title: Anti-rotavirus protein reduces stool output in infants with diarrhea: a randomized placebo-controlled trial.
abstract: OBJECTIVE
  Rotavirus infection is a leading cause of morbidity and mortality in children younger than 5 years of age. Current treatment options are limited. We assessed the efficacy of a llama-derived, heavy-chain antibody fragment called anti-rotavirus protein (ARP1), in modifying the severity and duration of diarrhea in male infants with rotavirus infection.
  
  
  METHODS
  We performed a double-blind, placebo-controlled trial of 176 male infants (6-24 months old) with severe rotavirus-associated diarrhea at Dhaka Hospital, Bangladesh. The infants were randomly assigned to groups given oral ARP1 (15-30 mg/kg/day, n = 88) or placebo (maltodextrin, n = 88) for a maximum of 5 days. The primary outcomes were severity (stool output) and duration of diarrhea and fecal excretion of rotavirus. Secondary outcomes were intake of oral rehydration salt solution, severity of vomiting, and serum levels of rotavirus-specific IgA.
  
  
  RESULTS
  In infants with only rotavirus infection, total cumulative stool output was 305.47 g/kg body weight among those given placebo (n = 63) and 237.03 g/kg body weight among those given ARP1 (n = 61) (a difference of 68.44 g/kg body weight or 22.5%; 95% confidence interval: 18.27-118.59 g/kg body weight; P =.0079). There was a significant reduction in rate of stool output (g/kg/d) in the ARP1 group compared with the placebo group (61%; P = .002). ARP1 had no significant effect in infants with concomitant infections or on any other measured outcomes. No adverse events could be linked to ARP1.
  
  
  CONCLUSIONS
  In a placebo-controlled trial, ARP1 reduced stool output in male infants with severe rotavirus-associated diarrhea. Clinicaltrials.gov number: NCT01259765.
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh. Electronic address: sasarker@icddrb.org.
authors.forename: Shafiqul A
authors.initials: SA
authors.lastname: Sarker
authors.forename: Martin
authors.initials: M
authors.lastname: Jäkel
authors.forename: Shamima
authors.initials: S
authors.lastname: Sultana
authors.forename: Nur H
authors.initials: NH
authors.lastname: Alam
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Bardhan
authors.forename: Mohammod J
authors.initials: MJ
authors.lastname: Chisti
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Salam
authors.forename: Winfried
authors.initials: W
authors.lastname: Theis
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.forename: Leon G J
authors.initials: LG
authors.lastname: Frenken
mesh_terms: D003968:Diarrhea, Infantile / Q000188:drug therapy*; D004311:Double-Blind Method; D005243:Feces / Q000821:virology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000188:drug therapy*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D007128:Immunoglobulin Fragments; D014764:Viral Proteins
keywords: ARP1; Acute Diarrhea; Anti-Rotavirus Intervention; CI; Clinical Study; ELISA; ICDDR, B; International Centre for Diarrhoeal Disease Research, Bangladesh; ORS; Pediatric; anti-rotavirus protein 1; confidence interval; enzyme-linked immunosorbent assay; oral rehydration salts