The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus,which aids in the understanding of its underlying pathogenic mechanism.In this study,analys...The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus,which aids in the understanding of its underlying pathogenic mechanism.In this study,analyses of the characteristic of the H1N1 virus infection-related genes,their biological functions,and infection-related reversal drugs were performed.Additionally,we used multi-dimensional bioinformatics analysis to identify the key genes and then used these to construct a diagnostic model for the H1N1 virus infection.There was a total of 169 differently expressed genes in the samples between 21 h before infection and 77 h after infection.They were used during the protein-protein interaction(PPI)analysis,and we obtained a total of 1725 interacting genes.Then,we performed a weighted gene co-expression network analysis(WGCNA)on these genes,and we identified three modules that showed significant potential for the diagnosis of the H1N1 virus infection.These modules contained 60 genes,and they were used to construct this diagnostic model,which showed an effective prediction value.Besides,these 60 genes were involved in the biological functions of this infectious virus,like the cellular response to type I interferon and in the negative regulation of the viral life cycle.However,20 genes showed an upregulated expression as the infection progressed.Other 36 upregulated genes were used to examine the relationship between genes,human influenza A virus,and infection-related reversal drugs.This study revealed numerous important reversal drug molecules on the H1N1 virus.They included rimantadine,interferons,and shikimic acid.Our study provided a novel method to analyze the characteristic of different genes and explore their corresponding biological function during the infection caused by the H1N1 virus.This diagnostic model,which comprises 60 genes,shows that a significant predictive value can be the potential biomarker for the diagnosis of the H1N1 virus infection.展开更多
Background: A number of conservation and societal issues require understanding how species are distributed on the landscape, yet ecologists are often faced with a lack of data to develop models at the resolution and e...Background: A number of conservation and societal issues require understanding how species are distributed on the landscape, yet ecologists are often faced with a lack of data to develop models at the resolution and extent desired, resulting in inefficient use of conservation resources.Such a situation presented itself in our attempt to develop waterfowl distribution models as part of a multi-disciplinary team targeting the control of the highly pathogenic H5N1 avian influenza virus in China.Methods: Faced with limited data, we built species distribution models using a habitat suitability approach for China's breeding and non-breeding(hereafter, wintering) waterfowl.An extensive review of the literature was used to determine model parameters for habitat modeling.Habitat relationships were implemented in GIS using land cover covariates.Wintering models were validated using waterfowl census data, while breeding models, though developed for many species, were only validated for the one species with sufficient telemetry data available.Results: We developed suitability models for 42 waterfowl species(30 breeding and 39 wintering) at 1 km resolution for the extent of China, along with cumulative and genus level species richness maps.Breeding season models showed highest waterfowl suitability in wetlands of the high-elevation west-central plateau and northeastern China.Wintering waterfowl suitability was highest in the lowland regions of southeastern China.Validation measures indicated strong performance in predicting species presence.Comparing our model outputs to China's protected areas indicated that breeding habitat was generally better covered than wintering habitat, and identified locations for which additional research and protection should be prioritized.Conclusions: These suitability models are the first available for many of China's waterfowl species, and have direct utility to conservation and habitat planning and prioritizing management of critically important areas, providing an example of how this approach may aid others faced with the challenge of addressing conservation issues with little data to inform decision making.展开更多
Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, part...Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 ug hemagglutinin antigen, with or without aluminum hydroxide （N-OH）. We classified the participants into six age categories （〉61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years） and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer （GMT） of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. Results The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. Conclusion The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.展开更多
The actual incidence of human H7N9 infection is supposed to be much higher than the documented laboratoryconfirmed cases.In this study,we estimated the number of the actual H7N9 cases in Jiangsu,China using a probabil...The actual incidence of human H7N9 infection is supposed to be much higher than the documented laboratoryconfirmed cases.In this study,we estimated the number of the actual H7N9 cases in Jiangsu,China using a probabilistic multiplier model.Then,disability adjusted life years(DALYs),direct and indirect economic loss caused by this disease were calculated and analyzed.Till September 2017,the estimated total number of H7N9 cases was 2952[median,90%probability range(PR):1487-22094],which was 11.8 times(5.9-88.4)as large as the reported number.The median morbidity was estimated to be 4(90%PR:2-29)per 100000 population.The total DALYs loss was 16548 years,and the total economic loss(direct and indirect)was estimated to be RMB 1044618758(US$16.7 M).The average economic loss for per case and for per year was RMB 353868(US$56440)and RMB 232137502(US$37.0 M),respectively.The actual burden of human H7N9 infections was much heavier than what was documented.Our study provided an approach to estimate actual burden of infectious diseases using laboratory-confirmation.展开更多
Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics.In this s...Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics.In this study,we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data.The impact of the choice of tree-priors,informative epidemiological priors,and evolutionary parameters on the transmission potential estimation is evaluated.North American Influenza A(H1N1)pdm09 hemagglutinin(HA)gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number(R_(0)).Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models.Path-sampling marginal likelihood estimation is conducted to assess model fit.A bibliographic search to gather surveillancebased R_(0)values were consistently lower(mean≤1.2)when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness(mean≥1.3 to≤2.88 days).The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates.While there was no certain impact of clock rate and tree height on the R_(0)estimation,an opposite relationship was observed between coalescent and birth-death tree priors.There was no significant difference(p=0.46)between the birth-death model and surveillance R0 estimates.This study concludes that treeprior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters.The study also reports a consensus between the sequence-based R_(0)estimation and surveillanceased R_(0)stimates.Altogether,these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.展开更多
The epidemic of H7N9 bird flu in eastern China in early 2013 has caused much attention from researchers as well as public health workers.The issue on modeling the transmission risks is very interesting topic.In this a...The epidemic of H7N9 bird flu in eastern China in early 2013 has caused much attention from researchers as well as public health workers.The issue on modeling the transmission risks is very interesting topic.In this article,this issue is debated and discussed in order to promote further researches on prediction and prevention of avian influenza viruses supported by better interdisciplinary datasets from the surveillance and response system.展开更多
Background:The potential for emergence of antiviral drug resistance during influenza pandemics has raised great concern for public health.Widespread use of antiviral drugs is a significant factor in producing resistan...Background:The potential for emergence of antiviral drug resistance during influenza pandemics has raised great concern for public health.Widespread use of antiviral drugs is a significant factor in producing resistant strains.Recent studies show that some influenza viruses may gain antiviral drug resistance without a fitness penalty.This creates the possibility of strategic interaction between populations considering antiviral drug use strategies.Methods:To explain why,we develop and analyze a classical 2-player game theoretical model where each player chooses from a range of possible rates of antiviral drug use,and payoffs are derived as a function of final size of epidemic with the regular and mutant strain.Final sizes are derived from a stochastic compartmental epidemic model that captures transmission within each population and between populations,and the stochastic emergence of antiviral drug resistance.High treatment levels not only increase the spread of the resistant strain in the subject population but also affect the other population by increasing the density of the resistant strain infectious individuals due to travel between populations.Results:We found two Nash equilibria where both populations treat at a high rate,or both treat at a low rate.Hence the game theoretical analysis predicts that populations will not choose different treatment strategies than other populations,under these assumptions.The populations may choose to cooperate by maintaining a low treatment rate that does not increase the incidence of mutant strain infections or cause case importations to the other population.Alternatively,if one population is treating at a high rate,this will generate a large number of mutant infections that spread to the other population,in turn incentivizing that population to also treat at a high rate.The prediction of two separate Nash equilibria is robust to the mutation rate and the effectiveness of the drug in preventing transmission,but it is sensitive to the volume of travel between the two populations.Conclusions:Model-based evaluations of antiviral influenza drug use during a pandemic usually consider populations in isolation from one another,but our results show that strategic interactions could strongly influence a population's choice of antiviral drug use policy.Furthermore,the high treatment rate Nash equilibrium has the potential to become socially suboptimal(i.e.non-Pareto optimal)under model assumptions that might apply under other conditions.Because of the need for players to coordinate their actions,we conclude that communication and coordination between jurisdictions during influenza pandemics is a priority,especially for influenza strains that do not evolve a fitness penalty under antiviral drug resistance.展开更多
We focus on in this paper the convergence rate of the L-N estimators for the fixed effect β in Poisson-Gamma models which are typical hierarchical generalised linear models（HGLMs）. Under the proper assumptions on r...We focus on in this paper the convergence rate of the L-N estimators for the fixed effect β in Poisson-Gamma models which are typical hierarchical generalised linear models（HGLMs）. Under the proper assumptions on response variables and some smoothing conditions, we obtain the strong consistency and the convergence rate of the L-N estimator based on the combination of L-N and quasi-likelihood.展开更多
基金supported by the major national S&T projects for infectious diseases(2018ZX10301401)the Key Research&Development Plan of Zhejiang Province(2019C04005)the National Key Research,and the Development Program of China(2018YFC2000500).
