Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation

Andrew Preston, Hans de Graaf, Muktar Ibrahim, Alison Hill, Diane Gbesemete, Andrew Vaughn, Andrew Gorringe, Anne-Marie Buisman, Saul Faust, Kent Kester, Guy Berbers, Dimitri Diavotopoulos, Robert Read

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

RATIONALE: Bordetella pertussis is one of the leading causes of vaccine preventable death and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infection might be a target of future vaccine strategies but has not been demonstrated to occur.

OBJECTIVE: To demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define microbiological and immunological features of pre-symptomatic infection.

METHODS: Healthy subjects aged 18-45 years with an anti-pertussis toxin IgG concentration of <20 IU/ml were inoculated intranasally with non-attenuated, wild type Bordetella pertussis strain B1917. Safety, colonisation and shedding were monitored over 17 days in an in-patient facility. Colonisation was assessed by culture and qPCR. Azithromycin was administered from day 14. The inoculum dose was escalated aiming to colonise at least 70% of participants. Immunological responses were measured.

RESULTS: 34 participants were challenged in groups of four or five. The dose was gradually escalated from 103 colony forming units (0% colonised) to 105 colony forming units (80% colonised). Minor symptoms were reported in a minority of participants. Azithromycin eradicated colonisation in 48 hours in 88% of colonised individuals. Anti-pertussis toxin IgG seroconversion occurred in nine out of 19 colonised participants and in none of the participants who were not colonised. Nasal wash was a more sensitive method to detect colonisation than pernasal swabs. No shedding of Bordetella pertussis was detected in systematically collected environmental samples.

INTERPRETATION: Bordetella pertussis colonisation can be deliberately induced and leads to a systemic immune response without causing pertussis symptoms.ClinicalTrials.gov:NCT03751514.

Original languageEnglish
Pages (from-to)1-35
Number of pages35
JournalClinical Infectious Diseases
Early online date28 Sep 2019
DOIs
Publication statusPublished - 28 Sep 2019

Keywords

  • Bordetella pertussis
  • human challenge
  • carriage
  • immune response

Fingerprint Dive into the research topics of 'Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation'. Together they form a unique fingerprint.

Cite this