title: Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial.
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.
  
  
  BACKGROUND
  Registered at Clinicaltrials.gov NCT01841099.
authors.forename: Kelsey D J
authors.initials: KD
authors.lastname: Jones
authors.forename: Barbara
authors.initials: B
authors.lastname: Hünten-Kirsch
authors.forename: Ahmed M R
authors.initials: AM
authors.lastname: Laving
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Munyi
authors.forename: Moses
authors.initials: M
authors.lastname: Ngari
authors.forename: Jenifer
authors.initials: J
authors.lastname: Mikusa
authors.forename: Musa M
authors.initials: MM
authors.lastname: Mulongo
authors.forename: Dennis
authors.initials: D
authors.lastname: Odera
authors.forename: H Samira
authors.initials: HS
authors.lastname: Nassir
authors.forename: Molline
authors.initials: M
authors.lastname: Timbwa
authors.forename: Moses
authors.initials: M
authors.lastname: Owino
authors.forename: Greg
authors.initials: G
authors.lastname: Fegan
authors.forename: Simon H
authors.initials: SH
authors.lastname: Murch
authors.forename: Peter B
authors.initials: PB
authors.lastname: Sullivan
authors.forename: John O
authors.initials: JO
authors.lastname: Warner
authors.forename: James A
authors.initials: JA
authors.lastname: Berkley
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002662:Child Health Services; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006798:Housing; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases; D008297:Male; D044342:Malnutrition / Q000188:drug therapy* / Q000473:pathology; D019804:Mesalamine / Q000008:administration & dosage*; D010865:Pilot Projects; D011203:Poverty; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine