To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 (El9) isolates collected from an outbreak associated with hand, foot and mouth disease (HFMD) in Tai'an city of Sha...To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 (El9) isolates collected from an outbreak associated with hand, foot and mouth disease (HFMD) in Tai'an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid (VP1) genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions (5′-UTR). Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.展开更多
Hand, foot, and mouth disease (HFMD) is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontan...Hand, foot, and mouth disease (HFMD) is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,展开更多
Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explo...Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explored. Methods Total of 2 325 cases with HFMD were recorded by distributing them into exterior syndrome stage, interior syndrome stage, severe syndrome stage and recovered syndrome stage, respectively, and the main symptoms and subsidiary symptoms of different stages of HFMD have been observed. The major and minor pathogenesis of HFMD in different stages were obtained, and compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD". Results It was found that the major pathogenesis of exterior stage was defined as "the invation of the wenevil to the defender of the body with the collaterals got involved ", and the minor as "qi deficiency"; in interior stage, "the fury of Gan-Yang" was the main pathogenesis, and "qi in chaos and qi deficiency" was the minor; in severe syndrome stage, "the damage of heart, liver and lung" was the main pathogenesis, and "qi in chaos" was the minor; and the pathogenesis of recovered stage was "qi-yin deficiency". Compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD", it showed that "the obstruction of the fei-pi qi by the mixture of shi-re evil" and "the mixture of shi-re" in vivo was quite difficult to be explained in completely different context in the general situation; in the severe stage, the TCM clinical characteristics of syndrome differentiation might lose; in the early acute severe cases, the phenomenon that xin-yang and fei-qi almost ran out was difficult to be observed, then, the line between the severe and the acute severe became vague.Conclusions The theory of syndrome differentiation by stages of HFMD was reasonable in the actual situation of clinical description on HFMD which was expected to be further tested and widely applied in the "zheng" differentiation-treatment of HFMD in the future.展开更多
In recent years,the number of hand,foot,and mouth disease(HFMD)cases in China has continued to grow,and the disease has become a serious public health issue.Xinjiang Uygur Autonomous Region is located in the arid area...In recent years,the number of hand,foot,and mouth disease(HFMD)cases in China has continued to grow,and the disease has become a serious public health issue.Xinjiang Uygur Autonomous Region is located in the arid areas of Northwest China,where the epidemiological trend of HFMD is gradually increasing and characterized by geographical heterogeneity.In this study,based on the HFMD case data in all counties and cities in Xinjiang,we employed statistical and GIS spatial analyses,and geographic probe models to characterize the spatiotemporal differentiation of HFMD epidemics in Xinjiang during the period of 2009–2018,and quantitatively analyzed the factors influencing the spatial differentiation of HFMD epidemics.The results showed that HFMD incidence rate in Xinjiang had non-stationary temporal characteristics on the interannual and monthly scales,and the monthly variation characteristics of HFMD epidemic were quite different in southern and northern Xinjiang.The spatial distribution characteristics of HFMD epidemics showed a north–south spatial differentiation pattern with the Tianshan Mountains as the boundary;cold spot and hot spot of HFMD epidemics in Xinjiang have shifted from scattered to concentrated,and the spatial differentiation pattern had gradually stabilized.Moreover,the dominant factors influencing the spatial differentiation of HFMD epidemics in Xinjiang were socioeconomic factors,such as per capita GDP and urbanization rate,while the basic factors affecting its spatial differentiation were natural environmental factors.The spatial differentiation and evolution patterns of HFMD epidemics differed between northern and southern Xinjiang.Specifically,the leading role of socioeconomic factors is more obvious in southern Xinjiang than in northern Xinjiang,while natural environmental factors(e.g.,dryness and relative humidity)contribute to the prevalence of HFMD epidemics in northern Xinjiang,and the perturbing effect of these factors was more prominent than other factors.The results of this study can provide a scientific basis for the prevention of HFMD epidemics and early warning of HFMD epidemics in Xinjiang.展开更多
