Nowhere has drug-resistant TB generated more alarm than in South Africa, where synergies between endemic TB and HIV have caused 'explosive'increases in TB incidence and case- fatality rates. The most resistant form of TB, extensively drug resistant tuberculosis (XDR-TB), is increasingly prevalent in South Africa. An important obstacle to improving survival for XDR-TB is the lack of a rapid, biomarker that serves to identify viable Mtb, allow drug susceptibility testing in clinical sputum samples and detect Mtb persisters. Utilizing three novel recombinant reporter mycobacteriophages, we have developed assays with superior test characteristics that will allow us to characterize complex drug resistance and mycobacterial persistence in vivo to improve treatment outcomes for drug-resistant TB/HIV patients. This proposal is a result of an ongoing funded collaboration between researchers at Albert Einstein College of Medicine, the KwaZulu-Natal Research Institute for Research in Tuberculosis and HIV/AIDS (K-RITH), and the Centre for AIDS Programme of Research in South Africa (CAPRISA). This is an innovative approach with the potential to make a substantial impact in our ability to rapidly diagnose drug-resistant tuberculosis thereby improving treatment outcomes, reducing transmission and preventing amplification of drug resistance on treatment.

Public Health Relevance

In order to rapidly diagnose patients with drug-resistant tuberculosis (TB) and HIV, we have developed a reporter phage assay, which works rapidly in human sputum to detect first and second-line TB drug-resistance using a fluorescent and colorimetric reporter. By rapidly diagnosing drug-resistant TB we may improve survival, decrease patients'infectivity and reduce community spread of drug-resistant tuberculosis strains, particularly in HIV endemic settings.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56AI106543-01A1
Application #
8697724
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
Jacobs, Gail G
Project Start
2013-08-15
Project End
2014-07-31
Budget Start
2013-08-15
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$514,104
Indirect Cost
$206,257
Name
Albert Einstein College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Panas, Michael W; Jain, Paras; Yang, Hui et al. (2014) Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids. Proc Natl Acad Sci U S A 111:13264-71