Nature：无法确定H7N9是否将导致致命瘟疫

　　湖南长沙的一个活禽市场，卫生部门的工作人员正对一只活鸡进行药签取样，以检测是否感染H7N9型禽流感病毒。

　　中国H7N9型禽流感病毒感染者分布图，黑色代表死亡病例。

　　北京时间4月15日消息，据英国《自然》杂志报道，研究人员怀疑H7N9型禽流感病毒可能就“潜伏”在活禽市场，原因在于人类感染病例快速增多。不到两周前，中国出现首例人感染H7N9病毒病例。病毒学家并不清楚这种病毒是否会快速蔓延扩散，在动物宿主体内扎根，导致未来出现人类感染爆发，或者变异成一种易于在人之间传播的病毒，从而引发一场致命瘟疫。

　　为了找到这些问题的答案，科学家从多个角度对H7N9病毒进行研究。他们正对野生鸟类和数以千计的家禽进行检测，分析他们发现的病毒，同时对曾与感染者有过接触的人群进行监视。中国卫生部门表示中国目前有400家实验室正对这种病毒进行研究，寻找和分析可能出现的基因变异。

　　美国明尼苏达州大学传染病研究与政策中心负责人迈克尔-奥斯特霍尔姆表示：“未来一个月，我们将投入最大努力进行研究，希望能够彻底了解这种病毒。”据《自然》杂志报道，中国东部已经有11座城市出现感染病例，感染者共24人，其中8人死亡。一些出现感染病例的城市相隔几百公里。短时间内在面积如此巨大的地区出现大量感染病例——一周前只在两座城市出现3例感染病例——让人感到非常担忧。

　　科学家迫切希望找到H7N9病毒的源头。H7N9病毒导致感染者出现类似流感的症状，绝大多数报告的感染者出现重度肺炎。迄今为止，对感染病例进行的研究在很大程度上并不具有决定性，一些患者在患病前不久曾与家禽或者其他动物接触，其他一些患者并不存在这种现象。上周末，H7N9病毒在上海和杭州活禽市场的鸡、鸽子和鸭子身上发现，这些市场也因此成为病毒源头的主要怀疑对象。在此之后，政府已经屠杀了数万只活禽，关闭上海、南京和杭州的活禽市场。

　　浙江省医学科学院郭潮潭表示，在活禽身上发现的H7N9病毒的基因序列与在人类感染者发现的病毒高度相似。香港大学流感病毒学家马里克-佩里斯指出，虽然H7N9病毒可能存在其他源头——例如哺乳动物，但短时间内在面积巨大的地区出现很多人类感染病例只能由“病毒来自活禽市场”进行解释，因为来自一个地点或者多个地点的活禽会进入多个市场。

　　不过，多种被感染的活禽可能并不是最初的源头，因为活禽市场会发生大面积交叉感染。佩里斯表示研究人员必须追踪到这些活禽的农场和批发商，对涉及这些活禽的整个供应链进行检测。H7禽流感病毒主要感染鸭子、大雁、涉禽和海鸥等野生鸟类，偶尔感染家禽。香港大学传染病专家袁国勇(Kwok-Yung Yuen)指出，已报告的人类感染者生活在长江三角洲和上海崇明岛附近，前者是很多野生鸟类的栖息地，后者是一个著名观鸟胜地。他说：“野鸭和大雁可能携带这种病毒。”

　　然而，研究人员并未在这一地区的野鸟身上检测到H7N9病毒。荷兰环保组织“湿地国际”的候鸟迁徙路线项目负责人塔基-穆德库尔表示：“有关这种特定病毒源头、生态学特征或者储存宿主的特定信息目前还很少，现在就对这些问题做出假设还为时尚早。”值得一提的是，穆德库尔还负责联系联合国粮食及农业组织，召集亚太迁徙水鸟与禽流感工作组会议。

