Agnes Gwela: Immune mechanisms in severe malnutrition

My name is Agnes Gwela. I'm a postdoctoral immunologist currently based at the KEMRI Wellcome Trust Research Unit in Kilifi, Kenya. I work on understanding the impact of malnutrition on immunity in children.

Our research is globally informed by the observation from clinical trials and epidemiological studies that malnutrition results in an increased risk of incidence, severity, and case fatality from common infections. And this is very predominant in low- and middle-income countries, and that's specifically in Africa and South Asia. We are trying to understand why is malnutrition resulting in this increased vulnerability in children. And ultimately, we hope to improve that.

A recent study I did is actually based on this fact that we see this intricate link between undernutrition and infection. And the most plausible hypothesis is, knowing that the immune system is a barrier in the body that protects you from infection, we think that if you're getting sick, if you're malnourished, then it means that perhaps malnutrition is causing a breakdown in that barrier. And that's why you're getting sick. So, we recently looked at how a particular set of immune cells called neutrophils, and these are very specialised cells in guarding the body against bacterial infections, are impacted by undernutrition, if at all. We had very interesting findings because we initially thought we would just find this global eradication of function, but what we found was differential impact. If you look at specific aspects of the functions of those cells, you find some functions actually conserved in the context of malnutrition, whereas some functions are really, really severely blunted by undernutrition. So that was interesting.

The big question in the field of malnutrition at the moment is actually the mechanisms. We know that malnourished children get sick more than others and die more. The question is why. And we have, with other scientists or other studies, published various findings, but clearly these have been either insufficient or inappropriately designed to answer that question. We still have a lot of gaps in our knowledge. For example, in immunology and just understanding; the immune system is a plethora of so many cells, and just studying one cell type is not enough. We really need this global picture of how the entirety of the immune system actually works together and either is impaired by malnutrition or not, whichever way, and how those interactions ultimately result in this phenotype that we are seeing, that if you're malnourished, you get sicker or you’re more likely to die from illness.

Of course, our focus group are these malnourished children. We want the children to survive. They are dying young, that's not a good thing. You know that this is in some of the UN sustainable goals. And one of them is to improve child health. And so, we hope that the work we do will inform guidelines, because the current guidelines are either not sufficient to optimally tackle the problem or maybe inappropriate. Maybe we are using the wrong key for the right door in a way. We hope to design new interventions and also just to inform the field, because a lot of the studies that were done in malnourished children occurred very early on, and there have been recent advances in science in the analysis. Now we are capable of doing omics analysis and really going in depth. If you are inquiring about what's wrong with a cell, you can go from the top of the cell membrane and really go deep into the nucleus and look at the molecular phenotype or genotype and be able to really answer those questions in depth, and we still have not done that. We hope, by answering these questions, we will inform the field to design new interventions and then inform guidelines and ultimately improve clinical care for these children.

My vision for the future is for every child to survive. It's very heart breaking when you walk through the wards. It's an emotional part that you don't actually like to interact with. But at the end of the day, these are not numbers. These are children. And we want them to survive. We want them to live beyond their fifth birthday, and after that, their chances of survival to adulthood are much better. And so that critical period between zero to five is a part where, if we get the right interventions and target them adequately and appropriately, then we really can improve the survival of these children.