Viral aetiology of influenza-like illness in Belgium during the influenza A(H1N1)2009 pandemic

The purpose of this investigation was to determine the proportion of influenza-like illness (ILI) attributable to specific viruses during the influenza A(H1N1)2009 pandemic and to describe the demographic and clinical characteristics of ILI due to respiratory viruses in Belgium. Nasopharyngeal swabs were collected from ILI patients by general practitioners (GPs) and paediatricians (PediSurv) and analysed for viruses. Of 139 samples collected from children <5 years of age by PediSurv, 86 were positive, including 28 influenza (20%), 27 respiratory syncytial virus (RSV) (19%), 21 rhinovirus (17%), 12 human metapneumovirus (hMPV) (9%) and ten parainfluenza virus (PIV) (7%). Of 810 samples received from GPs, 426 were influenza (53%). Of 312 influenza-negative samples, 41 were rhinovirus (13%), 13 RSV (4%), 11 PIV (4%) and three hMPV (1%). Influenza mostly affected the 6-15 years old age group. Other respiratory viruses were commonly detected in the youngest patients. Similar clinical symptoms were associated with different respiratory viruses. Influenza A(H1N1)2009 was the most detected virus in ILI patients during the 2009-2010 winter, suggesting a good correlation between ILI case definition and influenza diagnosis. However, in children under 5 years of age, other respiratory viruses such as RSV were frequently diagnosed. Furthermore, our findings do not suggest that the early occurrence of the influenza A(H1N1)2009 epidemic impacted the RSV epidemic in Belgium.     

The viral etiology of an influenza-like illness during the 2009 pandemic

Many viruses are known to cause influenza-like illness (ILI); however, in nearly 50% of patients, the etiologic agent remains unknown. The distribution of viruses in patients with ILI was investigated during the 2009 A/H1N1 influenza pandemic (A/H1N1p). From June 2009 to January 2010, 660 patients with suspected influenza were questioned and examined, and nasal swabs were collected. All patient samples were tested for influenza virus, and 286 negative nasal swabs were tested further for 18 other respiratory viruses using real-time RT-PCR. Two waves of ILI were observed in the epidemic curve (weeks 35-42 and 42-49). At least eight viruses co-circulated during this period: human rhinovirus (HRV) (58), parainfluenza 1-4 viruses (PIV) (9), human Coronavirus (hCoV) OC43 (9), enterovirus (5), adenovirus (AdV) (4), and human metapneumovirus (hMPV) (2); however, 204 samples remained negative for all viruses tested. ILI symptoms, according to the Centers for Disease Control and Prevention criteria for ILI definition, were reported in 75% of cases. These patients had positive swabs for A/H1N1p, HRV, hCoV-OC43, PIV, AdV, and hMPV without significant difference with non-ILI patients. This study found that many respiratory viruses circulated during this period and that the A/H1N1p did not impact on the kinetics of other respiratory viruses. The proportion of non-documented cases remains high. ILI could not distinguish A/H1N1p infection from that due to other respiratory viruses. However, in multivariate anlaysis, cough, chills, hyperemia, and dyspnea were associated significantly with influenza virus versus other respiratory viruses.     

流感病毒快速检测方法在儿童流感样病例病原诊断中的应用

目的对一种流感病毒快速检测方法在儿童流感样病例病原诊断中的应用效果进行评估。方法 2010年12月至2011年4月采集流感样病例患儿咽拭子标本350例,使用甲型及乙型流感病毒抗原检测试剂盒（QuickNaviTM-Flu,胶乳免疫层析法）进行抗原检测,并与病毒分离法进行比较。对于抗原检测和病毒分离法结果不相符的标本采用RT-PCR验证。结果 QuickNaviTM-Flu抗原快速检测流感病毒的结果与病毒分离法的一致性好,其检测甲型流感病毒的敏感度为89.9%,特异度为94.4%。经RT-PCR验证,14例抗原检测与病毒分离法结果不相符样本中13例结果为阳性（与抗原检测一致）,使得该抗原检测方法的敏感度和特异度升至91.0%和99.6%。抗原检测乙型流感病毒经RT-PCR验证前后的结果一致,敏感度和特异度分别为87.5%和100%。该方法检测出的阳性标本中包括了甲3型、乙型（Victoria和Yamagata系）流感病毒和新发的2009甲型H1N1,并与常见的呼吸道病毒之间无交叉反应。结论 QuickNaviTM-Flu作为流感病毒抗原检测的试剂盒,可一次同时检测出甲型和乙型流感病毒,耗时短,操作简便,具有良好的敏感度和特异度,适用于流感样病例病原的快速诊断。     

