Influenza A (H5N1) in Hong Kong: an overview

Worldwide pandemics of human influenza virus caused extensive morbidity and mortality around the world had been documented in the 20th century. However, the mechanisms involved in the emergence of novel influenza virus and the epidemiological factors leading to pandemics are unpredictable. Southern China is postulated as the epicentre of influenza epidemics due to its agricultural-based communities and high population density. Pandemic influenza viruses are through to arise from avian viruses through genetic reassortment among influenza viruses. An influenza virus (H5N1) known to infect only birds previously was found to infect human causing disease and death in Hong Knog in 1997 and the outbreak involved 18 patients with six deaths. Prior to the human outbreak, the H5N1 virus was found to cause extensive death in chickens in three farms in Hong Kong. The significance of this outbreak raised worldwide concern on the possibilities that such an influenza virus may become the next influenza pandemic strain. Investigations were initiated to find the source of the virus. In addition the extend of spread in individuals in contact with the index case and infected poultry was studied by H5-specific serology. Results demonstrated that individuals in close contact with the index case or with exposure to poultry were at risk of being infected. Out of the 18 cases of human infection, eleven had severe infection with symptoms of pneumonia and multi-organ failure. All severe cases presented with lower respiratory infection and lymphopenia and six eventually died. Case-fatality ratio was high among patients over 12 years of age (five out of nine). Control measures aimed at reducing exposure of human to potential H5-positive poultry were instituted which included culling of all poultry in Hong Kong, the segregation of water fowls and chicken, and the introduction of import control measures for chickens. Such measures had successfully controlled the outbreak and continuous surveillance of the poultry in Hong Kong of H5N1 infection is maintained to minimize future human exposure.     

中国大陆首例人感染禽流感病毒(H5N1)的调查与确认

目的确认2005年10月湖南省湘潭县发生的一起家庭聚集性（姐弟二人）不明原因肺炎病例的病因.方法访谈病例发病前后的相关知情人,重现病家暴露环境及发病时间序列,查阅临床病志,对病例和病死禽的密切接触者进行医学观察.采集病例咽拭子,应用逆转录-聚合酶链反应（RT-PCR）和实时荧光定量PCR法,检测A/H5N1亚型特异的核酸片段,接种SPF鸡胚进行病毒分离.应用马血球血凝抑制试验和微量中和试验检测患者急性期和恢复期血清抗A/H5特异性抗体滴度.结果姐（病例1）弟（病例2）二人分别在其家鸡开始死亡2天和4天后出现发热和肺炎症状,病例1死于急性呼吸窘迫综合征和多器官功能衰竭,病例2痊愈.病例1病后第8天的血清A/H5抗体阴性,病例2急性期和恢复期血清抗体滴度呈4倍以上升高.192名密切接触者中,仅1名（接诊过病例1的医生）出现上呼吸道症状,但血清标本经微量中和试验阴性.结论病例2为中国大陆第一例感染禽流感病毒（H5N1）的确诊病例,病例1为临床诊断病例.二者发病最可能是感染了相同家庭环境中病死禽传播的H5N1病毒,调查中未发现两病例之间有互相传播的证据.     

Seroprevalence of Antibodies to Avian Influenza Virus A (H5N1) among Residents of Villages with Human Cases, Thailand, 2005

In 2005, we assessed the seroprevalence of neutralizing antibodies to avian influenza virus A (H5N1) among 901 residents of 4 villages in Thailand where at least 1 confirmed human case of influenza (H5N1) had occurred during 2004. Although 68.1% of survey participants (median age 40 years) were exposed to backyard poultry and 25.7% were exposed to sick or dead chickens, all participants were seronegative for influenza virus (H5N1).     

湖南省2005-2017年人感染禽流感流行病学特征分析

目的 对湖南省发现的所有人感染禽流感病例进行流行病学特征分析，为防控策略的制定和调整提供科学依据。方法 对疫情概况、病例三间分布和暴露史进行描述，并报道家庭聚集性病例。结果 湖南省已发现人感染H5N1病例6例，人感染H5N6病例4例，人感染H7N9病例99例，人感染H9N2病例6例。病例主要发生在11月至次年4月。H5N1病例分布在5个市州，H5N6病例分布在4个市州，H9N2病例分布在3个市州，H7N9病例分布在13个市州。4种亚型人感染禽流感在男性和女性中均有发生。H5N1、H5N6和H9N2病例年龄较小，H7N9病例以中老年为主。51.0%的病例为农民。95.5%的病例有禽类或禽类污染的环境暴露史。湖南省已发现H5N1、H5N6疑似家庭聚集性病例和H7N9确诊家庭聚集性疫情。结论 禽类和禽类环境是人感染禽流感病毒的主要来源，开展环境监测有利于疾病的预测预警。禽流感病毒存在有限非持续的人传人现象，密切监测病毒基因变化，对密切接触者实行医学观察，对于防止二代病例发生有重要意义。     

