Phylogenetics and phylogeographic characteristics of coxsackievirus A16 in hand foot and mouth disease and herpangina cases collected in Beijing, China from 2019 to 2021

Abstract

Coxsackievirus A16 (CV‐A16) is a significant pathogen responsible for causing hand foot and mouth disease (HFMD) and herpangina (HA). This study aimed to investigate the recent evolution and spread of CV‐A16 by monitoring HFMD and HA cases in 29 hospitals across 16 districts in Beijing from 2019 to 2021. The first five cases of HFMD and the first five cases of HA each month in each hospital were included in the study. Real‐time reverse transcription polymerase chain reaction was used to identify CV‐A16, CV‐A6, and EV‐A71. From each district, two to four CV‐A16 positive samples with a relatively long sampling time interval every month were selected for sequencing. A total of 3344 HFMD cases and 2704 HA cases were enrolled in this study, with 76.0% (2541/3344) of HFMD and 45.4% (1227/2704) of HA cases confirmed to be infected by enterovirus. Among the EV‐positive samples, CV‐A16 virus was detected in 33.61% (854/2541) of HFMD cases and 13.4% (165/1227) of HA cases, with the predominant cluster being B1a. Both B1a and B1b had a co‐circulation of local and imported strains, with different origin time (1993 vs. 1995), different global distribution (14 countries vs. 10 countries), and different transmission centers but mainly distributed in the southern and eastern regions of Beijing. Strengthening surveillance of HFMD in southern and eastern regions will improve the prevention and control efficiency of enterovirus infections.

Circulating trends of hand, foot, and mouth disease in Hubei Province, China: Impact from the COVID-19 pandemic

“…The evolutionary branch of B1b in Hubei after 2018 remained stable and was the dominant subtype. This finding is consistent with those of other regions in China in recent years [ 25 ]. There was no significant mutation in the gene sequence, and only slight differences were found in VP1 sequences in different years.…”

First detection of multiple cases related to CV‐A16 strain of B1c clade in Beijing in 2022

“…5,15 There was also co-circulation in Beijing but the dominant type was B1a clade. 12 In the previous reports, B1c clade was detected in France and Japan around 2010. 16 The epidemics and wide spreading of the virus occurred in India during 2009-2018.…”

“…In recent years, the Beijing area has exhibited a co-circulation of the B1a and B1b genotypes; however, the B1a genotype has been identified as the predominant strain in this region. 12 Previous literature has reported the identification of one case of B1c in a hospital in Beijing in 2016 20 ; however, it was not confirmed whether it was a local case in Beijing. Therefore, B1c remains quite rare in Beijing, as it is in other parts of the country.…”

“…Selection of representative sets of CV-A16 VP1 sequences was described by Li et al 12,13 In brief, the 216 representative VP1 sequences encompassed isolates from 25 different countries and spanned a period from 1951 to 2020 and were selected from distinct branches of the neighbor-joining (NJ) phylogenetic tree of all VP1 sequences of CV-A16 in GenBank. The selection process was designed to ensure that the data set was as representative as possible, taking into account the collection country and date characteristics of the isolates.…”

Epidemiological and etiological investigations of hand, foot, and mouth disease in Jiashan, northeastern Zhejiang Province, China, during 2016 to 2022

“…Most patients have mild symptoms; however, a small number have aseptic meningitis, encephalitis and acute flaccid paralysis, and some critically ill children show rapid disease progression and may die ( 2 , 3 ). HFMD has caused significant medical, social, and economic burdens to the global community, and has become a major public health problem worldwide, especially in East and Southeast Asia ( 4 , 5 ). In China, HFMD outbreaks have occurred annually in the past decade.…”