Comparative effectiveness of interventions for preventing tuberculosis: systematic review and network meta-analysis of interventional studies

BACKGROUND: Tuberculosis (TB) is the leading infectious cause of death globally. Several preventive measures are employed to prevent TB, yet there is a paucity of evidence on the effectiveness of these interventions. Therefore, this study aimed to identify the most effective interventions for reducing TB incidence. METHODS: A systematic search was undertaken across five relevant databases including PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to February 22, 2023. Bayesian network meta-analysis (NMA) was conducted to compare the effectiveness of preventive interventions including preventive therapy, nutritional intervention, targeted screening, and vaccination in reducing TB incidence. Subgroup analysis was conducted to investigate the effectiveness of TB preventive treatments. FINDINGS: Overall 82 articles were included in the NMA. Preventive therapy (OR = 0.44, 95% CrI 0.36–0.52), BCG vaccination (OR = 0.62, 95% CrI 0.39–0.98) and TB candidate vaccines (OR = 0.67, 95% CrI 0.46–0.98) were more effective than placebo or no intervention. When all active interventions were considered, preventive therapy ranked as the best intervention. Of the preventive treatments, isoniazid (OR = 0.46, 95% CrI 0.35–0.55), isoniazid plus rifampicin (OR = 0.56, 95% CrI 0.32–0.97), isoniazid plus rifapentine (OR = 0.49, 95% CrI 0.29–0.83), isoniazid plus ethambutol (OR = 0.39, 95% CrI 0.15–0.99), isoniazid plus streptomycin (OR = 0.12, 95% CrI 0.02–0.55), rifampicin (OR = 0.41, 95% CrI 0.18–0.92), and rifampicin plus pyrazinamide (OR = 0.51, 95% CrI 0.29–0.87) surpassed placebo/none. INTERPRETATION: Our study suggested that when all available preventive interventions are considered, preventive therapy is likely the most effective intervention. Within TB preventive treatments, isoniazid plus streptomycin is likely ranked at the top. This comparative study provides important information for policymakers and stakeholders, enabling them to make informed decisions on preventive strategies, whilst considering local resources and capacity constraints. FUNDING: 10.13039/501100001797Curtin University strategic scholarship and Australian National Health and Medical Research Council, through an Emerging Leadership Investigator grant.