Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997-1998

In 1997, outbreaks of highly pathogenic influenza A (H5N1) among poultry coincided with 18 documented human cases of H5N1 illness. Although exposure to live poultry was associated with human illness, no cases were documented among poultry workers (PWs). To evaluate the potential for avian-to-human transmission of H5N1, a cohort study was conducted among 293 Hong Kong government workers (GWs) who participated in a poultry culling operation and among 1525 PWs. Paired serum samples collected from GWs and single serum samples collected from PWs were considered to be anti-H5 antibody positive if they were positive by both microneutralization and Western blot testing. Among GWs, 3% were seropositive, and 1 seroconversion was documented. Among PWs, approximately 10% had anti-H5 antibody. More-intensive poultry exposure, such as butchering and exposure to ill poultry, was associated with having anti-H5 antibody. These findings suggest an increased risk for avian influenza infection from occupational exposure.     

Antibody response in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts

The first documented outbreak of human respiratory disease caused by avian influenza A (H5N1) viruses occurred in Hong Kong in 1997. The kinetics of the antibody response to the avian virus in H5N1-infected persons was similar to that of a primary response to human influenza A viruses; serum neutralizing antibody was detected, in general, >/=14 days after symptom onset. Cohort studies were conducted to assess the risk of human-to-human transmission of the virus. By use of a combination of serologic assays, 6 of 51 household contacts, 1 of 26 tour group members, and none of 47 coworkers exposed to H5N1-infected persons were positive for H5 antibody. One H5 antibody-positive household contact, with no history of poultry exposure, provided evidence that human-to-human transmission of the avian virus may have occurred through close physical contact with H5N1-infected patients. In contrast, social exposure to case patients was not associated with H5N1 infection.     

Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997.

In May 1997, a 3-year-old boy in Hong Kong died of a respiratory illness related to influenza A (H5N1) virus infection, the first known human case of disease from this virus. An additional 17 cases followed in November and December. A case-control study of 15 of these patients hospitalized for influenza A (H5N1) disease was conducted using controls matched by age, sex, and neighborhood to determine risk factors for disease. Exposure to live poultry (by visiting either a retail poultry stall or a market selling live poultry) in the week before illness began was significantly associated with H5N1 disease (64% of cases vs. 29% of controls, odds ratio, 4.5, P=.045). By contrast, travel, eating or preparing poultry products, recent exposure to persons with respiratory illness, including persons with known influenza A (H5N1) infection, were not associated with H5N1 disease.     

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.     

Seroprevalence of avian influenza A/H5N1 among poultry farmers in rural Indonesia, 2007

Since 2003, about a third (> 150 cases) of human cases of highly pathogenic avian influenza (HPAI) A/H5N1 worldwide are reported from Indonesia. We measured the seroprevalence of H5N1 among Indonesian poultry farmers and assessed the risk factors for and knowledge of H5N1 infection. In 2007, poultry workers and farm residents were interviewed about risk factors for knowledge of and then examined for the seropositivity of H5N1 virus. Four hundred ninety-five of 622 farmers (80%) from 12 farms participated in the study. Of these, 71% were male, with a median age of 29 years. None tested positive for H5N1 virus. Masks were never worn by 54% of participants; 86% were afraid of becoming infected. For the preceding six months, 1 farm was confirmed as having poultry infected with H5N1 virus. No evidence of subclinical infection with avian influenza A/H5N1 virus was found among poultry farmers, although exposure of the farmers to this virus may have been limited. However, we recommend sustaining ongoing surveillance and control efforts.     

Global epidemiology of human infections with highly pathogenic avian influenza A (H5N1) viruses

