Long-term Epidemiological and etiological characteristics of hand foot mouth disease in Huai'an , Jiangsu Province , 2009 -2022 / 公共卫生与预防医学

Objective The long-term epidemiological and etiological characteristics of hand, foot and mouth disease (HFMD) in Huai’an, Jiangsu were analyzed to provide scientific evidence for the prevention of HFMD. Methods The data of HFMD reports, etiological diagnosis and in Huai’an from 2009 to 2022 were described and analyzed. Results A total of 78 535 cases were reported from 2009 to 2022 , with 14-year average annual incidence rate of 114.71/100 000. Before 2020, the incidence rate of HFMD in Huai’an showed the epidemic intensity increased every other year on the whole, and the average annual incidence rate during the COVID-19 pandemic (2020-2022) (55.69/100 000) was significantly lower than that in previous years (2009-2019) (129.95/100 000). The joinpoint regression analysis showed that the best fitting model from 2009 to 2022 had no joinpoints, APC=AAPC=-1.24%. The overall trend showed a monotonously decreasing trend, but the trend was not statistically significant. The male-to-female distribution ratio was 1.53:1, and the age distribution was mainly under 5 years old, especially in scattered children. The epidemic season was from April to July. The results of etiological surveillance showed that the co-epidemic of Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) during the early stages had changed to the co-epidemic of CV-A16 and CV-A6 in the current period. Conclusion The burden of HFMD in Huai’an was large, and the epidemic intensity increased every other year was affected by the COVID-19 pandemic. The epidemiological features after the COVID-19 pandemic should be further monitored.

Analysis of whole-genome sequences of coxsackievirus A4 strains isolated in Jiangsu Province from 2015 to 2022 / 中华微生物学和免疫学杂志

Objective:To retrospectively analyze the molecular epidemiological features and genetic recombination of coxsackievirus A4 (CVA4) strains isolated in Jiangsu from 2015 to 2022.Methods:Throat or anal swab samples were collected from patients with herpangina or hand, foot and mouth disease (HFMD). Real-time PCR was used to detect CVA4. A comprehensive and systematic phylogenetic analysis was conducted based on 72 whole genomes and 99 VP1 sequences of CVA4 strains. Several bioinformatics software including DNAStar, MEGA7.0 and Similarity plots3.5.1 was used for analysis of homology, genetic recombination and amino acid variation sites.Results:Four genotypes (A, B, C and D) and five sub-genotypes (C1-C5) of CVA4 were identified based on the VP1 nucleotide sequences. C2 was the predominant sub-genotype causing HFMD. The Jiangsu strains showed high homology with the CVA4 prototype in the P1 region, and higher identity with other strains of enterovirus group A (EV-A) in the P2 and P3 regions. Genetic recombination analysis revealed that the Jiangsu strains had three genetic recombination patterns with other EV-A epidemic strains in the P2, P3 and 3′-UTR regions. These recombination patterns took place during the sustained and widespread circulation of CVA4 in people and increased the transmissibility of CVA4.Conclusions:This study analyzes the phylogenetic and molecular features of 28 whole genomes of Jiangsu CVA4 strains, which helps to better understand the genomic diversity of CVA4. By analyzing the genetic recombination and amino acid mutations in the VP1 region, this study elucidates the evolution and transmission of CVA4, which is conducive to the control and prevention of CVA4 infection.

On Prevention and Treatment of Infectious Diseases in Summer Based on TCM Theory of Heat Epidemic / 浙江中医药大学学报

[Objective]To provide insights into the clinical diagnosis and treatment of infectious diseases in summer through probing into the theory of heat epidemic and its characteristics formulated by famous doctors in the past dynasties.[Methods]The etiology,pathogenesis and treatment of heat epidemic were analyzed by summarizing the discussions of various doctors from different angles and at different levels,and the differentiation and treatment rules of several common summer infectious diseases were explored on the basis of the application of heat epidemic theory.[Results]The etiology and pathogenesis of heat epidemic can be classified as excessive main Qi,evil abundance and Yin deficiency,transpiration of summer heat and diffuse ptomaine.Its treatment can be roughly divided into interior-clearing and exterior-harmonizing,blood-cooling and orifice-unblocking.On the basis,the article explored the etiology,pathogenesis and treatment of summer infectious diseases,such as hand-foot-and-mouth disease,dengue and Corona Virus Disease 2019(COVID-19),which have certain similarities with heat epidemic.[Conclusion]The theory of heat epidemic,closely related to the syndrome and treatment rules of three types of summer infectious diseases,can be the tentative basis for clinical diagnosis and treatment of summer infectious diseases with traditional Chinese medicine.

