Effectiveness of a multifaceted prevention programme for melioidosis in diabetics (PREMEL): a stepped-wedge cluster-randomised controlled trial

ABSTRACTBackgroundMelioidosis, an often-fatal infectious disease caused by the environmental Gram-negative bacillus Burkholderia pseudomallei, is endemic in tropical countries. Diabetes mellitus and environmental exposure are important risk factors for melioidosis acquisition. We aim to evaluate the effectiveness of a multifaceted prevention programme for melioidosis in diabetics in northeast Thailand.Methodology/Principal FindingsFrom April 2014 to December 2018, we conducted a stepped-wedge cluster-randomized controlled behaviour change trial in 116 primary care units (PCUs) in Ubon Ratchathani province, northeast Thailand. The intervention was a behavioural support group session to help diabetic patients adopt recommended behaviours, including wearing rubber boots and drinking boiled water. We randomly allocated the PCUs to receive the intervention starting in March 2016, 2017 and 2018. All diabetic patients were contacted by phone yearly, and the final follow-up was December 2018. Two primary outcomes were hospital admissions involving infectious diseases and culture-confirmed melioidosis. Of 9,056 diabetics enrolled, 6,544 (72%) received a behavioural support group session. During 38,457 person-years of follow-up, we observed 2,195 (24%) patients having 3,335 hospital admissions involved infectious diseases, 80 (0.8%) melioidosis, and 485 (5%) deaths. In the intention-to-treat analysis, implementation of the intervention was not associated with primary outcomes. In the per-protocol analysis, patients who received a behavioural support group session had lower incidence rates of hospital admissions involving infectious diseases (incidence rate ratio [IRR] 0.89; 95%CI 0.80-0.99, p=0.03) and of all-cause mortality (IRR 0.54; 95%CI 0.43-0.68, p<0.001). There was a borderline evidence of a lower incidence rate of overall melioidosis in those who received a behavioural support group session (IRR 0.57; 95%CI 0.31-1.08, p=0.09).Conclusions/SignificanceReceiving the multifaceted prevention programme of melioidosis could reduce the rate of hospital admissions involving infectious diseases and mortality. Policy makers in melioidosis-endemic areas should consider implementing a melioidosis prevention programme in diabetes and continuing evaluation of the effectiveness of the programme.Author summaryMelioidosis, an infectious disease caused by environmental bacterium Burkholderia pseudomallei, is endemic in tropical countries. Diabetes mellitus is the most important risk factor, and routes of infection include skin inoculation, ingestion and inhalation. Prevention guidelines recommend that residents, rice farmers and visitors should wear protective gear such as rubber boots when in direct contact with soil and environmental water, and consume only boiled or bottled water. Here, we conducted a cluster randomized controlled trial to evaluate effectiveness of a multifaceted prevention programme of melioidosis in diabetic patients in northeast Thailand. We enrolled 9,056 diabetic patients in 2014. We randomly allocated primary care units as the unit of randomization to receive the intervention starting in March 2016, 2017 and 2018. All diabetic patients were contacted by phone yearly. We found that diabetic patients who received a behavioural support group session had lower incidence rates of hospital admissions involving infectious diseases and of all-cause mortality. We found a borderline evidence of a lower incidence rate of melioidosis in those who received the intervention. We propose that policy makers in melioidosis-endemic countries should consider implementing a melioidosis prevention programme.