活禽交易市场短期休市措施对控制市场H7N9病毒污染效果的评价

目的评估活禽交易市场短期休市措施对降低市场H7N9禽流感病毒污染及人感染H7N9发病的成效。方法收集整理2014年2月至2017年5月,中山市活禽交易市场短期休市信息、市场环境H7RT-PCR检测数据,及人感染H7N9发病数据。RRX=休市后第X周市场环境H7样本阳性率/休市前1周阳性率×100%。结果共实施3轮短期休市。第一轮:2014年2月10日至23日,期间周边地市未同步休市。恢复交易后,环境阳性率持续上升,RR1=0.40(95%CI:0.28-0.59),RR3=0.63(95%CI:0.32-1.24),RR4=0.83(95%CI:0.48-1.46),2015年5月份报告2例人感染H7N9病例。第二轮:2015年2月19日至28日,全省统一部署,周边地市同步休市。恢复交易后,环境阳性率持续维持在10%以下,RR1=0.15(95%CI:0.07-0.34),RR2=0.21(95%CI:0.10-0.41),RR3=0.03(95%CI:0.00-0.18),RR4=0.10(95%CI:0.04-0.27),该流行季未再报告病例。第三轮:2017年1月8日至21日,期间周边地市未同步休市。恢复交易后,环境阳性率持续上升,RR1=0.25(95%CI:0.09-0.68),RR3=0.37(95%CI:0.14-1.00),RR4=1.07(95%CI:0.54-2.11),2017年2月报告2例人感染H7N9病例。结论单个城市的短期休市,即使时间长达2周,一旦恢复交易,市场环境阳性率迅速上升,人感染发病的风险再次增加;区域性多个城市同步休市,市场环境阳性率能持续维持在低水平,极大地减少人感染发病的风险。     

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。     

人感染H7N9禽流感1例

目的 分析1例确诊人感染H7N9禽流感重症患者临床和流行病学特点,并对治疗方法进行探讨.方法 对该患者的临床、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 该患者为55岁男性,从事活禽贩卖及宰杀职业,以咳嗽、咳黄脓痰、发热为首发症状,病程早期出现胸闷、呼吸困难及痰中带血,无明显上呼吸道症状;实验室检查:血白细胞、淋巴细胞及中性粒细胞计数降低,血乳酸脱氢酶及超敏C反应蛋白增高.胸部CT显示双肺炎,右肺为主;短期内病灶进展快,出现急性肺损伤.给予氧疗、奥司他韦、抗感染药物、激素、免疫球蛋白等治疗.结论 人感染H7N9禽流感临床进展快,以肺部损伤为主,与接触活禽有关.     

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。     

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。     

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。     

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。     

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。     

福建省首例人感染H7N9禽流感病例实验室诊断和病毒序列分析

摘要 目的 应用real-time RT-PCR和病毒序列测定等方法对福建省首例人感染H7N9禽流感病例开展实验室诊断。方法 采集人感染H7N9禽流感病例呼吸道标本并提取RNA,分别采用甲乙型流感通用引物和探针、季节性流感（包括H3N2、H1N1、H1N1pdm）特异性引物和探针以及H7N9特异性引物和探针进行荧光PCR检测。利用自行设计的引物扩增病毒基因组节段,测定并分析病毒基因组序列。结果 real-time RT-PCR结果表明,应用甲型通用引物扩增结果阳性,乙型及季节性流感（包括H3N2、H1N1以及H1N1pdm）扩增结果均为阴性,特异性H7N9亚型流感病毒扩增结果阳性。序列测定获得的病毒4个节段的序列与已公布的人感染H7N9禽流感病毒序列高度一致。结论 病例呼吸道标本中存在人感染H7N9禽流感病毒,病毒的基因与近期国内流行的人感染H7N9禽流感病毒高度类似。     

Contact reductions from live poultry market closures limit the epidemic of human infections with H7N9 influenza

An early steep increase in the number of humans infected with avian influenza A(H7N9) virus was observed in China, raising great public concern domestically and internationally. Little is known about the dynamics of the transmission contacts between poultry and human populations, although such understanding is essential for developing effective strategies to control this zoonosis. In this study, we evaluated the effects of contact reductions from live poultry markets (LPMs) closures on the transmission of H7N9 virus during epidemics in Guangdong Province, China. A mathematical model of the poultry-to-person transmission dynamics of H7N9 virus was constructed. The parameters in the model were estimated from publicly available data on confirmed cases of human infection and information on LPMs closure during 2013–2017. By fitting the model, we measured the time-dependent contact quantity of the susceptible population to LPMs. The results showed that periodic intervention strategies can greatly reduce the magnitude of outbreaks, and the earlier interventions for policy are implemented, the smaller is the outbreak. The control efforts for LPMs to decrease the contact quantity are critical in preventing epidemics in the long term. This model should provide important insights for the development of a national intervention strategy for the long-term control of avian influenza virus epidemics.     