Analysis of recessive infection of hand, foot and mouth disease and associated risk factors among healthy children and guardians in Qingdao / 中国学校卫生

Objective@#To investigate the recessive infection rate of healthy children and guardians in different epidemic periods of hand, foot and mouth disease (HFMD) in Qingdao, analyze the risk factors affecting recessive infection, so as to provide the basis for HFMD prevention and control.@*Methods@#In the nonepidemic period of 2022, the random cluster sampling method was used to selected 546 children and guardians from 4 childcare institutions in Laoshan District and Pingdu City. In the epidemic period of 2023, 690 children and guardians were selected from 6 childcare institutions in Shibei District, Laoshan District and Pingdu District. A questionnair survey was conducted in the epidemic period. Logistic regression analysis was used to analyze the factors affecting the recessive infection. Dominance analysis was used to explore the relative importance of the risk factors affecting recessive infection.@*Results@#The results showed that the recessive infection rates of healthy children and guardians in the epidemic period were 18.84% and 13.62%, respectively; the recessive infection rates were 9.09% and 4.44% in the nonepidemic period, respectively. The results of multivariate Logistic analysis showed that rural areas (OR=4.71, 95%CI=2.57-8.61) and recessive infection of guardians (OR=18.62, 95%CI=7.45-46.56) were positively correlated with recessive infection of HFMD in healthy children (P<0.05). Washing hands (OR=0.09, 95%CI=0.04-0.20), using towels alone (OR=0.17, 95%CI=0.07-0.40), and EV71 vaccination (OR=0.42, 95%CI=0.20-0.87) were negatively correlated with recessive infection of HFMD in healthy children (P<0.05). Public toilets (OR=3.02, 95%CI=1.50-6.09) and drying bedding once per quarter (OR=3.89, 95%CI=1.75-8.68) were positively correlated with recessive infection of HFMD in healthy guardians. Housing with good lighting (OR=0.31, 95%CI=0.12-0.79), and tableware disinfection (OR=0.31, 95%CI=0.15-0.65) were negatively correlated with recessive infection of HFMD in healthy guardians (P<0.05). The results showed that recessive infection of guardians was relatively the most important for healthy children (41.51%), and tableware disinfection was relatively the most important for recessive infection of guardians (28.87%).@*Conclusions@#The recessive infections of HFMD are common among healthy populations in Qingdao, and the recessive infection rate among children during the epidemic period is relatively higher. Guardians play an important role in the recessive infection of healthy children. Therefore, healthy education should be strengthened for key populations, especially to enhance parents awareness of prevention and control to reduce the occurrence of recessive infections of hand, foot and mouth disease in children and guardians.

Analysis of epidemiological characteristics of the clustered cases of hand， foot and mouth disease in Pudong New Area， Shanghai， 2017‒2022 / 上海预防医学

ObjectiveTo analyze the epidemiological characteristics and etiology of clustered outbreaks of hand， foot， and mouth disease （HFMD） in Pudong New Area， Shanghai from 2017 to 2022， and to provide a scientific basis for the prevention and control of HFMD in the area. MethodsThe data related to HFMD clustered outbreaks from 2017 to 2022 were obtained from the Pudong New Area HFMD outbreak database. Descriptive analysis was conducted to explore the outbreak scope， seasonal characteristics， distribution of occurrence settings， and etiological composition. ResultsFrom 2017 to 2022， Pudong New Area reported a total of 2 547 HFMD clusters， involving 8 884 cases， with an average of 3.49 cases per event. The majority of events （78.52%） had between 2 and 4 cases. The peak reporting periods for clustered HFMD from 2017 to 2019 and in 2021 were during the summer （May‒July） and autumn （September‒November）. The seasonal pattern was less distinct in 2020 and 2022， likely due to the impact of the COVID-19 pandemic. The majority of clustered outbreaks occurred in childcare facilities （44.64%）， followed by households/neighborhood committees （44.21%）， with schools accounting for a smaller proportion （12.39%）. The etiology revealed the coexistence of multiple enterovirus genotypes， with a positive detection rate of 60.46%， and CoxA6 being the dominant strain. ConclusionHFMD clustered outbreaks in Pudong New Area show fluctuating trends， with significant yearly differences in the number of incidents. The predominant seasons for outbreaks are summer and autumn， with CoxA6 identified as the dominant strain. The implementation of prevention and control measures for COVID-19 significantly reduced the occurrence of HFMD outbreaks. Continuous monitoring and focus on large-scale clustered outbreaks in key institutions are essential for the future.

