Dataset Information

Circulation of Coxsackievirus A6 in hand-foot-mouth disease in Guangzhou, 2010-2012.

ABSTRACT: BACKGROUND: Hand, foot and mouth disease (HFMD) is usually caused by Enterovirus 71(EV71), and Coxsackievirus A16 (CV-A16) in Guangzhou, the biggest city of South China. However, Coxsackievirus A6 (CV-A6) were observed increased dramatically from 2010-2012. METHODS: In order to understand and to describe the epidemiologic and genetic characteristics of CV-A6, specimens of 5482 suspected HFMD cases were collected and examined by real-time fluorescence PCR. All samples positive for enteroviruses were analyzed by descriptive statistics. Phylogenetic analysis of CV-A6 based on the VP1 sequences was performed to investigate molecular and evolutionary characteristics. RESULTS: Coxsackievirus A6 increased dramatically from 9.04% in 2010 to 23.21% in 2012 and became one of the main causative agents of HFMD in Guangzhou. CV-A6 attack rates were highest in one to two year olds (33.14%). Typical clinic symptoms of CV-A6 HFMD include fever (589/720, 81.81%), maculopopular rash and vesicular exanthema around the perioral area (408/720, 56.66%), intraoral (545/720, 75.69%), the buttock (395/720, 54.86%), the trunk (244/720, 33.89%), the knee (188/720, 26.11%), and the dorsal aspects of hands (437/720, 60.69%). Phylogenetic analysis showed the CV-A6 isolates in this study belonged to Cluster A1 and were similar to those found in Shanghai in 2011 and 2012 (JX495148, KC414735), Shenzhen in 2011 (JX473394), Japan in 2011 (AB649243, AB649246), France in 2010(HE572928), Thailand in 2012(JX556564) and Israel in 2012 and 2013(.KF991010, KF991012).

SUBMITTER: Di B

PROVIDER: S-EPMC4169826 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Circulation of Coxsackievirus A6 in hand-foot-mouth disease in Guangzhou, 2010-2012.

Di Biao B Zhang Ying Y Xie Huaping H Li Xiaoquan X Chen Chun C Ding Peng P He Peng P Wang Dahu D Geng Jinmei J Luo Lei L Bai Zhijun Z Yang Zhicong Z Wang Ming M

Virology journal 20140901

<h4>Background</h4>Hand, foot and mouth disease (HFMD) is usually caused by Enterovirus 71(EV71), and Coxsackievirus A16 (CV-A16) in Guangzhou, the biggest city of South China. However, Coxsackievirus A6 (CV-A6) were observed increased dramatically from 2010-2012.<h4>Methods</h4>In order to understand and to describe the epidemiologic and genetic characteristics of CV-A6, specimens of 5482 suspected HFMD cases were collected and examined by real-time fluorescence PCR. All samples positive for en ...[more]

PMID: 25178398

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Project description: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.

Project description:BackgroundEvidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai.MethodsThis was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings.ResultsThere were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae.ConclusionsIn our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

Project description:Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

Dataset Information

Circulation of Coxsackievirus A6 in hand-foot-mouth disease in Guangzhou, 2010-2012.

Publications

Circulation of Coxsackievirus A6 in hand-foot-mouth disease in Guangzhou, 2010-2012.

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