The efficacy and safety of Postdischarge Malaria Chemoprevention (PDMC) on mortality and readmissions in children with severe acute malnutrition

Severe acute malnutrition (SAM) in children under five years of age is associated with a very high in-hospital mortality. However, they also have a very high risk of dying after they have been discharged from the hospital to continue treatment in community health facilities. Almost half of them do not survive the first 6 months post-discharge. The cause of death likely reflects the high risk of infections during a time when their nutritional status and immunity have not yet fully recovered. It is hypothesised that malaria infection post-discharge may be an important contributor in areas with moderate to high malaria transmission. Our group recently demonstrated that providing three months of malaria chemoprevention during this post-discharge period to children with severe anaemia, another high-risk group of post-discharge mortality, prevented 3 out of every 4 post-discharge deaths. The World Health Organisation (WHO) now recommends post-discharge malaria chemoprevention (PDMC) for hospitalised children with severe anaemia living in malaria-endemic areas. Children with SAM are likely to benefit from this intervention. However, PDMC has not yet been evaluated in this high-risk group. We propose a clinical trial involving 538 children with SAM in Uganda and Malawi. Hospitalised children under 5 years with SAM will be randomised to receive either 4 months of weekly malaria prophylaxis with an antimalarial called dihydroartemisinin-piperaquine or a placebo after being discharged from the hospital. The aim is to determine if malaria prophylaxis reduces their risk of dying or being re-hospitalised. Children will be followed up on for a total of 6 months. The study also aims to assess the safety of weekly prophylaxis dihydroartemisinin-piperaquine by conducting nested cardiac monitoring using ECGs and measuring the drug levels at specific time points. The study will also have a health-economic component to determine the potential cost-effectiveness of PDMC. Lastly, we shall assess whether this intervention is acceptable to healthcare providers and the parents or guardians. The study is designed to inform national ministries of health and WHO. We hope our findings will result in a policy recommendation for PDMC in children with SAM in malaria-endemic countries in Africa, similar to our previous PDMC studies in children with severe anaemia. This study provides a platform for 4 PhD students from Africa and supports the development of a specialised laboratory technique for assessing antimalarial drug levels in Africa. The project will take 4 years to complete and involves partners from Malawi, Uganda, South Africa, the UK, and Norway.