江西省首例高致病性H5N1人禽流感临床特点分析

目的了解高致病性H5N1人禽流感病例的临床表现、实验室检查、影像学特征、治疗及其预后。方法对2005年12月在江西省遂川县人民医院收治的1例高致病性H5N1人禽流感的临床表现、实验室检查、心电图、影像学改变、病理变化和治疗等多方面的资料进行总结。结果患者经逆转录-聚合酶链反应（RT-PCR）、实时荧光定量PCR（real-time PCR）方法和病毒分离确诊为高致病性H5N1人禽流感病例。患者发病前有禽流感环境暴露史，以发热、畏寒起病，伴流感样症状，继之出现咳嗽、咳脓痰和脓血痰，病情进行性加重，出现腹泻和呼吸困难，伴外周血白细胞和淋巴细胞明显降低、大量尿蛋白、肝功能和心肌酶谱明显异常及血清白蛋白明显降低。发病第6天后痰培养多次发现耐苯唑西林肺炎球菌，在病情明显加重后，痰培养出现其他细菌和真菌。发病初期（第5天）胸部影像学可见右肺中下高密度病灶，继之迅速发展至双肺，出现急性呼吸窘迫综合征（ARDS）样肺部表现。经抗病毒、抗细菌、抗真菌、糖皮质激素和对症治疗未见好转，于发病后第27天死于感染性休克和多器官功能衰竭。病理表现为双肺弥漫性肺泡损伤合并感染，继发弥漫性血管内凝血（DIC）；淋巴组织中淋巴细胞明显减少，组织细胞增生；心肌水肿、空泡变性；肾小管广泛坏死。结论高致病性H5N1人禽流感患者病变进展为ARDS合并多器官功能损害时。预后不佳。     

湖南省高致病性人禽流行性感冒一例临床分析

目的 了解高致病性H5N1人禽流行性感冒(流感)病例的临床表现、实验室检查、影像学特征、治疗及其预后.方法 对2009年1月在湖南省怀化市第一人民医院收治的1例高致病性H5N1人禽流感的临床表现、实验室检查、影像学改变和治疗等多方面的资料进行回顾总结.结果 患者经RT-PCR、实时荧光定量PCR方法确诊为高致病性H5N1人禽流感病例.患者发病前有禽流感环境暴露史,以咳嗽、咳痰起病,继而出现高热、咯血,病情进行性加重,出现呼吸困难,伴外周血WBC和淋巴细胞明显降低,肝功能和心肌酶谱明显异常.发病第6天胸部影像学可见右肺实变,继而迅速扩展至双肺,出现急性呼吸窘迫综合征(ARDS)样肺部表现.经抗病毒、抗细菌、精皮质激素、呼吸机支持和对症治疗未见好转,于发病后第12天死于多器官功能衰竭.结论 高致病性H5N1人禽流感病变进展快,出现ARDS合并多器官功能损害时,预后不佳.     

H5N1人禽流感的临床诊治

1959年首次分离到A群H5N1亚型禽流感病毒,1997年5月中国香港首次发生人禽流感流行,发病18例、死亡6例,说明A群H5N1亚型病毒是强致病性,并证明其为致禽、兽及人共患的病毒。事隔7年,2004年再次在东北亚、东南亚禽流感疫点频繁暴发,既有大批家禽、野禽（如青海湖野鸟）死亡。也有人感染禽流感、兽类（如泰国虎）死亡的报道。进人2005年流行季节H5N1亚型在土耳其禽流感多点暴发,已发生人禽流感11例,死亡4例,并同时在欧洲波兰、罗马尼亚、伊朗、希腊以及非洲尼日利亚等国家出现禽流感疫点,引起全球重视。这是进入21世纪以来,     

