Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis

Dominik Zenner, Netta Beer, Ross J Harris, Marc CI Lipman, Helen R. Stagg, Marieke J van der Werf

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI.

Purpose: To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children.

Data Sources: PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied.

Study Selection: Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB).

Data Extraction: 2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol.

Data Synthesis: The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to 0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53 [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered treatment efficacy.

Limitation: Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies.

Conclusion: Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin.

Primary Funding Source: U.K. National Institute for Health Research. (PROSPERO: CRD42016037871).

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalAnnals of Internal Medicine
Issue number4
Early online date1 Aug 2017
Publication statusPublished - 15 Aug 2017

Keywords / Materials (for Non-textual outputs)

  • Adult
  • Antitubercular Agents/adverse effects
  • Chemical and Drug Induced Liver Injury/etiology
  • Child
  • Drug Combinations
  • Humans
  • Isoniazid/adverse effects
  • Latent Tuberculosis/drug therapy
  • Network Meta-Analysis
  • Pyrazinamide/adverse effects
  • Rifampin/adverse effects


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