108例人感染H7N9禽流感病例临床特点分析

国家和各省市卫生部门及国家媒体网站等收集2013年4月23日18：00之前通报确诊的108例人感染H7N9禽流感患者的相关资料信息，并进行分析。     

安徽省人感染H7N9禽流感病毒基因组特征分析

目的 分析安徽省2013年分离的5株人感染H7N9禽流感病毒全基因组特征。方法 从美国国家生物技术信息中心(NCBI)和全球禽流感基因共享数据库(GISAID)中下载具有代表性的H7N9、H7N3、H7N7和H9N2等毒株序列,运用分子生物信息学软件分析病毒全基因组特征。结果 我省流行的H7N9病毒HA基因与A/duck/Fujian/6390/2010(H7N3)相似度最高,NA基因与A/northern shoveler/Hong Kong/MPL133/2010(H2N9)株相似度最高,6个内部基因片段与中国北京、香港、湖南、江苏地区分离的H9N2毒株相似度接近。氨基酸序列比对发现NS1蛋白218~230位氨基酸缺失、M2蛋白的N31S突变、HA蛋白的G186V 、Q226L突变以及NA蛋白69~73位的删除,并且我省人感染H7N9病毒均带有PB2的E627K突变,同时PA-100A、PA-356R、PA-409N这些易感人类的特征氨基酸也在本次流行的H7N9病毒中发现;此外HA蛋白裂解位点仅有1个碱性氨基酸、糖基化位点高度保守以及未发现NA蛋白R294K突变也是我省H7N9病毒主要特征。结论 我省人感染H7N9病毒与中国其他省份流行株高度同源,该病毒获得跨种传播、毒力增强、耐药等能力均与病毒蛋白功能域有关。     

福建省人感染H7N9禽流感诊疗特征分析

目的 分析福建省人感染H7N9禽流感诊疗特征,以期为疾病防控和临床救治提供参考。方法 采用SPSS 23.0、SAS9.2软件对福建省人感染H7N9禽流感诊疗特征进行描述性分析。结果 福建省共报告108例病例,死亡28人,病死率25.93%。病例从发病到就诊、住院、确诊和抗病毒治疗中位数分别为3 d、5 d、7 d和6 d,死亡病例组发病至死亡中位数16 d,从发病至实验室确诊比早期提前1 d。一半以上病例没有在5 d内使用抗病毒治疗药物,死亡风险可能没有得到有效降低。46.3%的病例伴有基础疾病,随年龄增长患基础疾病和重症率增加(Z=4.75,P<0.01; Z=5.07,P<0.01)。男女病死率比较,差异无统计学意义(χ²=28.37,P<0.01),各年龄组病死率比较,差异无统计学意义(χ²=2.23,P=0.53)。患心血管疾病(OR=2.60,95%CI:1.06~6.39)、出现肺炎(OR=1.27,95%CI:1.13~1.42)、重症(OR=1.24,95%CI:1.13~1.42)、需进ICU(OR=3.80,95%CI:1.20~11.99)、合并细菌感染需要使用抗生素(OR=1.19,95%CI:1.08~1.32)和需使用激素(OR=7.47,95%CI:1.64~33.95)等因素增加病死风险。结论 福建省人感染H7N9禽流感病例诊断能力较早期有所提高,抗病毒治疗仍不及时。当患者伴有心血管疾病和需要使用激素等危险因素时,应积极加强救治,降低病死率。     

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。     

新疆地区人感染H7N9禽流感病例流行病学特征分析

目的 描述和分析新疆人感染H7N9禽流感病例流行病学特征,为新疆地区防控人感染H7N9禽流感提供理论依据和防控建议。方法 收集2014年1月至2017年12月新疆地区人感染H7N9禽流感病例13例的流行病学信息,分析疾病的三间分布特征。结果 新疆地区13例人感染H7N9病例死亡11例,病死率84.61%,男女性别比2.25∶1,发病年龄介于35-83岁之间,平均年龄62.8岁。病例发病时间集中在夏季至冬季,发病地点以乌鲁木齐市最多。大部分病例均有禽类暴露史。发病至诊断时间间隔位于6~16 d之间,平均10 d。发病到死亡间隔时间位于5~21 d之间,平均发病到死亡天数为11 d。结论 60岁以上男性是新疆地区人感染H7N9禽流感病例高危人群,应建议其避免禽类暴露。提高医院医生对于H7N9禽流感病例的早期识别,早诊断,早用抗病毒药物治疗,降低病例死亡风险。     

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。     

国内102例人感染H7N9禽流感特点初步分析

目的初步总结人感染H7N9禽流感的特点。方法利用目前国家和各省市卫生部门及国家媒体网站公布的人感染H7N9禽流感病例的有关资料,用描述性分析方法,总结该病的流行病学和临床特点。结果人感染H7N9禽流感传染源可能为携带H7N9禽流感病毒的禽类。目前尚未发现人传人的情况。人发病一般表现为流感样症状,但是重症患者病情发展迅速,多在5～7d出现重症肺炎,病死率较高。用神经氨酸酶抑制剂早期抗病毒治疗有效。结论人感染H7N9禽流感是人类新发传染病,病情较凶险。应重视动物和人间疫情防控以及疾病的早发现、早诊断、早治疗。     

宁波市人感染H7N9禽流感病例流行病学及临床特征分析

目的了解2014年宁波市人感染H7N9禽流感的流行特征和临床特点.方法 采用流行病学个案调查与描述性分析方法.结果 2014年宁波市共确诊H7N9禽流感病例15例,死亡4例;病例发病前均有禽类暴露史;103名密切接触者均未感染;大部分病例有慢性基础性疾病.结论 老年男性人群为H7N9禽流感发病的主要人群,加强人群及外环境监测是防控H7N9工作的重点.     

