Professor Jay Berkley works in the KEMRI/Wellcome Trust Collaborative Research Programme in Kilifi, Kenya. His research interests include tackling infection and inflammation to prevent mortality in malnourished children. He is also an expert advisor on severe acute malnutrition to the Ministries of Health, and the World Health Organisatio
Malnutrition underlies between a quarter and a third of childhood mortality worldwide. It increases susceptibility to infectious diseases such as pneumonia and diarrhoea. A better understanding of the relationship between the child and the bacteria in their gut helps develop better treatments such as food supplementation or preventive treatment with low dose antibiotics.
Research in Medicine needs to ultimately translate into better treatment of patients. Researchers at the Nuffield Department of Medicine, University of Oxford, collaborate to develop better care and improved preventive measures. Findings in the laboratory are translated into changes in clinical practice, from Bench to Bedside.
Q: What are the main challenges for a paediatrician working in Kenya?
JB: I think when a lot of people think about Kenya and Africa they think of tropical diseases, but in fact the kind of problems that children get in countries like Kenya are usually the same problems that children get worldwide: things like pneumonia and diarrhoea and neonatal problems are the main causes of deaths in children. We also have things like malaria, but they are not the main causes. I think that one of the key problems is that these are diseases of poverty, so people are very poor. It means also they can’t access and pay for health care in a way that they could do in a country like this. When I first went to Africa, I went to Ghana as a student for a one year period and soon after arriving I met a doctor who said the biggest frustration was that however hard he worked on that day, the same number of children would still arrive on the following day. And I think that is a frustration a lot of people feel – that they are up against a tidal wave of problems. I think that is a reason why a lot of people want to go into research, to try and make a difference which is bigger than an individual doctor could make working on the ground.
Q: How would you describe severe acute malnutrition and what are its consequences?
JB: Malnutrition arises because children don’t get the right kinds of foods, or enough of the right kinds of foods. In many ways malnutrition underlies a lot of other diseases. We know of a lot of other infectious diseases children become much more susceptible to when they have malnutrition. In the long term, malnutrition causes children not to grow properly, and it causes delaying of brain development and essentially a sort of loss of potential for earning and intellectual capacity in the future. When malnutrition becomes severe, then there are changes in the metabolism and the physiology of the body, so a lot of processes slow down and they start to become a bit dysfunctional. We know that particularly in the gut, the gut slows down and it tends to get overgrown by bacteria which are not normally present and the absorption of food is impaired. We know that children with severe malnutrition are very susceptible to infection, and interestingly we don’t know exactly why they are susceptible. It is likely to be due to these barriers like in the skin, the gut, in the lungs, which keep bacteria and other microbes out of our bodies, it is likely that those barriers break down and allow passage of microbes, but we don’t know exactly what is wrong with the immune system or any other systems which are making children susceptible to infections.
Q: What is the impact of malnutrition on causes of childhood mortality in the developing world?
JB: We know from the epidemiological studies that malnutrition underlies probably a quarter to a third of all childhood mortality worldwide, probably slightly higher in many developing country settings, and it does so by increasing the frequency of common diseases like pneumonia and diarrhoea and also increasing the mortality of those diseases. That also becomes a vicious cycle because when a child gets pneumonia or gets diarrhoea they use up energy and nutrients, and they also don’t eat as much so it means that the children become more malnourished as a result of each infection and that results in a vicious cycle.
Q: What are the most important lines of research that have developed over the last five or ten years?
JB: There has been an increasing awareness that there are things that can be done. There is often a feeling that more emphasis needs to be placed on agricultural reform and the national policies, but those often happen very slowly. The kind of thing that can be done and will have resulted from research are things like vitamin A and zinc supplementation, which have impacted all causes of mortality specifically diarrhoea and pneumonia in children. I think that some of the exciting research at the moment is about the relationship between a child and the bacteria that are living in their gut. We know that normally we host a large number of bacteria in fact more bacteria in our gut than cells in the rest of our body, and that we live in a peaceful relationship with those bacteria and those bacteria help in breaking down food, synthesising some nutrients and regulating the absorption of nutrients to our bodies. So a lot of research is going on in that at the moment. We are currently looking at the issue of whether you can prevent serious infections in children with malnutrition and we are doing a large randomised trial of low dose antibiotics every day in a large group of children with severe malnutrition to see if we can prevent infections, and we are doing that at the same time as trying to understand the effects on the immune system.
Q: Why does your line of research matter, why should we put money into it?
JB: I think that the obvious answer is the immense burden of ill health due to under nutrition. Various estimates, between a quarter and a third of all childhood death, really justify it as an area. It is something that is also not really getting better: although worldwide malnutrition is dropping in areas such as where I work in East Africa, the rates of malnutrition are not declining, we still have problems with droughts, with political instability causing malnutrition. The big funders like the Wellcome Trust, the Bill & Melinda Gates foundation, and the World Bank have all set under nutrition as a key strategic area.
Q: How does your research fit into translational medicine within the department?
JB: It is an area that cuts across many topics. I have talked about directly working with patients, doing randomised trials, and particularly the objective of our group is to do various high quality randomised trials of both anti-infective medications and also nutrients to prevent deaths from infection. That cuts across many areas of immunology, microbiology, also measuring and assessing nutrients status. We are also working with the Nuffield Department of Obstetrics and Gynaecology to look through ultrasound at how babies grow before they are born, the impact of that on malnutrition.