Diagnostic value of hs-CRP and PCT combined with IL-6 in children with severe hand-foot-mouth disease / 中国现代医生

@#Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.

Analysis of enterovirus serotype results in Dapeng New District， Shenzhen from 2016 to 2022 / 上海预防医学

ObjectiveTo provide a basis for human enteroviruses prevention and control by monitoring the enterovirus （EV） and its main virus types. MethodsSamples of hand-foot-and-mouth disease， herpetic angina and fever clinic patients in Dapeng New District of Shenzhen from 2016 to 2022 were tested for EV with real-time polymerase chain reaction （PCR）. To identify the isolates of EV， VP1 genes of EV were amplified with nested reverse transcription PCR， and then sequenced.A geneticphylogenetic tree was constructed based on the VP1 gene. ResultsAmong the 1 124 suspected hand-foot-and-mouth disease cases， 740 （65.84%） tested EV positive. Coxsackievirus A6 （CVA6） and Coxsackievirus A16 （CVA16） were the main two serotypes with regular cycle trends. Of the 137 suspected herpetic angina cases， 88 （64.23%） were EV positive， with Coxsackievirus A4 （CVA4） and CVA16 as the dominant serotypes. Among 428 respiratory infection specimens， 71 （16.59%） were EV positive. Coxsackievirus A4 （CVA4） was the predominant serotype which caused herpetic angina and respiratory infection. The epidemic EV isolates CVA6 from Shenzhen had a close genetic relationship with isolates in China’s mainland. ConclusionThe main serotypes EV CVA6 and CVA16 which caused hand-foot-and-mouth disease exhibit cyclical trends . The risk of EV transmitted from abroad is low， but their genetic variation and virulence change should be monitored continuously. In addition， the monitoring of dominant isolates CVA4 which cause herpetic angina and respiratory infection should be strengthened.

Epidemiological and etiological characteristics of hand-foot-mouth disease in Tongren City from 2018 to 2022 / 中国学校卫生

Objective@#To analyze the epidemiological and etiological characteristics of hand-foot-mouth disease (HFMD) in Tongren City during 2018 to 2022, so as to provide the reference for HFMD effective prevention and control.@*Methods@#Monitoring data on HFMD in Tongren City from 2018 to 2022 was collected from National Infectious Disease Reporting Information Management System. Descriptive epidemiological method was conducted on the data analysis.@*Results@#A total of 14 376 cases of HFMD were reported in Tongren City during 2018 to 2022, the average annual incidence rate of HFMD was 89.43/100 000. Totally 47 severe cases were reported, accounting for 0.33% of the total cases. The incidence rates of HFMD were generally declining trend during 2018 to 2022 (124.68/100 000, 95.37/100 000, 78.50/100 000, 61.63/100 000, 87.80/100 000) ( χ 2 trend =393.05, P <0.01), mainly occurred during April to July (48.13%), among children under 5 years old (95.72%). During 2018 to 2022, a total of 967 laboratory diagnosed cases reported in different years, regions, age groups showed significant differences in pathogen composition ratio ( χ 2=169.62, 456.65 , 167.96, P <0.05). From 2018 to 2022, the dominant pathogen of HFMD was constantly changing. Other enteroviruses were the dominant epidemic strains in 2018 and 2022 (33.04%, 37.62%), CoxA 6 was the dominant epidemic strain in 2019 to 2020 ( 68.75 %, 50.78%), and CoxA16 was the dominant epidemic strain in 2021(43.30%).In 2018, one case was infected with CoxA16 and EV71.The difference of pathogen composition ratio varied in different years ( χ 2=169.62, P <0.01).@*Conclusions@#The prevalence of HFMD in Tongren City has showed a declining trend during 2018 to 2022, and the dominant strain of HFMD has changed in recent years. The pathogen monitoring of HFMD should be strengthened to timely grasp the distribution and changes of pathogens, so as to provide a basis for the precise prevention and control of HFMD.

