Avian flu pandemic: Can we prevent it?

Outbreaks of highly pathogenic H5N1 avian influenza in Southeast Asia, Europe and Africa have led to devastating consequences for poultry, and have resulted in numerous infections in humans. Although these infections from the animal reservoir continue to accumulate, the virus does not seem to spread extensively among humans. However, for example, a process of genetic reassortment could occur in a human who is co-infected with avian influenza A virus and a human strain of influenza A virus. The resulting new virus might then be able to easily infect humans and spread from human to human. Therefore, many experts expect the occurrence of a pandemic due to a mutant virus which can be easily transmitted among humans. Thus, currently, a major public health concern is the next influenza pandemic; yet it remains unclear how to control such a crisis. In this paper, we investigate relations between the evolution of virulence and an effectiveness of pandemic control measures after the emergence of mutant avian influenza; one is an elimination policy of infected birds with avian influenza and the other is a quarantine policy of infected humans with mutant avian influenza. We found that each of these prevention policies can be ineffective (i.e., increase human morbidity or mortality). Further, interestingly, the same intervention might, under the same conditions, increase human morbidity and decrease human mortality, or vice versa. Our practical findings are that the quarantine policy can effectively reduce both human morbidity and mortality but the elimination policy increases either human morbidity or mortality in a worst case situation.     

Prevention of avian influenza epidemic: what policy should we choose?

Human-to-human transmission of the avian influenza has been extremely rarely reported, and is considered as limited, inefficient and unsustained. However, experts warn an occurrence of “mutant avian influenza”, which can easily spread among humans, because the avian influenza is already endemic, in particular in Asian poultry, and it is evolving in domestic and wild birds, pigs and humans. Outbreak of such mutant avian influenza in the human world may have devastating consequences, which are comparable with these for the 1918 “Spanish influenza”. In this paper we develop a mathematical model for the spread of the mutant avian influenza, and explore the effectivity of the prevention policies, namely the elimination policy which increases the effective additional death rate of the infected birds and the quarantine policy which reduces the number of infective contacts.     

Avian-human influenza epidemic model

A mathematical model is proposed to interpret the spread of avian influenza from the bird world to the human world. Our mathematical model warns that two types of the outbreak of avian influenza may occur if the humans do not prevent the spread of avian influenza. Moreover, it suggests that we cannot feel relieved although the total infected humans are kept at low level. In order to prevent spread of avian influenza in the human world, we must take the measures not only for the birds infected with avian influenza to exterminate but also for the humans infected with mutant avian influenza to quarantine when mutant avian influenza has already occurred. In particular, the latter measure is shown to be important to stop the second pandemic of avian influenza.     

21世纪的首次大流行：2009甲型（H1N1）流感

2009年4月初,在墨西哥和美国出现一种新型甲型（H1N1）流感病毒。该病毒通过人-人传播迅速在全球范围蔓延。该病毒拥有来自人流感病毒、禽流感病毒和猪流感病毒的基因片段,其HA基因与引发1918年大流行的流感病毒株的HA基因同源性很高。该病毒倾向于感染儿童、青少年、孕妇,以及具有心肺疾病的人。据观察,它在人群中的传播能力高于季节性流感。部分感染患者具有在季节性流感中罕见的呕吐和腹泻症状。先前的流感病毒大流行和2009年爆发的甲型H1N1流感病毒大流行表明,由于流感病毒变异速度快、容易发生基因重排,新产生的变异毒株很可能造成新的大流行,威胁人类健康。由于禽流感病毒和人流感病毒都能感染猪,猪被认为是通过基因重排生成新的大流行病毒的＂混合容器＂。     

Influenza type A in humans,mammals and birds: determinants of virus virulence,host-range and interspecies transmission

The virulence of a virus is determined by its ability to adversely affect the host cell, host organism or population of host organisms. Influenza A viruses have been responsible for four pandemics of severe human respiratory disease this century. Avian species harbour a large reservoir of influenza virus strains, which can contribute genes to potential new pandemic human strains. The fundamental importance of understanding the role of each of these genes in determining virulence in birds and humans was dramatically emphasised by the recent direct transmission of avian influenza A viruses to humans, causing fatal infection but not community spread. An understanding of the factors involved in transmission between avian and mammalian species should assist in the development of better surveillance strategies for early recognition of influenza A virus strains having human pandemic potential, and possibly in the design of anti-viral strategies.     

