Pawloski L C, Queenan A M, Cassiday P K, Lynch A S, Harrison M J, Shang W, Williams M M, Bowden K E, Burgos-Rivera B, Qin X, Messonnier N, Tondella M L
Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Clin Vaccine Immunol. 2014 Feb;21(2):119-25. doi: 10.1128/CVI.00717-13. Epub 2013 Nov 20.
Pertussis 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 pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is 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 and prn sequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481 in the prn gene (prnIS481 positive). The first prnIS481-positive isolate was found in 1994, and the next prnIS481-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 the prn gene, 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 in prn2 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-deficient B. pertussis isolates throughout the United States.
百日咳在美国出现了显著的卷土重来之势，报告病例数回升至创纪录水平，上一次出现这种情况还是在20世纪50年代。已观察到缺乏百日咳黏附素（无细胞百日咳疫苗的一种关键抗原成分）的百日咳博德特氏菌分离株，这表明百日咳博德特氏菌正因疫苗免疫而失去百日咳黏附素。通过常规PCR以及随后的蛋白质免疫印迹和prn测序分析，对来自暴发和监测研究的1300株分离株（1935年至2009年收集的历史分离株、2010年加利福尼亚百日咳暴发的分离株、2010 - 2012年美国常规监测的分离株以及2012年华盛顿百日咳暴发的分离株）进行筛查，最终鉴定出306株百日咳黏附素缺陷型分离株。在这些百日咳黏附素缺陷型菌株中，有276株被鉴定为prn基因中有一个IS481（prnIS481阳性）。首个prnIS481阳性分离株于1994年被发现，而下一个prnIS481阳性分离株直到2010年才被检测到。百日咳黏附素缺陷型分离株的流行率在2012年大幅上升至所收集分离株的50%以上。百日咳黏附素缺陷型分离株的序列分析揭示了prn基因中的各种突变类型，包括两个缺失、导致终止密码子的单核苷酸替换、启动子中的倒位以及导致移码突变的单核苷酸插入。除一种突变类型外，所有突变类型均在prn2等位基因中被发现。CDC 013是百日咳黏附素阳性分离株（203/994）中占主导的脉冲场凝胶电泳（PFGE）图谱，但仅在5%（16/306）的百日咳黏附素缺陷型分离株中被发现。有趣的是，PFGE图谱CDC 002和CDC 237占已鉴定的百日咳黏附素缺陷型分离株的55%（167/306）。这些结果表明，近期在美国，百日咳黏附素缺陷型百日咳博德特氏菌分离株急剧增加。
