·高被引論文摘要·

被引頻次：96

浙江省人感染H7N9禽流感流行特征與防控對策

陳恩富，柴程良，孫繼民

目的：分析人感染H7N9禽流感的流行特征、研究進展和目前防控面臨的問題，提出防控對策。方法：采用流行病學(xué)個案調(diào)查與描述性分析方法，收集人感染H7N9禽流感確診病例流行病學(xué)和防控措施相關(guān)資料，分析病例流行病學(xué)特征和疫情防控措施效果。結(jié)果浙江省共確診人感染H7N9禽流感病例44例，死亡6例；男性27例，占61.36%；平均年齡60.18歲（32～86歲）；≥50歲35例，占79.55%；農(nóng)民和離退人員30例，占68.18%。40例（90.91%）集中于杭州和湖州。78.38%（29/37）有慢性基礎(chǔ)性疾病，78.95%（30/38）發(fā)病前有禽類暴露史；病例的1004名密切接觸者均未發(fā)現(xiàn)感染。病例可疑暴露場所外環(huán)境標(biāo)本H7N9陽性率高達43.21%（35/81）。暫停市場活禽交易對控制疫情有效。結(jié)論：人感染H7N9禽流感流行特征尚未完全明了，需要多部門聯(lián)合開展監(jiān)測、研究和防控。

人感染H7N9禽流感；流行病學(xué)；控制策略

來源出版物：中國公共衛(wèi)生, 2013, 29(5): 625-627

被引頻次：48

H7亞型禽流感病毒概述

朱聞斐，高榮保，王大燕，等

摘要：自2002年以來，全球報道的人感染H7亞型禽流感病毒病例超過100人，波及荷蘭、意大利、加拿大、美國以及英國等國家。人感染H7亞型禽流感病毒的臨床表現(xiàn)由結(jié)膜炎至輕微的上呼吸道疾病，甚至是肺炎。2013年3月31日，中國報道了上海市和安徽省兩地共3例H7N9亞型禽流感病毒（AIVs）感染死亡病例。由于從家禽中分離到的H7亞型流感病毒不斷增加，

而且H7亞型AIVs感染人所導(dǎo)致的嚴(yán)重的臨床癥狀，因此該亞型流感病毒對人類健康造成嚴(yán)重威脅，所以我們必須提高對H7亞型AIVs的認(rèn)識，并要加強人群和動物中流感病毒的持續(xù)監(jiān)測以及疫苗和藥物的研究，以應(yīng)對可能由于H7亞型AIVs引起的流感大流行。

關(guān)鍵詞：H7亞型禽流感病毒；人感染H7亞型；H7N9；H7病原學(xué)特征

來源出版物：病毒學(xué)報, 2013, 29(3): 245-249

被引頻次：45

科學(xué)認(rèn)識H7N9，有效防控人感染禽流感病毒

毛青

摘要：自2013年2月以來，華東地區(qū)上海市、安徽省、江蘇省、浙江省先后發(fā)生不明原因重癥肺炎病例，大多數(shù)患者病前曾有活禽鳥接觸史，經(jīng)病原體分離鑒定后，于3月31日將其確診為人感染H7N9禽流感病毒（avian influenza virus，AIV）。截止到2013年4月15日共確診病例63例，死亡14例。目前病例均為散發(fā)，并未見人際間傳播。

