Approximately half of all children in Pakistan are stunted, 15% are wasted, and 40% are underweight. Stunting serves as a clinical marker for lifelong impairments in physical, immunological (including reduced vaccine immunogenicity), neurocognitive, and socioeconomic potential. Environmental Enteric Dysfunction (EED) is thought to be a key factor underlying malnutrition and subsequently stunting in children residing in low-and- middle income countries (LMICs) such as Pakistan. EED is an acquired, subclinical, small intestinal condition attributed to a continuous burden of immune stimulation by fecal-oral exposure to enteropathogens leading to a persistent acute phase response and chronic inflammation. EED is an excellent example of the interplay between infectious diseases and chronic malnutrition. Limited expertise and a paucity of formal training programs in pediatric infectious diseases and gastroenterology and nutrition in Pakistan are impeding progress in addressing this significant burden of disease. Through this proposal, we aim to build sustainable capacity in pediatric infectious disease and gastroenterology and nutrition research, specifically related to EED and its complications such as vaccine failure, undernutrition and subsequent growth failure in children residing in Pakistan. Training through this grant will leverage ongoing collaborative research projects and didactic (doctoral and graduate) programs currently offered at the Aga Khan University (AKU), Pakistan. We will achieve this via three training pathways of varying durations. Track I will include a series of short-term courses and workshops to be conducted on topics covering advanced wet bench laboratory skills, epidemiology, clinical nutrition and bioethics, all with an infectious diseases focus. Track II will leverage graduate programs (Master?s) in Epidemiology and Biostatistics and Clinical Research at AKU and in Data Science at the University of Virginia, USA for training candidates. Track III will produce PhD scholars working in the fields of mucosal immunology, organoids, developmental origins of health and diseases as well as clinical nutrition. Two prior successful cycles of this grant have firmly laid the foundation of infectious diseases research at AKU. We plan to leverage this framework in the next five years by producing a cadre of local, independent scientists studying the interplay of communicable and non-communicable diseases, which remain a neglected area of research throughout the world, and particularly in LMICs such as Pakistan. The overall impact of this training program will be to empower in-country local researchers to significantly reduce the burden of EED with an overarching goal of pediatric infectious disease and gastroenterology and nutrition research in Pakistan.
This D43 International Research Training Grant award will: a) Build a training program at the Aga Khan University (AKU), Pakistan; 2) Develop research capacity in infectious and gastrointestinal disease; 3) Emphasize three areas of critical importance to child survival in Pakistan; undernutrition as an enteric infectious disease (i.e., Environmental Enteric Dysfunction ? EED), vaccine efficacy, and understanding and reversing the vicious association of the cycle between maternal-child undernutrition and infectious diseases. This work will be executed in collaboration with colleagues from the University of Virginia (UVa). Through this proposal, we aim to produce a cadre of high quality, independent local scientists and build sustainable capacity in pediatric infectious disease and gastroenterology and nutrition research, specifically related to EED and its complications such as vaccine failure, undernutrition and subsequent growth failure in children residing in Pakistan.
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