The transmission and prevalence of Hand,Foot and Mouth Disease(HFMD)are affected by a variety of natural and socio-economic environmental factors.This study aims to quantitatively investigate the non-stationary and sp...The transmission and prevalence of Hand,Foot and Mouth Disease(HFMD)are affected by a variety of natural and socio-economic environmental factors.This study aims to quantitatively investigate the non-stationary and spatially varying associations between various environmental factors and HFMD risk.We collected HFMD surveillance cases and a series of relevant environmental data from 2013 to 2021 in Xi'an,Northwest China.By controlling the spatial and temporal mixture effects of HFMD,we constructed a Bayesian spatiotemporal mapping model and characterized the impacts of different driving factors into global linear,non-stationary and spatially varying effects.The results showed that the impact of meteorological conditions on HFMD risk varies in both type and magnitude above certain thresholds(temperature:30°C,precipitation:70 mm,solar radiation:13000 kJ/m^(2),pressure:945 hPa,humidity:69%).Air pollutants(PM_(2.5),PM_(10),NO_(2))showed an inverted U-shaped relationship with the risk of HFMD,while other air pollutants(O_(3),SO_(2))showed nonlinear fluctuations.Moreover,the driving effect of increasing temperature on HFMD was significant in the 3-year period,while the inhibitory effect of increasing precipitation appeared evident in the 5-year period.In addition,the proportion of urban/suburban/rural area had a strong influence on HFMD,indicating that the incidence of HFMD firstly increased and then decreased during the rapid urbanization process.The influence of population density on HFMD was not only limited by spatial location,but also varied between high and low intervals.Higher road density inhibited the risk of HFMD,but higher night light index promoted the occurrence of HFMD.Our findings further demonstrated that both ecological and socioeconomic environmental factors can pose multiple driving effects on increasing the spatiotemporal risk of HFMD,which is of great significance for effectively responding to the changes in HFMD epidemic outbreaks.展开更多
Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA1...Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level. In this study, we performed systematic epidemiological analyses of HFMD-related enteroviruses using the data of 64 published papers that met the inclusion criteria, and conducted phylogenetic analyses based on 12,080 partial VP1 sequences identified in China before 31 st June 2018. We found that EVA71 prevalence has decreased sharply but other enteroviruses have increased rapidly from 2008 to 2016 and that one subtype of each enterovirus is represented during the epidemic. In addition, four genotypes EVA71_C4, CVA16_B1, CVA6_D and CVA10_C are the most predominant enterovirus strains and collectively they cause over 90% of all HFMD cases in China according to the phylogenetic trees using representative partial VP1 sequences. These four major enterovirus genotypes have different geographical distributions, and they may cocirculate with other genotypes and serotypes. These results suggest that more molecular epidemiological studies should be performed on several enteroviruses simultaneously, and such information should have implications for virological surveillance, disease management, vaccine development and policy-making on the prevention and control of HFMD.展开更多
This paper presents an empirical analysis of the epidemiological data concerning the 18445 HFMD-infected cases in Beijing in 2008.The main findings are as follows.(i) Seasonal variations in incidence were observed,wit...This paper presents an empirical analysis of the epidemiological data concerning the 18445 HFMD-infected cases in Beijing in 2008.The main findings are as follows.(i) Seasonal variations in incidence were observed,with a peak observed during the summer season,especially in May.Male patients outnumber female patients by 1.57:1.(ii) Most cases occurred in children 4 years old or younger.Outperforming Weibull distribution and Gamma distribution as to model fitness when analyzing patient ages,log-normal distribution indicates that the estimated mean age is 3.4 years.(iii) The age distribution seems to indicate cyclic peaks with roughly one-year intervals.(iv) Correlation analyses (ρ=0.9864) show that time of birth in different months has an impact on the chance of being infected by HFMD.Birth month seems to present a high risk factor on infants and young children.(v) The morbidity rate is 132.7/100000 during the HFMD epidemic in Beijing in 2008.The morbidity map shows that the risks of HFMD infection in areas close to the city center and suburbans are much lower than those in the urban-rural transition zones.Spatial risks inferred from the morbidity map demonstrate a clear circular pattern.(vi) The prevention and control measures taken by the public health departments seem to be effective during the summer season,resulting in the early ending of the epidemic (one month earlier than the natural season) and reduced outbreak size.展开更多
基金This work was supported by Chinese Center for Disease Control and Prevention and Ministry of Health,China.
文摘To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 (El9) isolates collected from an outbreak associated with hand, foot and mouth disease (HFMD) in Tai'an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid (VP1) genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions (5′-UTR). Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.
