Grippe A (H1N1) et SDRA : caractéristiques des patients admis en réanimation et prise en charge. Revue de la littérature

Novel influenza A (H1N1) at the origin of the 2009 pandemic flu developed mainly in subjects of less than 65 years contrary to the seasonal influenza, which usually developed in elderly patients of more than 65 years. Elderly subjects are partly protected by old meetings with close stocks. Influenza A(H1N1) can arise in serious forms within 60 to 80% of cases a fulminant acute respiratory distress syndrome (ARDS) “malignant and fulminant influenza” in subjects without any comorbidity, which makes the gravity and the fear of this influenza. The fact that this influenza A (H1N1) can develop in healthy young patients and evolve in few hours to a severe ARDS with a refractory hypoxemia gave to the foreground the possible interest of the recourse to extracorporeal oxygenation (ECMO) in some selected severe ARDS (5–10%). The first publications of patients admitted in intensive care unit (ICU) for severe influenza A (H1N1) often associated to an ARDS reported a mortality rate from 15 to 40%. This mortality variability may be explained in part by different studied populations, ARDS characteristics and human and material resources in the ICUs between the countries. Indeed, the highest mortality rates (30–40%) have been reported by in Mexico which were affected the first by pandemic flu and which were not prepared. A bacterial pneumonia was associated to H1N1 influenza in approximately 30% of the cases as at admission in ICU or following the days of the admission justifying an early antibiotherapy associated to the antiviral treatment by oseltamivir (Tamiflu^®). Obesity, pregnancy and respiratory diseases (asthma, COPD) seem to be associated to the development of a severe viral pneumonia due to influenza A (H1N1) often with ARDS. Older age, high APACHE II and SOFA scores and a delay of initiation of the antiviral treatment by oseltamivir are associated to higher morbidity and mortality. Other analyses of the results obtained from the first published papers included more patients and future studies would permitted to better define the role of therapeutics such as steroids and ECMO.     

Cover Image

Influenza A (H1N1) viruses are distributed worldwide and pose a threat to public health. Swine, as a natural host and mixing vessel of influenza A (H1N1) virus, play a critical role in the transmission of this virus to humans. Furthermore, swine influenza A (H1N1) viruses have provided all eight genes or some genes to the genomes of influenza strains that historically have caused human pandemics. Hence, persistent surveillance of influenza A (H1N1) virus in swine herds could contribute to the prevention and control of this virus. Here, we report a novel reassortant influenza A (H1N1) virus generated by reassortment between 2009 pandemic H1N1 viruses and swine viruses. We also found that this virus is prevalent in swine herds in Shandong Province, eastern China. Our findings suggest that surveillance of the emergence of the novel reassortant influenza A (H1N1) virus in swine is imperative.     

Co‐circulation and characterization of HPAI‐H5N1 and LPAI‐H9N2 recovered from a duck farm,Yogyakarta, Indonesia

In July 2016, an avian influenza outbreak in duck farms in Yogyakarta province was reported to Disease Investigation Center (DIC), Wates, Indonesia, with approximately 1,000 ducks died or culled. In this study, two avian influenza (AI) virus subtypes, A/duck/Bantul/04161291‐OR/2016 (H5N1) and A/duck/Bantul/04161291‐OP/2016 (H9N2) isolated from ducks in the same farm during an AI outbreak in Bantul district, Yogyakarta province, were sequenced and characterized. Our results showed that H5N1 virus was closely related to the highly pathogenic AI (HPAI) H5N1 of clade 2.3.2.1c, while the H9N2 virus was clustered with LPAI viruses from China, Vietnam and Indonesia H9N2 (CVI lineage). Genetic analysis revealed virulence characteristics for both in avian and in mammalian species. In summary, co‐circulation of HPAI‐H5N1 of clade 2.3.2.1c and LPAI‐H9N2 was identified in a duck farm during an AI outbreak in Yogyakarta province, Indonesia. Our findings raise a concern of the potential risk of the viruses, which could increase viral transmission and/or threat to human health. Routine surveillance of avian influenza viruses should be continuously conducted to understand the dynamic and diversity of the viruses for influenza prevention and control in Indonesia and SEA region.     

