新疆首例人感染H7N9禽流感病例流行病学调查

目的分析新疆首例人感染H7N9禽流感病例流行病学特征,探讨该病例可能的感染来源,为新疆制定人感染H7N9禽流感防控措施提供依据。方法对一例不明原因肺炎病例展开现场流行病学调查,在病原学排查的同时对病例及其密切接触者和可疑感染来源进行流行病学调查,采集相关标本送实验室检测,并应用描述流行病学方法进行分析。结果该病例有明确的禽类养殖及无防护措施的禽排泄物及其污染环境暴露史,呼吸道标本检测出人感染H7N9禽流感病毒,相关外环境和家禽标本H7N9禽流感病毒核酸检测阳性,环境标本分离禽流感病毒与人标本中分离的禽流感病毒HA片段和NA片段同源性为99.9%和100.0%,未发现人与人之间传播病例。结论该病例为新疆确诊的首例人感染H7N9禽流感病例,传播途径可能为禽—环境—人或者禽—人;加强门诊医生诊断敏感性和强化不明原因肺炎监测工作是及时发现与处理人感染H7N9禽流感疫情的重要手段。     

2017-2018年陕西省H7N9禽流感病毒流行特征及基因进化分析

目的 整理和分析2017-2018年陕西省H7N9禽流感病毒流行分布和基因特性,为防控决策提供实证依据。方法 采集陕西省外环境样本、H7N9病例及关联样本,用荧光定量PCR检测H7N9亚型流感病毒,H7N9 阳性标本的病毒分离和基因测序分析由国家流感中心完成。结果 2017年5月至2018年3月,陕西省142个监测点外环境外环境H7N9核酸阳性率仅4.91‰。同时,本省共报告7例H7N9病例和2起禽间疫情。病毒序列分析发现:部分H7N9病毒中HA蛋白裂解位点插入“KRTA”氨基酸基序,具有对禽类高致病性的分子特征。血凝素(HA)和神经氨酸酶(NA)基因进化树分析结果显示陕西省H7N9禽流感病毒与长三角来源的H7N9序列高度同源。结论 陕西H7N9病毒流行株具有遗传多样性,同时存在低致病性和高致病性两个变种。今后应继续做好禽流感病原学监测和遗传变异分析,为防控工作提供依据。     

H6N1亚型禽流感病毒跨种属传播研究进展

禽流感病毒H6N1亚型广泛存在于水禽和陆禽,是最常分离到的甲型流感病毒亚型,遗传分析表明该病毒可能是高致病禽流感病毒H5N1的前体。随着病毒基因的持续进化,H6N1可跨种间屏障传播至哺乳动物,其对于哺乳动物小鼠、猪和雪貂已经具有较强感染能力。血清流行病学调查结果显示少数人H6禽流感病毒抗体阳性,2013年5月,我国台湾出现全球首例人类感染H6N1亚型流感病毒。因此,H6N1病毒宿主范围不断扩大,在这些宿主内可发生病毒基因突变、基因重配,进而演变为具有感染人类潜能的新变异株的可能。本文从病原学、流行病学、病毒感染哺乳动物和人类等方面对H6N1亚型禽流感病毒的研究进展进行综述,以期为H6N1禽流感病毒的防控提供参考。     

广州市人感染H7N9禽流感病毒高致病性变异株监测与基因进化分析

目的 通过对广州市人感染H7N9禽流感病毒高致病性变异株基因变异和进化特点进行分析,掌握本地区H7N9病毒病原学特点,为疾病防控提供参考。方法 选取2017年广州市人感染H7N9禽流感病毒阳性标本10份,提取核酸扩增HA、NA、M基因进行测序,通过生物信息学软件分析病毒重要蛋白突变情况和遗传进化特点。结果 广州地区H7N9禽流感病毒基因同源性差异较大,大部分毒株基因与广东毒株同源性最高,部分毒株基因与河南、内蒙古等地毒株同源性最高。监测到5株病毒为H7N9禽流感病毒高致病性变异株,部分病毒出现了HA蛋白Q226L的突变,提示对人呼吸道上皮细胞SAα-2, 6Gal受体结合能力增加。HA蛋白和NA蛋白上糖基化位点均有一定的增加和缺失突变。HA、NA和M1蛋白上毒力相关位点均突变增强。M2蛋白均呈现耐药突变,同时监测到2株高致病性突变株出现对神经氨酸酶抑制剂的耐药突变。遗传进化结果显示,HA基因和NA基因在华南和华东分支均有分布,M1基因进化特点相对复杂,分别与华南地区H9N2、H7N9病毒,及北方地区的H7N9病毒重组。结论 2017年广州地区发现2株对达菲耐药的人感染H7N9禽流感病毒高致病性变异株。H7N9禽流感病毒在广州地区不断发生进化重组,具有遗传多样性和复杂性,提示高致病性耐药株有向华南以外地区传播的风险。     

编者按:人感染H7N9禽流感及其他动物源性流感

正根据世界卫生组织近日发布的文件,我国在第5波人感染H7N9禽流感疫情中已报告517例确诊病例,达历年报告病例数峰值,占累计报告病例数的40%。据官方统计,人感染H7N9禽流感的病死率接近40%。因此,我国目前正在经历的第5波人感染H7N9禽流感疫情引发世界范围内广泛关注。人感染H7N9禽流感是由甲型H7N9禽流感病毒感染引起的急性呼吸道传染病。甲型H7N9禽流感病毒是甲型流感病毒的一个亚型,为新型重配病毒。编码HA的基因来源于H7N3,     

人感染H7N9禽流感病毒全基因组扩增与测序方法的建立北大核心CSCD

目的为了解人感染H7N9禽流感病毒基因特征从而更有效地防控疫情,需建立获得人感染H7N9禽流感病毒全基因序列的扩增和测序方法。方法采用鸡胚分离H7N9禽流感病毒,提取标本和毒株病毒RNA,自行设计引物,通过一步法RT-PCR扩增其全基因组片段,纯化PCR产物后测定核苷酸序列,利用生物信息学软件拼接各节段序列并初步分析其特征。结果本研究中的引物能特异地扩增各基因的目的片段,通过序列拼接可以获得H7N9禽流感全基因组序列。经分析8个节段序列与近期国内流行的人感染H7N9禽流感病毒序列高度同源。结论该方法能有效地获得人感染H7N9禽流感病毒全基因组序列,可为进一步分析其基因特征奠定基础。     

近期中国禽流感病毒的流行病学调查及其演变

正禽流感病毒(AIVs)通常具有种属特异性,感染宿主主要限于禽类。流行范围较广,值得注意的是其很少发生跨种传播感染人类和其他哺乳动物。1中国过去爆发的禽流感疫情及流行病学调查亚洲的第一株H9N2低致病性禽流感病毒(LPAIV)和H5N1高致病性禽流感病毒(HPAIV)分别于1994年和1996年分离自中国广东省。2013年3月     

H7N9亚型禽流感病毒研究进展

H7N9亚型禽流感病毒(H7N9 AIV)是危害家禽养殖的主要病原体之一,其不仅制约家禽养殖业的健康发展,而且表现出对人类较强的传染性和较高的致死率,严重威胁公共卫生安全。2013年我国首次报道人类感染H7N9 AIV事件,病毒溯源发现家禽体内存在H7N9 AIV,但无明显症状。2017年,H7N9 AIV出现变异株,表现出对家禽的高致病性,随后我国推出H5/H7二价苗,并在全国实施家禽强制免疫接种,有效控制了H7N9 AIV在我国家禽中的流行以及人类感染事件的发生,成为我国控制人兽共患传染病的成功案例。由于我国家禽养殖和AIV的复杂性,全面和持续的流行病学监测对于H7N9禽流感的防控仍然至关重要。本文针对2013年至今H7N9 AIV的流行特征、遗传变异特点及疫苗研究等内容作简要论述,以期为禽流感的预防和控制提供参考。     

2株欧亚与北美谱系重排H6N8亚型禽流感病毒的遗传进化及分子特征分析北大核心CSCD

目的解析监测中发现的欧亚与北美谱系重组H6N8亚型禽流感病毒的遗传进化及分子特征,为禽流感病毒跨洲际传播及基因重排研究提供支持。方法2019年秋季在图牧吉地区采集雁鸭类粪便样品,分离H6N8亚型禽流感病毒并进行全基因序列测定,分析其遗传进化及分子特征。结果共采集雁鸭类粪便及拭子样品5062份,分离到2株H6N8LPAIV(TMJ43、TMJ120)。遗传进化分析显示,分离株病毒NA与北美的阿拉斯加地区所分离的H3N8亚型AIV的NA节片聚集在同一进化分支,HA和其它6个内部基因节片均属于欧亚进化分支,且两株禽流感病毒分别有不同的重配发生。2株H6N8亚型禽流感病毒为欧亚谱系与北美谱系基因重排毒株,其中N8基因最近一次欧亚与北美基因节片重排发生在2016年。分子特征分析显示,HA蛋白的碱性裂解位点为PQIETR↓GLF,符合低致病性禽流感病毒的特征。在NP蛋白,发生了具有增强鸡禽流感毒力的A184K突变。在TMJ43,NS1蛋白发生了能增强哺乳动物毒力的A/P42S突变。结论在我国内蒙古地区分离的2株H6N8亚型禽流感病毒为欧亚谱系和北美谱系的重排毒株,两毒株均发生了增强家禽和哺乳动物感染能力的突变。表明北美毒株通过候鸟迁徙进入我国,与欧亚谱系毒株发生重配并在野鸟中频繁出现,可为禽流感病毒的跨洲际传播研究提供信息支持。     

H9亚型禽流感病毒HA基因的克隆与序列分析

目的扩增、克隆H9N2 HA基因,并进行序列分析,为H9N2流感病毒种间及跨种传播机制研究奠定基础。方法设计特异性引物,扩增克隆H9N2亚型禽流感病毒,测序后进行序列分析。结果成功克隆出4株H9N2亚型禽流感病毒,全长均为1.7 kb,ORF为1 683 bp,编码560个氨基酸;联机检索,与参考毒株比对核苷酸和氨基酸同源性均在90%以上。结论成功克隆4株H9N2亚型禽流感病毒,序列分析显示其核苷酸和推导氨基酸与参考毒株高度同源。     

The Effects of Genetic Variation on H7N9 Avian Influenza Virus Pathogenicity

Since the H7N9 avian influenza virus emerged in China in 2013, there have been five seasonal waves which have shown human infections and caused high fatality rates in infected patients. A multibasic amino acid insertion seen in the HA of current H7N9 viruses occurred through natural evolution and reassortment, and created a high pathogenicity avian influenza (HPAI) virus from the low pathogenicity avian influenza (LPAI) in 2017, and significantly increased pathogenicity in poultry, resulting in widespread HPAI H7N9 in poultry, which along with LPAI H7N9, contributed to the severe fifth seasonal wave in China. H7N9 is a novel reassorted virus from three different subtypes of influenza A viruses (IAVs) which displays a great potential threat to public health and the poultry industry. To date, no sustained human-to-human transmission has been recorded by the WHO. However, the high ability of evolutionary adaptation of H7N9 and lack of pre-existing immunity in humans heightens the pandemic potential. Changes in IAVs proteins can affect the viral transmissibility, receptor binding specificity, pathogenicity, and virulence. The multibasic amino acid insertion, mutations in hemagglutinin, deletion and mutations in neuraminidase, and mutations in PB2 contribute to different virological characteristics. This review summarized the latest research evidence to describe the impacts of viral protein changes in viral adaptation and pathogenicity of H7N9, aiming to provide better insights for developing and enhancing early warning or intervention strategies with the goal of preventing highly pathogenic IAVs circulation in live poultry, and transmission to humans.     

Minimal molecular constraints for respiratory droplet transmission of an avian–human H9N2 influenza A virus

Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian–human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.     

Avian influenza virus infections in humans

Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable of efficient human-to-human transmission could trigger another influenza pandemic. The recent isolation of this virus in extrapulmonary sites of human diseases suggests that the high fatality of this infection may be more than just the result of a cytokine storm triggered by the pulmonary disease. The emergence of resistance to adamantanes (amantadine and rimantadine) and recently oseltamivir while H5N1 vaccines are still at the developmental stage of phase I clinical trial are causes for grave concern. Moreover, the to-be pandemic strain may have little cross immunogenicity to the presently tested vaccine strain. The relative importance and usefulness of airborne, droplet, or contact precautions in infection control are still uncertain. Laboratory-acquired avian influenza H7N7 has been reported, and the laboratory strains of human influenza H2N2 could also be the cause of another pandemic. The control of this impending disaster requires more research in addition to national and international preparedness at various levels. The epidemiology, virology, clinical features, laboratory diagnosis, management, and hospital infection control measures are reviewed from a clinical perspective.     

