Large-scale spatial-transmission models of infectious disease

During transmission of seasonal endemic diseases such as measles and influenza, spatial waves of infection have been observed between large distant populations. Also, during the initial stages of an outbreak of a new or reemerging pathogen, disease incidence tends to occur in spatial clusters, which makes containment possible if you can predict the subsequent spread of disease. Spatial models are being used with increasing frequency to help characterize these large-scale patterns and to evaluate the impact of interventions. Here, I review several recent studies on four diseases that show the benefits of different methodologies: measles (patch models), foot-and-mouth disease (distance-transmission models), pandemic influenza (multigroup models), and smallpox (network models). This review highlights the importance of the household in spatial studies of human diseases, such as smallpox and influenza. It also demonstrates the need to develop a simple model of household demographics, so that these large-scale models can be extended to the investigation of long-time scale human pathogens, such as tuberculosis and HIV.     

2009甲型H1N1流感病毒的研究综述

2009年4月初,出现1种新型甲型（H1N1）流感病毒,并通过人—人传播蔓延全球,文章介绍了该病毒的分类与宿主范围,并对其病毒学及分子特征进行了概述,最后指出加强对猪群中流行的流感病毒监管的必要性及研制通用疫苗的重要性。     

A highly conserved neutralizing epitope on group 2 influenza A viruses

Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.     

AA鸡禽流感母源抗体和免疫抗体消长变化的研究

[目的]为AA鸡的禽流感预防提供依据。[方法]用不同剂量的2种禽流感疫苗免疫8日龄AA鸡,通过血凝抑制(HI)试验研究AA鸡禽流感母源抗体和免疫抗体的消长变化。[结果]AA鸡禽流感母源抗体在1~7日龄时缓慢下降,之后迅速下降,表明其半衰期约为2 d。2种禽流感疫苗均可用于AA鸡的预防接种,免疫后15 d,免疫抗体HI效价达到保护临界值,20 d时达到峰值,然后缓慢下降,43日龄时仍在临界值以上。2种不同剂量的禽流感灭活油乳剂疫苗接种后所产生的HI抗体效价的峰值差异极显著。[结论]选用禽流感灭活油乳剂疫苗,免疫剂量为0.5 ml/只,免疫时间为8日龄,整个饲养期免疫1次,即可预防商品代AA鸡禽流感。     

SOME PROBLEMS OF COSMICAL PHYSICS,SOLVED AND UNSOLVED

The Great success of theoretical investigations in recent times naturally leads enterprising spirits to use them not only in interpreting what we know or can verify by observation, but to lead us into regions where experiment is not available as a check. I believe that this does nothing but good in times like ours, when there is no danger of the doctrines even of a master being unduly pressed, if the evidence of observed fact turns against them. At the same time, we must not expect too much of pure intellect unchecked by observation. Theories that do not stand the test of time pass for the most part into complete oblivion, and we are apt to forget how appallingly large a mass of wreekage the total of them represents. The next generation remembers chiefly those that survive, and does not take full advantage of the lesson of how easy it is for an apparently inevitable conslusion to be wrong. Unless the argument carried its own verification by some accurate and previously unforeseen numerical coincidence, it is hard indeed to tell if we are on the right track.     

Assessment of vaccination strategies against highly pathogenic avian influenza in China

Vaccination for highly pathogenic avian influenza (HPAI) has been implemented in China for a decade, however, the virus is still present in poultry. A series of recombinant vaccines, Re-1 to Re-7, have been developed and used, and Re-8 will also be used in clinical settings to prevent the prevailing flu strains. The question remains, when can China eradicate the disease? Here, we review the epidemiology of H5 HPAI along with the development, usage and problems of vaccines. Further suggestions for controlling the disease in China are provided.     

Are we ready for pandemic influenza?

During the past year, the public has become keenly aware of the threat of emerging infectious diseases with the global spread of severe acute respiratory syndrome (SARS), the continuing threat of bioterrorism, the proliferation of West Nile virus, and the discovery of human cases of monkeypox in the United States. At the same time, an old foe has again raised its head, reminding us that our worst nightmare may not be a new one. In 2003, highly pathogenic strains of avian influenza virus, including the H5N1 and H7N7 subtypes, again crossed from birds to humans and caused fatal disease. Direct avian-to-human influenza transmission was unknown before 1997. Have we responded to these threats by better preparing for emerging disease agents, or are we continuing to act only as crises arise? Here we consider progress to date in preparedness for an influenza pandemic and review what remains to be done. We conclude by prioritizing the remaining needs and exploring the reasons for our current lack of preparedness for an influenza pandemic.     