文摘The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus,which aids in the understanding of its underlying pathogenic mechanism.In this study,analyses of the characteristic of the H1N1 virus infection-related genes,their biological functions,and infection-related reversal drugs were performed.Additionally,we used multi-dimensional bioinformatics analysis to identify the key genes and then used these to construct a diagnostic model for the H1N1 virus infection.There was a total of 169 differently expressed genes in the samples between 21 h before infection and 77 h after infection.They were used during the protein-protein interaction(PPI)analysis,and we obtained a total of 1725 interacting genes.Then,we performed a weighted gene co-expression network analysis(WGCNA)on these genes,and we identified three modules that showed significant potential for the diagnosis of the H1N1 virus infection.These modules contained 60 genes,and they were used to construct this diagnostic model,which showed an effective prediction value.Besides,these 60 genes were involved in the biological functions of this infectious virus,like the cellular response to type I interferon and in the negative regulation of the viral life cycle.However,20 genes showed an upregulated expression as the infection progressed.Other 36 upregulated genes were used to examine the relationship between genes,human influenza A virus,and infection-related reversal drugs.This study revealed numerous important reversal drug molecules on the H1N1 virus.They included rimantadine,interferons,and shikimic acid.Our study provided a novel method to analyze the characteristic of different genes and explore their corresponding biological function during the infection caused by the H1N1 virus.This diagnostic model,which comprises 60 genes,shows that a significant predictive value can be the potential biomarker for the diagnosis of the H1N1 virus infection.
基金supported by the United States Geological Survey(Ecosystems Mission Area)the National Science Foundation Small Grants for Exploratory Research(No.0713027)Wetlands International
文摘Background: A number of conservation and societal issues require understanding how species are distributed on the landscape, yet ecologists are often faced with a lack of data to develop models at the resolution and extent desired, resulting in inefficient use of conservation resources.Such a situation presented itself in our attempt to develop waterfowl distribution models as part of a multi-disciplinary team targeting the control of the highly pathogenic H5N1 avian influenza virus in China.Methods: Faced with limited data, we built species distribution models using a habitat suitability approach for China's breeding and non-breeding(hereafter, wintering) waterfowl.An extensive review of the literature was used to determine model parameters for habitat modeling.Habitat relationships were implemented in GIS using land cover covariates.Wintering models were validated using waterfowl census data, while breeding models, though developed for many species, were only validated for the one species with sufficient telemetry data available.Results: We developed suitability models for 42 waterfowl species(30 breeding and 39 wintering) at 1 km resolution for the extent of China, along with cumulative and genus level species richness maps.Breeding season models showed highest waterfowl suitability in wetlands of the high-elevation west-central plateau and northeastern China.Wintering waterfowl suitability was highest in the lowland regions of southeastern China.Validation measures indicated strong performance in predicting species presence.Comparing our model outputs to China's protected areas indicated that breeding habitat was generally better covered than wintering habitat, and identified locations for which additional research and protection should be prioritized.Conclusions: These suitability models are the first available for many of China's waterfowl species, and have direct utility to conservation and habitat planning and prioritizing management of critically important areas, providing an example of how this approach may aid others faced with the challenge of addressing conservation issues with little data to inform decision making.
基金supported by the Infectious Disease Prevention and Control Major Research plan from the Ministry of Science and Technology of China-the Platform of Construction of Clinical Trial of Vaccine. (Project number 2009ZX0004-806)
文摘Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 ug hemagglutinin antigen, with or without aluminum hydroxide （N-OH）. We classified the participants into six age categories （〉61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years） and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer （GMT） of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. Results The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. Conclusion The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.
基金supported by the Science&Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention under Grant(BE2015714&BE2017749)supported by the Key Medical Discipline of Jiangsu Science&Technology Project under Grant(epidemiology,ZDXKA2016008)+1 种基金supported by the National Science and Technology Major Project under Grant(2015ZX09101044)the Jiangsu Provincial Medical Youth Talents under Grant(QNRC2016539)
文摘The actual incidence of human H7N9 infection is supposed to be much higher than the documented laboratoryconfirmed cases.In this study,we estimated the number of the actual H7N9 cases in Jiangsu,China using a probabilistic multiplier model.Then,disability adjusted life years(DALYs),direct and indirect economic loss caused by this disease were calculated and analyzed.Till September 2017,the estimated total number of H7N9 cases was 2952[median,90%probability range(PR):1487-22094],which was 11.8 times(5.9-88.4)as large as the reported number.The median morbidity was estimated to be 4(90%PR:2-29)per 100000 population.The total DALYs loss was 16548 years,and the total economic loss(direct and indirect)was estimated to be RMB 1044618758(US$16.7 M).The average economic loss for per case and for per year was RMB 353868(US$56440)and RMB 232137502(US$37.0 M),respectively.The actual burden of human H7N9 infections was much heavier than what was documented.Our study provided an approach to estimate actual burden of infectious diseases using laboratory-confirmation.
