Influenza A （HIN1） transmission by road traffic between cities and towns

Influenza A (H1N1) was spread widely between cities and towns by road traffic and had a major impact on public health in China in 2009. Understanding regulation of its transmission is of great significance with urbanization ongoing and for mitigation of damage by the epidemic. We analyzed influenza A (H1N1) spatiotemporal transmission and risk factors along roads in Changsha, and combined diffusion velocity and floating population size to construct an epidemic diffusion model to simulate its transmission between cities and towns. The results showed that areas along the highways and road intersections had a higher incidence rate than other areas. Expressways and county roads played an important role in the rapid development stage and the epidemic peak, respectively, and intercity bus stations showed a high risk of disease transmission. The model simulates the intensity and center of disease outbreaks in cities and towns, and provides a more complete simulation of the disease spatiotemporal process than other models.     

Genome evolution of novel influenza A （H1N1 ） viruses in humans

The epidemic situation of A H1N1 flu arose in North America in April 2009, which rapidly expanded to three continents of Europe, Asia and Africa, with the risk ranking up to 5. Until May 13th, the flu virus of A H1N1 had spread into 33 countries and regions, with a laboratory confirmed case number of 5728, including 61 deaths. Based on IRV and EpiFluDB database, 425 parts of A H1N1 flu virus sequence were achieved, followed by sequenced comparison and evolution analysis. The results showed that the current predominant A H1N1 flu virus was a kind of triple reassortment A flu virus： （i） HA, NA, MP, NP and NS originated from swine influenza virus; PB2 and PA originated from bird influenza virus; PB1 originated from human influenza virus. （ii） The origin of swine influenza virus could be subdivided as follows： HA, NP and NS originated from classic swine influenza virus of H1N1 subtype; NA and MP originated from bird origin swine influenza virus of H1N1 subtype. （iii） A H1N1 flu virus experienced no significant mutation during the epidemic spread, accompanied with no reassortment of the virus genome. In the paper, the region of the representative strains for sequence analysis （A/California/04/2009 （H1N1） and A/Mexico/4486/2009 （H1N1）） included USA and Mexico and was relatively wide, which suggested that the analysis results were convincing.     

Influence of extreme weather and meteorological anomalies on outbreaks of influenza A (H1N1)

Biological experiments and epidemiological evidence indicate that variations in environment have important effect on the occurrence and transmission of epidemic influenza.It is therefore important to understand the characteristic patterns of transmission for prevention of disease and reduction of disease burden.Based on case records,we analyzed the environmental characteristics including climate variables in Changsha,and then constructed a meteorological anomaly susceptive-infective-removal (SIR) model on the basis of the results of influenza A (H1N1) transmission.The results showed that the outbreak of influenza A (H1N1) in Changsha showed significant correlation with meteorological conditions;the spread of influenza was sensitive to meteorological anomalies,and that the outbreak of influenza A (H1N1) in Changsha was influenced by a combination of absolute humidity anomalous weather conditions,contact rates of the influenza patients and changes in population movements.These findings will provide helpful information regarding prevention strategies under different conditions,a fresh understanding of the emergence and re-emergence of influenza outbreaks,and a new perspective on the transmission dynamics of influenza.     

Subtyping of type A influenza by sequencing the variable regions of HA gene specifically amplified with RT-PCR

The outbreak of a novel influenza A （H1N1） virus across the globe poses a threat to human health. It is of paramount importance to develop a rapid, reliable and inexpensive diagnostic procedure. Based on the bioinformatic information from public database, primers specific for influenza A virus surface protein haemagglutinin （HA） of several subtypes （including H1, H2, H3, H5, H7 and H9） were designed. Primer-specific PCR products were subiected to sequencing for accurately distinguishing H1 and H3 subtypes from others. This sequencing-based detection method will not only be applied to rapid detection and simultaneous subtype identification of new influenza A virus H1N1, but also provide the strategies to monitor other new types of influenza virus with explosive potential.     

