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.

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.

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.

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.

Tratamento de manifestação bucal exacerbada da doença de mão, pé e boca com apdt / Exacerbated oral manifestations of hand, foot and mouth disease: case report / Manifestaciones orales exacerbadas de la enfermedad de manos, pies y boca: reporte de un caso

Introdução: A doença da mão, pé e boca (DMPB) é uma infecção viral contagiosa que afeta principalmente crianças, mas também pode afetar adultos. É causada por diferentes tipos de enterovírus, sendo o CV-A16 e o EV-A71 os mais comuns. A transmissão ocorre pelo contato direto com fluidos corporais infectados ou por meio de objetos contaminados. Apresenta sintomas como febre, dor de garganta, falta de apetite e erupções cutâneas nas mãos, pés e boca. Embora a maioria dos casos seja leve e resolva- se espontaneamente, complicações graves, incluindo problemas neurológicos, podem ocorrer. O diagnóstico geralmente é clínico, com base nos sintomas e nas características das lesões. O tratamento é sintomático, com o uso de analgésicos e antitérmicos para aliviar a dor e a febre. No caso de lesões bucais graves a terapia fotodinâmica antimicrobiana (aPDT) em combinação com a fotobiomodulação com laser de baixa potência tem sido utilizada como uma abordagem promissora. A aPDT é capaz de eliminar microrganismos, incluindo vírus, independentemente de sua resistência aos antimicrobianos, e a fotobiomodulação auxilia na modulação da resposta inflamatória, alívio da dor e na cicatrização. Os lasers de baixa potência são a fonte de luz mais adequada para a fotoinativação viral, devido à sua interação precisa com o fotossensibilizante e a capacidade de fornecer a energia necessária para o efeito virucida. Metodologia: Relato de caso qualitativo e descritivo. Objetivo: Este relato de caso tem como objetivo descrever o tratamento de lesões bucais graves da DMPB combinando aPDT e fotobiomodulação com laser de baixa potência. Resultados: O tratamento mostrou resultados promissores no alívio dos sintomas e na melhora do quadro clínico. Conclusão: Mesmo em manifestações exacerbadas da doença de mão, pé e boca, podemos notar melhoras significativas nas lesões bucais após a aPDT com azul de metileno em combinação com a fotobiomodulação com laser de baixa potência.

Introduction: Hand, foot and mouth disease (HFMD) is a contagious viral infection that mainly affects children, but can also affect adults. It is caused by different types of enterovirus, with CV-A16 and EV-A71 being the most common. Transmission occurs through direct contact with infected body fluids or through contaminated objects. Symptoms include fever, sore throat, lack of appetite and rashes on the hands, feet and mouth. Although most cases are mild and resolve spontaneously, serious complications, including neurological problems, can occur. Diagnosis is usually clinical, based on the symptoms and characteristics of the lesions. Treatment is symptomatic, with the use of analgesics and antipyretics to relieve pain and fever. In the case of severe mouth lesions, antimicrobial photodynamic therapy (aPDT) in combination with low-power laser photobiomodulation has been used as a promising approach. aPDT is capable of eliminating microorganisms, including viruses, regardless of their resistance to antimicrobials, and photobiomodulation helps to modulate the inflammatory response, relieve pain and promote healing. Low-power lasers are the most suitable light source for viral photoinactivation, due to their precise interaction with the photosensitizer and their ability to provide the necessary energy for the virucidal effect. Methodology: Qualitative and descriptive case report. Objetive: This case report aims to describe the treatment of severe oral lesions of BPPD by combining aPDT and low-power laser photobiomodulation. Results: The treatment showed promising results in relieving symptoms and improving the clinical picture. Conclusion: Even in exacerbated manifestations of hand, foot and mouth disease, we can see significant improvements in mouth lesions after aPDT with methylene blue in combination with low-power laser photobiomodulation.