　　不管H7N9病毒的源头来自何处，科学家都要解答一个关键疑问，即这种病毒是否已在家禽体内扎根，形成储存宿主，进而有可能导致持续的不定时发生的人类传染病。中国卫生部门正试图了解当前的疫情达到怎样的程度。联合国粮农组织跨界动植物病虫害紧急预防系统代理负责人文森特-马丁表示，与H5N1型禽流感病毒不同——自2003年爆发以来，H5N1病毒已经在亚洲以及其他地区造成数百万禽类和数百人死亡——H7N9并不会在禽类身上引起严重疾病，这让控制疫情的努力复杂化。对中国的60亿只家禽中的患病个体进行例行监视，以发现H7N9病毒几乎是不可能的。世界卫生组织位于东京的流感病毒研究所的病毒学家田代真人表示：“这也就意味着阻止病毒从动物扩散到人几乎无法做到。”

　　每一次感染新的宿主，病毒便有了一个进行繁殖并在人群中间传播的新机会。不过，目前尚未发现这种病毒能够在人之间传播的证据。专家们指出确认并跟踪新出现的可疑重症肺炎病例以及他们的密切接触者至关重要，必要的时候还需对他们进行隔离。

　　研究H7N9病毒分子生物学特征的科学家表示，H7N9的基因材料似乎来自于至少3种已知的禽流感病毒。这种病毒的关键成分——表面的血凝素(H)蛋白发生变异，导致病毒的攻击偏好从鸟类细胞转移到哺乳动物细胞。科学家正在密切关注这种变化。这种变化意味着病毒可能变成更容易在人际之间传播的形态。

　　英国爱丁堡大学研究人类致病病毒变异的专家安德鲁-兰堡指出，由于流感病毒变异速度很快，比较每一个感染者的病毒序列可以确定H7N9病毒是否进行人际传播。如果很多患者出现非常相似的病毒序列，说明病毒可能在人与人之间传播；如果病毒序列存在很大差异，则说明每位患者因为与鸟类接触独立感染。迄今为止，只有4名感染者的病毒序列公布。不过，病毒学家正在对更多感染者进行测序同时将结果上传到全球共享禽流感数据组织的数据库。

　　田代真人表示如果开始出现人际传播，进一步的扩散将不可避免。在此之前，人类从未出现大规模感染H7或N9病毒的情况，缺少对这些病毒的抵抗能力。一旦出现大规模流行，很可能造成大量人死亡。不过，现在就预测疫情将发展到何种程度还为时尚早。毕竟，传染病专家刚刚开始了解这种新出现的病毒。

与H7N9相关的拓展阅读：

• 北京首例H7N9患儿转入普通病房
• H7N9病毒有易感染哺乳类动物的特征
• 卫计委：H7N9病例仍然散发未现人传人证据
• 北京确认一4岁男童携带H7N9病毒 暂无临床症状
• 全国确诊人感染H7N9禽流感60例 更多信息请点击：有关H7N9更多资讯

