{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:09:19Z","timestamp":1790352559676,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T00:00:00Z","timestamp":1569628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["115910"],"award-info":[{"award-number":["115910"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Bordetella pertussis is among the leading causes of vaccine-preventable deaths and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infections might be a target of future vaccine strategies, but has not been demonstrated. Our objective was to demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define the microbiological and immunological features of presymptomatic infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Healthy subjects aged 18\u201345 years with an antipertussis toxin immunoglobin G (IgG) concentration of &amp;lt;20 international units\/ml were inoculated intranasally with nonattenuated, wild-type Bordetella pertussis strain B1917. Safety, colonization, and shedding were monitored over 17 days in an inpatient facility. Colonization was assessed by culture and quantitative polymerase chain reaction. Azithromycin was administered from Day 14. The inoculum dose was escalated, aiming to colonize at least 70% of participants. Immunological responses were measured.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There were 34 participants challenged, in groups of 4 or 5. The dose was gradually escalated from 103 colony-forming units (0% colonized) to 105 colony-forming units (80% colonized). Minor symptoms were reported in a minority of participants. Azithromycin eradicated colonization in 48 hours in 88% of colonized individuals. Antipertussis toxin IgG seroconversion occurred in 9 out of 19 colonized participants and in none of the participants who were not colonized. Nasal wash was a more sensitive method to detect colonization than pernasal swabs. No shedding of Bordetella pertussis was detected in systematically collected environmental samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Bordetella pertussis colonization can be deliberately induced and leads to a systemic immune response without causing pertussis symptoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT03751514.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz840","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T19:28:14Z","timestamp":1567625294000},"page":"403-411","source":"Crossref","is-referenced-by-count":79,"title":["Controlled Human Infection With Bordetella pertussis Induces Asymptomatic, Immunizing Colonization"],"prefix":"10.1093","volume":"71","author":[{"given":"Hans","family":"de Graaf","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Academic Unit of Clinical Experimental Sciences, National Institute of Health Research (NIHR) Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muktar","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton General Hospital, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison R","family":"Hill","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton General Hospital, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Gbesemete","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Academic Unit of Clinical Experimental Sciences, National Institute of Health Research (NIHR) Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"Vaughan","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton General Hospital, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gorringe","sequence":"first","affiliation":[{"name":"Public Health England, Salisbury, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Preston","sequence":"first","affiliation":[{"name":"The Milner Centre for Evolution and Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie M","family":"Buisman","sequence":"first","affiliation":[{"name":"Centre for Infectious Disease and Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul N","family":"Faust","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Academic Unit of Clinical Experimental Sciences, National Institute of Health Research (NIHR) Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent E","family":"Kester","sequence":"first","affiliation":[{"name":"Translational Science and Biomarkers, Sanofi Pasteur, Swiftwater, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A M","family":"Berbers","sequence":"first","affiliation":[{"name":"Centre for Infectious Disease and Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri A","family":"Diavatopoulos","sequence":"first","affiliation":[{"name":"Section of Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Radboud Center for Infectious Diseases, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Read","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences, University of Southampton, Academic Unit of Clinical Experimental Sciences, National Institute of Health Research (NIHR) Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,28]]},"reference":[{"key":"2020071109144442400_CIT0001","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/S1473-3099(17)30390-0","article-title":"An update of the global burden of pertussis in children younger than 5 years: a modelling study","volume":"17","author":"Yeung","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2020071109144442400_CIT0002","first-page":"Cd001478","article-title":"Acellular vaccines for preventing whooping cough in children","author":"Zhang","year":"2014","journal-title":"Cochrane Database Syst 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