Introducción: La enfermedad de manos, pies y boca (EMPB) es una infección vírica contagiosa que afecta principalmente a los niños, aunque también puede afectar a los adultos. Está causada por diferentes tipos de enterovirus, siendo el CV-A16 y el EV-A71 los más comunes. La transmisión se produce por contacto directo con fluidos corporales infectados o a través de objetos contaminados. Los síntomas incluyen fiebre, dolor de garganta, falta de apetito y erupciones en manos, pies y boca. Aunque la mayoría de los casos son leves y se resuelven espontáneamente, pueden producirse complicaciones graves, incluidos problemas neurológicos. El diagnóstico suele ser clínico, basado en los síntomas y las características de las lesiones. El tratamiento es sintomático, con el uso de analgésicos y antipiréticos para aliviar el dolor y la fiebre. En el caso de lesiones bucales graves, la terapia fotodinámica antimicrobiana (aPDT) en combinación con la fotobiomodulación láser de baja potencia se ha utilizado como un enfoque prometedor. La aPDT es capaz de eliminar los microorganismos, incluidos los virus, independientemente de su resistencia a los antimicrobianos, y la fotobiomodulación ayuda a modular la respuesta inflamatoria, aliviar el dolor y favorecer la cicatrización. Los láseres de baja potencia son la fuente de luz más adecuada para la fotoinactivación viral, debido a su interacción precisa con el fotosensibilizador y a su capacidad para proporcionar la energía necesaria para el efecto virucida. Metodología: Caso clínico cualitativo y descriptivo. Objetivo: Este caso clínico pretende describir el tratamiento de lesiones orales severas de BPPD mediante la combinación de aPDT y fotobiomodulación con láser de baja potencia. Resultados: El tratamiento mostró resultados prometedores en el alivio de los síntomas y la mejora del cuadro clínico. Conclusión: Incluso en las manifestaciones exacerbadas de la enfermedad de manos, pies y boca, podemos observar mejoras significativas en las lesiones bucales tras la aPDT con azul de metileno en combinación con fotobiomodulación con láser de baja potencia.

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.

Etiologic analysis of hand, foot, and mouth disease in a sentinel surveillance hospital in Guangzhou City in 2017-2021 / 公共卫生与预防医学

Objective To investigate etiologic characteristics of hand, foot, and mouth disease (HFMD) in a sentinel hospital in Guangzhou from 2017 to 2021, and to provide a scientific basis for the prevention and control of HFMD. Methods Descriptive epidemiologic methods were used to analyze the etiologic characteristics of mild cases of HMFD during 2017-2021. Results A total of 1 633 specimens of mild cases of HMFD were collected from 2017 to 2021. The total enterovirus (EV) positive rate was 78.41%, among which the positive rates of the main pathogen Cox A6, Cox A16, Cox A10, and EV71 were 40.83%, 17.68%, 6.13%, and 1.62%, respectively. The total positive rate of enteroviruses and the positive rate of enteroviruses of all types in each year were statistically different (P<0.001). In 2017-2021, the prevalence of HFMD in Guangzhou was mainly Cox A6, followed by Cox A16 which had the highest positive rate in 2018 (24.62%). The positive rate of EV71 decreased year by year. Cox A6 was highly prevalent from June to December every year, while the detection rate of Cox A16 was high from April to August every year. The positive detection rate of EV71 was high from January to May in 2017 and low from 2018 to 2021, with no epidemic peak. Conclusion From 2017 to 2021, the main pathogen of HMFD in Guangzhou is Cox A6, not EV71 or CoxA16, which suggests that it is of great significance to strengthen the monitoring of epidemic trend of HFMD for the prevention and control of HFMD.

Study on the effect of temperature on the risk of hand, foot and mouth disease in Chengdu / 公共卫生与预防医学

Objective To explore the effect of temperature on the risk of hand-foot-and-mouth disease (HFMD) and population susceptibility. Methods The data of HFMD cases in Chengdu from January 1, 2016 to October 31, 2022 were collected, and local meteorological data during the same period were also collected. Distributional lag nonlinear models were developed. The relative risk (RR) of morbidity at different temperatures and different lags was calculated. Differences in the relative risk levels of different populations were analyzed and compared. Results A total of 263 776 cases of HFDM were reported in Chengdu during the study period. The distribution of HFMD was periodic. For the overall population, the short-term average temperature and RR showed a “U”-shaped relationship. When the lag time was 0-7 days, the cumulative RR was 1.59 (95%CI: 1.18-2.14) at the average temperature of -0.5℃ and 2.16 (95%CI: 1.60-2.91) at the average temperature of 34.5℃. The RR values under high and low temperatures decreased with increasing lag period. When the lag time was extended, the average temperature and RR showed an inverted “U”-shaped relationship, with higher RR at moderate temperatures and increasing as the lag period increased. The results of the subgroups showed that the RR of onset among scattered children was higher at high and low temperatures. Conclusion The risk effect of temperature on the onset of HFMD in different populations is variable and changes with the lag period, and the prevention and control measures should be adjusted in a timely and targeted manner.

