Department of Pediatrics, School of Medicine, University of Minnesota, USA
Karolinska Institutet, Sweden
Instructor in Clinical Investigation, The Rockefeller University, USA
St. Johns Medical College and Hospital, CBCI Society for Medical Education, Bangalore
As a medical student at St. John’s Medical College, I spent evenings shadowing research assistants working with malnourished children in Bangalore’s crowded housing colonies. We were studying the fascinating concept of infections and nutrition, although my task was to play with the children while their mothers were being interviewed. When I came down with typhoid, I was somewhat piqued that I could not complete this project, but was quietly devastated when I realized that one of my young playmates had the same infection, but never recovered. Why were the outcomes of infections different in different people? During my fellowship at the University of Minnesota in pediatric infectious diseases, my mentor, Prof Edward Kaplan continued to motivate and mystify me with this question. When I encountered children admitted with invasive Streptococcus pyogenes infection (also the cause of the simple sore throat) who suffered extreme outcomes, Prof Kaplan gently led me on a journey of exploration of host and pathogen factors that deepened the mystery for me and kindled the desire to pursue this quest.
The Rockefeller University Clinical Scholarship subsequently transported me to Aaron Diamond AIDS Research Center, New York, where my training in research methods, immunology and molecular biology opened up new horizons. We observed an unusually high prevalence of severe skin abscesses among otherwise well-preserved youth with HIV in the Rockefeller Hospital HIV clinic. Work on methicillin-resistant Staphylococcus aureus in the setting of HIV infection was well underway, and this taught me the fascinating ways that both bacterial and viral pathogens can interact with the human host and cause different manifestations of disease. Under the guidance of Profs Martin Markowitz and David Ho, I experienced heady days grasping fun facts about HIV drug resistance and the immune response after initiating treatment in early HIV infection. Knowledge about transmitted and acquired HIV drug resistance unearthed a whole set of new questions related to inferior therapeutic responses, and I expanded my research horizon to include assessment of nutrition and clinical outcomes in HIV infection. An award from the International Nutrition Foundation in 2006 enabled me to return to India and work with children with HIV and anemia. Prof Anura Kurpad, the Dean of Research at my alma mater, St Johns, provided inspiration and expertise in this area. I began to appreciate better the interplay between malnutrition, iron deficiency as well as anemia of inflammation in HIV disease outcome, and subsequently expanded this pilot study to a multi-centric trial in South India, supported by the Indian Council of Medical Research.
My own clinical experience as a pediatrician at St. John’s Medical College Hospital was humbling and made me ponder about what possible interventions could improve clinical outcomes. I worked with Indian and international collaborators to design and implement a multi-institutional randomized controlled trial assessing the use of mobile phone interventions to improve medication adherence among HIV-infected individuals in India. Within this context, my research team worked on identifying new HIV drug resistance-associated mutations, understanding viral evolutionary pathways and characterizing circulating Indian viral strains at the molecular level, with the aim of advancing our understanding of HIV medicine globally. I decided to focus on the youngest afflicted population in the HIV world, and study questions related to host-virus interaction and drug resistance evolution. Are current dosing strategies of combination antiretroviral therapy appropriate in children? Is the viral decay rate in infants who start early treatment sufficiently rapid to provide clues to possible eradication strategies? My journey brought me in contact with a fascinating array of expertise within India – dedicated basic scientists, bioinformatics experts and engineers skilled in mathematical modeling of biological outcomes; all of who brought in tremendous synergy which galvanized these studies. I am deeply appreciative of the Wellcome Trust-DBT India Alliance for providing this outstanding opportunity and for being the catalyst that will make these studies possible.