Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial

BMC Medicine

James A Berkley⁷  John O Warner⁴  Peter B Sullivan⁸  Simon H Murch¹  Greg Fegan⁷  Moses Owino⁵  Molline Timbwa²  H Samira Nassir³  Dennis Odera²  Musa M Mulongo²  Jenifer Mikusa²  Moses Ngari²  Caroline W Munyi³  Ahmed MR Laving⁶  Barbara Hünten-Kirsch³  Kelsey DJ Jones⁴ 

[1] Warwick Medical School, University of Warwick, Warwick, UK;KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya;Baraka Health Centre, German Doctors Nairobi, Nairobi, Kenya;Imperial-Wellcome Centre for Global Health Research and Section of Paediatrics, Imperial College London, Norfolk Place, London W2 1PG, UK;Ministry of Health, Government of Kenya, Nairobi, Kenya;Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya;Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Department of Paediatrics, University of Oxford, Oxford, UK

关键词: Tropical gastroenterology;    Mucosal immunity;    Malnutrition;    Inflammatory bowel disorders;    Barrier function;   

Others  :  1121544
DOI  :  10.1186/s12916-014-0133-2

 received in 2014-05-27, accepted in 2014-07-17,  发布年份 2014

【 摘 要 】

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.

Trial registration

Registered at Clinicaltrials.gov NCT01841099 webcite.

【 授权许可】

   
2014 Jones et al.; licensee BioMed Central

【 图 表 】

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