Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

Abstract

Background Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010–2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. Results A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010–2012 followed by an apparent decline during 2013–2017. However, the activities of CVA16 increased gradually during 2018–2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10–3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. Conclusions The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010–2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.

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

“…36 in 2013 and during 2015-2019 in Beijing. 11 The etiological and phylogenetic analysis of HFMD in southern China showed that the predominant virus was also CV-A6 in 2020. 37 The analysis of symptoms caused by different pathogens suggested that the rash in patients affected by CV-A6 and Other enteroviruses spread to a wider distribution, and CV-A6 even on the face.…”

“…10 The prevalence of CV-A16 showed obvious periodic fluctuations in Beijing from 2010 to 2018, with the detection rate increasing every other year. 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.…”

“…showed that the decreasing prevalence of strains from the D2 genotype combined with the booming viruses from the D3 sub-genotype summarized the circulation pattern of CV-A6 in the mainland of China between 2008 and 2015. 12 Hu et al 11 showed that the dominant strains…”

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

“…Similar to EV71, CVA16 was considered the predominant agent responsible for the HFMD outbreaks in many regions of China in the last decade [2,[19][20][21]. Phylogenetically, there are three genotypes of CV-A16 (Genotypes A, B and D) detected worldwide [19].…”

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

“…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. Combined with that study, our result of CV-A6 detection rate increasing from 2019 to 2020 reflected that CV-A6 strains rose epidemic peak every 2 years.…”