Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward
1 Division for Infectious Diseases, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway
2 Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway
3 Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway
4 Centre for Intervention Science in Maternal and Child Health and Centre for International Health, University of Bergen, PO Box 7804, N-5020 Bergen, Norway
5 Division of Infectious Disease Control, Norwegian Institute of Public Health, PO Box 4404 Nydalen, N-0403 Oslo, Norway
6 Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Centre for Immune Regulation (CIR), University of Oslo, PO Box 4950 Nydalen, N-0424 Oslo, Norway
7 Department of Pathology, Oslo University Hospital, Rikshospitalet, PO Box 4950 Nydalen, N-0424 Oslo, Norway
8 Department of Research & Development, Haukeland University Hospital, N-5021 Bergen, Norway
9 Department of Medical Microbiology, Haukeland University Hospital, N-5021 Bergen, Norway
10 National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway
11 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore 21205, MA, USA
12 Department of Pediatrics, School of Medicine, University of Virginia, P.O. Box 800326, MR4 Room 4012C, 409 Lane Road, Charlottesville, VA 22908, USA
13 Department of Anesthesia and Intensive Care, Haukeland University Hospital, N-5021 Bergen, Norway
14 Department of Clinical Medicine, University of Bergen, N-5020 Bergen, Norway
BMC Infectious Diseases 2014, 14:482 doi:10.1186/1471-2334-14-482Published: 4 September 2014
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.
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.
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.
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.