Fuel for Survival: metabolic interventions to prevent neonatal sepsis

Children are most likely to die in the first month of life, the newborn period. Severe infection is a leading cause. Most of these deaths occur in low-income countries where intensive care is not available, and even where it is available, we don't understand why some newborns get sepsis and how to optimally care for them. Large human studies have given us insight into what might help - giving newborns the tuberculosis vaccine BCG reduces risk for death by 38% - an effect that my research showed was driven by a rapid expansion of white blood cells called neutrophils, that clear invading microbes. However, we don't know why BCG is not effective of all newborns. Separate human studies have shown us that delaying when a newborn is first breastfed even by two hours increases the risk for infectious death. Why this is, and how this impacts on the protection given by the BCG vaccine is unknown. My research will answer these question by mining big data derived from blood samples of newborns in a low resource setting, testing the link between BCG vaccination and newborn feeding using preclinical models, and then finding promising interventions that can be coupled with BCG vaccination to prevent severe infections. Since interventions for newborn feeding must match the community context where the baby is born, with support for the mother to offer breast milk a top priority, I will also work closely with communities to communicate my research in ways that are useful to them. Taken together, our proposed work will find out how newborn nutrition impacts on the immune response to severe infection, identify feasible and low-cost strategies to improve newborn immune resilience, and work with community to ensure these interventions work for them.