An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: A Singapore retrospective cohort study, 2013–2018

Min, Nyo; Ong, Y. H.; Han, Alvin X.; Ho, Si Xian; Yen, Emmerie Wong Phaik; Ban, Kenneth; Maurer‐Stroh, Sebastian; Chong, Chia Yin; Chu, Justin Jang Hann

doi:10.1371/journal.pntd.0008885

Cited by 24 publications

(17 citation statements)

References 32 publications

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“…320/322 CVA16 patients with available demographic and clinical information were included for analysis in the present study. Most (59.4%) of these patients were male, in agreement with previous reports ( Le et al, 2020 ; Min et al, 2021 ). The median age was 20.82 months.…”

Section: Resultssupporting

confidence: 93%

Coxsackievirus A16 in Southern Vietnam

et al. 2021

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Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies.Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis.Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96–31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases.Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2–3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.

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Section: Resultssupporting

confidence: 93%

Coxsackievirus A16 in Southern Vietnam

et al. 2021

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“…These four genotypes were also with the highest frequency in France during 2014-2015 ( 15 ). CV-A6 was detected a high proportion in HFMD or herpangina children in vast locations and time span ( 16 ), and it was the predominant pathogen in Guangdong in 2015, Singapore in 2013-2018 and Guizhou in 2019 ( 17 , 18 ). Studies ( 19 ) showed that CV-A6 detection rate was low in 2010-2012, then increased in 2013, 2015, 2017 and remained high in 2018, while decreased in 2014, 2016 and 2019.…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020

et al. 2022

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BackgroundThe changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China.MethodFrom January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes.ResultA total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world.ConclusionsThe predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

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“…CVA16 and EVA71 are the two best known viruses which cause mild herpangina and hand-foot-and-mouth disease (HFMD) in young children. Several HFMD outbreaks associated with co-circulation of EVA71 and CVA16 have been reported in China, Japan, Korea, Malaysia, Singapore, Vietnam, and Thailand [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Of notice, there are three fatal reports of CVA16 infection: one is of a child who had HFMD associated with myocarditis, the second is of an adult who had pneumonitis, and the third is of a child who had HFMD associated with acute pancreatitis [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic and Cross Neutralization Analyses of Coxsackievirus A16 Circulating in Taiwan from 1998 to 2021 Suggest Dominant Genotype B1 can Serve as Vaccine Candidate

Cheng

Chiu

Huang

et al. 2022

Viruses

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Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000–2003, 2005, 2007–2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5′-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16.

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An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: A Singapore retrospective cohort study, 2013–2018

Cited by 24 publications

References 32 publications

Coxsackievirus A16 in Southern Vietnam

Coxsackievirus A16 in Southern Vietnam

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020

Genetic and Cross Neutralization Analyses of Coxsackievirus A16 Circulating in Taiwan from 1998 to 2021 Suggest Dominant Genotype B1 can Serve as Vaccine Candidate

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