论文标题：Identifying key bird species and geographical hotspots of avian influenza A (H7N9) virus in China

期刊：Infectious Diseases of Poverty

作者：Benyun Shi, Xiao-Ming Zhan, Jin-Xin Zheng, Hongjun Qiu, Dan Liang, Yan-Ming Ye, Guo-Jing Yang, Yang Liu and Jiming Liu

发表时间：2018/10/11

数字识别码：10.1186/s40249-018-0480-x

原文链接：https://idpjournal.biomedcentral.com/articles/10.1186/s40249-018-0480-x?utm_source=WeChat&utm_medium=Website_linksSocial_media_organic&utm_content=CelZha-MixedBrand-multijournal-Multidisciplinary-China&utm_campaign=ORG_AWA_CZH_BMCWechat_dailyposts_blogs

微信链接：https://mp.weixin.qq.com/s/cybNvdI1_sIPDS9Jzm5GkQ

原文作者：Benyun Shi, Xiao-Ming Zhan, Jin-Xin Zheng, Hongjun Qiu, Dan Liang, Yan-Ming Ye, Guo-Jing Yang, Yang Liu and Jiming Liu

自2013年2月中国发现甲型禽流感H7N9病毒以来，禽流感疫情一直在长三角地区蔓延，至今仍在我国东部地区持续并周期性爆发。最近的一次H7N9禽流感疫情，发生在2016年10月至2017年上半年（见图1）。截至目前，H7N9禽流感共导致约1565人感染、612人死亡，累计感染和死亡人数不断增加，对人类健康和社会经济造成了严重的影响。

图1. 2013年至今，中国范围内人感染H7N9禽流感疫情。

农业部和世界动物卫生组织（OIE）联合考察组通过对H7N9疫情的调查表明，目前人感染H7N9的风险主要来自活禽市场环境。然而，发表在《自然》网站的专栏文章也曾指出，这种新病毒可能已在野生鸟类中传播，并且已有相关证据表明，鸟类迁徙在禽流感病毒的传播中起着至关重要的作用。作为禽流感病毒的天然宿主，许多候鸟在迁徙过程中会在相同的栖息地或停歇地停留，在此过程中，禽流感病毒可能通过受鸟类粪便污染的地表水等途径进行传播。有鉴于此，近期发表在国际期刊Infectious Diseases of Poverty上的文章Identifying key bird species and geographical hotspots of avian influenza A (H7N9) virus in China，系统研究和评估了与禽流感时空传播相关的关键鸟种，并绘制了其时空分布及热点地区。

本文作者首先从GISAID库中，采集了中国范围内所有从鸡身上分离出的H7N9基因序列，并对HA和NA基因片段进行了系统发育学分析（见图2）。结果显示，H7N9禽流感在我国东部沿海呈现三次流行浪潮。第一次传播2013年发生在浙江和江苏，然后于2014年逐渐传向中国南部省份（江西、福建和广东）。2014年至2017年，疫情几乎覆盖了中国东部所有省份，并且新的H7N9禽流感毒株可能已经出现。

图2. 基于184条HA和NA基因片段生成的H7N9禽流感系统发育树。

中国东部地区，包括长三角和珠三角地区，是我国的三大鸟类迁徙路线之一，禽流感传播的风险特别高。在该迁徙路线上，东部沿海省份，如福建、广东、浙江、江苏等，都有候鸟的栖息地或停歇地，且地理分布较为集中。在越冬季或繁殖期，许多鸟类聚集在人口密度高的栖息地或停歇地，为不同候鸟之间以及候鸟与家禽之间的禽流感病毒传播提供了有利的条件。其次，受感染的候鸟迁徙至其他地方时，又会引发新的感染。因此，在禽流感高流行地区，可以对受感染的鸟类实施主动检测，为禽流感病毒引入新地区提供早期预警。

为了调查候鸟迁徙与H7N9禽流感传播中的关系，分析各种候鸟的迁移模式，作者进一步利用公民科学的思路，联合中国民间观鸟组织，收集和整理了中国1100多种常见鸟类的时空分布数据（见图3）。通过分别分析中国东部六个省市H7N9禽流感时间序列和候鸟时空分布之间的滞后相关性，作者进一步确定了各个省市与H7N9禽流感病毒相关的关键迁徙鸟种，以及这些鸟种迁徙的重要地理热点，这为禽流感的主动监测和控制提供了重要的哨兵信号和决策依据。