關(guān)鍵詞：H7N9；人；感染；禽流感；病毒

來源出版物：第三軍醫(yī)大學(xué)學(xué)報, 2013, 35(8): 693-695

被引頻次：43

中國大陸130例人感染H7N9禽流感病例流行病學(xué)特征分析

閆鐵成，肖丹，王波

摘要：目的：描述和分析人感染H7N9禽流感病例的流行病學(xué)分布特征，為該傳染病的防控提供科學(xué)依據(jù)。方法：收集中國大陸2013年3月30日—5月20日期間報告的人感染H7N9禽流感確診病例130例，利用χ2檢驗、線性趨勢檢驗和空間自相關(guān)分析，描述并分析病例的三間分布特征。結(jié)果：130例確診病例中，報告發(fā)病時間的104例，同時報告發(fā)病時間和確診時間的103例。死亡病例36例，其中，同時報告發(fā)病時間和死亡時間的21例。首例病例發(fā)生于2月19日，末例病例發(fā)生于5月3日，病例的發(fā)病高峰出現(xiàn)在3月末至4月中旬。21例病例發(fā)病至死亡的平均時間為（16±8）d（6～36 d），103例病例發(fā)病至確診的平均時間為（9±5）d（1～39 d），發(fā)病至確診的平均時間呈下降趨勢（F= 37.56，P＜0.001）。確診病例中，男性、50歲及以上者居多，分別占69.6%（87/125）和72.8%（91/125）。病例分布于中國10個省（直轄市），存在空間自相關(guān)性（Z=3.90，P= 0.001），浙江、上海、江蘇3個省（直轄市）報告的病例總數(shù)占病例總數(shù)的81.5%。結(jié)論男性、中老年是人感染H7N9禽流感的主要易感人群。我國東南沿海是人禽流感的重點監(jiān)測地區(qū)。

關(guān)鍵詞：禽流感；流行病學(xué)；性別分布

來源出版物：中華疾病控制雜志, 2013, 17(8): 651-654

被引頻次：38

國內(nèi)102例人感染H7N9禽流感特點初步分析

韓明鋒，冉獻貴，趙鳳德

摘要：目的：初步總結(jié)人感染H7N9禽流感的特點。方法：利用目前國家和各省市衛(wèi)生部門及國家媒體網(wǎng)站公布的人感染H7N9禽流感病例的有關(guān)資料，用描述性分析方法，總結(jié)該病的流行病學(xué)和臨床特點。結(jié)果：人感染H7N9禽流感傳染源可能為攜帶H7N9禽流感病毒的禽類。目前尚未發(fā)現(xiàn)人傳人的情況。人發(fā)病一般表現(xiàn)為流感樣癥狀，但是重癥患者病情發(fā)展迅速，多在5～7 d出現(xiàn)重癥肺炎，病死率較高。用神經(jīng)氨酸酶抑制劑早期抗病毒治療有效。結(jié)論：人感染H7N9禽流感是人類新發(fā)傳染病，病情較兇險。應(yīng)重視動物和人間疫情防控以及疾病的早發(fā)現(xiàn)、早診斷、早治療。

關(guān)鍵詞：流感病毒A型，H7N9亞型；禽流感；流行病學(xué)；疾病特征

來源出版物：傳染病信息, 2013 (2): 68-70

被引頻次：36

H7N9病毒的來源和重組模式

張寶，黃克勇，郭勁松，等

摘要：目的：通過序列分析揭示H7N9病毒的來源和重組產(chǎn)生模式。方法：收集H7N9序列，運用BLAST、MEGA5.0等生物信息學(xué)軟件分析序列相似性、多序列比對、構(gòu)建進化樹，確定H7N9病毒各節(jié)段序列的親緣序列，模擬H7N9重組產(chǎn)生方式。結(jié)果：系統(tǒng)進化樹顯示HA、NA、PB2和NS節(jié)段最近緣關(guān)系序列只有一個；而PB1、PA、NP和MP節(jié)段序列，分布于不同的兩個分枝。通過組合分析親緣序列，可以將目前流行的H7N9病毒分為5型：A、B、A/Shanghai/1/2013-H7N9、A/Pigeon/Shanghai/S1069-H7N9和A/Zhejiang/HZ1/2013-H7N9。A型又可以分為A1和A2亞型。結(jié)論：通過對序列的組合分析，推測此次H7N9病毒流行至少由5個病毒經(jīng)過4次重組產(chǎn)生，產(chǎn)生兩個主要流行株A和B型。A1和A2亞型的出現(xiàn)是同一次重組過程中產(chǎn)生兩株不同產(chǎn)物；A/Pigeon/Shanghai/S1069-H7N9是A型H7N9病毒在流行期間與當(dāng)?shù)豀9N2病毒的再一次重組產(chǎn)生。A/Zhejiang/HZ1/2013-H7N9是A2亞型和B型重組后產(chǎn)生的混合型。

