Effects of a community-based intervention bundle on household transmission of extended spectrum β-lactamase-producing Escherichia coli in rural Burkina Faso to target community-level drivers of antimicrobial resistance in sub-Saharan Africa: a cluster-randomised trial.

BACKGROUND: In sub-Saharan Africa, invasive antimicrobial-resistant infections often originate from community-level acquisition. In this study, we aimed to evaluate the effect of a cluster-level intervention on individual-level extended spectrum β-lactamase-producing Escherichia coli (ESBL-E) acquisition. We assessed whether a behavioural intervention bundle targeting suboptimal antibiotic use and hygiene practices reduced household-level acquisition of ESBL-E. METHODS: We conducted a cluster-randomised controlled trial in 22 village clusters in Nanoro district, Burkina Faso. We enrolled 12 randomly selected households per cluster to assess the intervention effect on ESBL-E household transmission. The intervention comprised three rounds delivered at 3-month intervals and combined WHO Access, Watch, Reserve-based educational and feedback sessions for formal and informal medicine providers with community health education campaigns. Consenting household members provided stool samples before, during, and after intervention rollout, alongside a pre-post household water, sanitation, and hygiene (WASH) survey. ESBL-E acquisition was defined as a transition from a negative to a positive stool sample between consecutive sampling visits, with transition hazards estimated using continuous-time Markov models. We estimated intervention effects on ESBL-E acquisition using Bayesian Markov models. Cox frailty models assessed associations between WASH exposures and acquisition. The study is registered with ClinicalTrials.gov (NCT05378880). FINDINGS: 1203 individuals were enrolled between Oct 11, 2022, and Feb 19, 2024. At baseline, 346 (57%) of 604 individuals in the control household group and 291 (49%) of 599 individuals in the intervention household group tested positive for ESBL-E colonisation. Pre-intervention acquisition incidence rates were 3·8 per 100 person-days (95% credible interval [CrI] 2·0-9·9) in the intervention group and 3·5 per 100 person-days (95% CrI 1·8-9·6) in the control group. The intervention did not change the risk of ESBL-E acquisition in months 1-6 (hazard ratio [HR] 1·02 [95% CrI 0·78-1·31]) but was associated with a reduction in months 6-9 (HR 0·82 [95% CrI 0·56-1·14], probability of a reduction p[HR<1]=0·88). Acquisition risk was higher in the rainy season (peak HR 1·73 [95% CI 1·49-2·00]), whereas improved sanitation was associated with lower risk (HR 0·77 [95% CI 0·59-1·00]). INTERPRETATION: Findings, although inconclusive, were consistent with a modest intervention-related reduction in ESBL-E acquisition incidence. Higher acquisition rates associated with rainy seasons and poor sanitation highlight the need to tackle environmental drivers of antimicrobial resistance transmission in addition to antibiotic use in rural sub-Saharan Africa. FUNDING: EU Joint Programme Initiative on Antimicrobial Resistance CABU-EICO.