Abstract:   From 1997 through 2007, human infections with highly pathogenic avian influenza A (H5N1) viruses resulted in rare, sporadic, severe and fatal cases among persons in 14 countries in Asia, the Middle East, Eastern Europe and Africa. Of 369 reported human H5N1 cases that occurred from 1997 through 2007, overall mortality was 60%. Ten antigenically and genetically distinct clades of H5N1 viruses have been identified to date, and strains from four clades have infected humans. Surveillance has focused upon hospitalized cases of febrile acute lower respiratory tract disease among persons with exposure to sick or dead poultry, or to a human H5N1 case. Detection of H5N1 virus infection is based primarily upon collection of respiratory tract specimens from suspected cases for RT-PCR testing. Most human H5N1 cases were previously healthy children or young adults who developed severe acute pulmonary or multi-organ disease following direct or close contact with sick or dead H5N1 virus–infected poultry. Occasional clusters of H5N1 cases have occurred, predominantly among blood-related family members. Limited human-to-human H5N1 virus transmission has been reported or could not be excluded in some clusters. The frequency of asymptomatic or clinically mild H5N1 virus infection is unknown, but limited investigations suggest that such infections have been rare since 2003. There is no evidence of sustained human-to-human H5N1 virus spread. However, H5N1 viruses continue to circulate and evolve among poultry in many countries, and there are many unanswered questions about human infection with H5N1 viruses. Thus, the pandemic influenza threat presented by H5N1 viruses persists.     

Lack of evidence of avian-to-human transmission of avian influenza A (H5N1) virus among poultry workers, Kano, Nigeria, 2006

BACKGROUND: In February 2006, poultry outbreaks of highly pathogenic avian influenza A (H5N1) virus were confirmed in Nigeria. A serosurvey was conducted to assess H5N1 transmission among poultry workers and laboratory workers in Nigeria. METHODS: From 21 March through 3 April 2006, 295 poultry workers and 25 laboratory workers with suspected exposure to H5N1 virus were administered a questionnaire to assess H5N1 exposures, medical history, and health care utilization. A serum specimen was collected from participants to test for H5N1 neutralizing antibodies by microneutralization assay. RESULTS: The 295 poultry workers reported a median of 14 days of exposure to suspected or confirmed H5N1-infected poultry without antiviral chemoprophylaxis and with minimal personal protective equipment. Among 25 laboratory workers, all handled poultry specimens with suspected H5N1 virus infection. All participants tested negative for H5N1 neutralizing antibodies. CONCLUSIONS: Despite widespread exposure to poultry likely infected with H5N1 virus, no serological evidence of H5N1 virus infection was identified among participants. Continued surveillance for H5N1 cases in humans and further seroprevalence investigations are needed to assess the risk of avian-to-human transmission, given that H5N1 viruses continue to circulate and evolve among poultry.     

Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

In Egypt, efforts to control highly pathogenic H5N1 avian influenza virus in poultry and in humans have failed despite increased biosecurity, quarantine, and vaccination at poultry farms. The ongoing circulation of HP H5N1 avian influenza in Egypt has caused >100 human infections and remains an unresolved threat to veterinary and public health. Here, we describe that the failure of commercially available H5 poultry vaccines in Egypt may be caused in part by the passive transfer of maternal H5N1 antibodies to chicks, inhibiting their immune response to vaccination. We propose that the induction of a protective immune response to H5N1 is suppressed for an extended period in young chickens. This issue, among others, must be resolved and additional steps must be taken before the outbreaks in Egypt can be controlled.     

Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model

Avian influenza A H5N1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. Probable human-to-human transmission has been documented rarely, but H5N1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. The pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. However, the relative contribution of human internal protein genes or other molecular changes to the efficient transmission of influenza viruses among humans remains poorly understood. Here, we report on a comparative ferret model that parallels the efficient transmission of H3N2 human viruses and the poor transmission of H5N1 avian viruses in humans. In this model, an H3N2 reassortant virus with avian virus internal protein genes exhibited efficient replication but inefficient transmission, whereas H5N1 reassortant viruses with four or six human virus internal protein genes exhibited reduced replication and no transmission. These findings indicate that the human virus H3N2 surface protein genes alone did not confer efficient transmissibility and that acquisition of human virus internal protein genes alone was insufficient for this 1997 H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host. These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait.     

