Jones, Kelsey D. J., Hünten-Kirsch, Barbara, Laving, Ahmed M. R., Munyi, Caroline W., Ngari, Moses, Mikusa, Jenifer, Mulongo, Musa M., Odera, Dennis, Nassir, H. Samira, Timbwa, Molline, Owino, Moses, Fegan, Greg, Murch, Simon, Sullivan, Peter B., Warner, J. O. (John O.) and Berkley, James A. (2014) Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction : a pilot randomized controlled trial. BMC Medicine, Volume 12 (Number 1). Article number 133. doi:10.1186/s12916-014-0133-2 ISSN 1741-7015.

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Abstract

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.

Item Type:	Journal Article
Subjects:	R Medicine > RA Public aspects of medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Malnutrition in children -- Treatment, Inflammatory bowel diseases
Journal or Publication Title:	BMC Medicine
Publisher:	BioMed Central Ltd.
ISSN:	1741-7015
Official Date:	14 August 2014
Dates:	Date Event 14 August 2014 Published 17 July 2014 Accepted 27 May 2014 Submitted
Volume:	Volume 12
Number:	Number 1
Number of Pages:	14
Article Number:	Article number 133
DOI:	10.1186/s12916-014-0133-2
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	28 December 2015
Date of first compliant Open Access:	28 December 2015
Funder:	Wellcome Trust (London, England), National Institute for Health Research (Great Britain) (NIHR), National Institute for Health Research (Great Britain). Biomedical Research Centre
Grant number:	092088 (WT), 083579 (WT),

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