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 .
Community-wide deworming to significantly reduce and/or break transmission of soil-transmitted helminths in endemic populations can reverse the effects of these infections on host immune responses. In this study, the effect of large-scale, community-wide deworming with albendazole, on the changes to hookworm-modulated host immune response and protective immunity to bystander antigens (tuberculosis and vaccines) will be studied, in both adults and children and furthermore, whether this effect will be sustained in the post deworming period will also be studied. This study will demonstrate the potential additional benefits of deworming and is of particular importance to communities with a high burden of hookworm infection.
