Professor James A Berkley
MBBS MTropMed MRCP MD FRCPCH FMedSci
Professor of Paediatric Infectious Diseases
- Director of the CHAIN Network (www.chainnetwork.org)
- Affiliate Professor in Global Health (University of Washington)
- Senior Clinical Research Fellow based in Kilifi, Kenya
- Consultant Paediatrician (Allergy, Immunology & ID)
Serious infections in vulnerable children and newborns
Childhood Infection and Nutrition
My research career has primarily been within the KEMRI/Wellcome Trust Research Programme in Kilifi, Kenya and the Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine at the University of Oxford. My early research career addressed 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
Current trials include 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 Trust Global Health Trials scheme. I am leading a multicentre trial in Kenya and Malawi of modified F75 therapeutic feeds for severe malnutrition to address the metabolic effects of re-feeding and osmotic diarrhoea from carbohydrate malabsorption; and a clinical trial of ready-to-use therapeutic food (RUSF) amongst severely immunocompromised older children and adults with HIV infection.
Current observational work includes 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 WT fellowship);
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
We are determining antimicrobial resistance to potential antimicrobial combinations for neonatal sepsis and conducting a PK study to assess the potential for using IV and oral fosfomycin (NeoFosfo) leading to clinical trials in neonatal sepsis.
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:
We recently completed the largest study of the clinical and molecular epidemiology of group B Streptococcus (GBS) carriage and invasive disease across different demographies, 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.
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. Funding is from a MRC/DfID/Wellcome Trust 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.
Mallewa J. et al, (2018), The Lancet HIV, 5, e231 - e240
Mramba L. et al, (2017), BMJ, j3423 - j3423
Mwangome M. et al, (2017), The American Journal of Clinical Nutrition, ajcn149815 - ajcn149815
Berkley JA. et al, (2016), The Lancet Global Health, 4, e464 - e473
Seale AC. et al, (2016), Nature Microbiology, 1
Seale AC. et al, (2016), Emerging Infectious Diseases, 22, 224 - 232
Williams PCM. et al, (2018), The Lancet Infectious Diseases, 18, e33 - e44
Standing JF. et al, (2018), Clinical Pharmacology & Therapeutics, 104, 1165 - 1174
Jones KDJ. et al, (2014), BMC Medicine, 12
Ngari MM. et al, (2017), Paediatric and Perinatal Epidemiology, 31, 233 - 242
Berkley JA., (2010), JAMA, 303, 2051 - 2051
Nabwera HM. et al, (2017), International Breastfeeding Journal, 12
Bacterial infections and Nutrition - A Primer
Berkley J., (2020), Nutrition and Infectious Diseases Shifting the Clinical Paradigm
Campion-Smith TJ. et al, (2020), PeerJ, 8, e9175 - e9175
Obiero CW. et al, (2020), Archives of disease in childhood
Zakayo SM. et al, (2020), International journal for equity in health, 19
Gonzales GB. et al, (2020), Scientific reports, 10
Fosfomycin as a potential treatment for neonatal sepsis An open label randomised clinical trial evaluating safety and pharmacokinetics
Obiero C. et al, (2020), Lancet Infectious Diseases
Drukker L. et al, (2020), American Journal of Obstetrics and Gynecology, 222, 602.e1 - 602.e15
Kahindi J. et al, (2020), International breastfeeding journal, 15
Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status
Pett SL. et al, (2020), AIDS
Guarino A. et al, (2020), Journal of pediatric gastroenterology and nutrition, 70, 694 - 701