Tuberculosis (TB) is the leading cause of infectious disease death globally, and accounts for 4 out of 10 deaths in HIV-infected individuals. Although progress has been made in decreasing incidence and mortality from TB, the current trends are woefully insufficient to achieve the WHO End TB goal of fewer than 10 TB cases per 100,000 population by 2035. Innovative research to develop new diagnostic, therapeutic and prevention tools are critically needed. Thus, training the next generation of scientists with expertise to carry out translational studies in TB and TB/HIV co-infection in high burden settings is an important priority. The goal of this K24 competitive renewal is to continue to mentor promising young investigators in clinical and translational patient- oriented research in TB, HIV and Global Health. My current K24 has been very successful in supporting mentorship for 33 trainees, and in allowing me to expand my research program substantially to include molecular epidemiology, TB immunology and clinical trials. The current K24 supported 36 publications, including 26 with a mentee as first author. Mentees were also successful in submitting extramural grants, including NIH K career development awards and making the transition from K awards to their first R01 grants. In this competitive renewal, I will expand my own training to: 1) understand how human genetics and epigenetics can elucidate mechanisms underlying susceptibility and resistance to Mtb infection; 2) gain further expertise in spatial epidemiology and spatial statistics to inform studies of TB transmission; and 3) enhance my mentorship and leadership skills to prepare my trainees for careers in patient-oriented research. This additional training will enhance my mentorship of trainees participating in our ongoing R01 studies examining: the role of casual contact in TB transmission; and host genetic polymorphisms associated with resistance to Mtb infection. The K24 continuation will also facilitate a pilot epigenetic study investigating two novel specific research aims: 1) to assess candidate DNA methylation sites for association with resistance to Mtb infection; and 2) to identify epigenetic predictors of resistance to Mtb infection using an epigenome-wide approach. The research from my ongoing R01 studies and the proposed new pilot study will generate novel insights into factors associated with TB transmission and susceptibility to Mtb infection to inform the development of epidemiologic interventions and preventive therapeutics to reduce the number of new Mtb infections. Further, the data and specimens generated will provide numerous training opportunities for my mentees to develop their own career development projects.

Public Health Relevance

Tuberculosis is the leading infectious disease cause of death worldwide and accounts for 4 out of every 10 death in HIV-infected individuals. Neel Gandhi, M.D., is a physician-scientist at Emory University dedicated to patient-oriented research in TB, HIV and global health. Continuation of this K24 award will provide the needed protected time for Dr. Gandhi to provide mentorship to young investigators pursuing these fields and to expand his research program in the emerging areas of genetics, epigenetics, spatial epidemiology and spatial statistics.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
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Srinivasan, Sudha
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Emory University
Public Health & Prev Medicine
Schools of Public Health
United States
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Bozio, Catherine H; Flanders, W Dana; Finelli, Lyn et al. (2018) Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia. Open Forum Infect Dis 5:ofy061
Peloquin, Charles A; Phillips, Patrick P J; Mitnick, Carole D et al. (2018) Increased Doses Lead to Higher Drug Exposures of Levofloxacin for Treatment of Tuberculosis. Antimicrob Agents Chemother 62:
Auld, Sara C; Shah, N Sarita; Mathema, Barun et al. (2018) Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities. Eur Respir J 52:
Brust, James C M; Shah, N Sarita; Mlisana, Koleka et al. (2018) Improved Survival and Cure Rates With Concurrent Treatment for Multidrug-Resistant Tuberculosis-Human Immunodeficiency Virus Coinfection in South Africa. Clin Infect Dis 66:1246-1253
Haddad, Maryam B; Raz, Kala M; Lash, Timothy L et al. (2018) Simple Estimates for Local Prevalence of Latent Tuberculosis Infection, United States, 2011-2015. Emerg Infect Dis 24:1930-1933
Auld, Sara C; Shah, N Sarita; Cohen, Ted et al. (2018) Where is tuberculosis transmission happening? Insights from the literature, new tools to study transmission and implications for the elimination of tuberculosis. Respirology :
Magee, M J; Gandhi, N R; Kornfeld, H (2018) A dual purpose for household contact investigations: preventing TB disease and improving diabetes outcomes. Int J Tuberc Lung Dis 22:594-595
Nelson, Kristin N; Shah, N Sarita; Mathema, Barun et al. (2018) Spatial Patterns of Extensively Drug-Resistant Tuberculosis Transmission in KwaZulu-Natal, South Africa. J Infect Dis 218:1964-1973
Turner, Richard D; Chiu, Christopher; Churchyard, Gavin J et al. (2017) Tuberculosis Infectiousness and Host Susceptibility. J Infect Dis 216:S636-S643
Kapwata, Thandi; Morris, Natashia; Campbell, Angela et al. (2017) Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients in KwaZulu-Natal, South Africa. PLoS One 12:e0181797

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