Urban structure and the risk of influenza A (H1N1) outbreaks in municipal districts

Changsha was one of the most affected areas during the 2009 A (H1N1) influenza pandemic in China. Here, we analyze the spatial–temporal dynamics of the 2009 pandemic across Changsha municipal districts, evaluate the relationship between case incidence and the local urban spatial structure and predict high-risk areas of influenza A (H1N1). We obtained epidemiological data on all cases of influenza A (H1N1) reported across municipal districts in Changsha during period May 2009–December 2010 and data on population density and basic geographic characteristics for 239 primary schools, 97 middle schools, 347 universities, 96 malls and markets, 674 business districts and 121 hospitals. Spatial–temporal K functions, proximity models and logistic regression were used to analyze the spatial distribution pattern of influenza A (H1N1) incidence and the association between influenza A (H1N1) cases and spatial risk factors and predict the infection risks. We found that the 2009 influenza A (H1N1) was driven by a transmission wave from the center of the study area to surrounding areas and reported cases increased significantly after September 2009. We also found that the distribution of influenza A (H1N1) cases was associated with population density and the presence of nearest public places, especially universities (OR = 10.166). The final predictive risk map based on the multivariate logistic analysis showed high-risk areas concentrated in the center areas of the study area associated with high population density. Our findings support the identification of spatial risk factors and high-risk areas to guide the prioritization of preventive and mitigation efforts against future influenza pandemics.     

从引发自墨西哥的A(H1N1)型流感说起

2003年春夏暴发的SARS疫情,带给我们的恐惧和惊慌仍然记忆犹新;今年4月由墨西哥引发继而波及全球21个国家和地区的A(H1N1)型流感事件,给世人呈现的却是中国人在处置时的镇定自若和从容不迫.     

甲型H1N1流感病毒性肺炎的临床及影像学表现3例报告

目的:总结3例甲型H1N1流感病毒性肺炎患者的呼吸道表现和胸部影像学特点,积累临床经验.方法:回顾性分析3例甲型H1N1流感患者入院时的呼吸道表现特点和胸部影像学动态变化.结果:3例男性患者,均有慢性基础病和吸烟史,发热持续1周以上,伴有咳嗽、咳痰、胸闷及气促等,但无咽痛和流涕症状.可有紫绀,咽部充血,双下肺散在湿啰音等表现.3例患者胸部X线和CT平扫检查显示双肺下野斑片状、云絮状、磨玻璃样或网格状高密度影等特征性表现,后期出现纤维化改变,双肺正常组织呈过度充气状态.结论:根据肺部影像学表现,结合临床,可做出甲型H1N1流感病毒性肺炎的诊断.     

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.     

2009年甲型H1N1流感临床研究回顾

2009年全球爆发的甲型H1N1流感由一种源于猪流感病毒、致人急性呼吸道疾病的新型流感病毒所致.本文总结了甲型H1N1流感病毒感染病例的临床特征、治疗及研究展望.     

媒体报道对禽流感(H7N9)传播影响的研究

研究媒体报道对传染病传播的影响。建立了受媒体影响的禽流感(H7N9)传播动力学模型,得到了模型的基本再生数。利用V函数、Dulac函数及极限方程理论等方法对模型进行了动力学性态的分析。证明了当基本再生数不大于1时,无病平衡点全局渐近稳定;当基本再生数大于1时,地方病平衡点全局渐近稳定。进一步,数值模拟显示了媒体报道对H7N9传播的具体影响。可通过媒体报道来控制传染病的规模。     

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.     

甲型H1N1流行与气象因子显著关联

2009年3月18日,墨西哥发现甲型H1N1流感疑似病例:2009年4月21日,美国疾病预防控制中心(CDC)报告2名儿童感染甲型H1N1流感病毒.随后,墨西哥、美国、加拿大等国家出现大量病例,甲型H1N1流感自美洲暴发流行.随着甲型H1N1流感在全球蔓延,世界卫生组织(WHO)将警告级别由3级逐渐提升为6级,表明全球进入流感大流行阶段.截至2010年4月14日,超过213个国家和地区报告了经实验室确诊的甲型H1N1流感病例,至少17770人死亡.     