Epidemiological characteristics of hand, foot and mouth disease clusters in kindergartens and schools in Jinshan District / 预防医学

Objective@#To investigate the epidemiological characteristics of clusters of hand, foot and mouth disease (HFMD) in kindergartens and schools in Jinshan District, Shanghai Municipality from 2016 to 2021, so as to provide insights into improving the prevention and control measurements of HFMD in Jinshan District.@*Methods@#Data of HFMD cases in Jinshan District from 2016 to 2021 were collected through Chinese Disease Prevention and Control Information System, and data pertaining to HFMD clusters in kindergartens and schools were also collected. The scale, temporal distribution, regional distribution and distribution of cluster places were descriptively analyzed. @*Results@#Totally 338 HFMD clusters involving 974 cases were identified in kindergartens and schools in Jinshan District from 2016 to 2021, with an average attack rate of 9.89%. The number of cases in each cluster ranged from 2 to 12 cases, with a median number of 2 (interquartile range, 1) cases, and there were 223 clusters involving 2 cases, accounting for 65.98%. The duration of clusters ranged from 1 to 16 days, with a median duration of 4 (interquartile range, 3) days. HFMD peaked from April to June (136 clusters, 40.24%) and from September to December (176 clusters, 52.07%). All the 11 streets and towns (high-tech zones) were reported HFMD clusters, and the three largest number of clusters were reported in Zhujing Town (72 clusters, 21.30%), Shanyang Town (63 clusters, 18.64%) and Tinglin Town (40 clusters, 11.83%). There were 268 HFMD clusters in kindergartens (79.29%) and 70 in schools (20.71%), and the prevalence of HFMD clusters was higher in kindergartens than in schools (35.51% vs. 17.03%; χ2=31.507, P<0.001). @*Conclusions@#HFMD clusters in kindergartens and schools showed seasonal characteristics from 2016 to 2021 in Jinshan District, which predominantly occurred in Zhujing Town, Shanyang Town and Tinglin Town, and kindergartens were the main places.

Coverage of enterovirus 71 vaccine among children born between 2018 and 2021 in Ningbo City / 预防医学

Objective@# To investigate the coverage of enterovirus 71 (EV71) vaccine among children born between 2018 and 2021 in Ningbo City, Zhejiang Province, so as to provide insights into formulating EV71 vaccination strategy.@*Methods@#Data pertaining to demography and EV71 vaccination among children born between 2018 and 2021 in Ningbo City were obtained from the Zhejiang Immunization Information Management System, and the coverage of vaccination, full-dose vaccination and timely vaccination of EV71 vaccine were analyzed. @*Results@#Totally 416 176 children were born between 2018 and 2021, including 216 977 boys (52.14%) and 199 199 girls (47.86%). The coverage rates of vaccination, full-dose vaccination and timely vaccination was 61.50%, 58.70% and 32.53%, respectively. The coverage rates of vaccination, full-dose vaccination and timely vaccination among local children (71.43%, 70.04% and 40.24%) were higher than those among migrant children (54.05%, 50.18% and 26.73%; P<0.05). The coverage rates of vaccination, full-dose vaccination and timely vaccination among urban children (67.72%, 65.06% and 40.37%) were higher than those among rural children (54.11%, 51.14% and 23.21%; P<0.05). The coverage rates of vaccination were 54.98%, 61.24%, 65.10% and 66.72%, the coverage rates of full-dose vaccination were 52.16%, 58.72%, 62.44% and 63.39%, and the coverage rates of timely vaccination were 22.47%, 25.86%, 39.14% and 48.03% by the born year from 2018 to 2021, all showing increasing trends year by year (P<0.05). @*Conclusion@#The coverage of vaccination, full-dose vaccination and timely vaccination of EV71 vaccine appears a tendency towards a rise among the 2018-2021 birth cohorts in Ningbo City, while the coverage of timely vaccination need to be improved. Health education for EV71 vaccination should be enhanced for rural and migrant children.