图3. 与禽流感疫情相关关键鸟种的时空分布图。

禽流感疫情的爆发和时空传播涉及从微观层面到宏观层面多个学科的复杂因素，如病毒的进化机制和宿主的时空移动等。从微观层面的分子进化学角度，禽流感病毒具有两大主要特点：首先，禽流感病毒的感染周期短,通常在感染之后很短的时间内宿主的免疫系统会自动产生免疫对抗感染,这使得病毒很容易局部灭绝。同时，部分禽流感病毒之间能够获得交叉免疫,导致毒株之间产生很强的适应性差异。这种传播脆弱性，加上病毒的遗传变异，导致几乎每年都会产生一波新的病毒感染。其次，当某个宿主个体被多个低致病禽流感毒株共同感染时，病毒有可能发生重配而产生新的病毒。已有研究表明，在禽流感病毒的阳性采样中，发生共同感染的几率高达61%，而且越是新型流感病毒越容易导致共同感染。这就为实现禽流感疫情的早期预警和主动监测提出了一个挑战。作者指出，未来可以从大数据的角度，通过空间生物学方法、计算流行病模型和系统发育动力学等多学科方法的交叉融合，系统研究候鸟迁徙与多种禽流感病毒传播、重组之间的关系，从更深层次揭示禽流感病毒的基因序列，用科学方法追踪病毒的起源，探索其传播和演化模式，从而实施科学有效的防控措施。

摘要：

Background

In China since the first human infection of avian influenza A (H7N9) virus was identified in 2013, it has caused serious public health concerns due to its wide spread and high mortality rate. Evidence shows that bird migration plays an essential role in global spread of avian influenza viruses. Accordingly, in this paper, we aim to identify key bird species and geographical hotspots that are relevant to the transmission of avian influenza A (H7N9) virus in China.

Methods

We first conducted phylogenetic analysis on 626 viral sequences of avian influenza A (H7N9) virus isolated in chicken, which were collected from the Global Initiative on Sharing All Influenza Data (GISAID), to reveal geographical spread and molecular evolution of the virus in China. Then, we adopted the cross correlation function (CCF) to explore the relationship between the identified influenza A (H7N9) cases and the spatiotemporal distribution of migratory birds. Here, the spatiotemporal distribution of bird species was generated based on bird observation data collected from China Bird Reports, which consists of 157 272 observation records about 1145 bird species. Finally, we employed a kernel density estimator to identify geographical hotspots of bird habitat/stopover that are relevant to the influenza A (H7N9) infections.

Results

Phylogenetic analysis reveals the evolutionary and geographical patterns of influenza A (H7N9) infections, where cases in the same or nearby municipality/provinces are clustered together with small evolutionary differences. Moreover, three epidemic waves in chicken along the East Asian–Australasian flyway in China are distinguished from the phylogenetic tree. The CCF analysis identifies possible migratory bird species that are relevant to the influenza A(H7N9) infections in Shanghai, Jiangsu, Zhejiang, Fujian, Jiangxi, and Guangdong in China, where the six municipality/provinces account for 91.2% of the total number of isolated H7N9 cases in chicken in GISAID. Based on the spatial distribution of identified bird species, geographical hotspots are further estimated and illustrated within these typical municipality/provinces.

Conclusions

In this paper, we have identified key bird species and geographical hotspots that are relevant to the spread of influenza A (H7N9) virus. The results and findings could provide sentinel signal and evidence for active surveillance, as well as strategic control of influenza A (H7N9) transmission in China.

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期刊介绍:

Infectious Diseases of Poverty (https://idpjournal.biomedcentral.com/, 2.708 - 2-year Impact Factor, 3.126 - 5-year Impact Factor) is an open access, peer-reviewed journal publishing topic areas and methods that address essential public health questions relating to infectious diseases of poverty. These include various aspects of the biology of pathogens and vectors, diagnosis and detection, treatment and case management, epidemiology and modeling, zoonotic hosts and animal reservoirs, control strategies and implementation, new technologies and application. Transdisciplinary or multisectoral effects on health systems, ecohealth, environmental management, and innovative technology are also considered.

（来源：科学网）