Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial
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Date
2014Author
Munyi, Caroline W
Ngari, Moses
Mikusa, Jenifer
Mulongo, Musa M
Odera, Dennis
Owino, Moses
Jones, Kelsey DJ
Berkley, James A
Language
enMetadata
Show full item recordAbstract
Background
Environmental enteric dysfunction (EED) is an acquired syndrome of impaired gastrointestinal mucosal barrier function that is thought to play a key role in the pathogenesis of stunting in early life. It has been conceptualized as an adaptive response to excess environmental pathogen exposure. However, it is clinically similar to other inflammatory enteropathies, which result from both host and environmental triggers, and for which immunomodulation is a cornerstone of therapy.
Methods
In this pilot double-blind randomized placebo-controlled trial, 44 children with severe acute malnutrition and evidence of EED were assigned to treatment with mesalazine or placebo for 28 days during nutritional rehabilitation. Primary outcomes were safety and acceptability of the intervention.
Results
Treatment with mesalazine was safe: there was no excess of adverse events, evidence of deterioration in intestinal barrier integrity or impact on nutritional recovery. There were modest reductions in several inflammatory markers with mesalazine compared to placebo. Depression of the growth hormone – insulin-like growth factor-1 axis was evident at enrollment and associated with inflammatory activation. Increases in the former and decreases in the latter correlated with linear growth.
Conclusions
Intestinal inflammation in EED is non-essential for mucosal homeostasis and is at least partly maladaptive. Further trials of gut-specific immunomodulatory therapies targeting host inflammatory activation in order to optimize the growth benefits of nutritional rehabilitation and to address stunting are warranted. Funded by The Wellcome Trust.
Citation
Department of Paediatrics and Child Health,Publisher
University of Nairobi
Description
Article
Collections
- Faculty of Health Sciences (FHS) [10377]