Characterization of the reconstructed 1918 Spanish influenza pandemic virus

The pandemic influenza virus of 1918-1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of trypsin, caused death in mice and embryonated chicken eggs, and displayed a high-growth phenotype in human bronchial epithelial cells. Moreover, the coordinated expression of the 1918 virus genes most certainly confers the unique high-virulence phenotype observed with this pandemic virus.     

Emergence of drug-resistant influenza virus: population dynamical considerations

Given the considerable challenges to the rapid development of an effective vaccine against influenza, antiviral agents will play an important role as a first-line defense if a new pandemic occurs. The large-scale use of drugs for chemoprophylaxis and treatment will impose strong selection for the evolution of drug-resistant strains. The ensuing transmission of those strains could substantially limit the effectiveness of the drugs as a first-line defense. Summarizing recent data on the rate at which the treatment of influenza infection generates resistance de novo and on the transmission fitness of resistant virus, we discuss possible implications for the epidemiological spread of drug resistance in the context of an established population dynamic model.     

禽流感病毒疫苗研究进展

疫苗接种仍然是防控禽流感的最有效措施之一,目前有紧急接种、预防接种、系统接种及替代接种等4种常见形式。禽流感疫苗的主要类型包括灭活全病毒疫苗、亚单位疫苗、重组病毒载体疫苗、DNA疫苗、复制缺陷型疫苗、病毒样颗粒疫苗及通用疫苗等,影响其免疫效果的因素有免疫原选择及佐剂类型、病毒变异、决策机构的反应速度、免疫覆盖率、疫苗质量及稳定性、遗传结构及机体免疫状态、加强免疫方案等。鉴于传统禽流感疫苗不能对不同亚型禽流感病毒（AIV）及变异株提供交叉保护,且所使用的油佐剂副作用较大,对动物机体损伤较严重,今后应加强研制新型免疫佐剂及其他更安全高效的新型疫苗来弥补现有禽流感疫苗的不足。     

h指数及其衍生指标评估兽用疫苗领域单篇专利的适用性探索

随着禽流感、非洲猪瘟等疾病的出现,兽用疫苗的开发研制成为了动物防疫体系建设的重要一环,同时兽用疫苗领域国际竞争日益激烈,直接影响到我国相关企业的生存和发展,因此国家必须加强对兽用疫苗领域专利质量和专利保护的重视.本文以计量学中的h指数及其衍生指标为对象,研究其与传统专利价值评估指标的关系,通过相关性分析来筛选评估兽用疫苗领域高价值专利的指标.结果表明:h指数、g指数和hg指数这三个指标,与传统专利价值评估指标相关性强,且计算简便,相对于传统指标,能够快速准确地对兽用疫苗领域专利价值进行预估.     

A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission

The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show that only a modest change in the 1918 influenza hemagglutinin receptor binding site alters the transmissibility of this pandemic virus. Two amino acid mutations that cause a switch in receptor binding preference from the human alpha-2,6 to the avian alpha-2,3 sialic acid resulted in a virus incapable of respiratory droplet transmission between ferrets but that maintained its lethality and replication efficiency in the upper respiratory tract. Furthermore, poor transmission of a 1918 virus with dual alpha-2,6 and alpha-2,3 specificity suggests that a predominant human alpha-2,6 sialic acid binding preference is essential for optimal transmission of this pandemic virus. These findings confirm an essential role of hemagglutinin receptor specificity for the transmission of influenza viruses among mammals.     

Impact of the COVID-19 pandemic on agricultural exports

The COVID-19 outbreak has shocked the world's economies in the year of 2020. As this pandemic spreads around the globe, many experts feared that the global food supplies might start running short, especially if supply chains were disrupted. COVID-19 also added to the uncertainty of the business operation. Therefore, it is critical to understand how COVID-19 pandemic affected global food supply and market. In this study, we investigate the impact of COVID-19 on agricultural export companies in China using a unique firm-level survey data. We found that although on average agricultural businesses experienced declines in the exports, exports of some agricultural products especially grain and oil held strong and even increased, implying the essential demand for staple food during the pandemic. Not surprisingly, exports of medicinal herb also increased significantly during the pandemic. However, exports of goods such as edible fungus and horticultural products sharply decreased. Our results also showed that in general, impact of COVID-19 on smaller firms was more severe than that on larger firms. The results of this study can provide useful guidance and implications for agricultural businesses and policy makers on their COVID-19 mitigation efforts to navigate this global pandemic.     