2014-2018年中山市人感染H7N9禽流感病例特征分析

目的 了解2014年1月至2018年5月中山市人感染H7N9禽流感病例临床特征并分析其流行病学特征。方法 收集整理2014年1月至2018年5月中山市H7N9病例个案调查资料。结果 中山市累计报告15例H7N9病例,其中3岁以下女童3人,临床表现为上呼吸道感染,预后良好。12例成人病例,年龄34-78岁(中位数54岁),男性占58.3%(7/12)。成人病例发病后4-8 d(中位数5 d)均出现呼吸困难、严重低氧血症等重症肺炎表现,需要呼吸机辅助通气治疗措施。4例(26.7%)死亡,其中3例为50岁以上且有高血压等基础疾病。60.0%(9/15)发病时间集中于1月下旬至2月上旬。10例可能传播途径为禽类接触传播,其中6例从市场购买活禽回家并亲自宰杀。2例有活禽市场暴露但无活禽直接接触史,可能传播途径为禽类市场空气传播。共发现3起聚集性疫情,其中2起发生人传人的可能性大。结论 在H7N9流行季节,尤其是1月下旬至2月上旬疫情高发期,中山市应采取综合措施,降低居民,尤其是50岁以上有基础疾病者,从市场购买活禽回家及宰杀活禽等高风险行为。     

Epidemiological and viral genome characteristics of the first human H7N9 influenza infection in Guangdong Province,China

Background

The first H7N9 human case in south of China was confirmed in Guangdong Province on August 2013, outside of the typical influenza season. For investigating the H7N9 virus source and transmission in the local community, we analyze the epidemiology and genome features of the virus isolated from the first human infection detected in Guangdong Province.

Methods

The data including medical records, exposure history and time line of events for the H7N9 patient and close contacts was collected. Variation and genetic signatures of H7N9 virus in Guangdong was analyzed using ClustalW algorithm and comparison with mutations associated with changes in biological characteristics of the virus.

Results

The female patient had a history of poultry exposure, and she was transferred from a local primary hospital to an intensive care unit (ICU) upon deterioration. No additional cases were reported. Similar to previous infections with avian influenza A (H7N9) virus, the patient presented with both upper and lower respiratory tract symptoms. Respiratory failure progressed quickly, and the patient recovered 4 weeks after the onset of symptoms. Genome analysis of the virus indicated that the predicted antigen city and internal genes of the virus are similar to previously reported H7N9 viruses. The isolated virus is susceptible to neuraminidase (NA) inhibitors but resistant to adamantine. Although this virus contains some unique mutations that were only detected in avian or environment-origin avian influenza A (H7N9) viruses, it is still quite similar to other human H7N9 isolates.

Conclusions

The epidemiological features and genome of the first H7N9 virus in Guangdong Province are similar to other human H7N9 infections. This virus may have existed in the environment and live poultry locally; therefore, it is important to be alert of the risk of H7N9 re-emergence in China, including emergence outside the typical influenza season.     

成都市首例人感染H9N2禽流感病例调查与分析

目的总结分析成都市首例人感染H9N2禽流感病例流行病学调查结果,为今后科学应对类似疾病提供参考。方法采用现场流行病学和实验室检测相结合的方法,收集病例临床和流行病学资料,采集并检测病例、相关环境等标本,分析可能的感染来源、流行病学特征和临床特征。结果病例发病前10天内有禽类接触史,其标本经检测为H9N2禽流感病毒阳性;病例长期患有慢性疾病,此次发病后进展较快,经积极治疗无效后死亡;其居住环境、家中剩余鸡肉和周边市场检出H9禽流感阳性。结论该病例感染来源为周边市场感染H9N2禽流感病毒的鸡;对严重基础疾病者,感染H9N2禽流感病毒可导致重症或诱发死亡。     

新型H7N9禽流感病毒研究进展

新型H7N9禽流感病毒对中国的突袭引起了全球的高度关注。本文从H7N9禽流感病毒可能的起源和基因重组事件、病毒基因的多样性、重要突变位点与病毒致病性、采样与实验室检测、流行病学调查、临床症状、治疗、疫苗研究和预防等多个方面对国际、国内有关H7N9禽流感病毒的研究进展进行综述,以期为H7N9禽流感病毒的防控提供参考。     

2013-2017年浙江省绍兴市27例人感染H7N9禽流感病例流行特征分析

目的 分析浙江省绍兴市2013-2017年人感染H7N9禽流感病例流行病学特征。方法 收集2013-2017年绍兴市确诊的人感染H7N9禽流感病例临床特征和流行病学资料进行分析。结果 2013-2017年绍兴市共报告27例人感染H7N9禽流感确诊病例,88.89%的病例发生在冬春季,70.37%的病例患有慢性基础性疾病,74.07%的病例首发症状以发热为主。74.07%的病例有活禽市场暴露史,病例可疑暴露农贸市场外环境标本H7阳性率(16.45%)高于非农贸市场(3.51%),差异有统计学意义(χ²=23.240,P<0.001)。结论 绍兴地区人感染H7N9禽流感具有明显的季节性,男性、50岁以上人群、农民和基础性疾病患者是感染的高危人群。病例暴露于H7阳性率高的农贸市场可能是导致发病的主要原因。