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.     

感染人类的禽流感病毒A（H5N1）研究进展

禽流感病毒A（H5N1）[avian influenza（H5N1） viruses]之前一直存在于鸟类，但却能导致人类疾病，并且具有高致死性和广泛流行的威胁。本文在综合了第二届世界卫生组织（World Health Organization，WHO）感染人类禽流感病毒A（H5N1）临床诊断咨询会议公布的研究信息基础上，对2005年的报告进行了更新。     

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。     

Avian influenza A (H5N1) infection with respiratory failure and meningoencephalitis in a Canadian traveller

In an urban centre in Alberta, an otherwise healthy 28-year-old woman presented to hospital with pleuritic chest and abdominal pain after returning from Beijing, China. After several days, this was followed by headache, confusion and, ultimately, respiratory failure, coma and death. Microbiology yielded influenza A subtype H5N1 from various body sites and neuroimaging was consistent with meningoencephalitis. While H5N1 infections in humans have been reported in Asia since 1997, this is the first documented case of H5N1 influenza in the Western Hemisphere. The present case demonstrated the typical manifestation of H5N1 influenza but, for the first time, also confirmed previous suggestions from human and animal studies that H5N1 is neurotropic and can manifest with neurological symptoms and meningoencephalitis.     

Avian influenza H5N1 viral and bird migration networks in Asia

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.Migratory birds play important roles in the geographic spread of various zoonotic agents (1). Among these agents, the avian influenza viruses (AIVs) have been shown to be transmitted over long distances during the seasonal migration of birds (2, 3). Wild waterfowl, in particular, are considered the natural reservoir of low-pathogenic avian influenza (LPAI) viruses and have been shown to spread LPAI viruses along migratory flyways in Asia, Africa, and the Americas (4–7). However, one of the fundamental unknowns remaining is the role played by wild birds in the regional spread of AIV (8–11).Highly pathogenic avian influenza (HPAI) H5N1 first appeared in Asia in 1996 (12), and subsequently spread to Europe, the Middle East, and Africa, causing many human casualties and major economic loss in the booming Asian poultry sector. Despite the low transmissibility of HPAI H5N1 from birds to humans and from humans to humans, the high fatality rate reported in humans after the onset of the epidemic and the potential for H5N1 to become pandemic through migratory bird flyways raised serious concerns (13). The Qinghai lineage of H5N1, in particular, expanded from Qinghai to Eurasia and into the Indian subcontinent and northern and central Africa along migratory flyways. It was also shown experimentally that some species of birds shed the virus before the onset of clinical signs or with no clinical signs (14, 15). This suggests that the large-scale transmission of H5N1 by migratory birds could potentially go undetected. Using satellite telemetry, Gaidet et al. reported that one infected white-faced whistling duck (Dendrocygna viduata) survived HPAI H5N2 infection and was able to migrate for at least 655 km, when tracked with a satellite transmitter for 47 d (16). Other studies have shown that the direction of the geographic spread of HPAI H5N1 is consistent with the major bird migration routes (17, 18). A number of studies have also suggested that long-distance migration may lead to immunosuppression in birds and migratory performance is negatively affected by viral infections (19–21). However, it should be noted that HPAI H5N1 is rarely reported in living and healthy wild birds (22–24).Recently, HPAI H5N1 clade 2.3.2, the dominant subclade in Asia, was detected in migratory birds during their migration in Mongolia, South Korea, and Japan, and was shown to be associated with wild waterfowl infections (25–27). Furthermore, an isolate of HPAI H5N1 from a common buzzard (Buteo buteo) in Bulgaria showed close genetic proximity to clade 2.3.2.1 isolates from wild birds in the Tyva Republic and Mongolia, suggesting that the HPAI H5N1 viruses of clade 2.3.2 have spread westward and pose a public health threat (28). These numerous studies have directed our attention to the roles played by migratory birds in the spread of HPAI H5N1 viruses in the last decade.In this study, we constructed networks of bird and viral gene migrations to evaluate the roles of migratory birds in the spread of HPAI H5N1 clades 2.3.2 before 2007, and 2.3.2.1 on and after 2007 (clade 2.3.2 for abbreviation) in Asia. We assembled a unique database of satellite tracking data on wild bird migration patterns, records of HPAI H5N1 outbreaks, and both the viral hemagglutinin (HA) gene and whole-genome nucleotide sequences over the period 2003–2012. The objective of this study was to analyze the association between the networks of bird migration, the networks of viral gene flow, and the timing of HPAI H5N1 outbreaks at different geographic locations.     

SARS与人禽流感的异同

SARS与禽流感都是21世纪新发重大突发性呼吸道传染性疾病.2003年SARS在全球的暴发流行曾殃及近30个国家和地区[1],其中包括发达国家与发展中国家,造成了巨大的经济损失.目前人禽流感已波及15个国家和地区[2],几乎均为公共卫生措施相埘薄弱的发展中国家.     

Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.     