Epidemiological features of hand, foot, and mouth disease among children under 6 years in Wuxing District / 预防医学

Objective@# To investigate the epidemiological characteristics of hand, foot, and-mouth disease (HFMD) among children under 6 years in Wuxing District, Huzhou City from 2013 to 2021, so as to provide insights into HFMC control among children. @* Methods @#The surveillance on HFMD and enterovirus 71 (EV71) vaccination among children under 6 years in Wuxing District, Huzhou City from 2013 to 2021 were captured from China Disease Prevention and Control Information System, and the temporal, human and spatial distributions of HFMD cases and pathogenic detection results were descriptively analyzed.@*Results @#A total of 14 272 HFMD cases under 6 years were reported in Wuxing District from 2013 to 2021, with an average annual incidence rate of 465.75/104. There were 8 313 male children with HFMD (522.39/104 incidence) and 5 959 female children with HFMD (404.55/104 incidence), and higher incidence of HFMD was seen among male children than among female children (χ2=239.228, P<0.001). Most HFMD cases were found among children at ages of 1 to 3 years (10 006 cases, 70.11%), and the incidence of HFMD peaked during the period between May and July and between October and December each year. High incidence of HFMD was seen in Zhili Township (741.50/104), Yangjiabu Street (546.99/104) and Balidian Township (438.68/104). There were 717 laboratory-confirmed HFMD cases (5.02%), including 106 EV71-positive cases (14.78%) and 177 CoxA16-positive cases (24.69%). A total of 56 288 doses of EV71 vaccines were administered in Wuxing District from 2017 to 2021, with an annual average full-dose vaccination rate of 14.87%. The detection of EV71 infection was significantly lower after EV71 vaccination than before vaccination (4.49% vs. 24.93%; χ2=62.932, P<0.001).@* Conclusions @#The incidence of HFMD peaks in summer and winter among children under 6 years in Wuxing District, which predominantly occurs among children at ages of 1 to 3 years. The incidence of HFMD is high in Zhili Township, Yangjiabu Street and Balidian Township, and the number of EV71-positive cases significantly reduces after EV71 vaccination than before vaccination.

Prevalence trend of hand-foot-mouth disease in children and its correlation with meteorological factors in Kaizhou District, Chongqing in 2018 - 2021 / 公共卫生与预防医学

Objective To analyze the incidence trend of hand-foot-mouth disease (HFMD) and its correlation with meteorological factors in Children in Kaizhou District, Chongqing from 2018 to 2021, and to provide a theoretical basis for the diagnosis and treatment of HFMD in children. Methods The HFMD epidemic information was collected from 2018 to 2021 in Kaizhou District of Chongqing by using the China Disease Surveillance Information and Report Management System. The epidemiological characteristics of HFMD were descriptively analyzed, and the correlation between HFMD incidence and meteorological factors was analyzed by multiple regression. Results A total of 5 121 HFMD cases were reported in Kaizhou District of Chongqing from 2018 to 2021, with an average annual incidence of 143.30/100 000. The incidence of HFMD fluctuated from 120.87/100,000 to 159.78/100,000 from 2018 to 2021, showing a downward trend year by year. There were 2929 males and 2192 females with HFMD. The incidence of HFMD was the highest in early childhood (70.13/100 000), followed by pre-school age (43.06/100 000). There was significant difference in the incidence of HFMD among different age groups (χ2=53.497, P<0.05). The cases were mainly scattered children (3127 cases, 61.06%). The second was nursery children (1627 cases, 31.77%). In addition, there were 289 cases of students (5.64%). There were 1084 laboratory-confirmed cases in Kaizhou District of Chongqing from 2018 to 2021, including 269 (24.82%) children with EV71 infection, 178 (16.42%) children with Cox A16 infection, and 637 (58.76%) children with other enterovirus infections. There were significant differences in pathogen composition among different years (Z=32.75, P<0.05). From 2018 to 2021, the proportion of EV71 increased year by year, while COX16 and other enterovirus infections showed a downward trend year by year. Average daily temperature (OR=1.873) and average daily pressure (OR=-1.498) were independent risk factors for HFMD in Kaizhou District of Chongqing (P<0.05). Conclusion The reported incidence of HFMD in Kaizhou District of Chongqing shows a decreasing trend, and the incidence is closely related to temperature and atmospheric pressure. It is still necessary to strictly implement the prevention and control measures in key population in the season of high incidence. The main virus is EV71, which can be vaccinated with EV71 HFMD vaccine to reduce the occurrence of severe cases.