Virological diagnosis of respiratory virus infection in patients attending an emergency department during the influenza season

To investigate the burden of influenza-like illness (ILI), patients attending an emergency department during the influenza season were tested for several common respiratory viruses, using PCR-based methods. Influenza A viruses were detected in 25 of 103 recruited patients (24%), rhinoviruses in 15%, and respiratory syncytial virus in only one. The data suggest that triage criteria based on ILI case definitions would not contain the spread of the influenza virus during pandemic alerts and could lead to unnecessary isolation of patients with other infections. Application of broader triage criteria followed by timely molecular diagnosis could be effective in preventing new respiratory agent transmission.     

The pathogenesis of influenza virus infections: the contributions of virus and host factors

Influenza viruses cause acute respiratory inflammation in humans and symptoms such as high fever, body aches, and fatigue. Usually these symptoms improve after several days; however, the 2009 pandemic H1N1 influenza virus [influenza A(H1N1) 2009] is more pathogenic than seasonal influenza viruses and the pathogenicity of highly pathogenic H5N1 viruses is still higher. The 1918 influenza pandemic virus caused severe pneumonia, resulting in an estimated 50 million deaths worldwide. Several virulence factors have been identified in these virus strains, but host factors are also responsible for the pathogenesis of infections caused by virulent viruses. Here, we review the contributions of both virus and host factors to the pathogenesis of these viral infections.     

Imbalanced anti-H1N1 immunoglobulin subclasses and dysregulated cytokines in hospitalized pregnant women with 2009 H1N1 influenza and pneumonia in Shenyang, China

Influenza virus can cause an acute respiratory illness of variable intensity. In our study, we describe the clinical and immunological characteristics of pregnant and nonpregnant women who were hospitalized with 2009 H1N1 influenza and pneumonia in Shenyang, China, from November 2009 to January 2010. Forty-two female patient infected with H1N1 were divided into groups according to pregnancy. Clinical data were collected. Cytokines and anti-H1N1 IgG subclasses were detected. We observed significant lymphopenia, hypoproteinemia, reduced CD4(+)T cell counts and CD4(+)/CD8(+) ratios, reduced anti-H1N1 IgG subclasses IgG2 and IgG3 constituent ratios, elevated C reactive protein and interleukin-10 levels with regard to nonpregnant H1N1 group. Compared with the healthy pregnant group, the pregnant H1N1 group showed elevated aspartate aminotransferase and glutamic alanine aminotransferase levels, an increased interferon-gamma and interleukin-10 levels and reduced anti-H1N1 IgG subclasses IgG2, IgG3 and IgG4 combination ratios. There was a statistically significant association between imbalanced anti-H1N1 immunoglobulin subclasses and dysregulated cytokines in pregnant women with H1N1 infection.     

广东省深圳市流感流行特征分析

目的 掌握深圳市流感流行规律,了解甲流大流行以后流感的流行趋势.方法 对深圳市流感样病例监测数据、病原学检测结果和暴发疫情资料进行分析.结果 深圳市的流感样病例百分比(ILI％)为4.67％,呈逐年下降趋势,ILI年龄构成以0-4岁为主(占54.2％).流感病毒分离平均阳性率为10.6％,按月分析流感病毒分离阳性率与ILI％变化趋势呈正相关(r=0.447,P =0.001).全市报告了482起ILI暴发疫情,以乙型流感为主(占63.9％).2010年深圳市季节性流感出现了春季和夏季流行高峰,分别以乙型Victoria系和甲型H1N1亚型为优势株;2011年为冬春季和秋季高峰,以甲型H1N1和季节性H3亚型为优势株;2012年出现了冬春季和夏季高峰,以乙型(Victoria系和Yamagata系)和季节性H3亚型为优势株;2013年出现了春、秋、冬季三个流行高峰,分别以甲型H1N1、季节性H3和乙型Yamagata系为优势株.结论 深圳市季节性流感每年均出现2-3个流行高峰,分别在冬春季和夏秋季,每年流行高峰出现的时间不同,每年流行的型别不同.     