Phylogeography of H5N1 avian influenza virus in Indonesia

Highly pathogenic avian influenza (HPAI ) viruses of the H5N1 subtype are a major concern to human and animal health in Indonesia. This study aimed to characterize transmission dynamics of H5N1 over time using novel Bayesian phylogeography methods to identify factors which have influenced the spread of H5N1 in Indonesia. We used publicly available hemagglutinin sequence data sampled between 2003 and 2016 to model ancestral state reconstruction of HPAI H5N1 evolution. We found strong support for H5N1 transmission routes between provinces in Java Island and inter‐island transmissions, such as between Nusa Tenggara and Kalimantan Islands, not previously described. The spread is consistent with wild bird flyways and poultry trading routes. H5N1 migration was associated with the regions of high chicken densities and low human development indices. These results can be used to inform more targeted planning of H5N1 control and prevention activities in Indonesia.     

H1N1 influenza A presenting as bacterial tracheitis

Six cases of bacterial tracheitis (BT) occurring early in the 2009 flu season have been isolated in conjunction with the H1N1 strain of influenza A (H1N1). No previous H1N1 cases have presented as BT in the literature to date. We would like to discuss viral coinfection in BT patients and how this new strain may affect the rate and type of presentation encountered. The life-threatening potential of BT and the pandemic proportion of H1N1 highlight a possibly dangerous combination that should be recognized by the otolaryngology community. In hospitalized patients with presumed BT, consideration should be given to routine H1N1 testing and the addition of antiviral medication when indicated as this entity is further investigated.     

Risk Factors for Exposure to Influenza A Viruses,Including Subtype H5 Viruses,in Thai Free‐Grazing Ducks

Free‐grazing ducks (FGD) have been associated with highly pathogenic avian influenza (HPAI) H5N1 outbreaks and may be a viral reservoir. In July–August 2010, we assessed influenza exposure of Thai FGD and risk factors thereof. Serum from 6254 ducks was analysed with enzyme‐linked immunosorbent assay (ELISA) to detect antibodies to influenza A nucleoprotein (NP), and haemagglutinin H5 protein. Eighty‐five per cent (5305 ducks) were seropositive for influenza A. Of the NP‐seropositive sera tested with H5 assays (n = 1423), 553 (39%) were H5 ELISA positive and 57 (4%) suspect. Twelve per cent (74 of 610) of H5 ELISA‐positive/suspect ducks had H5 titres ≥ 1 : 20 by haemagglutination inhibition. Risk factors for influenza A seropositivity include older age, poultry contact, flock visitors and older purchase age. Study flocks had H5 virus exposure as recently as March 2010, but no HPAI H5N1 outbreaks have been identified in Thailand since 2008, highlighting a need for rigorous FGD surveillance.     

Avian Influenza H5N1 Surveillance and its Dynamics in Poultry in Live Bird Markets,Egypt

H5N1, a highly pathogenic avian influenza (H5N1 HPAI), is an endemic disease that is significant for public health in Egypt. Live bird markets (LBMs) are widespread in Egypt and play an important role in HPAI disease dynamics. The aim of the study was to evaluate the H5N1 HPAI prevalence in representative LBMs from 2009 to 2014, assess the effects of other variables and evaluate past outbreaks and human cases. It was found that ducks and geese are high‐risk species and that the prevalence of H5N1 HPAI was higher immediately after the political crises of 2011. The end of a calendar year (June to December) was a high‐risk period for positive samples, and the risk in urban LBMs was twice the risk in rural LBMs. Winter and political unrest was associated with higher H5N1 HPAI prevalence. Both human and poultry populations will continue to rise in Egypt, so continued poultry outbreaks are likely to be linked to more human cases. LBMs will continue to play a role in the dynamics of poultry disease in Egypt, and there is a need to reorganize markets in terms of biosecurity and traceability. It may also be beneficial to reduce inter‐governorate inter‐regional movements associated with poultry trade through promotion of regional trade or in the alternative provide sanitary features along the poultry market chain to reduce the speed of H5N1 HPAI infections. Policy formulation, design and enforcement must be pro‐poor, and consideration of the sociocultural and economic realities in Egypt is important. The LBMs provide ideal platforms to carry out sound surveillance plans and mitigate zoonotic risks of H5N1 HPAI to humans.     

