Improving the Diagnosis, Treatment, and Prevention of Whooping Cough: A Characterization of the Currently Circulating Strains of Bordetella Pertussis in the United States

Open Access
Author:
Meyer, Jessica A
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Eric Thomas Harvill, Thesis Supervisor
  • Chen Pei David Tu, Honors Advisor
  • Richard John Frisque, Faculty Reader
Keywords:
  • pertussis
  • bordetella
  • whooping
  • cough
  • vaccine
  • acellular
  • antibiotic
  • healthcare
Abstract:
Prior to the advent of a whooping cough vaccine in the 1950s, hundreds of thousands of pertussis cases were reported annually in the United States. Although the vaccine era has seen a remarkable decline in cases, incidence has been steadily increasing since the 1980s, hitting a 50- year high of 48,000 cases in 2012. Several recent studies have demonstrated the continued genetic shift in pertussis strains since the pre-vaccine era, while other research endeavors have suggested the inadequacy of current acellular vaccines to prevent infection and transmission. In this study, we characterize 35 currently circulating strains of Bordetella pertussis, the main causative agent of whooping cough, collected through the Collaborative Pediatric Critical Care Research Network, the Centers for Disease Control and Prevention, and several U.S. children’s hospitals. We have established a more comprehensive profile of the current strains by evaluating isolate-specific variations in susceptibility to competitive inhibition and clinically used antibiotics, genomic sequence, pulsed-field gel electrophoresis (PFGE) type, virulence factor production, in vivo growth, and acellular vaccine protective response. Our analysis indicates consistent sensitivity to clinical antibiotics and a lack of competitive inhibition. However, there is tremendous variation in PFGE types and virulence factor alleles, particularly filamentous hemagglutinin (FHA) and pertactin (PRN), the latter of which demonstrates strain-specific diversity in antibody recognition. Despite similar growth in vivo, strains also exhibited differences in host immunity and vaccine protective response, suggesting that vaccination may not protect as adequately against clinical isolates, particularly PRN-negative strains, as it does against a lab strain from the pre-vaccine era.