Complete genome comparative analysis of Coxsackievirus A6 causing hand,foot and mouth disease and herpangina in Yunnan Province in 2018 / 中国生物制品学杂志

@#ObjectiveTo analyze the genome-wide characteristics of 17 strains of Coxsackievirus A6(CVA6)that cause hand,foot and mouth disease(HFMD)and herpangina(HA)in Yunnan Province in 2018,and understand the genetic differences between different pathogenic CVA6.MethodsA total of 1 909 stool samples clinically diagnosed as HFMD and HA in Kunming Children′s Hospital in 2018 were randomly selected for detection using enterovirus group A universal primers and screening of CVA6 positive samples. The CVA6 whole genome sequence was amplified with CVA6 whole genome primers,spliced by BioEdit splicting software,and analyzed for the whole genome characteristics by BioEdit,MEGA 7.0,Simplot,Heml 1.0 and Phyre2softwares.ResultsA total of 929 CVA6 positive samples were screened,and 17CVA6 complete gene sequences were obtained(9 of which were clinically diagnosed as HFMD and 8 were clinically diagnosed as HA). All 17 CVA6 strains were in type IV clade on the whole phylogenetic tree. No significant recombination occurred in HA and HFMD representative strains,while mutations occurred in non-structural protein 3D region. HFMD and HA representative strains showed differences in VP1 loci S597T,Q705L and Q663L. Online predictive analysis showed that the secondary structure of VP1 was consistent with that of CVA6 with no change.ConclusionThe 17 CVA6 strains causing HFMD and HA had high genomic homology,as well as nucleotide and amino acid differences,which may affect the replication and adaptability of CVA6.

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.

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.

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.

Epidemiological characteristics of hand, foot and mouth disease in Zhejiang Province from 2016 to 2019 / 预防医学

Objective@#To investigate the epidemiological characteristics of hand, foot and mouth disease ( HFMD ) in Zhejiang Province, so as to provide insights into HFMD control.@*Methods@#The incidence of HFMD in Zhejiang Province from 2016 to 2019 was collected from National Notifiable Disease Reporting System. The temporal distribution, human distribution, regional distribution and pathogenic typing of HFMD were descriptively analyzed in Zhejiang Province from 2016 to 2019.@*Results@#Totally 642 305 cases with HFMD were reported in Zhejiang Province from 2016 to 2019, including 121 severe cases and 9 fatal cases. The annual incidence of HFMD was 335.88/105, 147.76/105, 435.63/105 and 221.77/105, respectively. The incidence of HFMD peaked from May to July each year, and the three highest annual incidence included Ningbo, Jinhua and Wenzhou cities, while the lowest annual incidence was seen in Zhoushan City. The HFMD cases were predominantly found in children at ages of 1 to 5 years ( 537 738 cases, 83.72% ), and in children living at home ( 419 408 cases, 65.30% ). The average annual incidence of HFMD was higher in males than in females ( 328.23/105 vs. 239.99/105; P<0.05). The dominant pathogens gradually shifted from enterovirus 71 ( EV71 ) to Coxsachievirus A16 ( CA16 ), and other enteroviruses remained as the main pathogenic subtypes.@*Conclusions@#The incidence HFMD was high in summer and autumn in Zhejiang Province from 2016 to 2019. Children living at home are at a high risk of HFMD, and CA16 type gradually became the dominant pathogen of HFMD.

The Prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease / 预防医学

Objective@#To establish a prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease, so as to provide insights into analyses of communicable disease epidemics with limited or missing surveillance data.@*Methods@#The incidence of hand, foot and mouth disease in Zhejiang Province during the period from the first week of 2015 through the 39th week of 2021 was retrieved from the China Information System for Disease Control and Prevention, and the Baidu index of hand, foot and mouth disease and herpangina was collected via the Baidu search engine during the same period. The correlation between the Baidu index and time series of hand, foot and mouth disease was examined using wavelet analysis. In addition, a random forest training model was created based on the Baidu index and incidence of hand, foot and mouth disease, and the fitting effectiveness was evaluated using the mean percentage error, while the Baidu index of herpangina was included in the model to predict the epidemic trend of herpangina during the study period.@*Results@#The Baidu index of herpangina and hand, foot and mouth disease, and the Baidu index and incidence of hand, foot and mouth disease all appeared two peaks at the 26th and 52th week. The phase difference was less than 0.1 week between the Baidu index and time series of hand, foot and mouth disease, and the mean percentage error of the training model was 13.07%, with high concordance between the predicted number and actual report number of cases with hand, foot and mouth disease. The numbers of herpangina cases were predicted to be 28 822, 27 341, 28 422, 51 782, 52 457 and 5 691 from 2015 to 2020, and there were totally 48 702 herpangina cases reported until the 39th week of 2021. Like hand, foot and mouth disease, the incidence of herpangina peaked between May and July.@*Conclusion@#The random forest training model based on the Baidu index and incidence of hand, foot and mouth disease is feasible to predict the epidemic trend of herpangina.

