Department of Epidemiology and Health Statistics, Shandong University, Jinan, People's Republic of China.
PLoS One. 2012;7(12):e52073. doi: 10.1371/journal.pone.0052073. Epub 2012 Dec 18.
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.
柯萨奇病毒 A10（CV-A10）和 A6（CV-A6）已与全球日益增多的散发性手足口病（HFMD）病例和暴发事件相关。然而，我们对这些新病原体的流行病学和遗传特征的了解还远远不够。本研究旨在探讨 CV-A10 和 CV-A6 在 HFMD 中的流行情况及其在中国的遗传特征。我们在 2009 年 3 月至 2011 年 8 月期间对三个 HFMD 高发地区进行了基于医院的监测。从临床诊断为 HFMD 的儿童中采集粪便样本。采用实时 PCR 检测和 5'UTR/VP1 区测序对肠道病毒进行检测和基因分型。基于 VP1 序列进行系统发育分析和选择压力分析。采用逻辑回归模型确定主要肠道病毒血清型引起重症 HFMD 的影响。结果显示，1748 份粪便样本中 92.0%检测出肠道病毒阳性，最常见的血清型为 EV-71（944 份，54.0%）和 CV-A16（451 份，25.8%）。CV-A10 和 CV-A6 分别单独作为病原体在 82 例（4.7%）和 44 例（2.5%）病例中被检测到。感染 CV-A10 和 EV-71 与重症 HFMD 的高风险独立相关（OR=2.66，95%CI：1.40-5.06；OR=4.81，95%CI：3.07-7.53），调整年龄和性别后。系统发育分析显示，基于 VP1 序列的基因簇与明显的地理和时间起源相关。CV-A10 的 VP1 的整体 ω 值为 0.046，CV-A6 的 VP1 的整体 ω 值为 0.047，在 CV-A10 和 CV-A6 的 VP1 中均未检测到阳性选择位点，表明净化选择塑造了 CV-A10 和 CV-A6 的进化。我们的研究表明，多种肠道病毒基因型作为病毒病原体在中国引起 HFMD。近年来，CV-A10 和 CV-A6 与 EV-71 和 CV-A16 一起共同循环。CV-A10 感染也可能与重症 HFMD 独立相关。
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