2009年杭州市甲型H1N1流感监测现状分析

目的探讨2009年杭州市甲型H1N1流感的流行规律、临床表现和病原学特征。方法对2009年杭州市13家流感监测哨点医院的每日门诊流感样病例和甲型H1N1流感确诊病例的流行病学进行分析。采用RT—PCR方法对咽拭子中血凝素（HA）基因进行扩增和测序,并用DNASTAR软件进行序列分析。全文数据采用SPSS12．0软件进行统计分析,率的比较采用χ^2检验。结果流感样病例监测显示,第28周之前,疫情处于平稳状态,之后全市流感样病例逐渐增多。第35周时达到高峰,全市流感样病例就诊比例为7．47％（5442／72859）。之后疫情回落,但到第41周时又再次回升,至第46周出现第二次高峰,全市流感样病例就诊比例达到11．32％（11034／97436）。第38周以前,杭州市人群中主要流行株是季节性H1N1型,其次有少量的乙型和季节性流感H1N1型,到第44周,甲型H1N1流感成为唯一的优势流行株,主要易感人群是11～25岁的青少年,以学生居多。序列分析显示,2009年杭州市甲型H1N1流感病毒株与北美株、中国其他地区的毒株以及疫苗株同源性达到99％,关键位点高度保守,但与季节性流感病毒株同源性只有70％。结论2009年杭州市流感疫情发展迅速,人群中流行的优势毒株为甲型流感H1N1型,易感人群为青少年,目前未发现变异株及高致病株,但仍需进一步监测。     

A Meta‐Analysis of the Prevalence of Influenza A H5N1 and H7N9 Infection in Birds

Despite a much higher rate of human influenza A (H7N9) infection compared to influenza A (H5N1), and the assumption that birds are the source of human infection, detection rates of H7N9 in birds are lower than those of H5N1. This raises a question about the role of birds in the spread and transmission of H7N9 to humans. We conducted a meta‐analysis of overall prevalence of H5N1 and H7N9 in different bird populations (domestic poultry, wild birds) and different environments (live bird markets, commercial poultry farms, wild habitats). The electronic database, Scopus, was searched for published papers, and Google was searched for country surveillance reports. A random effect meta‐analysis model was used to produce pooled estimates of the prevalence of H5N1 and H7N9 for various subcategories. A random effects logistic regression model was used to compare prevalence rates between H5N1 and H7N9. Both viruses have low prevalence across all bird populations. Significant differences in prevalence rates were observed in domestic birds, farm settings, for pathogen and antibody testing, and during routine surveillance. Random effects logistic regression analyses show that among domestic birds, the prevalence of H5N1 is 47.48 (95% CI: 17.15–133.13, P < 0.001) times higher than H7N9. In routine surveillance (where surveillance was not conducted in response to human infections or bird outbreaks), the prevalence of H5N1 is still higher than H7N9 with an OR of 43.02 (95% CI: 16.60–111.53, P < 0.001). H7N9 in humans has occurred at a rate approximately four times higher than H5N1, and for both infections, birds are postulated to be the source. Much lower rates of H7N9 in birds compared to H5N1 raise doubts about birds as the sole source of high rates of human H7N9 infection. Other sources of transmission of H7N9 need to be considered and explored.     

Complete genome sequence of a novel influenza A H1N2 virus circulating in swine from Central Bajio region,Mexico