Relationship between the expression of peripheral blood stimulating molecules CD80, CD86 and the therapeutic effects of children with severe hand, foot, and mouth dise / 中国热带医学

@#Abstract: Objective　To observe the expression of peripheral blood stimulating molecules CD80 and CD86 in children with severe hand, foot, and mouth disease (HFMD), and to analyze the relationship between them and the therapeutic effects of children. Methods　The clinical data of 252 children with severe HFMD treated in Wuhan Hospital of Traditional Chinese Medicine from March 2017 to March 2021 were collected retrospectively. All children were treated with standardized treatment and the therapeutic effects was evaluated. The baseline data and laboratory test results of children were recorded, and the positive rates of CD80 and CD86 cells in peripheral blood were detected by flow cytometry. Logistic regression was used to analyze the relationship between the above indexes and the therapeutic effects of children. The receiver operating curve (ROC) was drawn to evaluate the value of the above indicators in predicting the therapeutic effects of children. Results　After standardized treatment, 48 children were ineffective, and 204 children were effective; the levels of serum CD80 [(2.28±0.84)% vs (2.12±0.33 )%] and CD86 [(3.35±0.96)% vs (2.23±0.41)%] in children were significantly lower than those at admission (t=2.851, 16.991; P<0.05). The levels of blood lactic acid, serum C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), CD80 and CD86 at admission in the ineffective group were significantly higher than those of the effective group (P<0.05). Logistic regression analysis showed that the overexpression of serum CRP (OR=10.929), MMP-9 (OR=1.926), CD80 (OR=3.943) and CD86 (OR=1.947) at admission might be the risk factors of ineffective (all P<0.05). The results of the goodness of fit test for the model showed that, the goodness of fit was high (χ2=6.245, P=0.620); the model collinearity results showed that the variance inflation factors (VIF) values of each variable were <2, and there was no collinearity among the main indicators; the results of the individual independence test for the model showed that Durbin-Watson statistics (D-W)=0.279 and there was poor mutual independence among main indicators. ROC curve analysis showed that the area under the curve(AUC) of serum CD80 at admission in predicting the therapeutic effects of children was 0.762, the cut-off value was 2.390%, and the specificity, sensitivity and Youden index were 0.598, 0792 and 0.390 respectively; the AUC predicted by CD86 was 0.739, the cut-off value was 3.280%, and the specificity, sensitivity and Youden index were 0.510, 0.896 and 0.406 respectively; the AUC by combined prediction was 0.823, and the specificity, sensitivity and Youden index were 0.696, 0.833 and 0.529 respectively. Conclusions　Peripheral blood stimulating molecules CD80 and CD86 are involved in the progression of HFMD. Their overexpression may suggest a high risk of treatment ineffectiveness in children with severe HFMD. Early dynamic monitoring of the expression of serum CD80 and CD86 has a certain predictive value for the therapeutic effect of children.

Expression and clinical significance of vitamin D receptor in children with hand, foot and mouth disease / 中国小儿急救医学

Objective:To detect the expression level of vitamin D receptor(VDR) in children with hand, foot, and mouth disease(HFMD), and explore its potential value in the diagnosis and treatment of children with HFMD.Methods:A total of 82 children with HFMD hospitalized in the Second Affiliated Hospital of Xi′an Jiaotong University and Xi′an Children′s Hospital from May 2017 to May 2019 were selected as the case group.At the same time, 42 healthy children who underwent physical examination in the Child Health Department during the same period were randomly selected as the control group.Peripheral blood of two groups of children was extracted to detect and compare the expression levels of VDR mRNA in mononuclear cells, and the correlation between the expression level of VDR and HFMD and the correlation with various clinical characteristics were analyzed.Results:The relative expression of VDR in children with EV71 HFMD was 2.03%±0.38%, which was lower than that in children of control group(3.11%±1.29%), and the difference was statistically significant( t=-3.586, P=0.001). However, the relative expression of VDR in children with CA16 HFMD was 3.69%±1.79%, which was higher than that in children of control group, and the difference was not statistically significant( t=1.043, P=0.305). Among children with EV71 HFMD, the relative expression level of VDR was significantly different between the mild group and the severe group(2.18%±0.44% vs. 1.84%±0.17%, t=2.199, P= 0.041). There was no statistical difference regarding the relative expression level of VDR between mild and severe CA16 HFMD(4.16%±1.73% vs. 2.93%±1.73%, t=1.587, P=0.129). Conclusion:Compared with healthy children, the expression level of VDR is significantly lower in children with EV71 HFMD, and may be related to the severity of EV71 HFMD.

