Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis

Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -...

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Published in:	Clinical infectious diseases Vol. 64; no. 12; p. 1670
Main Authors:	Marks, Suzanne M, Mase, Sundari R, Morris, Sapna Bamrah
Format:	Journal Article
Language:	English
Published:	United States 15.06.2017
Subjects:	Antitubercular Agents - administration & dosage Antitubercular Agents - economics Antitubercular Agents - therapeutic use Cost-Benefit Analysis Disease Progression Drug Resistance, Multiple, Bacterial - drug effects Ethambutol - economics Ethambutol - therapeutic use Fluoroquinolones - economics Fluoroquinolones - therapeutic use Humans Latent Tuberculosis - drug therapy Latent Tuberculosis - economics Pyrazinamide - economics Pyrazinamide - therapeutic use Treatment Outcome Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - economics treatment cost contacts tuberculosis multidrug-resistant
ISSN:	1537-6591, 1537-6591
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Abstract	Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.
AbstractList	Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown.BACKGROUND.Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown.We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval.METHODS.We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval.We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen.RESULTS.We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen.Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.CONCLUSIONS.Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects. Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.
Author	Morris, Sapna Bamrah Marks, Suzanne M Mase, Sundari R
Author_xml	– sequence: 1 givenname: Suzanne M surname: Marks fullname: Marks, Suzanne M organization: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention,Atlanta, Georgia – sequence: 2 givenname: Sundari R surname: Mase fullname: Mase, Sundari R organization: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention,Atlanta, Georgia – sequence: 3 givenname: Sapna Bamrah surname: Morris fullname: Morris, Sapna Bamrah organization: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention,Atlanta, Georgia
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References	29017257 - Clin Infect Dis. 2017 Oct 15;65(8):1433-1434. doi: 10.1093/cid/cix576.
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SubjectTerms	Antitubercular Agents - administration & dosage Antitubercular Agents - economics Antitubercular Agents - therapeutic use Cost-Benefit Analysis Disease Progression Drug Resistance, Multiple, Bacterial - drug effects Ethambutol - economics Ethambutol - therapeutic use Fluoroquinolones - economics Fluoroquinolones - therapeutic use Humans Latent Tuberculosis - drug therapy Latent Tuberculosis - economics Pyrazinamide - economics Pyrazinamide - therapeutic use Treatment Outcome Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - economics
Title	Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis
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