Best Evidence Analyses and Commentary

Pertussis Vaccine Resistance Emerging in the U.S.
Michael Golding, PharmD Candidate; Katherine Tromp, PharmD
June 21, 2013

Pertussis, an illness characterized by a whooping cough, is caused by the bacteria Bordetella Pertussis. The disease frequently affects young children and infants. In the prevaccine era, pertussis was very common and a major cause of childhood mortality in the United States. Since the institution of routine childhood vaccinations, the incidence of pertussis has reduced from 150 reported cases per 100,000 persons in 1940, to a low of 0.5 per 100,000 in 1976.1 Since the 1980's, the incidence of the disease has gradually increased to 13.3 cases per 100,000 in 2012, the highest total since 1955.2


One explanation for the increasing prevalence of pertussis is the adaptation of the bacteria due to vaccine selection pressure. A mutated, pertactin-negative B. pertussis strain has been reported in other countries such as France, Finland, and Japan.3 Pertactin is one of many antigenic components used in the current pertussis vaccine. Pertactin is a protein that helps B. pertussis attach to the lining of the airways. Pertactin-negative B. pertussis strains have been found to have similar lethality and transmissibility compared to traditional strains. A letter published in the New England Journal of Medicine in February shows the first known occurrence of pertactinnegative B. pertussis strains in the United States.4 In the letter, researchers analyzed the pertactin genes in 12 isolates of B. pertussis cultured from children hospitalized in Philadelphia during 2011 and 2012. By the use of Western blotting, they found that 11 of the 12 isolates did not contain the pertactin protein. Pulsed-field gel electrophoresis showed multiple mutations to the gene encoding pertactin, resulting in non-expression of the protein. It was concluded that further research is needed in different geographical regions throughout the United States to determine if their findings are local, or if a more widespread shift in B. pertussis strains has occurred.


It is important to note that of the 12 B. pertussis isolates in the report, only two were collected from patients greater than 6 months of age; therefore many of the subjects were unvaccinated or under-vaccinated. Because of this, it is unknown if pertactin-negative B. pertussis is more likely to cause disease in individuals who are fully vaccinated. Although the report confirms that pertactin-negative B.pertussis variants are now in the United States, it remains to be seen whether this is a major cause of the increasing incidence of infection.


The Center for Disease Control (CDC) has acknowledged these findings. They report that other factors such as increased reporting, awareness, recognition by clinicians, better lab diagnostic testing, and the vaccine formulation change from whole cell to acellular in the 1990's are mainly responsible for the increasing incidence. The CDC also reports that the pertussis vaccine remains effective against the pertactin-negative variants because it contains other components that produce an immune response. In addition to pertactin, the current acellular pertussis vaccines also contain combinations of inactivated pertussis toxin (PT), filamentous hemagglutinin, and fimbriae, each of which can produce an immune response.3 They conclude that the vaccine continues to be a safe and effective tool in the prevention of pertussis infections.



1.       Faulkner, Amanda. et. al. Chapter 10: Pertussis. VPD Surveillance Manual. 5th. Center for Disease Control, 2011. 10/1-10/11. E-copy.

2.       2012 Provisional Pertussis Surveillance Report. Center for Disease Control.  January 4, 2013. 61(52). Accessed online: April 3, 2013. Web Address:

3.       Pertactin-Negative Pertussis Strains. National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases.  Last updated February 12, 2013. Accessed Online April 3, 2013. Web Address:

4.       Queenan, AM, PK Cassiday, and A Evangelista. "Pertactin-Negative Variants of Bordetella pertussis in the United States." New England Journal of Medicine. 386.6 (2013): 583-584. Web. 4 Apr. 2013.


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