基金supported by National Foundation of China (project No.2013ZX10004-202)National Basic Research Program of China (973 Program,2011CB504902)National Natural Science Foundation of China (project Nos.30900063,81101303,81373049)
文摘Hand, foot, and mouth disease (HFMD) is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,
基金supported by the development and construction project of State Administration of l Traditional Chinese Medicine (200907001-3)the key science and technology project of Shenzhen (201003134, 201002110)
文摘Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explored. Methods Total of 2 325 cases with HFMD were recorded by distributing them into exterior syndrome stage, interior syndrome stage, severe syndrome stage and recovered syndrome stage, respectively, and the main symptoms and subsidiary symptoms of different stages of HFMD have been observed. The major and minor pathogenesis of HFMD in different stages were obtained, and compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD". Results It was found that the major pathogenesis of exterior stage was defined as "the invation of the wenevil to the defender of the body with the collaterals got involved ", and the minor as "qi deficiency"; in interior stage, "the fury of Gan-Yang" was the main pathogenesis, and "qi in chaos and qi deficiency" was the minor; in severe syndrome stage, "the damage of heart, liver and lung" was the main pathogenesis, and "qi in chaos" was the minor; and the pathogenesis of recovered stage was "qi-yin deficiency". Compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD", it showed that "the obstruction of the fei-pi qi by the mixture of shi-re evil" and "the mixture of shi-re" in vivo was quite difficult to be explained in completely different context in the general situation; in the severe stage, the TCM clinical characteristics of syndrome differentiation might lose; in the early acute severe cases, the phenomenon that xin-yang and fei-qi almost ran out was difficult to be observed, then, the line between the severe and the acute severe became vague.Conclusions The theory of syndrome differentiation by stages of HFMD was reasonable in the actual situation of clinical description on HFMD which was expected to be further tested and widely applied in the "zheng" differentiation-treatment of HFMD in the future.
基金supported by the National Natural Science Foundation of China(41861037)the Third Xinjiang Scientific Expedition Program(2021xjkk0902).
文摘In recent years,the number of hand,foot,and mouth disease(HFMD)cases in China has continued to grow,and the disease has become a serious public health issue.Xinjiang Uygur Autonomous Region is located in the arid areas of Northwest China,where the epidemiological trend of HFMD is gradually increasing and characterized by geographical heterogeneity.In this study,based on the HFMD case data in all counties and cities in Xinjiang,we employed statistical and GIS spatial analyses,and geographic probe models to characterize the spatiotemporal differentiation of HFMD epidemics in Xinjiang during the period of 2009–2018,and quantitatively analyzed the factors influencing the spatial differentiation of HFMD epidemics.The results showed that HFMD incidence rate in Xinjiang had non-stationary temporal characteristics on the interannual and monthly scales,and the monthly variation characteristics of HFMD epidemic were quite different in southern and northern Xinjiang.The spatial distribution characteristics of HFMD epidemics showed a north–south spatial differentiation pattern with the Tianshan Mountains as the boundary;cold spot and hot spot of HFMD epidemics in Xinjiang have shifted from scattered to concentrated,and the spatial differentiation pattern had gradually stabilized.Moreover,the dominant factors influencing the spatial differentiation of HFMD epidemics in Xinjiang were socioeconomic factors,such as per capita GDP and urbanization rate,while the basic factors affecting its spatial differentiation were natural environmental factors.The spatial differentiation and evolution patterns of HFMD epidemics differed between northern and southern Xinjiang.Specifically,the leading role of socioeconomic factors is more obvious in southern Xinjiang than in northern Xinjiang,while natural environmental factors(e.g.,dryness and relative humidity)contribute to the prevalence of HFMD epidemics in northern Xinjiang,and the perturbing effect of these factors was more prominent than other factors.The results of this study can provide a scientific basis for the prevention of HFMD epidemics and early warning of HFMD epidemics in Xinjiang.
基金This work was supported by grants from the National Natural Science Foundation of China(L.S.,grant number:42201448),(K.L.,grant number:82273689)Natural Science Foundation of Hubei Province(L.S.,grant number:2022CFB610).