人禽流行性感冒的研究进展

人禽流行性感冒（以下称“人禽流感”）是由禽甲型流感病毒某些亚型的毒株引起的急性呼吸道传染病。禽流行性感冒（简称“禽流感”，avianinfluenza）是由禽流感病毒引起的一种烈性禽类传染病。国际兽疫局（OIE）将其定为A类传染病，并列入国际生物武器公约动物类传染病名单。我国农业部1999年颁布的《一、二、三类动物疫病病种名录》也将其列为一类传染病。禽流感于1878年首次报道于意大利，1901年证实其病原体为病毒，1955年经血清学鉴定为A型流感病毒。历史上禽流感病毒主要感染家禽及野生鸟类等低等脊椎动物。1997年5月，我国香港特别行政区1例3岁儿童死于原因不明的多脏器功能衰竭，同年8月经美国疾病预防和控制中心（CDC）以及世界卫生组织（WHO）荷兰鹿特丹国家流感中心鉴定为禽甲型流感病毒H5N1。这是世界上首次证实禽甲型流感病毒H5N1感染人类…。之后相继有H9N2、H7N7亚型感染人类和H5N1再次感染人类的报道。至2006年7月26日出现人感染高致病性禽流感暴发的国家和地区有13个，成为人类面临的又一挑战，严重威胁着全球公共卫生安全。本文就人感染高致病性禽流感的一些研究进展进行综述。     

成人H7N9禽流感首现患者6例临床分析

目的 分析6例H7N9禽流感首现患者的临床和流行病学特点,并对治疗方法进行探讨.方法 对我院6例H7N9禽流感患者的临床表现、流行病学资料、实验室检查、影像学资料进行回顾性分析.结果 6例患者均在闵行江川地区发病,均有发热、咳嗽,大多有痰中带血和呼吸困难（5/6）,部分患者伴畏寒寒战（1/6）、恶心（2/6）、呕吐（2/6）.血常规正常或下降（5/6）,淋巴细胞有不同程度下降（5/6）,C反应蛋白、门冬氨酸氨基转移酶、肌酸激酶和乳酸脱氢酶均明显升高（6/6）,胸部CT检查显示双肺磨玻璃样及实变阴影,具有短期内病灶进展快的特点;6例患者中进展为急性呼吸窘迫综合征4例,并最终死亡,2例无急性呼吸窘迫综合征者存活.结论 人感染H7N9禽流感为新发传染性疾病,可导致严重的呼吸窘迫综合症,死亡率高.     

人禽流感——临床医师面对的问题

散发时有报道,流行潜在威胁禽流感系由甲型禽流感病毒株某些亚型引起的急性呼吸道传染病,通常情况下主要为禽类的传染病,但亦可引起多种哺乳类动物感染,如猪、犬等。我国香港特别行政区于1997年首次报道18例由高致病性禽流感病毒H5N1感染的患者,其中6例死亡,使人们认识到禽流感病毒可在人类引起严重疾病。以后世     

H6亚型流感病毒在小鼠肺内的适应性传代研究

目的为了进一步探讨H6亚型禽流感病毒(AIV)对哺乳动物的感染与致病能力,建立H6亚型AIV哺乳动物感染模型。方法用H6N1亚型AIV感染BALB/c小鼠,并在小鼠肺组织中连续传代,测定病毒的EID50。观察感染鼠临床症状和体征,评价病毒的致病性。结果经8～9代的适应后,该病毒即对小鼠产生明显的致病性,小鼠表现出精神萎靡、食欲减退、竖毛、弓背等临床症状。测定鼠肺适应株病毒H6N1-P8-M1、H6N1-P9-M2、H6N1-P8-M3的EID50分别为108.5、106.75和108.25/ml,三毒株感染鼠在发作期全部死亡。H6N1-P0组小鼠感染后14d仍全部存活。结论 H6N1亚型AIV与其他亚型相似,同样具有经适应后对哺乳动物呈现高致病性的能力,提示应关注H6亚型AIV对人类的潜在风险,得到的毒力增强鼠肺适应株为H6N1流感病毒疫苗和药物研究以及致病分子机制研究提供了动物模型。     

美国《Emerging infectious diseases》2006年第11期有关人兽共患病论文摘译

鸭科鸟类在西古北区的迁徙和H5N1亚型高致病性禽流感病毒的传播；南美洲鸭和鸥对H5N1亚型高致病性禽流感病毒的易感性；针对全国流行性感冒的社会长期规划设计；以色列蜱传回归热的分子生物特征；一例发生在狗体内的H5N1亚型商致病性禽流感；     

