Evolution of Bordetella pertussis Under the Influence of Vaccination and its Molecular-Genetic Properties
DOI:
https://doi.org/10.15407/Keywords:
B. pertussis, molecular-genetic properties, antigens, acellular vaccine, whole-cell vaccine, vaccine prophylaxis, re-emergent infectionAbstract
In recent decades, there has been a global trend of increasing incidence of pertussis and changes in its epidemiological characteristics toward re-emergent properties. This trend has become especially pronounced in the post-COVID-19 pandemic period in the European Region (87,558 cases in 2023), including Ukraine (7,545 cases in 2024). One of the reasons for this situation is considered the introduction of the acellular pertussis vaccine (aP) in some countries, due to its shorter duration of post-vaccination immunity and the loss of certain antigens by circulating Bordetella pertussis strains under the pressure of specific post-vaccination antibodies. However, in Ukraine, the whole-cell pertussis vaccine (wP) is currently used for routine immunization. The aim of this work is to summarize scientific information on the biological properties of B. pertussis circulating in different regions and formed under the influence of aP and wP vaccines. The virulence factors of B. pertussis are analyzed, including those with antigenic properties used in aP vaccines. An analysis of existing scientific data on the molecular-genetic and antigenic characteristics of B. pertussis variants using aP and wP vaccines was carried out. It is concluded that long-term vaccination against pertussis, on the one hand, leads to a sharp decrease in the incidence of this infection, and on the other hand, contributes to the further evolution of B. pertussis, promoting changes or loss of certain antigens and further genetic distance from vaccine strains of both aP and wP types. This allowed the pathogen to evade specific immunity at both the individual and population levels and caused an increase in incidence. The aP vaccines accelerate such evolutionary changes to a greater extent. At the same time, the genetic diversity of variants in territories using aP vaccines is greater compared to those using wP (which may even be limited to clonal variants). A trend is observed toward increasing similarity of B. pertussis strains circulating worldwide. This may be due to the same direction of evolutionary changes and intensive population migration processes, which turn the globe into a single epidemic zone. One of the negative trends is the emergence of macrolide-resistant B. pertussis variants, which are widespread in China and still sporadically observed in Europe. All of the above contribute to the loss of vaccine controllability of pertussis and the emergence of a tendency to transition at this stage to re-emergent infections. This requires the widespread implementation of molecular-genetic monitoring in the epidemiological surveillance of pertussis and the improvement of vaccination strategy and tactics based on its results.
Downloads
References
Bailon, H., León-Janampa, N., Padilla, C., & Hozbor, D. (2016). Increase in pertussis cases along with high prevalence of two emerging genotypes of Bordetella pertussis in Perú, 2012. BMC infectious diseases, 16, 422. https://doi.org/10.1186/s12879-016-1700-2
Barkoff, A. M., Kastrin, T., Seme, K., Vitek, M. G., Mertsola, J., & He, Q. (2024). Prevalence of Pertactin-Deficient Bordetella pertussis Isolates, Slovenia. Emerging infectious diseases, 30(11), 2429-2432. https://doi.org/10.3201/eid3011.231393
Bart, M. J., van der Heide, H. G., Zeddeman, A., Heuvelman, K., van Gent, M., & Mooi, F. R. (2015). Complete Genome Sequences of 11 Bordetella pertussis Strains Representing the Pandemic ptxP3 Lineage. Genome announcements, 3(6), e01394-15. https://doi.org/10.1128/genomeA.01394-15
Belcher, T., Dubois, V., Rivera-Millot, A., Locht, C., & Jacob-Dubuisson, F. (2021). Pathogenicity and virulence of Bordetella pertussis and its adaptation to its strictly human host. Virulence, 12(1), 2608-2632. https://doi.org/10.1080/21505594.2021.1980987
Brandal, L. T., Vestrheim, D. F., Bruvik, T., Roness, R. B., Bjørnstad, M. L., Greve-Isdahl, M., Steens, A., & Brynildsrud, O. B. (2022). Evolution of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology, 41(6), 913-924. https://doi.org/10.1007/s10096-022-04453-0
Burnham-Marusich, A. R., Olsen, R. K., Scarbrough, J., Kvam, A., Yang, W., Zimmerman, L., Dunn, J. J., Merkel, T., & Kozel, T. R. (2020). Tracheal colonization factor A (TcfA) is a biomarker for rapid and specific detection of Bordetella pertussis. Scientific reports, 10(1), 15002. https://doi.org/10.1038/s41598-020-72092-6
Carriquiriborde, F., Regidor, V., Aispuro, P. M., Magali, G., Bartel, E., Bottero, D., & Hozbor, D. (2019). Rare Detection of Bordetella pertussis Pertactin-Deficient Strains in Argentina. Emerging infectious diseases, 25(11), 2048-2054. https://doi.org/10.3201/eid2511.190329
de Paula, V. G., de Sousa, R. S., da Silva, R. C. M. R., Alves, E. G., Caetano, A. R., Ianella, P., & de Campos, T. A. (2024). fim3-24/ptxP-3 genotype is associated to whooping cough outbreak in Brazilian Midwest: The selection of Bordetella pertussis strains driven by vaccine immunization. Infection, genetics and evolution. Journal of molecular epidemiology and evolutionary genetics in infectious diseases, 121, 105599. https://doi.org/10.1016/j.meegid.2024.105599
Du, Q. Q., Hu, Y. H., Meng, Q. H., Yu, D., & Yao, K. H. (2024). Unique factors to consider when exploring the surge in reported pertussis cases in China. The Lancet. Microbe, 5(12), 100959. https://doi.org/10.1016/j.lanmic.2024.100959
ECDC. Vaccine Scheduler. Pertussis: Recommended vaccinations. URL: https://vaccine-schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=3&SelectedCountryIdByDisease=166.
