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Pertussis outbreaks have occurred in several industrialised countries using acellular pertussis vaccines (ACVs) since the 1990s. High prevalence of pertactin (PRN)-deficient isolates has been found in these countries.


To evaluate in Europe: (i) whether proportions of PRN-deficient strains increased in consecutive collections of clinical isolates; (ii) if the frequency of PRN-deficient strains in countries correlated with the time since ACV introduction; (iii) the presence of pertussis toxin (PT)-, filamentous haemagglutinin (FHA)- or fimbriae (Fim)-deficient isolates.


clinical isolates were obtained from different European countries during four periods (EUpert I–IV studies): 1998 to 2001 (n = 102), 2004 to 2005 (n = 154), 2007 to 2009 (n = 140) and 2012 to 2015 (n = 265). The isolates’ selection criteria remained unchanged in all periods. PRN, PT, FHA and Fim2 and Fim3 expression were assessed by ELISA.


In each period 1.0% (1/102), 1.9% (3/154), 6.4% (9/140) and 24.9% (66/265) of isolates were PRN-deficient. In EUpert IV, PRN-deficient isolates occurred in all countries sampled and in six countries their frequency was higher than in EUpert III (for Sweden and the United Kingdom, p < 0.0001 and p = 0.0155, respectively). Sweden and Italy which used ACVs since the mid 1990s had the highest frequencies (69%; 20/29 and 55%; 11/20, respectively) while Finland, where primary immunisations with ACV containing PRN dated from 2009 had the lowest (3.6%). Throughout the study, no PT- or FHA-deficient isolate and one Fim2/3-deficient was detected.


Results suggest that the longer the period since the introduction of ACVs containing PRN, the higher the frequency of circulating PRN-deficient isolates.


