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: 10366052
• 负责人: Sitara Swarna Rao Ajjampur
• 金额: $ 6.8万
• 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/10366052
• 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; aged; base; career; cohort; cytokine; data visualization; early childhood; experience; follow-up; helminth infection; human disease; immune system function; immunoregulation; implementation science; improved; 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 .

项目摘要 在这个新兴的全球领导者奖的申请，西塔拉Ajjampur博士计划研究的影响， 对钩虫的全社区驱虫调节了对旁观者抗原和疫苗的免疫应答 在印度南部。这项研究将建立在一个正在进行的以社区为基础的随机分组试验之上。 （Deworm 3研究）。这项研究对印度的2个公共卫生问题有潜在的影响：社区- 广泛驱虫和改善幼儿疫苗接种反应。长期目标是 申请的目的是在印度建立一个关于蠕虫和寄生虫感染的独立研究项目。 这符合K43奖的目标，即启动和支持独立的研究事业。 在与公共卫生优先事项相一致的领域， Ajjampur博士计划利用以前在流行病学和实验室基础上进行的经验， 在杰出导师的指导下学习。此奖励提供的受保护时间将 让她有一个广泛的重点与动手实验室培训免疫测定以及流动 细胞计数和疫苗学的实验室方面。她还将接受研究设计、定量 传染病流行病学的研究方法，统计分析，包括回归分析， 荟萃分析.她将与她的导师一起进行系统综述，以进一步开发手稿和数据 可视化技能，在顶级期刊上发表。她计划接受定性研究方法的培训， 实施科学，以了解干预战略的效力，适用于被忽视的寄生虫 将研究结果转化为政策变化。 以前的工作已经描述了抗蠕虫治疗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以及疫苗的保护性反应的影响 应答在印度，一个优秀的现场研究中心和随访Deworm 3研究队列的工作人员的组合 已发现钩虫感染占优势的人口;以及强大的研究设施， 来自基督教医学院、韦洛雷和美国国立卫生研究院的该领域杰出领导人的指导提供了一个 这是一个巨大的机会，可以全面剖析社区范围内驱虫的免疫效果， 在这些人群中，并确定这些影响是否在驱虫后持续。 具体的指标将包括研究社区范围的驱虫对1）免疫稳态的影响 在成人中2）对不相关但共同的旁观者抗原的免疫应答（M.结核病）， 3)儿童对白喉、百日咳和流感嗜血杆菌B的疫苗反应。研究持续时间 将为5年，最初的磨合期，然后是招募和检测钩虫样本- 感染和未感染的成年人。此外，还招募了一批出生后的儿童（6岁以下 周）将随访至3岁，以评估对疫苗的纵向免疫应答。