Strategies for mitigating an influenza pandemic

Development of strategies for mitigating the severity of a new influenza pandemic is now a top global public health priority. Influenza prevention and containment strategies can be considered under the broad categories of antiviral, vaccine and non-pharmaceutical (case isolation, household quarantine, school or workplace closure, restrictions on travel) measures. Mathematical models are powerful tools for exploring this complex landscape of intervention strategies and quantifying the potential costs and benefits of different options. Here we use a large-scale epidemic simulation to examine intervention options should initial containment of a novel influenza outbreak fail, using Great Britain and the United States as examples. We find that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2-3 weeks unless more than 99% effective. School closure during the peak of a pandemic can reduce peak attack rates by up to 40%, but has little impact on overall attack rates, whereas case isolation or household quarantine could have a significant impact, if feasible. Treatment of clinical cases can reduce transmission, but only if antivirals are given within a day of symptoms starting. Given enough drugs for 50% of the population, household-based prophylaxis coupled with reactive school closure could reduce clinical attack rates by 40-50%. More widespread prophylaxis would be even more logistically challenging but might reduce attack rates by over 75%. Vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy. Estimates of policy effectiveness will change if the characteristics of a future pandemic strain differ substantially from those seen in past pandemics.     

Modelling disease outbreaks in realistic urban social networks

Most mathematical models for the spread of disease use differential equations based on uniform mixing assumptions or ad hoc models for the contact process. Here we explore the use of dynamic bipartite graphs to model the physical contact patterns that result from movements of individuals between specific locations. The graphs are generated by large-scale individual-based urban traffic simulations built on actual census, land-use and population-mobility data. We find that the contact network among people is a strongly connected small-world-like graph with a well-defined scale for the degree distribution. However, the locations graph is scale-free, which allows highly efficient outbreak detection by placing sensors in the hubs of the locations network. Within this large-scale simulation framework, we then analyse the relative merits of several proposed mitigation strategies for smallpox spread. Our results suggest that outbreaks can be contained by a strategy of targeted vaccination combined with early detection without resorting to mass vaccination of a population.     

成都市某大型企业传染病风险及防制对策分析

目的：分析某大型企业传染病发生风险因素，探讨防制对策。方法：设计调查表，进行现场调查，结合本地传染病历史数据和文献进行分析。结果：在没有暴发疫情的情况下，该企业传染病年总体发病数在233例以上。该企业具有员工数量大、流动性强、18—25岁年龄组占81．25％等特点，员工存在免疫空白、人群密度高、自我保护能力差、人员接触密切、配套措施不足等风险。结论：该企业可能发生暴发疫情的传染病危险度分为高、中、低三个等级；防制对策主要有加强疾病监测、健康教育、适时接种疫苗等。     

Herd immunity to helminth infection and implications for parasite control

Despite much research on immunological responses to helminth parasites, knowledge of the dynamic interplay between levels of herd immunity in humans and the rates of exposure, establishment and mortality of parasites remains limited. We describe here a simple mathematical model for the population dynamics of helminth infections which mirrors the development of a degree of acquired immunity within populations which are genetically heterogeneous with respect to immunological responsiveness. We interpret observed patterns in the age-specific intensity of infection and attempt to understand the possible effects of control measures based on chemotherapy and vaccination. Mass chemotherapy can, in some circumstances, reduce the level of herd immunity such that average worm burdens in the adult age classes rise above their precontrol levels. When certain individuals or groups are predisposed to heavy infection, selective or targeted drug treatment can have significantly greater impact than mass or random application. Conversely, model predictions suggest that effective parasite control by vaccination (if and when vaccines become available) is difficult to achieve in communities that are genetically heterogeneous in their ability to mount protective responses to infection.     

Modelling vaccination strategies against foot-and-mouth disease

Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in advance of an outbreak, or combinations of reactive vaccination and culling strategies during an epidemic. Consistent with standard epidemiological theory, mass prophylactic vaccination could reduce greatly the potential for a major epidemic, while the targeting of high-risk farms increases efficiency. Given sufficient resources and preparation, a combination of reactive vaccination and culling might control ongoing epidemics. We also explore a reactive strategy, 'predictive' vaccination, which targets key spatial transmission loci and can reduce markedly the long tail that characterizes many FMD epidemics. These analyses have broader implications for the control of human and livestock infectious diseases in heterogeneous spatial landscapes.     

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.     