Acute respiratory infection and influenza-like illness viral etiologies in Brazilian adults

Influenza-like illness (ILI) definitions have been used worldwide for influenza surveillance. These different case definitions can vary with regard to sensitivity and predictive values for laboratory confirmed influenza. The literature has indicated the inclusion of other viruses may be the cause of these variable results. The objective of the study was to evaluate ILI national sentinel criteria and viral etiologies in adults diagnosed with acute respiratory infection (ARI) and/or ILI from 2001 to 2003 in Sao Paulo, Brazil. Clinical and laboratory evaluations were observed from 420 adults and collected on a daily basis from outpatient care units at University Hospital. The ILI definition included: fever plus at least one respiratory symptom (cough and/or sore throat) and one constitutional symptom (headache, malaise, myalgia, sweat or chills, or fatigue). DFA and RT-PCR for influenza, parainfluenza, respiratory syncytial virus, adenovirus, enterovirus, coronavirus, rhinovirus, and metapneumovirus were performed on nasal washes and 61.8% resulted positive. The respiratory viruses detected most often were influenza and rhinovirus. ILI was reported for 240/420 patients (57.1%), with influenza and rhinovirus etiologies accounting for 30.9% and 19.6%, respectively. Rhinovirus peak activity was concurrent with the influenza season. These findings highlight the implications of other viruses in ILI etiology and suggest that during the influenza season, this clinical overlap must be considered in the diagnosis and clinical management of patients.     

Clinical evaluation of rapid point-of-care testing for detection of novel influenza A (H1N1) virus in a population-based study in Spain

Limited information exists on the performance of antigen-based rapid influenza diagnostic tests (RIDT) in diagnosing the novel influenza A pandemic (H1N1) 2009 virus. Large studies evaluating these tests in consecutive patients with a broad clinical spectrum of influenza-like illnesses are needed. We assessed the ClearView® Exact Influenza A & B test (Inverness Medical, Cologne, Germany) in comparison with real-time (r)RT-PCR for detection of the novel influenza A (H1N1) in a population-based prospective study of 1016 adults and children with suspected influenza in Spain. Three hundred and one (29.6%) patients had a positive sample with the rRT-PCR assay for influenza A and B viruses, with 297 (29.2%) confirmed cases of the novel influenza A pandemic (H1N1) 2009 virus. Fifty (16.8%) patients with confirmed A (H1N1) 2009 virus were admitted to hospital, with six of them to the intensive care unit. In comparison with rRT-PCR, the ClearView® Exact Influenza A & B test had a sensitivity of 19% (95% CI 14–23), a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 75% (95% CI 72–78). The sensitivity of the test remained low across all demographic and clinical strata. Although a positive RIDT performed well in predicting PCR-confirmed infection with pandemic H1N1 virus, the sensitivity was very low and a negative test result was a poor predictor of the absence of infection.     

2009-2010年山西省流感／甲型H1N1流感的病原学监测分析

目的分析掌握山西省2009--2010年流感／甲型H1N1流感的流行特征,为预测和防控流感／甲型H1N1流感流行提供科学依据。方法对哨点医院和集体发热疫情进行监测采样,采用病毒核酸检测法和细胞培养法分离鉴定流感／甲型H1N1流感病毒,并对2009年5月至2010年4月山西省录入“中国流感监测信息系统”的流感样病例监测报告数据及其样本病原学监测数据进行统计分析。结果山西省全年均有流感病毒活动,2009年流行优势毒株为甲型H1N1流感病毒,流行最高峰在11月（阳性率为58．1％,甲型H1N1占88．1％）,主要导致59岁以下人群发病,其中5-24岁年龄组阳性率较高,进入2010年后乙型（Victoria系）流感病毒的活动有所增加,成为流行株。结论流感样病例监测和病原学监测,可以及时反映流感活动状况,对于掌握该省流感／甲型H1N1流感流行规律有着重要意义。     