何谓H7N9禽流感——应正确认识和积极防治

H7N9型禽流感（H7N9 avian influenza）是一种新型禽流感病毒引起,并且可导致人类感染,于2013年3月31日在中国上海和安徽两地率先报告。     

Histopathological findings in a critically ill patient with avian influenza A (H7N9)

To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23^rd day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient’s clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39^th day after symptom onset, despite corticosteroid treatment.     

H7N9禽流感及相关疫情分析评估

2016年10月起至今发生的第5波人感染H7N9禽流感疫情比前4波严重,截止至2017年3月8日,本波疫情感染者数量已达历年累积报告数的40.00%。病原学研究发现最近广东分离的两株H7N9病毒在HA的链接肽位置发生插入性变异导致对禽致病性有所增强,但绝大多数分离株与前4波疫情中H7N9病毒病原学特征无明显区别;流行病学调查研究显示,除有3起可能人传人事件外,与前4波比较,患者之间也没有明显的流行病学关联。因此,基于疫情分析及风险评估认为H7N9禽流感仍会扩散传播并继续发生新发病例,但流行病学和病原学分析认为该病毒在人际间持续传播的可能性低。本综述认为加强H7N9禽流感病原学与流行病学的研究具有重要的公共卫生意义。     

鸭源H7N9亚型禽流感病毒感染SPF鸡转录组学分析

目的 为了分析鸭源H7N9亚型禽流感病毒感染SPF鸡后宿主基因表达水平的变化。方法 以鸭源H7N9亚型禽流感病毒感染SPF鸡,收集肺脏进行高通量测序。结果 与对照组相比,感染组得到差异表达基因740个,其中上调基因有602个,下调基因有138个。GO条目分析发现,差异基因主要涉及免疫应答反应和炎症反应等。经KEGG 数据库比对注释及富集分析显示有7个通路富集显著,其中Toll-like信号通路有11个基因表达上调,分别为IL-6、TLR4、PIK3、IRF7、MD-2、IRF5、MYD88、CD86、STAT1、TLR2和CCL4,NOD-like受体信号通路有7个基因表达上调,分别为IRF7、CTSB、P2RX7、CYBB、PSTPIP1、HSP90AA1和NAMPT。结论 鸭源H7N9亚型病毒感染SPF鸡后,免疫相关基因表达明显增强。在Toll-like信号通路中, TLR4在MD-2的协助下被激活,随后依赖MYD88途径激活下游的IRF5,继而引起CCL4、IL-6显著表达。同时NLRP3炎症体在H7N9亚型病毒感染过程中也发挥着重要作用。     

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.     

Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus

The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.Human infection with a novel avian-origin H7N9 influenza A virus causing severe respiratory symptoms and mortality was first reported in eastern China in March 2013 (1). To date, the novel virus has caused two outbreaks of human infection, including 375 known cases and 115 deaths as of 11 March 2014 (2). Phylogenetic analysis suggests that the virus is a triple reassortant of H7, N9, and H9N2 avian influenza viruses (3, 4). The H7 and N9 genes may have been transferred from migratory birds to domestic ducks and then to chickens in the live poultry markets (3–5), after which reassortment with enzootic H9N2 viruses formed the H7N9 viruses identified in humans (3–5).H9N2 influenza virus has low pathogenicity for avians, replicating mainly in the upper respiratory tract and causing mild or no overt signs of illness in specific pathogen-free (SPF) chickens (6). In 1994, the H9N2 subtype was first identified in chicken farms in the Guangdong province of south China (7); it has since become widespread in chickens and has caused great economic loss from reduced egg production and highly lethal coinfections (8–11). To reduce the impact of H9N2 infection in chickens, the flocks have been vaccinated since 1998 with commercial inactivated vaccines, such as A/chicken/Guangdong/SS/1994 (Ck/GD/SS/94), A/chicken/Shandong/6/1996 (Ck/SD/6/96), and A/chicken/Shanghai/F/1998 (Ck/SH/F/98) (8, 12, 13). These H9N2 vaccines initially limited the outbreaks and virus spread. However, despite multiple doses, the H9N2 vaccines became less effective, especially after 2007, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks and has caused sporadic disease outbreaks (8, 10, 12–20). However, the recent prevalence and molecular evolution of the H9N2 viruses in chickens especially in the flocks receiving large-scale vaccination, and their role in the emergence of human H7N9 virus, are not fully understood. In this study, we systematically investigated the prevalence and evolution of H9N2 viruses mainly focusing on farm chickens and their role in the genesis of the novel H7N9 viruses.