Fu, P., Zhou, J., Yang, C., Nijiati, Y., Zhou, L., Yan, G., Lu, G., Zhai, X., & Wang, C. (2023). Molecular Evolution and Increasing Macrolide Resistance of Bordetella pertussis, Shanghai, China, 2016-2022. Emerging infectious diseases, 30(1), 29-38. https://doi.org/10.3201/eid3001.221588
Gutiérrez-Ferman, J. L., Villarreal-Treviño, L., Ramírez-Aranda, J. M., Camacho-Ortiz, A., Ballesteros-Elizondo, M. R., Moreno-Juárez, M. R., Mendoza-Olazarán, S., de la O Cavazos, M. E., Villarreal-Pérez, J. Z., Gómez-Govea, M. A., & Garza-González, E. (2018). Emerging of ptxP3 lineage in Bordetella pertussis strains circulating in a population in northeastern Mexico. Epidemiology and infection, 146(16), 2096-2101. https://doi.org/10.1017/S0950268818002303
Hallander, H. O., Advani, A., Donnelly, D., Gustafsson, L., & Carlsson, R. M. (2005). Shifts of Bordetella pertussis variants in Sweden from 1970 to 2003, during three periods marked by different vaccination programs. Journal of clinical microbiology, 43(6), 2856-2865. https://doi.org/10.1128/JCM.43.6.2856-2865.2005
Heininger, U., Martini, H., Eeuwijk, J., Prokić, I., Guignard, A. P., Turriani, E., Duchenne, M., & Berlaimont, V. (2024). Pertactin deficiency of Bordetella pertussis: Insights into epidemiology, and perspectives on surveillance and public health impact. Human vaccines & immunotherapeutics, 20(1), 2435134. https://doi.org/10.1080/21645515.2024.2435134
Hu, Y., Zhou, L., Du, Q., Shi, W., Meng, Q., Yuan, L., Hu, H., Ma, L., Li, D., & Yao, K. (2025). Sharp rise in high-virulence Bordetella pertussis with macrolides resistance in Northern China. Emerging microbes & infections, 14(1), 2475841. https://doi.org/10.1080/22221751.2025.2475841
Kilgore, P. E., Salim, A. M., Zervos, M. J., & Schmitt, H. J. (2016). Pertussis: Microbiology, Disease, Treatment, and Prevention. Clinical microbiology reviews, 29(3), 449-486. https://doi.org/10.1128/CMR.00083-15
Li, Z., Xiao, F., Hou, Y., Jia, B., Zhuang, J., Cao, Y., Ma, J., Zhao, J., Xu, Z., Jia, Z., Liu, F., Pang, L., & Liu, J. (2025). Genomic epidemiology and evolution of Bordetella pertussis under the vaccination pressure of acellular vaccines in Beijing, China, 2020-2023. Emerging microbes & infections, 14(1), 2447611. https://doi.org/10.1080/22221751.2024.2447611
Ma, L., Caulfield, A., Dewan, K. K., & Harvill, E. T. (2021). Pertactin-Deficient Bordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis. Emerging infectious diseases, 27(6), 1561-1566. https://doi.org/10.3201/eid2706.203850
Marimón, J. M., Montes, M., Vizuete, N., Alvarez Guerrico, L., Aginagalde, A. H., Mir-Cros, A., González-López, J. J., & Vicente, D. (2024). Pertussis Outbreak During 2023 in Gipuzkoa, North Spain. Vaccines, 12(10), 1192. https://doi.org/10.3390/vaccines12101192
Martin, S. W., Pawloski, L., Williams, M., Weening, K., DeBolt, C., Qin, X., Reynolds, L., Kenyon, C., Giambrone, G., Kudish, K., Miller, L., Selvage, D., Lee, A., Skoff, T. H., Kamiya, H., Cassiday, P. K., Tondella, M. L., & Clark, T. A. (2015). Pertactin-negative Bordetella pertussis strains: evidence for a possible selective advantage. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 60(2), 223-227. https://doi.org/10.1093/cid/ciu788
Miettinen, M., Barkoff, A. M., Nyqvist, A., Savolainen-Kopra, C., Antikainen, J., Mertsola, J., Ivaska, L., & He, Q. (2024). Macrolide-resistant Bordetella pertussis strain identified during an ongoing epidemic, Finland, January to October 2024. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 29(49), 2400765. https://doi.org/10.2807/1560-7917.ES.2024.29.49.2400765