原文阅读：Urgent search for flu source
Researchers suspect H7N9 virus is in bird markets as human cases rise rapidly.
Virologists know its name: H7N9. What they don’t yet know is whether this novel avian influenza virus — first reported in humans in China less than two weeks ago — will rapidly fizzle out, become established in animal hosts to fuel future human outbreaks, or morph into a virus that can spread easily between people and spark a deadly pandemic.
In a frantic effort to find answers, scientists are bearing down on H7N9 on multiple fronts. They are testing wild birds and thousands of domestic fowl; analysing the viruses they find; and trying to trace people who have been exposed to infected patients. Chinese health authorities say that they have 400 laboratories looking for genetic changes in the virus.
“We are going to be sitting with bated breath over the next month to find out what happens,” says Michael Osterholm, who heads the University of Minnesota’s Center for Infectious Disease Research and Policy in Minneapolis. As Nature went to press, 24 human cases, including 8 deaths, had been reported in 11 cities, some a few hundred kilometres apart, in eastern China (see map). So many cases in such a short time over such a wide area — up from three cases in two cities a week ago — is “a very concerning situation”, says Osterholm.
Scientists urgently want to find out which sources are stoking the human infections that result in flu-like symptoms and, in most reported cases, severe pneumonia. So far, investigations of the cases remain largely inconclusive: some patients had contact with poultry or other animals just before falling ill, whereas others had not. Late last week, the H7N9 virus was found in chickens, pigeons and ducks in live bird markets in Shanghai and Hangzhou — making markets the leading suspected source. Authorities have since culled tens of thousands of birds and closed down markets in Shanghai, Nanjing and Hangzhou.
The genetic sequences of the H7N9 viruses found in the birds are highly similar to those isolated from human patients, says Chao-Tan Guo, a virologist at the Zhejiang Academy of Medical Sciences in Hangzhou. Although the virus might have come from other sources, including mammals, the pattern of many human cases over a wide area in a short time could be explained by live markets alone, because birds from one or a few sources would be transported to multiple markets, says Malik Peiris, a flu virologist at the University of Hong Kong.
But the various bird species found to be infected may not be the original source, because much cross-infection can occur in live markets. Investigators must now trace which farms and wholesalers the birds came from, Peiris says, and test birds up through the supply chain.
Researchers know that H7 flu viruses mainly infect wild birds such as ducks, geese, waders and gulls, and that they occasionally jump into poultry flocks. Kwok-Yung Yuen, an infectious-disease expert at the University of Hong Kong, notes the proximity of the reported human cases to the Yangtze river delta, home to many wild birds, and to Chongming Island near Shanghai, a renowned site for watching migratory birds. “It’s likely wild ducks and geese that are carrying it,” he suggests.
But this H7N9 virus has not yet been detected in wild birds in the area. “There is very little specific information on the source of this particular virus strain, its ecology or reservoir, and it is premature to be hypothesizing on the vectors,” says Taej Mundkur, who is flyways programme manager for conservation group Wetlands International in the Netherlands. He also co-convenes the Asia-Pacific Working Group on Migratory Waterbirds and Avian Influenza with the Food and Agriculture Organization of the United Nations (FAO).
Hidden reservoir
Wherever the virus originated, a crucial question is whether it could become established in poultry, creating a reservoir that might lead to continued, sporadic human infections.
Health authorities in China are trying to learn to what extent that has happened already. Unlike its cousin H5N1 — which has killed millions of birds and several hundred people in Asia and elsewhere since 2003 — H7N9 does not cause serious bird disease, greatly complicating efforts to control it, says Vincent Martin, interim head of the FAO’s Emergency Prevention System for Transboundary Animal and Plant Pests and Diseases (EMPRES) in Rome. It would be next to impossible to detect H7N9 through routine surveillance for sick poultry among China’s 6 billion domestic birds. “This means stopping animal-to-human transmission is impossible,” says Masato Tashiro, a virologist at the Influenza Virus Research Center in Tokyo, the World Health Organization’s influenza reference and research centre in Japan.
Each time the virus encounters new human hosts, it has fresh opportunities to mutate and to acquire the ability to spread between people. That does not seem to have occurred yet. But experts say that it will be crucial to identify and track new cases of suspicious severe pneumonia and their close contacts, and to isolate people if necessary. Researchers working on the molecular biology of the virus say that it seems to derive from a reassortment of genetic material from at least three known bird-flu groups (see Nature http://doi.org/k4j; 2013). A key component — the haemagglutinin (H) protein on the surface of the virus — already contains mutations known to shift its binding preference from bird cells to those of mammals. Scientists are watching for telltale changes that could signal a shift towards a form that is more transmissible between humans.
Because flu viruses evolve rapidly, comparing viral sequences from each of the human cases might reveal whether person-to-person transmission is occurring, says Andrew Rambaut, an expert in the evolution of human viral pathogens at the University of Edinburgh, UK. If many patients have very similar viral sequences, then that would imply human spread; if viral sequences are more diverse, it would imply that each person had separately picked up infections from birds. Only four sequences from four human cases are so far available, but virologists are sequencing more and posting them on the GISAID flu database.
If human-to-human transmission does start to occur, “further spread may be inevitable”, warns Tashiro. Humanity has never been widely exposed to H7 or N9 flu viruses, and so lacks resistance to these subtypes. If a pandemic were to occur, it would probably have a severe toll. But it is too early to predict how events will unfold; experts in emerging infectious disease are only just becoming acquainted with the latest villain in their roster.