Spatial epidemiological analysis of severe hand, foot and mouth disease in Guangxi, 2014-2018 / 中国热带医学

@#Abstract: Objective　To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods　Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results　From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions　Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

Epidemiological characteristics of hand, foot and mouth disease in Nanping City, Fujian Province from 2012 to 2021 / 中国热带医学

@#Abstract: Objective　To analyze the epidemic characteristics of hand, foot and mouth disease (HFMD) in Nanping City, Fujian province and to provide the basis for formulating effective prevention and control measures as well as evaluating the efficacy of prevention and treatment. Methods　Descriptive epidemiological method was used to analyze the incidence data of HFMD in Nanping City from 2012 to 2021. Results　A total of 49 231 cases of HFMD were reported in Nanping City from 2012 to 2021. The incidence fluctuated greatly over the 10-year period, ranging from 76.10/100 000 to 308.93/100 000, with an average incidence of 184.99/100 000 per year. The overall incidence and the number of cases showed a fluctuating downward trend over time, but the incidence was high in the next year, and there were statistically significant differences in the incidence rates between different years(χ2=8 169.176, P<0.001). There were significant regional differences in the incidence, the top three average annual incidence rates were: Guanze County (370.76/100 000), Zhenghe County (295.31/100 000) and Wuyishan City (250.31/100 000). There were two peaks of HFMD incidence each year, with the first occurring in May and June and the second occurring in September and October. The incidence rate was higher among males (215.86/100 000) than females (152.93/100 000), and males were more susceptible than females (RR=1.412, 95%CI=1.387-1.438). The cases were mainly aged 0-4 years, accounting for 86.25% (42 461/49 231) of all cases, and the incidence rate gradually decreased with increasing age (χ2trend=570,105.801, P<0.001). The majority of cases (85.22%, 41 953/49 231) occurred in children living in scattered areas, followed by children in kindergartens (12.39%, 6 101/49 231). The etiological results showed a total of 3 476 laboratory-confirmed cases, and the proportion of three (classes) of enterovirus positivity varied each year, with different pathogen compositions showing statistical significance (χ2=584.613, P<0.001). In addition to the years 2015-2017, during which Cox A16 and EV71 were the dominant strains, other years were dominated by other enteroviruses, with EV71 being the main type in severe and fatal cases of HFMD in Nanping City. Conclusion　Nanping City should strengthen health education for children living in the diaspora and in day-care centers, enhance surveillance of epidemics and pathogenology, improve vaccination rates against EV71, focus on the detection and typing of other enteroviruses, and implement effective prevention and control measures for HFMD.

Clinical Characteristics of 131 Children with Hand,Foot,and Mouth Disease Infected with EV71 and Preventive Effect of EV71 Vaccination / 昆明医科大学学报

Objective To analyze the clinical features of children with EV71 positive hand,foot,and mouth disease(HFMD)and EV71 vaccination,and to explore the relationship between the occurrence of severe disease and the preventive effect of EV71 vaccine.Methods From January 1,2020 to December 31,2022,the clinical data of 131 children with HFMD diagnosed with EV71 infection in Kunming Children's Hospital were retrospectively analyzed.The stool samples of patients with clinically confirmed HFMD were selected for enterovirus nucleic acid detection.The clinical data and EV71 vaccination status of children with universal enterovirus positive and EV71 positive HFMD were analyzed.Results Among the 131 positive cases detected,there were 116 mild cases and 15 severe cases.Among the 80 children who received phone consultations about their EV71 vaccine status,17 were vaccinated,and 63 were not vaccinated.The vaccinated children were all mild cases,while among the unvaccinated children,6 were severe cases.From 2020 to 2022,the period from April to September each year is the peak period for detecting EV71-positive hand,foot,and mouth disease(χ2 = 125.705,P = 0.000).The positive detection rate for children under 1 year old and over 5 years old was higher than that for children aged 1 to 5 years(χ2 = 8.765,P = 0.033),and there was no significant difference in the positive detection rate between boys and girls(χ2 = 1.221,P = 0.269).Conclusion EV71 vaccine is of great significance in reducing the occurrence of severe cases.Combined with the current low vaccination rate in Kunming,Yunnan Province,it is suggested that relevant institutions should continue to increase the publicity of EV71 vaccination.

