Effectiveness and safety of tuberculosis preventive treatment for contacts of patients with multidrug-resistant tuberculosis: a systematic review and meta-analysis

Abstract

Background: Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk.

Objectives: To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB.

Data sources: EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions.

Study eligibility criteria: We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease.

Participants: Contacts of patients with MDR-TB.

Interventions: TPT.

Assessment of risk of bias: A modified version of the Newcastle-Ottawa Scale was used.

Methods of data synthesis: Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed.

Results: Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively.

Discussion: TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.

Keywords: Contact; Meta-analysis; Multidrug-resistant tuberculosis; Preventive treatment; Risk of progression.