Article

Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6

Emerging Infectious Diseases (Impact Factor: 7.33). 10/2012; 18(10):1702-4. DOI: 10.3201/eid1810.120813
Source: PubMed

ABSTRACT TO THE EDITOR: Coxsackievirus A6 (CVA6) is a human enterovirus associated with herpangina in infants. In the winter of 2012, we evaluated a cluster of 8 patients, 4 months-3 years of age, who were brought for treatment at Boston Children's Hospital (Boston, MA, USA) with a variant of hand, foot, and mouth disease (HFMD) that has now been linked to CVA6 (Table). During this same period, the Boston Public Health Commission's syndromic surveillance system detected a 3.3-fold increase in emergency department discharge diagnoses of HFMD. In the United States, HFMD typically occurs in the summer and early autumn and is characterized by a febrile enanthem of oral ulcers and macular or vesicular lesions on the palms and soles; the etiologic agents are most often CVA16 and enterovirus 71.

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Available from: Ilan Youngster, Jun 30, 2015
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    ABSTRACT: BACKGROUND: Hand, foot and mouth disease (HFMD) is caused by members of the family Picornaviridae in the genus Enterovirus. It has been reported that coxsackievirus A6 (CVA6) infections are emerging as a new and major cause of epidemic HFMD. Sporadic HFMD cases positive for CVA6 were detected in the mainland of China in recent years. To strengthen the surveillance of CVA6 infections and outbreak control, the clinical diagnosis is urgently needed to distinguish the CVA6 infection disease from other infections. METHODS: In order to develop a sensitive quantitative real-time RT-PCR assay for rapid detection of CVA6 RNA, primers and probe were designed to target the VP1 gene segment of CVA6. The conservation of the target segment was firstly analyzed by bioinformatic technology. The specificity of the real-time RT-PCR was further confirmed by detecting other related viruses and standard curves were established for the sensitivity evaluation. The pharyngeal swab samples from the EV71 and CVA16 unrelated HFMD patients were applied for CVA6 detection through the established method. RESULTS: Based on the primer--probe set to detect the target VP1 gene segment of CVA6, the quantitative real-time RT-PCR assay could discriminate CVA6 infection from other resemble viral diseases with a potential detection limit of 10 viral copies/ml. The specificity of the assay was determined by sequence alignment and experimentally tested on various related viruses. The standard curve showed that the amplification efficiency of templates with different concentrations of templates was almost the same (R2 >0.99). Evaluation of the established method with pharyngeal swabs samples showed good accordance with the results from serology diagnosis. CONCLUSION: This study is the first report developing a VP1 gene-based quantitative real-time RT-PCR for rapid, stable and specific detection of CVA6 virus. The real-time RT-PCR established in this study can be used as a reliable method for early diagnosis of CVA6 infection.
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    ABSTRACT: 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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