title: Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward.
abstract: BACKGROUND
  Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea in resource-limited regions. It is also an important cause of diarrhea in travellers to these areas.To evaluate the protective efficacy of new ETEC vaccines that are under development, there is a need to increase the capacity to undertake Phase IIB (human challenge) clinical trials and to develop suitable challenge models.
  
  
  METHODS
  An in-hospital study was performed where fasting adult volunteers were experimentally infected with 1 × 106 to 1 × 109 colony forming units (CFUs) of the wild-type ETEC strain TW10598, which had been isolated from a child with diarrhea in West Africa in 1997. We recorded symptoms and physical signs and measured serum immune response to the TW10598 bacterium.
  
  
  RESULTS
  We included 30 volunteers with mean age 22.8 (range 19.8, 27.4) years. The most common symptoms were diarrhea (77%), abdominal pain (67%), nausea (63%), and abdominal cramping (53%). Seven subjects (23%) experienced fever, none were hypotensive. Most of the volunteers responded with a substantial rise in the level of serum IgA antibodies against the challenge strain.
  
  
  CONCLUSIONS
  We established the capacity and methods for safely undertaking challenge studies to measure the efficacy of ETEC vaccine candidates in a hospital ward. Strain TW10598 elicited both clinical symptoms and an immune response across the doses given.
authors.forename: Steinar
authors.initials: S
authors.lastname: Skrede
authors.forename: Hans
authors.initials: H
authors.lastname: Steinsland
authors.affiliation: Centre for Intervention Science in Maternal and Child Health and Centre for International Health, University of Bergen, PO Box 7804, N-5020 Bergen, Norway. Halvor.Sommerfelt@cih.uib.no.
authors.forename: Halvor
authors.initials: H
authors.lastname: Sommerfelt
authors.forename: Audun
authors.initials: A
authors.lastname: Aase
authors.forename: Per
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: Nina
authors.initials: N
authors.lastname: Langeland
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
authors.forename: Marianne
authors.initials: M
authors.lastname: Saevik
authors.forename: Marita
authors.initials: M
authors.lastname: Wallevik
authors.forename: Dag Harald
authors.initials: DH
authors.lastname: Skutlaberg
authors.forename: Marit Gjerde
authors.initials: MG
authors.lastname: Tellevik
authors.forename: David A
authors.initials: DA
authors.lastname: Sack
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Anne Berit
authors.initials: AB
authors.lastname: Guttormsen
mesh_terms: D015746:Abdominal Pain / Q000382:microbiology; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D054307:Enterotoxigenic Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D064368:Healthy Volunteers; D006805:Human Experimentation; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D022361:Escherichia coli Vaccines