Learn to fight from the war

In March 2009, a novel type A （H1N1） influenza broke out in North America and rapidly spread all over the world. So far, more than 17000 cases of infection have been reported. The alert level announced by the World Health Organization （WHO） has upgraded sharply to Level 5, indicating that the century long ＂arms race＂ between humans and the influenza has entered a new phase.     

Epidemiological and risk analysis of the H7N9 subtype influenza outbreak in China at its early stage

Dozens of human cases infected with H7N9 subtype avian influenza virus (AIV) have been confirmed in China since March, 2013. Distribution data of sexes, ages, professions and regions of the cases were analyzed in this report. The results showed that the elderly cases, especially the male elderly, were significantly more than expected, which is different from human cases of H5N1 avian influenza and human cases of the pandemic H1N1 influenza. The outbreak was rated as a Grade Ⅲ (severe) outbreak, and it would evolve into a Grade IV (very severe) outbreak soon, using a method reported previously. The H7N9 AIV will probably circulate in humans, birds and pigs for years. Moreover, with the driving force of natural selection, the virus will probably evolve into highly pathogenic AIV in birds, and into a deadly pandemic influenza virus in humans. Therefore, the H7N9 outbreak has been assumed severe, and it is likely to become very or extremely severe in the future, highlighting the emergent need of forceful scientific measures to eliminate any infected animal flocks. We also described two possible mild scenarios of the future evolution of the outbreak.     

Secondary structural analysis of the mRNA regions encoding the hemagglutinin cleavage site basic amino acids of the avian influenza virus H5N1 subtype samples

Here we report the codon bias and the mRNA secondary structural features of the hemagglutinin （HA） cleavage site basic amino acid regions of avian influenza virus H5N1 subtypes. We have developed a dynamic extended folding strategy to predict RNA secondary structure with RNAstructure 4.1 program in an iterative extension process. Statistical analysis of the sequences showed that the HA cleavage site basic amino acids favor the adenine-rich codons, and the corresponding mRNA fragments are mainly in the folding states of single-stranded loops. Our sequential and structural analyses showed that to prevent and control these highly pathogenic viruses, that is, to inhibit the gene expression of avian influenza virus H5N1 subtypes, we should consider the single-stranded loop regions of the HA cleavage site-coding sequences as the targets of RNA interference.     

Orisin and future distribution of the new A （H 1N1 ） influenza virus emerging in North America in 2009

The origin of the new A （H1N1） influenza virus recently emerging in North America is a hot controversial topic of significance in disease control and risk assessment. Some experts claimed that it was an unusually mongrelized mix of human, avian and swine influenza viruses, while some others concluded that it was totally a simple re-assortment hybrid of two lineages of swine influenza viruses. Here the phylogenetic diversity of the viral PB1, PA and PB2 gene sequences using online web servers, and the results suggest that all the 8 genetic segments of the new virus were possibly from two lineages of swine influenza viruses, and one of the lineage was a mongrelized mix of human, avian and swine influenza viruses emerging in the world approximately 10 years ago. Considering the recent epidemiological trends of the new virus, we believe it will spread more widely in the world and persist long in human populations. It also could spread among swine populations. The future wide spreading of the new virus may coincide the disappearance of a subtype of previous human influenza A virus.     

Spatial epidemiology of networked metapopulation: an overview

An emerging disease is one infectious epidemic caused by a newly transmissible pathogen, which has either appeared for the first time or already existed in human populations, having the capacity to increase rapidly in incidence as well as geographic range. Adapting to human immune system, emerging diseases may trigger large-scale pandemic spreading, such as the transnational spreading of SARS, the global outbreak of A（H1N1）, and the recent potential invasion of avian influenza A（H7N9）. To study the dynamics mediating the transmission of emerging dis- eases, spatial epidemiology of networked metapopulation provides a valuable modeling framework, which takes spatially distributed factors into consideration. This review elaborates the latest progresses on the spatial metapopula- tion dynamics, discusses empirical and theoretical findings that verify the validity of networked metapopulations, and the sketches application in evaluating the effectiveness of disease intervention strategies as well.     

