BACKGROUND: Cluster randomised trials (CRTs) of TB interventions have achieved mixed results, with many lacking significant reductions in outcomes. Contamination in CRTs, resulting from short and long-term movement between clusters and the general population, may dilute the impact of measured intervention.METHODS: We systematically reviewed the literature to identify CRTs that aimed to capture the population-level effects of the intervention on TB. Details of trial designs, interventions, outcomes, populations, cluster configurations, and geographic data were extracted to produce text summaries, descriptive statistics, and spatial analyses. RESULTS: We screened 1,039 abstracts and included 20 reports from seven CRTs. The median number of clusters was 32 (IQR 23-61), with populations ranging from 400-50,000 individuals per cluster. Four trials reported spatial data, from which the mean distance between clusters was 12.3 km (range 3.71-35.9). Several trials acknowledged design limitations, such as small cluster sizes and population mobility, which could have led to underestimations of intervention impact. Trials used various geographic, social, and pre-existing TB measures to select and allocate study clusters. Data on the potential for contamination are inconsistent.CONCLUSION: Gaps remain in the reporting of methods and results, suggesting necessary improvements to standardised reporting tools. These insights can inform recommendations for improved CRT design and reporting practices.
BACKGROUND: The WHO recommends shorter TB preventive treatment (TPT) regimens and decentralised delivery models to improve effectiveness. This study evaluated the safety of a 3-month rifampicin-isoniazid (3RH) regimen administered by community health workers (CHWs) in households in Cameroon and Uganda.METHODS: A cluster-randomised trial was conducted among child contacts of TB patients. We compared the safety of 3RH delivered by CHWs at home (intervention) vs standard-of-care, facility-based administration of 3RH. Safety outcomes included adverse events (AEs), serious adverse events (SAEs), and adverse reactions (ARs). We described the steps from symptom identification by CHWs to classification by a clinician.RESULTS: Of 1,316 children initiated on 3RH, AEs were reported in 8.7% (81/936) in the intervention arm versus 11.3% (43/380) in the standard-of-care arm, P = 0.15. Overall, 37 SAEs occurred in 36 children, all non-medication related. There were 16 ARs reported, occurring in 1.0% (9/936) of children in the intervention arm and 1.6% (6/380) in the standard-of-care arm, P = 0.22. During 4,608 follow-up visits, 21 children reporting AR symptoms were identified by CHWs, 16 were assessed by clinicians, and 4 ARs were confirmed.CONCLUSIONS: The 3RH regimen was safe, including when administered by trained CHWs in community settings, supporting its use in decentralised healthcare models.