上海市黄浦区1例人感染高致病性禽流感病例现场流行病学分析

人感染高致病性禽流感是由H5N1血清型引起的禽流感,其发病率和死亡率都很高,危害巨大。1997年中国香港首次证实禽流感病毒（H5N1）感染人类以后,世界各地相继报道了多例禽流感病毒感染人并导致死亡事件,禽流感病毒已对人类健康构成严重威胁,引起了全世界的关注。     

H5N1禽流感病毒感染孕鼠的研究

目的用H5N1禽流感病毒感染昆明孕鼠,检测病毒在感染孕鼠各组织脏器中的复制及分布情况,并证明病毒能否通过孕鼠的胎盘垂直传染给胎鼠。方法用虎源H5N1亚型禽流感病毒滴鼻感染妊娠10-12 d的昆明孕鼠,观察孕鼠感染后的临床症状。接种病毒后第3、4、5、6和7 d分别处死3只孕鼠,取孕鼠的肺、脑、脾、肾、子宫、胎盘及胎鼠,利用RT-PCR、Real-time PCR和病毒分离方法检测各组织中的病毒核酸和病毒滴度,并进行病理组织学与免疫组织化学检测。结果昆明孕鼠接种病毒后第3 d,即可在肺、脑、脾、肾、子宫及胎盘组织中检测出H5N1禽流感病毒核酸,并从子宫、胎盘分离出H5N1禽流感病毒;感染后第6 d,从胎鼠体内检测到病毒核酸并分离出H5N1禽流感病毒。结论H5N1亚型禽流感病毒可以感染孕鼠,在孕鼠子宫和胎盘复制,感染后期可通过胎盘屏障传给胎鼠。     

人高致病性禽流感一例并文献复习

目的提高临床医师对人禽流感的认识。方法分析辽宁省首例H5N1型人禽流感患者的临床资料及文献复习。结果患者女性,31岁,来自辽宁省黑山县禽流感疫区,发病前与病死鸡有密切接触史,以“发热8d,咳嗽、气短5d,腹泻3d”为主诉于2005年11月7日由黑山县医院转入中国医科大学附属第一医院发热门诊进行隔离治疗。患者入院时呈重症肺炎、呼吸衰竭的表现,入院后末梢血白细胞减少,细胞免疫功能低下,心肌受累,ALT等多种酶学异常。经积极支持疗法、对症及抗病毒、抗感染治疗,患者病情逐渐好转,于2005年11月29日痊愈出院。该患者于出院后第9天（2005年12月8日）被确诊为H5N1型人禽流感。结论本例高致病性人禽流感的成功救治是多学科密切协作的结果,与恰当的支持、对症治疗以及积极预防和及时处理并发症密不可分。     

安徽省阜阳市首例H5N1型人禽流感临床报告

目的了解人感染高致病性H5N1型禽流感流行病学和临床学特征及防治手段。方法对本院收治的1例人感染高致病性H5N1型禽流感病例的相关资料进行回顾性分析。结果患者为26岁年轻孕妇,有病、死家禽接触史,临床表现为以急性呼吸窘迫综合征为主的全身多器官功能障碍,治疗上采取了以机械通气为主的综合性措施,治愈出院。结果提高对人感染高致病性H5N1型禽流感诊断的警惕性,及早干预是降低病死率的关键环节。     

ARDS associated with pneumonia caused by avian influenza A H7N9 virus treated with extracorporeal membrane oxygenation

