Directly observed therapy for treating tuberculosis

Abstract

Background Tuberculosis (TB) requires at least six months of treatment. If treatment is incomplete, patients may not be cured and drug resistance may develop. Directly Observed Therapy (DOT) is a specific strategy, endorsed by the World Health Organization, to improve adherence by requiring health workers, community volunteers or family members to observe and record patients taking each dose. Objectives To evaluate DOT compared to self‐administered therapy in people on treatment for active TB or on prophylaxis to prevent active disease. We also compared the effects of different forms of DOT. Search methods We searched the following databases up to 13 January 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS and m RCT. We also checked article reference lists and contacted relevant researchers and organizations. Selection criteria Randomized controlled trials (RCTs) and quasi‐RCTs comparing DOT with routine self‐administration of treatment or prophylaxis at home. Data collection and analysis Two review authors independently assessed risk of bias of each included trial and extracted data. We compared interventions using risk ratios (RR) with 95% confidence intervals (CI). We used a random‐effects model if meta‐analysis was appropriate but heterogeneity present (I 2 statistic > 50%). We assessed the quality of the evidence using the GRADE approach. Main results Eleven trials including 5662 participants met the inclusion criteria. DOT was performed by a range of people (nurses, community health workers, family members or former TB patients) in a variety of settings (clinic, the patient's home or the home of a community volunteer). DOT versus self‐administered Six trials from South Africa, Thailand, Taiwan, Pakistan and Australia compared DOT with self‐administered therapy for treatment. Trials included DOT at home by family members, community health workers (who were usually supervised); DOT at home by health staff; and DOT at health facilities. TB cure was low with self‐administration across all studies (range 41% to 67%), and direct observation did not substantially improve this (RR 1.08, 95% CI 0.91 to 1.27; five trials, 1645 participants, moderate quality evidence ). In a subgroup analysis stratified by the frequency of contact between health services in the self‐treatment arm, daily DOT may improve TB cure when compared to self‐administered treatment where patients in the self‐administered group only visited the clinic every month (RR 1.15, 95% CI 1.06 to 1.25; two trials, 900 participants); but with contact in the control becoming more frequent, this small effect was not apparent (every two...

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…These meta-analyses are summarised in table 2. [186][187][188] The three meta-analyses were concordant in showing that supervised therapy was effective in reducing non-adherence and improving treatment completion. The meta-analyses also showed that no benefits were associated with DOTS compared with self-administered therapy when microbiological failure and relapse were examined as clinical endpoints.…”

“…187 The incidence of acquired drug resistance was the same whether supervised therapy was given at home, in a health facility, by a family member, or by a community health-care provider. 186 None of these analyses identified single study effect or bias. Despite this apparent absence of an effect, the DOTS programme is useful because it is an example of political commitment by governments and ensures the continuous supply of good-quality drugs, which directly affects pharmacokinetic variability.…”

“…Since then, at least five randomised controlled trials and five prospective observational studies, in which patients were assigned to self-administered therapy or supervised therapy (ie, DOTS), have been reported. [186][187][188] Recent meta-analyses of these prospective studies, in which quality was assessed and studies were ranked using standard evidence-based medicine criteria, examined the outcomes of therapy failure and acquired drug resistance. These meta-analyses are summarised in table 2.…”

“…The meta-analyses also showed that no benefits were associated with DOTS compared with self-administered therapy when microbiological failure and relapse were examined as clinical endpoints. [186][187][188][189] Pasipanodya and colleagues 187 showed that…”

“…People with MDR tuberculosis, particularly those with highly resistant strains, are often hospitalised for treatment, which increases costs for the health-care system and the patient, increases the chance of nosocomial transmission of disease, and also loss to follow-up, compared with community-based care. 480 Although drugresistant tuberculosis therapy is still almost always given as DOT, a recent Cochrane systematic review 186 questioned the effectiveness of DOT. Indeed, some evidence showed that DOT might actually represent a barrier to adherence through increased transportation costs, inability to work or go to school, and discrimination experienced from health-care providers, other patients, and the community.…”