Rhinovirus frequently detected in elderly adults attending an emergency department

The general aim was to investigate the burden of respiratory virus illness in a hospital emergency department, during two different epidemic seasons. Consecutive patients attending an emergency department during two study periods (February/March 2009 and 2010) were enrolled using broad inclusion criteria (fever/preceding fever and one of a set of ICD-9 codes suggestive of respiratory illness); nasopharyngeal washes were tested for the most common respiratory viruses using PCR-based methods. Influenza A virus was detected in 24% of samples collected in February/March 2009, whereas no samples tested positive for influenza during February/March 2010 (pandemic H1N1 Influenza A having circulated earlier in October-December 2009). Rhinovirus (HRV) was detected in 16% and 8% of patients recruited over the two study periods, respectively. Other respiratory viruses were detected rarely. Patient data were then analyzed with specific PCR results, comparing the HRV-positive group with virus-positive and no virus-detected groups. Individuals over 65 years old with HRV presented with signs, symptoms and underlying conditions and were admitted to hospital as often as the other enrolled patients, mainly for dyspnoea and chronic obstructive pulmonary disease acute exacerbation. Conversely, younger individuals with HRV, although presenting with respiratory signs and symptoms, were generally diagnosed with non-respiratory conditions. HRV was detected frequently in elderly patients attending the emergency department for respiratory distress without distinguishing clinical features. Molecular diagnosis of lower respiratory tract infections and surveillance of infectious diseases should include tests for HRV, as this virus is associated frequently with hospitalization of the elderly.     

254例急性呼吸道感染病例病原学调查分析

目的 分析急性呼吸道感染病例的病毒病原构成,掌握主要病原体活动水平及变化规律,了解丰台地区急性呼吸道感染病原谱.方法 以2010-2012年成人急性呼吸道感染病例为研究对象,收集病例基础信息,采集鼻咽拭子标本,使用多重PCR及RT-PCR对流感病毒、呼吸道合胞病毒、腺病毒、副流感病毒、偏肺病毒、冠状病毒、鼻病毒、博卡病毒和肺炎支原体等9种病原进行检测,数据分析使用SPSS 17.0软件.结果 254例标本中154例检测阳性,阳性率为60.63％,男女阳性检出率无统计学差异.冬春季致病病原体以流感病毒、副流感病毒及支原体为主,夏季仅检出副流感和支原体.流感样病例的主要病原体为流感病毒及副流感病毒;肺炎病例致病病原体主要为肺炎支原体.2010-2011年流感流行季甲型流感病毒为优势病原,2011-2012年流感流行季乙型流感病毒为优势病原.结论 2010-2012年间,北京丰台地区引起成人急性呼吸道感染的主要病原为流感病毒、支原体和副流感病毒.不同季节的优势病原不同.     

No apoptotic deaths and different levels of inductions of inflammatory cytokines in alveolar macrophages infected with influenza viruses

Influenza viruses are reported to infect mainly the respiratory tract epithelium of hosts. Our studies in a pig model show that influenza A viruses infect alveolar macrophages that constitutively reside in the respiratory tract, without causing apoptosis. Tumor necrosis factor alpha was the inflammatory cytokine most highly induced in these macrophages. In vivo, alveolar macrophages infected with human H3N2 influenza virus showed greater expression of tumor necrosis factor alpha than did alveolar macrophages infected with human H1N1 influenza virus. Induction of specific inflammatory cytokine such as TNF-alpha is a polygenic trait that involves the HA and NA genes. Markedly elevated expression of tumor necrosis factor alpha may be responsible for the high mortality rate caused by H3N2 influenza virus infection in elderly patients.