Abstract
Drug-resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but this situation is slowly changing. If the world is to drastically reduce the incidence of DR-TB, we must stop creating new DR-TB as an essential first step. The DR-TB epidemic that is ongoing should also be directly addressed. First-line drug resistance must be rapidly detected using universal molecular testing for resistance to at least rifampin and, preferably, other key drugs at initial TB diagnosis. DR-TB treatment outcomes must also improve dramatically. Effective use of currently available, new, and repurposed drugs, combined with patient-centered treatment that aids adherence and reduces catastrophic costs, are essential. Innovations within sight, such as short, highly effective, broadly indicated regimens, paired with point-of-care drug susceptibility testing, could accelerate progress in treatment outcomes. Preventing or containing resistance to second-line and novel drugs is also critical and will require high-quality systems for diagnosis, regimen selection, and treatment monitoring. Finally, earlier detection and/or prevention of DR-TB is necessary, with particular attention to airborne infection control, case finding, and preventive therapy for contacts of patients with DR-TB. Implementing these strategies can overcome the barrier that DR-TB represents for global TB elimination efforts, and could ultimately make global elimination of DR-TB (fewer than one annual case per million population worldwide) attainable. There is a strong cost-effectiveness case to support pursuing DR-TB elimination; however, achieving this goal will require substantial global investment plus political and societal commitment at national and local levels.
Highlights
WORLD HEALTH ORGANIZATION (WHO) guidelines have recommended since 2009—and strongly recommend— that TB programs perform routine rapid drug susceptibility testing (DST), for RMP resistance at least, among all individuals diagnosed with TB.[14]
whole-genome sequencing (WGS) could become the future of DST, but several obstacles must first be overcome in terms of speed, accuracy of predicting phenotypic resistance, demonstration of improved clinical outcomes, and resource requirements.[32]
On a more distant horizon, a highly effective, shortcourse ‘universal’ TB regimen indicated for all DSand Drug-resistant tuberculosis (DR-TB) could represent a major step toward TB and DR-TB elimination,[50] such regimens still carry several uncertainties and would likely remain universal for a limited time only.[51,52]
Summary
Drug-resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but this situation is slowly changing. The prevalence of MDR- or RRTB among TB patients with no previous treatment is 3.5% worldwide, and exceeds 1% in most high TB burden countries.[3] WHO guidelines have recommended since 2009—and strongly recommend— that TB programs perform routine rapid drug susceptibility testing (DST), for RMP resistance at least, among all individuals diagnosed with TB.[14] The End TB Strategy recommends universal DST at the time of diagnosis as a key component of patientcentered care,[1] and the 90-(90)-90 targets include identifying and appropriately treating 90% of MDRand RR-TB cases.[15] The WHO makes additional recommendations for patient-centered treatment approaches without mandatory hospitalization, a shorter 9–12-month treatment regimen, and the introduction of new drugs under specific conditions.[14] In the area of DR-TB prevention, guidelines advocate high-quality treatment of DS-TB, evaluation of close contacts for co-prevalent DR-TB and possible preventive therapy,[16] and improved infection control at health facilities and congregate settings.[17]. Despite success rates of .80% for standard MDR-TB treatment in recent clinical trials.[22] and some national programs,[23] the latest global treatment success rate for MDR-TB is 55%.3 currently fewer than one in four individuals with MDR- or RR-TB worldwide receives corresponding treatment, and only an estimated one in seven are successfully treated (Figure 2)
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