A novel recombinant lineage’s contribution to the outbreak of coxsackievirus A6-associated hand, foot and mouth disease in Shanghai, China, 2012-2013

Abstract

Since late 2012, coxsackievirus A6 (CVA6) has gradually become the predominant pathogen responsible for hand-foot-mouth disease (HFMD) in several provinces of China. A total of 626 patients diagnosed with HFMD in Shanghai, China from January 2012 to September 2013 were enrolled in this study. Of these, 292 CVA6 infected cases were subjected to clinical analyses. Whole-genome sequencing, recombination and phylogenetic analyses were also performed. A recombinant CVA6 monophyletic lineage was found during an outbreak of CVA6-associated HFMDs in Shanghai, China in November 2012, and accounted for 21.9% (64/292) of the CVA6 strains during the study period. Recombination analyses showed that the 2C gene of the novel CVA6 virus was probably derived from a coxsackievirus A4 (CVA4) strain circulating in the population. Clinical observation showed that this recombinant CVA6 virus led to a more generalized rash than did the non-recombinant CVA6 virus. This newly emerged CVA6 lineage was associated with a considerable proportion of HFMD cases from 2012 to 2013 in Shanghai, and poses a potential threat to public health.

Characterization of genome sequences and clinical features of coxsackievirus A6 strains collected in Hyogo, Japan in 1999‐2013

“…In the analysis of the complete genome, CV‐A6 strains related to the HFMD outbreak in 2011 and 2013 were grouped in the same cluster as strains (GenBank accession number KM114057 and KP144345), which were also associated with HFMD. CV‐A6 strain isolated from the Chinese HFMD patient in 2013 (GenBank accession number KJ541155)was also classified in this cluster . CV‐A6 strains that caused the symptoms of HFMD overseas had been prevalent in Hyogo Prefecture.…”

“…CV-A6 strain isolated from the Chinese HFMD patient in 2013 (GenBank accession number KJ541155)was also classified in this cluster. 33 CV-A6 strains that caused the symptoms of HFMD overseas had been prevalent in Hyogo Prefecture. Although severely symptomatic HFMD was caused by CV-A6 in the United States in 2011-2012, 34 CV-A6 infection rarely leads to CNS disease.…”

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

“…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. In addition, a genetic analysis of complete CV-A6 genomes showed that strains collected during the 2012–2013 outbreak in Shanghai, China, were recombinant compared with strains collected before 2009 and were more frequently associated with generalized rash ( 29 ). …”

Two Genotypes of Coxsackievirus A2 Associated with Hand, Foot, and Mouth Disease Circulating in China since 2008

“…Some clinical observations showed that infection with the recombinant CV-A6 virus was associated with different clinical features from on generalized rash [28, 29]. However, there is limited report about the relationship between the recombination of CV-A2 and clinical symptoms.…”