Dr Maureen Kelley

Maureen Kelley is Associate Professor of Bioethics at The Ethox Centre in Nuffield Department of Population Health, University of Oxford. She serves as an ethics advisor and collaborating social scientist for CHAIN. Dr. Kelley is a moral philosopher and qualitative researcher by training, specializing in reproductive, maternal, newborn and child health. Her research addresses practical ethical challenges that adversely impact the health of women and children considered to be vulnerable due to social, economic, or political circumstances. In particular, she is interested in improving care for preventable diseases and adverse health outcomes, such as malnutrition, stillbirth, preterm birth, infection, and maternal-neonatal death during childbirth. In child health she has focused on improving access to health care for children living without parents—orphans, migrant children, foster children, and homeless youth. Dr. Kelley has worked extensively in international settings, conducting research and helping to develop clinical and research ethics training programs in maternal-child health. She is leading a new collaborative initiative, sponsored by the Wellcome Trust, across the major overseas programs in tropical medicine at Oxford on the ethical inclusion of vulnerable women, children, and families in research. The REACH project will explore ways to mitigate vulnerability and develop strategies for promoting agency and resilience among women, children and families through research.

Coordination Team

The coordination team works to implement and harmonize The CHAIN Network’s research activities across international sites while taking into account each sites’ specific capacities. They manage the fundamentals such as finances, website and database management, progress reports, design of research tools such as the “Case Report Forms” and “Standard Operating Procedures” (i.e. CRFs and SOPs). The team also oversees logistics, communication, as well as sample processing and handling. Their main goals are to insure that protocols are correctly implemented and to actively troubleshoot with local partners to solve or mitigate any issues.

Dr. Judd L. Walson, MD, MPH

Dr. Judd Walson, an Associate Professor at the University of Washington, completed his Internal Medicine and Pediatrics training at Duke University, and his fellowship in Infectious Disease at the University of Washington. He also holds a Masters in Public Health from Tufts University. Dr. Walson has extensive experience in designing and implementing clinical trials in resource-limited settings and has lead complex projects in Kenya, Ethiopia, Bangladesh, Thailand and Nepal. His research focuses on the intersection between infection (particularly parasitic and bacterial enteric infection), and growth and development. Dr. Walson is currently the Principal Investigator of a large NIH randomized trial in Kenya evaluating the use of azithromycin to reduce post discharge mortality and is the Kenya site Principal Investigator for a seven country trial of interventions to reduce diarrhea associated mortality in young children. In addition, he is also the Principal Investigator of DeWorm3, a large multi-country trial based at the Natural History Museum in London which is designed to evaluate the feasibility of interrupting the transmission of soil-transmitted helminths, or intestinal worms in Benin, India and Malawi. Dr. Walson also directs the Global Health Strategic Analysis and Research Training Program (START), an innovative collaboration between the Bill & Melinda Gates Foundation and the University of Washington. This program provides analytic support to organizations working in both global and domestic public health. Dr. Walson will capitalize on his broad research and management experience as co-Principal Investigator of The CHAIN Network with Professor Jay Berkley.

Professor Jay Berkley

Jay Berkley is the Principal Investigator of the CHAIN Network and co-directs the Network with Judd L. Walson. Jay is based full-time at the KEMRI/Wellcome Trust Research Programme in Kilifi, Kenya. Jay is a Professor of Paediatric Infectious Diseases at the University of Oxford in the UK and Affiliate Professor in Global Health at the University of Washington. Dr. Berkley is an expert adviser to the Ministries of Health and the World Health Organization on child health, malnutrition and antimicrobials.

Jay lead a research group working on serious infection and survival in highly vulnerable groups of infants and children. Major achievements include the largest systematic study of invasive bacterial infection in children worldwide; the first comprehensive study of viral causes of pneumonia in Africa; risks for pneumonia treatment failure; diagnostic strategies for meningitis and the performance of simple clinical syndromes in targeting of antimicrobial treatment. These have been important contributors to the introduction of conjugate vaccines in Africa, and have directly informed WHO and national management guidelines.

Current trials include a large multicentre RCT in Kenya and Uganda aiming to improve empiric first-line antimicrobial treatment in severely malnourished children (FLACSAM). Phase 1 is determining pharmacokinetics in malnourished children, and the presence and acquisition of ESBL and other forms of antimicrobial resistance influencing. Phase II examines efficacy on mortality, nutritional recovery, costs to health services and families, and consequences of antimicrobial resistance. A multicentre RCT in Kenya and Malawi is examining modified F75 therapeutic feeds for severe malnutrition to address re-feeding syndrome and osmotic diarrhoea from carbohydrate malabsorption. This RCT is being done together with Dr Robert Bandsma and Dr Wieger Voskuijl from the CHAIN Network. On breastfeeding, a pilot trial is ongoing which exploits approaches known to be successful in neonates to optimize the lactation for infants under 6 months old with acute malnutrition. We will determine if exclusive breastfeeding can be attained and retained after discharge; and if breastmilk alone is sufficient for recovery of acutely malnourished infants, together with Dr Martha Mwangome from the CHAIN Network.