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。     

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.     

Genetic Characterization and Pathogenicity of H7N7 and H7N9 Avian Influenza Viruses Isolated from South Korea

H7 low pathogenic avian influenza viruses (LPAIVs) can mutate into highly pathogenic avian influenza viruses (HPAIVs). In addition to avian species, H7 avian influenza viruses (AIVs) also infect humans. In this study, two AIVs, H7N9 (20X-20) and H7N7 (34X-2), isolated from the feces of wild birds in South Korea in 2021, were genetically analyzed. The HA cleavage site of the two H7 Korean viruses was confirmed to be ELPKGR/GLF, indicating they are LPAIVs. There were no amino acid substitutions at the receptor-binding site of the HA gene of two H7 Korean viruses compared to that of A/Anhui/1/2013 (H7N9), which prefer human receptors. In the phylogenetic tree analysis, the HA gene of the two H7 Korean viruses shared the highest nucleotide similarity with the Korean H7 subtype AIVs. In addition, the HA gene of the two H7 Korean viruses showed high nucleotide similarity to that of the A/Jiangsu/1/2018(H7N4) virus, which is a human influenza virus originating from avian influenza virus. Most internal genes (PB2, PB1, PA, NP, NA, M, and NS) of the two H7 Korean viruses belonged to the Eurasian lineage, except for the M gene of 34X-2. This result suggests that active reassortment occurred among AIVs. In pathogenicity studies of mice, the two H7 Korean viruses replicated in the lungs of mice. In addition, the body weight of mice infected with 34X-2 decreased 7 days post-infection (dpi) and inflammation was observed in the peribronchiolar and perivascular regions of the lungs of mice. These results suggest that mammals can be infected with the two H7 Korean AIVs. Our data showed that even low pathogenic H7 AIVs may infect mammals, including humans, as confirmed by the A/Jiangsu/1/2018(H7N4) virus. Therefore, continuous monitoring and pathogenicity assessment of AIVs, even of LPAIVs, are required.     

福建省2013-2018年人感染H7N9禽流感病例流行病学特征分析

目的 分析福建省人感染H7N9禽流感(H7N9)的流行病学特征,为防控提供依据。方法 收集福建省2013年3月— 2018年7月H7N9病例相关资料,采用描述性流行病学方法分析其流行病学特征。结果 福建省共确诊H7N9病例108例:因病毒性不明原因肺炎确诊的病例(肺炎病例)占84.26%(91/108);发病集中在12月至次年4月,合计占95.37%(103/108);发病具有一定程度的地域集中性。肺炎病例中,男性占81.32%(74/91),发病年龄为54.9± 17.1岁,发病前有禽类接触史者占91.21%(83/91);病例预后与病例发现方式关系密切,与其发病时间、发病地点、发病年龄、发病-诊疗的时间间隔间均无显著关联。结论 加强福建省H7N9防控工作应结合其流行病学特征着重加强不明原因肺炎病例的监测、检测工作。     

Genetic characterization of influenza A virus subtypes H11N6, H11N7, and H11N9 isolated from free‐grazing ducks,Thailand

Influenza A viruses (IAVs) infect avian species and several mammalian species including humans. Anseriformes water birds are an important reservoir of IAVs. In this study, we identified and characterized IAV subtypes H11N6 (n = 5), H11N7 (n = 3), and H11N9 (n = 3) isolated during the influenza surveillance program in free‐grazing ducks from 2012 to 2015 in Thailand. Eleven IAV‐H11 viruses were characterized by either whole genome sequencing (n = 5) or HA and NA gene sequencing (n = 6) for phylogenetic and amino acid analyses. Phylogenetic analysis showed that Thai IAV‐H11 were grouped into Avian Eurasian lineage. Amino acid analysis showed that all Thai IAV‐H11 viruses have low pathogenic avian influenza (LPAI) characteristics and sensitive to Oseltamivir and Amantadine. Novel reassortant viruses (IAV‐H11N7 and IAV‐H11N9) have been observed. The reassortant viruses contained NP, M, and NS gene segments which originate from intercontinental sources which never been reported in Thai IAVs. In summary, this study demonstrated high genetic diversity of IAV‐H11 circulating in free‐grazing ducks. Free‐grazing ducks infected with IAVs generated novel reassortant IAV‐H11. Thus, surveillance of IAVs in free‐grazing ducks should be routinely conducted to monitor novel reassortant viruses and subsequently potential virulence viruses.