關(guān)鍵詞：H7N9；禽流感；重組；生物信息學(xué)

來源出版物：南方醫(yī)科大學(xué)學(xué)報, 2013, 33(7): 1017-1021

被引頻次：21

H7N9禽流感病毒研究現(xiàn)狀

江麗芳

摘要：2013年3月在中國華東地區(qū)爆發(fā)了一場嚴(yán)重的人類感染禽流感疫情，導(dǎo)致此次疫情的病原體為一種全新的H7N9禽流感病毒，該病毒以其對人類的高致病性及遠高于H5N1禽流感病毒的傳播速度而引起全球廣泛關(guān)注。本文就H7N9禽流感病毒的病原學(xué)、致病的分子基礎(chǔ)、流行病學(xué)、臨床特征及防治措施等方面的研究現(xiàn)狀進行綜述，旨在了解人感染H7N9禽流感的研究進展，為人感染H7N9禽流感的有效防控提供科學(xué)依據(jù)。

關(guān)鍵詞：H7N9禽流感病毒；病原學(xué)；流行病學(xué)；致病性；臨床特征；防治措施

來源出版物：中山大學(xué)學(xué)報：醫(yī)學(xué)科學(xué)版, 2013, 34(5): 651-656

被引頻次：19

人感染H7N9禽流感流行特征與防控策略

陳健，毛盛華，胡家瑜，等

摘要：2013年3月31日中國大陸出現(xiàn)新型禽流感疫情，此次的H7N9禽流感病毒為全球首次發(fā)現(xiàn)的新亞型流感病毒，可能由3種流感病毒重組后產(chǎn)生。截至5月31日，我國內(nèi)地共報告確診病例131例，死亡39例。而在上海市報告的33例確診病例中，29例發(fā)病于4月6日上海市關(guān)閉活禽交易市場前，其余4例發(fā)病于關(guān)閉后的第一個潛伏期內(nèi)。33例病例中60歲以上患者占66.7%（22/33）；15例死亡病例中，60歲以上患者占80%（12/15）；90.91%（30/33）的病例具有可疑的動物或環(huán)境暴露史。此次疫情呈散發(fā)，雖然出現(xiàn)了2起家庭聚集性病例，但目前還沒有明確的人傳人的證據(jù)。疫情發(fā)生后，上海市人民政府適時啟動了流感流行應(yīng)急預(yù)案Ⅲ級響應(yīng)，通過突發(fā)公共衛(wèi)生事件應(yīng)急響應(yīng)、關(guān)閉全市活禽交易、健康教育、風(fēng)險溝通等手段，及時有效地控制了疾病的傳播。本文分析這次疫情防控工作的得失并提出建議，供今后的防疫工作借鑒參考。

關(guān)鍵詞：禽流感；H7N9亞型流感病毒A型；流行病學(xué)；傳染病控制

來源出版物：第二軍醫(yī)大學(xué)學(xué)報, 2013, 34(6): 585-590

被引頻次：19

杭州市下城區(qū)4例人感染H7N9禽流感病例的臨床與流行病學(xué)特征分析

壽鈞，周曉紅，何玉芳，等

摘要：目的：對杭州市下城區(qū)2013年確診報告的4例人感染H7N9禽流感病例進行臨床和流行病學(xué)分析，為進一步科學(xué)防控人禽流感提供依據(jù)。方法：對確診病例和病例的密切接觸者進行個案調(diào)查，采用熒光雙標(biāo)記探針反轉(zhuǎn)錄-聚合酶鏈反應(yīng)檢測H7N9禽流感病毒。對病例的呼吸道標(biāo)本進行人感染H7N9禽流感病毒核酸檢測。結(jié)果：4例病例表現(xiàn)為重癥肺炎并呈進行性加重，

