Flu: TrailMap-One Health

世界同以往一样接近于出现由H5 N1流感病毒引起的流感大流行。这是一种致命的禽流感病毒，目前的毒株被称为进化枝2.3.4.4b，现已蔓延到五大洲，地理分布前所未有。这种病毒杀死野鸟和家禽。该病毒似乎还具有额外的环境适应力，因为它在冬季以外通常不会持续存在禽流感的地区存活了整个夏季。更令人担忧的是，吃过死鸟尸体的野生哺乳动物也被感染了，通常会造成致命的后果。在英国，这包括狐狸和水獭，在美洲，海狮和其他海洋哺乳动物。到目前为止，只有11人被报告感染，但该病毒现在已经进入养殖或驯养的动物，包括西班牙的养殖水貂，芬兰的养殖狐狸和波兰的猫。与野生食腐动物或海洋哺乳动物相比，人类与这些动物之间的接触要频繁得多，因此，由于接触携带病毒的动物，更多人类感染或“溢出”的可能性增加了。在人口层面上，我们也面临着这种禽流感变异并引发流行病甚至新的大流行的风险。以前所有的流感大流行都起源于最初在野鸟中传播的病毒。大多数禽流感病毒，包括这一种，不能立即引起新的大流行，因为它们不适合在人类气道中有效复制或通过空气传播，即使它们可以感染人类。上个世纪的大流行性流感病毒有时在感染中间家养哺乳动物（如猪）并发生突变后到达人类。在这样的时刻，政府面临着真正困难的决定，即投入多少时间和金钱来为特定菌株的大流行做准备。我们是应该储备抗病毒药物和配套疫苗，投资于个人防护设备，还是静观其变？在21世纪初，一种不同的H5 N1病毒株引起了公共卫生问题，但从未获得适应性突变，转化为大流行病毒。这个有什么不同吗2005年，该病毒在溢出事件中杀死了大约50%的感染者。由于目前很少有人感染2.3.3.4b型H5 N1毒株，我们并不真正知道这种病毒对人类有多危险，以及大流行会有多严重。为了回答这些问题，我们需要将新病毒与以前的毒株进行比较，评估中间动物宿主的易感性，并在分子水平上了解这种病毒进一步适应人类的障碍。我们建议作为一个联合体，采取多管齐下的方法，深入评估目前进化枝2.3.4.4b H5 N1禽流感病毒对人类的溢出感染和大流行的可能性。当代病毒将与21世纪初的病毒以及1968年和2009年确实导致人类大流行的其他流感病毒进行比较。我们将使用最先进的方法来研究病毒/宿主分子相互作用，并确定这些相互作用如何随进化枝2.3.4.4b病毒的不同分离株和不同宿主物种之间而变化。我们将考虑病毒与儿童和成人的人体呼吸道的相互作用，以了解谁最有可能感染和传播病毒，谁最有可能患病。我们将结合建模方法来为监测提供信息，询问病毒最有可能在哪里以及如何感染可能作为中间宿主的哺乳动物。我们将开发一套系统，如果病毒真的要跨物种传播，就可以评估抗病毒药物或疫苗等缓解措施。

The world is as close as ever to the emergence of an influenza pandemic caused by an H5N1 influenza virus. This is a deadly bird flu virus and the current strain, known as clade 2.3.4.4b, has now spread across 5 continents, a geographically unprecedented distribution. The virus kills wild birds as well as poultry. The virus also appears to have additional environmental resilience in that it has survived over the summer in regions where bird flu does not normally persist outside of winter. More worryingly, wild mammals that have scavenged dead bird carcasses have been infected, often with fatal consequence. In the UK this includes foxes and otters, in the Americas, sea lions and other marine mammals. So far, only 11 people have been reported infected, but the virus has now found its way into farmed or domesticated animals including farmed mink in Spain, farmed foxes in Finland and cats in Poland. There is much higher and more frequent contact between humans and these animals compared to the wild scavengers or marine mammals, so the likelihood of more human infections, or 'spillovers', from exposure to an animal carrying the virus has increased. At the population level, we are also at risk that this bird flu mutates and gives rise to an epidemic or even a new pandemic. All previous influenza pandemics have originated from viruses that originally circulated in wild birds. Most avian influenza viruses, including this one, cannot immediately cause a new pandemic because they are not adapted for efficient replication in the human airway or for transmission through the air, even if they can infect humans. The pandemic influenza viruses of the last century have sometimes reached humans after infecting and mutating in an intermediate domestic mammal such as pigs. At times like this governments are faced with truly difficult decisions about how much time and money to invest in pandemic preparation for a particular strain. Should we stockpile antivirals and matched vaccines and invest in PPE, or wait and see what develops? In the early 2000s a different strain of H5N1 caused public health concern but never acquired the adaptive mutations to transform into a pandemic virus. Is this one any different? The virus in 2005 killed around 50% of the people it infected during spillover events. Because so few people have been infected as of yet by the current clade 2.3.3.4b H5N1 strain we don't really know how dangerous this virus is for humans and how severe a pandemic would be. To answer these questions, we need to compare the new virus to previous strains, to assess the susceptibility of intermediate animal hosts, and to understand the barriers for this virus to acquire further adaptation to humans at the molecular level. We propose to work as a consortium and take a multipronged approach to risk assess in depth the current clade 2.3.4.4b H5N1 avian influenza viruses for human spillover infection and pandemic potential. The contemporary viruses will be compared with those of the early 2000s, and with other influenza viruses that did cause human pandemics in 1968 and 2009. We will use state of the art approaches to study virus/host molecular interactions, and define how these vary with different isolates of the clade 2.3.4.4b virus and between different host species. We will consider the interactions the virus makes with the human airway from children and adults, to understand who is most likely to be infected by and transmit the virus and who is most at risk of disease. We will incorporate modelling approaches to inform surveillance, asking where and how the virus is most likely to infect mammals that could serve as intermediate hosts. We will develop systems by which mitigations such as antiviral drugs or vaccines could be assessed, if the virus were indeed to jump species.