@article{8a46db468eab4af6b5158d9b9dc04900,
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.",
keywords = "Challenge, ETEC, Experimental infection, Inpatient",
author = "Steinar Skrede and Hans Steinsland and Halvor Sommerfelt and Audun Aase and Per Brandtzaeg and Nina Langeland and Cox, {Rebecca J.} and Marianne S{\ae}vik and Marita Wallevik and Skutlaberg, {Dag H.} and Tellevik, {Marit G.} and Sack, {David A.} and Nataro, {James P.} and Guttormsen, {Anne B.}",
note = "Funding Information: This work was supported by the Global Health and Vaccination (GLOBVAC) Research Program under Research Council of Norway (www.rcn.no) contract 185872/S50, project «Developing vaccines against diarrhea caused by Escherichia coli and Shigella (EntVac), the Haukeland University Hospital Strategic Research Program, and the European Union{\textquoteright}s Seventh Framework Programme for research, technological development and demonstration under Grant Agreement no 261472-STOPENTERICS. The immunological studies were also supported by GLOBHELS Project No. 192536. The volunteers participating in this study are gratefully acknowledged. We thank Dr. Per Espen Akselsen (HUH) for helping with recruitment of volunteers and for providing quality control for preparing the inocula. We are indebted to the study nurses Hanne S{\o}yland, Ane Berge and {\AA}sa Kristine Jonassen at Department of Medicine, HUH, for recruitment and to the Centre for Tropical and Imported Infectious Diseases at HUH by Dr. Kristine M{\o}rch and to Cecilie H. Isachsen in preparing the inocula. We thank the Department of Medical Microbiology at HUH for the help of Christoffer Lindemann, Olav Lutro, Kristin Kilhus, Heidi Syre, Marianne T. Wilhelmsen, and Elling Ulvestad, as well as Kurt Hanevik and Sabrina Moyo at the Department of Clinical Science at HUH for laboratory contributions and quality control observations. We also thank the ETEC diagnostic team Monica Gundersen, Rebecca Breistein og Bente Skjellstad at the Department of Medical Microbiology, HUH. We thank Jane K. N{\o}stbakken, Emilia Lohndal, Geir Bredholt, and Turid Helen F. Lunde at the Influenza Centre, Department of Clinical Science at HUH, for collecting and/or processing blood and saliva samples; Merete Bolstad and Kalpana Sinnadurai at the National Institute of Public Health, Oslo, Norway for immunological analysis of blood samples. We thank Sofie Livia and Eileen Barry at the Center for Vaccine Development, University of Maryland School of Medicine for preparing the master and working cell banks of the challenge strain. We thank Karen Kotloff (Center for Vaccine Development, University of Maryland, USA), Anne Ma Dyrhol-Riise (University of Oslo, Norway) and A Louis Bourgeois for discussions and advice in connection with project development. Finally, we thank the staff at the Infectious Diseases ward 5, and Drs. Mamoun Elzubair, Bj{\o}rn Blomberg, {\O}ystein Power, Trond Bruun and other colleagues at the HUH who were involved in supervising the study subjects. Publisher Copyright: {\textcopyright} 2014 Skrede et al.; licensee BioMed Central Ltd.",
year = "2014",
month = sep,
day = "4",
doi = "10.1186/1471-2334-14-482",
language = "English (US)",
volume = "14",
journal = "BMC infectious diseases",
issn = "1471-2334",
publisher = "BioMed Central",
number = "1",
}