Sharp rise in high-virulence Bordetella pertussis with macrolides resistance in Northern China

Abstract

Objective: To elucidate the evolution of antigen genotype and antimicrobial resistance distribution of Bordetella pertussis (B. pertussis) from 2019 to 2023 in northern China.Methods: Polymerase chain reaction (PCR) amplification and sequencing were utilized to identify the seven antigen genotypes (ptxA, ptxC, ptxP, prn, fim2, fim3, tcfA). E-test and Kirby-Bauer (K-B) disc diffusion were employed to determine the minimum inhibitory concentration (MIC) and zone of inhibition for B. pertussis against antimicrobial agents. Subsequently, 50 isolates were chosen for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.Results: A total of 442 B. pertussis isolates were determined. The strains with high virulence harboring ptxP3 allele surged from 13.5% (21/155) in 2019-2021 to 93.0% (267/287) in 2022-2023. Concurrently, the erythromycin resistance B. pertussis (ERBP) in ptxP3 isolates markedly rose from 42.9% (9/21) in 2019-2021 to 100% (267/267) in 2022-2023. Compared to ptxP1 isolates, the majority of ptxP3 isolates (76.0%,219/288) exhibited the ptxA1/ptxC1/prn2/fim2-1/fim3A/tcfA-2 genotype, which differed more in alleles from the vaccine strain (ptxA2/ptxC1/ptxP1/prn1/fim2-1/fim3A/tcfA-2). Among the 442 confirmed patients, the children aged 3-14 years escalated rapidly from 13.5% in 2019 to 45.6% in 2023. The MT28 strains was responsible for 66.0% (33/50) of the tested ones, in which ERBP was prevalent at 87.9% (29/33). All the present sequenced ptxP3-ERBP strains (31/31) were clustered into the sub-lineage IVd.Conclusions: These results suggested the clonal spread of ptxP3-ERBP lineage of B. pertussis with high virulence and macrolides resistance could be an important cause of the recent pertussis resurgence in China. Furthermore, the increased cases among preschool and school-aged children underscores the importance of booster vaccination in this population.