Infections, nutrition and survival

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. Interview recorded in 2019

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Childhood Nutrition & Immunity

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.

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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.