Emergence and spread of MT28 ptxP3 allele macrolide-resistant Bordetella pertussis from 2021 to 2022 in China

Fu, Pan; Zhou, Jie; Meng, Jianhua; Liu, Zhiwei; Nijiati, Yaxier; He, Leiyan; Li, Chunling; Chen, Saige; Wang, Aimin; Yan, Gangfeng; Li, Guoping; Zhou, Lijun; Zhai, Xiaowen

doi:10.1016/j.ijid.2023.01.005

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…In the late 2010s, a novel MRBP strain carrying the ptxP3 allele emerged in mainland China [ 22 , 34 , 35 ]. ptxP3 confers the strain with an increased pertussis toxin-production ability, and the ptxP3 strain is considered to be more virulent in humans than the ptxP1 strain according to a previous study on MSBP [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-genome comparison of two same-genotype macrolide-resistant Bordetella pertussis isolates collected in Japan

Koide,

Uchitani,

Yamaguchi

et al. 2024

PLoS ONE

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The emergence of macrolide-resistant Bordetella pertussis (MRBP) is a significant problem because it reduces treatment options for pertussis and exacerbates the severity and spread of the disease. MRBP has been widely prevalent in mainland China since the 2010s and has been sporadically detected in other Asian countries. In Japan, two MRBP clinical strains were first isolated in Tokyo and Osaka between June and July 2018. The isolates BP616 in Osaka and BP625 in Tokyo harbored the same virulence-associated allelic genes (including ptxP1, ptxA1, prn1, fim3A, and fhaB3) and MT195 genotype and exhibited similar antimicrobial susceptibility profiles. However, despite their simultaneous occurrence, a distinguishable epidemiological link between these isolates could not be established. To gain further insight into the genetic relationship between these isolates in this study, we performed whole-genome analyses. Phylogenetic analysis based on genome-wide single-nucleotide polymorphisms revealed that the isolates belonged to one of the three clades of Chinese MRBP isolates, but there were 11 single-nucleotide polymorphism differences between BP616 and BP625. Genome structure analysis revealed two large inversions (202 and 523 kbp) and one small transposition (3.8 kbp) between the genomes. These findings indicate that the two Japanese MRBP isolates are closely related to Chinese MRBP isolates but are genomically distinct, suggesting that they were introduced into Japan from mainland China through different transmission routes.

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Section: Discussionmentioning

confidence: 99%

Whole-genome comparison of two same-genotype macrolide-resistant Bordetella pertussis isolates collected in Japan

Koide,

Uchitani,

Yamaguchi

et al. 2024

PLoS ONE

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“…We have carried out continuous surveillance of B. pertussis stains and pertussis in Shanghai since 2016, and obtained strains and corresponding clinical data covering the transition period pre- and post-COVID-19. We previously described the genotype dynamics of ptxP3 -MRBP based on a subset of strains by multi-locus variable-number tandem-repeat analysis (MLVA) 22,23 Compared with traditional typing methods such as MLVA, whole-genome sequencing (WGS) provides finer resolution and more comprehensive information including virulence and antimicrobial genes. In this study, we took advantages of WGS and sequenced culture-positive B. pertussis stains between June 2016 and March 2024.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 However, the situation in China is changing, as ptxP3-MRBP strains have been identified in multiple regions of China since 2017. [21][22][23][24] In Shanghai, we previously reported that ptxP3-MRBP had replaced ptxP1 strains and dominated infections after 2020, with a substantially increased infections in older, vaccinated children. 22,23 Similar situation was recently identified in Beijing.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22][23][24] In Shanghai, we previously reported that ptxP3-MRBP had replaced ptxP1 strains and dominated infections after 2020, with a substantially increased infections in older, vaccinated children. 22,23 Similar situation was recently identified in Beijing. During 2021-2022, ptxP3-MRBP accounted for 78.8% patients, and the proportion of patients in children over three years old doubled than before.…”

Section: Introductionmentioning

confidence: 99%

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Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused byptxP3macrolide-resistantBordetella pertussisMT28 clone in China: a genomic epidemiology study