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  1. Campbell P, McIntyre P, Quinn H, Hueston L, Gilbert GL, McVernon J. Increased population prevalence of low pertussis toxin antibody levels in young children preceding a record pertussis epidemic in Australia. PLoS One. 2012;7(4):e35874.  https://doi.org/10.1371/journal.pone.0035874  PMID: 22558249 
  2. Amirthalingam G, Gupta S, Campbell H. Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review. Euro Surveill. 2013;18(38):20587.  https://doi.org/10.2807/1560-7917.ES2013.18.38.20587  PMID: 24084340 
  3. Winter K, Glaser C, Watt J, Harriman KCenters for Disease Control and Prevention (CDC). Pertussis epidemic--California, 2014. MMWR Morb Mortal Wkly Rep. 2014;63(48):1129-32. PMID: 25474033 
  4. van der Maas NA, Mooi FR, de Greeff SC, Berbers GA, Spaendonck MA, de Melker HE. Pertussis in the Netherlands, is the current vaccination strategy sufficient to reduce disease burden in young infants? Vaccine. 2013;31(41):4541-7.  https://doi.org/10.1016/j.vaccine.2013.07.060  PMID: 23933365 
  5. Kilgore PE, Salim AM, Zervos MJ, Schmitt HJ. Pertussis: Microbiology, Disease, Treatment, and Prevention. Clin Microbiol Rev. 2016;29(3):449-86.  https://doi.org/10.1128/CMR.00083-15  PMID: 27029594 
  6. Weigand MR, Peng Y, Loparev V, Batra D, Bowden KE, Burroughs M, et al. The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement. J Bacteriol. 2017;199(8):e00806-16.  https://doi.org/10.1128/JB.00806-16  PMID: 28167525 
  7. Barkoff AM, Mertsola J, Guillot S, Guiso N, Berbers G, He Q. Appearance of Bordetella pertussis strains not expressing the vaccine antigen pertactin in Finland. Clin Vaccine Immunol. 2012;19(10):1703-4.  https://doi.org/10.1128/CVI.00367-12  PMID: 22914363 
  8. Martin SW, Pawloski L, Williams M, Weening K, DeBolt C, Qin X, et al. Pertactin-negative Bordetella pertussis strains: evidence for a possible selective advantage. Clin Infect Dis. 2015;60(2):223-7.  https://doi.org/10.1093/cid/ciu788  PMID: 25301209 
  9. Bouchez V, Brun D, Cantinelli T, Dore G, Njamkepo E, Guiso N. First report and detailed characterization of B. pertussis isolates not expressing Pertussis Toxin or Pertactin. Vaccine. 2009;27(43):6034-41.  https://doi.org/10.1016/j.vaccine.2009.07.074  PMID: 19666155 
  10. Lam C, Octavia S, Ricafort L, Sintchneko V, Gilbert L, Wood N, et al. Emergence of pertactin deficient Bordetella pertussis in Australia is due to independent events. 10th International Symposium on Bordetella; 2013 Sep 8-11, Dublin, Ireland. Poster.
  11. Stefanelli P, Fazio C, Fedele G, Spensieri F, Ausiello CM, Mastrantonio P. A natural pertactin deficient strain of Bordetella pertussis shows improved entry in human monocyte-derived dendritic cells. New Microbiol. 2009;32(2):159-66. PMID: 19579693 
  12. Zeddeman A, van Gent M, Heuvelman CJ, van der Heide HG, Bart MJ, Advani A, et al. Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012. Euro Surveill. 2014;19(33):20881.  https://doi.org/10.2807/1560-7917.ES2014.19.33.20881  PMID: 25166348 
  13. Lam C, Octavia S, Ricafort L, Sintchenko V, Gilbert GL, Wood N, et al. Rapid increase in pertactin-deficient Bordetella pertussis isolates, Australia. Emerg Infect Dis. 2014;20(4):626-33.  https://doi.org/10.3201/eid2004.131478  PMID: 24655754 
  14. Williams MM, Sen K, Weigand MR, Skoff TH, Cunningham VA, Halse TA, et al. CDC Pertussis Working Group. Bordetella pertussis Strain Lacking Pertactin and Pertussis Toxin. Emerg Infect Dis. 2016;22(2):319-22.  https://doi.org/10.3201/eid2202.151332  PMID: 26812174 
  15. Bart MJ, van der Heide HG, Zeddeman A, Heuvelman K, van Gent M, Mooi FR. Complete Genome Sequences of 11 Bordetella pertussis Strains Representing the Pandemic ptxP3 Lineage. Genome Announc. 2015;3(6):e01394-15.  https://doi.org/10.1128/genomeA.01394-15  PMID: 26607899 
  16. Hegerle N, Paris AS, Brun D, Dore G, Njamkepo E, Guillot S, et al. Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin. Clin Microbiol Infect. 2012;18(9):E340-6.  https://doi.org/10.1111/j.1469-0691.2012.03925.x  PMID: 22717007 
  17. European Centre for Disease Prevention and Control (ECDC). Vaccine Schedule - Pertussis. [Accessed 4 Apr 2017] Available from: http://vaccine- schedule.ecdc.europa.eu/pages/scheduler.aspx
