Why the Increase in Pertactin-Deficient Pertussis?
Jennie H. Kwon, DO, Erik R. Dubberke, MD, MSPH
Pertactin-Negative Bordetella pertussis Strains: Evidence for a Possible Selective Advantage
Martin SW, Pawloski L, Williams M, et al
Clin Infect Dis. 2015;60:223-227
PERTUSSIS INFECTION IN THE UNITED STATES
Pertussis acellular vaccines are made of multiple inactivated components of Bordetella pertussis, including the immunogen pertactin. Pertactin is believed to enhance binding to respiratory epithelial cells and resist neutrophil-mediated clearance, thus affecting transmission and disease severity. On February 7, 2013, a letter published in the New England Journal of Medicine described the appearance of pertactin-deficient (PRN-) strains in the United States.[1] More recently, 1300 surveillance- and outbreak-related B pertussis isolates from 1935 to 2012 revealed an increase in PRN- strains.[2] Martin and colleagues conducted a retrospective study to describe the epidemiologic and clinical significance of PRN- B pertussis infections.
Isolates from 753 patients collected from May 2011 to February 2013 from eight states were included in the analysis. Six states were from the Enhanced Pertussis Surveillance/Emerging Infections Program Network sites (Colorado, Connecticut, Minnesota, New Mexico, New York, Oregon). The other two states (Washington, Vermont) had epidemic levels of pertussis in 2012 and a large number of stored isolates. All isolates from case patients were sent to the Centers for Disease Control and Prevention for analysis. Data on demographics, symptoms, and vaccine history were collected and linked to the isolates.
Overall, 640/753 (85%) of the B pertussis isolates were PRN-. In review of demographics and clinical variables, there was a significant difference in age distribution between the PRN- and PRN+ groups (P = .01). More patients with PRN+ pertussis reported apnea (P = .005). There was a trend towards increased risk for hospitalization with PRN+ strains, with 6% of patients with PRN+ strains hospitalized compared with 3% of patients with PRN- strains (P = .11). Patients who had received at least one dose of vaccine had a significantly higher odds of having PRN- B pertussiscompared with unvaccinated patients (unadjusted odds ratio [OR], 3.2; 95% confidence interval [CI], 1.9-5.3). When patients were restricted to those aged 1 year or older and those who were age-appropriately vaccinated, the OR increased to 3.7 (unadjusted OR, 3.7; 95% CI, 1.9-7.1). The investigators concluded that the greater odds of having PRN- B pertussis when fully vaccinated according to schedule suggests that vaccinated persons have greater susceptibility to PRN- strains compared with PRN+ strains.
VIEWPOINT
This study is notable for the large repository of samples tested and correlation with demographic and clinical data. Weaknesses of this study include the potential for incomplete vaccination histories, the influence of predominant circulating strains (samples were included from outbreak periods), and the inability to account for patients with mild disease who did not seek care.
Regardless, the study documents the increasing prevalence of pertactin-deficient strains in the United States and correlates this with vaccination histories. What is less clear is the clinical significance of PRN- strains. This strain has not been described to be antibiotic-resistant and, as observed in this study, does not differ in clinical presentation from PRN+ strains. Further understanding of the epidemiology and clinical outcomes of PRN- strains are necessary to expand the evidence base to develop the next generation of pertussis vaccinations and to further define the clinical significant of PRN- strains.
In conclusion, fully vaccinated patients with B pertussis infections have a 2- to 4-fold greater odds of having PRN- B pertussis infection; further investigation is needed to understand the clinical implications of this finding and to enable the development of future vaccinations.