H5N1-infected cells in lung with diffuse alveolar damage in exudative phase from a fatal case in Vietnam

Necropsied lung tissues of three fatal cases with avian influenza A virus (H5N1) infection in Vietnam were analyzed to detect H5N1 virus-infected cells. Formalin-fixed and paraffin-embedded lung tissue sections showed typical histological features of diffuse alveolar damage (DAD) in all cases. Immunohistochemistry for the influenza A virus nucleoprotein antigen revealed positive signals of bronchiolar and alveolar epithelial cells in only one patient, who exhibited DAD with an exudative phase and died on the 6th day after onset. However, no signal was detected in the other two cases of DAD with a proliferative phase. These patients died on day 16 and day 17 after onset, respectively. H5N1 virus antigens were detected predominantly in epithelial cells in terminal bronchioles and in alveoli, i.e., type I and type II alveolar pneumocytes, and in alveolar macrophages. The pathogenesis of exudative DAD caused by H5N1 infection is discussed.     

Surveillance of the first case of human avian influenza A (H7N9) virus in Beijing,China

Purpose

Human infections with avian influenza A (H7N9) virus manifested in China in March 2013. The first case infected with H7N9 virus in Beijing involved a family member of a chicken dealer and was reported in April 2013. The clinical and epidemiological characteristics of this case and her parents were examined to illustrate some key traits regarding this novel H7N9 virus.

Methods

The index case was subjected to intensive clinical examination in order to observed the clinical process. Real-time PCR was used to confirm cases infected with H7N9 virus. The index case was administered oseltamivir (45 mg, twice daily) at the early stage of the infection. Sera were collected from the index case and her parents from the onset of illness onwards. The subjects were followed for 4 weeks.

Results

The sera were confirmed by neutralizing antibody tests. The index case’s clinical manifestation progressed quickly. The pharyngeal swab tested positive for influenza A based on the detection of influenza A antigen (rapid influenza diagnostic test) 15 h after the onset of fever and was positive for H7N9 virus. The patient’s temperature dropped to 36.2 °C 18 h after treatment by oseltamivir (32 h after fever). Cough and other symptoms alleviated rapidly. A number of specimens from the environment of this cluster and from the feces specimens tested positive for viral RNA of the H7N9 virus on the fourth day following onset of the index case’s illness. Pharyngeal swabs of the mother tested positive for H7N9 virus twice, but she showed no clinical symptoms. Four weeks after disease onset, the family did not present any clinical symptoms, and the results of the physical examination and blood tests were normal. The mother and the case’s sera had a fourfold increased neutralizing antibody titer.

Conclusion

Early diagnosis and early initiation of the treatment of confirmed infections is the most effective strategy for managing H7N9 virus infection. Human beings exposed to H7N9 virus may develop asymptomatic infection.     

山西省首例高致病性禽流感A/H5N1病毒感染患者的救治体会

目的 探索高致病性禽流感A/H5N1病毒感染(简称人禽流感)病例的临床特点及治疗体会.方法 对2009年1月17口山西省太原市第四人民医院收治的1例人禽流感患者的临床表现、实验室检查、影像学改变及治疗方法等进行总结.结果 患者鼻咽抽取物A/H5N1病毒经逆转录聚合酶链反应(RT-PCR)、实时PCR榆测A/H5N1病毒核酸阳性,确诊为人禽流感病例.患儿女,2岁11个月,体重11 kg.患儿平素体健,发病的有活禽屠宰市场环境暴露史.以发热、咳嗽、呼吸困难为主要症状;肺部病灶进展快,病程第8天肺部病变迅速进展,x线胸片呈"白肺",病情迅速进展为ARDS,静脉应用甲泼尼龙165 mg(15 mg·kg-1·d-1)及无创通气治疗,病程第9天病情有所好转,肺部病灶明显吸收;病程第11天开始给予奥司他韦及100 ml高滴度A/H5N1病毒疫苗免疫血浆,后患者病情日见好转,氧合指数及各种酶学指标恢复正常,肺内病灶明显吸收;病程第28大患者好转出院.结论 人禽流感发现晚、病情重、进展快,临床主要表现为严重的ARDS;有效的氧疗及呼吸支持是治疗的基础;糖皮质激素对肺部病灶的吸收有一定疗效,使用剂量有待进一步探讨;A/H5N1病毒疫苗免疫血浆治疗可能对改善患者的预后有一定帮助.     