人感染H7N9禽流感26例临床特征与病毒基因分析研究

目的探讨人感染H7N9禽流感病毒患者的流行病学和临床特征,以及病毒分子生物学特征。方法收集湖南省2013、2014年确诊的26例人感染H7N9禽流感病毒患者的资料,对人和禽分离的H7N9病毒进行鉴定和测序分析。结果26例患者中,发热和咳嗽是最常见的起病症状,所有患者均存在肺炎;20例(76.92%)出现急性呼吸窘迫综合征(ARDS),25例(96.15%)初诊时白细胞下降或正常,发病至开始进行抗病毒治疗的平均时间为10 d。10例死亡,病死率达38.46%。患者分离的H7N9病毒株测序分析表明,发生了H7基因Gln226Leu和Gly186Val替换,PB2基因Asp701Asn突变。结论急性呼吸系统损害是人感染H7N9禽流感的主要临床表现,活禽暴露是人感染H7N9禽流感的重要危险因素,H7N9禽流感病毒基因发生了部分位点的适应性突变,更容易从禽类向人跨种传播引起人类严重疾病,需加强病原学监测。     

Highly pathogenic avian influenza H5N1, Thailand, 2004

In January 2004, highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first confirmed in poultry and humans in Thailand. Control measures, e.g., culling poultry flocks, restricting poultry movement, and improving hygiene, were implemented. Poultry populations in 1,417 villages in 60 of 76 provinces were affected in 2004. A total of 83% of infected flocks confirmed by laboratories were backyard chickens (56%) or ducks (27%). Outbreaks were concentrated in the Central, the southern part of the Northern, and Eastern Regions of Thailand, which are wetlands, water reservoirs, and dense poultry areas. More than 62 million birds were either killed by HPAI viruses or culled. H5N1 virus from poultry caused 17 human cases and 12 deaths in Thailand; a number of domestic cats, captive tigers, and leopards also died of the H5N1 virus. In 2005, the epidemic is ongoing in Thailand.     

New DIVA vaccine for the protection of poultry against H5 highly pathogenic avian influenza viruses irrespective of the N-subtype

Most human cases of highly pathogenic H5N1 avian influenza virus (HPAIV) infection are the result of direct contact with infected poultry. Therefore, infection of poultry should be prevented to avoid human exposure. One method to combat HPAIV outbreaks relies on depopulation. An alternative or supplementary method is the use of DIVA (discriminating infected from vaccinated animals) vaccines to prevent infection of animals on holdings surrounding an outbreak. Discrimination between infected and vaccinated animals is often based on the ‘heterologous neuraminidase’ strategy. This implies that a suitable vaccine can only be selected when the N-subtype of the outbreak strain is known. Thus, at least two vaccines with different N-subtypes must be available, allowing a switch of vaccine in the event that one of them matches the outbreak strain. However, such vaccines cannot be used preventively in situations in which the N-subtype of the outbreak strain is unknown. In order to circumvent these drawbacks we generated a recombinant influenza virus containing the HA gene of a contemporary H5N1 HPAIV strain in combination with the NA gene of a human type B influenza virus. An inactivated vaccine based on this virus protected chickens against clinical disease, and completely prevented virus shedding after H5N1 HPAIV challenge infection. Serological analyses confirmed that the vaccine complied with the DIVA principle. Since NA of type B does not occur in avian influenza strains, this vaccine is suitable as a DIVA vaccine against any H5 HPAIV, and may be used preventively without compromising the DIVA principle.     

Single dose of oil-adjuvanted inactivated vaccine protects chickens from lethal infections of highly pathogenic H5N1 influenza virus

The highly pathogenic H5N1 influenza viruses are endemic in poultry in many countries, but continuously infect humans and cause human mortality. H5N1 influenza viruses have been regarded as a pandemic candidate. In a pandemic event by this virus, the protection of poultry with an effective vaccine will help to greatly reduce the spread of this virus to humans since it easily infects poultry. Here we showed that immunization with one dose of oil-adjuvanted inactivated H5N1 vaccine could protect chickens from lethal infection by highly pathogenic H5N1 influenza virus until 12 weeks post-immunization. The complete protection of chickens depended on the amount of HA antigens in the vaccine. Complete homologous protection required over 1.25 μg of HA antigens and complete heterologous protection required over 5.0 μg of HA antigens. The bivalent H5N1 inactivated vaccine composed of 1.25 μg of each antigen from clade 1 and clade 2.3.4 H5N1 influenza virus completely protected chickens from the lethal challenge of both viruses. When we determined the induction of antibody subtypes in tissues including nasal cavity, trachea, and lungs, the IgG subtype of antibody was induced more than the IgM or IgA subtype of antibody. Taken together, our results suggest that one dose of oil-adjuvanted inactivated H5N1 vaccine could provide chickens with sterile immunity against the homologous highly pathogenic H5N1 influenza virus.     

Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China

During February 2013–March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013–May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely.