Treatment outcomes from community-based drug resistant tuberculosis treatment programs: a systematic review and meta-analysis

Pamela Weiss 3 Wenjia Chen 2 Victoria J Cook 0 1 James C Johnston 0 1 0 Division of Respirology, University of British Columbia , Vancouver , Canada 1 The British Columbia Center for Disease Control , 655 West 12th Avenue, Vancouver, BC V5Z4R4 , Canada 2 Collaboration for Outcomes Research and Evaluation, University of British Columbia , 2405 Wesbrook Mall, Vancouver , Canada 3 School of Humanitarian Studies, Royal Roads University , 2005 Sooke Rd, Victoria, British Columbia Background: There is increasing evidence that community-based treatment of drug resistant tuberculosis (DRTB) is a feasible and cost-effective alternative to centralized, hospital-based care. Although several large programs have reported favourable outcomes from community-based treatment, to date there has been no systematic assessment of community-based DRTB treatment program outcomes. The objective of this study was to synthesize available evidence on treatment outcomes from community based multi-drug resistant (MDRTB) and extensively drug resistant tuberculosis (XDRTB) treatment programs. Methods: We performed a systematic review and meta-analysis of the published literature to examine treatment outcomes from community-based MDRTB and XDRTB treatment programs. Studies reporting outcomes from programs using community-based treatment strategies and reporting outcomes consistent with WHO guidelines were included for analysis. Treatment outcomes, including treatment success, default, failure, and death were pooled for analysis. Meta-regression was performed to examine for associations between treatment outcomes and program or patient factors. Results: Overall 10 studies reporting outcomes on 1288 DRTB patients were included for analysis. Of this population, 65% [95% CI 59-71%] of patients had a successful outcome, 15% [95% CI 12-19%] defaulted, 13% [95% CI 9-18%] died, and 6% [95% CI 3-11%] failed treatment for a total of 35% [95% CI 29-41%] with unsuccessful treatment outcome. Meta-regression failed to identify any factors associated with treatment success, including study year, age of participants, HIV prevalence, XDRTB prevalence, treatment regimen, directly observed therapy (DOT) location or DOT provider. Conclusions: Outcomes of community-based MDRTB and XDRTB treatment outcomes appear similar to overall treatment outcomes published in three systematic reviews on MDRTB therapy. Work is needed to delineate program characteristics associated with improved treatment outcomes. - Background Drug resistant tuberculosis (DRTB) is a global health concern that undermines recent successes in tuberculosis (TB) control [1]. DRTB includes both multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB; MDRTB strains are resistant to the two most-effective first-line anti-TB drugs, while XDRTB is resistant to four highly effective anti-TB drugs [2]. Worldwide there are approximately 650,000 cases of MDRTB of which 10% are XDRTB [3,4]. Without significant scale-up in diagnostic and treatment capacity for DRTB, MDRTB and XDRTB could become the dominant forms of TB worldwide [1]. Treatment of MDRTB and XDRTB requires secondline anti-TB drugs that are more costly, less efficacious and more toxic than first-line drugs [4,5], and require 20 months of medical therapy [6]. Treatment is typically delivered using the WHO DOTS-Plus model and traditionally involves prolonged inpatient treatment that enables enhanced monitoring of adverse drug reactions, ensures adherence, and may prevent spread within the community [7,8]. Unfortunately, resource limitations often force patients to wait months for inpatient therapy, during which time they can spread to other people in their community. Inpatient therapy also increases the risk of nosocomial transmission, particularly in low-resource settings. To address these challenges, many DRTB treatment programs have incorporated community participation in the DRTB treatment. Community-based directly observed therapy (cb-DOTS) programs are low-cost treatment programs that utilize family members, neighbours, coworkers, local health care workers (HCWs) or former patients to directly observe treatment rather than requiring hospitalizations or frequent visits to a health care facility. For drug-susceptible TB, cb-DOTS appears comparable or better than hospital-based approaches [9-11]. Many research groups have examined treatment outcomes of community-based DRTB treatment models and report good results, however to date no systematic evaluation of cb-DRTB programs has been reported in the literature. Our objective was to synthesize available evidence on treatment outcomes from community based multi-drug resistant (MDRTB) and extensively drug resistant tuberculosis (XDRTB) treatment programs. We performed a systematic review and meta-analysis to investigate treatment outcomes in community-based MDRTB and XDRTB treatment programs. For the purpose of this study, community-based refers to treatment that occurs on an outpatient basis, and includes participation by community members in treatment delivery. Treatment outcomes were examined and pooled for analysis. Program and patient characteristics were also analyzed to determine the effect these variables had on treatment success. Methods The present review have been reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) (Additional file 1). Search strategy A methodical strategy was used to identify relevant publications. Our search strategy was modeled after Johnston et al. [12] and Orenstein et al. [13] with slight modification. The search was limited to English language publications in the EMBASE, MEDLINE, International Pharmaceutical Abstracts and BIOSIS databases and the Web of Science that were published between January 1990 and August 2012. Keyword searches were conducted on both titles and abstracts to identify relevant publications using combinations of the keywords MDR*, XDR*, drug resistant, drug-resistant, multidrug, multi-drug, extensively, TB, tuberculosis, directly observed, DOTS, DOTS-Plus, cb-DOTS, treatment, community, outpatient, public participation, community-based, decentralized, home-based, ambulatory, clinic, community health worker, and CHW. A search of EBM reviews was also conducted to determine existing systematic reviews on this topic. This included Database of Abstracts of Reviews and Effects, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. Citations were all thoroughly reviewed and it was determined that no systematic reviews were published on this subject. Online archives of several journals were also methodically searched manually from January 1990 (when available). Journals searched included American Journal of Respiratory and Critical Care Medicine, Clinical Infectious Disease, Chest, International Journal of Tuberculosis and Lung Disease, and Journal of Infectious Disease. Bibliographic searches of identif (...truncated)