Infection of immunocompromised patients by avian H9N2 influenza A virus

Avian influenza A (H9N2) virus is transmitted sporadically from avian species to human causing mild diseases in immunocompetent person. We report two cases of human infection in immunocompromised patients in Hong Kong between 2008 and 2009. One patient had uneventful recovery with viral shedding at day 10 after symptom onset despite her underlying acute lymphoblastic leukaemia. The other patient with post-bone marrow transplant chronic graft-versus-host disease and bronhioltis obliterans went into respiratory failure. Genetic analysis revealed that these cases were caused by different genetic variants which are circulating in poultry in this region. Review of literature identified another 9 human cases reported in Southern China since 1988. It is possible that human infection with H9N2 is more common than what has been recognized. Continuous surveillance of H9N2 influenza virus infection in human is warranted.     

ARDS associated with pneumonia caused by avian influenza A H7N9 virus treated with extracorporeal membrane oxygenation

This is a sporadic H7N9 avian influenza case that was the first severe imported case in Beijing and the first case of Hebei province in China. A 61‐year‐old female who had rapidly progressive pneumonia with respiratory distress and bilateral exduation and consolidation changes on chest X‐ray and computerized tomography (CT) scan that did not respond to ordinary antibiotics was diagnosed with influenza A (H7N9) infection in our hospital on July 19, 2013. Intravenous peramivir, veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) and continuous veno‐venous hemofiltration were given on the same day of lab diagnosis because of severe acute respiratory distress syndrome and acute renal failure. With antimicrobial therapy and other supportive treatment, clinical symptoms and oxygenation of the patient improved gradually. VV‐ECMO was successfully removed on the 13th day. The testing for influenza A (H7N9) turned negative on day 16 since the antivirus therapy. Twenty‐three days after hospitalization, blood stream infection with multidrug‐resistant Acinetobacter Baumannii occurred, which lead to septic shock and death. Whether or not the influenza season in north China, the influenza screening should be carried out as a conventional test for the patients who are suspected of viral pneumonia. For the patients who need mechanical ventilation and ECMO support, the lung protective strategy under the guidance of transpulmonary pressure may be helpful for recovering the lung.     

Specificity,kinetics and longevity of antibody responses to avian influenza A(H7N9) virus infection in humans

ObjectivesThe long-term dynamics of antibody responses in patients with influenza A(H7N9) virus infection are not well understood.MethodsWe conducted a longitudinal serological follow-up study in patients who were hospitalized with A(H7N9) virus infection, during 2013–2018. A(H7N9) virus-specific antibody responses were assessed by hemagglutination inhibition (HAI) and neutralization (NT) assays. A random intercept model was used to fit a curve to HAI antibody responses over time. HAI antibody responses were compared by clinical severity.ResultsOf 67 patients with A(H7N9) virus infection, HAI antibody titers reached 40 on average 11 days after illness onset and peaked at a titer of 290 after three months, and average titers of ≥80 and ≥40 were present until 11 months and 22 months respectively. HAI antibody responses were significantly higher in patients who experienced severe disease, including respiratory failure and acute respiratory distress syndrome, compared with patients who experienced less severe illness.ConclusionsPatients with A(H7N9) virus infection who survived severe disease mounted higher antibody responses that persisted for longer periods compared with those that experienced moderate disease. Studies of convalescent plasma treatment for A(H7N9) patients should consider collection of donor plasma from survivors of severe disease between 1 and 11 months after illness onset.     

