Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward
Skrede, Steinar; Steinsland, Hans; Sommerfelt, Halvor; Aase, Audun; Brandtzaeg, Per; Langeland, Nina; Cox, Rebecca Jane; Sævik, Marianne; Wallevik, Marita; Skutlaberg, Dag Harald; Tellevik, Marit Gjerde; Sack, David A.; Nataro, James P.; Guttormsen, Anne Berit
Peer reviewed, Journal article
Published version
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https://hdl.handle.net/1956/8477Utgivelsesdato
2014-09-04Metadata
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Originalversjon
https://doi.org/10.1186/1471-2334-14-482Sammendrag
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.
Utgiver
BioMed CentralTidsskrift
BMC Infectious DiseasesOpphavsrett
Copyright 2014 Skrede et al.; licensee BioMed Central Ltd.Steinar Skrede et al.; licensee BioMed Central Ltd.