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 two 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 Sanger Institute. This is an innovative approach with the potential to make a substantial impact in our ability to comprehensively diagnose drug-resistant tuberculosis and characterize Mtb persister populations 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 second-line TB drug-resistance and persisters using a fluorescent and colorimetric reporter. By rapidly diagnosing drug-resistant TB and further characterizing persister cells 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
Research Project (R01)
Project #
5R01AI114900-04
Application #
9268718
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Lacourciere, Karen A
Project Start
2015-05-01
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine, Inc
Department
Type
DUNS #
079783367
City
Bronx
State
NY
Country
United States
Zip Code
10461