This is a sporadic H7N9 avian influenza case that was the first severe imported case in Beijing and the first case of Hebei province in China. A 61‐year‐old female who had rapidly progressive pneumonia with respiratory distress and bilateral exduation and consolidation changes on chest X‐ray and computerized tomography (CT) scan that did not respond to ordinary antibiotics was diagnosed with influenza A (H7N9) infection in our hospital on July 19, 2013. Intravenous peramivir, veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) and continuous veno‐venous hemofiltration were given on the same day of lab diagnosis because of severe acute respiratory distress syndrome and acute renal failure. With antimicrobial therapy and other supportive treatment, clinical symptoms and oxygenation of the patient improved gradually. VV‐ECMO was successfully removed on the 13th day. The testing for influenza A (H7N9) turned negative on day 16 since the antivirus therapy. Twenty‐three days after hospitalization, blood stream infection with multidrug‐resistant Acinetobacter Baumannii occurred, which lead to septic shock and death. Whether or not the influenza season in north China, the influenza screening should be carried out as a conventional test for the patients who are suspected of viral pneumonia. For the patients who need mechanical ventilation and ECMO support, the lung protective strategy under the guidance of transpulmonary pressure may be helpful for recovering the lung.     

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.Acute lung injury is a continuum of clinical and radiographic changes, terminating at its most severe, with acute respiratory distress syndrome. Infection with highly pathogenic avian influenza (HPAI) viruses of the H5N1 and more recent H7N9 subtypes often leads to acute lung injury whereas seasonal influenza viruses and the 2009 pandemic H1N1 influenza viruses do so more rarely. The underlying mechanisms of influenza-related acute lung injury remain unclear, and effective therapies are lacking. Viruses that are highly pathogenic to humans (e.g., H5N1 viruses) may differ intrinsically from the less pathogenic (LP) (e.g., seasonal H1N1) viruses in their replication competence, cell tropism, and/or cytokine dysregulation (1, 2). Early treatment of H5N1 disease with the antiinfluenza drug oseltamivir is helpful but does not ensure a favorable outcome (3). Thus, effective adjunctive therapies that do not compromise beneficial host defenses are needed (4).H5N1 (5) and H7N9 (6) influenza viruses target alveolar epithelial cells, which form the crucial gas exchange interface in the lung. These cells also help to maintain intraalveolar and intravascular fluid homeostasis by vectorial transport of sodium, chloride, and water from the apical to the basolateral surface of the alveolar epithelium [alveolar fluid clearance (AFC)]. Impaired AFC and increased alveolar protein permeability (APP) contribute to acute lung injury (7). Therapies that normalize alveolar fluid clearance are likely to be free of off-target effects, unlike immunomodulation, that may promote virus replication.Human bone marrow-derived multipotent mesenchymal stromal cells (MSCs) have applications in multiple clinical disorders, including sepsis, myocardial infarction, diabetes, and acute renal failure (8). Allogeneic MSC therapy has beneficial preclinical effects on endotoxin-, bacteria-, and ventilator-induced acute lung injury (9) via MSC secretion of the soluble paracrine growth factors angiopoietin-1 (Ang1) and keratinocyte growth factor (KGF) (9, 10). MSCs can also transfer mitochondria and microvesicles that modulate immunity and epithelial response to injury (11). Current clinical trials are testing MSCs as a therapy for sepsis and acute respiratory distress syndrome (12). However, little is known about the impact of MSCs on acute respiratory viral infections, including influenza, with the exception of a study in which MSCs failed to reduce influenza-induced lung injury in mice (13). Here, we showed that influenza A/H5N1 virus infection dysregulates AFC and APP in vitro by inducing infected cells to release soluble mediators that down-regulate alveolar sodium and chloride transporters. When we cocultured alveolar epithelium with MSCs, these injury mechanisms were prevented or reduced. We then treated mice infected with influenza A/H5N1 with MSCs and demonstrated a clinically significant reduction in lung pathology and increased survival in association with a modulation of these pathogenic mechanisms in vivo.     

Avian influenza A (H5N1) infection in a child

A previously healthy, 9-year-old girl was admitted to the hospital with respiratory insufficiency. She had mild and severe respiratory symptoms for 3 weeks and 4 days before admission, respectively. She had a history of close contact with her domestic poultry, which was infected with avian influenza A (H5N1). She was isolated with the air-borne transmission prevention mode of treatment. Acute respiratory distress syndrome (ARDS) was documented from the time of admission and mechanical ventilation was introduced without improvement. She had multiple episodes of diarrhea for 2 days. Her condition deteriorated and she expired in 4 days. Throat swab RT-PCR and viral culture for avian influenza A (H5N1) were positive.     