發(fā)病至首次就診平均時間為2 d，首次住院為5 d，確診時間為7 d。4病例呈高度散發(fā)，病例之間無流行病學(xué)關(guān)聯(lián)，發(fā)病時間均為春季，均有農(nóng)貿(mào)市場暴露史。對病例采取隔離治療、密切接觸者進行醫(yī)學(xué)觀察、疫點終末消毒、農(nóng)貿(mào)市場停止活禽交易等綜合措施后，疫情得到有效控制。結(jié)論：4例人感染高H7N9禽流感病例發(fā)病與農(nóng)貿(mào)市場暴露有關(guān)，暫未發(fā)現(xiàn)人傳人的證據(jù)。早期發(fā)現(xiàn)和救治患者是提高患者預(yù)后的關(guān)鍵，要加強人感染H7N9禽流感疫情監(jiān)測，及時科學(xué)處置疫情，以控制疫情擴散。

關(guān)鍵詞：人感染H7N9禽流感；臨床；流行病學(xué)

來源出版物：疾病監(jiān)測, 2013, 28(8): 657-659

被引頻次：17

H7N9禽流感病毒感染及其實驗室診斷

董曉毅，孫長貴

摘要：至2013年4月23日，新型H7N9亞型的禽流感病毒已經(jīng)在中國感染了108人，并致22人死亡?？茖W(xué)家發(fā)現(xiàn)甲型禽流感病毒H7N9源自3種病毒株的重配，并出現(xiàn)了實質(zhì)性的突變。H7N9病毒擁有幾個哺乳動物流感病毒的特征，從而形成了對人類的感染力，因此需重視其大規(guī)模流行的潛力。本文對該病毒的生物學(xué)特性、流行病學(xué)、臨床表現(xiàn)和實驗室診斷進行了簡要綜述。

關(guān)鍵詞：H7N9；禽流感病毒；感染

來源出版物：實驗與檢驗醫(yī)學(xué), 2013, 31(2): 105-107

被引頻次：986

來源出版物：New England Journal of Medicine, 2013, 368(20): 1888-1897

被引頻次：377

Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: Clinical analysis and characterisation of viral genome

Chen, Y; Liang, WF; Yang, SG; et al.

Abstract: Background: Human infection with avian influenza A H7N9 virus emerged in eastern China in February, 2013, and has been associated with exposure to poultry. We report the clinical and microbiological features of patients infected with influenza A H7N9 virus and compare genomic features of the human virus with those of the virus in market poultry in Zhejiang, China. Methods: Between March 7 and April 8, 2013, we included hospital inpatients if they had new-onset respiratory symptoms, unexplained radiographic infiltrate, and laboratory-confirmed H7N9 virus infection. We recorded histories and results of haematological, biochemical, radiological, and microbiological investigations. We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. We tested for co-infections and monitored serum concentra- tions of six cytokines and chemokines. We collected cloacal swabs from 86 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples. We identified and subtyped isolates by RT-PCR sequencing. RNA extraction, complementary DNA synthesis, and PCR sequencing were done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient's and the chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and NS genes. Findings: We identified four patients (mean age 56 years), all of whom had contact with poultry 3-8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. Two patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs. The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken. All viral gene segments were of avian origin. The H7 of the isolated viruses was closest to that of the H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu and Gly186Val substitutions in human virus H7 (associated with increased affinity for alpha-2,6-linked sialic acid receptors) and the PB2 Asp701Asn mutation (associated with mammalian adaptation). Ser31Asn mutation, which is associated with adamantane resistance, was noted in viral M2. Interpretation: Cross species poultry-to-person transmission of this new reassortant H7N9 virus is associated with severe pneumonia and multiorgan dysfunction in human beings. Monitoring of the viral evolution and further study of disease pathogenesis will improve disease management, epidemic control, and pandemic preparedness.

來源出版物：The Lancet, 2013, 381(9881): 1916-1925

被引頻次：255

Clinical findings in 111 cases of influenza A (H7N9) virus infection

Gao, HN; Lu, HZ; Cao, B; et al.

Abstract: Background: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. Methods: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. Results: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombo-cytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reversetranscriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P = 0.02). Conclusions: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death.

來源出版物：New England Journal of Medicine, 2013, 368(24): 2277-2285

被引頻次：255

Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: Phylogenetic, structural, and coalescent analyses

Liu, D; Shi, WF; Shi, Y; et al.

