Candidate. Dr. Jyoti Mathad is an Infectious Diseases-trained physician-scientist who has spent the past five years conducting research in India. She helped establish a cohort of pregnant women, developed strong scientific collaborations with Indian scientists, trained an Indian research team, and authored 8 publications related to her research. She has documented that the immune changes that occur in pregnancy impact the performance of tests to detect latent tuberculosis (TB) infection. She hypothesizes that these changes contribute to the documented increase in active TB incidence in postpartum women. Career Development Plan. Dr. Mathad?s immediate and long-term goals are the following: 1) To determine the impact of pregnancy on the host immune response to M. tuberculosis 2) To conduct a longitudinal study to identify immune correlates during pregnancy that predict the development of active TB in postpartum HIV-infected women 3) To become an expert in the pathogenesis of infectious diseases in pregnant women by gaining knowledge in translational laboratory science in immunology and statistical analysis of large data sets. 4) To become an independent physician-scientist, using the knowledge and training obtained during this grant period to design and submit an R01 proposal in year 4 of this grant 5) To become a mentor to young investigators in the US and India Dr. Mathad will develop these skills through coursework and the implementation of her research in India. Environment. The proposed research and training will take place at Weill Cornell Medical College (USA), at Byramjee Jeejeebhoy Medical College (India) and the National Institute for Research in Tuberculosis (India). The collaborations between these institutions will provide Dr. Mathad with strong mentorship. Research. Each year, over 200,000 pregnant and postpartum women worldwide develop active TB. Understanding the immunologic mechanisms by which pregnancy increases the risk of developing active TB has important implications for disease prevention strategies for pregnant women and their children.
Aim 1 : Compare the host immune responses to M. tuberculosis in 600 pregnant and non-pregnant women in Pune, India.
This aim will test the hypothesis that pregnant women have an increased abundance of regulatory immune cells (CD4+CD25+Foxp3+) and cell products (TGF-?, IL-10) and a decrease in helper T cells and their products (IFN-?, IL-2) after ex vivo stimulation of PBMCs collected in the late 3rd trimester with M. tuberculosis antigens. Dr. Mathad will enroll both HIV-infected (n=300) and ?uninfected (n=300) women.
Aim 2 : Identify the immune correlates that predict active postpartum TB in a cohort of 300 HIV-infected pregnant women. The primary hypothesis is that the magnitude of decrease in IFN-? and other cell-mediated immune cytokines during the 3rd trimester will correlate with the development of active TB in the first postpartum year.
Of the nearly 800,000 Indian women diagnosed with active TB in 2015, 70% were in their reproductive years? the current challenges are to determine why women are more vulnerable than men during this time of their lives and to find a way to protect them. Working in India for the past five years, Dr. Mathad has documented that IFN-? production in response to M. tuberculosis antigens decreases significantly in pregnant women, and she will now specifically define the impact of pregnancy on the response to M. tuberculosis by comparing the immune response in pregnant women versus non-pregnant controls. She will also identify specific immune changes in pregnancy that correlate with the development of active postpartum TB in HIV-infected pregnant women, which will help identify the pregnant women most likely to develop active TB and improve the diagnosis and prevention of TB in pregnant women and their infants.
| Li, Katherine T; Naik, Shilpa; Alexander, Mallika et al. (2018) Screening and diagnosis of gestational diabetes in India: a systematic review and meta-analysis. Acta Diabetol 55:613-625 |
| LaCourse, Sylvia M; Cranmer, Lisa M; Bekker, Adrie et al. (2018) Symptom screening for active tuberculosis in pregnant women living with HIV. Cochrane Database Syst Rev 2018: |
