Sample records for pandemic swine-origin influenza

  1. Reassortment Networks and the evolution of pandemic H1N1 swine-origin influenza.

    Bokhari, Shahid H; Pomeroy, Laura W; Janies, Daniel A


    Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo.

  2. A simple Pichia pastoris fermentation and downstream processing strategy for making recombinant pandemic Swine Origin Influenza a virus Hemagglutinin protein.

    Athmaram, T N; Singh, Anil Kumar; Saraswat, Shweta; Srivastava, Saurabh; Misra, Princi; Kameswara Rao, M; Gopalan, N; Rao, P V L


    The present Influenza vaccine manufacturing process has posed a clear impediment to initiation of rapid mass vaccination against spreading pandemic influenza. New vaccine strategies are therefore needed that can accelerate the vaccine production. Pichia offers several advantages for rapid and economical bulk production of recombinant proteins and, hence, can be attractive alternative for producing an effective influenza HA based subunit vaccine. The recombinant Pichia harboring the transgene was subjected to fed-batch fermentation at 10 L scale. A simple fermentation and downstream processing strategy is developed for high-yield secretory expression of the recombinant Hemagglutinin protein of pandemic Swine Origin Influenza A virus using Pichia pastoris via fed-batch fermentation. Expression and purification were optimized and the expressed recombinant Hemagglutinin protein was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot and MALDI-TOF analysis. In this paper, we describe a fed-batch fermentation protocol for the secreted production of Swine Influenza A Hemagglutinin protein in the P. pastoris GS115 strain. We have shown that there is a clear relationship between product yield and specific growth rate. The fed-batch fermentation and downstream processing methods optimized in the present study have immense practical application for high-level production of the recombinant H1N1 HA protein in a cost effective way using P. pastoris.

  3. Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the haemagglutinin of pandemic swine origin H1N1 influenza A virus.

    Klingbeil, Katharina; Lange, Elke; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter


    Pigs can be severely harmed by influenza, and represent important reservoir hosts, in which new human pathogens such as the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszky's disease of swine, pseudorabies virus (PrV) strain Bartha (PrV-Ba), to serve as vector for the expression of haemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.

  4. Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants.

    Klingbeil, Katharina; Lange, Elke; Blohm, Ulrike; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter


    Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba.

  5. Pandemic Swine-Origin H1N1 Influenza Virus Replicates to Higher Levels and Induces More Fever and Acute Inflammatory Cytokines in Cynomolgus versus Rhesus Monkeys and Can Replicate in Common Marmosets.

    Mooij, Petra; Koopman, Gerrit; Mortier, Daniëlla; van Heteren, Melanie; Oostermeijer, Herman; Fagrouch, Zahra; de Laat, Rudy; Kobinger, Gary; Li, Yan; Remarque, Edmond J; Kondova, Ivanela; Verschoor, Ernst J; Bogers, Willy M J M


    The close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. Although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. In the current study a head-to-head comparison was made between these species, by using a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009. In comparison to rhesus macaques, cynomolgus macaques developed significantly higher levels of virus replication in the upper airways and in the lungs, involving both peak level and duration of virus production, as well as higher increases in body temperature. In contrast, clinical symptoms, including respiratory distress, were more easily observed in rhesus macaques. Expression of sialyl-α-2,6-Gal saccharides, the main receptor for human influenza A viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus macaques relative to rhesus macaques. The study also shows that common marmosets, a New World non-human primate species, are susceptible to infection with pandemic H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1 influenza virus research because of the more uniform and high levels of virus replication, as well as temperature increases, which may be due to a more abundant expression of the main human influenza virus receptor in the trachea and bronchi.

  6. Swine-origin influenza-virus-induced acute lung injury:Novel or classical pathogenesis?

    Naoyoshi; Maeda; Toshimitsu; Uede


    Influenza viruses are common respiratory pathogens in humans and can cause serious infection that leads to the development of pneumonia.Due to their hostrange diversity,genetic and antigenic diversity,and potential to reassort genetically in vivo,influenza A viruses are continual sources of novel influenza strains that lead to the emergence of periodic epidemics and outbreaks in humans.Thus,newly emerging viral diseases are always major threats to public health.In March 2009,a novel influenza virus suddenly emerged and caused a worldwide pandemic.The novel pandemic influenza virus was genetically and antigenically distinct from previous seasonal human influenza A/H1N1 viruses;it was identified to have originated from pigs,and further genetic analysis revealed it as a subtype of A/H1N1,thus later called a swine-origin influenza virus A/H1N1.Since the novel virus emerged,epidemiological surveys and research on experimental animal models have been conducted,and characteristics of the novel influenza virus have been determined but the exact mechanisms of pulmonary pathogenesis remain to be elucidated.In this editorial,we summa-rize and discuss the recent pandemic caused by the novel swine-origin influenza virus A/H1N1 with a focus on the mechanism of pathogenesis to obtain an insight into potential therapeutic strategies.

  7. Crystal structure of swine major histocompatibility complex class I SLA-1 0401 and identification of 2009 pandemic swine-origin influenza A H1N1 virus cytotoxic T lymphocyte epitope peptides.

    Zhang, Nianzhi; Qi, Jianxun; Feng, Sijia; Gao, Feng; Liu, Jun; Pan, Xiaocheng; Chen, Rong; Li, Qirun; Chen, Zhaosan; Li, Xiaoying; Xia, Chun; Gao, George F


    The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1 0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIV(NW9); NSDTVGWSW) or Ebola virus (Ebola(AY9); ATAAATEAY) were determined in this study. The overall peptide-SLA-1 0401 structures resemble, as expected, the general conformations of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of SLA-1 0401 is that Arg(156) has a "one-ballot veto" function in peptide binding, due to its flexible side chain. S-OIV(NW9) and Ebola(AY9) bind SLA-1 0401 with similar conformations but employ different water molecules to stabilize their binding. The side chain of P7 residues in both peptides is exposed, indicating that the epitopes are "featured" peptides presented by this SLA. Further analyses showed that SLA-1 0401 and human leukocyte antigen (HLA) class I HLA-A 0101 can present the same peptides, but in different conformations, demonstrating cross-species epitope presentation. CTL epitope peptides derived from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding method. Three peptides were identified as potential cross-species influenza virus (IV) CTL epitopes. The binding motif of SLA-1 0401 was proposed, and thermostabilities of key peptide-SLA-1 0401 complexes were analyzed by circular dichroism spectra. Our results not only provide the structural basis of peptide presentation by SLA I but also identify some IV CTL epitope peptides. These results will benefit both vaccine development and swine organ-based xenotransplantation.

  8. It is not just AIV: From avian to swine-origin influenza virus

    GAO George F; SUN YePing


    @@ In March and early April 2009, a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States.The virus spreads worldwide by human-to-human transmission.Within a few weeks, it reached a pandemic level.The virus is a novel reassorment virus.It contains gene fragments of influenza virus of swine, avian and human emerged from a triple reassortant virus circulating in North American swine.The source triple-reassortant itself comprised genes derived from avian (PB2 and PA), human H3N2 (PB1) and classical swine (HA, NP and NS) lineages.In contrast, the NA and M gene segments have their origin in the Eurasian avian-like swine H1N1 lineage (Figure 1).

  9. Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses

    M.L.B. Hillaire (Marine); S.E. Vogelzang-van Trierum (Stella ); J.H.C.M. Kreijtz (Joost); G. de Mutsert (Gerrie); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Ab); G.F. Rimmelzwaan (Guus)


    textabstractVirus-specific CD8+ T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity

  10. Computer-aided assessment of pulmonary disease in novel swine-origin H1N1 influenza on CT

    Yao, Jianhua; Dwyer, Andrew J.; Summers, Ronald M.; Mollura, Daniel J.


    The 2009 pandemic is a global outbreak of novel H1N1 influenza. Radiologic images can be used to assess the presence and severity of pulmonary infection. We develop a computer-aided assessment system to analyze the CT images from Swine-Origin Influenza A virus (S-OIV) novel H1N1 cases. The technique is based on the analysis of lung texture patterns and classification using a support vector machine (SVM). Pixel-wise tissue classification is computed from the SVM value. The method was validated on four H1N1 cases and ten normal cases. We demonstrated that the technique can detect regions of pulmonary abnormality in novel H1N1 patients and differentiate these regions from visually normal lung (area under the ROC curve is 0.993). This technique can also be applied to differentiate regions infected by different pulmonary diseases.

  11. Triple-reassortant influenza A virus with H3 of human seasonal origin, NA of swine origin, and internal A(H1N1) pandemic 2009 genes is established in Danish pigs

    Krog, Jesper Schak; Hjulsager, Charlotte Kristiane; Larsen, Michael Albin


    This report describes a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004 to 2005, N2 from influenza A virus already established in swine, and the internal gene cassette from A(H1N1)pdm09 has spread in Danish pig herds. The virus has been...... detected in several Danish pig herds during the last 2-3 years and may possess a challenge for human as well as animal health....

  12. Developing vaccines against pandemic influenza.

    Wood, J M


    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illust...

  13. Influenza pandemic planning in Europe.

    Paget, J.; Aguilera, J.F.


    The World Health Organization strongly recommends that all countries prepare in advance multidisciplinary pandemic plans to prevent and control the next influenza pandemic. We carried out a survey of influenza surveillance methods among members of the European Influenza Surveillance Schemes, EISS, w

  14. Swine-Origin Influenza A Outbreak 2009 at Shinshu University, Japan

    Washizuka Shinsuke


    Full Text Available Abstract Background A worldwide outbreak of swine flu H1N1 pandemic influenza occurred in April 2009. To determine the mechanism underlying the spread of infection, we prospectively evaluated a survey implemented at a local university. Methods Between August 2009 and March 2010, we surveyed 3 groups of subjects: 2318 children in six schools attached to the Faculty of Education, 11424 university students, and 3344 staff members. Subjects with influenza-like symptoms who were diagnosed with swine flu at hospitals or clinics were defined as swine flu patients and asked to make a report using a standardized form. Results After the start of the pandemic, a total of 2002 patients (11.7% were registered in the survey. These patients included 928 schoolchildren (40.0%, 1016 university students (8.9%, and 58 staff members (1.7%. The incidence in schoolchildren was significantly higher than in the other 2 groups (P Conclusion Schoolchildren and university students are vulnerable to swine flu, suggesting that avoidance of close contact, especially among these young people, may be effective way in controlling future severe influenza pandemics, especially at educational institutions.

  15. Detection of swine-origin influenza A (H1N1) viruses using a paired surface plasma waves biosensor

    Su, Li-Chen; Chang, Ying-Feng; Li, Ying-Chang; Hsieh, Jo-Ping; Lee, Cheng-Chung; Chou, Chien


    In order to enhance the sensitivity of conventional rapid test technique for the detection of swine-origin influenza A (H1N1) viruses (S-OIVs), we used a paired surface plasma waves biosensor (PSPWB) based on SPR in conjunction with an optical heterodyne technique. Experimentally, PSPWB showed a 125-fold improvement at least in the S-OIV detection as compared to conventional enzyme linked immunosorbent assay. Moreover, the detection limit of the PSPWB for the S-OIV detection was enhanced 250-fold in buffer at least in comparison with that of conventional rapid influenza diagnostic test.

  16. An equine herpesvirus 1 (EHV-1) vectored H1 vaccine protects against challenge with swine-origin influenza virus H1N1.

    Said, Abdelrahman; Damiani, Armando; Ma, Guanggang; Kalthoff, Donata; Beer, Martin; Osterrieder, Nikolaus


    In 2009, a novel swine-origin H1N1 influenza A virus (S-OIV), antigenically and genetically divergent from seasonal H1N1, caused a flu pandemic in humans. Development of an effective vaccine to limit transmission of S-OIV in animal reservoir hosts and from reservoir hosts to humans and animals is necessary. In the present study, we constructed and evaluated a vectored vaccine expressing the H1 hemagglutinin of a recent S-OIV isolate using equine herpesvirus 1 (EHV-1) as the delivery vehicle. Expression of the recombinant protein was demonstrated by immunofluorescence and western blotting and the in vitro growth properties of the modified live vector were found to be comparable to those of the parental virus. The EHV-1-H1 vaccine induced an influenza virus-specific antibody response when inoculated into mice by both the intranasal and subcutaneous routes. Upon challenge infection, protection of vaccinated mice could be demonstrated by reduction of clinical signs and faster virus clearance. Our study shows that an EHV-1-based influenza H1N1 vaccine may be a promising alternative for protection against S-OIV infection.