The aim of this study was to perform the complete genome sequence of a swine influenza A H1N2 virus strain isolated from a pig in Guanajuato, México (A/swine/Mexico/GtoDMZC01/2014) and to report its seroprevalence in 86 counties at the Central Bajio zone. To understand the evolutionary dynamics of the isolate, we undertook a phylogenetic analysis of the eight gene segments. These data revealed that the isolated virus is a reassortant H1N2 subtype, as its genes are derived from human (HA, NP, PA) and swine (M, NA, PB1, PB2 and NS) influenza viruses. Pig serum samples were analysed by the hemagglutination inhibition test, using wild H1N2 and H3N2 strains (A/swine/México/Mex51/2010 [H3N2]) as antigen sources. Positive samples to the H1N2 subtype were processed using the field‐isolated H1N1 subtype (A/swine/México/Ver37/2010 [H1N1]). Seroprevalence to the H1N2 subtype was 26.74% in the sampled counties, being Jalisco the state with highest seroprevalence to this subtype (35.30%). The results herein reported demonstrate that this new, previously unregistered influenza virus subtype in México that shows internal genes from other swine viral subtypes isolated in the past 5 years, along with human virus‐originated genes, is widely distributed in this area of the country.     

Transplantation of solid organs procured from influenza A H1N1 infected donors

Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir.     

Seasonal flu-vaccination in the immunocompromised burns patient

Background and aimsInfluenza is a serious disease which can be life threatening. Patients with significant burns have reduced physiological reserve and are at risk both of incurring dangerous respiratory complications. In other susceptible patient groups the flu vaccine is used to reduce the risk of flu and lessen its effects.We aim to investigate whether there were any existing local and national trends in the use of flu vaccination in burns patients. Our second objective was to review any current evidence in the literature.MethodsA questionnaire was carried out of consultants in our own health board and of 5 of the major burns units in the UK to assess current practice.ResultsNone of the local respondent were aware of any existing guidelines. None of the external units contacted reported the use of a guideline for flu vaccination in burns patients. On searching the literature there were no existing studies investigating the use of flu vaccination in burns patients.ConclusionsThrough review of the literature on flu vaccination in immunocompromised patients we show how this could be extrapolated to patients with significant burns. We propose a guideline to aid in the decision to prescribe flu vaccine to patients with significant burns taking into account age, % TBSA burn and comorbidity. The decision to recommend the flu vaccine in this group should be considered on an individual basis. However, flu vaccination represents a simple, low-risk measure which could prevent the dangerous complications of influenza in an at risk group.     

Evaluation of Screening Assays for the Detection of Influenza A Virus Serum Antibodies in Swine

Increased surveillance of influenza A virus (IAV) infections in human and swine populations is mandated by public health and animal health concerns. Antibody assays have proven useful in previous surveillance programmes because antibodies provide a record of prior exposure and the technology is inexpensive. The objective of this research was to compare the performance of influenza serum antibody assays using samples collected from pigs (vaccinated or unvaccinated) inoculated with either A/Swine/OH/511445/2007 γ H1N1 virus or A/Swine/Illinois/02907/2009 Cluster IV H3N2 virus and followed for 42 days. Weekly serum samples were tested for anti‐IAV antibodies using homologous and heterologous haemagglutination‐inhibition (HI) assays, commercial swine influenza H1N1 and H3N2 indirect ELISAs, and a commercial influenza nucleoprotein (NP)‐blocking ELISA. The homologous HIs showed 100% diagnostic sensitivity, but largely failed to detect infection with the heterologous virus. With diagnostic sensitivities of 1.4% and 4.9%, respectively, the H1N1 and H3N2 indirect ELISAs were ineffective at detecting IAV antibodies in swine infected with the contemporary influenza viruses used in the study. At a cut‐off of S/N ≤ 0.60, the sensitivity and specificity of the NP‐blocking ELISA were estimated at 95.5% and 99.6%, respectively. Statistically significant factors which affected S/N results include vaccination status, inoculum (virus subtype), day post‐inoculation and the interactions between those factors (P < 0.0001). Serum antibodies against NP provide an ideal universal diagnostic screening target and could provide a cost‐effective approach for the detection and surveillance of IAV infections in swine populations.     