Evidence for avian influenza A infections among Iowa's agricultural workers

Background Identifying risk factors for zoonotic influenza transmission may aid public health officials in pandemic influenza planning. Objectives We sought to evaluate rural Iowan agriculture workers exposed to poultry for previous evidence of avian influenza virus infection. Methods In 2004, we enrolled 803 rural adult Iowans in a 2‐year prospective study of zoonotic influenza transmission. Their enrollment data and sera were compared with those of 66 adult controls enrolled at the University of Iowa in 2006 by using proportional odds modeling. Results Of the 803 participants 58·8% were male with a mean age of 55·6 years. Forty‐eight percent reported previous poultry exposure. Sera were studied by microneutralization techniques for antibodies against avian H4, H5, H6, H7 and H9 viruses. Touching live birds was associated (OR 1·2; 95% CI 1·02–1·8) with increased antibody titer against H5 virus. Similarly, participants who reported hunting wild birds had increased antibody titers against H7 virus (OR 2·8; 95%CI 1·2–6·5) and subjects who reported recent exposure to poultry had increased antibody titers against H6 (OR 3·4; 95% CI 1·4–8·5) and H7 viruses (OR 2·5, 95% CI 1·1–5·7). There was no evidence of elevated antibody against avian H4 or H9 viruses. Conclusions These data suggest that hunting and exposure to poultry may be important risk factors for avian influenza virus infection among rural US populations. Agriculture workers should be included in influenza pandemic plans.     

Avian influenza A (H5N1) infectious in both birds and humans in South-Eastern Asian countries

Avian influenza affects most types of birds and occurs in epidemics on poultry farms. The fatal disease is named "highly pathogenic avian influenza" and is caused by influenza A virus subtypes H5 and H7. The natural reservoir is the migratory waterfowl that occasionally infects domestic poultry. In 1997 in Hong Kong, 18 persons were infected and 6 of them died. At the end of 2003 and the beginning of 2004, avian influenza H5N1 infected numerous farms in several South-Eastern Asian countries. The virus was transmitted to humans in close contact with infected birds. A total of 34 persons were infected and 23 of them died. There is currently a considerable concern about the H5N1 avian influenza that has infected humans: the high virulence, evolution rate, the possibility of recombination with other influenza viruses, how H5N1 variants that infect humans or different approaches to the development of influenza vaccines.     

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。     

2014-2018年中山市人感染H7N9禽流感病例特征分析

目的 了解2014年1月至2018年5月中山市人感染H7N9禽流感病例临床特征并分析其流行病学特征。方法 收集整理2014年1月至2018年5月中山市H7N9病例个案调查资料。结果 中山市累计报告15例H7N9病例,其中3岁以下女童3人,临床表现为上呼吸道感染,预后良好。12例成人病例,年龄34-78岁(中位数54岁),男性占58.3%(7/12)。成人病例发病后4-8 d(中位数5 d)均出现呼吸困难、严重低氧血症等重症肺炎表现,需要呼吸机辅助通气治疗措施。4例(26.7%)死亡,其中3例为50岁以上且有高血压等基础疾病。60.0%(9/15)发病时间集中于1月下旬至2月上旬。10例可能传播途径为禽类接触传播,其中6例从市场购买活禽回家并亲自宰杀。2例有活禽市场暴露但无活禽直接接触史,可能传播途径为禽类市场空气传播。共发现3起聚集性疫情,其中2起发生人传人的可能性大。结论 在H7N9流行季节,尤其是1月下旬至2月上旬疫情高发期,中山市应采取综合措施,降低居民,尤其是50岁以上有基础疾病者,从市场购买活禽回家及宰杀活禽等高风险行为。     

Emergence and predominance of an H5N1 influenza variant in China

The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.     

Risk factors for highly pathogenic avian influenza (HPAI) H5N1 infection in backyard chicken farms, Thailand

To reduce the risk of highly pathogenic avian influenza (HPAI) H5N1 infection in humans, the pathways by which HPAI is spread in poultry must be determined. Backyard poultry farmers are particularly vulnerable to the threat of HPAI, with both their health and livelihoods at risk. Identifying the risk factors for HPAI infection in backyard farms should allow control measures to be better targeted. To study the risk factors of HPAI H5N1 infection, we carried out a case-control study on backyard chicken farms in Thailand, analyzing 104 case farms and 382 control farms. Data on farming practices and environmental characteristics were analyzed using multivariate logistic regression models. We show that farms where owners bought live chickens from another backyard farm had a higher risk of HPAI H5N1 infection (OR 3.34, 95% CI 1.72–6.47), while those where owners used a disinfectant to clean poultry areas were exposed to lower risk (OR 0.48, 95% CI 0.26–0.87). Our results highlight the important role of the trade of poultry between farms in the transmission of HPAI H5N1, in addition to farming practices and environmental characteristics. Findings from this study may help to tailor prevention measures to the local circumstances of backyard farms in different regions of the world.     