重症甲型H1N1流行性感冒肺炎高分辨率计算机X线断层扫描表现的动态变化

目的 探讨重症甲型H1N1流行性感冒(流感)肺炎高分辨率计算机X线断层扫描(HRCT)表现及动态变化.方法 回顾性分析36例临床确诊的重症甲型H1N1流感肺炎1个月内100次HRCT资料,分析其肺部病变出现、进展及吸收时间和影像学特点.结果 发病初期行HRCT检查(3d内)6例,小片磨玻璃密度影3例,小片实变影3例.病变进展期(发病3d后)36例患者均表现为双肺多发弥漫分布的磨玻璃密度影伴或不伴实变,其中主要呈弥漫磨玻璃密度影9例,占25.0％；弥漫磨玻璃密度影伴实变影20例,占55.6％;主要呈肺实变影7例,占19.4％；合并胸膜病变10例,占27.8％.在发病(8.0±2.6)d内病变进展最为明显,发病(16.0±4.8)d后为吸收期,36例病变均明显吸收,23例出现肺间质增生,占63.9％.病灶的动态变化分三型,包括先进展后吸收型、进展和吸收并存后吸收型和逐渐吸收型,以先进展后吸收型为主,占41.7％.结论 HRCT可准确显示重症甲型H1N1流感肺炎的病变形态和范围,监测其动态变化.     

Influenza-associated bacterial pathogens in patients with 2009 influenza A (H1N1) infection: impact of community-associated methicillin-resistant Staphylococcus aureus in Queensland, Australia

Background: Secondary bacterial pneumonia due to community onset methicillin‐resistant Staphylococcus aureus (MRSA) has become a highly publicised cause of influenza‐associated death. There is a risk that case reports of fatal outcomes with post‐influenza MRSA pneumonia may unduly influence antibiotic prescribing. Aims: The aim of this study was to demonstrate the incidence of community‐onset MRSA pneumonia in 2009 H1N1 influenza patients. Methods: The microbiology records of patients positive for influenza A (H1N1) in 2009 were reviewed for positive blood or respiratory tract cultures and urinary pneumococcal antigen results within a Queensland database. Patients with such positive results within 48 h of hospital admission and a positive H1N1 influenza result in the prior 6 weeks were included. Results: In 2009, 4491 laboratory‐confirmed pandemic influenza A (H1N1) infections were detected. Fifty patients (1.1% of the H1N1 cohort) who were hospitalised with H1N1 and who had a bacterial respiratory tract pathogen were identified. Streptococcus pneumoniae (16 patients; 32%), Staphylococcus aureus (13 patients; 26%) and Haemophilus influenzae (9 patients; 18%) were the most commonly cultured organisms. Of the cohort of 4491 patients, MRSA was detected in only two patients, both of whom were admitted to intensive care units and survived after prolonged admissions. Conclusions: Influenza‐associated community‐onset MRSA pneumonia was infrequently identified in the 2009 H1N1 season in Queensland, despite community‐onset MRSA skin and soft tissue infections being very common. Although post‐influenza MRSA pneumonia is of great concern, its influence on empiric‐prescribing guidelines should take into account its incidence relative to other secondary bacterial pathogens.     

Management of the 2009 A/H1N1 influenza pandemic in patients with hematologic diseases: a prospective experience at an Italian center

Data derived from epidemiologic surveillance adopted at our center in hematologic and stem cell transplant patients during the 2009 influenza A (H1N1)v pandemic are reported. Of the 52 patients with influenza-like disease we observed, 37 underwent a real-time PCR evaluation and 21 had a confirmed diagnosis. Of the RT-PCR-confirmed cases, 23.8% were children (age <18 years) and 9.5% were >65 years; 47.6% presented with a pulmonary infiltrate and 33.3% with respiratory failure. Pulmonary involvement was observed more frequently in patients with comorbidities. All patients received a course of oseltamivir therapy starting an average of 1 day (range <1-2) after the onset of symptoms. No patient was transferred to the intensive care unit. The viral disease had a generally favorable outcome despite the high frequency of pulmonary involvement. A prompt clinical evaluation with an early antiviral and supportive therapy may have played a beneficial role in the outcome.     