Pandemic policy and planning considerations for universities: findings from a tabletop exercise

The potential for a novel influenza virus to cause a pandemic represents a significant threat to global health. Planning for pandemic flu, as compared to planning for other types of hazards, presents some unique challenges to businesses, communities, and education institutions. To identify and address the challenges that may be faced by major metropolitan universities during a flu pandemic, a tabletop exercise was developed, offered, and evaluated. Its purpose was to assess existing University of Washington (UW) plans and policies for responding to an influenza pandemic. On May 31, 2006, more than 50 participants, including UW administrators and unit leaders and a number of key external partners, participated in a tabletop exercise designed to simulate all phases of an influenza pandemic. This exercise revealed existing gaps in university pandemic influenza plans and policies, including issues related to isolation and quarantine, continuity of operations, disaster mental health services, integration of volunteers into a disaster response, tracking travel of university students and personnel, communication problems, and ways to meet the needs of resident and foreign students and faculty during an outbreak. Policy and planning recommendations are offered that address each of these challenges faced by UW as well as other major research universities and colleges.     

Simulating the effect of quarantine on the spread of the 1918–19 flu in Central Canada

Quarantine is often proposed and sometimes used to control the spread of infectious diseases through a human population. Yet there is usually little or no information on the effectiveness of attempting to quarantine humans that is not of an anecdotal or conjectural nature. This paper describes how a compartmental model for the geographic spread of infectious diseases can be used to address the potential effectiveness of human quarantine. The model is applied to data from the historical record in central Canada around the time of the 1918–19 influenza epidemic. Information on the daily mobility patterns of individuals engaged in the fur trade throughout the region prior to, during, and immediately after the epidemic are used to determine whether rates of travel were affected by informal quarantine policies imposed by community leaders. The model is then used to assess the impact of observed differences in travel on the spread of the epidemic. Results show that when mobility rates are very low, as in this region, quarantine practices must be highly effective before they alter disease patterns significantly. Simulation results suggest, though, that effectiveness varies depending on when the limitation on travel between communities is implemented and how long it lasts, and that a policy of introducing quarantine at the earliest possible time may not always lead to the greatest reduction in cases of a disease.     

Population-wide emergence of antiviral resistance during pandemic influenza

Background

The emergence of neuraminidase inhibitor resistance has raised concerns about the prudent use of antiviral drugs in response to the next influenza pandemic. While resistant strains may initially emerge with compromised viral fitness, mutations that largely compensate for this impaired fitness can arise. Understanding the extent to which these mutations affect the spread of disease in the population can have important implications for developing pandemic plans.

Methodology/Principal Findings

By employing a deterministic mathematical model, we investigate possible scenarios for the emergence of population-wide resistance in the presence of antiviral drugs. The results show that if the treatment level (the fraction of clinical infections which receives treatment) is maintained constant during the course of the outbreak, there is an optimal level that minimizes the final size of the pandemic. However, aggressive treatment above the optimal level can substantially promote the spread of highly transmissible resistant mutants and increase the total number of infections. We demonstrate that resistant outbreaks can occur more readily when the spread of disease is further delayed by applying other curtailing measures, even if treatment levels are kept modest. However, by changing treatment levels over the course of the pandemic, it is possible to reduce the final size of the pandemic below the minimum achieved at the optimal constant level. This reduction can occur with low treatment levels during the early stages of the pandemic, followed by a sharp increase in drug-use before the virus becomes widely spread.

Conclusions/Significance

Our findings suggest that an adaptive antiviral strategy with conservative initial treatment levels, followed by a timely increase in the scale of drug-use, can minimize the final size of a pandemic while preventing large outbreaks of resistant infections.     

