Long term efficacy of DOTS regimens for tuberculosis: systematic review

Abstract

Objective To identify published studies assessing tuberculosis recurrence after successful treatment with standard short course regimens for six months to determine the strength and sufficiency of evidence to support current guidelines. Design Systematic review. Data sources Medline, Embase, Cochrane clinical trials register, specialist tuberculosis journals, and reference lists. Only English language publications were eligible. Review methods Studies were included irrespective of methodology or quality. Abstracted information included inclusion and exclusion criteria for participants, duration of follow-up, and definitions of treatment success and disease recurrence. The primary outcome was the proportion of successfully treated patients recorded with recurrent tuberculosis during the follow-up period. Results 17 study arms from 16 studies met the inclusion criteria; 10 were controlled clinical trials and six were either studies done under programmatic conditions or observational studies from functioning tuberculosis programmes. Although several clinical trials supported the use of daily treatment regimens, studies reporting tuberculosis recurrence after intermittent regimens were limited. Few studies carried out under routine programmatic conditions reported disease recurrence. Overall there was wide variation in recurrence after successful treatment, ranging from 0% to 14%. Considerable heterogeneity across studies precluded the systematic assessment of factors contributing to tuberculosis recurrence. Conclusions Despite DOTS (directly observed treatment, short course) being implemented for more than 10 years and millions of patients treated for tuberculosis, few studies have assessed the ability of standard DOTS regimens to result in lasting cure for patients treated under routine programmatic conditions. INTRODUCTIONThe DOTS (directly observed treatment, short course) strategy for tuberculosis control was launched by the World Health Organization in 1995.1 The strategy, although based around short course treatment regimens for a minimum of six months, also includes tenets such as political commitment, good management practices, sputum smear microscopy for diagnosis, and the direct observation of doses to ensure adherence. To date DOTS remains the cornerstone of global efforts at tuberculosis control.2 Before the implementation of DOTS, tuberculosis treatment in many resource poor settings was chaotic, non-standardised, and poorly monitored and consequently had little epidemiological impact on the incidence of tuberculosis. 3 The introduction of the DOTS strategy encompassing standardised regimens for six months through directly observed treatment has led to improvements in treatment outcomes for many patients.By 2005, 187 countries were implementing DOTS, with 4.9 million cases of tuberculosis treated under the strategy in that year alone. 4 WHO reports that 84% of new (previously untreated) patients registered with DOTS worldwide in 2004 were "successfully treated." 4 Despite this apparent achievem...

Is the directly observed therapy short course (DOTS) an effective strategy for tuberculosis control in a developing country?

“…Levels of disease recurrence after successful treatment ranged from 0% in a small controlled clinical trial in Singapore to 14% among miners in South Africa. High rates of recurrence were also seen in the observational studies carried out within DOTS programmes in India [23] .…”

“…Another systematic review by Cox et al in 2008 assessed the ability of standard DOTS therapy to result in lasting cure for patients treated under routine programmatic conditions [23] . A total of 16 studies met the inclusion criteria; ten of them were controlled clinical trials and six were either studies done under programmatic conditions or observational studies from functioning tuberculosis programmes.…”

Intracellular Time Course, Pharmacokinetics, and Biodistribution of Isoniazid and Rifabutin following Pulmonary Delivery of Inhalable Microparticles to Mice

“…Chemotherapeutic regimens for TB require prolonged administration of multiple drugs through the oral route, but their ability to provide a lasting cure has not yet been established (7). We (18,21,29,30,38; H. Sen, J. Suryakumar, R. Sinha, R. Sharma, and P. Muttil, 3 September 2003, PCT patent application PCT/ IB2003/004694) and others (19, 23-26, 39, 40) have investigated several aspects of respirable or inhalable microparticles for treatment of pulmonary TB, first proposed by Hickey et al (22,33,34).…”

Intermittent or daily short course chemotherapy for tuberculosis in children: Meta-analysis of randomized controlled trials

“…It is also postulated that intermittent therapy may be even more effective than daily therapy (in continuation phase) because it makes the organisms re-enter the phase of multiplication when the bactericidal drugs act best (23)(24). Fewer doses, even if they are larger, usually reduce drug costs and may cause fewer side effects (7).…”

“…Overall there was wide variation in recurrence after successful treatment, ranging from 0% to 14%. Considerable heterogeneity across studies precluded the systematic assessment of factors contributing to tuberculosis recurrence" (23).…”