Coxsackievirus B4: an underestimated pathogen associated with a hand, foot, and mouth disease outbreak

Xiao, Jingwei; Zhang, Yong; Sun, Dianjianyi; Lu, Huanhuan; Han, Zhaoxia; Song, Yang; Yan, Dongmei; Zhu, Shuangli; Pei, Yaowen; Xu, Wenbo; Wang, Xianjun

doi:10.1007/s00705-021-05128-5

Cited by 10 publications

(18 citation statements)

References 54 publications

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“…This study found that EV-Bs accounted for 37.70% in the single EV infection HFMD cases, consisting of CV-B1 (21.47%) and CV-A9 (10.99%). In the HFMD outbreaks of Shandong, China in 2009, 17.4% were CV-B strains, 11.8% were CV-B4 and in 2011 [28], CV-B5, CV-A16 and EV-A71 were the three main serotypes [29]. In Korea from 2012 to 2019, a total of 45 EV types were detected from 4399 samples with EV-associated symptoms, with EV-A71 the most detected (15.8%), E-30 (10.0%), CV-B5 (7.8%), CV-A6 (7.6%) and CV-A10 (7.4%).…”

Section: Virusmentioning

confidence: 99%

Co-infection and enterovirus B: post EV-A71 mass vaccination scenario in China

Guo

Cong

et al. 2022

BMC Infect Dis

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Background Hand, foot, and mouth disease (HFMD) is a common child infectious disease caused by more than 20 enterovirus (EV) serotypes. In recent years, enterovirus A71 (EV-A71) has been replaced by Coxsackievirus A6 (CV-A6) to become the predominant serotype. Multiple EV serotypes co-circulate in HFMD epidemics, and this study aimed to investigate the etiological epidemic characteristics of an HFMD outbreak in Kunming, China in 2019. Methods The clinical samples of 459 EV-associated HFMD patients in 2019 were used to amplify the VP1 gene region by the three sets of primers and identify serotypes using the molecular biology method. Phylogenetic analyses were performed based on the VP1 gene. Results Three hundred and forty-eight cases out of 459 HFMD patients were confirmed as EV infection. Of these 191 (41.61%) were single EV infections and 34.20% had co-infections. The EVs were assigned to 18 EV serotypes, of which CV-A6 was predominant (11.33%), followed by CV-B1 (8.93%), CV-A4 (5.23%), CV-A9 (4.58%), CV-A 16 (3.49%) and CV-A10 and CVA5 both 1.96%. Co-infection of CV-A6 with other EVs was present in 15.25% of these cases, followed by co-infection with CV-A16 and other EVs. The VP1 sequences used in the phylogenetic analyses showed that the CV-A6, CV-B1 and CV-A4 sequences belonged to the sub-genogroup D3 and genogroups F and E, respectively. Conclusion Co-circulation and co-infection of multiple serotypes were the etiological characteristic of the HFMD epidemic in Kunming China in 2019 with CV-A-6, CV-B1 and CV-A4 as the predominant serotypes. This is the first report of CV-B1 as a predominant serotype in China and may provide valuable information for the diagnosis, prevention and control of HFMD.

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Section: Virusmentioning

confidence: 99%

Co-infection and enterovirus B: post EV-A71 mass vaccination scenario in China

Guo

Cong

et al. 2022

BMC Infect Dis

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“…The CV‐B4 genotypes A to E were identified 11 . Sixty‐five partial VP1 sequences were stochastically selected to give 33 CV‐B4 isolates from this study and 32 strains in GenBank and used to construct a phylogenetic tree.…”

Section: Resultsmentioning

confidence: 99%

Coxsackievirus B: The important agent of hand, foot, and mouth disease

Liu

Zhang

Guo

et al. 2023

Journal of Medical Virology

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Hand, foot, and mouth disease (HFMD) is a common pediatric infectious illness caused by enteroviruses (EVs). EV-A serotypes are the main pathogens associated with HFMD. In this study, 213 stool samples from 213 children with severe HFMD in Yunnan, China in 2013, 2015, and 2016 were further analyzed retrospectively for EV-B infection. A total of 70.0% of the specimens tested positive for EV.20 EV serotypes were detected. The predominant serotype was enterovirus A71 (EV-A71, 27.7%), followed by coxsackievirus B4 (CV-B4, 16.4%), CV-A16 (9.9%), CV-B5 (6.6%), and Echovirus 9 (E-9,4.7%). EV-A and EV-B accounted for 45.1% and 41.3%, respectively. Among the positive specimens, 28.6% were CV-Bs. Co-infection was present in 19.3% of these cases. In the study, CV-B5 and the majority of CV-B4 isolates belonged to genotypes VI and C3, respectively. This result indicates that EV-B, especially CV-Bs, might be the important agents associated with HFMD and this knowledge will contribute to the prevention and treatment of the disease.

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“…The topology of the phylogenetic tree was constructed based on VP1 and 3Dpol, which differed significantly, and such recombination events occurred more frequently than in CVA16 [ 44 ]. The most frequent recombination occurred in the currently predominant D and E genotypes [ 12 ]. Genotype D contained five sequences distributed in Cameroon, Australia, the United States, Romania, and France.…”

Section: Discussionmentioning

confidence: 99%

“…In May 2011, an HFMD outbreak was reported in Shandong Province, China, caused by CVB4 [ 12 ]. Subsequently, we sequenced and analyzed surveillance specimens from healthy children in Shandong Province in 2010 to understand the hidden circulation and genetic diversity of CVB4 in the population.…”

Section: Introductionmentioning

confidence: 99%

Genomic Epidemiology and Transmission Dynamics of Global Coxsackievirus B4

Xiao

Song

et al. 2023

Viruses

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The aim of this study was to determine the global genetic diversity and transmission dynamics of coxsackievirus B4 (CVB4) and to propose future directions for disease surveillance. Next-generation sequencing was performed to obtain the complete genome sequence of CVB4, and the genetic diversity and transmission dynamics of CVB4 worldwide were analyzed using bioinformatics methods such as phylogenetic analysis, evolutionary dynamics, and phylogeographic analysis. Forty complete genomes of CVB4 were identified from asymptomatic infected individuals and hand, foot, and mouth disease (HFMD) patients. Frequent recombination between CVB4 and EV-B multiple serotypes in the 3Dpol region was found and formed 12 recombinant patterns (A-L). Among these, the CVB4 isolated from asymptomatic infected persons and HFMD patients belonged to lineages H and I, respectively. Transmission dynamics analysis based on the VP1 region revealed that CVB4 epidemics in countries outside China were dominated by the D genotype, whereas the E genotype was dominant in China, and both genotypes evolved at a rate of > 6.50 × 10−3 substitutions/site/year. CVB4 spreads through the population unseen, with the risk of disease outbreaks persisting as susceptible individuals accumulate. Our findings add to publicly available CVB4 genomic sequence data and deepen our understanding of CVB4 molecular epidemiology.

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Coxsackievirus B4: an underestimated pathogen associated with a hand, foot, and mouth disease outbreak

Cited by 10 publications

References 54 publications

Co-infection and enterovirus B: post EV-A71 mass vaccination scenario in China

Co-infection and enterovirus B: post EV-A71 mass vaccination scenario in China

Coxsackievirus B: The important agent of hand, foot, and mouth disease

Genomic Epidemiology and Transmission Dynamics of Global Coxsackievirus B4

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