  18. van Gent M, Heuvelman CJ, van der Heide HG, Hallander HO, Advani A, Guiso N, et al. Analysis of Bordetella pertussis clinical isolates circulating in European countries during the period 1998-2012. Eur J Clin Microbiol Infect Dis. 2015;34(4):821-30.  https://doi.org/10.1007/s10096-014-2297-2  PMID: 25527446 
  19. Advani A, Hallander HO, Dalby T, Krogfelt KA, Guiso N, Njamkepo E, et al. Pulsed-field gel electrophoresis analysis of Bordetella pertussis isolates circulating in Europe from 1998 to 2009. J Clin Microbiol. 2013;51(2):422-8.  https://doi.org/10.1128/JCM.02036-12  PMID: 23175253 
  20. Barkoff AM, Gröndahl-Yli-Hannuksela K, He Q. Seroprevalence studies of pertussis: what have we learned from different immunized populations. Pathog Dis. 2015;73(7):ftv050.  https://doi.org/10.1093/femspd/ftv050  PMID: 26208655 
  21. Barkoff AM, Guiso N, Guillot S, Xing D, Markey K, Berbers G, et al. A rapid ELISA-based method for screening Bordetella pertussis strain production of antigens included in current acellular pertussis vaccines. J Immunol Methods. 2014;408:142-8.  https://doi.org/10.1016/j.jim.2014.06.001  PMID: 24925807 
  22. Heikkinen E, Xing DK, Olander RM, Hytönen J, Viljanen MK, Mertsola J, et al. Bordetella pertussis isolates in Finland: serotype and fimbrial expression. BMC Microbiol. 2008;8(1):162.  https://doi.org/10.1186/1471-2180-8-162  PMID: 18816412 
  23. Mooi FR, van Oirschot H, Heuvelman K, van der Heide HG, Gaastra W, Willems RJ. Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution. Infect Immun. 1998;66(2):670-5. PMID: 9453625 
  24. Parkhill J, Sebaihia M, Preston A, Murphy LD, Thomson N, Harris DE, et al. Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Nat Genet. 2003;35(1):32-40.  https://doi.org/10.1038/ng1227  PMID: 12910271 
  25. Hallander H, Advani A, Riffelmann M, von König CH, Caro V, Guiso N, et al. Bordetella pertussis strains circulating in Europe in 1999 to 2004 as determined by pulsed-field gel electrophoresis. J Clin Microbiol. 2007;45(10):3257-62.  https://doi.org/10.1128/JCM.00864-07  PMID: 17699646 
  26. Thierry-Carstensen B, Dalby T, Stevner MA, Robbins JB, Schneerson R, Trollfors B. Experience with monocomponent acellular pertussis combination vaccines for infants, children, adolescents and adults--a review of safety, immunogenicity, efficacy and effectiveness studies and 15 years of field experience. Vaccine. 2013;31(45):5178-91.  https://doi.org/10.1016/j.vaccine.2013.08.034  PMID: 23994021 
  27. Safarchi A, Octavia S, Luu LD, Tay CY, Sintchenko V, Wood N, et al. Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model. Vaccine. 2015;33(46):6277-81.  https://doi.org/10.1016/j.vaccine.2015.09.064  PMID: 26432908 
  28. Pawloski LC, Queenan AM, Cassiday PK, Lynch AS, Harrison MJ, Shang W, et al. Prevalence and molecular characterization of pertactin-deficient Bordetella pertussis in the United States. Clin Vaccine Immunol. 2014;21(2):119-25.  https://doi.org/10.1128/CVI.00717-13  PMID: 24256623 
  29. Hegerle N, Guiso N. Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines. Expert Rev Vaccines. 2014;13(9):1135-46.  https://doi.org/10.1586/14760584.2014.932254  PMID: 24953157 
  30. Otsuka N, Han HJ, Toyoizumi-Ajisaka H, Nakamura Y, Arakawa Y, Shibayama K, et al. Prevalence and genetic characterization of pertactin-deficient Bordetella pertussis in Japan. PLoS One. 2012;7(2):e31985.  https://doi.org/10.1371/journal.pone.0031985  PMID: 22348138 
  31. Hiramatsu Y, Miyaji Y, Otsuka N, Arakawa Y, Shibayama K, Kamachi K. Significant Decrease in Pertactin-Deficient Bordetella pertussis Isolates, Japan. Emerg Infect Dis. 2017;23(4):699-701.  https://doi.org/10.3201/eid2304.161575  PMID: 28322702 
  32. Miyaji Y, Otsuka N, Toyoizumi-Ajisaka H, Shibayama K, Kamachi K. Genetic analysis of Bordetella pertussis isolates from the 2008-2010 pertussis epidemic in Japan. PLoS One. 2013;8(10):e77165.  https://doi.org/10.1371/journal.pone.0077165  PMID: 24124606 
  33. Zöldi V, Sane J, Nohynek H, Virkki M, Hannila-Handelberg T, Mertsola J. Decreased incidence of pertussis in young adults after the introduction of booster vaccine in military conscripts: Epidemiological analyses of pertussis in Finland, 1995-2015. Vaccine. 2017;35(39):5249-55.  https://doi.org/10.1016/j.vaccine.2017.08.008  PMID: 28823620 

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