甲型H1N1流行性感冒56例流行病学和临床学分析

目的 了解学校甲型H1N1流行性感冒(流感)暴发的流行病学和临床特征.方法 将56例确诊患者的流行病学调查和临床资料录入EPIDATA数据库,采用STATA软件分析其流行病学和临床学特点,采用RT-PCR法进行甲型H1N1流感病毒核酸检测.率的比较采用χ2检验,多个样本均数的比较采用单因素方差分析.结果 50例患者为同一小学学生,5例为密切接触者,发病高峰为2009年6月18日和19日.患者从发病至就诊、发病至人院、病程及住院时间的中位数分别为0、2、6和7 d.主要临床表现为发热56例、咳嗽54例、咳痰31例、扁桃体肿大25例和咽痛18例.合并症的发生率为10.7%(6例),主要为急性支气管炎.患者在发病后7 d之内、发病8～10 d及10 d以上咽拭子甲型H1N1流感病毒核酸阳性率分别为74.39%、5.13%和0,差异有统计学意义(χ2=95.0412,P＜0.01).单用奥司他韦治疗,奥司他韦联合中药治疗及单用中药治疗患者的病程分别为8.88、9.31和10 d,差异无统计学意义(F=0.37,P=0.6927).17例有可疑接触史患者的平均潜伏期为1 d.结论 甲型H1N1流感病情温和,其流行病学和临床表现与普通季节性流感类似.建议将甲型H1N1流感传染期判断标准调整为患者自出现症状前1 d至发病后10 d.     

A broadly neutralizing human monoclonal antibody is effective against H7N9

Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains.Influenza, a zoonotic viral disease, is responsible for substantial human morbidity and mortality yearly, with periodic elevations due to emergence of novel viral strains, either through mutation or genetic reassortment in a variety of animal reservoirs, including pigs, birds, and seals. Antigenic naivety within the population, coupled with the advent of a virus strain that can effectively transmit via respiratory droplets, can lead to epidemic or pandemic outbreaks. In addition, viruses with increased virulence, such as H5N1 and H7N9, are associated with enhanced morbidity and case fatality, estimated at 30–60% despite the availability of current antiviral therapy.Patients hospitalized with H7N9 infection typically manifest a high fever and cough, hypoxemia, and opacities and/or consolidations on chest radiology, with associated findings including shock, acute kidney injury, and the development of acute respiratory distress syndrome (ARDS). The high mortality associated with H7N9 infection and development of ARDS is similar to what has been reported for H5N1. An associated cytokine storm has been described in both of these patient groups, with proinflammatory cytokines/chemokines documented in plasma and pulmonary lavage samples (1–3). The increased cytokine responses have recently been correlated with increased severity and mortality observed in patients (2–4). Elevated levels of interleukin (IL)-10, IL-6, IL-8, and macrophage inflammatory protein-1β (MIP-1β) in plasma were found to be predictive of a less favorable or fatal outcome. Furthermore, IL-1β, interferon (IFN)-γ, MIP-1α, and MIP-1β were all significantly elevated in the bronchial lavage samples at a 100- to 1,000-fold increase compared with plasma concentrations, and tumor necrosis factor (TNF)-α was only detected in the lavage samples. Mouse models for H5N1 and H7N9 infection mimic this cytokine response and the lung pathology of ARDS (2). We therefore sought to examine the role of a broadly neutralizing antibody, VIS410, in mitigating this “cytokine storm” in infected mice and lowering lung viral concentrations in this sublethal H7N9 model. Since this agent would likely be used in combination with a neuraminidase inhibitor, we investigated the effect of VIS410 compared to, and in combination with, oseltamivir.Additionally, the DBA mouse has been found to have much higher susceptibility to influenza infection than either C56BL/6 or BALB/c mice (5, 6). A variety of influenza viruses, including H5N1 and influenza B viruses, have been shown to be lethal to DBA mice without prior adaptation (7, 8). We reasoned that to complement the cytokine measurements in BALB/c mice, a lethal DBA mouse model could be used to examine the effect of VIS410 on mortality, thereby providing an appropriate model of the significant morbidity and mortality associated with H7N9 infection in humans. We therefore additionally evaluated VIS410 in a lethal model of H7N9 disease.     