Abstract: Background: On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events. Methods: We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties. Findings: The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades. Interpretation: The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future.

來源出版物：The Lancet, 2013, 381(9881): 1926-1932

被引頻次：235

Epidemiology of human infections with avian influenza A (H7N9) virus in China

Li, Q; Zhou, L; Zhou, MH; et al.

Abstract: Background: The first identified cases of avian influenza A (H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. Methods: Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptasepolymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts inwhom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. Results: Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. Conclusions: Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

來源出版物：New England Journal of Medicine, 2014, 370(6): 520-532

被引頻次：186

Characterization of H7N9 influenza A viruses isolated from humans

Watanabe, T; Kiso, M; Fukuyama, S; et al.

Abstract: Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-tohuman transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission(1), and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively. In mice, Anhui/1 and Shanghai/1 were more pathogenic than a control avian H7N9 virus (A/duck/Gunma/466/2011 (H7N9); Dk/GM466) and a representative pandemic 2009 H1N1 virus (A/California/4/2009 (H1N1pdm09); CA04). Anhui/1, Shanghai/1 and Dk/GM466 replicated well in the nasal turbinates of ferrets. In nonhuman primates, Anhui/1 and Dk/GM466 replicated efficiently in the upper and lower respiratory tracts, whereas the replicative ability of conventional human influenza viruses is typically restricted to the upper respiratory tract of infected primates. By contrast, Anhui/1 did not replicate well in miniature pigs after intranasal inoculation. Critically, Anhui/1 transmitted through respiratory droplets in one of three pairs of ferrets. Glycan arrays showed that Anhui/1, Shanghai/1 and A/Hangzhou/1/2013 (H7N9) (a third human A(H7N9) virus tested in this assay) bind to human virus-type receptors, a property that may be critical for virus transmissibility in ferrets. Anhui/1 was found to be less sensitive in mice to neuraminidase inhibitors than a pandemic H1N1 2009 virus, although both viruses were equally susceptible to an experimental antiviral polymerase inhibitor. The robust replicative ability in mice, ferrets and nonhuman primates and the limited transmissibility in ferrets of Anhui/1 suggest that A(H7N9) viruses have pandemic potential.

來源出版物：Nature, 2013, 501(7468): 551-555

被引頻次：181

The genesis and source of the H7N9 influenza viruses causing human infections in China

Lam, TTY; Wang, J; Shen, YY; et al.

Abstract: A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths(1,2). Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic(1,3,4). However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known(5). Using a combination of active surveillance, screening of virus archives, and evolutionary analyses,here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

來源出版物：Nature, 2013, 502(7470): 241-244

被引頻次：178

Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection : A descriptive study

Chen, HY; Yuan, H; Gao, RB; et al.

Abstract: Background: Human infections with different avian influenza viruses-eg, H5N1, H9N2, and H7N9-have raised concerns about pandemic potential worldwide. We report the first human infection with a novel reassortant avian influenza A H10N8 virus. Methods: We obtained and analysed clinical, epidemiological, and virological data from a patient from Nanchang City, China. Tracheal aspirate specimens were tested for influenza virus and other possible pathogens by RT-PCR, viral culture, and sequence analyses. A maximum likelihood phylogenetic tree was constructed. Findings: A woman aged 73 years presented with fever and was admitted to hospital on Nov 30, 2013. She developed multiple organ failure and died 9 days after illness onset. A novel reassortant avian influenza A H10N8 virus was isolated from the tracheal aspirate specimen obtained from the patient 7 days after onset of illness. Sequence analyses revealed that all the genes of the virus were of avian origin, with six internal genes from avian influenza A H9N2 viruses. The aminoacid motif GlnSerGly at residues 226-228 of the haemagglutinin protein indicated avian-like receptor binding preference. A mixture of glutamic acid and lysine at residue 627 in PB2 protein-which is associated with mammalian adaptation- was detected in the original tracheal aspirate samples. The virus was sensitive to neuraminidase inhibitors. Sputum and blood cultures and deep sequencing analysis indicated no co-infection with bacteria or fungi. Epidemiological investigation established that the patient had visited a live poultry market 4 days before illness onset. Interpretation: The novel reassortant H10N8 virus obtained is distinct from previously reported H10N8 viruses. The virus caused human infection and could have been associated with the death of a patient.