Expression and clinical significance of laboratory of genetics and physiology 2, retinoic acid inducible gene I and melanoma differentiation associated gene 5 in children with hand, foot and mouth disease / 中国小儿急救医学

Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.

Whole-genome sequence analysis of coxsackievirus A10 strains isolated in Jiangsu Province from 2015 to 2022 / 中华微生物学和免疫学杂志

Objective:To analyze the whole-genome sequences of coxsackievirus A10 (CVA10) strains isolated in Jiangsu Province from 2015 to 2022 and their molecular epidemiological characteristics.Methods:Forty-five CVA10 isolates circulating in Jiangsu Province during 2015 to 2022 were selected for whole-genome sequencing. Phylogenetic trees were constructed based on the whole genome, VP1, P1, P2 and P3 sequences of CVA10 strains. Bioinformatics software, including DNAStar, MEGA7.0 and Similarity plots3.5.1, was used for analysis of homology, genetic recombination and major amino acid variation sites.Results:The nucleotide and amino acid sequence homology of the whole-genome sequences of 45 CVA10 strains was 90.3%-99.1% and 97.9%-99.8%, respectively. The nucleotide sequence homology of P1 region was the highest (92.1%-100.0%), while the nucleotide sequence homology of P3 region ranged from 84.7% to 100.0%. In contrast to the diversity of nucleotide sequences, the amino acid sequences of each region were conserved. A phylogenetic analysis based on the complete VP1 sequences of CVA10 strains revealed eight genotypes: A-H. The CVA10 isolates in Jiangsu Province and other prevalent strains in China mainly belonged to genogroup C. Results of the phylogenetic analysis based on the whole-genome sequences and complete VP1 sequences were consistent. Phylogenetic analysis bases on different gene segments and Simplot recombination analysis revealed that Jiangsu isolates GD07/Lianyungang/2017 and N180/Suqian/2016 showed high homology with the CVA10 prototype in the P1 region, but had recombination sites with other strains of enterovirus group A in the P2, P3, 5′-UTR and 3′-UTR regions. Compared with the prototype strain AY421767/Kowalik/2004, the Jiangsu isolates showed frequent variations in the VP1 region and many other major amino acid sites, which might result in some imperceptible changes in capsid structure and potential receptor-binding sites.Conclusions:By analyzing the evolution and genetic recombination features of CVA10 strains at the genome level in Jiangsu Province, this study elucidated the influence of genetic recombination and amino acid site mutation on CVA10 infection, providing basic data for the prevention and control of hand-foot-mouth disease in Jiangsu Province.

Etiological and clinical features of hand, foot and mouth disease caused by coxsackievirus A10 in Qingdao city, 2014—2021 / 中华微生物学和免疫学杂志

