A review and meta‐analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand‐foot‐mouth disease in China and global implications

Zhao, Tongtong; Du, Juan; Sun, Dianjianyi; Zhu, Quan‐Rong; Chen, Lin‐Yi; Wang, Hongzhi; Wang, Shuai; Liu, Yaqiong; Cui, Fuqiang; Lu, Qing‐Bin

doi:10.1002/rmv.2087

Cited by 35 publications

(34 citation statements)

References 64 publications

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“…The EV-A71 vaccine has no cross-immunity against CV-A16 and Other Enteroviruses [ 39 ], thus increasing the proportion of Other Enteroviruses causing HFMD, especially the sharp increase in CV-A6 we have shown. The increasing prevalence of CV-A6 may result in future HFMD outbreaks, however it may be missed as a cause due to its complex clinical manifestations [ 40 ]. Furthermore, it was also shown that CV-A6 accounted for 62.33% of severe HFMD in Kunming in 2018 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Spatial–temporal-demographic and virological changes of hand, foot and mouth disease incidence after vaccination in a vulnerable region of China

et al. 2022

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Background The enterovirus 71 (EV-A71) vaccine has been used in Hefei for several years, and the epidemiological significance of vaccination in this area is unclear. We aims to explore the spatial–temporal-demographic and virological changes of hand, foot and mouth disease (HFMD) after vaccination in China. Methods The data for HFMD from 2012 to 2020 were downloaded with the help of HFMD reporting system of Hefei Center for Disease Control and Prevention and combined with the EV-A71 vaccination status in Hefei. The study defined the period between 2012 to 2016 as the pre-vaccination period and explored the effect of vaccination on the incidence of HFMD by comparing the changes of HFMD before and after vaccination in terms of spatial, temporal, demographic and virological aspects. Results During the study period, a higher incidence occurred in urban area and the random distribution changed to a slight cluster after vaccination. HFMD incidence had inconsistent seasonality over years, with one or two incidence peaks in varying years. The morbidity decreased from 215.22/105 in 2012–2016 to 179.81/105 in 2017–2020 (p < 0.001). Boys, 0–4 years old children and Scattered children were more susceptible to HFMD compared with the others, the proportions decreased after vaccination except in Scattered children. The main pathogenic enterovirus gradually changed from EV-A71 to Other Enteroviruses, especially coxsackieviruses A6 (CV-A6) after the implementation of EV-A71 vaccination. Conclusions The EV-A71 vaccine was effective in reducing the incidence of HFMD and changing the spatial, temporal, demographic, and virological characteristic. These changes should be considered during the vaccination implementation to further reduce the disease burden of HFMD.

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Section: Discussionmentioning

confidence: 99%

Spatial–temporal-demographic and virological changes of hand, foot and mouth disease incidence after vaccination in a vulnerable region of China

et al. 2022

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“…11 Nonetheless, in recent years, CV-A6-associated HFMD outbreaks 12,13 and the overall trend of the epidemic of CV-A6-associated HFMD was increasing in China. 14 The clinical features of CV-A6-associated HFMD are slightly different from representing so-called atypical HFMD, with the skin eruptions spreading to the trunk, neck, and legs, and high fever with a shorter duration. 15,16 Although the severe rate of HFMD caused by CV-A6 was low (0.10%), CV-A6 can cause a high incidence of onychomadesis (28.0%).…”

Section: Introductionmentioning

confidence: 99%

“…15,16 Although the severe rate of HFMD caused by CV-A6 was low (0.10%), CV-A6 can cause a high incidence of onychomadesis (28.0%). 14 It is important to understand the changing epidemiology of the viral strains causing HFMD. The study by Yang et al…”

Section: Introductionmentioning

confidence: 99%

Epidemiological characteristics of hand, foot, and mouth disease clusters during 2016–2020 in Beijing, China