基金National Institutes of Health(NIH)Centers for Excellence in Influenza Research and Surveillance(contract#HHSN272201400006C)National Institute of Allergy and Infectious Diseases,National Institutes of Health,Department of Health and Human Services,under Contract No.75N93021C00018(NIAID Centers of Excellence for Influenza Research and Response,CEIRR)。
文摘Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics.In this study,we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data.The impact of the choice of tree-priors,informative epidemiological priors,and evolutionary parameters on the transmission potential estimation is evaluated.North American Influenza A(H1N1)pdm09 hemagglutinin(HA)gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number(R_(0)).Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models.Path-sampling marginal likelihood estimation is conducted to assess model fit.A bibliographic search to gather surveillancebased R_(0)values were consistently lower(mean≤1.2)when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness(mean≥1.3 to≤2.88 days).The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates.While there was no certain impact of clock rate and tree height on the R_(0)estimation,an opposite relationship was observed between coalescent and birth-death tree priors.There was no significant difference(p=0.46)between the birth-death model and surveillance R0 estimates.This study concludes that treeprior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters.The study also reports a consensus between the sequence-based R_(0)estimation and surveillanceased R_(0)stimates.Altogether,these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.
文摘The epidemic of H7N9 bird flu in eastern China in early 2013 has caused much attention from researchers as well as public health workers.The issue on modeling the transmission risks is very interesting topic.In this article,this issue is debated and discussed in order to promote further researches on prediction and prevention of avian influenza viruses supported by better interdisciplinary datasets from the surveillance and response system.
基金This work was supported by a research grant to CTB from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.The funders had no role in the design,analysis,writing,or decision to submit the manuscript for publication.
文摘Background:The potential for emergence of antiviral drug resistance during influenza pandemics has raised great concern for public health.Widespread use of antiviral drugs is a significant factor in producing resistant strains.Recent studies show that some influenza viruses may gain antiviral drug resistance without a fitness penalty.This creates the possibility of strategic interaction between populations considering antiviral drug use strategies.Methods:To explain why,we develop and analyze a classical 2-player game theoretical model where each player chooses from a range of possible rates of antiviral drug use,and payoffs are derived as a function of final size of epidemic with the regular and mutant strain.Final sizes are derived from a stochastic compartmental epidemic model that captures transmission within each population and between populations,and the stochastic emergence of antiviral drug resistance.High treatment levels not only increase the spread of the resistant strain in the subject population but also affect the other population by increasing the density of the resistant strain infectious individuals due to travel between populations.Results:We found two Nash equilibria where both populations treat at a high rate,or both treat at a low rate.Hence the game theoretical analysis predicts that populations will not choose different treatment strategies than other populations,under these assumptions.The populations may choose to cooperate by maintaining a low treatment rate that does not increase the incidence of mutant strain infections or cause case importations to the other population.Alternatively,if one population is treating at a high rate,this will generate a large number of mutant infections that spread to the other population,in turn incentivizing that population to also treat at a high rate.The prediction of two separate Nash equilibria is robust to the mutation rate and the effectiveness of the drug in preventing transmission,but it is sensitive to the volume of travel between the two populations.Conclusions:Model-based evaluations of antiviral influenza drug use during a pandemic usually consider populations in isolation from one another,but our results show that strategic interactions could strongly influence a population's choice of antiviral drug use policy.Furthermore,the high treatment rate Nash equilibrium has the potential to become socially suboptimal(i.e.non-Pareto optimal)under model assumptions that might apply under other conditions.Because of the need for players to coordinate their actions,we conclude that communication and coordination between jurisdictions during influenza pandemics is a priority,especially for influenza strains that do not evolve a fitness penalty under antiviral drug resistance.
基金Supported by the National Natural Science Foundation of China(10371005)Scientific Research Funds of the Excellent Young Teachers Program of the Ministry of Education China(VE00074)
文摘We focus on in this paper the convergence rate of the L-N estimators for the fixed effect β in Poisson-Gamma models which are typical hierarchical generalised linear models（HGLMs）. Under the proper assumptions on response variables and some smoothing conditions, we obtain the strong consistency and the convergence rate of the L-N estimator based on the combination of L-N and quasi-likelihood.