Molecular patterns of avian influenza A viruses

Avian influenza A viruses could get across the species barrier and be fatal to humans. Highly pathogenic avian influenza H5N1 virus was an example. The mechanism of interspecies transmission is not clear as yet. In this research, the protein sequences of 237 influenza A viruses with different subtypes were transformed into pseudo-signals. The energy features were extracted by the method of wavelet packet decomposition and used for virus classification by the method of hierarchical clustering. The clustering results showed that five patterns existed in avian influenza A viruses, which associated with the phenotype of interspecies transmission, and that avian viruses with patterns C and E could across species barrier and those with patterns A, B and D might not have the abilities. The results could be used to construct an early warning system to predict the transmissibility of avian influenza A viruses to humans.     

Isolation and characterization of H7N9 viruses from live poultry markets--Implication of the source of current H7N9 infection in humans

On March 31, 2013, the National Health and Family Planning Commission announced that human infections with a previously undescribed influenza A (H7N9) virus had occurred in Shanghai and Anhui Province, China. To investigate the possible origins of the H7N9 viruses causing these human infections, we collected 970 samples, including drinking water, soil, and cloacal and tracheal swabs of poultry from live poultry markets and poultry farms in Shanghai and Anhui Province. Twenty samples were positive for the H7N9 influenza virus. Notably, all 20 viruses were isolated from samples collected from live poultry markets in Shanghai. Phylogenetic analyses showed that the six internal genes of these novel human H7N9 viruses were derived from avian H9N2 viruses, but the ancestor of their HA and NA genes is uncertain. When we examined the phylogenetic relationship between the H7N9 isolates from live poultry markets and the viruses that caused the human infections, we found that they shared high homology across all eight gene segments. We thus identified the direct avian origin of the H7N9 influenza viruses that caused the human infections. Importantly, we observed that the H7N9 viruses isolated from humans had acquired critical mutations that made them more "human-like". It is therefore imperative to take strong measures to control the spread of H7N9 viruses in birds and humans to prevent further threats to human health.     

Molecular characterization of H1N1 influenza A viruses from human cases in North America

Subtypes of H1N1 influenza virus can be found in humans in North America, while they are also associated with the infection of swine. Characterization of the genotypes of viral strains in human populations is important to understand the source and distribution of viral strains. Genomic and protein sequences of 10 isolates of the 2009 outbreak of influenza A （H1N1） virus in North America were obtained from GenBank database. To characterize the genotypes of these viruses, phylogenetic trees of genes PB2, PB1, PA, HA, NP, NA, NS and M were constructed by Phylip3.67 program and N-Linked glycosylation sites of HA, NA, PB2, NS1 and M2 proteins were analyzed online by NetNGlyc1.0 program. Phylogenetic analysis indicated that these isolates are virtually identical but may be recombinant viruses because their genomic fragments come from different viruses. The isolates also contain a characteristic lowly pathogenic amino acid motif at their HA cleavage sites （IPSIQSR↓GL）, and an E residue at position 627 of the PB2 protein which shows its high affinity to humans. The homologous model of M proteins showed that the viruses had obtained the ability of anti-amantadine due to the mutation at the drug-sensitive site, while sequence analysis of NA proteins indicated that the viruses are still susceptible to the neuraminidase inhibitor drug （i.e. oseltamivir and zanamivir） because no mutations have been observed. Our results strongly suggested that the viruses responsible for the 2009 outbreaks of influenza A （H1N1） virus have the ability to cross species barriers to infect human and mammalian animals based on molecular analysis. These findings may further facilitate the therapy and prevention of possible transmission from North America to other countries.     

