Understanding the ecology, epidemiology and evolution of the 2017 outbreak of highly-pathogenic H5N8 avian influenza virus in a wild mute swans

高致病性禽流感（HPAI）病毒给家禽业造成重大经济损失，并对动物和人类健康构成重大威胁。高致病性禽流感首次引起关注是在20世纪90年代末，当时H5N1型病毒在亚洲出现，导致数亿只禽类被扑杀，500多人死亡。2013年，随着一种属于H5N8亚型的新型毒株在中国出现，高致病性禽流感重新成为全球威胁。自2014年以来，H5N8病毒在全球的传播速度让科学家们感到惊讶。该菌株在亚洲、北美、欧洲以及最近的非洲迅速传播。疫情向北美的蔓延是前所未有的，据估计给当地企业造成了约33亿美元的损失。去年10月发表的一份报告得出结论，H5N8病毒的全球传播主要是由长途鸟类迁徙造成的。2016年秋季，欧洲各地野生和养殖鸟类中H5N8疫情的报告有所增加，并向西传播，直到12月底到达英国。威尔士、苏格兰和英格兰都报告了野生鸟类感染禽流感的病例。迄今为止最大的一次暴发发生在英格兰南部多塞特海岸阿伯茨伯里的大量野生哑天鹅（约750只）中。虽然（到目前为止）只有9只天鹅被实验室证实感染了H5N8病毒，但自疫情爆发以来，超过175只未经检测的天鹅死亡，远远超过正常死亡率。首例H5N8感染是在2016年12月23日在天鹅养殖场发现的一只死天鹅中发现的。尽管死亡率似乎已从2017年1月第二周的明显高峰下降，但仍在发现高于正常水平的死鸟，当局仍认为疫情是当前和持续的（2017年2月2日）。这次暴发虽然对鸟类种群具有毁灭性，但可以告诉我们很多关于高致病性禽流感如何在野生鸟类中传播的信息。牛津大学的鸟类学家对这些长寿的天鹅进行了长期的生态学研究，并对它们进行了单独的圈圈研究；对于大多数鸟类，我们知道年龄、性别、父母和其他变量。至关重要的是，正是这些人在2008年初爆发了H5N1型高致病性禽流感。然而，在2008年，只有10只天鹅死亡，几乎所有的天鹅都不到3岁。我们在2008年疫情爆发后的研究表明，年龄较大的鸟类更有可能产生抗体反应，这可能有助于对禽流感提供免疫保护。具体来说，几乎所有3岁以上的鸟类都有流感抗体，年龄较大的鸟类有更多不同流感病毒株的抗体。因此，我们假设以前接触过常见的轻度流感可能保护了这些野生鸟类免受H5N1感染。目前的疫情提供了在同一野生鸟类种群中直接比较H5N1和H5N8高致病性禽流感流行病学的可能性，我们认为这是全世界独一无二的机会。在H5N8爆发期间，欧洲其他地方也报告了高鸟类死亡率，通过比较阿伯茨伯里H5N8和H5N1爆发的生态学和流行病学，我们可能能够找出原因。我们的目标是找出H5N8病毒是如何以及从哪里进入人群的，它在被发现之前在当地存在了多长时间，以及病毒是如何在人群中传播的。为此，我们将对从受感染禽类中恢复的病毒的基因组进行测序，并使用既定的统计方法分析这些基因组。我们将观察鸟类携带的抗体，看看是否有些鸟类，特别是年龄较大的鸟类，由于以前接触过无害的禽流感病毒株而免受严重疾病的侵害。这将有助于我们了解人类和长寿鸟类对流感的免疫力是否相似或不同，并扩展我们对这种病毒如何在野生鸟类中传播的理解。

Highly pathogenic avian influenza (HPAI) viruses cause substantial economic losses to the poultry industry, and pose a significant threat to animal and human health. HPAI first came to prominence in the late 1990s with the emergence from Asia of the H5N1 lineage, which resulted in the culling of 100s of millions of birds and more than 500 human deaths. HPAI resurfaced as a global threat in 2013, with the emergence in China of a novel strain belonging to subtype H5N8. The speed of global H5N8 spread since 2014 has surprised scientists. The strain spread rapidly through Asia, North America, Europe, and most recently, Africa. The spread to North America is unprecedented, at an estimated cost of ~$3.3 billion to businesses there. A report published last October concluded that H5N8 global spread was driven primarily by long-distance bird migration.Reports of H5N8 outbreaks in both wild and farmed birds across Europe increased in autumn 2016, spreading westwards until they reached the UK in late December. Cases in wild birds have been reported in Wales, Scotland and England. The largest outbreak to date is ongoing within a large population (~750) of wild mute swans in Abbotsbury, on the Dorset coast in southern England. Although only 9 swans (so far) have laboratory confirmed H5N8 infections, more than 175 untested swans have died since the start of the outbreak, vastly in excess of normal mortality. The first H5N8 infection was detected in a dead swan found at the Swannery on 23rd December 2016. Although mortality appears to have decreased from the apparent peak in the second week of January 2017, an above-normal number of dead birds are still being recovered and the outbreak is still considered to be current and ongoing by the authorities (2nd February 2017). This outbreak, whilst devastating for the bird population, could tell us much about how HPAI spreads in wild birds. The long-lived swans have been subjected to long-term ecological study by ornithologists at the University of Oxford and are individually ringed; for most birds we know age, sex, parentage and other variables. Crucially, exactly the same population suffered an outbreak of H5N1 HPAI in early 2008. However, in 2008 only 10 swans died, almost all of which were <3 years old. Our research after the 2008 outbreak showed that older birds were more likely to have antibody responses that might help give immunological protection against avian influenza. Specifically almost all birds >3 years old harbour influenza antibodies and older birds have antibodies to a broader range of different influenza strains. Thus we hypothesise that previous exposure to common, mild forms of influenza may have protected these wild birds against H5N1 infection.The current outbreak offers the potential to directly compare H5N1 and H5N8 HPAI epidemiology in the same population of wild birds, an opportunity that we think is unique worldwide. High bird mortality during H5N8 outbreaks have been reported elsewhere in Europe, and by comparing the ecology and epidemiology of the H5N8 and H5N1 outbreaks at Abbotsbury we may be able to find out the cause of this. We aim to find out how, and from where, the H5N8 virus entered the population, how long it was present locally before it was detected, and how the virus spread through the population. To do this we will sequence the genomes of the viruses recovered from affected birds, and analyse these genomes using established statistical methods. We will look at the antibodies that birds in the population carry, to see if some birds, particularly the older ones, are protected against severe disease as a result of previous exposure to harmless strains of avian influenza. This will help us understand if immunity to flu in humans and long-lived birds is similar or different, and extend our understanding of how this virus spreads in wild birds.