甲型流行性感冒病毒抗原酶联免疫吸附检测试剂盒的研制及应用

目的 研制检测靶位针对甲型流行性感冒(流感)病毒核蛋白的甲型流感病毒抗原检测试剂盒,建立能检测甲型流感病毒所有亚型的方法.方法 采用双抗体夹心法检测标本中的甲型流感病毒,建立甲型流感病毒抗原ELISA方法,并对该试剂盒的灵敏性、特异性、精确性、稳定性进行测试和临床考核.结果 甲型流感病毒抗原ELISA试剂盒核蛋白检测下限为7.63 ng/Ml,灵敏度是血球凝集方法的256倍,是美国Quickdel公司胶体金产品的16倍;与乙型流感病毒、呼吸道合胞病毒、呼吸道腺病毒、副流感病毒Ⅰ/Ⅲ型、肺炎支原体、鸡新城疫病毒、鸡法氏囊病毒、鸡传染性支气管炎病毒均无交叉,特异度为100%;批内、批间变异系数(CV)值均<15%,符合国家标准;在4℃以下的稳定性可达1年,能通过37℃7 d加速试验.可检测亚型分别为H1N1、H3N2、H5N1和H9N2的甲型流感病毒.人流感病毒临床试验表明,与常规细胞培养方法比较,阳性符合率为93.44%,阴性符合率为99.31%;禽流感病毒临床试验表明,与常规细胞培养方法比较,阳性符合率为95.45%,阴性符合率为98.09%.结论 甲型流感病毒抗原ELISA试剂盒灵敏性、特异性强,可用于人甲型流感病毒和禽流感病毒感染的流行病学调查.     

An avian outbreak associated with panzootic equine influenza in 1872: an early example of highly pathogenic avian influenza?

Please cite this paper as: Morens and Taubenberger (2010) An avian outbreak associated with panzootic equine influenza in 1872: an early example of highly pathogenic avian influenza? Influenza and Other Respiratory Viruses 4(6), 373–377. Background An explosive fatal epizootic in poultry, prairie chickens, turkeys, ducks and geese, occurred over much of the populated United States between 15 November and 15 December 1872. To our knowledge the scientific literature contains no mention of the nationwide 1872 poultry outbreak. Objective To understand avian influenza in a historical context. Results The epizootic progressed in temporal-geographic association with a well-reported panzootic of equine influenza that had begun in Canada during the last few days of September 1872. The 1872 avian epizootic was universally attributed at the time to equine influenza, a disease then of unknown etiology but widely believed to be caused by the same transmissible respiratory agent that caused human influenza. Conclusions Another microbial agent could have caused the avian outbreak; however, its strong temporal and geographic association with the equine panzootic, and its clinical and epidemiologic features, are most consistent with highly pathogenic avian influenza. The avian epizootic could thus have been an early instance of highly pathogenic avian influenza.     

Genomic and Phylogenetic Characterization of Novel,Recombinant H5N2 Avian Influenza Virus Strains Isolated from Vaccinated Chickens with Clinical Symptoms in China

Infection of poultry with diverse lineages of H5N2 avian influenza viruses has been documented for over three decades in different parts of the world, with limited outbreaks caused by this highly pathogenic avian influenza virus. In the present study, three avian H5N2 influenza viruses, A/chicken/Shijiazhuang/1209/2013, A/chicken/Chiping/0321/2014, and A/chicken/Laiwu/0313/2014, were isolated from chickens with clinical symptoms of avian influenza. Complete genomic and phylogenetic analyses demonstrated that all three isolates are novel recombinant viruses with hemagglutinin (HA) and matrix (M) genes derived from H5N1, and remaining genes derived from H9N2-like viruses. The HA cleavage motif in all three strains (PQIEGRRRKR/GL) is characteristic of a highly pathogenic avian influenza virus strain. These results indicate the occurrence of H5N2 recombination and highlight the importance of continued surveillance of the H5N2 subtype virus and reformulation of vaccine strains.