Molecular characterization of H3N2 and H4N6 subtypes avian influenza viruses isolated from mallards in Poyang Lake, China in 2010

Poyang Lake is the largest inland freshwater lake in China and contains many species of wild birds and waterfowls.We conducted a survey of avian influenza viruses in nine semi-artificial waterfowl farms in Poyang Lake during January to March of 2010.Out of 1036 cloacal swabs collected,three H3N2 and one H4N6 influenza viruses were isolated from healthy mallards.All the isolates were genetically and phylogenetically characterized.The analysis of putative HA cleavage sites showed that all the four isolates possessed the molecular characteristics(QTRGL for H3N2 viruses,PEKASR for H4N6 virus) of lowly pathogenic avian influenza(LPAI) virus.The phylogenetic analysis of the viral genomes showed that all four virus isolates clustered in the Eurasian clade of influenza viruses.The M gene of the viruses possessed the highest homology with highly pathogenic H5N1 influenza viruses.In addition,co-infection of H3N2 and H4N6 in the same farm was observed.And interestingly,we isolated two subtypes viruses(H3N2 and H4N6) and their progeny virus(H3N2) with evidence of genome reassortment from the same farm,in which the PB1 and PB2 gene segments of H4N6 replaced those of the H3N2 strain.The results of animal infection experiments showed that all the four isolated viruses were lowly pathogenic to chickens and not pathogenic to mice,which was consistent with the results of genetic analysis.     

The mutation network for the hemagglutinin gene from the novel influenza A （H1N1 ） virus

A mutation network for the hemagglutinin gene （HA） of the novel type A （H1N1） influenza virus was constructed. Sequence homology analysis indicated that one HA sequence type from the viruses mainly isolated from Mexico was likely the original type in this epidemic. Based on the 658A and 1408T mutations in HA, the viruses evolving into this epidemic were divided into three categories, the Mexico, the transitional and the New York type. The three groups of viruses presented distinctive clustering features in their geographic distributions.     

Distribution and risk factors of hand,foot, and mouth disease in Changchun,northeastern China

Hand, foot, and mouth disease （HFMD） is a public health problem, and there have been increasing numbers of outbreaks in mainland China since 2008. Over 17,000 HFMD cases have been reported in Changchun between 2008 and 2011. This study characterized the temporal and spatial distribution of the disease and iden- tified the risk factors for HFMD. The main findings were as follows： （i） there were significant differences in HFMD incidence among age groups, with 86.8 % of reported cases in children younger than 5 years old, and boys showed a higher incidence than girls （〈6 years）; （ii） The disease affected the whole region and spanned a large geographic area, but there was a higher incidence in urban areas （median = 242 per 10,000 persons） and urban-rural border areas （median = 135 per 10,000 persons）, compared with rural areas （median = 75 per 10,000 persons）; and （iii） the incidence of HFMD in Changchun was significantly asso- ciated with the distance to the nearest freeway, GDP per capita, and the type of township.     

Special features of the 2009 pandemic swine-origin influenza A H1N1 hemagglutinin and neuraminidase

Since the 2009 pandemic H1N1 swine-origin influenza A virus (09 S-OIV) has reminded the world about the global threat of the ever changing influenza virus,many questions regarding the detailed re-assortment of influenza viruses yet remain unanswered.Influenza A virus is the causative agent of the pandemic flu and contains 2 major antigenic glycoproteins on its surface:(i) hemagglutinin (HA);and (ii) neuraminidase (NA).The structures of the 09 S-OIV HA and NA proteins (09H1 and 09N1) have recently been resolved in our laboratory and provide some clues as to why the 09 S-OIV re-assortment virus is highly infectious with severe consequences in humans.For example,the 09H1 is highly similar to the HA of the 1918 influenza A pandemic virus in overall structure and especially in regards to its 5 defined antibody binding epitopes.For 09N1,its most distinctive feature is the lack of a 150-loop active site cavity,which was previously predicted to be present in all N1 NAs,and we hypothesize that the 150-loop may play a important role in the substrate specificity (α2,3 or α2,6 linked sialic acid receptors) and enzymatic mechanism of influenza NA.Combination of the HA and NA with special characteristics for the 09 S-OIV might contribute to its high increased transmissibility in humans.     

