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Professor James A Berkley

Professor James A Berkley

Podcast interview

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.

James Berkley

Professor of Paediatric Infectious Diseases

  • Affiliate Professor in Global Health (University of Washington)
  • Senior Clinical Research Fellow
  • Consultant Paediatrician (Allergy, Immunology & ID)

Childhood Infection and Nutrition

My research career has primarily been within the KEMRI/Wellcome Trust Research Programme in Kilifi, Kenya. My early research career focussed on large epidemiological studies addressing the aetiology, clinical features and risks for mortality of serious infections in infants and children. Major achievements include the largest and most comprehensive study of invasive bacterial infection worldwide; the first comprehensive study of viral causes of pneumonia in Africa; and studies identifying risks for failing pneumonia treatment; diagnostic strategies for meningitis and the performance of clinical syndromes in targeting of antimicrobial treatment. These have been major contributors to the introduction of conjugate vaccines in Africa, and have directly informed WHO and national management guidelines.

The main focus of my research group is serious infection and survival in highly vulnerable groups of infants and children in Africa:

Malnutrition, infection & survival

We recently completed a large multicentre randomised clinical trial of long-term daily antimicrobial prophylaxis to prevent mortality in severely malnourished children; and several proof-of principle trials of gut immunomodulation in growth failure, and polyunsaturated fatty acids within therapeutic feeds for severe malnutrition.

Ongoing, is a large multicentre trial in Kenya and Uganda is examining alternative first-line antimicrobials in severely malnourished children to prevent mortality (FLACSAM). In phase I, we are determining pharmacokinetics in malnourished children, and the presence and acquisition of ESBL and other forms of antimicrobial resistance influencing antimicrobial choices. Phase II examines efficacy on mortality, nutritional recovery, costs to health services and families, and consequences of antimicrobial resistance. Funding is by the MRC/DfID/Wellcome Global Health Trials scheme.

Work on inflammatory activation and functional immune responses to ex vivo pathogen challenge in severely malnourished children is ongoing (Kelsey Jones Wellcome fellowship).

A longitudinal birth cohort is ongoing to study 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 is ongoing (Rosie Crane Wellcome fellowship)

We are using spatial and temporal Bayesian models to examine proximate and environmental determinants of malnutrition in Kenya on a national scale to maps how determinants may differ in different places (e.g. rural/urban), in collaboration with UNICEF. Funded by Wellcome.

CHAIN: the Childhood Acute Illness & Nutrition Network

I am the Director of the CHAIN Network studying acute illness and recovery in relation to nutritional status at sites in Africa and South Asia. CHAIN 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 under 2 years old. CHAIN is funded by the Bill & Melinda Gates Foundation and is in collaboration with the University of Washington.

Neonates and infants in resource-poor settings

The Kilifi Perinatal and Maternal Health (KIPMAT) study is examining background, maternal and delivery-associated risk factors for adverse birth outcomes and neonatal infection. KIPMAT has built detailed surveillance into routine maternity care pathways in Kilifi and provides the umbrella for several studies.

A major focus of the group is invasive newborn infection. We recently completed the largest study of the clinical and molecular epidemiology of group B Streptococcus (GBS) carriage and invasive disease across different demographies, providing insight into the evolution of GBS with socio-economic development and informing vaccine design (Anna Seale WT fellowship). We are currently collaborating with the University of Witwatersrand on an international network on GBS, leading up to maternal vaccine trials.  

Following our studies using conventional microbiology, we are now investigating the aetiology of neonatal sepsis in the first 48 hours of life using multiplex molecular methods, taking advantage of surveillance and archived maternal and cord from KIPMAT. Funded by WHO/TDR.

In development are studies of legacy and novel antimicrobial regimens to treat community or hospital acquired neonatal sepsis. This will involve PK studies, re-evaluating the MIC of archived bacterial isolates to alternative antimicrobial combinations, and substantive clinical trials.

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 determine if exclusive breastfeeding can be attained and retained after discharge; and if breastmilk alone is sufficient for recovery of acutely malnourished infants. Funding is from a MRC/DfID/Wellcome Global Health Trials trial development grant (Martha Mwangome). Other work on breastfeeding is investigating the roles of families and community peers in influencing breastfeeding and complimentary feeding in the community.

Key publications

Recent publications

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