  17. Molecular epidemiology of novel swine origin influenza virus (S-OIV from Gwalior, India, 2009

    Shukla Jyoti


    Full Text Available Abstract Background The H1N1pandemic virus is a newly emergent human influenza A virus that is closely related to a number of currently circulating pig viruses in the 'classic North American' and 'Eurasian' swine influenza virus lineages and thus referred as S-OIV. Since the first reports of the virus in humans in April 2009, H1N1 virus has spread to 168 countries and overseas territories. India also witnessed severe H1N1 pandemic virus epidemic with considerable morbidity and mortality in different parts starting from May 2009. Findings The suspected swine flu outbreak from Gwalior India during October- December 2009 was confirmed through S-OIV HA gene specific RT-LAMP and real time RT-PCR. Positive samples through CDC real time and Lamp assay were further processed for isolation of the virus. Full HA gene sequencing of the H1N1 isolates of Gwalior, India revealed 99% homology with California and other circulating novel swine flu viruses. Three major changes were observed at nucleotide level, while two major amino acid shifts were observed at the position C9W and I30M corresponding to the ORF with prototype strain. The HA gene sequence phylogeny revealed the circulation of two genetically distinct lineages belonging to Clade VII and Clade I of S-OIV. Conclusions Our findings also supported the earlier report about circulation of mixed genogroups of S-OIV in India. Therefore continuous monitoring of the genetic makeup of this newly emergent virus is essential to understand its evolution within the country.

  18. Efficacy of vaccination with different combinations of MF59-adjuvanted and nonadjuvanted seasonal and pandemic influenza vaccines against pandemic H1N1 (2009) influenza virus infection in ferrets.

    van den Brand, Judith M A; Kreijtz, Joost H C M; Bodewes, Rogier; Stittelaar, Koert J; van Amerongen, Geert; Kuiken, Thijs; Simon, James; Fouchier, Ron A M; Del Giudice, Giuseppe; Rappuoli, Rino; Rimmelzwaan, Guus F; Osterhaus, Albert D M E


    Serum antibodies induced by seasonal influenza or seasonal influenza vaccination exhibit limited or no cross-reactivity against the 2009 pandemic swine-origin influenza virus of the H1N1 subtype (pH1N1). Ferrets immunized once or twice with MF59-adjuvanted seasonal influenza vaccine exhibited significantly reduced lung virus titers but no substantial clinical protection against pH1N1-associated disease. However, priming with MF59-adjuvanted seasonal influenza vaccine significantly increased the efficacy of a pandemic MF59-adjuvanted influenza vaccine against pH1N1 challenge. Elucidating the mechanism involved in this priming principle will contribute to our understanding of vaccine- and infection-induced correlates of protection. Furthermore, a practical consequence of these findings is that during an emerging pandemic, the implementation of a priming strategy with an available adjuvanted seasonal vaccine to precede the eventual pandemic vaccination campaign may be useful and life-saving.

  19. Impact of information on intentions to vaccinate in a potential epidemic: Swine-origin Influenza A (H1N1).

    Chanel, Olivier; Luchini, Stéphane; Massoni, Sébastien; Vergnaud, Jean-Christophe


    Vaccination campaigns to prevent the spread of epidemics are successful only if the targeted populations subscribe to the recommendations of health authorities. However, because compulsory vaccination is hardly conceivable in modern democracies, governments need to convince their populations through efficient and persuasive information campaigns. In the context of the swine-origin A (H1N1) 2009 pandemic, we use an interactive study among the general public in the South of France, with 175 participants, to explore what type of information can induce change in vaccination intentions at both aggregate and individual levels. We find that individual attitudes to vaccination are based on rational appraisal of the situation, and that it is information of a purely scientific nature that has the only significant positive effect on intention to vaccinate.

  20. Pandemic Influenza Vaccines – The Challenges

    Rebecca Cox


    Full Text Available Recent years’ enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.

  1. Pandemic Influenza and Canada's Children

    Joanne M Langley


    Full Text Available Paediatricians and others who care for children are familiar with the regular epidemic of respiratory illnesses that accompanies the annual visit of influenza virus each winter. In recent years, media interest in new strains of influenza has generated much public interest in, and often anxiety about, the threat of an influenza pandemic. Around the world, local, regional and national jurisdictions are engaged in contingency planning for the inevitable surge of illness, shortage of human and material resources, and societal disruption that is expected to accompany this event. In the present Paediatric Infectious Disease Note, we review briefly the potential implications of pandemic influenza for Canadian children, and the actions that paediatricians and others who care for children can take to prepare for this inevitable event.

  2. Seasonal influenza: Waiting for the next pandemic

    Angela Clem


    Full Text Available With the ongoing cases of H1N1 influenza (aka Swine Flu occurring around the globe, seasonal influenza has a tendency to be overlooked by the media and general population as a source of illness and death. Yet, these pandemic influenza viruses arise from these seasonal influenza viruses. This article will provide an overview of seasonal influenza, its prevention and treatment, and the global surveillance system in place, used to detect the next influenza pandemic.

  3. In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009

    Christopher; VAVRICKA; GAO; George; F


    The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza viruses.We analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes.We compared their differences and similarities systematically.Based on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor.The D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported work.This HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion function.The 2009 S-OIV HA also has an extra glycosylation site at position 276.Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation site.The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined.These results are critical for understanding the pathogenicity of the virus and host immune response against the virus.

  4. Pandemic influenza and hospital resources

    Nap, Raoul E.; Andriessen, Maarten P. H. M.; Meessen, Nico E. L.; Van der Werf, Tjip S.


    Using estimates from the Centers for Disease Control and Prevention, the World Health Organization, and published models of the expected evolution of pandemic influenza, we modeled the surge capacity of healthcare facility and intensive care unit (ICU) requirements over time in northern Netherlands

  5. Introduction of a Novel Swine-Origin Influenza A (H1N1 Virus into Milwaukee, Wisconsin in 2009

    Swati Kumar


    Full Text Available On 17 April 2009, novel swine origin influenza A virus (S-OIV cases appeared within the United States. Most influenza A diagnostic assays currently utilized in local clinical laboratories do not allow definitive subtype determination. Detailed subtype analysis of influenza A positive samples in our laboratory allowed early confirmation of a large outbreak of S-OIV in southeastern Wisconsin (SEW. The initial case of S-OIV in SEW was detected on 28 April 2009. All influenza A samples obtained during the 16 week period prior to 28 April 2009, and the first four weeks of the subsequent epidemic were sub typed. Four different multiplex assays were employed, utilizing real time PCR and end point PCR to fully subtype human and animal influenza viral components. Specific detection of S-OIV was developed within days. Data regarding patient demographics and other concurrently circulating viruses were analyzed. During the first four weeks of the epidemic, 679 of 3726 (18.2% adults and children tested for influenza A were identified with S-OIV infection. Thirteen patients (0.34% tested positive for seasonal human subtypes of influenza A during the first two weeks and none in the subsequent 2 weeks of the epidemic. Parainfluenza viruses were the most prevalent seasonal viral agents circulating during the epidemic (of those tested, with detection rates of 12% followed by influenza B and RSV at 1.9% and 0.9% respectively. S-OIV was confirmed on day 2 of instituting subtype testing and within 4 days of report of national cases of S-OIV. Novel surge capacity diagnostic infrastructure exists in many specialty and research laboratories around the world. The capacity for broader influenza A sub typing at the local laboratory level allows timely and accurate detection of novel strains as they emerge in the community, despite the presence of other circulating viruses producing identical illness. This is likely to become increasingly important given the need for

  6. Using routine surveillance data to estimate the epidemic potential of emerging zoonoses: application to the emergence of US swine origin influenza A H3N2v virus.

    Simon Cauchemez

    Full Text Available BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case. However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations. METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic. Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G and among the subset of the first detected cases in each cluster (F. If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1-G; otherwise R can be estimated by 1-F when the case detection rate is low. In more general cases, bounds on R can still be derived. CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary.

  7. Pandemic Influenza Pediatric Office Plan Template



    This is a planning tool developed by pediatric stakeholders that is intended to assist pediatric medical offices that have no pandemic influenza plan in place, but may experience an increase in patient calls/visits or workload due to pandemic influenza.

  8. Pandemic influenza guidance for corporations.


    The purpose of this guidance document is to assist members of the American College of Occupational and Environmental Medicine (ACOEM), and the organizations for which they work, in managing the impact of a pandemic of influenza or other contagious respiratory disease on patients, employees, and business. This guidance document outlines actions to take before and during an influenza pandemic on the basis of two main strategies: (1) reducing the spread of the virus within facilities; and (2) providing medical care and medical surveillance to client/patient populations. Facilities in which ACOEM members serve include government agencies and the military, universities, and corporations, which generally have multiple locations/sites and their own medical staff, with members responsible for medical care and disease control. This guidance is for organizations with outpatient occupational medicine services, to be used as appropriate. Medical centers should also use guidance that addresses additional employee and external patient care needs.1–3 The ACOEM fully supports implementation of occupational influenza programs that conform with guidance from the Centers for Disease Control and Prevention (CDC), with other guidance from the US Department of Health and Human Services (DHHS), and Occupational Safety and Health Administration (OSHA) regulations and guidance.

  9. Chest Radiographic Findings of Novel Swine-Origin Influenza A (H1N1) Virus Infection in Children

    Bae, So Young; Hong, Eun Sook; Paik, Sang Hyun; Park, Seong Jin; Cha, Jang Gyu; Lee, Hae Kyung [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Jang, Yun Woo [Dept. of Radiology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)


    To analyze chest radiographic findings in children infected with laboratory confirmed novel swine-origin influenza A (H1N1) virus. Three hundred seventy-two out of 2,014 children with laboratory confirmed H1N1 infection and who also underwent a chest radiograph from September to November 2009 were enrolled in this study. Patients were divided into in-patients, out-patients, and patients with co-infections and further subdivided into with underlying disease and without underlying disease as well as age (<2 years old, 2-5 years, 5-10 years, 10-18 years old). The initial radiographs were evaluated for radiographic findings and the anatomic distribution of abnormalities. The initial radiographs were abnormal in 154 (41.39%) patients. The predominant radiographic findings were peribronchial wall opacity found in 85 (22.84%) patients and hyperinflation observed in 69 (18.54%) patients. Further, 75 (71.42%) patients exhibited central predominance and the right lower lung zone was also commonly involved. There were statistically significant differences in the radiological findings between in-patient and out-patient groups. However, there were no significant differences in the radiographic findings between in-patients and the co-infection group with respect the presence of underlying disease and age. Initial radiographs of children with laboratory confirmed H1N1 virus were abnormal in 41.39% of cases. The common radiographic findings included peribronchial opacities, hyperinflation, lower lung zonal distribution, and central predominance

  10. Economic and policy implications of pandemic influenza.

    Smith, Braeton J.; Starks, Shirley J.; Loose, Verne W.; Brown, Theresa Jean; Warren, Drake E.; Vargas, Vanessa N.


