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

Abstract

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.

Projected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa

“…10,11 We predict that this effect would be notable across most endemic settings in Africa with an effective routine implementation of the intervention. 23 PDMC would have the largest impact in the highest burden settings; e.g. in Nigeria and the DRC, where we estimate only 3 children need to be given PDMC to prevent a hospitalised malaria episode.…”

“…For simplicity, we assumed that for each course of PDMC, caregivers either gave all 3 doses or none, which was relatively consistent with observations during implementation (only 1.5% of children received 1-2 doses of DP per treatment course, with the remainder taking all or none). 23 The DP protection is applied to all children in the PDMC intervention group, except children in states T U , T S and P AL (currently symptomatic and treated). When children leave the T U and T S states and return to S , we assume they have the same protection as those who did take PDMC.…”

“…Hospitalised SMA cases are eligible for PDMC. PDMC with DP is incorporated as in the post-discharge cohort model, except that adherence is lower as measured in a recent PDMC implementation study 23 (Table S2). We also further stratify the model compartments in children given PDMC to track which courses of PDMC have been taken (any combination of the 1 st , 2 nd and 3 rd courses).…”

“…The adherence to the three full doses of PDMC drugs was lower in an implementation study of PDMC within routine clinical practice compared to the near-perfect adherence observed in clinical trials (Table S2). 23 This lower adherence is estimated to reduce protective efficacy against hospitalised malaria during weeks 3-14 from 86% to 75%, resulting in an overall protective efficacy over the 6 months of 53% (as opposed to 62% with perfect adherence). This relatively high overall efficacy results from PDMC taking effect in the earlier post-discharge period when malaria risk is highest.…”

“…In Nigeria and the DRC, 54 (range 47-62) and 50 (range 44-57) children need to be given PDMC to prevent one death, respectively. subnational (administrative area 1) regions and incorporate imperfect adherence to the three prescribed courses of PDMC as observed in ref 23 . The assumption in these results is that 50% of cases requiring hospitalisation access hospital care, but there is negligible change in these outputs when this percentage is varied.…”