Outside of Africa, type 2 diabetes (DM) accounts for as much of the global TB burden as HIV and this fraction is highest in the developing world. Though the strong association between DM and TB has been clearly demonstrated, evidence that DM negatively affects TB clinical outcomes is not as clear, leaving several questions unanswered. The potential causes for potential suboptimal response to treatment among diabetics - low concentrations of anti-TB drugs, poor glycemic control, higher mycobacterial burden at the initiation of therapy, for example - have not been rigorously explored. We will recruit and prospectively follow 600 smear and culture positive TB patients in Rio de Janeiro, Brazil where the DM problem is climbing substantially and a TB epidemic has not subsided.
The specific aims of the study are 1) To estimate the burden of DM and the impact of DM on TB treatment outcomes among patients with smear- positive pulmonary TB in Rio de Janeiro, Brazil, 2) Evaluate the impact of poor diabetic control on response to TB treatment among patients with TB and DM, and, 3) Using pharmacokinetic/pharmaocdynamic (PK/PD) modeling, determine the key contributing factors to poor microbiologic outcomes among patients being treated for pulmonary TB with or without DM. Our multidisciplinary approach will provide the best evidence to date addressing the complex interactions between these two diseases and inform management strategies for developing countries facing these converging epidemics.

Public Health Relevance

With an estimated 285 million people currently living with type 2 diabetes and expectations that this number will climb to over 400 million by 2030, countries in the developing world with already epidemic levels of tuberculosis are at particular risk of suffering the effects of these two converging epidemics. The purpose of this study is to prospectively enroll and follow a cohort of pulmonary tuberculosis patients with and without diabetes in Rio de Janeiro, Brazil in order to measure and compare TB treatment outcomes between these patients. We will address the key contributing factors to poorer treatment responses in patients affected by both diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI097494-02
Application #
8607116
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Mason, Robin M
Project Start
2013-02-01
Project End
2018-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
$532,880
Indirect Cost
$81,178
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218