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Child mortality from infectious diseases in the tropics has decreased, but a high fatality rate in hospital and post-discharge remains for vulnerable groups such as newborns and malnourished children. The CHAIN Networks looks at preventable causes of death across 9 sites in Africa and South Asia, conducting clinical trials to improve treatments and guidelines, to improve outcomes.

My name is Jay Berkley, I am a Professor of Paediatric infectious diseases; I’ve been based at the overseas KEMRI Wellcome Trust Research Programme in Kilifi for about 21 years. My research is in causes of death, and what we can do to prevent death in the most vulnerable groups of children in developing countries. In a broad sense, it is addressing groups such as children with malnutrition, or newborn infants. More specifically, my main focus is on infections and antibiotic trials to try and improve treatment of severe infections in children.

Although there has been progress in reducing child mortality, we are still seeing a very high mortality rate, particularly in newborns. There are also other high-risk groups where we don’t seem to see any reduction in the fatality rates when children get admitted to hospital. Another thing that has emerged from recent research from us and others is that after children are discharged from hospital, there is still considerable mortality.

Some of the studies that we have done have shown that for every child that dies in hospital, another one dies post-discharge. A big focus of our research is understanding the post-discharge period – is it a problem that hasn’t been treated sufficiently in hospital, or is it something about the child’s environment or another infection that they are exposed to? Understanding these things helps us make treatments more effective – our aim is to fight tropical illnesses.

Our largest study, the CHAIN Network which stands for Childhood Acute Illness and Nutrition Network, is a study including typical hospitals across 9 sites Africa and South Asia. In those sites we are looking at potentially preventable causes of mortality in children after all the recommended treatments have been applied. At the sites we make sure that they are following the guidelines and treatments that are available. We then follow a large cohort of about 4,000 children who are at an increased risk of mortality too see what factors are leading to the increased risk of mortality in hospital and after discharge. The purpose is to then take some of the findings into clinical trials in order to directly improve outcomes.

We have just finished a small but intensive trial of a potentially new antibiotic treatment for neonatal sepsis. We are doing a very large trial of first-line antibiotics for severely ill malnourished children. We are doing those trials because there is an emerging, increasing problem with antimicrobial resistance. In the settings where we work, typically people don’t have any information on what exact bacteria are causing illness or what the sensitivity of resistance to antibiotics is. We need policies which are going to be able to be used in those typical settings. These are settings where the vast majority of children are treated.

There is information around, but it typically comes from university hospitals or private hospitals where only a tiny proportion of children get treated. By investing in research in the more generalizable population, we are providing information and improvements in guidelines, and knowledge which will improve outcomes in a much broader sense.

With regards to translational medicine, we do a lot of work in the laboratory. Firstly, we do a lot of work on characterizing what kinds of infections children have. Sometimes that uses normal microbiology techniques, and sometimes it uses much more advanced modern molecular techniques for detecting bacteria, for detecting resistance and other types of infections.

We also do a lot of work with partners overseas and other labs, looking at the effect that undernutrition and infections have on children’s metabolism. By getting this very detailed data and putting it together with the detailed information that we collect from the children themselves, we are then able to look at what pathways might be intervenable – what pathways could be interrupted or changed which would then improve outcomes. We can translate those findings from the laboratory into initially smaller trials, where we look at safety, or look at whether the pathways are being affected, and then into larger trials, to go into policy, to improve outcomes.

This interview was recorded in May 2019

Jay Berkley

Professor Jay Berkley studies serious infection diseases and survival in highly vulnerable groups of infants and children. He is the Director of the CHAIN Network that aims to better understand infectious, immune, metabolic, nutritional and social factors that could be modified to reduce mortality in hospital and after discharge amongst the most vulnerable children.

Translational Medicine

From bench to bedside

Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.