Site; Soil; Statistical Data Interpretation; TNF gene; Testing; Time; Training; Transforming Growth Factor beta; Translating; Treatment Efficacy; Trichocephalus trichiura; Tuberculosis; Uganda; United States National Institutes of Health; Vaccination; Vaccines; Work; career; cohort; cytokine; data visualization; early childhood; experience; follow-up; helminth infection; human disease; immune system function; immunoregulation; implementation science; improved; infection rate; laboratory experience; low and middle-income countries; mathematical model; medical schools; neglect; pathogen; pathogenic bacteria; pathogenic virus; postnatal period; prenatal; programs; public health priorities; recruit; research facility; response; skills; standard of care; systematic review; targeted treatment; tool; transmission process; vaccine response; vaccinology

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 .

项目概要 在此次全球新兴领袖奖申请中，Sitara Ajjampur 博士计划研究以下因素的影响： 针对钩虫调节对旁观者抗原和疫苗的免疫反应进行社区范围的驱虫 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有潜在影响：社区- 广泛驱虫并改善幼儿对疫苗接种的反应。本次活动的长远目标 该申请旨在在印度建立一个关于蠕虫和寄生虫感染的独立研究计划。 这符合 K43 奖启动和支持独立研究事业的目标 中低收入国家的领域符合公共卫生优先事项。 Ajjampur 博士计划借鉴之前进行流行病学和实验室研究的经验 在杰出导师的指导下学习。该奖项提供的受保护时间将 让她能够通过免疫分析和流程方面的实验室实践培训获得广泛的关注 疫苗学的细胞计数和实验室方面。她还将接受研究设计、定量研究方面的培训 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。她将与导师一起进行系统审查，以进一步开发手稿和数据 在顶级期刊上发表文章的可视化技能。她计划接受定性研究方法和 实施科学，以了解干预策略的功效，应用于被忽视的寄生生物 感染并将研究结果转化为政策变化。 先前的工作描述了抗蠕虫治疗在逆转免疫调节方面的作用 钩虫感染对其他细菌或病毒病原体以及疫苗的保护性反应的影响 回应。在印度，优秀的现场站点和跟踪 Deworm3 研究队列的工作人员相结合 已发现钩虫感染占优势的人群；和强大的研究设施 来自基督教医学院、韦洛尔和美国国立卫生研究院 (NIH) 的该领域杰出领导者的指导，提供了 全面剖析社区驱虫免疫效果的巨大机会 在这些人群中进行检测，并确定这些影响在驱虫后是否持续存在。 具体指标将包括研究社区范围内驱虫对 1) 免疫稳态的影响 2) 成人对不相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、百日咳和乙型流感嗜血杆菌的疫苗反应。学习期限 最初的磨合期将是 5 年，然后是招募和测试钩虫样本 - 感染和未感染的成年人。此外，还招募了一组产后儿童（6岁以下） 周）将随访至 3 岁，以评估对疫苗的纵向免疫反应。