    Pandemic influenza has become a serious global health concern; in response, governments around the world have allocated increasing funds to containment of public health threats from this disease. Pandemic influenza is also recognized to have serious economic implications, causing illness and absence that reduces worker productivity and economic output and, through mortality, robs nations of their most valuable assets - human resources. This paper reports two studies that investigate both the short- and long-term economic implications of a pandemic flu outbreak. Policy makers can use the growing number of economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. Experts recognize that pandemic influenza has serious global economic implications. The illness causes absenteeism, reduced worker productivity, and therefore reduced economic output. This, combined with the associated mortality rate, robs nations of valuable human resources. Policy makers can use economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. In this paper economists examine two studies which investigate both the short- and long-term economic implications of a pandemic influenza outbreak. Resulting policy implications are also discussed. The research uses the Regional Economic Modeling, Inc. (REMI) Policy Insight + Model. This model provides a dynamic, regional, North America Industrial Classification System (NAICS) industry-structured framework for forecasting. It is supported by a population dynamics model that is well-adapted to investigating macro-economic implications of pandemic influenza, including possible demand side effects. The studies reported in this paper exercise all of these capabilities.

  11. Influenza Pandemic Infrastructure Response in Thailand


    Influenza viruses change antigenic properties, or drift, every year and they create seasonal outbreaks. Occasionally, influenza viruses change in a major way, called a “shift." If an influenza virus shifts, the entire human population is susceptible to the new influenza virus, creating the potential for a pandemic. On this podcast, CDC's Dr. Scott Dowell discusses responding to an influenza pandemic.  Created: 3/5/2009 by Emerging Infectious Diseases.   Date Released: 3/5/2009.

  12. Corticosteroid treatment ameliorates acute lung injury induced by 2009 swine origin influenza A (H1N1 virus in mice.

    Chenggang Li

    Full Text Available BACKGROUND: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. METHODOLOGY/PRINCIPAL FINDINGS: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. CONCLUSIONS/SIGNIFICANCE: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1 mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1 pandemics.

  13. Pandemic Influenza: A Never-Ending Story

    Kageyama, Seiji


    A novel pandemic influenza emerged in 2009, something that hasn't been seen since 1977. The following issues will be introduced and discussed in this review: the history of influenza pandemics, the emergence of the novel pandemic influenza of 2009, epidemics in the southern and northern hemispheres after the recognition of index cases in the United States, mortality, viral characteristics, prevention in the household setting, clinical aspects, diagnosis, treatment and immunization. Some questions have been answered. However, a number of other questions remain. Scientific research must follow up on these unanswered questions. PMID:24031128

  14. Optimal pandemic influenza vaccine allocation strategies for the Canadian population.

    Ashleigh R Tuite

    Full Text Available BACKGROUND: The world is currently confronting the first influenza pandemic of the 21(st century. Influenza vaccination is an effective preventive measure, but the unique epidemiological features of swine-origin influenza A (H1N1 (pH1N1 introduce uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and mortality. METHODOLOGY/PRINCIPAL FINDINGS: We developed a deterministic, age-structured compartmental model of influenza transmission, with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and mortality. In all scenarios, prioritization of high-risk individuals (those with underlying chronic conditions and pregnant women, regardless of age, markedly decreased the frequency of severe outcomes. When individuals with underlying medical conditions were not prioritized and an age group-based approach was used, preferential vaccination of age groups at increased risk of severe outcomes following infection generally resulted in decreased mortality compared to targeting vaccine to age groups with higher transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the epidemic peak. CONCLUSIONS/SIGNIFICANCE: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable morbidity and mortality, but the benefits are

  15. Influenza in the immediate post-pandemic era : A comparison with seasonal and pandemic influenza in hospitalized patients

    Rahamat-Langendoen, J. C.; Tutuhatunewa, E. D.; Scholvinck, E. H.; Hak, E.; Koopmans, M.; Niesters, H. G. M.; Riezebos-Brilman, A.


    Background: Comparative data on severity and treatment of seasonal, pandemic and post-pandemic influenza virus infections are scarce. Objectives: To systematically analyze characteristics of hospitalized patients with influenza in the post-pandemic period compared to seasonal and pandemic influenza.

  16. 77 FR 13329 - Pandemic Influenza Vaccines-Amendment


    ... HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines--Amendment ACTION: Notice of... influenza vaccines, which has been amended a number of times. The original pandemic influenza vaccine... (2010). The major actions taken by this pandemic influenza vaccine declaration are the following:...

  17. Avian influenza and pandemic influenza preparedness in Hong Kong.

    Lam, Ping Yan


    Avian influenza A H5N1 continues to be a major threat to global public health as it is a likely candidate for the next influenza pandemic. To protect public health and avert potential disruption to the economy, the Hong Kong Special Administrative Region Government has committed substantial effort in preparedness for avian and pandemic influenza. Public health infrastructures for emerging infectious diseases have been developed to enhance command, control and coordination of emergency response. Strategies against avian and pandemic influenza are formulated to reduce opportunities for human infection, detect pandemic influenza timely, and enhance emergency preparedness and response capacity. Key components of the pandemic response include strengthening disease surveillance systems, updating legislation on infectious disease prevention and control, enhancing traveller health measures, building surge capacity, maintaining adequate pharmaceutical stockpiles, and ensuring business continuity during crisis. Challenges from avian and pandemic influenza are not to be underestimated. Implementing quarantine and social distancing measures to contain or mitigate the spread of pandemic influenza is problematic in a highly urbanised city like Hong Kong as they involved complex operational and ethical issues. Sustaining effective risk communication campaigns during interpandemic times is another challenge. Being a member of the global village, Hong Kong is committed to contributing its share of efforts and collaborating with health authorities internationally in combating our common public health enemy.

  18. Europe's preparedness for an influenza pandemic: commentary.

    Paget, W.J.


    The paper in this month's edition of the European Journal of Public Health on Europe's preparedness for an influenza pandemic is highly relevant in the light of the emergence of the influenza A (H5N1) virus in humans in Southeast Asia and more recently, in Turkey and Iraq. The paper provides a nic

  19. Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings

    Li Ping, E-mail: [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Su Dongju, E-mail: [Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Zhang Jifeng, E-mail: [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Xia Xudong, E-mail: [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Sui Hong, E-mail: [Department of Statistics, Harbin Medical University, 240 Xue Fu Road, Harbin 150086 (China); Zhao Donghui, E-mail: [Centers for Disease Control and Prevention of Heilongjiang, 187 Xiang An Street, Harbin 150036 (China)


    Objective: The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods: High-resolution CT (HRCT) findings of 106 patients with presumed/laboratory-confirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results: The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n = 29, 27.4%), with unilateral or bilateral consolidation (n = 50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p < 0.01, {chi}{sup 2} test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions: The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S

  20. Business continuity management and pandemic influenza.

    Dalton, Craig B


    Pandemic influenza planning presents challenges for both government and businesses. Effective cooperation and communication before and during a pandemic will help mitigate the major threats to societal function. The major challenges for government include communicating a realistic estimate of pandemic risk, managing community anxiety, communicating the need for rationing of vaccines and antiviral medications, setting standards for preparedness, and gaining the trust of essential service workers. For businesses the challenges are tailoring generic planning guides to local use, and making links with local and regional partners in pandemic planning.

  1. Antiviral Strategies for Pandemic and Seasonal Influenza

    Fang Fang


    Full Text Available While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein.

  2. Containing pandemic influenza with antiviral agents.

    Longini, Ira M; Halloran, M Elizabeth; Nizam, Azhar; Yang, Yang


    For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available.

  3. Pandemic influenza and pediatric intensive care

    Nap, Raoul E.; Andriessen, Maarten P. H. M.; Meessen, Nico E. L.; Albers, Marcel J. I. J.; van der Werf, Tjip S.


    Objective: To assess the adequacy of preparedness planning for an influenza pandemic by modeling the pediatric surge capacity of healthcare facility and pediatric intensive care unit (PICU) requirements over time. Governments and Public Health authorities have planned preparedness activities and tra

  4. The shifting demographic landscape of pandemic influenza.

    Shweta Bansal

    Full Text Available As Pandemic (H1N1 2009 influenza spreads around the globe, it strikes school-age children more often than adults. Although there is some evidence of pre-existing immunity among older adults, this alone may not explain the significant gap in age-specific infection rates.Based on a retrospective analysis of pandemic strains of influenza from the last century, we show that school-age children typically experience the highest attack rates in primarily naive populations, with the burden shifting to adults during the subsequent season. Using a parsimonious network-based mathematical model which incorporates the changing distribution of contacts in the susceptible population, we demonstrate that new pandemic strains of influenza are expected to shift the epidemiological landscape in exactly this way.Our analysis provides a simple demographic explanation for the age bias observed for H1N1/09 attack rates, and suggests that this bias may shift in coming months. These results have significant implications for the allocation of public health resources for H1N1/09 and future influenza pandemics.

  5. Ethical considerations in pandemic influenza planning.

    Garrett, J Eline; Vawter, Dorothy E; Prehn, Angela W; DeBruin, Debra A; Gervais, Karen G


    Although the timing and severity of the next influenza pandemic is impossible to predict, there is broad agreement that one will occur. Preparation is vital to mitigating its effects. A severe influenza pandemic like that which began in 1918 would be unlike other disasters in nature, scale, and duration. It could cripple normal business operations and disrupt global distribution of essential goods and services. It could force ethical decisions that many in a country accustomed to relative abundance are poorly prepared to make. Although sound evidence and clinical and public health expertise are needed to make informed decisions, so is an understanding of our common and diverse values. This article outlines some of the challenges the state would face during a pandemic, especially concerning the rationing of resources and care. It also describes a process currently underway to develop guidelines for how the state should approach the ethical questions that would arise.

  6. Identification and Epidemiology of Severe Respiratory Disease due to Novel Swine-Origin Influenza A (H1N1 Virus Infection in Alberta

    George Zahariadis


    Full Text Available BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1 strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1 in Canada.

  7. Waves of El Nino-southern Oscillation and Influenza Pandemics

    Olusegun Steven Ayodele Oluwole


    Influenza pandemics have occurred at irregular intervals for over 500 years, unlike seasonal influenza epidemics which occur annually. Although the risk factors are known, the basis for the timing of influenza pandemic waves are unknown. Coherence of peaks of El Niño and influenza pandemic in 2009–2010, however, suggests that both waves are coupled. This study was done to determine the relation of influenza pandemics to the peaks and waveforms of El Niño southern oscillation (ENSO). ENSO cy...

  8. Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children.

    Wijngaard, C.C. van den; Asten, L. van; Koopmans, M.P.G.; Pelt, W. van; Nagelkerke, N.J.D.; Wielders, C.C.H.; Lier, A. van; Hoek, W. van der; Meijer, A.; Donker, G.A.; Dijkstra, F.; Harmsen, C.; Sande, M.A.B. van der; Kretzschmar, M.


    Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. F

  9. What hospitals should do to prepare for an influenza pandemic.

    Toner, Eric; Waldhorn, Richard


    This article offers recommendations on what hospitals should do to prepare for an influenza pandemic and proposes specific actions and priorities for the purpose of making the discussion of hospital pandemic preparedness issues more operationally useful.

  10. Developing Vaccines to Combat Pandemic Influenza

    Othmar G. Engelhardt


    Full Text Available Influenza vaccine manufacturers require antigenically relevant vaccine viruses that have good manufacturing properties and are safe to use. In developing pandemic vaccine viruses, reverse genetics has been employed as a rational approach that can also be used effectively to attenuate the highly virulent H5N1 virus and at the same time place the H5 HA and N1 NA on a background of PR8, a virus that has been used over many decades to provide high yielding vaccine viruses. Reverse genetics has also been used successfully alongside classical reassorting techniques in the development of (swine flu pandemic A(H1N1v vaccine viruses.

  11. Influenza: From zoonosis to pandemic


    Probable epidemic influenza outbreaks have been described as early as the 5th century BC, as part of the Cough of Perinthus associated with the winter solstice, in Hippocrates' Corpus Hippocraticum “Of the Epidemics” [1]. The word “influenza” was first introduced in the 16th century, defining the illness of the cold season that in the early 1930s was shown to be caused by “filterable agents”, since then called influenza viruses. Three types or genera of influenza viruses have been recognised ...