Objective:To investigate the molecular features of hand, foot and mouth disease (HFMD) caused by coxsackievirus A10 (CVA10) in Qingdao and analyze the clinical features of mild and severe cases.Methods:A total of 6 677 cases of HFMD routinely monitored by Qingdao Women and Children Hospital from 2014 to 2021 were enrolled. Throat swab samples were collected. Clinical data of these cases were retrospectively analyzed. Virus nucleic acid was extracted from the samples and the serotypes of enteroviruses were identified. The VP1 genes of CVA10 strains were amplified and sequenced. A phylogenetic tree based on the VP1 gene sequences was constructed using MEGA7. 0 software. SPSS23.0 software was used for statistical analysis.Results:There were 285 cases positive for CVA10, including 183 males and 102 females, and children under five years old accounted for 89.8%. Most of CVA10 infection occurred between the months of April to September. The count of white blood cells, the percentage of neutrophils, the concentration of hemoglobin, and the levels of aspartate aminotransferase and alanine transaminase were significantly higher in severe patients than in mild patients. Besides, chest radiography and brain CT revealed more abnormalities in severe patients, and the duration of ECG monitoring was longer in them. Compared with mild cases, severe cases developed rash early than fever with rash mostly on buttocks ( P<0.05). Phylogenetic analysis showed that most of the CVA10 strains circulating in Qingdao between 2014 and 2021 belonged to clade Ⅰ, and there were two variations A23V and I283V in the amino acid sequence of clade Ⅰ. Conclusions:This study showed that children of all ages were susceptible to CVA10, especially those under five years old. CVA10 showed complex and diverse epidemic trends in different regions and years.

School outbreak of hand, foot and mouth disease in Northern Luzon, Philippines, October 2022

@#Objective: On 24 September 2022, the Regional Public Health Unit in Ilocos received a report of a cluster of suspected hand, foot and mouth disease (HFMD) in one school in Balungao, Pangasinan Province, the Philippines. On 4 October 2022, the public health unit sent a team from the Field Epidemiology Training Program – Intermediate Course to conduct an outbreak investigation. Methods: Active case-finding was conducted at the school. A suspected case was defined as any student or staff member with mouth ulcers and papulovesicular or maculopapular rash on the palms, fingers, soles of the feet or buttocks occurring from 1 September to 5 October 2022. We interviewed school officials about possible sources of infection and students’ activities. We collected oropharyngeal swab samples for testing. Findings were used for descriptive analysis. Results: Nine suspected cases of HFMD were detected, with the highest number of cases (6, 67%) occurring in children in grade 1. The majority of cases (7, 78%) were 6 years old, and five cases (56%) were male. Seven (78%) of the cases had been exposed to a confirmed case of HFMD, as reported by their parents or guardians and teachers. Six cases (67%) were positive for coxsackievirus A16 and two (22%) for enterovirus. Discussion: The causative agents of this outbreak were coxsackievirus A16 and other enteroviruses. Direct contact with a confirmed case was the source of transmission, with a lack of physical distancing in classrooms likely contributing to transmission. We recommended that the local government implement measures to control the outbreak.

Serotype detection and phylogenetic analysis of coxsackievirus A2 causing hand, foot and mouth disease in Yunnan Province in 2021 / 中华微生物学和免疫学杂志

Objective:To analyze the non-enterovirus A71 (non-EVA71) and non-coxsackievirus A16 (non-CVA16) enteroviruses causing hand, foot and mouth disease (HFMD) in Kunming and Qujing of Yunnan Province in 2021 by sequencing the VP4/VP2 and VP1 genes and to analyze the phylogenetic characteristics of the VP1 gene of CVA2, aiming to provide reference for the prevention and control of CVA2.Methods:The samples were made and extracted strictly according to the Laboratory Manual for Hand, Foot and Mouth Disease (China Center for Disease Control and Prevention, 2018 Edition). VP4/VP2 junction regions were firstly amplified and sequenced by MD91/OL68-1 primers. These sequences were firstly edited and then "blasted" on the GenBank to determine the virus serotype. To analyze the phylogenetic characteristics of CVA2, the entire VP1 gene sequences were amplified in two segments using enterovirus species A primers. Virus serotype was again confirmed online by "Enterovirus Genotyping Tool Version 0.1". The sequences of the reference virus genotypes/sub-genotypes were downloaded according to the reference. The phylogenetic trees were constructed by Mega5.2 software and the genetic characteristics were analyzed.Results:A total of 749 non-EVA71 and non-CVA16 enteroviruses were detected in the two areas in 2021. Group A enteroviruses were the main pathogens, with CVA16 as the predominant virus, and a small number of group B enteroviruses were reported. Only five strains of CVA2 were detected with a detection rate of 0.67% (5/749), indicating that CVA2 was a rare pathogen for HFMD in the two areas. The sequencing and serotyping results were consistent using the two genomic regions of VP4/VP2 junction region and VP1 region. Phylogenetic analysis showed that three Kunming strains belonged to genotype A, while two Qujing strains belonged to genotype D.Conclusions:The detection rate of CVA2 in Kunming and Qujing was 0.67% in 2021. CVA2 was a rare pathogen for HFMD in the two regions. Phylogenetic analysis showed genotypes A and D spread in Kunming and Qujing, respectively, but had not caused epidemics. To our knowledge, this was the first report of genotype A of CVA2 in China. Strengthening the laboratory surveillance especially molecular epidemiological surveillance is valuable for the monitor and analysis of transmission source for CVA2.