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。     

Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection

A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced “cytokine storm” at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.In March 2013, an influenza outbreak caused by a unique avian-origin H7N9 influenza A virus emerged in the Yangtze River Delta on China’s eastern seaboard (1–5). Along with other groups, we characterized this human pathogen and established that the 2013-H7N9 HA is distinct from that of any previously identified H7 influenza A virus (2). To date, the H7N9 virus has caused 134 confirmed cases in nine provinces. Most patients were hospitalized with severe symptoms, particularly pneumonia (97.3%) and acute respiratory distress syndrome (ARDS; 71.2%), leading to high rates (75%) of intensive care unit admissions and mechanical ventilation (66%), and >30% mortality (6, 7).Our understanding of the relative contributions of viral and host factors to severe influenza, including these H7N9 cases, is far from complete. Multivariate analysis has shown that coexisting medical conditions are the only identified independent risk factors to date for moderate to severe H7N9-associated ARDS (6). It also seems that elevated concentrations of inflammatory mediators in plasma (hypercytokinemia) are indicative of poor disease outcomes in patients with H7N9 infections (5, 8). For example, Chen et al. (5) observed substantially higher plasma cytokine levels in a fatal case of H7N9 virus influenza compared with those in a patient who survived. Zhou et al. (8) then found that the circulating cytokines in H7N9-infected patients could reach concentrations comparable to those characteristic of H5N1 pneumonia. Even so, although suggestive that hypercytokinemia may predict, or reflect, severe disease following H7N9 infection, such observations provide little insight into mechanisms. Furthermore, the question of whether plasma cytokine levels are a direct reflection of what is happening in the infected lung has not been explored previously for any human influenza pneumonia.As with many influenza cases, it is far from clear why some (but not all) H7N9-infected individuals develop very severe symptoms. What is known is that the IFN-induced transmembrane protein-3 (IFITM3) can restrict influenza virus replication by preventing endocytosed virus particles from entering the host cytoplasm (9, 10). As a consequence, relative to the WT IFITM3^+/+ controls, genetically disrupted IFITM3^−/− mice are extremely vulnerable to infection with even low pathogenic influenza viruses (11). In humans, homozygosity for the SNP rs12252-C (C/C in contrast to the WT T/T or F1 T/C) is associated with truncation of the N-terminal 21 amino acids of the IFITM3 protein, which, in turn, affects IFITM3 localization (12). This association of the C/C phenotype with severe disease emerged from the analysis of hospitalized patients in China (13) and Europe (11) during the 2009 H1N1 pandemic. However, because the pandemic H1N1 (pH1N1) virus generally caused a mild infection, there was no a priori reason to think that C/C individuals might be even more compromised by the highly pathogenic H7N9 strain.What we show here is that the IFITM3 rs12252-C/C genotype (vs. C/T or T/T) tends to be predictive of severe H7N9-induced disease. In addition, early and persisting high cytokine/chemokine levels in plasma [especially IL-6, IL-8, and macrophage inflammatory protein (MIP)-1β] are associated with poor clinical outcomes, although whether this is causative or simply a consequence of greater and more prolonged virus replication is not altogether clear. Also apparent from the analysis of bronchoalveolar lavage (BAL) samples is that at least some of those high cytokine/chemokine concentrations in blood are likely a “spillover” from local production in the infected lung. This study thus suggests further approaches that might be used to probe mechanisms, while providing useful predictive measures of outcome that should be of help in managing severe influenza.     

北京市2009年甲型H1N1流行性感冒危重症与死亡病例流行病学特征及其影响因素分析

目的 了解北京市2009年甲型H1N1流行性感冒(流感)危重症与死亡病例的流行病学特征,探讨影响甲型H1N1流感病情严重程度的主要因素.方法 利用北京市2009年甲型H1N1流感病例个案信息进行描述性分析和多因素Logistic回归分析.结果 北京市2009年甲型H1N1流感感染率为66.1/10万,25～60岁组人群感染率最高,为86.8/10万.0～5岁组和60岁以上年龄组危重症感染率(12.5/10万,3.9/10万)、死亡率(0.9/10万,0.7/10万)和病死率(2.4%,3.3%)较高.549例危重症病例中学龄前儿童110例,比例最高,占20.0%,69例死亡病例中离、退休人员17例,比例最高,占24.6%.超过70.0%的危重症和死亡病例均在发病后2 d内到医院就诊.危重症病例和死亡病例中,均以有心血管疾病的病例比例最高,其次为慢性肺部疾病.多因素Logistic回归分析显示,甲型H1N1流感病例中,60岁以上、慢性肺部疾病及心血管疾病可能导致其病情较重,OR值分别为3.586(95%CI 1.586～8.117)、2.126(95%CI 1.178～3.835)和1.954(95%CI 1.126～3.391).结论 60岁以上、伴心血管疾病及慢性肺部疾病等因素可能加重甲型H1N1流感病例病情.     