Moosa, F., du Plessis, M., Weigand, M. R., Peng, Y., Mogale, D., de Gouveia, L., Nunes, M. C., Madhi, S. A., Zar, H. J., Reubenson, G., Ismail, A., Tondella, M. L., Cohen, C., Walaza, S., von Gottberg, A., & Wolter, N. (2023). Genomic characterization of Bordetella pertussis in South Africa, 2015-2019. Microbial genomics, 9(12), 001162. https://doi.org/10.1099/mgen.0.001162
Mosiej, E., Zawadka, M., Krysztopa-Grzybowska, K., Polak, M., Augustynowicz, E., Piekarska, K., & Lutyńska, A. (2015). Sequence variation in virulence-related genes of Bordetella pertussis isolates from Poland in the period 1959-2013. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology, 34(1), 147-152. https://doi.org/10.1007/s10096-014-2216-6
Niinikoski, V., Barkoff, A. M., Mertsola, J., & He, Q. (2024). Bordetella pertussis isolates in Finland after acellular vaccination: serotype change and biofilm formation. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 30(5), 683.e1-683.e3. https://doi.org/10.1016/j.cmi.2024.01.021
Polak, M., & Lutyńska, A. (2017). The importance of Bordetella pertussis strains which do not produce virulence factors in the epidemiology of pertussis. Postepy higieny i medycyny doswiadczalnej (Online), 71(0), 367-379. https://doi.org/10.5604/01.3001.0010.3821
Rodrigues, C., Bouchez, V., Soares, A., Trombert-Paolantoni, S., Aït El Belghiti, F., Cohen, J. F., Armatys, N., Landier, A., Blanchot, T., Hervo, M., REMICOQ study group, Toubiana, J., & Brisse, S. (2024). Resurgence of Bordetella pertussis, including one macrolide-resistant isolate, France, 2024. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 29(31), 2400459. https://doi.org/10.2807/1560-7917.ES.2024.29.31.2400459
Rodríguez-Medina, N., Gutiérrez-Ferman, J., Villarreal-Treviño, L., Garza-Ramos, U., Maldonado-Garza, H. J., Bárcenas-Walls, J., Ortiz-López, R., de-la-O-Cavazos, M., Treviño-Garza, C., Ballesteros-Elizondo, M. R., & Garza-González, E. (2023). Genome Sequences of Bordetella pertussis Isolates from Outbreaks in Northeastern Mexico. Microbiology resource announcements, 12(5), e0009623. https://doi.org/10.1128/mra.00096-23
Safarchi, A., Octavia, S., Nikbin, V. S., Lotfi, M. N., Zahraei, S. M., Tay, C. Y., Lamichhane, B., Shahcheraghi, F., & Lan, R. (2019). Genomic epidemiology of Iranian Bordetella pertussis: 50 years after the implementation of whole cell vaccine. Emerging microbes & infections, 8(1), 1416-1427. https://doi.org/10.1080/22221751.2019.1665479
Safarchi, A., Saedi, S., Octavia, S., Sedaghatpour, M., Bolourchi, N., Tay, C. Y., Lamichhane, B., Shahcheraghi, F., & Lan, R. (2021). Evolutionary genomics of recent clinical Bordetella pertussis isolates from Iran: wide circulation of multiple ptxP3 lineages and report of the first ptxP3 filamentous hemagglutinin-negative B. pertussis. Infection, genetics and evolution: Journal of molecular epidemiology and evolutionary genetics in infectious diseases, 93, 104970. https://doi.org/10.1016/j.meegid.2021.104970
Sharma, N. C., Anandan, S., Devanga Ragupathi, N. K., Muthuirulandi Sethuvel, D. P., Vasudevan, K., Kumar, D., Gupta, S. K., Sangal, L., & Veeraraghavan, B. (2021). Genetic Diversity of Clinical Bordetella Pertussis ST2 Strains in comparison with Vaccine Reference Strains of India. Journal of genomics, 9, 38-42. https://doi.org/10.7150/jgen.58823
Teruya, S., Hiramatsu, Y., Nakamura, K., Fukui-Miyazaki, A., Tsukamoto, K., Shinoda, N., Motooka, D., Nakamura, S., Ishigaki, K., Shinzawa, N., Nishida, T., Sugihara, F., Maeda, Y., & Horiguchi, Y. (2020). Bordetella Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses CaV3.1 as the Cell Surface Receptor. mBio, 11(2), e03146-19. https://doi.org/10.1128/mBio.03146-19
