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

Thandile Nkosi-Gondwe, Bjarne Robberstad, Mavuto Mukaka, Richard Idro, Robert O Opoka, Saidon Banda, Melf-Jakob Kühl, Feiko O Ter Kuile, Bjorn Blomberg, Kamija S Phiri, Thandile Nkosi-Gondwe, Bjarne Robberstad, Mavuto Mukaka, Richard Idro, Robert O Opoka, Saidon Banda, Melf-Jakob Kühl, Feiko O Ter Kuile, Bjorn Blomberg, Kamija S Phiri

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. A map of Zomba depicting…
Fig 1. A map of Zomba depicting the study site catchment area.
Fig 2. Consolidated Standards of Reporting Trials…
Fig 2. Consolidated Standards of Reporting Trials (CONSORT) flow diagram of the PMC delivery trial.
Fig 3. Kaplan Meir curves illustrating the…
Fig 3. Kaplan Meir curves illustrating the adherence by the total number of PMC doses that were administered in each trial arm.
Fig 4. Forest plots illustrating adherence to…
Fig 4. Forest plots illustrating adherence to PMC in each trial arm.

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