北京市2009年甲型H1N1流行性感冒危重症与死亡病例流行病学特征及其影响因素分析

目的 了解北京市2009年甲型H1N1流行性感冒(流感)危重症与死亡病例的流行病学特征,探讨影响甲型H1N1流感病情严重程度的主要因素.方法 利用北京市2009年甲型H1N1流感病例个案信息进行描述性分析和多因素Logistic回归分析.结果 北京市2009年甲型H1N1流感感染率为66.1/10万,25～60岁组人群感染率最高,为86.8/10万.0～5岁组和60岁以上年龄组危重症感染率(12.5/10万,3.9/10万)、死亡率(0.9/10万,0.7/10万)和病死率(2.4%,3.3%)较高.549例危重症病例中学龄前儿童110例,比例最高,占20.0%,69例死亡病例中离、退休人员17例,比例最高,占24.6%.超过70.0%的危重症和死亡病例均在发病后2 d内到医院就诊.危重症病例和死亡病例中,均以有心血管疾病的病例比例最高,其次为慢性肺部疾病.多因素Logistic回归分析显示,甲型H1N1流感病例中,60岁以上、慢性肺部疾病及心血管疾病可能导致其病情较重,OR值分别为3.586(95%CI 1.586～8.117)、2.126(95%CI 1.178～3.835)和1.954(95%CI 1.126～3.391).结论 60岁以上、伴心血管疾病及慢性肺部疾病等因素可能加重甲型H1N1流感病例病情.     

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。     

Clinical study of invasive pulmonary aspergillosis following influenza A H1N1

This study to analyze the clinical characteristics of patients with invasive pulmonary aspergillosis (IPA) following influenza A (H1N1) infection.We retrospectively analyzed 10 cases with IPA following H1N1 infection. The clinical manifestations, laboratory examination results, chest computed tomography, and treatments were analyzed.Clinical manifestations: all 10 cases had typical flu-like symptoms at the onset of the disease, among which 7 patients developed dyspnea in the late stage, and 8 patients had hemoptysis. Laboratory examination: the absolute and percentage of peripheral blood lymphocytes in all 10 patients were declined, among which 5 cases were with decreased CD3⁺ CD4⁺ T cells/lymphocytes; 9 cases with increased bronchoalveolar lavage fluid galactomannan; 6 cases with increased serum galactomannan; 1 case with bronchoalveolar lavage fluid cultured aspergillus fumigatus; and 2 cases with aspergillus by second-generation sequencing. Chest computed tomography: all patients showed multiple diffused ground-glass opacities at the beginning, along with linear or reticular interstitial changes. Two cases had multiple subarachnoid nodules with halo signs, 3 cases had consolidation in multiple segments of both lungs, 2 cases had cavities, and 4 cases were with pleural effusion. Treatment: 10 patients were treated with antiviral and anti-Aspergillus drugs after admission. Four patients received respiratory support. All 10 cases were cured and discharged.Early diagnosis of IPA in influenza A (H1N1) patients is the key to successful treatment.     

Acute exacerbation of idiopathic pulmonary fibrosis after pandemic influenza A (H1N1) vaccination

We report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) after pandemic influenza (H1N1) vaccination. A 57-year-old man, who had been diagnosed with IPF in September 2008, was admitted to our hospital in December 2009 because of aggravation of dyspnea and fever two days after H1N1 vaccination. Chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities. We diagnosed AE-IPF. Corticosteroid and cyclophosphamide were effective. Although the efficacy of influenza vaccination in patients with chronic lung diseases is well established, physicians should keep in mind that influenza vaccination has the potential to cause AE-IPF.