Circulation of Coxsackievirus A10 and A6 in Hand-Foot-Mouth Disease in China, 2009–2011

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.

“Eczema Coxsackium” and Unusual Cutaneous Findings in an Enterovirus Outbreak

“…1 Over the past 5 years, CVA6 has also been implicated in HFMD outbreaks in Finland, France, Spain, India, Taiwan, Japan, Singapore, China, and Boston, Massachusetts. [2][3][4][5][6][7][8][9][10][11] The atypical cutaneous features characterizing the 2011-2012 North American CVA6-associated HFMD outbreak have not been clearly defined.…”

Three-step method for the amplification of the coxsackievirus A10 genome

“…Currently, only two full-length genomes of CV-A10 have been reported (Oberste et al, 2004;Hu et al, 2011), probably because of the regional nature of its distribution or because it is underemphasized (Hu et al, 2011;Lu et al, 2012;He et al, 2013). Thus, there is very little information about the genetics and evolution of CV-A10.…”

“…In addition, outbreaks or sporadic cases may also be caused by other human enteroviruses, such as CV-A10. In recent years, CV-A10-related HFMD has been associated with increasingly common but sporadic cases of HFMD, and by global outbreak events (Blomqvist et al, 2010;Wu et al, 2010;Yu and Song, 2010;Davia et al, 2011;Lu et al, 2012;Mirand et al, 2012;He et al, 2013). All of these studies strongly demonstrated that CV-A10 infections are an important cause of HFMD.…”

“…In rare cases, patients also develop neurological complications, such as encephalomyelitis and aseptic meningitis (McMinn, 2002;Shah et al, 2003;Pérez-Vélez et al, 2007). Several large epidemics of HFMD have been reported in the Asia Pacific region, particularly in Southeast Asia, since 1997 (Lu et al, 2012). Previous studies have shown that outbreaks of HFMD are mainly caused by human enterovirus 71 (EV-71), CV-A6, and CV-A16 (Chang et al, 1999;Yan et al, 2001;Lin et al, 2003;Osterback et al, 2009;Zhang et al, 2009;Zhang et al, 2010).…”

EV71 vaccines: a first step towards multivalent hand, foot and mouth disease vaccines

“…These viruses contribute to HA and classic or atypical HFMD outbreaks and they can cause severe disease with neurological complications [17][18][19][20][21]. Based on global molecular epidemiology surveillance, EV71, CVA16, CVA6 and CVA10 are the most prevalent pathogens of HFMD in children [1,3,[17][18][19][20][21].…”