Sequence and epitope analysis of surface proteins of avian influenza H5N1 viruses from Asian patients

Avian influenza virus strain H5N1 is a highly patho- genic type A influenza virus that has caused several outbreaks of severe poultry plagues in the past. H5N1 preferentially binds to receptors with α2-3 linked sialic acids on the surface of avian epithe…     

Spatial analyzing system for urban land use management based on GIS and multi-criteria assessment modeling

Urban land management requires the integration of a wide range of data on ecological process, environmental process and process on urban planning and development. This paper combined land suitability modeling with remote sensing （RS）, landscape ecological analysis and geographic information system （GIS） to develop a spatial analyzing system for urban expansion land management. The spatial analyzing system incorporates the use of a multi-criteria mechanism in GIS for the suitability evaluation of urban expansion land. Grey relational analysis （GRA） was combined with analytic hierarchy process （AHP） to address the uncertainties during the process of evaluation. This approach was applied to explicitly identify constraints and opportunities for future land conservation and development in Changsha City, China. Validation of the methodology showed a high degree of coincidence with the previous independent studies as regards ecological suitability. The methodology can be useful in environmental protection, land management and regional planning.     

Ensemble projection of 1―3℃ warming in China

Studies on the influences of climate change on biogeochemical cycles and on the key vulnerabilities and the risk from climate change suggest that annual surface temperature rise of 1 ℃, 2℃ and 3℃ above the present level would lead to changes in extreme weather and climate events, food production, fresh water resources, biodiversity, human mortality, etc. Here two sets of simulations as performed with seventeen atmosphere-ocean general circulation models （AOGCMs） for the Fourth Assessment Report of the Intergovernmental Panel on Climate Change （IPCC AR4）, i.e. the model outputs from the 20th Century Climate in Coupled Models （20C3M） and from the Special Report on Emissions Scenarios （SRES） emission scenarios B1, A1B and A2, are used to analyze spatial and temporal characteristics of the above values in China over the 21st century. The results indicate that the rate of warming varies from region to region. The above values are reached much later （earlier） when emission amount is lower （higher）, and spread of the time when the lower （higher） value is exceeded is narrower （wider） among the three scenarios. As far as the spatial pattern is concerned, the above values are crossed much earlier in northern China and the Tibetan Plateau with respect to the Yangtze-Huaihe River Valley and South China.     

Exploring the epidemic transmission network of SARS in-out flow in mainland China

The changing spatiotemporal patterns of the individual susceptible-infected-symptomatic-treated-recovered epidemic process and the interactions of information/material flows between regions,along with the 2002-2003 Severe Acute Respiratory Syndrome(SARS) epidemiological investigation data in mainland China,including three typical locations of individuals(working unit/home address,onset location and reporting unit),are used to define the in-out flow of the SARS epidemic spread.Moreover,the input/output transmission networks of the SARS epidemic are built according to the definition of in-out flow.The spatiotemporal distribution of the SARS in-out flow,spatial distribution and temporal change of node characteristic parameters,and the structural characteristics of the SARS transmission networks are comprehensively and systematically explored.The results show that(1) Beijing and Guangdong had the highest risk of self-spread and output cases,and prevention/control measures directed toward self-spread cases in Beijing should have focused on the later period of the SARS epidemic;(2) the SARS transmission networks in mainland China had significant clustering characteristics,with two clustering areas of output cases centered in Beijing and Guangdong;(3) Guangdong was the original source of the SARS epidemic,and while the infected cases of most other provinces occurred mainly during the early period,there was no significant spread to the surrounding provinces;in contrast,although the input/output interactions between Beijing and the other provinces countrywide began during the mid-late epidemic period,SARS in Beijing showed a significant capacity for spatial spreading;(4) Guangdong had a significant range of spatial spreading throughout the entire epidemic period,while Beijing and its surrounding provinces formed a separate,significant range of high-risk spreading during the mid-late period;especially in late period,the influence range of Beijing’s neighboring provinces,such as Hebei,was even slightly larger than that of Beijing;and(5) the input network had a low-intensity spread capacity and middle-level influence range,while the output network had an extensive high-intensity spread capacity and influence range that covered almost the entire country,and this spread and influence indicated that significant clustering characteristics increased gradually.This analysis of the epidemic in-out flow and its corresponding transmission network helps reveal the potential spatiotemporal characteristics and evolvement mechanism of the SARS epidemic and provides more effective theoretical support for prevention and control measures.