Delivery strategies for malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years old in Malawi: a protocol for a cluster randomized trial

Abstract

Background: Children initially hospitalized with severe anaemia in Africa are at high risk of readmission or death within 6 months after discharge. No intervention strategy specifically protects children during the post-discharge period. Recent evidence from Malawi shows that 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment with artemether-lumefantrine in children with severe malarial anaemia prevented 31% of deaths and readmissions. While a confirmatory multi-centre trial for PMC with dihydroartemisinin-piperaquine is on going in Kenya and Uganda, there is a need to design and evaluate an effective delivery strategy for this promising intervention.

Methods: This is a cluster-randomized trial with 5 arms, each representing a unique PMC delivery strategy. Convalescent children aged less than 5 years and weighing more than 5 kg admitted with severe anaemia and clinically stable are included. All eligible children will receive dihydroartemisinin-piperaquine at 2, 6 and 10 weeks after discharge either: 1) in the community without an SMS reminder; 2) in the community with an SMS reminder; 3) in the community with a community health worker reminder; 4) at the hospital with an SMS reminder; or 5) at the hospital without an SMS reminder. For community-based strategies (1, 2 and 3), mothers will be given all the PMC doses at the time of discharge while for hospital-based strategies (4 and 5) mothers will be required to visit the hospital each month. Each arm will consist of 25 clusters with an average of 3 children per cluster giving approximately 75 children and will be followed up for 15 weeks. The primary outcome measure is uptake of complete courses of PMC drugs.

Discussion: The proposed study will help to identify the most effective, cost-effective, acceptable and feasible strategy for delivering malaria chemoprevention for post-discharge management of severe anaemia in under-five children in the Malawian context. This information is important for policy decision in the quest for new strategies for malaria control in children in similar contexts.

Trial registration: ClinicalTrials.gov: NCT02721420 . Protocol registered on 29 March 2016.The study was not retrospectively registered but there was a delay between date of submission and the date it first became available on the registry.

Keywords: Children; Cluster randomised trial; Dihydroartemisinin-piperaquine; Malaria; Post-discharge malaria chemoprevention; Severe anaemia.

Conflict of interest statement

Ethics approval and consent to participate

The protocol and related documents (informed consent and participant information sheets) were submitted for review to the Institutional Review Boards (IRB) and Research Ethics Committees at the Malawi College of Medicine and the Regional Ethics Committee of Norway. The study was approved by the College Of Medicine research ethics committee (COMREC), approval number P.02/15/1679, and the Regional Ethics Committee of Norway, approval number 2015/537/REK vest. Written consent was obtained from legal guardians of the study participants prior to enrolment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Study flowchart adapted from the standard protocol items: recommendations for interventional trials (SPIRIT)