Emergence of drug resistance: implications for antiviral control of pandemic influenza

Given the danger of an unprecedented spread of the highly pathogenic avian influenza strain H5N1 in humans, and great challenges to the development of an effective influenza vaccine, antiviral drugs will probably play a pivotal role in combating a novel pandemic strain. A critical limitation to the use of these drugs is the evolution of highly transmissible drug-resistant viral mutants. Here, we develop a mathematical model to evaluate the potential impact of an antiviral treatment strategy on the emergence of drug resistance and containment of a pandemic. The results show that elimination of the wild-type strain depends crucially on both the early onset of treatment in indexed cases and population-level treatment. Given the probable delay of 0.5-1 day in seeking healthcare and therefore initiating therapy, the findings indicate that a single strategy of antiviral treatment will be unsuccessful at controlling the spread of disease if the reproduction number of the wild-type strain (R0s) exceeds 1.4. We demonstrate the possible occurrence of a self-sustaining epidemic of resistant strain, in terms of its transmission fitness relative to the wild-type, and the reproduction number R0s. Considering reproduction numbers estimated for the past three pandemics, the findings suggest that an uncontrollable pandemic is likely to occur if resistant viruses with relative transmission fitness above 0.4 emerge. While an antiviral strategy is crucial for containing a pandemic, its effectiveness depends critically on timely and strategic use of drugs.     

Absence of 2009 Pandemic H1N1 Influenza A Virus in Fresh Pork

The emergence of the pandemic 2009 H1N1 influenza A virus in humans and subsequent discovery that it was of swine influenza virus lineages raised concern over the safety of pork. Pigs experimentally infected with pandemic 2009 H1N1 influenza A virus developed respiratory disease; however, there was no evidence for systemic disease to suggest that pork from pigs infected with H1N1 influenza would contain infectious virus. These findings support the WHO recommendation that pork harvested from pandemic influenza A H1N1 infected swine is safe to consume when following standard meat hygiene practices.     

Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus

Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.     

Pre-clinical development of cell culture (Vero)-derived H5N1 pandemic vaccines

The rapid spread of avian influenza (H5N1) and its transmission to humans has raised the possibility of an imminent pandemic and concerns over the ability of standard influenza vaccine production methods to supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains, produced at a variety of manufacturing scales, were demonstrated to be highly immunogenic in animal models without the need for adjuvant. The vaccines induce cross-neutralising antibodies and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from other clades. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high-yield production of a candidate pandemic vaccine.     

Lessons from pandemic H1N1 2009 to improve prevention, detection, and response to influenza pandemics from a One Health perspective

In April 2009, a novel influenza A subtype H1N1 triple reassortant virus (novel H1N1 2009), composed of genes from swine, avian, and human influenza A viruses, emerged in humans in the United States and Mexico and spread person-to-person around the world to become the first influenza pandemic of the 21st century. The virus is believed to have emerged from a reassortment event involving a swine virus some time in the past 10 to 20 years, but pigs, pork, and pork products have not been involved with infection or spread of the virus to or among people. Because countries quickly implemented recently developed pandemic influenza plans, the disease was detected and reported and public health authorities instituted control measures in a timely fashion. But the news media's unfortunate and inappropriate naming of the disease as the "swine flu" led to a drop in the demand for pork and several countries banned pork imports from affected countries, resulting in serious negative economic impacts on the pork industry. With the continual circulation and interspecies transmission of human, swine, and avian influenza viruses in countries around the world, there are calls for strengthening influenza surveillance in pigs, birds, and other animals to aid in monitoring and assessing the risk of future pandemic virus emergence involving different species. We identify and discuss several lessons to be learned from pandemic H1N1 2009 from a One Health perspective, as stronger collaboration among human, animal, and environmental health sectors is necessary to more effectively prevent or detect and respond to influenza pandemics and thus improve human, animal, and environmental health and well-being.     

宠物鸟·疫病·公共卫生

宠物鸟种类多,来源地广,检验检疫预防措施缺乏,致使宠物鸟疫病不断传播,并造成人类的感染,已经威胁到公共卫生。宠物鸟疫病中以新城疫、禽流感、鹦鹉热最为常见,而且与人类关系密切,具有重要的公共卫生学意义。本文从宠物鸟在疫病流行传播中的意义、疫病的宿主感染谱、疫病的流行特征以及疫病的公共卫生学意义对新城疫、禽流感、鹦鹉热三种疫病进行了综述。表明宠物鸟疫病的感染率比较高,且严重危害人类健康。加强对宠物鸟疫病的检验检疫及预防,很好的防控宠物鸟类疫病具有非常重要的意义。     

Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine

The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.     

