Prevalence of Multiple Enteroviruses Associated with Hand, Foot, and Mouth Disease in Shijiazhuang City, Hebei Province, China: Outbreaks of Coxsackieviruses A10 and B3

Abstract

Hand, foot, and mouth disease (HFMD) has been one of the most common infectious diseases in Shijiazhuang City, as is the situation in China overall. In the National HFMD surveillance system, the pathogen detection was focused on EV-A71 and CVA16, and therefore, information on the other EVs is very limited. In order to identify the circulating EV serotypes in the HFMD outbreaks in Shijiazhuang City during 2010–2012, 4045 patients presented with HFMD were recruited in the study, and clinical samples were investigated. Typing of EV serotypes was performed using the molecular typing methods, and phylogenetic analyses based on entire VP1 sequences of human enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), CVA10 and CVB3 was performed. The results revealed that EV-A71 and CVA16 were the 2 most important pathogens but the circulating trends of the 2 viruses showed a shift, the spread of EV-A71 became increasingly weak, whereas the spread of CVA16 became increasingly stronger. CVA10 and CVB3 were the third and fourth most prevalent pathogens, respectively. Co-infection of two viruses at the same time was not found in these samples. Based on entire VP1 region sequences, the phylogenetic analysis revealed that C4a subgenotype EV-A71, B1a and B1b subgenotype CVA16 continued to evolve. The CVA10 strains were assigned to 4 genotypes (A–D), whereas the CVB3 strains were assigned to 5 genotypes (A–E), with clear geographical and temporal-specific distributions. The Shijiazhuang CVA10 sequences belonged to 4 epidemic lineages within genotype C, whereas the Shijiazhuang CVB3 sequences belonged to 2 epidemic lineages within genotype E, which may have the same origins as the strains reported in other part of China. CVA10 and CVB3, 2 pathogens that were previously infrequently detected, were identified as pathogens causing the HFMD outbreaks. This study underscores the need for detailed laboratory-based surveillances of HFMD in mainland China.

Improved Detection Limit in Rapid Detection of Human Enterovirus 71 and Coxsackievirus A16 by a Novel Reverse Transcription–Isothermal Multiple-Self-Matching-Initiated Amplification Assay

“…The results showed that EV71 and CVA16 were still the two major pathogens (33). In the evaluation, all the positive samples by our new approaches also tested positive by the corresponding qRT-PCRs.…”

Is a multivalent hand, foot, and mouth disease vaccine feasible?

“…EV-A71 and CV-A16 were responsible for 90.2% and 8.7% of fatal outcomes, respectively. 17,24,29,31,40,41,44,47,49,58,67 Although usually mild, CV-A16 infection may lead to neural and muscle cells apoptosis 118 and has occasionally been the cause of rhombencephalitis, brain stem encephalitis and acute flaccid paralysis, fatal pneumonitis and fulminant myocarditis with intractable shock. 8 Since 2004, the incidence of CV-A6-and CV-A10-associated HFMD epidemics has markedly increased worldwide [ Table 1].…”

“…Co-circulating CV-A10 strains isolated during the epidemic in the Hebei province between 2008 and 2012 were found to segregate into 4 clusters (A-D), the C genotype being further divided into 4 lineages. 24 All Chinese CV-A10 segregated into the B and C genotypes, genotype B in Shangdong and genotype C in the other provinces. Another phylogenetic analysis of CV-A10 strains indicated that they cluster into 7 genotypes (A to G).…”

“…37 Five genotypes (A-E) were assigned by phylogenetic analyses to coxsackieviruses CV-B3 and CV-B5. 24,124 All Chinese CV-B3 isolates segregated into genotype E but the presence of 2 divergent circulating genotype E strains in Shijiazhuang City (2010-2012) suggests the existence of 2 different lineages. Chinese CV-B3 strains clustered into a genogroup totally different from CV-B3 isolates from other countries.…”

“…Chinese CV-B3 strains clustered into a genogroup totally different from CV-B3 isolates from other countries. 24 The severity of the Linyi epidemic in 2009 was attributed to the introduction of an unusual and distinct CV-B5 lineage. 30 Echovirus 30 has been classified into 8 clusters (A-H) 23 and the E-30-associated HFMD outbreak in Guanxi (2010) has been attributed to a strain belonging to the H lineage.…”