文摘The transmission and prevalence of Hand,Foot and Mouth Disease(HFMD)are affected by a variety of natural and socio-economic environmental factors.This study aims to quantitatively investigate the non-stationary and spatially varying associations between various environmental factors and HFMD risk.We collected HFMD surveillance cases and a series of relevant environmental data from 2013 to 2021 in Xi'an,Northwest China.By controlling the spatial and temporal mixture effects of HFMD,we constructed a Bayesian spatiotemporal mapping model and characterized the impacts of different driving factors into global linear,non-stationary and spatially varying effects.The results showed that the impact of meteorological conditions on HFMD risk varies in both type and magnitude above certain thresholds(temperature:30°C,precipitation:70 mm,solar radiation:13000 kJ/m^(2),pressure:945 hPa,humidity:69%).Air pollutants(PM_(2.5),PM_(10),NO_(2))showed an inverted U-shaped relationship with the risk of HFMD,while other air pollutants(O_(3),SO_(2))showed nonlinear fluctuations.Moreover,the driving effect of increasing temperature on HFMD was significant in the 3-year period,while the inhibitory effect of increasing precipitation appeared evident in the 5-year period.In addition,the proportion of urban/suburban/rural area had a strong influence on HFMD,indicating that the incidence of HFMD firstly increased and then decreased during the rapid urbanization process.The influence of population density on HFMD was not only limited by spatial location,but also varied between high and low intervals.Higher road density inhibited the risk of HFMD,but higher night light index promoted the occurrence of HFMD.Our findings further demonstrated that both ecological and socioeconomic environmental factors can pose multiple driving effects on increasing the spatiotemporal risk of HFMD,which is of great significance for effectively responding to the changes in HFMD epidemic outbreaks.
基金supported by the TOTAL foundation,and the Grants from the National Science and Technology Major Project of China(2017ZX10103009-002)the "One Belt One Road" Project(153831KYSB20170043)of the Chinese Academy of Sciencesthe133 Project of Institut Pasteur of Shanghai,CAS.
文摘Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level. In this study, we performed systematic epidemiological analyses of HFMD-related enteroviruses using the data of 64 published papers that met the inclusion criteria, and conducted phylogenetic analyses based on 12,080 partial VP1 sequences identified in China before 31 st June 2018. We found that EVA71 prevalence has decreased sharply but other enteroviruses have increased rapidly from 2008 to 2016 and that one subtype of each enterovirus is represented during the epidemic. In addition, four genotypes EVA71_C4, CVA16_B1, CVA6_D and CVA10_C are the most predominant enterovirus strains and collectively they cause over 90% of all HFMD cases in China according to the phylogenetic trees using representative partial VP1 sequences. These four major enterovirus genotypes have different geographical distributions, and they may cocirculate with other genotypes and serotypes. These results suggest that more molecular epidemiological studies should be performed on several enteroviruses simultaneously, and such information should have implications for virological surveillance, disease management, vaccine development and policy-making on the prevention and control of HFMD.
基金supported by US NSF (Grant Nos. IIS-0839990 and IIS-0428241)US DHS (Grant No. 2008-ST-061-BS0002)+3 种基金the Ministry of Health of the People’s Republic of China (Grant No. 2009ZX10004-315100)the Chinese Academy of Sciences (Grant Nos. 2F07C01 and 2F08N03)the National Natural Science Fundation of China (Grant Nos. 40901219 and 60621001)China Postdoctoral Science Fund (Grant No. 20080440559)
文摘This paper presents an empirical analysis of the epidemiological data concerning the 18445 HFMD-infected cases in Beijing in 2008.The main findings are as follows.(i) Seasonal variations in incidence were observed,with a peak observed during the summer season,especially in May.Male patients outnumber female patients by 1.57:1.(ii) Most cases occurred in children 4 years old or younger.Outperforming Weibull distribution and Gamma distribution as to model fitness when analyzing patient ages,log-normal distribution indicates that the estimated mean age is 3.4 years.(iii) The age distribution seems to indicate cyclic peaks with roughly one-year intervals.(iv) Correlation analyses (ρ=0.9864) show that time of birth in different months has an impact on the chance of being infected by HFMD.Birth month seems to present a high risk factor on infants and young children.(v) The morbidity rate is 132.7/100000 during the HFMD epidemic in Beijing in 2008.The morbidity map shows that the risks of HFMD infection in areas close to the city center and suburbans are much lower than those in the urban-rural transition zones.Spatial risks inferred from the morbidity map demonstrate a clear circular pattern.(vi) The prevention and control measures taken by the public health departments seem to be effective during the summer season,resulting in the early ending of the epidemic (one month earlier than the natural season) and reduced outbreak size.