禽流感与人类健康

禽流感(avian influenza,AI)是由A型流感病毒(avian influenza virus)引起的一种禽类感染征或疾病综合症,高致病性禽流感(highly pathogenic avian influenza,HPAI)可引起禽类100％的死亡。由于抗原转变和抗原漂移,禽流感病毒是高度可变的。人禽流感是指高致病性禽流感病毒跨越物种界限,引起人类感染的一种新发传染病。目前,全球已发现H5N1、H7N7、H9N2等亚型禽流感病毒可感染人类。但目前还没有发现禽流感病毒具有在人群中相互传播的能力。对禽流感必须采用积极的预防策略。在加强监测的基础上,对家禽采用扑杀和免疫相结合的措施,可以有效地控制禽流感的流行。研制人类流感疫苗,是预防新的流感病毒株的流行的可靠保证。     

Airborne transmission of influenza A/H5N1 virus between ferrets

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.     

靶向甲型流感病毒血凝素的人源单克隆抗体研究进展

甲型流感病毒感染性强,宿主广泛,主要感染禽类,其次为哺乳动物。当跨物种传染事件发生时,有可能造成流感大流行,因此,对病毒实施及时有效的监控,以及研发抗流感病毒药物刻不容缓。流感病毒表面的糖蛋白血凝素在病毒入侵宿主细胞的过程中发挥了关键的作用,可作为单克隆抗体药物的主要靶点。针对血凝素的单克隆抗体能够有效抑制病毒传播,保护宿主。因此,本文综述了目前报道的针对甲型流感病毒血凝素糖蛋白的人单克隆抗体,为后续抗流感药物的研发提供新的思路和展望。     

Recombination in the hemagglutinin gene of the 1918 "Spanish flu"

When gene sequences from the influenza virus that caused the 1918 pandemic were first compared with those of related viruses, they yielded few clues about its origins and virulence. Our reanalysis indicates that the hemagglutinin gene, a key virulence determinant, originated by recombination. The "globular domain" of the 1918 hemagglutinin protein was encoded by a part of a gene derived from a swine-lineage influenza, whereas the "stalk" was encoded by parts derived from a human-lineage influenza. Phylogenetic analyses showed that this recombination, which probably changed the virulence of the virus, occurred at the start of, or immediately before, the pandemic and thus may have triggered it.     

Virus of the 1918 influenza pandemic era: new evidence about its antigenic character

In serums of unusually isolated Pacific islanders whose only exposure to influenza occurred during the era of the 1918 pandemic the residual neutralizing antibody was greatest to the PR/8 and BH strains of human type A influenza virus, significantly lower to swine influenza virus, and absent to equine or later human type A virus strains. The pandemic virus was thus antigenically closer to human type A strains isolated during the middle 1930's than to other known influenza virus types.     

The structure and receptor binding properties of the 1918 influenza hemagglutinin

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.     

H5亚型禽流感研究势态——基于Citespace的文献计量分析

为准确把握H5亚型禽流感的研究进展，本研究基于CNKI文献数据库中的393篇文献和Web of Science(WOS)文献数据库中的1 560篇文献为研究样本，通过信息可视化技术对2个数据库中的文献样本的发文国家、文献数量、高频被引文献、高频关键词、主要发表作者和机构等进行分析。结果表明:1)国际上中国和美国在该领域的研究较多，两国发文量占比可达56.80%；每年文献数量与禽流感疫情的严重程度密切相关。与CNKI文献样本相比，WOS文献样本的文献数量、高频被引文献的被引频次更具有优势，并且WOS文献样本中发文机构之间和发文作者之间的合作更密切。2)高频被引文献和高频关键词在一定程度上反映了该领域的研究热点，主要包括野鸟导致H5亚型禽流感病毒的传播和进化；H5亚型禽流感的流行病学、致病机制和免疫疗法；重组疫苗、灭活疫苗和基于血凝素HA的广谱疫苗等新型疫苗研发；H5亚型禽流感病毒突发的防控措施等内容。本研究认为在未来疫情的长期监测与预测、病毒的快速检测技术和新型疫苗的开发等仍是研究热点，为H5亚型禽流感领域工作者提供参考价值。