Other work within the research group includes a longitudinal community birth cohort on the onset of environmental enteric dysfunction and small intestinal bacterial overgrowth in relation to mode of feeding, acquisition of intestinal pathogens, diarrhoea episodes and antimicrobial usage; inflammatory activation and functional immune responses to ex vivo pathogen challenge in severely malnourished children; spatiotemporal modelling to examine proximate and environmental determinants of malnutrition; risk factors for adverse birth outcomes and neonatal infection; aetiology, clinical and molecular epidemiology of newborn serious bacterial infection; and antimicrobial resistance in community and hospital-acquired neonatal sepsis.

Social & Behavioral Science

Acute illness and undernutrition in children usually occur against a background of social and economic disadvantage. It is conceivable that no amount of nutritional or anti-infective interventions will be effective in preventing longer term post-discharge mortality if key social constraints exist. CHAIN’s social science working group aims to understand the contribution of modifiable social factors to mortality and to other poor outcomes of acutely ill children, both in hospital and in the post-discharge period. In addition, the Network seeks to understand the true societal and financial costs associated with poor nutrition and acute illness.

Nutrition & Metabolism

Team Leaders: Dr. Robert Bandsma

‘Undernutrition’ encompasses a range of macro- and micronutrient deficiencies that usually co-exist. For children with acute illness, metabolic disturbances affect nutrient metabolism, energy production and cellular homeostasis, while enteropathy impacts nutrient absorption and growth recovery. Evidence suggests that glycogen depletion reduces tolerance to physiological insults, such as hypoxia, while interfering with basic cellular membrane function. These nutritional and metabolic deficits are potential reasons why malnourished children fail to cope with infection and are mechanisms that may cause death without preceding warning signs. The Nutrition and Metabolism working group seeks to identify a definable metabolic phenotype that leads to inpatient death and that may be amenable to novel intervention.

Causes of Death

The causes of death among malnourished children are hard to elucidate and not well understood. The gold standard in establishing cause of death is to conduct post mortem studies but these are limited by social and cultural barriers. This working group focuses on the design of ethically and culturally appropriate tools to help improve acceptance of autopsy or of targeted tissue sampling in order to better understand the causes of death among children with acute illness and malnutrition.

Respiratory Disease and Tuberculosis

Many clinicians suspect that undiagnosed tuberculosis (TB) may be responsible for many cases of acute illness and malnutrition. However, TB is notoriously difficult to diagnose in children. A significant proportion of inpatient and post-discharge mortality may be due to either occult undiagnosed TB or to incident TB that occurs in the setting of continued vulnerability and susceptibility. If TB is an important factor in acute illness among undernourished children, they may benefit from empiric tuberculosis treatment. The Respiratory Disease and TB Working Group aims to utilize the cohort follow up to determine the frequency of undiagnosed TB among malnourished children suffering from acute illnesses.

Immunity & Invasive Infection

Children with malnutrition are at increased risk of life-threatening infection, even after therapeutic feeding. However, the nature of immunological dysfunction is unclear and only a small proportion of children with a sepsis-like clinical presentation have positive bacterial cultures. Using the CHAIN platform, this group will examine clinical data and tissue samples for evidence of invasive infection and impaired immune function associated with malnutrition.  This work will lead to a better understanding of the sepsis-like presentment that appears to cause death in many acutely unwell malnourished children.

Enteric function and infection

The enteric system is critical for the maintenance of normal immune function, and nutrient absorption. Alterations in the biology of the gut caused by pathogens or medical intervention may be associated with poor recovery from acute illness. The CHAIN Network’s Enterics group aims to understand the role of intestinal pathogens, enteropathy and gut microbiome in causing death and growth failure in acutely ill children in order to then target these with treatment interventions.

Undernutrition in Infancy

Team Leader: Dr. Martha Mwangome

Malnourished infants experience very high mortality and incidence of severe infections such as pneumonia and diarrhoea. However, nutritional rehabilitation guidelines for infants under 6 months are currently based on minimal evidence. This working group will describe the patterns and consequences of breastfeeding practices among children that are acutely unwell.  In addition, they will determine how inpatient re-lactation and other breast-feeding support prevents further deterioration in child health.

Acute Care and Monitoring

Children with malnutrition and an acute illness often die unexpectedly, usually with a rapid deterioration preceded by few warning signs. Unlike well-nourished children, mortality often occurs late in the hospitalization period or after discharge. The CHAIN Network will develop and validate tools that predict these deterioration at admission and during hospitalization.  Secondly we will better define clinical recovery during hospitalization and in the post-discharge period.