  12. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian Influenza virus (H5N1, H7N7 and swine-origin H1N1 (S-OIV

    Schoop Roland


    Full Text Available Abstract Background Influenza virus (IV infections are a major threat to human welfare and animal health worldwide. Anti-viral therapy includes vaccines and a few anti-viral drugs. However vaccines are not always available in time, as demonstrated by the emergence of the new 2009 H1N1-type pandemic strain of swine origin (S-OIV in April 2009, and the acquisition of resistance to neuraminidase inhibitors such as Tamiflu® (oseltamivir is a potential problem. Therefore the prospects for the control of IV by existing anti-viral drugs are limited. As an alternative approach to the common anti-virals we studied in more detail a commercial standardized extract of the widely used herb Echinacea purpurea (Echinaforce®, EF in order to elucidate the nature of its anti-IV activity. Results Human H1N1-type IV, highly pathogenic avian IV (HPAIV of the H5- and H7-types, as well as swine origin IV (S-OIV, H1N1, were all inactivated in cell culture assays by the EF preparation at concentrations ranging from the recommended dose for oral consumption to several orders of magnitude lower. Detailed studies with the H5N1 HPAIV strain indicated that direct contact between EF and virus was required, prior to infection, in order to obtain maximum inhibition in virus replication. Hemagglutination assays showed that the extract inhibited the receptor binding activity of the virus, suggesting that the extract interferes with the viral entry into cells. In sequential passage studies under treatment in cell culture with the H5N1 virus no EF-resistant variants emerged, in contrast to Tamiflu®, which produced resistant viruses upon passaging. Furthermore, the Tamiflu®-resistant virus was just as susceptible to EF as the wild type virus. Conclusion As a result of these investigations, we believe that this standard Echinacea preparation, used at the recommended dose for oral consumption, could be a useful, readily available and affordable addition to existing control options

  13. Hospital Viability during a Pandemic Influenza Outbreak


    poultry, is usually deadly. This current, more deadly virus is also known as H5N1 avian influenza, or bird flu . In the past several years, the bird ...Avian Flu: Avian or bird flu is caused by influenza viruses that occur naturally among wild birds. The H5N1 variant is deadly to domestic fowl and is...Health. Davenport, R. John. 2008. ―The next pandemic: Bird flu and the 1918 scourge yield harbingers of threats to come.‖

  14. Mutations at positions 186 and 194 in the HA gene of the 2009 H1N1 pandemic influenza virus improve replication in cell culture and eggs

    Balabanis Kara


    Full Text Available Abstract Obtaining suitable seed viruses for influenza vaccines poses a challenge for public health authorities and manufacturers. We used reverse genetics to generate vaccine seed-compatible viruses from the 2009 pandemic swine-origin influenza virus. Comparison of viruses recovered with variations in residues 186 and 194 (based on the H3 numbering system of the viral hemagglutinin showed that these viruses differed with respect to their ability to grow in eggs and cultured cells. Thus, we have demonstrated that molecular cloning of members of a quasispecies can help in selection of seed viruses for vaccine manufacture.

  15. National Strategy for Pandemic Influenza Implementation Plan


    Birds” to provide disease and biosecurity information to poultry producers, especially those with “ backyard ” production. The program provides...the proximity of the outbreak to major poultry areas, but with limited backyard flocks and strong biosecurity in large facilities, any outbreak would...pandemic, these viruses have the potential to impact the U.S. poultry industry. Some avian influenza viruses cause high mortality in chickens and are

  16. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.


    Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the up......Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses...

  17. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.


    Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses...... in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. Methods: This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA) I......, and II, and Sambucus Nigra (SNA). Furthermore, the predilection sites of swine influenza virus (SIV) subtypes H1N1 and H1N2 as well as avian influenza virus (AIV) subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. Results: SIV...

  18. Severe mortality impact of the 1957 influenza pandemic in Chile

    Chowell, Gerardo; Simonsen, Lone; Fuentes, Rodrigo


    INTRODUCTION: Epidemiological studies of the 1957 influenza pandemic are scarce, particularly from lower income settings. METHODS: We analyzed the spatial-temporal mortality patterns of the 1957 influenza pandemic in Chile including detailed age-specific mortality data from a large city and inves...

  19. Mathematical Assessment of Canada’s Pandemic Influenza Preparedness Plan

    Abba B Gumel


    Full Text Available OBJECTIVE: The presence of the highly pathogenic avian H5N1 virus in wild bird populations in several regions of the world, together with recurrent cases of H5N1 influenza arising primarily from direct contact with poultry, have highlighted the urgent need for prepared-ness and coordinated global strategies to effectively combat a potential influenza pandemic. The purpose of the present study was to evaluate the Canadian pandemic influenza preparedness plan.

  20. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.


    antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally...... amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. Conclusions: A difference in predilection sites between SIV...

  1. Abbreviated Pandemic Influenza Planning Template for Primary Care Offices



    The Abbreviated Pandemic Influenza Plan Template for Primary Care Provider Offices is intended to assist primary care providers and office managers with preparing their offices for quickly putting a plan in place to handle an increase in patient calls and visits, whether during the 2009-2010 influenza season or future influenza seasons.

  2. Considerable progress in European preparations for a potential influenza pandemic.

    Paget, J.


    The threat of an influenza pandemic has been heightened in the past two years by outbreaks of avian influenza concentrated in South East Asia which have resulted in human deaths. So far, the avian influenza virus seems difficult to transmit from human to human, but changes in the virus genome may we

  3. Waves of El Nino-southern Oscillation and Influenza Pandemics

    Olusegun Steven Ayodele Oluwole


    Full Text Available Influenza pandemics have occurred at irregular intervals for over 500 years, unlike seasonal influenza epidemics which occur annually. Although the risk factors are known, the basis for the timing of influenza pandemic waves are unknown. Coherence of peaks of El Niño and influenza pandemic in 2009–2010, however, suggests that both waves are coupled. This study was done to determine the relation of influenza pandemics to the peaks and waveforms of El Niño southern oscillation (ENSO. ENSO cycles from 1871–2015 which had El Niño phases were windowed from Multivariate El Niño Index. Influenza pandemic peaks were mapped to ENSO monthly time series. ENSO waveforms were compared graphically, and fitted to nonstationary cosinor models. Second order polynomial regression model was fitted to the peak and duration of El Niño. Agglomerative hierarchical cluster of ENSO waveforms was performed. All influenza pandemic peaks mapped to El Niño peaks, with lags of 0–5 months. ENSO waveforms during influenza pandemics share parameters of oscillation. Nonstationary cosinor models showed that ENSO cycles are complex waves. There was second order polynomial relationship between peak and duration of El Niños, p < 0.0001. ENSO waveforms clustered into four distinct groups. ENSO waveforms during influenza pandemics of 1889–1900, 1957–1958, and 1968–1969 linked closely. ENSO indices were significantly high from 7–16 months after onset of cycles, p < 0.0001. Surveillance for El Niño events to forecast periods of maximal transmission and survival of influenza A viruses is, therefore, crucial for public health control strategies.

  4. [Ethical principles of management and planning during influenza pandemic].

    Kubar', O I; Asatrian, A Zh


    The article is dedicated to an actual problem of ethical component inclusion into the system of management and planning of epidemic control measures during threat emergence and in the course of influenza pandemic (epidemic) progress. Data regarding development of international ethical guidelines during influenza including WHO recommendations are presented and analysis of normative documents in Russian Federation is given. A necessity of comprehension and accounting of ethical values in pandemic preparedness is shown, main directions of action and responsibility are revealed. Key ethical positions of planning and implementation of measures during influenza pandemic are outlined, compliance with those determines the level of public support and thus provides the effectiveness of the implemented measures.

  5. Early assessment of anxiety and behavioral response to novel swine-origin influenza A(H1N1.

    James Holland Jones

    Full Text Available BACKGROUND: Since late April, 2009, a novel influenza virus A (H1N1, generally referred to as the "swine flu," has spread around the globe and infected hundreds of thousands of people. During the first few days after the initial outbreak in Mexico, extensive media coverage together with a high degree of uncertainty about the transmissibility and mortality rate associated with the virus caused widespread concern in the population. The spread of an infectious disease can be strongly influenced by behavioral changes (e.g., social distancing during the early phase of an epidemic, but data on risk perception and behavioral response to a novel virus is usually collected with a substantial delay or after an epidemic has run its course. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from an online survey that gathered data (n = 6,249 about risk perception of the Influenza A(H1N1 outbreak during the first few days of widespread media coverage (April 28-May 5, 2009. We find that after an initially high level of concern, levels of anxiety waned along with the perception of the virus as an immediate threat. Overall, our data provide evidence that emotional status mediates behavioral response. Intriguingly, principal component analysis revealed strong clustering of anxiety about swine flu, bird flu and terrorism. All three of these threats receive a great deal of media attention and their fundamental uncertainty is likely to generate an inordinate amount of fear vis-a-vis their actual threat. CONCLUSIONS/SIGNIFICANCE: Our results suggest that respondents' behavior varies in predictable ways. Of particular interest, we find that affective variables, such as self-reported anxiety over the epidemic, mediate the likelihood that respondents will engage in protective behavior. Understanding how protective behavior such as social distancing varies and the specific factors that mediate it may help with the design of epidemic control strategies.

  6. Barriers to pandemic influenza vaccination and uptake of seasonal influenza vaccine in the post-pandemic season in Germany

    Böhmer Merle M


    Full Text Available Abstract Background In Germany, annual vaccination against seasonal influenza is recommended for certain target groups (e.g. persons aged ≥60 years, chronically ill persons, healthcare workers (HCW. In season 2009/10, vaccination against pandemic influenza A(H1N1pdm09, which was controversially discussed in the public, was recommended for the whole population. The objectives of this study were to assess vaccination coverage for seasonal (seasons 2008/09-2010/11 and pandemic influenza (season 2009/10, to identify predictors of and barriers to pandemic vaccine uptake and whether the controversial discussions on pandemic vaccination has had a negative impact on seasonal influenza vaccine uptake in Germany. Methods We analysed data from the ‘German Health Update’ (GEDA10 telephone survey (n=22,050 and a smaller GEDA10-follow-up survey (n=2,493, which were both representative of the general population aged ≥18 years living in Germany. Results Overall only 8.8% of the adult population in Germany received a vaccination against pandemic influenza. High socioeconomic status, having received a seasonal influenza shot in the previous season, and belonging to a target group for seasonal influenza vaccination were independently associated with the uptake of pandemic vaccines. The main reasons for not receiving a pandemic vaccination were ‘fear of side effects’ and the opinion that ‘vaccination was not necessary’. Seasonal influenza vaccine uptake in the pre-pandemic season 2008/09 was 52.8% among persons aged ≥60 years; 30.5% among HCW, and 43.3% among chronically ill persons. A decrease in vaccination coverage was observed across all target groups in the first post-pandemic season 2010/11 (50.6%, 25.8%, and 41.0% vaccination coverage, respectively. Conclusions Seasonal influenza vaccination coverage in Germany remains in all target groups below 75%, which is a declared goal of the European Union. Our results suggest that controversial

  7. Surveillance of influenza in Iceland during the 2009 pandemic.

    Sigmundsdottir, G; Gudnason, T; Ólafsson, Ö; Baldvinsdottir, G E; Atladottir, A; Löve, A; Danon, L; Briem, H


    In a pandemic setting, surveillance is essential to monitor the spread of the disease and assess its impact. Appropriate mitigation and healthcare preparedness strategies depend on fast and accurate epidemic surveillance data. During the 2009 influenza A(H1N1) pandemic, rapid improvements in influenza surveillance were made in Iceland. Here, we describe the improvements made in influenza surveillance during the pandemic , which could also be of great value in outbreaks caused by other pathogens. Following the raised level of pandemic influenza alert in April 2009, influenza surveillance was intensified. A comprehensive automatic surveillance system for influenza-like illness was developed, surveillance of influenza-related deaths was established and laboratory surveillance for influenza was strengthened. School absenteeism reports were also collected and compared with results from the automatic surveillance system. The first case of 2009 pandemic influenza A(H1N1) was diagnosed in Iceland in May 2009, but sustained community transmission was not confirmed until mid-August. The pandemic virus circulated during the summer and early autumn before an abrupt increase in the number of cases was observed in October. There were large outbreaks in elementary schools for children aged 6–15 years throughout the country that peaked in late October. School absenteeism reports from all elementary schools in Iceland gave a similar epidemiological curve as that from data from the healthcare system. Estimates of the proportion of the population infected with the pandemic virus ranged from 10% to 22%. This study shows how the sudden need for improved surveillance in the pandemic led to rapid improvements in data collection in Iceland. This reporting system will be improved upon and expanded to include other notifiable diseases, to ensure accurate and timely collection of epidemiological data.

