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)病毒给养禽业造成了巨大的经济损失，对动物和人类的健康构成了重大威胁。HPAI于20世纪90年代末首次出现，当时亚洲出现了H5N1病毒谱系，导致100多万只禽类被扑杀，500多人死亡。2013年，随着中国出现一种属于H5N8亚型的新毒株，高致病性禽流感再次成为全球威胁。自2014年以来，H5N8在全球的传播速度令科学家们感到惊讶。这种毒株在亚洲、北美、欧洲以及最近的非洲迅速蔓延。扩散到北美是史无前例的，估计那里的企业损失约33亿美元。去年10月发布的一份报告得出结论，H5N8在全球的传播主要是由鸟类的长途迁徙推动的。2016年秋季，欧洲各地野生和养殖鸟类爆发H5N8疫情的报道有所增加，向西传播，直到12月底到达英国。威尔士、苏格兰和英格兰已经报告了野生鸟类的病例。迄今为止最大的疫情发生在英格兰南部多塞特海岸阿伯茨伯里的一大群野生哑天鹅(约750只)中。虽然(到目前为止)只有9只天鹅被实验室确认感染H5N8，但自疫情爆发以来，已有175多只未经检测的天鹅死亡，远远超过正常死亡率。2016年12月23日，在Swannery发现的一只死天鹅中发现了第一例H5N8感染。尽管死亡率似乎较2017年1月第二周的明显峰值有所下降，但仍在恢复高于正常数量的死亡禽类，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造成了毁灭性的破坏，但可以告诉我们许多关于HPAI如何在野生鸟类中传播的信息。牛津大学的鸟类学家对长寿天鹅进行了长期的生态学研究，并将它们单独环抱在一起；对于大多数鸟类来说，我们知道年龄、性别、父母和其他变量。至关重要的是，2008年初，完全相同的人口遭受了H5N1高致病性禽流感暴发。然而，2008年只有10只天鹅死亡，几乎都是3岁大的。我们在2008年疫情爆发后的研究表明，年龄较大的禽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。具体地说，几乎所有3岁的禽类都有流感抗体，年龄较大的禽类对更广泛的不同流感毒株都有抗体。因此，我们推测，以前接触过普通、轻微形式的流感可能保护了这些野鸟免受H5N1感染。目前的疫情提供了直接比较同一群野鸟中H5N1和H5N8 HPAI流行病学的可能性，我们认为这是一个在世界范围内独一无二的机会。欧洲其他地方也报告了H5N8疫情期间禽类死亡率较高的情况，通过比较阿伯斯伯里H5N8和H5N1疫情的生态学和流行病学，我们可能能够找到这一原因。我们的目标是找出H5N8病毒是如何以及从哪里进入人群的，它在被检测到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。为了做到这一点，我们将对从受影响的鸟类中恢复的病毒的基因组进行排序，并使用现有的统计方法对这些基因组进行分析。我们将研究鸟类在种群中携带的抗体，以确定一些鸟类，特别是年长的鸟类，是否因以前接触无害的禽流感毒株而免受严重疾病的影响。这将有助于我们了解人类和长寿鸟类对流感的免疫力是相似还是不同，并扩大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.