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Rapid Screening for MDR-TB

A molecular probe was ≥99% sensitive and specific for multidrug TB resistance, compared with standard drug-susceptibility testing; results were available in 1 to 2 days.

The rising prevalence of multidrug-resistant TB (MDR-TB) and HIV infection is threatening to derail global TB control. A major problem in controlling MDR-TB is the lengthy turnaround time (weeks or months) for conventional culture and drug-susceptibility testing (DST). Rapid molecular methods are now available that can yield results in a day. As a prelude to a large demonstration project, a validation study of one such test, the MTBDRplus, was performed at a single site in Cape Town, South Africa. This assay uses DNA strip technology to detect mutations in three TB genes: rpoB (mutations associated with rifampin resistance), and katG and inhA (mutations associated with isoniazid resistance).

In the first portion of the study, 536 acid-fast bacillus (AFB) smear-positive specimens were tested using the MTBDRplus and standard culture with DST. Where both tests yielded results, sensitivity of the MTBDRplus was 99% for detecting rifampin and multidrug resistance and 94% for detecting isoniazid resistance; specificity was >99% in all three cases. In the study’s next segment, 20 selected AFB smear-negative but culture-positive specimens were subjected to DST and MTBDRplus testing. Sixteen such specimens yielded interpretable MTBDRplus results for rifampin, and 14 yielded interpretable MTBDRplus results for isoniazid. Among specimens for which both MTBDRplus and DST results were available, results were 100% correlated. MTBDRplus results were not interpretable for any of the 77 culture-negative specimens. MTBDRplus results were available within 1 to 2 days, compared with a mean of 42 days for culture and DST.

Comment: Detection of MDR-TB using the MTBDRplus was rapid, sensitive, and specific, compared with culture and DST. Because this assay does not depend on culture, it yielded results even in specimens that were contaminated or had no growth. DNA testing was successful even when the AFB smear was negative. These results indicate that DNA testing could revolutionize the control of MDR-TB.

Neil M. Ampel, MD

Published in Journal Watch Infectious Diseases April 23, 2008

Citation(s):

Barnard M et al. Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. Am J Respir Crit Care Med 2008 Apr 1; 177:787.

Copyright © 2008. Massachusetts Medical Society. All rights reserved.