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Published on: March 24, 2017
Intermittent Versus Daily Pulmonary Tuberculosis Treatment Regimens: A Meta-Analysis
Samuel Kasozi1, Justin Clark2, Suhail A R Doi3
1National Tuberculosis and Leprosy Control Program, Ministry of Health, Wandegeya, Uganda School of Public Health, Makerere University, Uganda School of Population Health, University of Queensland, Brisbane, Australia drsamuelkasozi@gmail.com.
Background:
Several systematic reviews suggest that intermittent pulmonary tuberculosis (TB) chemotherapy is effective, but intensity (daily versus intermittent) and duration of rifampicin use (intensive phase only versus both phases) have not been distinguished. In addition, the various outcomes (success, failure, relapse, and default) have only selectively been evaluated.
Methods:
We conducted a meta-analysis of proportions using all four outcomes as multi-category proportions to examine the effectiveness of WHO category 1 TB treatment regimens. Database searches of studies reporting treatment outcomes of HIV negative subjects were included and stratified by intensity of therapy and duration of rifampicin therapy. Using a bias-adjusted statistical model, we pooled proportions of the four treatment outcome categories using a method that handles multi-category proportions.
Results:
A total of 27 studies comprising of 48 data sets with 10,624 participants were studied. Overall, treatment success was similar among patients treated with intermittent (I/I) (88%) (95% CI, 81-92) and daily (D/D) (90%) (95% CI, 84-95) regimens. Default was significantly less with I/I (0%) (95% CI, 0-2) compared to D/D regimens (5%) (95% CI, 1-9). Nevertheless, I/I relapse rates (7%) (95% CI, 3-11) were higher than D/D relapse rates (1%) (95% CI, 0-3).
Conclusion:
Treatment regimens that are offered completely intermittently versus completely daily are associated with a trade-off between treatment relapse and treatment default. There is a possibility that I/I regimens can be improved by increasing treatment duration, and this needs to be urgently addressed by future studies.
Insights
Intermittent tuberculosis (TB) chemotherapy shows similar success rates to daily regimens but with less default. However, intermittent therapy is linked to higher relapse rates, suggesting a need for improved treatment strategies.
Area of Science:
- Pulmonary medicine
- Infectious diseases
- Clinical pharmacology
Background:
- Systematic reviews indicate intermittent pulmonary tuberculosis (TB) chemotherapy efficacy.
- Key treatment variables like intensity (daily vs. intermittent) and rifampicin duration remain undifferentiated.
- Previous evaluations selectively assessed outcomes like success, failure, relapse, and default.
Purpose of the Study:
- To conduct a meta-analysis of treatment outcomes for WHO category 1 TB regimens.
- To differentiate the effectiveness of daily versus intermittent chemotherapy intensity and rifampicin duration.
- To analyze all four treatment outcomes (success, failure, relapse, default) using a multi-category proportion approach.
Main Methods:
- Meta-analysis of proportions from 27 studies (10,624 participants).
- Inclusion of HIV-negative subjects reporting treatment outcomes.
- Stratification by chemotherapy intensity and rifampicin duration.
- Application of a bias-adjusted statistical model for multi-category proportions.
Main Results:
- Overall treatment success rates were comparable: 88% for intermittent (I/I) vs. 90% for daily (D/D).
- Significantly lower default rates were observed with I/I regimens (0%) compared to D/D (5%).
- Relapse rates were higher with I/I regimens (7%) than D/D regimens (1%).
Conclusions:
- A trade-off exists between treatment relapse and default for intermittent versus daily TB chemotherapy.
- Increasing treatment duration for intermittent regimens may improve outcomes.
- Future research should urgently address optimizing intermittent TB treatment strategies.
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