  8. Metabolic syndrome as an independent risk factor of hypoxaemia in influenza A (H1N1) 2009 pandemic.

    Bijani, Behzad; Pahlevan, Ali Asghar; Qasemi-Barqi, Reza; Jahanihashemi, Hassan


    A swine-origin influenza A (H1N1) emerged as a pandemic in 2009. We investigated the association between the overweight, metabolic syndrome and the severity of disease in the confirmed cases in Qazvin province, Iran. The study sample included all patients over 12 years old with confirmed influenza A (H1N1) in the province of Qazvin, Iran, in the 2009 pandemic, excluding pregnant women. To define overweight, sex and age-specific body mass index (BMI) cutoffs recommended by the International Obesity Task Force were used. Metabolic syndrome was defined by ATP III criteria. Multiple logistic regression analysis was performed to identify statistically independent predictors of hypoxaemia. Out of 55 confirmed cases, 28 (50.9%) were overweight and 24 (45.3%) were identified as having metabolic syndrome by ATP III criteria. Twenty four patients had hypoxaemia (arterial oxygen saturation below 90%) during the course of the disease. In multivariate logistic regression analysis, pulmonary co-morbidity (OR=9.54; 95% CI, 1.36 to 66.88; p= 0.023) and the metabolic syndrome (OR=18.66; 95% CI, 1.60 to 217.47; p= 0.019) were revealed to be independent risk factors for hypoxaemia in influenza A (H1N1) pdm09. The results of the present study reveal the role of the metabolic syndrome on the severity of influenza A (H1N1) pdm09 infection.

  9. Global Mortality Impact of the 1957-1959 Influenza Pandemic

    Viboud, Cécile; Simonsen, Lone; Fuentes, Rodrigo


    BACKGROUND: Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics. METHODS: We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background lev...

  10. Pandemic influenza dynamics and the breakdown of herd immunity.

    Katriel, Guy; Stone, Lewi


    Few if any attempts have been made to derive forecasts for the ongoing H1N1 pandemic as extrapolated from knowledge of seasonal influenza. Even simple back-of-the-envelope calculations are lacking. In this note we use first-approximation parameter estimates for the SIR model to compare seasonal and pandemic influenza, and then explore the implications of the existing classical epidemiological theory. In particular, we note the dramatic nonlinear increase in attack rate as a function of the percentage of susceptibles initially present in the population. This has severe consequences for the pandemic, given the general lack of immunity in the global population.

  11. Pandemic influenza vaccines and neuraminidase inhibitors: efficacy and side effects.

    Bijl, D


    At the time of the outbreak of the pandemic of New Influenza A (H1N1) pandemic influenza vaccines became available via an accelerated registration procedure. In 2005 large stocks of the neuraminidase inhibitor oseltamivir were built up in the Netherlands and other western countries. There was considerable doubt about the efficacy of this medicine. Initially reported positive effects of the drug were largely based on unpublished research, which was sponsored by the manufacturer and was partially written by ghostwriters. There now have been reports of rare and serious side effects. The first reports on the severity of the pandemic in Australia and New Zealand indicated a mild course.

  12. High-resolution computed tomography findings of swine-origin influenza A (H1N1) virus (S-OIV) infection: comparison with scrub typhus

    Jo, Bang Sil; Lee, In Jae; Lee, Kwanseop [Dept. of Radiology, Hallym Univ. College of Medicine, Seoul (Korea, Republic of)], E-mail:; Im, Hyoung June [Dept. of Occupational Medicine, Hallym Univ. College of Medicine, Seoul (Korea, Republic of)


    Background. Swine-origin influenza A (H1N1) virus (S-OIV) infection and scrub typhus, also known as tsutsugamushi disease can manifest as acute respiratory illnesses, particularly during the late fall or early winter, with similar radiographic findings, such as a predominance of ground-glass opacity (GGO). Purpose. To differentiate S-OIV infection from scrub typhus using high-resolution computed tomography (HRCT). Material and Methods. We retrospectively reviewed the HRCT findings of 14 patients with S-OIV infection and 10 patients with scrub typhus. We assessed the location, cross-sectional distribution, and the presence of a peribronchovascular distribution of GGO and consolidations on HRCT. We also assessed the presence of interlobular septal thickening, bronchial wall thickening, pneumothorax, pneumomediastinum, pleural effusion, and mediastinal or axillary lymph node enlargement. Results. Scrub typhus was more common than S-OIV in elderly patients (P < 0.001). The monthly incidences of S-OIV and scrub typhus infection reached a peak between October and November. About 86% of S-OIV patients and 80% of scrub typhus patients presented with GGO. About 67% of the GGO lesions in S-OIV had a peribronchovascular distribution, but this was absent in scrub typhus (P = 0.005). Consolidation (93% vs. 10%, P < 0.001) and bronchial wall thickening (43% vs. 0%, P = 0.024) were more frequent in S-OIV infection than scrub typhus. Interlobular septal thickening (90% vs. 36%, P = 0.013) and axillary lymphadenopathy (90% vs. 0%, P < 0.001) were more common in scrub typhus than S-OIV infection. Conclusion. There was considerable overlap in HRCT findings between S-OIV infection and scrub typhus. However, S-OIV showed a distinctive peribronchovascular distribution of GGO lesions. Consolidation and bronchial wall thickening were seen more frequently in S-OIV infection, whereas interlobular septal thickening and axillary lymphadenopathy were more common in scrub typhus. Thus, CT could

  13. Preparedness planning for pandemic influenza among large US maternity hospitals

    A Akers


    Full Text Available The objective of this investigation was to determine the state of pandemic influenza preparedness and to delineate commonly reported challenges among a sample of larger US national maternity hospitals. This was done given the recent emphasis on hospital disaster planning and the disproportionate morbidity and mortality that pregnant women have suffered in previous influenza pandemics. An internet-based survey was sent to all 12 members of the Council of Women's and Infants' Specialty Hospitals. Questions addressed hospital demographics and overall pandemic preparedness planning, including presence of a pandemic planning committee and the existence of written plans addressing communications, surge capacity, degradation of services, and advance supply planning. Nine of 12 (75% hospitals responded. All had active pandemic planning committees with identified leadership. The majority (78% had written formal plans regarding back-up communications, surge/overflow capacity, and degradation of services. However, fewer (44% reported having written plans in place regarding supply-line/stockpiling of resources. The most common challenges noted were staff and supply coordination, ethical distribution of limited medical resources, and coordination with government agencies. In conclusion, the majority of the Council of Women's and Infants' Specialty Hospitals maternity hospitals have preliminary infrastructure for pandemic influenza planning, but many challenges exist to optimize maternal and fetal outcomes during the next influenza pandemic.

  14. Genetic Analysis of Influenza A/H1N1 of Swine Origin Virus (SOIV) Circulating in Central and South America

    Sovero, Merly; Garcia, Josefina; Laguna-Torres, V. Alberto; Gomez, Jorge; Aleman, Washington; Chicaiza, Wilson; Barrantes, Melvin; Sanchez, Felix; Jimenez, Mirna; Comach, Guillermo; de Rivera, Ivette Lorenzana; Barboza, Alma; Aguayo, Nicolas; Kochel, Tadeusz


    Since the first detection of swine origin virus (SOIV) on March 28, 2009, the virus has spread worldwide and oseltamivir-resistant strains have already been identified in the past months. Here, we show the phylogenetic analysis of 63 SOIV isolates from eight countries in Central and South America, and their sensitivity to oseltamivir. PMID:20810843

  15. The Benefits and Risks of Pandemic Influenza Vaccines

    E.G. Wijnans (Leonoor)


    markdownabstractIn 2009 and 2010 the world experienced the first influenza pandemic of the 21st century. As the new influenza A(H1N1)pdm09 virus spread across the world, vaccines were being produced and licensed at an unprecedented scale and speed. In Europe, adjuvanted and non-adjuvanted H1N1pdm09

  16. Evidence for history-dependence of influenza pandemic emergence

    Hill, Edward M.; Tildesley, Michael J.; House, Thomas


    Influenza A viruses have caused a number of global pandemics, with considerable mortality in humans. Here, we analyse the time periods between influenza pandemics since 1700 under different assumptions to determine whether the emergence of new pandemic strains is a memoryless or history-dependent process. Bayesian model selection between exponential and gamma distributions for these time periods gives support to the hypothesis of history-dependence under eight out of nine sets of modelling assumptions. Using the fitted parameters to make predictions shows a high level of variability in the modelled number of pandemics from 2010–2110. The approach we take here relies on limited data, so is uncertain, but it provides cheap, safe and direct evidence relating to pandemic emergence, a field where indirect measurements are often made at great risk and cost.

  17. Pandemic influenza: human rights, ethics and duty to treat.

    Pahlman, I; Tohmo, H; Gylling, H


    The 2009 influenza A/H1N1 pandemic seems to be only moderately severe. In the future, a pandemic influenza with high lethality, such as the Spanish influenza in 1918-1919 or even worse, may emerge. In this kind of scenario, lethality rates ranging roughly from 2% to 30% have been proposed. Legal and ethical issues should be discussed before the incident. This article aims to highlight the legal, ethical and professional aspects that might be relevant to anaesthesiologists in the case of a high-lethality infectious disease such as a severe pandemic influenza. The epidemiology, the role of anaesthesiologists and possible threats to the profession and colleagueship within medical specialties relevant to anaesthesiologists are reviewed. During historical plague epidemics, some doctors have behaved like 'deserters'. However, during the Spanish influenza, physicians remained at their jobs, although many perished. In surveys, more than half of the health-care workers have reported their willingness to work in the case of severe pandemics. Physicians have the same human rights as all citizens: they have to be effectively protected against infectious disease. However, they have a duty to treat. Fair and responsible colleagueship among the diverse medical specialties should be promoted. Until disaster threatens humanity, volunteering to work during a pandemic might be the best way to ensure that physicians and other health-care workers stay at their workplace. Broad discussion in society is needed.

  18. Molecular detection and typing of influenza viruses : Are we ready for an influenza pandemic?

    MacKay, W. G.; van Loon, A. M.; Niedrig, M.; Meijer, A.; Lina, B.; Niesters, H. G. M.


    Background: We cannot predict when an influenza pandemic will occur or which variant of the virus will cause it. Little information is currently available on the ability of laboratories to detect and subtype influenza viruses including the avian influenza viruses. Objectives: To assess the ability o

  19. Molecular detection and typing of influenza viruses. Are we ready for an influenza pandemic?

    MacKay, W.G.; Loon, A.M. van; Niedrig, M.; Meijer, A.; Lina, B.; Niesters, H.G.M.


    BACKGROUND: We cannot predict when an influenza pandemic will occur or which variant of the virus will cause it. Little information is currently available on the ability of laboratories to detect and subtype influenza viruses including the avian influenza viruses. OBJECTIVES: To assess the ability o

  20. An Agent-Based Modeling for Pandemic Influenza in Egypt

    Khalil, Khaled M; Nazmy, Taymour T; Salem, Abdel-Badeeh M


    Pandemic influenza has great potential to cause large and rapid increases in deaths and serious illness. The objective of this paper is to develop an agent-based model to simulate the spread of pandemic influenza (novel H1N1) in Egypt. The proposed multi-agent model is based on the modeling of individuals' interactions in a space time context. The proposed model involves different types of parameters such as: social agent attributes, distribution of Egypt population, and patterns of agents' interactions. Analysis of modeling results leads to understanding the characteristics of the modeled pandemic, transmission patterns, and the conditions under which an outbreak might occur. In addition, the proposed model is used to measure the effectiveness of different control strategies to intervene the pandemic spread.

