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Meta-Analysis
. 2017 Jun 15;64(12):1670-1677.
doi: 10.1093/cid/cix208.

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

Suzanne M Marks  1 , Sundari R Mase  1 , Sapna Bamrah Morris  1
Affiliations
Meta-Analysis

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

Suzanne M Marks et al. Clin Infect Dis. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Clin Infect Dis. 2017 Oct 15;65(8):1433-1434. doi: 10.1093/cid/cix576. Clin Infect Dis. 2017. PMID: 29017257 No abstract available.

Abstract

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.

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.

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.

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.

Keywords: contacts; cost.; multidrug-resistant; treatment; tuberculosis.

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Conflict of interest statement

Potential conflicts of interest. All authors: No potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1
Figure 1
Of 6 comparison studies, 5 (Bamrah et al [19], Denholm et al [20], Schaaf et al [21], Adler-Shohet et al [22], Williams et al [23]) were used for tuberculosis incidence and treatment completion, and 4 (Bamrah, Denholm, Schaaf, Adler-Shohet) for treatment discontinuation due to adverse effects. Of 10 single-treatment-arm studies, 8 (Feja et al [8], Garcia-Prats et al [25], Horn et al [26], Lou et al [27], Miramontes et al [28], Papastavros et al [29], Ridzon et al [30], Seddon et al [31]) contributed to treatment completion and 8 (Feja, Garcia-Prats, Horn, Lou, Papastavros, Ridzon, Seddon, Younossian et al [32]) to treatment discontinuation due to adverse effects. Five no-treatment studies contributed to tuberculosis incidence. Abbreviations: LTBI, latent tuberculosis; MDR, multidrug-resistant; TB, tuberculosis.
Figure 2
Figure 2
Relative risks of tuberculosis incidence after multidrug-resistant latent tuberculosis treatment compared with no treatment, from meta-analysis of 5 comparison studies. Abbreviations: PM, person-months of observation with and following treatment; RR, relative risk.
See this image and copyright information in PMC

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MeSH terms