Detection of Influenza A Virus Nucleoprotein Antibodies in Oral Fluid Specimens From Pigs Infected Under Experimental Conditions Using a Blocking ELISA

In commercial swine populations, influenza is an important component of the porcine respiratory disease complex (PRDC) and a pathogen with major economic impact. Previously, a commercial blocking ELISA (FlockChek^™ Avian Influenza Virus MultiS‐Screen^® Antibody Test Kit, IDEXX Laboratories, Inc., Westbrook, ME, USA) designed to detect influenza A nucleoprotein (NP) antibodies in avian serum was shown to accurately detect NP antibodies in swine serum. The purpose of this study was to determine whether this assay could detect NP antibodies in swine oral fluid samples. Initially, the procedure for performing the NP‐blocking ELISA on oral fluid was modified from the serum testing protocol by changing sample dilution, sample volume, incubation time and incubation temperature. The detection of NP antibody was then evaluated using pen‐based oral fluid samples (n = 182) from pigs inoculated with either influenza A virus subtype H1N1 or H3N2 under experimental conditions and followed for 42 days post inoculation (DPI). NP antibodies in oral fluid were detected from DPI 7 to 42 in all inoculated groups, that is, the mean sample‐to‐negative (S/N) ratio of influenza‐inoculated pigs was significantly different (P < 0.0001) from uninoculated controls (unvaccinated or vaccinated‐uninoculated groups) through this period. Oral fluid versus serum S/N ratios from the same pen showed a correlation of 0.796 (Pearson's correlation coefficient, P < 0.0001). The results showed that oral fluid samples from influenza virus‐infected pigs contained detectable levels of NP antibodies for ≥42 DPI. Future research will be required to determine whether this approach could be used to monitor the circulation of influenza virus in commercial pig populations.     

Identification and genomic characterization of influenza viruses with different origin in Mexican pigs

Swine influenza is a worldwide disease, which causes damage to the respiratory system of pigs. The H1N1 and H3N2 subtypes circulate mainly in the swine population of Mexico. There is evidence that new subtypes of influenza virus have evolved genetically and have been rearranged with human viruses and from other species; therefore, the aim of our study was to identify and characterize the genetic changes that have been generated in the different subtypes of the swine influenza virus in Mexican pigs. By sequencing and analyzing phylogenetically the eight segments that form the virus genome, the following subtypes were identified: H1N1, H3N2, H1N2 and H5N2; of which, a H1N1 subtype had a high genetic relationship with the human influenza virus. In addition, a H1N2 subtype related to the porcine H1N2 virus reported in the United States was identified, as well as, two other viruses of avian origin from the H5N2 subtype. Particularly for the H5N2 subtype, this is the first time that its presence has been reported in Mexican pigs. The analysis of these sequences demonstrates that in the swine population of Mexico, circulate viruses that have suffered punctual‐specific mutations and rearrangements of their proteins with different subtypes, which have successfully adapted to the Mexican swine population.     

乳铁蛋白-DNA复合物检测评价甲型H1N1重症流感患者血浆中性粒细胞胞外诱捕网水平

目的建立乳铁蛋白-DNA复合物的相对定量检测方法,评价甲型H1N1重型流感及其他病原体感染者血浆样本中性粒细胞胞外诱捕网（NETs）的含量。 方法将DNA含量明确的血浆样本进行梯度稀释作为标准品,应用酶联免疫吸附法（ELISA）检测血浆中乳铁蛋白-DNA复合物含量。采用乳铁蛋白-DNA ELISA方法比较19例甲型H1N1重症流感患者与19例献血者（对照组）血浆乳铁蛋白-DNA复合物含量差异。 结果甲型H1N1重型重症流感患者血浆中乳铁蛋白-DNA复合物水平与游离DNA（cfDNA）和组蛋白-DNA复合物水平均呈正相关（r = 0.6763、P < 0.0001,r = 0.7560、P < 0.0001）。甲型H1N1重症流感患者血浆中乳铁蛋白-DNA复合物含量为[2.082（1.169,5.021）μg/ml],显著高于对照组[0.233（0.170,0.376）μg/ml],差异有统计学意义（P < 0.0001）,且乳铁蛋白-DNA复合物含量与甲型H1N1重症流感患者的急性生理与慢性健康评分（APACHEⅡ评分）呈正相关（r = 0.7379、P = 0.0005）。 结论血浆乳铁蛋白-DNA复合物含量可用于评价甲型H1N1重症流感患者NETs水平。     

