PMID: 11997715

Issn Print: 0025-7974

Publication Date: 2002/05/01


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Effectiveness of Directly Observed Therapy (DOT) for Tuberculosis: A Review of Multinational Experience Reported in 1990–2000

A. ROSS HILL; VIVEK M. MANIKAL; PAUL F. RISKA

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Excerpt

Directly observed therapy (DOT) for tuberculosis (TB) is widely recommended by experts (6,20,50,67,71,100) and has been endorsed by local (12,21,42,99), national (17), and international (104–5) health authorities as the “standard of care” for TB treatment, yet it remains controversial in some quarters. Critics have questioned the appropriateness and net effectiveness of “universal” DOT on pragmatic, scientific, and ethical grounds (4,6,25,47,96–7,108). They suggest that DOT may be poorly accepted and hence fail to improve outcome in some settings, that it may consume scarce resources better directed elsewhere, and that concurrent improvements in other aspects of previously ineffective TB programs, in accordance with the “DOTS strategy” of the World Health Organization (WHO) (105), may actually account for much of DOT’s alleged benefit (6,45,47,72,96–7,108). Skeptics may also cite the lack of critically designed trials and question the cost-effectiveness of building an infrastructure for DOT in districts that already achieve good results with unsupervised therapy (however, these often resort to selective DOT) (6,45,72,87,96). Thus an evidence-based review published in June 2001 rated the DOT option as having “unknown effectiveness” (47).
Modern chemotherapy of TB is highly successful provided a well-designed drug regimen is taken as planned. Even effective TB programs, however, fail to achieve long-term cure in a small minority of fully treated patients (typically 1%–5%) (40,48), and completion rates can fall below 50% when there are major impediments to “case-holding” (keeping patients engaged in treatment until they complete their designated drug regimen) (9,11,30,82). A poor treatment outcome may occur for behavioral reasons on the part of the patient (missed doses) or the program staff (faulty selection and dosing of drugs; ineffective case-holding due to administrative inconveniences, lax follow-up, nonsupportive interactions with patients, etc.) Other potential reasons are biologic in nature: impaired drug bioavailability related to enteric malabsorption (55) or pill formulation (92), poor penetration of circulating drug or drugs into infected sites (34), deletion of a key drug or drugs due to an adverse effect or acquired drug resistance, and—possibly—inadequate host defences (2,51,78). In addition, reinfection by a new strain of Mycobacterium tuberculosis during or after treatment (83,94), if it manifests clinically, is likely to be misinterpreted as a failure to eradicate the initial strain.
To clarify DOT’s actual “track record” we review the published treatment outcomes of contemporary (human immunodeficiency virus [HIV] era) DOT cohorts. We examine how often and why TB treatment was unsuccessful despite DOT, focusing on 2 critical outcome measures, treatment failure and posttreatment relapse (29,40,48). Given that faulty adherence to pill-taking is regarded worldwide as the foremost cause of poor outcome (13,19,40,62,72,74,91), DOT, if successfully implemented, should yield measurable reductions in failure and relapse in a variety of settings. We reasoned that the consistent application of DOT removes nonadherence from consideration: any remaining failures of a first-line regimen could then be attributed to biologic, not behavioral, problems.

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