Fu,

Yan,

et al. 2024

Preprint

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Background: The upsurge of pertussis post-COVID-19 and expansion of macrolide-resistant Bordetella pertussis (MRBP) pose significant public health challenges worldwide. China has experienced notable pertussis upsurge post-COVID-19, alongside an age shift to older children, vaccine escape and a notable rise in MRBP prevalence. We describe the genomic epidemiological investigation of these events. Method: We did a retrospective, population-based study using culture-positive B. pertussis from Children's Hospital of Fudan University (CHFU), the exclusive referral hospital for childhood notifiable infectious diseases, in Shanghai, China between June 2016 and March 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic proflie, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. Findings: Coincident with national situtation, pertussis cases upsurged post-COVID-19 in Shanghai. At CHFU, the number of confirmed cases (n=349) in the first three months of 2024 exceeded the total case of previously years (n≤177). Post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to widespread infection among older children (infant: 16%, 132/844), with vaccinated individuals surging from 31% (107/340) to 88% (664/756); MRBP prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-linage, macrolide-resistant novel clone with MLVA type 28, MR-MT28, uniquely capable of causing substantial infections among older children and vaccinated individuals, temporally strongly associated with the pertussis upsurge and epidemiological transition. MR-MT28 exhibited increased expression of antigen genes including pertussis toxin genes, along with high incidence of abnormal C-reactive protein, but associated with siginicantly milder clinical symtoms (e.g. wheezing, facial blushing, p<0.01), higher proportion of normal chest computed tomography (p<0.05) and lower hospitalization rate (p<0.01). Phylogenomic clustering analysis revealed a higher proportion of MR-MT28 strains grouping into clusters representing putative transmission. We reconstructed the evolutionary history of MR-MT28, and showed that it most likely originated in China around 2016 (95% highest probability density: 2013-2017) after acquring several mutations, including a novel antigen allele prn150 and 23S rRNA A2047G mutation. Approximately one quarter (26%, 50/195) of MR-MT28 has evolved into predicted PRN-deficient strains. MR-MT28 has been identified in four regions (Anhui, Shanghai, Beijing and Guangdong) of China and continuously detected in Shanghai and Beijing, suggesting domestic spread and colonization. Interpretation: We identified a ptxP3-linage, macrolide-resistant novel clone, MR-MT28, and provide evidence that pathogen evolution is more likely the primary factor driving pertussis upsurge, age shift and vaccine escape. MR-MT28 potentially poses a high global spread risk and warrants global surveillance. Macrolides may no longer be suitable as first-line drugs for pertussis treatment in China.

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“…pertussis may also be under selective pressure from macrolide antibiotics used for treatment of pertussis such as erythromycin or azithromycin [12]. Macrolide resistant strains of B. pertussis have recently emerged from the genetic background of ptxP1 strains in China [13][14][15] and very recently from ptxP3 background [16]. Although only a small number of macrolide resistant B. pertussis isolates have been reported in other countries, monitoring of the international spread of macrolide-resistant strains is of paramount importance [15].…”

Section: Introductionmentioning

confidence: 99%

Genomic epidemiology and multilevel genome typing ofBordetella pertussis

Payne

et al. 2023

Preprint

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Bordetella pertussisis responsible for the respiratory infectious disease pertussis (or whooping cough), which causes one of the most severe diseases in infants, although it can be prevented by whole cell and acellular vaccines. The recent resurgence of pertussis is partially due to pathogen adaptation to vaccines as well as resistance to antimicrobials. Surveillance of current circulating and emerging strains is therefore vital to understand the risks they pose to public health. Although there is increased genomics based typing, a genomic nomenclature for this pathogen has not been well established. Here, we implemented the Multilevel Genome Typing (MGT) system forB. pertussiswith five levels of resolution, which provide targeted typing of relevant lineages as well as discrimination of closely related strains at the finest scale. The low resolution levels can describe the distribution of alleles of major vaccine antigen genes such asptxP,fim3,fhaBandprnas well as temporal and spatial trends within theB. pertussisglobal population. Mid-resolution levels enables typing of antibiotic resistant lineages and Prn deficient lineages within theptxP3clade. High resolution levels can capture small-scale epidemiology such as local transmission events and has comparable resolution to existing genomic methods of strain relatedness assessment. The scheme offers stable MGT type assignments aiding harmonisation of typing and communication between laboratories. The scheme is available at www.mgtdb.unsw.edu.au/pertussis/, is regularly updated from global data repositories and accepts public data submissions. The MGT scheme provides a comprehensive, robust, and scalable system for global surveillance ofB. pertussis.

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Emergence and spread of MT28 ptxP3 allele macrolide-resistant Bordetella pertussis from 2021 to 2022 in China

Cited by 11 publications

References 29 publications

Whole-genome comparison of two same-genotype macrolide-resistant Bordetella pertussis isolates collected in Japan

Whole-genome comparison of two same-genotype macrolide-resistant Bordetella pertussis isolates collected in Japan

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused byptxP3macrolide-resistantBordetella pertussisMT28 clone in China: a genomic epidemiology study

Genomic epidemiology and multilevel genome typing ofBordetella pertussis

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