Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Abstract

ABSTRACTPertussis has shown a striking resurgence in the United States, with a return to record numbers of reported cases as last observed in the 1950s.Bordetella pertussisisolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting thatB. pertussisis losing pertactin in response to vaccine immunity. Screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 California pertussis outbreak, U.S. isolates from routine surveillance between 2010-2012, and isolates from the 2012 Washington pertussis outbreak) by conventional PCR and later by Western blotting andprnsequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481in theprngene (prnIS481positive). The firstprnIS481-positive isolate was found in 1994, and the nextprnIS481-positive isolates were not detected until 2010. The prevalence of pertactin-deficient isolates increased substantially to more than 50% of collected isolates in 2012. Sequence analysis of pertactin-deficient isolates revealed various types of mutations in theprngene, including two deletions, single nucleotide substitutions resulting in a stop codon, an inversion in the promoter, and a single nucleotide insertion resulting in a frameshift mutation. All but one mutation type were found inprn2 alleles. CDC 013 was a predominant pulsed-field gel electrophoresis (PFGE) profile in the pertactin-positive isolates (203/994) but was found in only 5% (16/306) of the pertactin-deficient isolates. Interestingly, PFGE profiles CDC 002 and CDC 237 represented 55% (167/306) of the identified pertactin-deficient isolates. These results indicate that there has been a recent dramatic increase in pertactin-deficientB. pertussisisolates throughout the United States.