Cui

Yang

Zheng

et al. 2022

Journal of Medical Virology

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Hand, foot, and mouth disease (HFMD) is an infectious disease that usually occurs in children under 5 years and is caused by a group of enteroviruses. This study aimed to investigate the epidemiological characteristics of HFMD clusters from 2016 to 2020 in Tongzhou, Beijing, and explored the genetic evolution of CV-A6. The HFMD case information came from the Information System of China Center for Disease Control and Prevention (CDC), as well as the clusters information verification and on-site investigation by Tongzhou CDC. ARIMA model was applied to forecast HFMD clusters in 2020. Totally 440 HFMD clusters were reported during 2016-2020. The large peak of the clusters occurred in April-July, followed by a smaller peak in October-November during 2016-2019. However, in 2020, the two peaks disappeared. The main site of HFMD clusters was childcare facilities (65.0%) and mostly occurred in urban areas (46.1%). The detection rate of CV-A6 was the highest (36.1%), and cases with CV-A6 infection had the highest proportion of fever. The phylogenetic analysis based on CV-A6 VP1 gene showed that the predominant strains mainly located in Group F during 2016-2017, while changed into Group A during 2018-2020. HFMD clusters presented seasonality, mainly located in childcare facilities and urban areas, and CV-A6 was the major causative agent. Targeted prevention and control measures should be taken to reduce HFMD clusters.

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“…As the surveillance data indicated, CVA6 was detected infrequently in the past years, while it occupied 90% of the ‘other’ associated cases in 2017 [ 10 ]. It had been reported that CVA6 was associated with increasingly sporadic HFMD outbreaks in some countries [ 22 , 23 ]. Furthermore, cases associated with this type featured a clinical symptom of onychomadesis sometimes [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple molecular characteristics of circulating enterovirus types among paediatric hand, foot and mouth disease patients after EV71 vaccination campaign in Wuxi, China

et al. 2022

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The molecular properties of the circulating causative agents of hand, foot and mouth disease (HFMD) in Wuxi remain unclear, posing diagnostic and prevention challenges. Additionally, in several regions of mainland China, the EV71 immunisation drastically reduced related cases and altered the HFMD pathogen spectrum, while the precise situation in Wuxi remained unknown. To address these issues, paediatric HFMD cases diagnosed in the clinic were enrolled and anal swabs were acquired in the spring of 2019. The 5′-UTR and VP1 genes were interpreted using RT-nPCR with degenerate primers to confirm their genotypes. Following that, the entire genome sequences of each viral type were recovered, allowing for the interpretation of several molecular properties. A total of 249 clinically confirmed HFMD cases had their anal swabs taken for viral identification, from which the genome sequences of seven genotypes were recovered. Coxsackievirus A16 is the most prevalent type, followed by Coxsackievirus A6, A10, A2, A4, A5 and Echovirus 11, all of which were genetically determined for the first time in Wuxi. Phylogenetic and recombination analyses were used to evaluate their evolutionary relationships with other strains found in other regions. Noticeably, a CVA16 subtype, responsible for a large proportion of the observed cases, phylogenetically clustered within clade B1a along with some strains from other countries, was the first one to be reported in China. Furthermore, some recombination events were inferred from strains detected in sporadic cases, particularly the recombination between CVA2 and CVA5 strains. Our investigation elucidated the multiple molecular characteristics of the HFMD causal enterovirus strains in Wuxi, underlining the potential hazards associated with these circulating viral types in the population and aiding in future surveillance and prevention of this disease.

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A review and meta‐analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand‐foot‐mouth disease in China and global implications

Cited by 35 publications

References 64 publications

Spatial–temporal-demographic and virological changes of hand, foot and mouth disease incidence after vaccination in a vulnerable region of China

Spatial–temporal-demographic and virological changes of hand, foot and mouth disease incidence after vaccination in a vulnerable region of China

Epidemiological characteristics of hand, foot, and mouth disease clusters during 2016–2020 in Beijing, China

Multiple molecular characteristics of circulating enterovirus types among paediatric hand, foot and mouth disease patients after EV71 vaccination campaign in Wuxi, China

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