后疫情时代中国散发疫情综合评价体系构建及应用

 为增强散发疫情防控的科学性，从疫情防控、疫情溯源以及疫情背景3个维度，疫情持续时间、确诊病例、发现途径、流动人口管理政策、流调追踪、核酸检测等9个分指标，构建疫情散发防控效率评价指标体系，对2020年6月1日至2021年6月1日全国32个地区散发疫情的控制情况进行计算与评估。研究结果显示，中国散发疫情防控存在地区间防控效率差异明显、防控措施强度与疫情严重程度不相适应、地区间流动人口的管理政策缺乏统一的科学依据等问题，在此基础上提出了针对性的改进建议。     

Anthrax kills wild chimpanzees in a tropical rainforest

Infectious disease has joined habitat loss and hunting as threats to the survival of the remaining wild populations of great apes. Nevertheless, relatively little is known about the causative agents. We investigated an unusually high number of sudden deaths observed over nine months in three communities of wild chimpanzees (Pan troglodytes verus) in the Ta? National Park, Ivory Coast. Here we report combined pathological, cytological and molecular investigations that identified Bacillus anthracis as the cause of death for at least six individuals. We show that anthrax can be found in wild non-human primates living in a tropical rainforest, a habitat not previously known to harbour B. anthracis. Anthrax is an acute disease that infects ruminants, but other mammals, including humans, can be infected through contacting or inhaling high doses of spores or by consuming meat from infected animals. Respiratory and gastrointestinal anthrax are characterized by rapid onset, fever, septicaemia and a high fatality rate without early antibiotic treatment. Our results suggest that epidemic diseases represent substantial threats to wild ape populations, and through bushmeat consumption also pose a hazard to human health.     

Strategies for containing an emerging influenza pandemic in Southeast Asia

Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.     

Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys.

Infection of macaques with simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) are useful models for studies of immunotherapy and vaccination against HIV as well as for testing of antiviral drugs. Vaccine research showing protective immunity in immunized monkeys has indicated that it will be possible to develop a vaccine for prevention of human HIV infection, although many hurdles remain. The design of an HIV vaccine would be helped if the basis of the protective immunity could be elucidated. Passive immune prophylaxis offers a means to determine the relative role of antibodies in protection against infection. We have studied whether a transfer of antibodies can prevent HIV-2 and SIVsm (SIV of sooty mangabey origin) infection in cynomolgus monkeys. Sera with high antibody titres were collected, heat-treated and injected into naive animals 6 h before challenge with 10-100 monkey-infectious doses of live homologous virus. All control animals treated with normal monkey serum (n = 6) or no serum (n = 39) became infected by the challenge virus, whereas five out of seven animals pretreated with antibody-containing serum at a dose of 9 ml kg-1 resisted infection. Thus passively transferred antibodies can protect against a low-dose lentivirus challenge in a nonhuman primate.     

食物链养分管理——中国可持续发展面临的挑战

人类食物链养分的流动及其管理决定了资源、环境、社会经济、生产、食物安全等多个可持续发展目标的实现。结合近年研究结果和文献资料,系统地分析了我国未来可持续发展中食物链养分管理的重要性及其难点,提出了相应的优化食物链养分管理建议。分析结果表明,在21世纪,随着中国人口增长、社会经济发展和生活水平的逐步提高,食物链养分流量将进一步加大,更多的资源消耗和环境养分排放也随之而来;未来将面临更为严峻的食物链养分问题;目前的养分管理模式不适应于未来的需求,这些问题将是我国可持续发展面临的重要挑战。为此,提出优化食物营养结构以减少过量养分摄入、加快提高食物链养分利用效率和养分循环率、加强食物链养分管理研究等建议。     

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.     

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.     

现有病毒疫苗用于防治新冠肺炎的可行性分析

新冠肺炎的爆发严重危害人类健康和公共卫生安全,已引起全球范围内的高度关注。预防病毒性疾病最有效的措施是接种疫苗,但是目前还没有专门针对新型冠状病毒的疫苗。考虑到疫情的严重性,对同为RNA病毒的流感病毒、其他冠状病毒相关疫苗的研究进行了综述,并通过对这些病毒氨基酸水平的序列比对发现,新冠病毒的棘突糖蛋白与H1N1、H3N2、B型Victoria系和B型Yamagata系流感病毒的血凝素糖蛋白之间具有一定的相似性。由于血凝素糖蛋白是目前商用流感疫苗的主要作用靶点,因此推测,现有季节性商用流感疫苗在新冠肺炎的防控方面可能也具有一定的应用潜能。除此之外,由于新冠病毒与SARS冠状病毒的棘突糖蛋白和核蛋白之间均具有高度的相似性,而SARS冠状病毒疫苗又主要从上述两种蛋白研制而来,因此建议在短期内,可以将目前正在研制的SARS冠状病毒疫苗作为新冠病毒特效疫苗的替代物来使用。     

水产品中恩诺沙星药物残留检测方法研究进展

恩诺沙星属于喹诺酮类抗生素药物,具有广谱杀菌、耐药菌少等优点,被广泛用于水产养殖疾病的防治。该药物使用不当极易造成水产品中残留超标进而危害人体健康。主要从样品前处理技术和水产品中恩诺沙星残留检测方法两方面进行阐述,并对各种检测方法的特点进行分析讨论,以期为我国水产品中恩诺沙星残留的检测和监管提供参考。     