Etiological characteristics of hand, foot and mouth disease in Xi′an from 2019 to 2021 / 中华微生物学和免疫学杂志

Objective:To analyze the etiological and epidemiological characteristics of hand, foot and mouth disease (HFMD) in Xi′an from 2019 to 2021, so as to provide evidence for the prevention and control of HFMD.Methods:Stool specimens and anal swabs were collected from patients with HFMD. Enteroviruses (EVs) including enterovirus 71 (EV71), coxsackievirus A16 (CVA16), CVA6 and CVA10 were detected by RT-PCR. Excel 2007 and SPSS18.0 software were used for data collection and statistical analysis, respectively. The epidemiological data of HFMD cases were analyzed by descriptive epidemiology method. The VP1 gene sequence of the representative strain of each CVA6 genotype was downloaded. Phylogenetic trees were constructed using MEGA X software and the genetic characteristics were analyzed.Results:A total of 1 531 HFMD cases were involved and 1 365 were positive for EVs with a positive rate of 89.16%. The detection rates of EV71, CVA16, CVA6, CVA10 and other EVs were 1.31% (20/1 531), 32.46% (497/1 531), 38.47% (589/1 531), 5.09% (78/1 531) and 11.23% (172/1 531), respectively. There were significant differences in the pathogen composition in HFMD cases of different clinical types (χ 2=46.14, P<0.01) and occupations (χ 2=34.65, P<0.01) as well as in different years (χ 2=462.86, P<0.01). The average age was greater in patients with CVA16 infection than in those with CVA6 or CVA10 infection ( F=6.00, P<0.01). In 2019, the HFMD cases were mainly caused by CVA16, while in 2020 and 2021, the main pathogen was CVA6. Enterovirus-positive cases showed a bimodal distribution with the main peak from May to July and the secondary peak from September to November. CVA16 was the predominant pathogen in spring and summer, and CVA6 was the predominant pathogen in autumn. CVA6 was the dominant pathogen in eight districts and counties of Xi′an; CVA16 was the dominant pathogen in six districts and counties; CVA6 and CVA16 co-circulated in one district. The CVA6 isolates belonged to two evolutionary branches of D3a subtype. Conclusions:CVA6 and CVA16 were the prevalent pathogens of HFMD and CVA6 subtype D3a circulated in Xi′an from 2019 to 2021. The pathogen composition of HFMD cases showed obvious differences in population, time and regional distribution.

Bioinformatics analysis of VP1 of Coxsackievirus A10 / 公共卫生与预防医学

Objective To predict and analyze the physicochemical properties, structural characteristics, and antigenic epitopes of viral protein (VP) VP1 of Coxsackievirus A10 (CV-A10) by bioinformatics methods. Methods The physicochemical properties and structural characteristics of CV-A10 VP1 were predicted by ProtParam, SOPMA, SWISS-MODEL, PDBsum, and ProSA-web. The antigenic epitopes of CV-A10 VP1 were predicted and analyzed by DNAstar, ABCpred, Bepipred 2.0, ElliPro, DiscoTope-2.0, NetMHCpan-4.1, NetMHCIIpan-4.0, Consurf, VaxiJen v.2.0, AllerTOP v.2.0, ToxinPred2, and IEDB immunogenicity. Results Bioinformatics analysis showed that CV-A10 VP1 was a basic, unstable, and hydrophilic protein, of which the secondary structure mainly consisted of random coil. The analysis revealed that CV-A10 VP1 had multiple potential B and T cell antigenic epitopes as well as a dominant antigenic epitope based on the potential epitope. Conclusion CV-A10 VP1 has multiple potential sites that induce specific humoral and cellular immunity, providing important support for its experimental identification, molecular epidemiological studies, and vaccine development.