Infections and nutritional deficiencies, including iron deficiency, affect millions of young children in Low- and Middle-Income Countries (LMICs). Iron deficiency is reported as the most common cause of preventable death and disability in such settings. Iron is essential for effective immune responses, so iron deficiency could contribute to impaired immunity leading to poor responses to vaccines and infection susceptibility in infants. However, the ways in which iron deficiency, and treating infants with iron supplements, influence infant immunity in LMIC settings remains poorly explored.

The pump-priming project 'How does iron influence infant immune development? A systems immunology RCT sub-study in Bangladesh' is a sub-study of a recently published clinical trial of iron supplementation in Bangladesh, named "BRISC" - "Benefits and Risks of Iron Interventions in Young Children" (Pasricha et al, NEJM, 2021). This trial evaluated how iron interventions affect developmental and infection outcomes. Infants were enrolled at 8 months of age and were randomly assigned to receive either an iron treatment or placebo until 11 months of age, with follow-up at 20 months of age. Small volume blood samples were taken at each of these timepoints.

In this sub-study, Andrew Armitage from the University of Oxford and his team developed a pipeline for processing and preserving low-volume blood samples from a subset of BRISC infant participants at the rural clinical trial setting, followed by applying a state-of-the-art immunological method termed CyTOF for detailed immune characterisation - requiring only 125µL whole blood. CyTOF enables the researchers to delineate the constitution of white blood cells in circulation in great detail, to investigate how this changes during infant development, and whether iron treatments influence the trajectory of these changes. It is hoped that this general approach will become broadly applicable.

Armitage and his team have collected data from a total of 109 BRISC infant participants, with blood samples from each of the 3 timepoints above, acquiring data for approximately 200,000 white blood cells per sample. After completing the computational analysis, which is ongoing, the analysis will be linked to data collected concurrently from the same infants, including their immune responses to the measles-rubella vaccine, the diversity of microorganisms found in their intestine, as well as data on infection, growth and developmental outcomes. Together, the study will advance understanding of how nutrition can shape immune development in infants in settings were the ability to mount competent immune responses to immunisations and infections is of great importance. The data may also have potential to inform global health policy makers in developing guidelines regarding the use of iron treatments in infants in infection-susceptible populations.