Pathogenicity and transmissibility of three avian influenza A (H5N6) viruses isolated from wild birds

Since 2013, highly pathogenic H5N6 avian influenza viruses (AIVs) have emerged in poultry and caused sporadic human infections in Asia. The recent discovery of three new avian H5N6 viruses – A/oriental magpie-robin/Guangdong/SW8/2014 (H5N6), A/common moorhen/Guangdong/GZ174/2014 (H5N6) and A/Pallas's sandgrouse/Guangdong/ZH283/2015 (H5N6) – isolated from apparently healthy wild birds in Southern China in 2014–2015 raises great concern for the spread of these highly pathogenic AIVs (HPAIVs) and their potential threat to human and animal health. In our study, we conducted animal experiments and tested their pathogenicity in ducks, chickens and mice. Ducks can carry and shed the H5N6 HPAIVs, but show no ill effects. On the other hand, these H5N6 HPAIVs can efficiently infect, transmit and cause death in chickens. Due to the overlap of habitats, domestic ducks play an important role in circulating AIVs between poultry and wild birds. Our results raise the possibility that wild birds disseminate these H5N6 HPAIVs to poultry along their flyways and thus pose a great threat to the poultry industry. These viruses are also highly pathogenic to mice, suggesting they pose a potential threat to mammals and, thus, public health. One virus isolated in 2015 replicates much more efficiently and is more lethal in these animals than the two other viruses isolated in 2014. It seems that the H5N6 viruses tend to be more lethal as time passes. Therefore, it is necessary to vigilantly monitor H5N6 HPAIVs in wild birds and poultry.     

Intensive care management of life-threatening avian influenza A (H5N1)

A large proportion of patients with avian influenza A (H5N1) develop life-threatening manifestations, often including ARDS, acute renal failure and multiple organ failure that requires aggressive intensive care management. The pace of development of respiratory failure is often rapid and can occur in previously healthy hosts, mandating close observation and timely intervention of infected individuals. Use of standard, contact, droplet and airborne isolation precautions is recommended to protect healthcare workers. Key components of ARDS management encompass appropriate mechanical ventilation including limiting tidal volume to ≤6 mL/kg of predicted body weight, maintaining transpulmonary pressures ≤30 cm H₂O, and utilizing positive end–expiratory pressure to limit alveolar deflation and to improve oxygenation. Additional strategies include conservative fluid management and using nutrition supplemented with antioxidants. Use of corticosteroids is controversial for both early and late ARDS and although often used for avian influenza, beneficial effects on outcomes have not been demonstrated for corticosteroids. Prone positioning can improve oxygenation temporarily and might be useful as rescue therapy for severe hypoxemia. Administration of inhaled nitric oxide and high frequency oscillatory ventilation can improve oxygenation but have not been demonstrated to improve survival in ARDS—their role in avian influenza is uncertain and availability limited. Management of multiple organ failure may include vasopressor support for septic shock and renal replacement therapy for acute renal failure.     

Cytotoxic therapy for severe avian influenza A (H5N1) infection

The mortality rate in documented avian influenza A virus subtype H5N1 infection is still high, which is currently reported by WHO at about 50%. Post-mortem analyses in affected patients have revealed haemophagocytosis similar to that found in patients with haemophagocytic lymphohistiocytosis (HLH); such haemophagocytosis could be a very prominent post-mortem feature in H5N1 infection. There are also clinical similarities between H5N1 infection and HLH, such as massive hypercytokinaemia, cytopenia, and acute encephalitis. Importantly, patients with another severe viral infection that may be complicated by secondary HLH, severe Epstein-Barr-virus-associated HLH, have significantly better survival if specific HLH therapy (including the cytotoxic and pro-apoptotic drug etoposide) is initiated early, with survival reported to rise from about 50% to 90%. With this notable improvement in survival, specific HLH treatment, including cytotoxic therapy, could be considered in patients with severe avian influenza A infection complicated by secondary HLH.     

Review of clinical symptoms and spectrum in humans with influenza A/H5N1 infection

Abstract:   Influenza A/H5N1 infection has become the major emerging infectious disease of global concern again since late 2003. A history of exposure to dead or sick poultry or wild birds occurs in over 60% of cases of human H5N1 infection. The incubation period of avian-to-human transmission is generally between 2 and 5 days and the median duration of symptoms before hospitalization is about 4.5 days. The clinical spectrum has ranged from asymptomatic infection or mild influenza-like illness to severe pneumonia and multi-organ failure. Fever > 38°C, cough and dyspnoea are the major symptoms on presentation, whereas gastrointestinal symptoms such as watery diarrhoea, vomiting and abdominal pain are common early in the course of the disease. In contrast, upper respiratory tract symptoms are less prominent in human H5N1 infection when compared to seasonal influenza. Laboratory features of human H5N1 infection include leucopoenia, especially lymphopenia, elevated amino-transaminases, thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time, increased D-Dimer, increased serum lactate dehydrogenase and creatinine phospho-kinase, and hypoalbuminemia. A low absolute lymphocyte count on admission is associated with more severe disease and death. Radiographic abnormalities include multi-focal airspace consolidation, interstitial infiltrates, patchy or lobar involvement, with rapid progression to bilateral and diffuse ground-glass opacities consistent with ARDS. However, none of the clinical, laboratory and radiographic features are specific to H5N1 infection. A detailed exposure history needs to be elicited, including any close contact with sick or dead poultry, wild birds, other severely ill persons, travel to an area with A/H5N1 activity or work in laboratory handling samples possibly containing A/H5N1 virus.     

The WHO update on influenza A (H5N1) in Hong Kong

In May 1997 influenza A subtype H5N1 virus was isolated in the Special Administrative Region of Hong Kong from a child who died. Until then, the H5N1virus was known to infect only various species of birds, including chickens and ducks. After the first hum     

甲型H1NI流感研究进展

目前南半球大部分国家已经历了甲型H1N1流感流行高峰期,而北半球温带地区逐渐进入活跃期,部分国家和地区出现地区性暴发。尽管当前甲型H1N1的流行总体上比较温和,但随着发病人数的增加,重症及危重症病例数逐渐增多,死亡病例也在明显增加。本文复习近期文献,就目前甲型H1N1流感流行态势、临床特点、病毒变异和耐药以及疫苗等热点问题作一综述,为临床医师掌握最新研究动态、及时发现和救治重症及危重症病例、降低病死率提供帮助。