| Background and Objective: Since the hand,foot and mouth disease was classified as a Class C infectious disease in 2008,China has carried out close monitoring and extensive prevention.However,the annual mortality,risk of serious and fatal risks of hand,foot and mouth disease are still high,and the number of cases ranks first among Class C infectious diseases before influenza and other infectious diarrhea.The main epidemic strains of hand,foot and mouth disease are EV71 and CoxA16.EV71 is the main pathogen causing severe cases or death.The EV71 vaccine has been successfully developed and put into use,and the CoxA16 vaccine is also under development.The future spread of these two major pathogens can be controlled by the vaccine,but the pathogen CoxA4,which is co-transmitted with CoxA16 and CoxA10,is on the rise.In China 2008-Among the intestinal virus samples isolated in 2017,CoxA4 became the fifth largest hand,foot and mouth disease pathogen except EV71,CoxA16,CoxA6 and CoxA10.CoxA4 has the possibility of a large-scale epidemic similar to EV71 and CoxA16.Therefore,insisting on the study of CoxA4 is necessary and feasible,but there is less relevant research now.The Bayesian-Markov chain method is based on the prior probability used to select the best nucleotide replacement model.Regarding the optimization criteria Then use the posterior probability to quickly realize the accurate processing of large batches of data and complex models.Therefore,using this combination algorithm to carry out in-depth molecular evolution research on CoxA4 to grasp the evolutionary trend and genetic characteristics of CoxA4,it can make a more scientific and reasonable explanation of the genotyping of pathogens and the possible regional epidemic,and then be related to hand-foot-mouth disease Public health security has built a firewall.Materials and Methods: Take a swab sample of a child with foot,foot and mouth disease within 3 days of the onset,ensure that a special sampling cotton swab is used and immediately put it into the preservation solution.And quickly sent to the laboratory for storage at-20?,long-term storage,put-80?.Descriptive epidemiological statistical methods were used to investigate the age,gender,range of activity,pathogen distribution,and clinical characteristics of different pathogens symptom.A total of 231 CoxA4 VP1 gene sequences with clear separation time and place were obtained from the Genbank database.With reference to the Bayesian method(abbreviation of the Bayesian-Markov chain method)construction process,combined with the drawn BSP(Bayesian skyline plots,Bayesian skyline curves),analysis of the molecular evolution characteristics of CoxA4.The homologous recombination analysis and verification of CoxA4 gene sequence were performed using RDP and Simplot.Result: A total of 178 cases of hand,foot and mouth disease were reported from January to November 2017,with an average annual incidence of 37.24 / 100,000 and a severe rate of 0%.Children under 5 years of age accounted for 83.71% of the total number of cases,child care children accounted for 50.56% of the total number of cases,and scattered people accounted for 35.39% of the total number of cases.The etiology monitoring results showed that the dominant pathogenic strain of hand,foot and mouth disease was CoxA6,and the proportion of other pathogens containing CoxA4 increased by 9.46%,and the proportion of fever symptoms was 71.42%(P<0.05),which was significant.According to the analysis of the collected data,CoxA4VP1 reports appeared in 33 countries and regions around the world,which can be divided into four genotypes of A-D.Type C is further divided into C1,C2,and C3 types.Type A is further divided into A1 and A2 types.There are many subtypes of CoxA4 in mainland China,and A1,A2,C2,and D types are all discovered.The Bayesian skyline was plotted to analyze the genetic diversity of CoxA4.The evolution rate of the CoxA4 VP1 gene is 6.071E-3 replacement events per site per year on average.The mutation rates of the three codons of the amino acids encoded by CoxA4 were 1.0411,0.6343,and 1.3243,respectively.Homologous recombination found 8 recombination events,9 recombination strains.Conclusion: From January to November 2017,178 hand,foot and mouth samples were collected from Changchun,with a male / female ratio(85/93).Children aged 5 and under were concentrated(83.71%),with the largest number of childcare(90/178).The main pathogen was CoxA6(56.76%),and CoxA16,EV71,and CoxA10 were also detected.The detection rate of CoxA4 tends to increase,and other pathogens infected with CoxA4 are more prone to fever symptoms.CoxA16 infected sample is older.From 1996 to 2019,CoxA4 was divided into four A-D genotypes.The prevalent pathogens in mainland China are D-type(132/137),with 2 strains of A and 3 strains of C.The increase of CoxA4 VP1 gene polymorphism is related to the emergence of new genotypes,and the CoxA4 gene polymorphism showed an upward trend during 2005-2007 and 2011-2014.CoxA4 VP1 gene replacement rate is 6.071E-3 replacement events per site per year on average,and the probability of intratype recombination is 16%(8/50). |
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