The evolutionary emergence of pandemic influenza

Pandemic influenza remains a serious public health threat and the processes involved in the evolutionary emergence of pandemic influenza strains remain incompletely understood. Here, we develop a stochastic model for the evolutionary emergence of pandemic influenza, and use it to address three main questions. (i) What is the minimum annual number of avian influenza virus infections required in humans to explain the historical rate of pandemic emergence? (ii) Are such avian influenza infections in humans more likely to give rise to pandemic strains if they are driven by repeated cross-species introductions, or by low-level transmission of avian influenza viruses between humans? (iii) What are the most effective interventions for reducing the probability that an influenza strain with pandemic potential will evolve? Our results suggest that if evolutionary emergence of past pandemics has occurred primarily through viral reassortment in humans, then thousands of avian influenza virus infections in humans must have occurred each year for the past 250 years. Analyses also show that if there is epidemiologically significant variation among avian influenza virus genotypes, then avian virus outbreaks stemming from repeated cross-species transmission events result in a greater likelihood of a pandemic strain evolving than those caused by low-level transmission between humans. Finally, public health interventions aimed at reducing the duration of avian virus infections in humans give the greatest reduction in the probability that a pandemic strain will evolve.     

Modelling strategies for controlling SARS outbreaks

Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.     

The influenza pandemic of 2009: lessons and implications

Influenza is a moving target, which evolves in unexpected directions and is recurrent annually. The 2009 influenza A/H1N1 pandemic virus was unlike the 2009 seasonal virus strains and originated in pigs prior to infecting humans. Three strains of viruses gave rise to the pandemic virus by antigenic shift, reassortment, and recombination, which occurred in pigs as 'mixing vessels'. The three strains of viruses had originally been derived from birds, pigs, and humans. The influenza hemagglutinin (HA) and neuraminidase (NA) external proteins are used to categorize and group influenza viruses. The internal proteins (PB1, PB1-F2, PB2, PA, NP, M, and NS) are involved in the pathogenesis of influenza infection. A major difference between the 1918 and 2009 pandemic viruses is the lack of the pathogenic protein PB1-F2 in the 2009 pandemic strains, which was present in the more virulent 1918 pandemic strains. We provide an overview of influenza infection since 1847 and the advent of influenza vaccination since 1944. Vaccines and chemotherapy help reduce the spread of influenza, reduce morbidity and mortality, and are utilized by the global rapid-response organizations associated with the WHO. Immediate identification of impending epidemic and pandemic strains, as well as sustained vigilance and collaboration, demonstrate continued success in combating influenza.     

Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features

The last decade has seen the emergence of two new influenza A subtypes and they have become a cause of concern for the global community. These are the highly pathogenic H5N1 influenza A virus (H5N1) and the Pandemic 2009 influenza H1N1 virus. Since 2003 the H5N1 virus has caused widespread disease and death in poultry, mainly in south East Asia and Africa. In humans the number of cases infected with this virus is few but the mortality has been about 60%. Most patients have presented with severe pneumonia and acute respiratory distress syndrome. The second influenza virus, the pandemic H1N1 2009, emerged in Mexico in March this year. This virus acquired the ability for sustained human to human spread and within a few months spread throughout the world and infected over 4 lakh individuals. The symptoms of infection with this virus are similar to seasonal influenza but it currently affecting younger individuals more often. Fortunately the mortality has been low. Both these new influenza viruses are currently circulating and have different clinical and epidemiological characteristics.     

禽流感:一种人畜共患病

禽流感 (AvianInfluenza ,AI)是严重危害畜牧业与人类健康的一种传染性疾病。多年来在世界上许多国家和地区都发生过此病 ,危害严重 ,经济损失巨大。禽流感病毒可感染多种动物 ,包括人、猪、马、鲸、海豹和雪貂。禽流感病毒经变异或基因重组 ,已具备感染人的能力 ,有可能成为人类新型流感流行的潜在病原。本文对与禽流感病毒相关的流感疫情进行历史性的回顾 ,并对其人畜共患机制做了初步探讨