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Circulation of Coxsackievirus A10 and A6 in Hand-Foot-Mouth Disease in China, 2009–2011
Open accessAbstract
Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5'UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40-5.06; OR = 4.81, 95% CI: 3.07-7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.
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“EV71 and CVA16 are the two major causative agents in different areas, and other coxsackieviruses of species A, such as CVA10, CVA6, CVA4, CVA12, etc, have also been demonstrated to be involved [24]–[26].”
From Molecular Epidemiology of Human Enterovirus Associated with Aseptic Meningitis in Shandong Province, China, 2006–2012 (2014) · cites this paper as [24]
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“CVA10 is also associated with serious complications with a less effect than EV71 [24].”
From Molecular Epidemiology of Human Enterovirus Associated with Aseptic Meningitis in Shandong Province, China, 2006–2012 (2014) · cites this paper as [24]
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Cites
Virology, epidemiology, pathogenesis, and control of enterovirus 71
Solomon, T., Lewthwaite, P., Perera, D., Cardosa, M. J., McMinn, P. C., & Ooi, M. H. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70194-8 · Cited by 1,301
Nix, W. A., Oberste, M. S., & Pallansch, M. A. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.00542-06 · Cited by 896
Epidemiology and Control of Hand, Foot and Mouth Disease in Singapore, 2001-2007
Ang, L. W., Koh, B., Chan, K. P., Chua, L. T., James, L., & Goh, K. T. (2009) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.v38n2p106 · Cited by 364
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Coxsackievirus A6 and Hand, Foot, and Mouth Disease, Finland
Österback, R., Vuorinen, T., Linna, M., Susi, P., Hyypiä, T., & Waris, M. E. (2009) · Emerging infectious diseases · doi:10.3201/eid1509.090438 · Cited by 343
Co-circulation of coxsackieviruses A6 and A10 in hand, foot and mouth disease outbreak in Finland
Blomqvist, S., Klemola, P., Kaijalainen, S., Paananen, A., Simonen, M.-L., Vuorinen, T., & Roivainen, M. (2010) · Journal of Clinical Virology · doi:10.1016/j.jcv.2010.02.002 · Cited by 284
Mirand, A., Henquell, C., Archimbaud, C., Ughetto, S., Antona, D., Bailly, J., & Peigue‐Lafeuille, H. (2012) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2012.03789.x · Cited by 273
Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6, Japan, 2011
Fujimoto, T., Iizuka, S., Enomoto, M., Abe, K., YAMASHITA, K., Hanaoka, N., Okabe, N., Yoshida, H., Yasui, Y., Kobayashi, M., et al. (2012) · Emerging infectious diseases · doi:10.3201/eid1802.111147 · Cited by 233
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Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6
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Research works printed but not linked: 2
- H Yang, 2010, The genetic characterization of VP1 region of coxsackie virus A10 isolated from hand, foot and mouth disease cases in Shandong Province of China, Chin J Infect Dis, 28, 385
- Y-Q Wang, 2011, Molecular characterization of hand, foot and mouth disease related non-EV71 non-CoxA16 enterovirus in Beijing, Int J Virol, 18, 75
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“Eczema Coxsackium” and Unusual Cutaneous Findings in an Enterovirus Outbreak
Mathes, E. F. D., Oza, V. S., Frieden, I. J., Cordoro, K. M., Yagi, S., Howard, R., Kristal, L., Ginocchio, C. C., Schaffer, J. V., Maguiness, S., et al. (2013) · PEDIATRICS · doi:10.1542/peds.2012-3175 · Cited by 255
Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy
Aswathyraj, S., Arunkumar, G., Alidjinou, E. K., & Hober, D. (2016) · Medical Microbiology and Immunology · doi:10.1007/s00430-016-0465-y · Cited by 229
Esposito, S., & Principi, N. (2018) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-018-3206-x · Cited by 227
Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide
Bian, L., Wang, Y., Yao, X., Mao, Q., Xu, M., & Liang, Z. (2015) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2015.1058156 · Cited by 207
Takahashi, S., Liao, Q., Boeckel, T. P. V., Xing, W., Sun, J., Hsiao, V., Metcalf, C. J. E., Chang, Z., Liu, F., Zhang, J., et al. (2016) · PLoS Medicine · doi:10.1371/journal.pmed.1001958 · Cited by 144
Metadata
- Authors
- Lu, Q.-B., Zhang, X.-A., Wo, Y., Xu, H.-M., Li, X.-J., Wang, X.-J., Ding, S.-J., Chen, X.-D., He, C., Liu, L.-J., Li, H., Yang, H., Li, T.-Y., Liu, W., & Cao, W.-C.
- Affiliations
- Shandong University (CN)
- Beijing Institute of Microbiology and Epidemiology (CN)
- Corresponding author
- Liu, Wei
- Cao, Wu-Chun
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-12-18
- Volume
- 7
- Issue
- 12
- Pages
- e52073
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3525556
- OpenAlex
- W1984450481
- Cited by
- 135
- References
- 29
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 3 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 14 · 2015: 23 · 2014: 17 · 2013: 6
- FWCI
- 10.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Fund for Distinguished Young Scholars (30725032)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- hand, foot and mouth disease, coxsackievirus A10, coxsackievirus A6, enterovirus genotypes, phylogenetic analysis, purifying selection, China, hospital surveillance, 5' untranslated region
- MeSH terms
- China, Coxsackievirus Infections, Disease Outbreaks, Enterovirus, Female, Genotype, Hand, Foot and Mouth Disease, Humans, Male, Molecular Sequence Data, Phylogeny, Serotyping, Viral Proteins, Sentinel Surveillance, History, 21st Century
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