Epidemic Status And Genetic Characteristics Of Hand-Foot-Mouth Disease Among Surveillance Cases In Harbin From 2016 To 2021

Background Hand-foot-mouth disease(HFMD)is an acute febrile disease caused by enteroviruses(EV),characterized by herpes in the hands,feet,and mouth.Children under the age of 5 are more susceptible to infection.Although there were number of researches on HFMD around the world,there are still many key problems that cannot be solved.Heilongjiang Province is one of the regions with heavy HFMD in China.As the center of medical and health in the province,Harbin,the provincial capital,the HFMD sample probably collected from the whole province;Harbin has a high latitude and belongs to the temperate monsoon climate.At the same time,it is in the Songhua River basin.It is warm and rainy in summer,and sometimes the temperature between day and night is obvious.It is the regional factor of HFMD epidemic.In recent years,the frequency of HFMD outbreaks in Harbin is higher than the average level in Heilongjiang Province.Therefore,the study of clinical characteristics,pathogenic characteristics,gene recombination,molecular epidemiological characteristics of HFMD in Harbin can provide effective laboratory data for the timely arrangement of prevention and control of HFMD in Harbin,and provide a powerful prediction for diagnosis and treatment.It provides scientific basis for relieving the pressure of medical services,saving medical resources,and helping to improve the level and capacity of primary medical services.Method This study collected 2881 cases of oropharyngeal swabs,anal and other samples swab of HFMD submitted by the HFMD sentinel hospital(Harbin Children’s Hospital and Harbin the Sixth Hospital)and various district and county CDC from 2016 to 2021,and carry out statistical description and analysis.The enterovirus A71(EV-A71),coxsackievirus A10(CV-A10),coxsackievirus A16(CV-A16)and coxsackievirus A6(CV-A6)were screened by Real-time PCR.Carried some samples with positive CVA6、CV-A16 and EV-A71,carried out PCR amplification and sequencing for some VP1 genes,downloaded representative reference sequences from Gen Bank database,and constructed phylogenetic tree to analyse CV-A16、CV-A6 and EV-A71.Result 1.From 2016 to 2021,2881 samples were received for inspection,and 2005 samples were positive,and the positive detection rate was 69.86%.The details are as follows: from January to December in 2016,the positive detection rate was 68.58%(334/487).CV-A16 and CV-A6 were the main epidemic pathogens,with the positive proportions of 38.33% and 25.15% respectively.From January to December in 2017,the positive detection rate was 65.91%(348/528).EV-A71 was the main epidemic pathogen,with a positive rate of 46.84%.From January to December in 2018,the positive detection rate was 69.22%(596/861).CV-A6 and CV-A16 were the main epidemic pathogens,with the positive rates of 32.21% and 30.03% respectively.From January to December in 2019,the positive detection rate was 72.88%(602/826).CV-A16 and CV-A6 were the main epidemic pathogens,with the positive rates of 30.73% and 29.73% respectively.In 2020,due to the COVID-19 epidemic,only 11 samples(all negative)were received and not included in the analysis.From January to December in 2021,the positive detection rate was 74.40%(125/168).Other EV unclassified viruses and CVA16 were the main epidemic pathogens,with the positive rates of 47.20% and 31.20% respectively.There was no significant difference in the positive rate of HFMV in these years.EV-A71 was the main pathogen of severe cases.The positive pathogen spectrum of sentinel hospitals and district/county CDC samples was different,that is,the constituent ratio of CV-A6 and CV-A10 is significantly different.2.In Harbin,80.35% HFMD cases were infected by children who under 5 years old;There was no significant gender difference in the pathogenic typing of EV-A71,CVA6,CV-A10 and CV-A16 in children with HFMD,but there was gender difference in the pathogenic typing of other EV types(P<0.05),which male infection cases was more than females.The incidence of hand-foot-mouth disease in Harbin had obvious seasonality.The epidemic distribution throughout the year shows a single peak.The number of patients with hand-foot-mouth disease had increased since May,and the incidence peak was from July to August,and it decreases after September.The number of patients with hand-foot-mouth disease had increased significantly since May,and the incidence peak was from July to August,and then showed a downward trend..HFMD cases in Harbin are mainly concentrated in the main urban area of Harbin.3.CV-A16 and CV-A6 were the main pathogens of HFMD in Harbin,accounting for 27.53% and 26.23% respectively.From 2016 to 2021,CV-A6 belonged to D3 subtype,CV-A16 belonged to B1 a subtype and B1 b subtype,and EV-A71 belonged to C4 subtype,consistent with the trend of prevalence of dominant strains of various genotypes in China in recent years.Most of them have high homology with Beijing epidemic strains in various years,and no deletion or insertion of nucleotide fragments has been found overall.