安徽省首例人感染H5N6禽流感病例的调查与分析

目的 分析安徽省首例人感染H5N6禽流感病例发病与流行病学特征,为制定监测方案与防控措施提供科学依据。方法 对人感染H5N6禽流感病例、密切接触者、感染来源进行流行病学调查,采集相关生物和环境标本进行实验室检测,应用描述性流行病学方法进行分析。结果 安徽省首例人感染H5N6禽流感病例为单个散发病例,密切接触者无感染,早期临床表现无特异性,发病前一周有明确的病死禽接触史,病禽市场检出2份H5N6 阳性标本。结论 该病例为本地感染病例,感染来源与接触病死禽有关,未发现人传人的证据。     

福建省人感染H5N6禽流感病毒与外环境禽流感病毒相关性分析

目的 分析福建省外环境H5亚型禽流感病毒分布情况及与人感染H5N6禽流感的关系,为人感染禽流感的科学防治提供依据。方法 收集2013-2017年福建省外环境常规监测标本信息,进行统计分析。从数据库下载相关禽流感病毒基因序列,进行基因同源性比对和系统进化分析。结果 外环境监测结果统计分析显示:2013-2017年共采集样本4 903份,H5亚型阳性率为4.24%,且不同的网络实验室(χ²=101.033)、监测场所(χ²=45.526)、标本类型(χ²=31.751)和季节(χ²=48.174)阳性率均存在统计学差异(P<0.05)。福建省首例人感染H5N6禽流感(A/Fujian-Sanyuan/21099/2017)病毒全基因序列与6株福建省外环境H5N6病毒的同源性在85.1%~98.5%,与病家院中采集的1株加强监测外环境标本的HA和NA基因同源性分别为100.0%和99.9%。系统进化分析显示:福建省人感染H5N6病毒HA基因与加强监测的外环境H5N6病毒的进化距离最近,与其余6株距离较远,处在不同的进化分枝中,其基因源于H5N8病毒;而NA基因则与7株外环境H5N6病毒的进化距离较近,源于H5N6病毒。结论 福建省冬春季外环境中禽流感活动较为活跃,应加强活禽交易市场的卫生管理工作。福建省发现的首例人感染H5N6禽流感与外环境禽流感病毒的重配可能存在一定的相关性。     

Serological analysis of serum samples from humans exposed to avian H7 influenza viruses in Italy between 1999 and 2003

We evaluated the potential for avian-to-human transmission of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI) H7N1 and LPAI H7N3 viruses that were responsible for several outbreaks of influenza in poultry in Italy between 1999 and 2003. A serological survey of poultry workers was conducted by use of a combination of methods. Evidence of anti-H7 antibodies was observed in 3.8% of serum samples collected from poultry workers during the period in 2003 when LPAI H7N3 virus was circulating. These findings highlight the need for surveillance in people occupationally exposed to avian influenza viruses, so that they can be monitored for the risk of avian-to-human transmission during outbreaks of avian influenza caused by both LPAI and HPAI viruses.     

Cross-reactivity to highly pathogenic avian influenza H5N1 viruses after vaccination with nonadjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a potential priming strategy

Antigenically well-matched vaccines against highly pathogenic avian influenza H5N1 viruses are urgently required. Human serum samples after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 (H5N3) vaccine were tested for antibody to 1997-2004 human H5N1 viruses. Antibody responses to 3 doses of nonadjuvanted vaccine were poor and were higher after MF59-adjuvanted vaccine, with seroconversion rates to A/HongKong/156/97, A/HongKong/213/03, A/Thailand/16/04, and A/Vietnam/1203/04 of 100% (P < .0001), 100% (P < .0001), 71% (P = .0004), and 43% (P = .0128) in 14 subjects, respectively, compared with 27%, 27%, 0%, and 0% in 11 who received nonadjuvanted vaccine. These findings have implications for the rational design of pandemic vaccines against influenza H5.