Study On Epidemiological Characteristics Of Hand-Foot-and-Mouth Disease And Gene Recombination Of Other Enteroviruses In Hebei Province

Objectives The study analyzed the epidemiological characteristics and pathogen distribution characteristics of HFMD in Hebei between 2017 and 2019.The whole gene sequences of other enteroviruses were amplified by universal enterovirus whole genome amplification method to analyze the genetic characteristics and evolutionary recombination events of enteroviruses other than EV-A71 and CV-A16 in Hebei Province between 2011 and 2019.Methods The data of HFMD cases in Hebei Province between 2017 and 2019 were collected from National Notifiable Diseases Surveillance System,and the pathogen data of HFMD were collected from the Network Laboratory of HFMD in Hebei Province.Descriptive epidemiological method was used to analyze the epidemic and etiological characteristics of HFMD and in Hebei Province during 2017-2019.RD cells were used to isolate enteroviruses viruses from mild and severe cases of HFMD caused by other enteroviruses.The whole genome sequence of enterovirus was obtained by universal amplification of enterovirus genome.Sequence alignment and phylogenetic analysis were performed by MEGAX software,gene recombination signals were detected by RDP4 software,and gene recombination events were verified by Sim Plot3.5.1.Results 1 A total of 118915 HFMD cases were reported in Hebei Province during 2017-2019,including 133 severe cases and 6 deaths,with an average annual incidence of52.46/100000.From 2017 to 2019,the incidence peak of HFMD decreased year by year,as well as the number of severe cases and deaths.The incidence peak was during June to August every year,which accounts for 61.8% of all cases.The three cities with the highest annual average incidence were Baoding,Langfang and Tangshan,which were116.45/100000,90.06/100000 and 62.94/100000 respectively.The three cities with the highest severity rates during 2017-2019 were Hengshui City(0.72%),Qinhuangdao City(0.30%)and Xingtai City(0.17%).The cases were mainly occurred in children aged 0-5years old,which accounting for 89.53% of all the reported cases.HFMD mainly occurred in scattered children,accounting for 68.24% of the total cases.The ratio of HFMD morbidity between male and female was 1.47.2 A total of 20554 cases of HFMD were tested for enterovirus nucleic acid during 2017-2019,and 15194 cases were detected positive.The proportion of EV-A71,CV-A16 and other enterovirus was 10.52%,28.84%and 60.64% respectively.Among the severe cases,the proportion of EV-A71,CV-A16 and other enterovirus was 51%,39% and 10% respectively.3743 other enterovirus positive samples were further typed during 2018-2019,the proportion of CV-A6 and CV-A10 was53.94% and 13.49%.Every month during 2017-2019,other enterovirus positive samples were more than EV-A71 and CV-A16,accounting for more than 50% of all the cases.Among the positive samples in all cities,except Qinhuangdao and Shijiazhuang,other enteroviruses accounted for more than 50%.3 The evolutionary analysis showed that CVA6 isolates in Hebei Province were mainly D2 subtype before 2012,and the D3 subtype began to appear in 2013.All the CV-A6 isolates belonged to D3 subtype during 2014-2019,which were divided into two branches,one of which recombined with Hong Kong 2012 CV-A4 isolate(MH780724)in 2C region and P3 region.All the CV-A2 isolates detected in Hebei Province from 2015 to 2018 belonged to genotype D,and the CV-A2 isolates in Hebei Province(15238)were recombined with Jiangsu CV-A14(KP036482)in 2012,CVA8(MT648783)in Shandong Province in 2015.The isolates of CV-A2(15181),CV-A4 in Hebei,CV-A5 in Xiangyang and CV-A6 in Shanghai were recombined.All the CV-A4 isolates detected in Hebei Province from 2013 to 2017 belonged to genotype D.Hebei CVA4 isolates(17303)was a recombinant strain,which recombined with Shenzhen isolates(KX595281)in P2-P3 region.Conclusions 1 In recent years,the incidence of HFMD in Hebei Province showed an overall downward trend.There are obvious seasonal,regional and population distribution characteristics in the incidence of HFMD in Hebei.The incidence peak was during June to August every year,and the incidence rates in Baoding,Shijiazhuang and Langfang are higher than other cities.Most cases occurred in children under 5 years old,and the incidence rate of HFMD in male is higher than that in female.2 In recent years,the proportion of HFMD cases caused other enteroviruses has been increasing,and CV-A6 has gradually replaced EV-A71 as the main pathogen of mild and severe HFMD cases,warning that we should carry out systematic monitoring of the genotypic distribution of other enteroviruses in Hebei,and grasp the changes of the dominant types in time,so as to provide scientific basis for the prevention,control and disposal of public health emergencies related to new enteroviruses.3 The gene recombination phenomenon exists in CV-A2,CV-A4 and CV-A6 enteroviruses in Hebei Province.The whole genome characteristics of epidemic strains should be deeply studied to provide data support for early warning that enterovirus recombinant strains may cause large-scale epidemic and outbreak of hand-foot-mouth disease in this area.At the same time,the whole genome sequence database of other enteroviruses should be improved to provide direction for the research and development of antigen formulation of HFMD multivalent vaccine.Figure 27;Table 20;Reference 81...