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

Clin Infect Dis. 2017 Jun 15;64(12):1670-1677. doi: 10.1093/cid/cix208.

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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • 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

Substances

  • Antitubercular Agents
  • Fluoroquinolones
  • Pyrazinamide
  • Ethambutol