Benefits and safety of IRon supplementation with MAlaria chemoprevention to children in Malawi (IRMA) – A randomised controlled trial
Anaemia remains a critical global health problem, affecting 43% of preschool children worldwide. In Africa, 63% of children 6-59 months of age are anaemic, and in Malawi, anaemia is most prevalent among children under 24 months of age, peaking at 91% prevalence among children aged 9-11 months.
Current strategies to decrease anaemia focus on iron supplementation as supplements or as iron-containing micronutrient powders (MNPs). World Health Organisation guidelines recommend universal iron supplementation for children in areas where anaemia is prevalent with the goal of child development and functional outcomes. However, there is little evidence that these iron interventions, particularly MNPs, result in better development and other functional health outcomes in young children. In addition, anaemia and iron deficiency are prevalent in areas where infectious disease is ubiquitous and increasing iron levels in children can increase the incidence of these diseases.
Therefore, questions around the risk of these interventions, particularly the risk of malaria infection and diarrhoea, remain unanswered.
The latest generation alternatives for malaria chemoprevention in children and pregnancy – e.g., Dihydroartemisinin-Piperaquine (DP) – are safe and superior to the older formulations, thus deserving to be better evaluated. We propose that DP may protect children against increased iron-induced malaria risk in malaria-endemic areas.
Before advocating universal implementation of iron interventions, there is a need to confirm these iron interventions deliver functional health benefits and can be safely delivered in malaria-endemic settings.
This research project aims to determine if iron supplementation or iron-containing MNPs under DP cover is superior to DP alone or DP alone is superior to placebo in improving child cognitive development after both 6 months intervention and 6 months’ follow-up post intervention. This research also aims to identify the ideal mode of delivery for iron (MNPs vs iron supplements) and determine whether DP diminishes potential risks.
This is a four-arm parallel-group, double blinded, placebo controlled, triple dummy, individually randomised trial with the following arms; a) no intervention, b) DP alone, c) MNP+DP, and d) iron supplements+DP.
The trial will randomise 2168 six-month old children with haemoglobin concentration below 7.0g/dL recruited in health centres in Chikwawa district in Southern Malawi. We will measure the child’s cognitive, motor and language development using Bayleys assessments, child behaviour using Wolke’s rating scales, temperament, and quality of home stimulation using family care indicators. The safety of iron supplements and MNPs will be measured through a morbidity assessment.
Results will inform local, regional and global health policies, assist in developing clearer guidelines for iron supplementation in malaria endemic areas and potentially influence the health of millions of children in sub-Saharan Africa and the Asia Pacific.
Professor Sant-Rayn Pasricha, Principal Investigator, Population Health and Immunity Division, WEHI
Professor Kamija Phiri, Principal Investigator, Training and Research Unit of Excellence, College of Medicine
Dr Martin Mwangi, Trial Manager, Training and Research Unit of Excellence, College of Medicine
Dr Glory Mzembe, Team Coordinator, Training and Research Unit of Excellence, College of Medicine
Dr Ricardo Ataide, Trial Manager, Population Health and Immunity Division, WEHI
Chikondi Ngwira, Team Coordinator, Training and Research Unit of Excellence, College of Medicine
Maclean Vokhiwa, Neuro Assessment Coordinator, Training and Research Unit of Excellence, College of Medicine
Sabine Braat, Senior Trial Statistician, Population Health and Immunity Division, WEHI
Dr Alistair McLean, Trial Statistician, Population Health and Immunity Division, WEHI
Dr Owen Mtambo, Head of Data Science Department, Training and Research Unit of Excellence, College of Medicine
Mary Magoya, Senior Data Officer, Training and Research Unit of Excellence, College of Medicine
Ruth Mangisa, Data Officer, Training and Research Unit of Excellence, College of Medicine
Naomi Von Dinklage, Program Coordinator, Population Health and Immunity Division, WEHI