Implementation of new tools for multidrug-resistant tuberculosis detection and control

Abstract

Contrary to classical dogma, molecular epidemiological studies and mathematical modeling clearly show that the global drug-resistant tuberculosis (TB) epidemic is driven by transmission. Furthermore, there is mounting evidence demonstrating that amplification of resistance occurs during treatment, possibly as a result of insufficient active drugs being administered. To control the drug-resistant TB epidemic, it will be essential to implement new, rapid, and highly sensitive and specific diagnostic methods to decrease the diagnostic delay associated with culture-based testing. To date, three molecular-based diagnostic tests have been endorsed by the World Health Organization: MTBDRplus (Hain Lifescience, Nehren, Germany) Xpert MTB/RIF (Cepheid, Sunnyvale, United States) MTBDRsl (Hain Lifescience, Nehren, Germany). Implementation of the MTBDRplus assay reduced the laboratory turnaround time from 55days to 27days. This was further reduced to 1day with the implementation of the Xpert MTB/RIF assay. However, time to initiation of multidrug-resistant TB (MDR-TB) treatment was not significantly reduced, remaining at approximately 17days from receipt of drug-susceptibility testing (DST) results. In an attempt to reduce the time to initiation of MDR-TB treatment, some guidelines have recommended initiating MDR-TB treatment based on the diagnosis of rifampicin resistance alone (within 5days). However, this implies treating MDR-TB blindly until routine culture-based DST results are available (mean, 54days). This strategy may be highly effective in countries where second-line treatment has only recently been introduced, but may have significant consequences for patients with resistance beyond MDR-TB sensu stricto. Implementation of the MTBDRsl assay promises to reduce the time for DST for fluoroquinolones and second-line injectable drugs. These tests will form the foundation for DST for the implementation of the recently recommended shortened MDR-TB regimen. The impact of the implementation of these tests on treatment outcome using either the standard or shortened MDR-TB remains to be determined.