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余宏杰课题组在阐明人感染禽流感H7N9的流行病学特征变化及大流行风险评估领域取得重要进展

发表时间:2017-06-09

来源:中国病毒学论坛

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       在国家自然科学基金委员会国家杰出青年科学基金项目(81525023)的资助下,复旦大学公共卫生学院余宏杰课题组在人感染禽流感H7N9的流行病学特征变化和大流行风险评估领域取得重要进展,研究结果以“Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China. 2013–17: an epidemiological study of laboratory-confirmed case series”为题于2017年6月2日以快速通道形式,在国际著名医学期刊Lancet Infectious Diseases(IF 22.4)上在线发表。余宏杰教授是该论文的通讯作者,复旦大学公卫学院青年教师王锡玲和中国疾控中心博士生姜慧是共同第一作者。
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       自2013年3月中国发现了全球首例人感染禽流感H7N9病例以来,每年冬春季都会出现一波人感染禽流感H7N9疫情。该病毒可通过基因重配或适应性突变演变成为引起流感大流行的病毒,持续的病毒学和流行病学监测和研究是大流行风险评估的重要内容。在2016–2017年第五波疫情前,H7N9病毒为低致病性禽流感病毒,禽类感染该病毒后不出现临床症状。
 
       然而,2017年2月19日,中国疾控中心报告从广东的两例人感染禽流感H7N9病例中分离病毒株的测序结果显示,病毒的HA裂解位点插入了多个碱性氨基酸,提示该病毒已变异为高致病性禽流感病毒。此外,2016–2017年第五波疫情较往年出现得更早,报告病例数也超过了之前任何一波。因此,第五波疫情中,人感染禽流感H7N9的流行病学特征和临床严重性是否发生了变化?其引起大流行的风险是否增强?成为了国际科学界关注的焦点和急待解决的科学问题。
 
       余宏杰课题组自2013年始,在禽流感H7N9的流行病学、传播动力学和大流行风险评估等领域开展了持续研究,已在Lancet, BMJ, Lancet Infectious Diseases, Nature Communications和Clinical Infectious Disease等国际期刊发表数十篇论文。在以往研究基础上,本研究聚焦于2016–2017年第五波禽流感H7N9的流行病学特征和临床严重性,并与前四波进行比较,以揭示其流行病学特征、临床严重性和大流行风险是否发生了变化。
 
        研究发现,2016–2017年第五波疫情较往年出现的更早,地理扩散范围更广,发病更多(图1和图2)。从第一波到第五波疫情,16–59岁病例的比例从41%逐渐上升至57%(图3)。第四和第五波疫情中城乡结合部及农村病例的比例(63%和61%)高于前三波(39%,55%和56%),但各省情况不完全一致。约70%的病例发病前10天有家禽暴露史,活禽市场和散养家禽暴露仍是感染的两个主要途径。虽然农村和城乡结合部病例报告活禽市场暴露的比例较城市病例低,但是第五波疫情中仍有48%的农村病例及61%的城乡结合部病例报告了活禽市场暴露。H7N9住院病例的死亡、机械通气和入住重症监护室的风险与以往类似。
 
       研究结果表明,人感染禽流感H7N9的地理范围不断扩大,提示病毒在禽间的地理扩散范围更广泛。随着越来越多的城市活禽市场关闭,病毒可沿着家禽运输和交易的路线隐性传播,持续扩散到没有或没有严格执行活禽市场关闭的地区,包括尚未发现疫情的地区。
 
       本研究提示对活禽中的禽流感H7N9监测需进一步加强,并建议采取永久性活禽市场关闭,或在疫情发生前采取主动的活禽市场关闭措施。人间病例对于病死禽的暴露并未发生明显变化,但未来可随禽中循环的高致病性和低致病性禽流感H7N9病毒的比例的变化而变化。第五波疫情报告的病例数高于前四波,提示禽类中H7N9病毒的循环强度可能较前几波高。本研究创新在于全面阐明了2013–2017年人感染禽流感H7N9的流行病特征及临床严重性的变化,为大流行的风险评估及防控措施提供了科学证据。
 
       鉴于本研究的重要科学及公共卫生意义,Lancet Infectious Diseases以快速通道形式发表了论文,并同期邀请了WHO动物流感研究参比中心主任、国际著名流感病毒专家Richard Webby和广州医科大学附属第一医院杨子峰教授撰写了专家述评,指出:余宏杰课题组通过快速、全面地研究禽流感H7N9的流行病学特征,证明了人感染禽流感H7N9病例的临床严重性并未发生明显变化,回答了“第五波疫情中,禽流感H7N9病例数激增且出现了高致病性H7N9病毒株是否会改变其引起大流行的风险”这个关键科学问题。
(专家述评链接:http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30337-7/fulltext)
 
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图1. 2013–17中国大陆人感染禽流感H7N9病例的时间分布(A-流行曲线,B-波次别每周阳性占比热图)
 
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图2.人感染禽流感H7N9病例的地理分布(A-所有病例分布,B-第五波疫情,C-第五波疫情中发病的区县及新发区县)
 
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图3.人感染禽流感H7N9病例的年龄和性别分布(A-年龄分布,B–F-第一至第五波疫情病例的年龄及性别分布,G-所有病例的年龄及性别分布)
 
原文链接:http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30323-7/fulltext
 
Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China. 2013–17: an epidemiological study of laboratory-confirmed case series
 
Summary
 
Background
The avian influenza A H7N9 virus has caused infections in human beings in China since 2013. A large epidemic in 2016–17 prompted concerns that the epidemiology of the virus might have changed, increasing the threat of a pandemic. We aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of patients infected with A H7N9 in the 2016–17 epidemic compared with previous epidemics.
 
Methods
In this epidemiological study, we obtained information about all laboratory-confirmed human cases of A H7N9 virus infection reported in mainland China as of Feb 23, 2017, from an integrated electronic database managed by the China Center for Disease Control and Prevention (CDC) and provincial CDCs. Every identified human case of A H7N9 virus infection was required to be reported to China CDC within 24 h via a national surveillance system for notifiable infectious diseases. We described the epidemiological characteristics across epidemics, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital for routine clinical practice rather than for isolation purpose. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge using survival analysis techniques.
 
Findings
Between Feb 19, 2013, and Feb 23, 2017, 1220 laboratory-confirmed human infections with A H7N9 virus were reported in mainland China, with 134 cases reported in the spring of 2013, 306 in 2013–14, 219 in 2014–15, 114 in 2015–16, and 447 in 2016–17. The 2016–17 A H7N9 epidemic began earlier, spread to more districts and counties in affected provinces, and had more confirmed cases than previous epidemics. The proportion of cases in middle-aged adults increased steadily from 41% (55 of 134) to 57% (254 of 447) from the first epidemic to the 2016–17 epidemic. Proportions of cases in semi-urban and rural residents in the 2015–16 and 2016–17 epidemics (63% [72 of 114] and 61% [274 of 447], respectively) were higher than those in the first three epidemics (39% [52 of 134], 55% [169 of 306], and 56% [122 of 219], respectively). The clinical severity of individuals admitted to hospital in the 2016–17 epidemic was similar to that in the previous epidemics.
 
Interpretation
Age distribution and case sources have changed gradually across epidemics since 2013, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection with A H7N9 virus.
 
Funding
The National Science Fund for Distinguished Young Scholars.
 
(内容来源:中国病毒学论坛)