Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia—an observational cohort study

Abstract

BackgroundIn Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients.MethodsA standardised second-line drug (SLD) regimen was used in a non-governmental organisation–Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models.ResultsFrom February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m2, p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death.ConclusionsWe report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes.

Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania

“…In addition, the spectrum of mutations to genes that predict phenotypic resistance to anti-TB drugs determines treatment outcomes. Fortunately, 82.5% (47/57) of study participants achieved treatment success, similar to findings by Meressa et al, [44] in Ethiopia. This success rate is 30% higher than the global MDR-TB treatment success rate [15], positioning the WGS method along with culture based DST as a useful testing algorithm for rigorous microbiological monitoring that will accelerate the 2035 strategic END-TB vision to create a world population free of TB [45].…”

“…This success rate is 30% higher than the global MDR-TB treatment success rate [15], positioning the WGS method along with culture based DST as a useful testing algorithm for rigorous microbiological monitoring that will accelerate the 2035 strategic END-TB vision to create a world population free of TB [45]. Over 17% of study participants had unfavourable treatment outcomes (5% mortality and 12% lost-to-follow-up), similar to that reported by Meressa et al [44],. However, this is lower than that reported by Dheda et al, [46] and Milanov et al, [47] in South Africa and Bulgaria who both documented over 50% unfavourable treatment outcomes.…”

Unfavourable outcomes among patients with MDR-TB on the standard 24-month regimen in Maharashtra, India

“…13,14 Timely initiation of antiretroviral therapy (ART) or of continuation of ART for patients already on treatment, through effective TB-HIV linkage, nutritional supplementation for patients in low weight groups and treatment adherence support has helped in reducing deaths and LTFU, ensuring a treatment success of 79%. 15 Only one in 16 patients were initiated on treatment within 14 days, and this was a risk factor for death. We assume that many of these patients would have been very ill and contributed to a higher risk of death.…”

Challenges in the clinical assessment of novel tuberculosis drugs

“…Current treatment for MDR-TB requires ≥20 months of multidrug therapy, including ≥8 months of an injectable agent [7], and yet is successful in only 48% of patients [2], not very different from the cure rates in the pre-antibiotic era-- 30% for sputum smear positive and 80% for sputum smear negative, culture positive TB [8]. In some settings, though, higher success rates have been achieved with intensification of resources and/or enhancement of the treatment regimen [9–11]. Furthermore, MDR-TB treatment regimens are poorly tolerated and have significant toxicities.…”