Developing an effective anti-tuberculosis treatment cascade: from Edinburgh to Bangladesh

Treatment must be initiated promptly in any patient newly diagnosed with tuberculosis. The choice for initial treatment is a regimen ideally proven in a clinical trial to have high efficacy in preventing treatment failure and relapse. Over time, the choice of this initial regimen has changed with ever increasingly efficacious and effective drug combinations. The regimen is only changed when there is evidence for intolerance or bacteriological failure. Commonly, a fallback regimen in case of bacteriologic failure is again a standardized regimen promising a high probability of success. In industrialized countries and with the increasing access to rapidly available drug susceptibility test results, the fallback regimen’s composition is often individualized according to drug susceptibility test results. This may not always be appropriate as there might not be a good clinical correlation with laboratory test results. If a failing standard initial regimen is followed by another standard fallback regimen, we call this sequence the “cascade of treatment regimens”. In this presentation, we will delineate the history of the regimen cascade and the often encountered difficulties to find acceptance of new standards by the medical community. In doing so, we will honor individuals who pioneered new paradigms by providing pragmatic and programmatic assistance in moving the concept and implementation of the cascade of regimens forward towards full integration into national tuberculosis control programs.