Concurrent density dependence and independence in populations of arctic ground squirrels

No population increases without limit. The processes that prevent this can operate in either a density-dependent way (acting with increasing severity to increase mortality rates or decrease reproductive rates as density increases), a density-independent way, or in both ways simultaneously. However, ecologists disagree for two main reasons about the relative roles and influences that density-dependent and density-independent processes have in determining population size. First, empirical studies showing both processes operating simultaneously are rare. Second, time-series analyses of long-term census data sometimes overestimate dependence. By using a density-perturbation experiment on arctic ground squirrels, we show concurrent density-dependent and density-independent declines in weaning rates, followed by density-dependent declines in overwinter survival during hibernation. These two processes result in strong, density-dependent convergence of experimentally increased populations to those of control populations that had been at low, stable levels.     

The buffer effect and large-scale population regulation in migratory birds

Buffer effects occur when sites vary in quality and fluctuations in population size are mirrored by large changes in animal numbers in poor-quality sites but only small changes in good-quality sites. Hence, the poor sites 'buffer' the good sites, a mechanism that can potentially drive population regulation if there are demographic costs of inhabiting poor sites. Here we show that for a migratory bird this process can apply on a country-wide scale with consequences for both survival and timing of arrival on the breeding grounds (an indicator of reproductive success). The Icelandic population of the black-tailed godwit, Limosa limosa islandica, wintering in Britain has increased fourfold since the 1970s (ref. 5) but rates of change within individual estuaries have varied from zero to sixfold increases. In accordance with the buffer effect, rates of increase are greater on estuaries with low initial numbers, and godwits on these sites have lower prey-intake rates, lower survival rates and arrive later in Iceland than godwits on sites with stable populations. The buffer effect can therefore be a major process influencing large-scale population regulation of migratory species.     

Unbound or distant planetary mass population detected by gravitational microlensing

Since 1995, more than 500 exoplanets have been detected using different techniques, of which 12 were detected with gravitational microlensing. Most of these are gravitationally bound to their host stars. There is some evidence of free-floating planetary-mass objects in young star-forming regions, but these objects are limited to massive objects of 3 to 15 Jupiter masses with large uncertainties in photometric mass estimates and their abundance. Here, we report the discovery of a population of unbound or distant Jupiter-mass objects, which are almost twice (1.8(+1.7)(-0.8)) as common as main-sequence stars, based on two years of gravitational microlensing survey observations towards the Galactic Bulge. These planetary-mass objects have no host stars that can be detected within about ten astronomical units by gravitational microlensing. However, a comparison with constraints from direct imaging suggests that most of these planetary-mass objects are not bound to any host star. An abrupt change in the mass function at about one Jupiter mass favours the idea that their formation process is different from that of stars and brown dwarfs. They may have formed in proto-planetary disks and subsequently scattered into unbound or very distant orbits.     

Transmission potential of smallpox in contemporary populations.

Despite eradication, smallpox still presents a risk to public health whilst laboratory stocks of virus remain. One factor crucial to any assessment of this risk is R0, the average number of secondary cases infected by each primary case. However, recently applied estimates have varied too widely (R0 from 1.5 to >20) to be of practical use, and often appear to disregard contingent factors such as socio-economic conditions and herd immunity. Here we use epidemic modelling to show a more consistent derivation of R0. In isolated pre-twentieth century populations with negligible herd immunity, the numbers of cases initially rose exponentially, with an R0 between 3.5 and 6. Before outbreak controls were applied, smallpox also demonstrated similar levels of transmission in 30 sporadic outbreaks in twentieth century Europe, taking into account pre-existing vaccination levels (about 50%) and the role of hospitals in doubling early transmission. Should smallpox recur, such estimates of transmission potential (R0 from 3.5 to 6) predict a reasonably rapid epidemic rise before the implementation of public health interventions, because little residual herd immunity exists now that vaccination has ceased.     

Three different viruses observed from the tissues of diseased mandarin fishSiniperca chuatsi

Three different kinds of viruses, the spherical virus SCSV with a diameter of about 280 rm, the rhabdovirus SCRV with a size about 250 × 120 nm, and the baculovirus SCBV with a size about 200 × 100 nm, were observed from the tissues of diseased mandarin fishSiniperca chuatsi with outbreak of infection and acute lethality. This phenomenon implicated that the reason why the epizootic disease of mandarin fish could not be quenched by only one kind of virus vaccine can be explained by the fact that the fish may be infected by different kinds of viruses. Therefore, more attention should be paid to the complexity of virus pathogens in the prevention strategy for mandarin fish diseases.