Tsang, R. S. W., Shuel, M., Cronin, K., Deng, S., Whyte, K., Marchand-Austin, A., Ma, J., Bolotin, S., Crowcroft, N., Schwartz, K., Van Domselaar, G., Graham, M., & Jamieson, F. B. (2019). The evolving nature of Bordetella pertussis in Ontario, Canada, 2009-2017: strains with shifting genotypes and pertactin deficiency. Canadian journal of microbiology, 65(11), 823-830. https://doi.org/10.1139/cjm-2019-0128
Tsang, R. S., Shuel, M., Jamieson, F. B., Drews, S., Hoang, L., Horsman, G., Lefebvre, B., Desai, S., & St-Laurent, M. (2014). Pertactin-negative Bordetella pertussis strains in Canada: characterization of a dozen isolates based on a survey of 224 samples collected in different parts of the country over the last 20 years. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases, 28, 65-69. https://doi.org/10.1016/j.ijid.2014.08.002
van Gent, M., Heuvelman, C. J., van der Heide, H. G., Hallander, H. O., Advani, A., Guiso, N., Wirsing von Kőnig, C. H., Vestrheim, D. F., Dalby, T., Fry, N. K., Pierard, D., Detemmerman, L., Zavadilova, J., Fabianova, K., Logan, C., Habington, A., Byrne, M., Lutyńska, A., Mosiej, E., Pelaz, C., … Mooi, F. R. (2015). Analysis of Bordetella pertussis clinical isolates circulating in European countries during the period 1998-2012. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology, 34(4), 821-830. https://doi.org/10.1007/s10096-014-2297-2
Vodzak, J., Queenan, A. M., Souder, E., Evangelista, A. T., & Long, S. S. (2017). Clinical Manifestations and Molecular Characterization of Pertactin-Deficient and Pertactin-Producing Bordetella pertussis in Children, Philadelphia 2007-2014. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 64(1), 60-66. https://doi.org/10.1093/cid/ciw632
Wang, L., Lei, D., & Zhang, S. (2012). Acellular pertussis vaccines in China. Vaccine, 30(50), 7174-7178. https://doi.org/10.1016/j.vaccine.2012.10.009
WHO. Pertussis reported cases and incidence. URL: https://immunizationdata.who.int/global/wiise-detail-page/pertussis-reported-cases-and-incidence?CODE=Global&YEAR=
Xu, Z., Hu, D., Luu, L. D. W., Octavia, S., Keil, A. D., Sintchenko, V., Tanaka, M. M., Mooi, F. R., Robson, J., & Lan, R. (2022). Genomic dissection of the microevolution of Australian epidemic Bordetella pertussis. Emerging microbes & infections, 11(1), 1460-1473. https://doi.org/10.1080/22221751.2022.2077129
Xu, Z., Octavia, S., Luu, L. D. W., Payne, M., Timms, V., Tay, C. Y., Keil, A. D., Sintchenko, V., Guiso, N., & Lan, R. (2019). Pertactin-Negative and Filamentous Hemagglutinin-Negative Bordetella pertussis, Australia, 2013-2017. Emerging infectious diseases, 25(6), 1196-1199. https://doi.org/10.3201/eid2506.180240
Zadorozhna, V. I. & Doan, S. I. (2004). Whooping cough: an ancient infection in new conditions (epidemiological and microbiological aspects). Whooping cough: epidemiology, clinic and prevention - current state (Ed. Selnikova O. P., Chudna L. M., Grynevych O. Y.). K, 2004, 96 p. [In Ukrainian].
Zomer, A., Otsuka, N., Hiramatsu, Y., Kamachi, K., Nishimura, N., Ozaki, T., Poolman, J., & Geurtsen, J. (2018). Bordetella pertussis population dynamics and phylogeny in Japan after adoption of acellular pertussis vaccines. Microbial genomics, 4(5), e000180. https://doi.org/10.1099/mgen.0.000180
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Mikrobiolohichnyi Zhurnal
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