來源出版物：The Lancet, 2014, 383(9918): 714-721

被引頻次：171

Genetic analysis of novel avian A (H7N9) influenza viruses isolated from patients in China, February to April 2013

Kageyama, T; Fujisaki, S; Takashita, E; et al.

Abstract: Novel influenza viruses of the H7N9 subtype have infected 33 and killed nine people in China as of 10 April 2013. Their haemagglutinin (HA) and neuraminidase genes probably originated from Eurasian avian influenza viruses; the remaining genes are closely related to avian H9N2 influenza viruses. Several characteristic amino acid changes in HA and the PB2 RNA polymerase subunit probably facilitate binding to human-type receptors and efficient replication in mammals, respectively, highlighting the pandemic potential of the novel viruses. Humans are rarely infected with avian influenza viruses, with the exception of highly pathogenic avian influenza A(H5N1) viruses, which have caused 634 infections and 371 deaths as of 12 March 2013. A few isolated cases of human infection with viruses of the H7N2, H7N3, and H7N5 subtypes have been reported, but none were fatal. In 2003, in the Netherlands, 89 people were infected with an influenza virus of the H7N7 subtype that caused conjunctivitis and one fatality. On 19 February 2013, an 87 year-old man in Shanghai developed a respiratory infection and died on 4 March, and on 27 February 2013, a 27 year-old pork seller in a Shanghai market became ill and died on 10 March. A 35 year-old woman in ChuzhouCity in Anhui province (west of Shanghai), who had contact with poultry, became ill on 15 March 2013, and remains hospitalised in critical condition. There is no known epidemiological relationship among these three cases. A 38 yearold man in Hangzhou (Zhejiang province, south of Shanghai) became ill on 7 March 2013 and died on 27 March. All four cases presented with respiratory infections that progressed to severe pneumonia and breathing difficulties. On 31 March 2013, the Chinese Centre for Disease Control and Prevention announced the isolation in embryonated eggs of avian influenza viruses of the H7N9 subtype (designated A/Shanghai/1/2013, A/Shanghai/2/ 2013, and A/Anhui/1/2013) from the first three cases. The sequences of the coding regions of all eight viral genes were deposited in the influenza sequence database of the Global Initiative on Sharing All Influenza Data (GISAID) on 31 March (Table 1). On 5 April 2013, the Hangzhou Center for Disease Control and Prevention deposited the haemagglutinin (HA), neuraminidase (NA), and matrix (M) gene sequences of A/Hongzhou/1/2013 virus (Table 1), which was isolated in cell culture from samples obtained from the 38 yearold man. All four human influenza A(H7N9) viruses are similar at the nucleotide and amino acid levels, suggesting a common ancestor. The HA gene of the novel viruses belongs to the Eurasian lineage of avian influenza viruses and shares ca. 95% identity with the HA genes of low pathogenic avian influenza A(H7N3) viruses isolated in 2011 in Zhejiang province (south of Shanghai) (Figure 1, Table 2). The NA gene of the novel viruses is ca. 96% identical to the low pathogenic avian influenza A(H11N9) viruses isolated in 2010 in the Czech Republic.

來源出版物：Euro Surveill, 2013, 18(15): 7-21

被引頻次：159

Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs

Zhu, H; Wang, D; Kelvin, DJ; et al.

Abstract: The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure. Pigs were productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to naive pigs or ferrets. Under appropriate conditions, human-to-human transmission of the H7N9 virus may be possible.

來源出版物：Science, 2013, 341(6142): 183-186

Human infection with a novel avian-origin influenza A (H7N9) virus

Gao, RB; Cao, B; Hu, YW; et al.

Background: Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. Methods: We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerasechain-reaction assays, viral culturing, and sequence analyses. Results: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. Conclusions: Novel reassortant H7N9 viruses were associated with severe and fatal respiratorydisease in three patients.