  1. Avian influenza A viruses: from zoonosis to pandemic.

    Richard, Mathilde; de Graaf, Miranda; Herfst, Sander


    Zoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in poultry in numerous countries in Europe, Asia and Africa, and the recently emerged H7N9 viruses in China, due to their relatively high number of human fatalities and pandemic potential. To start a pandemic, zoonotic influenza A viruses should not only acquire the ability to attach to, enter and replicate in the critical target cells in the respiratory tract of the new host, but also efficiently spread between humans by aerosol or respiratory droplet transmission. Here, we discuss the latest advances on the genetic and phenotypic determinants required for avian influenza A viruses to adapt to and transmit between mammals.

  2. The securitisation of pandemic influenza: framing, security and public policy.

    Kamradt-Scott, Adam; McInnes, Colin


    This article examines how pandemic influenza has been framed as a security issue, threatening the functioning of both state and society, and the policy responses to this framing. Pandemic influenza has long been recognised as a threat to human health. Despite this, for much of the twentieth century it was not recognised as a security threat. In the decade surrounding the new millennium, however, the disease was successfully securitised with profound implications for public policy. This article addresses the construction of pandemic influenza as a threat. Drawing on the work of the Copenhagen School, it examines how it was successfully securitised at the turn of the millennium and with what consequences for public policy.

  3. Likely Correlation between Sources of Information and Acceptability of A/H1N1 Swine-Origin Influenza Virus Vaccine in Marseille, France

    Ninove, Laetitia; Sartor, Catherine; Badiaga, Sékéné; Botelho, Elizabeth; Brouqui, Philippe; Zandotti, Christine; De Lamballerie, Xavier; La Scola, Bernard; Drancourt, Michel; Gould, Ernest A.; Charrel, Rémi N.; Raoult, Didier


    Background In France, there was a reluctance to accept vaccination against the A/H1N1 pandemic influenza virus despite government recommendation and investment in the vaccine programme. Methods and Findings We examined the willingness of different populations to accept A/H1N1vaccination (i) in a French hospital among 3315 employees immunized either by in-house medical personnel or mobile teams of MDs and (ii) in a shelter housing 250 homeless persons. Google was used to assess the volume of enquiries concerning incidence of influenza. We analyzed the information on vaccination provided by Google, the website of the major French newspapers, and PubMed. Two trust Surveys were used to assess public opinion on the trustworthiness of people in different professions. Paramedics were significantly more reluctant to accept immunisation than qualified medical staff. Acceptance was significantly increased when recommended directly by MDs. Anecdotal cases of directly observed severe infections were followed by enhanced acceptance of paramedical staff. Scientific literature was significantly more in favour of vaccination than Google and French newspaper websites. In the case of the newspaper websites, information correlated with their recognised political reputations, although they would presumably claim independence from political bias. The Trust Surveys showed that politicians were highly distrusted in contrast with doctors and pharmacists who were considered much more trustworthy. Conclusions The low uptake of the vaccine could reflect failure to convey high quality medical information and advice relating to the benefits of being vaccinated. We believe that the media and internet contributed to this problem by raising concerns within the general population and that failure to involve GPs in the control programme may have been a mistake. GPs are highly regarded by the public and can provide face-to-face professional advice and information. The top-down strategy of vaccine

  4. An Agent-Based Modeling for Pandemic Influenza in Egypt

    Khalil, Khaled M.; Abdel-Aziz, M.; Nazmy, Taymour T.; Salem, Abdel-Badeeh M.


    Pandemic influenza has great potential to cause large and rapid increases in deaths and serious illness. The objective of this paper is to develop an agent-based model to simulate the spread of pandemic influenza (novel H1N1) in Egypt. The proposed multi-agent model is based on the modeling of individuals' interactions in a space time context. The proposed model involves different types of parameters such as: social agent attributes, distribution of Egypt population, and patterns of agents' i...

  5. Community Assessment Tool for Public Health Emergencies Including Pandemic Influenza



    The Community Assessment Tool (CAT) for Public Health Emergencies Including Pandemic Influenza (hereafter referred to as the CAT) was developed as a result of feedback received from several communities. These communities participated in workshops focused on influenza pandemic planning and response. The 2008 through 2011 workshops were sponsored by the Centers for Disease Control and Prevention (CDC). Feedback during those workshops indicated the need for a tool that a community can use to assess its readiness for a disaster—readiness from a total healthcare perspective, not just hospitals, but the whole healthcare system. The CAT intends to do just that—help strengthen existing preparedness plans by allowing the healthcare system and other agencies to work together during an influenza pandemic. It helps reveal each core agency partners' (sectors) capabilities and resources, and highlights cases of the same vendors being used for resource supplies (e.g., personal protective equipment [PPE] and oxygen) by the partners (e.g., public health departments, clinics, or hospitals). The CAT also addresses gaps in the community's capabilities or potential shortages in resources. While the purpose of the CAT is to further prepare the community for an influenza pandemic, its framework is an extension of the traditional all-hazards approach to planning and preparedness. As such, the information gathered by the tool is useful in preparation for most widespread public health emergencies. This tool is primarily intended for use by those involved in healthcare emergency preparedness (e.g., community planners, community disaster preparedness coordinators, 9-1-1 directors, hospital emergency preparedness coordinators). It is divided into sections based on the core agency partners, which may be involved in the community's influenza pandemic influenza response.

  6. Avian influenza A viruses: From zoonosis to pandemic

    M. Richard (Mathilde); M.T. de Graaf (Marieke); S. Herfst (Sander)


    textabstractZoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in poul

  7. INFLUENZA A H1N1 DE ORIGEN PORCINO: Métodos diagnósticos Influenza A H1N1 swine origin: diagnostic methods

    Manuel Antonio Vargas-Córdoba


    Full Text Available El diagnóstico de la infección por virus influenza reposa sobre técnicas virológicas directas e indirectas. Las diferentes pruebas diagnósticas poseen niveles de sensibilidad y especificidad variables que dependen en gran parte de las características genéticas y antigénicas del virus circulante. En el caso de la aparición de una nueva variante viral las pruebas disponibles en el mercado deben ser validadas para comprobar su eficiencia de detección para el nuevo virus. En caso de baja sensibilidad y especificidad, las pruebas deben ajustarse con el fin de mejorar su poder de detección del nuevo agente. Existen múltiples pruebas diagnósticas que presentan cada una sus ventajas y limitaciones y su selección dependerá de las condiciones específicas de cada laboratorio diagnóstico.The diagnosis of infection by influenza viruses relays on direct and indirect virologic techniques. Different diagnostic tests have variable sensitivities and specificities depending to a large extent on the genetic and antigenic features of the circulating virus. When a new viral variant appears, commercially available tests must be validated in order to verify their performance at detecting the new virus. If a low sensitivity or specificity is found, tests must be adjusted in order to improve their detection power for the new agent. There are multiple diagnostic tests, each one with its own advantages and limitations; so the selection of a test will depend on the specific conditions of a particular diagnostic laboratory.

  8. Optimal Allocation of Pandemic Influenza Vaccine Depends on Age, Risk and Timing

    Mylius, S.D.; Hagenaars, T.H.J.; Lugner, A.K.; Wallinga, J.


    The limited production capacity for vaccines raises the question what the best strategy is for allocating the vaccine to mitigate an influenza pandemic. We developed an age-structured model for spread of an influenza pandemic and validated it against observations from the Asian flu pandemic. Two str

  9. Spatial Transmission of 2009 Pandemic Influenza in the US.

    Julia R Gog


    Full Text Available The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed examination of the spatial dynamics of an emerging pathogen. In the US, the pandemic was characterized by substantial geographical heterogeneity: the 2009 spring wave was limited mainly to northeastern cities while the larger fall wave affected the whole country. Here we use finely resolved spatial and temporal influenza disease data based on electronic medical claims to explore the spread of the fall pandemic wave across 271 US cities and associated suburban areas. We document a clear spatial pattern in the timing of onset of the fall wave, starting in southeastern cities and spreading outwards over a period of three months. We use mechanistic models to tease apart the external factors associated with the timing of the fall wave arrival: differential seeding events linked to demographic factors, school opening dates, absolute humidity, prior immunity from the spring wave, spatial diffusion, and their interactions. Although the onset of the fall wave was correlated with school openings as previously reported, models including spatial spread alone resulted in better fit. The best model had a combination of the two. Absolute humidity or prior exposure during the spring wave did not improve the fit and population size only played a weak role. In conclusion, the protracted spread of pandemic influenza in fall 2009 in the US was dominated by short-distance spatial spread partially catalysed by school openings rather than long-distance transmission events. This is in contrast to the rapid hierarchical transmission patterns previously described for seasonal influenza. The findings underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza and highlight the need for further information on the movement and mixing patterns of this age group.

  10. Pandemic controllability: a concept to guide a proportionate and flexible operational response to future influenza pandemics.

    McCaw, J M; Glass, K; Mercer, G N; McVernon, J


    The 2009 H1N1 influenza pandemic posed challenges for governments worldwide. Strategies designed to limit community transmission, such as antiviral deployment, were largely ineffective due to both feasibility constraints and the generally mild nature of disease, resulting in incomplete case ascertainment. Reviews of national pandemic plans have identified pandemic impact, primarily linked to measures of transmissibility and severity, as a key concept to incorporate into the next generation of plans. While an assessment of impact provides the rationale under which interventions may be warranted, it does not directly provide an assessment on whether particular interventions may be effective. Such considerations motivate our introduction of the concept of pandemic controllability. For case-targeted interventions, such as antiviral treatment and post-exposure prophylaxis, we identify the visibility and transmissibility of a pandemic as the key drivers of controllability. Taking a case-study approach, we suggest that high-impact pandemics, for which control is most desirable, are likely uncontrollable with case-targeted interventions. Strategies that do not rely on the identification of cases may prove relatively more effective. By introducing a pragmatic framework for relating the assessment of impact to the ability to mitigate an epidemic (controllability), we hope to address a present omission identified in pandemic response plans.

  11. Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

    Fordyce, Sarah L; Bragstad, Karoline; Pedersen, Svend Stenvang;


    Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly...... respond to selection pressures, such as those imposed by the immunological host response and antiviral therapy. We have applied deep sequencing to characterize influenza intra-host variation in a transmission chain consisting of three cases due to oseltamivir-sensitive viruses, and one derived oseltamivir...

  12. The pandemic subject: Canadian pandemic plans and communicating with the public about an influenza pandemic.

    Maunula, Laena


    In this paper, I examine the goals for pandemic public communication as outlined in two Canadian plans for pandemic planning and infection control. I critique these strategies by drawing on Foucault's notions of governmentality and biopower. My argument is that the public health communication campaign goals reviewed rest upon a particular conceptualization of health in the context of pandemic planning as an individual/family duty, and that scientific/medical expert knowledge is most appropriate for guiding pandemic planning. This study contributes to a sociological understanding of how pandemic preparedness and infection control are represented in Canadian pandemic plans, how public health shapes pandemic communication messages in Canada, and the implications of those messages for subjectivity and notions of citizenship.