Changes and clinical significance of autophagy-related proteins Beclin-1 and cytochromes C in patients with hand, foot and mouth disease / 中华微生物学和免疫学杂志

Objective:To investigate the expression and clinical significance of Beclin-1 and cytochromes C (CytC) in patients with hand, foot and mouth disease (HFMD).Methods:Sixty children with HFMD were classified into two groups of severe group and common group with 30 cases in each group. Another thirty children who underwent circumcision and had no underlying disease were selected as control group. Serum Beclin-1, CytC and S100B levels were detected before and after treatment. The levels of Beclin-1 and CytC in cerebrospinal fluid (CSF) of children with severe HFMD were detected before and after treatment. Receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of Beclin-1 and CytC for the severity of HFMD.Results:Serum Beclin-1 and CytC levels in the severe group were higher than those in the other two groups ( P<0.01), and the common group showed significantly increased serum Beclin-1 and CytC levels as compared with the control group ( P<0.01). After treatment, the serum Beclin-1 and CytC levels decreased in both severe and common groups ( P<0.05). Compared with the common group, the severe group had remarkable increases in the levels of Beclin-1 and CytC in CSF ( P<0.01), which decreased significantly after treatment ( P<0.01). Serum Beclin-1 and CytC levels were positively correlated with the level of S100B protein. In the prediction of severe HFMD, serum CytC had the highest Youden value of 0.533 at the cut-off value of 38.785 ng/ml with a sensitivity of 56.67% and a specificity of 96.67%; serum Beclin-1 had the highest Youden value of 0.467 at the cut-off value of 6.560 ng/ml with a sensitivity of 46.67% and a specificity of 100.00%. Combined measurements of these two parameters had the highest predictive value for severe HFMD with a sensitivity of 76.67% and a specificity of 96.67%. Conclusions:Serum Beclin-1 and CytC levels were conducive to predict the severity and treatment outcomes of HFMD. Combined measurements of these two parameters had a higher predictive value for severe HFMD.

Pathogen surveillance and genetic characteristics of coxsackievirus A6 and A16 in children with hand, foot and mouth disease in Wenshan Prefecture of Yunnan Province, 2020 / 中华微生物学和免疫学杂志

Objective:To analyze the etiological characteristics of hand, foot and mouth disease (HFMD) cases and to investigate the genetic characteristics of VP1 region of coxsackievirus A6 (CVA6) and CVA16 strains in Wenshan prefecture of Yunnan Province in 2020.Methods:Virus RNA was extracted directly from stool samples of children with HFMD in Wenshan prefecture of Yunnan Province in 2020. Enterovirus (EV) VP4/VP2 junction region was amplified using MD91/OL68-1 primers and sequenced, and then the serotypes of EV isolates were preliminarily identified. Amplification and sequencing of the complete VP1 gene were performed. A phylogenetic tree was constructed by MEGA 5.2 software with the reference strains from GenBank. Genetic and molecular epidemiological characteristics of CVA6 and CVA16 were analyzed.Results:Thirty-two strains of EV and one strain of astrovirus MLB1 were detected in 317 specimens with an overall virus detection rate of 10.41% (33/317). Among the 32 EV strains, 31 (96.88%) were enterovirus species A (EVA) and one (3.12%) was EVB. EVC and EVD were not detected. CVA6 was the predominant EV, accounting for 62.50% (20/32), followed by CVA16 (18.75%, 6/32), CVA4 (9.37%, 3/32) and CVA10 (3.12%, 1/32). EVA71 was not detected. The phylogenetic analysis showed 20 CVA6 strains belonged to D3a sub-genotype and could be further divided into three clusters. Six CVA16 strains belonged to B1a sub-genotype, which was one of the predominant genotypes circulating in China, and could be divided into two clusters.Conclusions:The detection rate of pathogens causing HFMD in Wenshan prefecture in 2020 was 10.41% and the most common etiologic agents were CVA6 and CVA16. Based on the genetic analysis of the VP1 gene, the predominant genotype circulating in Wenshan prefecture in 2020 was CVA6 D3a sub-genotype, followed by CVA16 B1a sub-genotype. EVA71 was not detected.