发生甲型流感疫情时大学生体育行为变化调查研究——以河北省在校大学生为例

通过问卷调查对河北省6所大学在校大学生在发生甲型H1N1流感后的体育行为进行调查与研究,发现在疫情发生之后大学生的体育行为向积极的方向发展.在显性体育行为上,表现为参加体育锻炼的时间增多、参加项目增加等等;在隐性体育行为上,表现在参加体育锻炼的态度变得积极、体育绩效感增强等方面,并且所调查的绝大多数大学生有今后继续参加体育锻炼的愿望.讨论这种现象的原因,研究其与终身体育的关系.     

Official： China might have A（H1N1） Influenza vaccine by July

Chinese scientists have named the country＇s most recently discovered meat-eating dinosaur after its centuries-old Great Wall.
Xiongguanlong, the name of an early Cretaceous predator whose fossilized remains were found near the Jiayuguan, the western start point of the 8,850-km-long Ming Dynasty Great Wall, literally means ＂Dinosaur of the Grand Pass＂, said Li Daqing, a paleontologist with Gansu Provincial Bureau of Geo-Exploration and Mineral Development, on Friday.     

甲型H1N1流感在预防控制措施下的传播数学模型构建

从数学应用的角度,研究甲型H1N1流感的传播规律,将人群分为易感人群、病毒潜伏人群、发病人群、退出者人群四类. 分析了甲型H1N1流感在人群间的转化过程;日接触率和"聚集性突然爆发"事件被数学刻画,尝试性地构建了一个在预防控制阶段的传播数学模型.     

X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus

The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains-a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker-is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-A-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.     

Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors

H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects. Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-alpha2,6-galactose (SAalpha2,6Gal), whereas the latter prefer those ending in SAalpha2,3Gal (refs 3-6). A conversion from SAalpha2,3Gal to SAalpha2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor-binding haemagglutinin (HA) molecule that would enable avian H5N1 viruses to recognize human-type host cell receptors, it may be possible to predict (and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.     

禽流感病毒H5N1亚型RNA聚合酶蛋白表达纯化及晶体生长

通过使用原核表达载体大量表达H5N1病毒RNA聚合酶亚基PA-C257,PB1_N25,再经过GST亲和层析和Sephadex G-200层析柱纯化,获得了高纯度的蛋白复合体.采用悬滴气相扩散法筛选蛋白晶体,在1～1.5mol/L乙酸钠和pH7.9条件下获得了理想的晶体,为解析禽流感病毒RNA聚合酶三维结构并进一步认识其生物功能奠定了基础.     

Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia

A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2-4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.     

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.     

Increased substitution rate in H5N1 avian influenza viruses during mass vaccination of poultry

As a means of heated debate,mass vaccination of poultry has been used in some countries to control H5N1 highly pathogenic avian influenza(HPAI),which remains of global economic and public health significance.Theoretically,mass vaccination can act as an evolutionary selective force facilitating the emergence of vaccine-resistant viruses,similar to that widespread use of antibiotics facilitates the emergence of antibiotic-resistant bacteria.To support the hypothesis,the substitution rates in the two subunits,HA1 and HA2,of the viral hemagglutinin gene,were calculated using a Bayesian Markov Chain Monte Carlo(MCMC) approach.It was found that the rate in the HA1 subunit,but not in the HA2 subunit,increased significantly during periods of mass vaccination(2005 2010 in China and 2003 2009 in Indonesia),in contrast to the periods when no mass vaccination programs took place(1996 2004 in China and 2004 2008 in Thailand).Because substitutions in the HA1 subunit rather than in the HA2 subunit can lead to vaccine-resistant viruses,the results support that mass vaccination programs facilitate the emergence of vaccine-resistant viruses,which,in turn,will render mass vaccination programs less effective.Therefore,caution must be taken when adopting mass vaccination as a long-term strategy to control HPAI.     

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…