  13. Which factors are important in adults' uptake of a (pre)pandemic influenza vaccine?

    Zijtregtop, E A M; Wilschut, J; Koelma, N; Van Delden, J J M; Stolk, R P; Van Steenbergen, J; Broer, J; Wolters, B; Postma, Maarten; Hak, E


    Since 2008, (pre)pandemic vaccines against H5N1 influenza have been available and pandemic vaccines against new influenza H1N1 are currently produced In The Netherlands. the vaccination call for seasonal influenza among the recommended groups approximates 70% These statistics raise the question if a

  14. IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A(H1N1)Virus

    Chenggang Li; Chen Wang; Zhongwei Chen; Li Xing; Chong Tang; Xiangwu Ju; Feng Guo; Jiejie Deng; Yan Zhao; Peng Yang; Jun Tang; Penghui Yang; Huanling Wang; Zhongpeng Zhao; Zhinan Yin; Bin Cao; Xiliang Wang; Chengyu Jiang; Yang Sun; Taisheng Li; Chen Wang; Zhong Wang; Zhen Zou; Yiwu Yan; Wei Wang


    The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus(S-OIV H1N1)that infected almost every country in the world.Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury.In this report,we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease.The clinical efficacy of the antiviral oseltamivir(Tamiflu)administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model.Moreover,elevated levels of IL-17,Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing.IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice.These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics.

  15. H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.

    Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui


    The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.

  16. Diagnosis of 2009 Pandemic Influenza A (pH1N1) and Seasonal Influenza Using Rapid Influenza Antigen Tests, San Antonio, Texas, April-June 2009


    CDC Atlanta US. CDC protocol of realtime RTPCR for influenza A(H1N1) revision 1. 30 April 2009. Available at: csr / resources...2009; 325:483–7. 24. Munster VJ, de Wit E, van den Brand JM, et al. Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in Fer

  17. Nonpharmaceutical Interventions for Military Populations During Pandemic Influenza

    Selim Kilic


    Full Text Available Influenza causes substantial illness and loss of work days among young adults, and outbreaks can affect the preparedness of military units. In an influenza pandemic, people who live in confined settings have greater risk of infection. Military trainees are at particularly high risk. Because of likely unavailability of vaccines and antiviral drugs at the start of a pandemic and for many months thereafter, nonpharmaceutical interventions may be very important. During a pandemic, it seems prudent that military public health officials employ at least several nonpharmaceutical interventions. For example frequent handwashing and respiratory hygiene/cough etiquette should be strongly encouraged among soldiers. Head-to-toe sleeping, a “no-cost” intervention should be for crowded berthing areas. Isolation of patients with influenza and quarantine of their close contacts should be employed. Masks and alcohol-based hand rubs may be employed among those at highest risk. Finally, whenever possible military planners should, reduce crowding and limit the interaction of training cohorts to reduce risk of influenza virus transmission. [TAF Prev Med Bull. 2007; 6(4: 285-290

  18. Increase human metapneumovirus mediated morbidity following pandemic influenza infection.

    Liora Regev

    Full Text Available Human metapneumovirus (hMPV is a recently discovered respiratory pathogen, infecting mainly young children. The infected patients suffer from influenza like symptoms (ILS. In Israel the virus is mainly circulating in February to March. Here we report on an increased rate of hMPV infection in the winter season of 2009-10. The 2009-10 infection had several unique characteristics when compared to previous seasons; it started around January and a large number of infants were infected by the virus. Genetic analysis based on the viral L and F genes of hMPV showed that only subtypes A2 and B2 circulated in Israel. Additionally, we have identified a novel variant of hMPV within subgroup A2b, which subdivide it into A2b1 and A2b2. Finally, we showed that the hMPV infection was detected in the country soon after the infection with the pandemic influenza virus had declined, that infection with the pandemic influenza virus was dominant and that it interfered with the infection of other respiratory viruses. Thus, we suggest that the unusual increase in hMPV infection observed in 2009-10 was due to the appearance of the pandemic influenza virus in the winter season prior to 2009-10.

  19. The first influenza pandemic of the 21st century

    Al Hajjar, Sami; McIntosh, Kenneth


    The 2009 H1N1 influenza virus (formerly known as swine flu) first appeared in Mexico and the United States in March and April 2009 and has swept the globe with unprecedented speed as a result of airline travel. On June 11, 2009, the World Health Organization raised its pandemic level to the highest level, Phase 6, indicating widespread community transmission on at least two continents. The 2009 H1N1 virus contains a unique combination of gene segments from human, swine and avian influenza A v...

  20. Influenza A (H1N1) 2009: a pandemic alarm

    Madhu Khanna; Neha Gupta; Ankit Gupta; V K Vijayan


    At this critical juncture when the world has not yet recovered from the threat of avian influenza, the virus has returned in the disguise of swine influenza, a lesser known illness common in pigs. It has reached pandemic proportions in a short time span with health personnel still devising ways to identify the novel H1N1 virus and develop vaccines against it. The H1N1 virus has caused a considerable number of deaths within the short duration since its emergence. Presently, there are no effective methods to contain this newly emerged virus. Therefore, a proper and clear insight is urgently required to prevent an outbreak in the future and make preparations that may be planned well in advance. This review is an attempt to discuss the historical perspective of the swine flu virus, its epidemiology and route of transmission to better understand the various control measures that may be taken to fight the danger of a global pandemic.

  1. Influenza A pandemic (H1N1) 2009 virus infection

    BAI Lu; CAO Bin; WANG Chen


    The clinical spectrum of the 2009 pandemic influenza A (H1N1) infection ranged from self-limited mild illness to progressive pneumonia,or even a fatal outcome.We summarize the clinical manifestations,risk factors for severe and fatal cases,pathologic findings and treatment of this disease in this paper based on current reports from different regions of the world.

  2. Community Assessment Tool for Public Health Emergencies Including Pandemic Influenza

    ORAU' s Oak Ridge Institute for Science Education (HCTT-CHE)


    The Community Assessment Tool (CAT) for Public Health Emergencies Including Pandemic Influenza (hereafter referred to as the CAT) was developed as a result of feedback received from several communities. These communities participated in workshops focused on influenza pandemic planning and response. The 2008 through 2011 workshops were sponsored by the Centers for Disease Control and Prevention (CDC). Feedback during those workshops indicated the need for a tool that a community can use to assess its readiness for a disaster - readiness from a total healthcare perspective, not just hospitals, but the whole healthcare system. The CAT intends to do just that - help strengthen existing preparedness plans by allowing the healthcare system and other agencies to work together during an influenza pandemic. It helps reveal each core agency partners (sectors) capabilities and resources, and highlights cases of the same vendors being used for resource supplies (e.g., personal protective equipment [PPE] and oxygen) by the partners (e.g., public health departments, clinics, or hospitals). The CAT also addresses gaps in the community's capabilities or potential shortages in resources. This tool has been reviewed by a variety of key subject matter experts from federal, state, and local agencies and organizations. It also has been piloted with various communities that consist of different population sizes, to include large urban to small rural communities.

  3. Rapid detection of pandemic influenza in the presence of seasonal influenza

    Robertson Chris


    Full Text Available Abstract Background Key to the control of pandemic influenza are surveillance systems that raise alarms rapidly and sensitively. In addition, they must minimise false alarms during a normal influenza season. We develop a method that uses historical syndromic influenza data from the existing surveillance system 'SERVIS' (Scottish Enhanced Respiratory Virus Infection Surveillance for influenza-like illness (ILI in Scotland. Methods We develop an algorithm based on the weekly case ratio (WCR of reported ILI cases to generate an alarm for pandemic influenza. From the seasonal influenza data from 13 Scottish health boards, we estimate the joint probability distribution of the country-level WCR and the number of health boards showing synchronous increases in reported influenza cases over the previous week. Pandemic cases are sampled with various case reporting rates from simulated pandemic influenza infections and overlaid with seasonal SERVIS data from 2001 to 2007. Using this combined time series we test our method for speed of detection, sensitivity and specificity. Also, the 2008-09 SERVIS ILI cases are used for testing detection performances of the three methods with a real pandemic data. Results We compare our method, based on our simulation study, to the moving-average Cumulative Sums (Mov-Avg Cusum and ILI rate threshold methods and find it to be more sensitive and rapid. For 1% case reporting and detection specificity of 95%, our method is 100% sensitive and has median detection time (MDT of 4 weeks while the Mov-Avg Cusum and ILI rate threshold methods are, respectively, 97% and 100% sensitive with MDT of 5 weeks. At 99% specificity, our method remains 100% sensitive with MDT of 5 weeks. Although the threshold method maintains its sensitivity of 100% with MDT of 5 weeks, sensitivity of Mov-Avg Cusum declines to 92% with increased MDT of 6 weeks. For a two-fold decrease in the case reporting rate (0.5% and 99% specificity, the WCR and

  4. Pediatric Healthcare Response to Pandemic (H1N1) 2009 Influenza Stakeholder Meeting - Summary of Proceedings



    The goal of the meeting was to bring together subject matter experts to develop tools and resources for use by the pediatric healthcare community in response to 2009 (H1N1) pandemic influenza activity during the 2009 influenza season.

  5. Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis

    B. Ramezanpour (Bahar); E.S. Pronker (Esther); J.H.C.M. Kreijtz (Joost); A.D.M.E. Osterhaus (Albert); H.J.H.M. Claassen (Eric)


    textabstractA quantitative method is presented to rank strengths, weaknesses, opportunities, and threats (SWOT) of modified vaccinia virus Ankara (MVA) as a platform for pre-pandemic and pandemic influenza vaccines. Analytic hierarchy process (AHP) was applied to achieve pairwise comparisons among S

  6. Characterization of the 2009 pandemic A/Beijing/501/2009 H1N1 influenza strain in human airway epithelial cells and ferrets.

    Penghui Yang

    Full Text Available BACKGROUND: A novel 2009 swine-origin influenza A H1N1 virus (S-OIV H1N1 has been transmitted among humans worldwide. However, the pathogenesis of this virus in human airway epithelial cells and mammals is not well understood. METHODOLOGY/PRINCIPAL FINDING: In this study, we showed that a 2009 A (H1N1 influenza virus strain, A/Beijing/501/2009, isolated from a human patient, caused typical influenza-like symptoms including weight loss, fluctuations in body temperature, and pulmonary pathological changes in ferrets. We demonstrated that the human lung adenocarcinoma epithelial cell line A549 was susceptible to infection and that the infected cells underwent apoptosis at 24 h post-infection. In contrast to the seasonal H1N1 influenza virus, the 2009 A (H1N1 influenza virus strain A/Beijing/501/2009 induced more cell death involving caspase-3-dependent apoptosis in A549 cells. Additionally, ferrets infected with the A/Beijing/501/2009 H1N1 virus strain exhibited increased body temperature, greater weight loss, and higher viral titers in the lungs. Therefore, the A/Beijing/501/2009 H1N1 isolate successfully infected the lungs of ferrets and caused more pathological lesions than the seasonal influenza virus. Our findings demonstrate that the difference in virulence of the 2009 pandemic H1N1 influenza virus and the seasonal H1N1 influenza virus in vitro and in vivo may have been mediated by different mechanisms. CONCLUSION/SIGNIFICANCE: Our understanding of the pathogenesis of the 2009 A (H1N1 influenza virus infection in both humans and animals is broadened by our findings that apoptotic cell death is involved in the cytopathic effect observed in vitro and that the pathological alterations in the lungs of S-OIV H1N1-infected ferrets are much more severe.

  7. Pandemic influenza vaccines: meeting the supply, distribution and deployment challenges.

    Hessel, Luc


    An influenza pandemic will place an enormous strain on the world's vaccine production, distribution and administration systems. Following a pandemic declaration, industry's priority will be to deliver as much vaccine in as short a timeframe as possible. In respect to this challenge, manufacturers have successfully developed antigen-sparing strategies and significantly increased production capacity, with further growth planned assuming ongoing rising demand for seasonal vaccines. The combination of these factors has the potential to closer meet global needs for vaccine supply than ever before through increased availability of pandemic and pre-pandemic vaccines. The demonstration of cross-clade reactivity with H5N1 viruses makes the concept of pre-pandemic stockpiling and vaccination a reality for this subtype. Ensuring these vaccines are made available in a timely fashion to those who need them will present significant challenges. For local authorities, national governments and international organisations this means defining vaccine allocation and procurement processes as well as strengthening, and where necessary establishing, the critical health systems and infrastructure required for vaccine deployment. For vaccine producers this means addressing the technical and logistical issues associated with supply. This includes working with regulators to streamline key procedures, including generic labelling and batch release, while establishing flexibility in supply formats, including bulk and finished products, to maximise the speed of delivery. Similarly, the deployment of large quantities of vaccines in an emergency situation requires appropriate transport infrastructure and the distribution of associated medical supplies. As well as addressing these issues, specific consideration must be given to the logistics and storage aspects associated with stockpiling pre-pandemic vaccines. Finally, mutually agreed contractual arrangements between manufacturers and governments

  8. Economic Analysis of Pandemic Influenza Vaccination Strategies in Singapore

    Lee, Vernon J.; Tok, Mei Yin; Chow, Vincent T.; Phua, Kai Hong; Ooi, Eng Eong; Tambyah, Paul A.; Chen, Mark I.