Hemikolektomie bei Kolonischämie

Pandemic influenza A (H1N1) virus infection is rapidly spreading and has also become a common problem in Germany. Many cases with severe clinical presentation and death have been documented, especially in persons with underlying medical conditions. As of December 15, 2009, Germany has reported 119 H1N1-associated deaths. We report here the first H1N1-associated death in Germany, a 36-year-old woman with morbid obesity. The patient underwent a laparotomy with colon resection due to colon ischemia, a rare visceral complication in such cases. In this article an attempt has been made to reflect the state of requirements in terms of safety, occupational health, hygiene and working conditions with respect to activities involving logistics in the diagnostics, treatment (also surgical) and handling of such patients. Given the rapidly evolving nature the outbreak of human infection with the novel influenza A (H1N1) virus, influenza vaccination is recommended as the only way to prevent the infection of health care workers and patients with underlying medical conditions.     

甲型H1N1流感病例的血液学特点及临床分析

目的分析甲型H1N1流感患者的血液学特点。方法选择82例甲型H1N1流感患者、60例季节性流感患者和60名健康体检者,采用血细胞分析仪体积法、高频传导和激光散射法（VCS）技术对白细胞进行分类,统计分析白细胞总数（WBC）、淋巴及单核细胞百分比、平均淋巴细胞体积（MLV）、淋巴细胞体积变异度（LVD）、平均单核细胞体积（MMV）及单核细胞体积变异度（MVD）。组间计量资料差异比较采用ANOVA方差分析,两两比较采用q检验。结果甲型H1N1流感组,季节性流感组和健康对照组的WBC计数分别为（5．7±1．8）×10^9／L、（5．2±1．6）×10^9／L和（6．0±1．3）×10^9／L,比较差异无统计学意义（F=1．55,P〉0．05）;淋巴细胞百分比分别为（17．8±6．3）％、（34．6±7．3）％和（28．7±4．1）％,差异有统计学意义（F=38．36,P〈0．01）;单核细胞百分比分别为（13．2±4．4）％、（9．0±2．5）％和（6．3±1．4）％,差异有统计学意义（F=29．40,P〈0．01）。在WBC VCS参数分析中,甲型H1N1流感患者的MLV和LVD与健康对照组相近（q值分别为0．97和0．43,P值均〉0．05）,但明显低于季节性流感组（q值分别为5．69和6．46,P值均〈0．01）;而MMV和MVD均显著高于健康对照组和季节性流感组（F值分别为40．72和32．51,P值均〈0．01）。结论甲型H1N1流感早期,患者的血液学变化主要是淋巴细胞比例降低,单核细胞比例增高,而WBC总数无显著变化,能够灵敏地反映外周血淋巴细胞应激性形态改变的MLV和LVD低于季节性流感,反映单核细胞体积变化的形态学参数MMV和MVD增大。     

Factors Associated with the Emergence of Highly Pathogenic Avian Influenza A (H5N1) Poultry Outbreaks in China: Evidence from an Epidemiological Investigation in Ningxia, 2012

In April 2012, highly pathogenic avian influenza virus of the H5N1 subtype (HPAIV H5N1) emerged in poultry layers in Ningxia. A retrospective case–control study was conducted to identify possible risk factors associated with the emergence of H5N1 infection and describe and quantify the spatial variation in H5N1 infection. A multivariable logistic regression model was used to identify risk factors significantly associated with the presence of infection; residual spatial variation in H5N1 risk unaccounted by the factors included in the multivariable model was investigated using a semivariogram. Our results indicate that HPAIV H5N1‐infected farms were three times more likely to improperly dispose farm waste [adjusted OR = 0.37; 95% CI: 0.12–0.82] and five times more likely to have had visitors in their farm within the past month [adjusted OR = 5.47; 95% CI: 1.97–15.64] compared to H5N1‐non‐infected farms. The variables included in the final multivariable model accounted only 20% for the spatial clustering of H5N1 infection. The average size of a H5N1 cluster was 660 m. Bio‐exclusion practices should be strengthened on poultry farms to prevent further emergence of H5N1 infection. For future poultry depopulation, operations should consider H5N1 disease clusters to be as large as 700 m.