Adherence to community versus facility-based delivery of monthly malaria chemoprevention with dihydroartemisinin-piperaquine for the post-discharge management of severe anemia in Malawian children: A cluster randomized trial

Background The provision of post-discharge malaria chemoprevention (PMC) in children recently admitted with severe anemia reduces the risk of death and re-admissions in malaria endemic countries. The main objective of this trial was to identify the most effective method of delivering dihydroartemesinin-piperaquine to children recovering from severe anemia. Methods This was a 5-arm, cluster-randomized trial among under-5 children hospitalized with severe anemia at Zomba Central Hospital in Southern Malawi. Children were randomized to receive three day treatment doses of dihydroartemesinin-piperaquine monthly either; 1) in the community without a short text reminder; 2) in the community with a short message reminder; 3) in the community with a community health worker reminder; 4) at the facility without a short text reminder; or 5) at the facility with a short message reminder. The primary outcome measure was adherence to all treatment doses of dihydroartemesinin-piperaquine and this was assessed by pill-counts done by field workers during home visits. Poisson regression was utilized for analysis. Results Between March 2016 and October 2018, 1460 clusters were randomized. A total of 667 children were screened and 375 from 329 clusters were eligible and enrolled from the hospital. Adherence was higher in all three community-based compared to the two facility-based delivery (156/221 [70∙6%] vs. 78/150 [52∙0%], IRR = 1∙24,95%CI 1∙06–1∙44, p = 0∙006). This was observed in both the SMS group (IRR = 1∙41,1∙21–1∙64, p<0∙001) and in the non-SMS group (IRR = 1∙37,1∙18–1∙61, p<0∙001). Although adherence was higher among SMS recipients (98/148 66∙2%] vs. non-SMS 82/144 (56∙9%), there was no statistical evidence that SMS reminders resulted in greater adherence ([IRR = 1∙03,0∙88–1∙21, p = 0∙68). When compared to the facility-based non-SMS arm (control arm), community-based delivery utilizing CHWs resulted in higher adherence [39/76 (51∙3%) vs. 54/79 (68∙4%), IRR = 1∙32, 1∙14–1∙54, p<0∙001]. Interpretation Community-based delivery of dihydroartemesinin-piperaquine for post-discharge malaria chemoprevention in children recovering from severe anemia resulted in higher adherence compared to facility-based methods. Trial registration NCT02721420; ClinicalTrials.gov.