The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth Disease Epidemic patterns in Guangdong, China

Abstract

Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trendsofCVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China.

Ambulatory Pediatric Surveillance of Hand, Foot and Mouth Disease as Signal of an Outbreak of Coxsackievirus A6 Infections, France, 2014–2015

“…In addition, the dermatologic presentation of CV-A6 HFMD cases was more frequently unusual (63.3%), with eruptions extending beyond the typical sites of HFMD (i.e., soles, palms, buttocks, and knees or elbows) than in HFMD cases caused by other enterovirus serotypes. Our findings suggest that the clinical presentation of CV-A6 infections in France shifted to atypical HFMD during 2010–2014, as observed in China during 2008–2013 ( 18 ). In our study, the co-circulation of 6 virus lineages in 2014 is consistent with the hypothesis of multiple introductions of genetically distinct CV-A6 strains.…”

“…The extensive or unusual nature of the cutaneous manifestations of CV-A6 HFMD does not seem to increase the risk for severe systemic illness ( 21 ). Although to a lesser extent than with EV-A71, severe CV-A6 HFMD cases, defined by the presence of neurologic signs (e.g., meningitis, encephalitis, acute flaccid paralysis, and seizures) or cardiopulmonary signs, have been reported, with a frequency ranging from 3.6 % to 18.2% during the recent CV-A6 outbreaks in China ( 18 , 31 – 34 ). Meningitis rather than encephalitis was more frequently associated with severe CV-A6 HFMD ( 32 , 33 ).…”

Impact of Coxsackievirus A6 emergence on hand, foot, and mouth disease epidemic in Osaka City, Japan

“…CV-A6 strains were classified into seven genetic clades (A-G) based on the complete VP1 sequences as described in a KANBAYASHI ET AL. | 2117 previous report 29 (Figure 3). Furthermore, clade A was sub-classified into four genetic groups (A1-A4) ( Figure 3).…”

“…Phylogenetic analysis of CV‐A6 strains was performed with reference sequences in the GenBank database. CV‐A6 strains were classified into seven genetic clades (A‐G) based on the complete VP1 sequences as described in a previous report (Figure ). Furthermore, clade A was sub‐classified into four genetic groups (A1‐A4) (Figure ).…”

Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

“…Our CV-A6 findings are consistent with other reports from the region. 49, 78, 79, 80, 81 CV-A6 progressively became the most common virus detected among mild HFMD cases, apparently replacing other non-EV-A71 viruses, including CV-A16 in China, Thailand, Malaysia and Singapore. 11, 49, 82, 83, 84, 85, 86, 87 CV-A6 seems now to be associated with many outbreaks worldwide.…”