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 .

项目摘要 在这个新兴的全球领导奖申请中，Sitara Ajjampur博士计划研究 钩虫上的社区范围驱虫调节对旁观者抗原和疫苗的免疫反应 在印度南部。这项研究将建立在正在进行的基于社区的集群随机试验中 （虫3研究）。这项研究在印度有2个公共卫生问题的潜在影响：社区 - 广泛的驱虫和改善对幼儿疫苗接种的反应。这个长期目标 应用是在印度建立有关蠕虫感染和寄生虫感染的独立研究计划。 这与K43奖的目标保持一致，以启动和支持独立研究职业 在与公共卫生优先事项相吻合的领域的LMIC中。 Ajjampur博士计划基于在流行病学和实验室进行先前的经验基础 在高度著名导师的指导下进行研究。该奖项可用的受保护时间将 让她在免疫测定方面的动手实验室培训以及流动方面具有广泛的重点 疫苗学的细胞仪和实验室方面。她还将接受研究设计的培训，定量 传染病流行病学中的研究方法，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评价，以进一步开发手稿和数据 在顶级期刊上发布的可视化技能。她计划培训定性研究方法和 实施科学以了解干预策略的功效，适用于被忽视的寄生虫 感染并将研究结果转化为政策变化。 先前的工作描述了抗螺旋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以及疫苗的保护性反应的影响 回答。在印度，一个出色的现场地点和跟进虫子3研究队列的员工的组合 发现钩虫感染占主导地位的人口；以及强大的研究机构 来自该领域著名领导者的指导，来自基督教医学院，韦洛尔和NIH，提供了一个 巨大的机会，全面剖析社区范围驱虫的免疫学影响 在这些人群中，并确定这些影响是否在后期期间持续。 具体指标将包括研究社区范围驱虫对1）免疫稳态的影响 在成年人中2）对成人和成人无关但常见旁观者抗原（结核分枝杆菌）的免疫反应 3）儿童对白喉，百日咳和流感嗜血杆菌的疫苗反应。研究持续时间 最初的磨合期将为5年，然后是招募和测试样品。 感染和未感染的成年人。此外，在产后期间招募了一群儿童（6岁以下 几周）将在3岁之前进行随访，以评估对疫苗的纵向免疫反应。