Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiolog...Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.展开更多
Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp.mosquitos,causing the acute infectious disease,dengue fever(DF).Until 2019,no dengue outbreak had been reported in Haina...Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp.mosquitos,causing the acute infectious disease,dengue fever(DF).Until 2019,no dengue outbreak had been reported in Hainan Province for over 20 years.However,in early September of 2019,an increasing number of infected cases appeared and the DF outbreak lasted for over one month in Haikou City,Hainan Province.In our study,we collected 97 plasma samples from DF patients at three hospitals,as well as 1585 mosquito larvae samples from puddles in different areas of Haikou.There were 49(50.5%)plasma samples found to be strongly positive and 9(9.3%)plasma samples were weakly positive against the NS1 antigen.We discovered DENV both in the patient's plasma samples and mosquito larvae samples,and isolated the virus from C6/36 cells inoculated with the acute phase serum of patients.Phylogenetic analysis revealed that the new strains were the most closely related to the epidemic strain in the southern regions of China,belonging to lineageⅣ,genotypeⅠ,DENV-1.Compared to the seven closest strains from neighboring countries and provinces,a total of 18 amino acid mutations occurred in the coding sequences(CDS)of the new isolated strain,DENV1 HMU-HKU-2.Our data shows that dengue virus is re-emerged in Hainan,and pose new threats for public health.Thus regular molecular epidemiological surveillance is necessary for control and prevention of DENV transmission.展开更多
基金This study was supported by the National Key R&D Program of China(2020YFC120104)the National Institutes of Health+3 种基金the USA(AI136850)the National Natural Science Foundation of China(82072311)the Guang‑zhou Synergy Innovation Key Program for Health(201803040006 and 201508020263)the Guangzhou International Science and Technology Cooperation Program(2012J5100026).
文摘Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.
基金This work was supported by the Hainan Provincial Natural Science Foundation of China(Grant No.2019RC218)the National Natural Science Foundation of China(grant No.81860367,31460017)+5 种基金the Scientific Research Foundation of the Higher Education Institutions of Hainan Province,China(Grant No.Hnky2020-33)the Hainan Medical University novel coronavirus pneumonia project(Grant No.XGZX2020005)the Hainan Provincial Natural Science Foundation of China(Grant No.819QN360)State Key Laboratory of Virology 2018 Open Fund Project(2018IOV002)the National S&T Major Project"China Mega-Project for Infectious Disease"(Grant No.2018ZX10711001)the CAMS Innovation Fund for Medical Sciences(Grant No.2017-I2M-3-017).
文摘Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp.mosquitos,causing the acute infectious disease,dengue fever(DF).Until 2019,no dengue outbreak had been reported in Hainan Province for over 20 years.However,in early September of 2019,an increasing number of infected cases appeared and the DF outbreak lasted for over one month in Haikou City,Hainan Province.In our study,we collected 97 plasma samples from DF patients at three hospitals,as well as 1585 mosquito larvae samples from puddles in different areas of Haikou.There were 49(50.5%)plasma samples found to be strongly positive and 9(9.3%)plasma samples were weakly positive against the NS1 antigen.We discovered DENV both in the patient's plasma samples and mosquito larvae samples,and isolated the virus from C6/36 cells inoculated with the acute phase serum of patients.Phylogenetic analysis revealed that the new strains were the most closely related to the epidemic strain in the southern regions of China,belonging to lineageⅣ,genotypeⅠ,DENV-1.Compared to the seven closest strains from neighboring countries and provinces,a total of 18 amino acid mutations occurred in the coding sequences(CDS)of the new isolated strain,DENV1 HMU-HKU-2.Our data shows that dengue virus is re-emerged in Hainan,and pose new threats for public health.Thus regular molecular epidemiological surveillance is necessary for control and prevention of DENV transmission.