    Background All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. Methodology We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. Principal Findings The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4–0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. Conclusions The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines. PMID:19771173

  9. Economic analysis of pandemic influenza vaccination strategies in Singapore.

    Vernon J Lee

    Full Text Available BACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. METHODOLOGY: We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay depending on the perceived risk of the next pandemic occurring. PRINCIPAL FINDINGS: The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. CONCLUSIONS: The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.

  10. Influenza pandemic preparedness: motivation for protection among small and medium businesses in Australia

    MacIntyre C Raina


    Full Text Available Abstract Background Community-wide preparedness for pandemic influenza is an issue that has featured prominently in the recent news media, and is currently a priority for health authorities in many countries. The small and medium business sector is a major provider of private sector employment in Australia, yet we have little information about the preparedness of this sector for pandemic influenza. This study aimed to investigate the association between individual perceptions and preparedness for pandemic influenza among small and medium business owners and managers. Methods Semi-structured face-to-face interviews were conducted with 201 small and medium business owners or managers in New South Wales and Western Australia. Eligible small or medium businesses were defined as those that had less than 200 employees. Binomial logistic regression analysis was used to identify the predictors of having considered the impact of, having a plan for, and needing help to prepare for pandemic influenza. Results Approximately 6 per cent of participants reported that their business had a plan for pandemic influenza, 39 per cent reported that they had not thought at all about the impact of pandemic influenza on their business, and over 60 per cent stated that they required help to prepare for a pandemic. Beliefs about the severity of pandemic influenza and the ability to respond were significant independent predictors of having a plan for pandemic influenza, and the perception of the risk of pandemic influenza was the most important predictor of both having considered the impact of, and needing help to prepare for a pandemic. Conclusion Our findings suggest that small and medium businesses in Australia are not currently well prepared for pandemic influenza. We found that beliefs about the risk, severity, and the ability to respond effectively to the threat of pandemic influenza are important predictors of preparedness. Campaigns targeting small and medium

  11. Ethics for pandemics beyond influenza: Ebola, drug-resistant tuberculosis, and anticipating future ethical challenges in pandemic preparedness and response.

    Smith, Maxwell J; Silva, Diego S


    The unprecedented outbreak of Ebola virus disease (EVD) in West Africa has raised several novel ethical issues for global outbreak preparedness. It has also illustrated that familiar ethical issues in infectious disease management endure despite considerable efforts to understand and mitigate such issues in the wake of past outbreaks. To improve future global outbreak preparedness and response, we must examine these shortcomings and reflect upon the current state of ethical preparedness. To this end, we focus our efforts in this article on the examination of one substantial area: ethical guidance in pandemic plans. We argue that, due in part to their focus on considerations arising specifically in relation to pandemics of influenza origin, pandemic plans and their existing ethical guidance are ill-equipped to anticipate and facilitate the navigation of unique ethical challenges that may arise in other infectious disease pandemics. We proceed by outlining three reasons why this is so, and situate our analysis in the context of the EVD outbreak and the threat posed by drug-resistant tuberculosis: (1) different infectious diseases have distinct characteristics that challenge anticipated or existing modes of pandemic prevention, preparedness, response, and recovery, (2) clear, transparent, context-specific ethical reasoning and justification within current influenza pandemic plans are lacking, and (3) current plans neglect the context of how other significant pandemics may manifest. We conclude the article with several options for reflecting upon and ultimately addressing ethical issues that may emerge with different infectious disease pandemics.

  12. Response to the 2009 influenza A(H1N1) pandemic in Italy.

    Rizzo, C; Rota, M C; Bella, A; Giannitelli, S; De Santis, S; Nacca, G; Pompa, M G; Vellucci, L; Salmaso, S; Declich, S


    In Italy, the arrival of the 2009 pandemic influenza A(H1N1) virus triggered an integrated response that was mainly based on the 2006 National Pandemic Preparedness and Response Plan. In this article we analyse the main activities implemented for epidemiological surveillance, containment and mitigation of the pandemic influenza and the lesson learned from this experience. Overall, from week 31 (27 July – 2 August) of 2009 to week 17 (26 April – 2 May) of 2010, we estimate that there were approximately 5,600,000 cases of influenza-like illness (ILI) who received medical attention (with almost 2,000 laboratory-confirmed cases of pandemic influenza from May to October 2009). A total of 1,106 confirmed cases were admitted to hospital for serious conditions, of whom 532 were admitted to intensive care units. There were 260 reported deaths due to pandemic influenza. Approximately 870,000 first doses of the pandemic vaccine were administered, representing a vaccine coverage of 4% of the target population. One of the possible reasons for the low uptake of the pandemic vaccine in the target population could be the communication strategy adopted, for both the general population and healthcare workers, which turned out to be a major challenge. Active involvement of all health professionals (at local, regional and national level) in influenza pandemic preparedness and response should be encouraged in the future.

  13. Behavioural intentions in response to an influenza pandemic

    Schaalma Herman


    Full Text Available Abstract Background Little is known regarding which behavioural responses can be expected if an influenza pandemic were to occur. Methods A survey comprising questions based on risk perception theories, in particular PMT, was conducted with a Dutch sample. Results Although fear that an influenza pandemic may occur was high, participants do not feel well informed. General practitioners and local health authorities were considered trustworthy sources of information and the information considered most urgent pertained to which protective measures should be taken. Participants reported an intention to comply with recommendations regarding protective measures. However, response and self efficacy were low. Maladaptive behaviours can be expected. Increasing numbers of ill individuals and school closures are also expected to lead to a decreased work force. Participants indicated wanting antiviral drugs even if the supply were to be insufficient. Conclusions Messages regarding health protective behaviours from local health authorities should anticipate the balance between overreacting and underreacting. Also, when protective recommendations from health professionals conflict with company policies, it is unclear how employees will react.

  14. The 2015 global production capacity of seasonal and pandemic influenza vaccine.

    McLean, Kenneth A; Goldin, Shoshanna; Nannei, Claudia; Sparrow, Erin; Torelli, Guido


    A global shortage and inequitable access to influenza vaccines has been cause for concern for developing countries who face dire consequences in the event of a pandemic. The Global Action Plan for Influenza Vaccines (GAP) was launched in 2006 to increase global capacity for influenza vaccine production to address these concerns. It is widely recognized that well-developed infrastructure to produce seasonal influenza vaccines leads to increased capacity to produce pandemic influenza vaccines. This article summarizes the results of a survey administered to 44 manufacturers to assess their production capacity for seasonal influenza and pandemic influenza vaccine production. When the GAP was launched in 2006, global production capacity for seasonal and pandemic vaccines was estimated to be 500million and 1.5billion doses respectively. Since 2006 there has been a significant increase in capacity, with the 2013 survey estimating global capacity at 1.5billion seasonal and 6.2billion pandemic doses. Results of the current survey showed that global seasonal influenza vaccine production capacity has decreased since 2013 from 1.504billion doses to 1.467billion doses. However, notwithstanding the overall global decrease in seasonal vaccine capacity there were notable positive changes in the distribution of production capacity with increases noted in South East Asia (SEAR) and the Western Pacific (WPR) regions, albeit on a small scale. Despite a decrease in seasonal capacity, there has been a global increase of pandemic influenza vaccine production capacity from 6.2 billion doses in 2013 to 6.4 billion doses in 2015. This growth can be attributed to a shift towards more quadrivalent vaccine production and also to increased use of adjuvants. Pandemic influenza vaccine production capacity is at its highest recorded levels however challenges remain in maintaining this capacity and in ensuring access in the event of a pandemic to underserved regions.

  15. Household transmission of influenza A(H1N1pdm09 in the pandemic and post-pandemic seasons.

    Itziar Casado

    Full Text Available The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1pdm09 in the pandemic and post-pandemic seasons.During the 2009-2010 and 2010-2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1pdm09 to ask about the symptoms, risk factors and vaccination status of each household member.In the 405 households with a patient laboratory-confirmed for influenza A(H1N1pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14-19% presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009-2010 and 19% in the 2010-2011 season (p=0.049, an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010-2011 season than in the 2009-2010 season (adjusted odds ratio: 1.72; 95% CI 1.17-2.54, and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08-1.03.The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.

  16. Hygrothermal environment may cause influenza pandemics through immune suppression.

    Wu, Xian-Lin; Luo, Yu-Hong; Chen, Jia; Yu, Bin; Liu, Kang-Li; He, Jin-Xiong; Lu, Su-Hong; Li, Jie-Xing; Wu, Sha; Jiang, Zhen-You; Chen, Xiao-Yin


    Over the past few decades, climate warming has caused profound changes in our living environment, and human diseases, including infectious diseases, have also been influenced by these changes. However, it remains unclear if a warm-wet climate can influence the infectivity of influenza and result in influenza pandemics. This study focused on observations of how the hydrothermal environment influences the infectivity of the influenza virus and the resulting immunoreactions of the infected mice. We used a manual climatic box to establish the following 3 environments with different temperatures and humidity: normal environment (T: 24 ± 1°C, RH: 50% ± 4%), wet environment (T: 24 ± 1 °C, RH: 95% ± 4%) and warm-wet environment (T: 33 ± 1 °C, RH: 95% ± 4%), and the mice were fed and maintained in these 3 different environments. After 14 days, half of the mice were infected with H1N1 (A/FM1/1/47, a lung adapted strain of the flu virus specific for the mouse lung) virus for 4 d After establishing the animal model, we observed the microstructure of the lung tissue, the Th1/Th2 T cell subsets, the Th17/Treg balance, the expression of cytokines in the peripheral blood serum and the expression of the immune recognition RLH signal pathway. The results showed that mice in different environments have different reaction. Results showed that after infection, the proportion of Th1/Th2 and Th17/Treg cells in the spleen was significantly increased, and these proportions were increased the most in the infected group kept in wet-hot conditions. After infection, the mRNA levels and protein expression of the RLH (RIG-1-like helicases) signal pathway components were up-regulated while the uninfected animals in the 3 diverse environments showed no significant change. The infected mice kept in the wet and warm-wet environments showed a slight elevation in the expression of RLH pathway components compared to infected mice maintained in the normal environment. Our study suggested that

  17. Learning from the 2009 H1N1 pandemic: prospects for more broadly effective influenza vaccines

    Ethan C. Settembre; Philip R. Dormitzer; Rino Rappuoli


    Calls to develop a universal influenza vaccine have increased in the wake of the 2009 H1 N1 influenza pandemic. This demand comes at a time when analyses of the human antibody repertoire, informed by structures of complexes between broadly neutralizing antibodies and influenza hemagglutinin, have revealed the target of a class of broadly neutralizing antibodies. Recent studies suggest a path forward to more broadly protective influenza vaccines.%@@ Calls to develop a universal influenza vaccine have increased in the wake of the 2009 H1 N1 influenza pandemic.This demand comes at a time when analyses of the human antibody repertoire, informed by structures of complexes between broadly neutralizing antibodies and influenza hemagglutinin, have revealed the target of a class of broadly neutralizing antibodies.Recent studies suggest a path forward to more broadly protective influenza vaccines.

  18. Evaluation of Three Live Attenuated H2 Pandemic Influenza Vaccine Candidates in Mice and Ferrets


    H2 influenza viruses have not circulated in humans since 1968, and therefore a significant portion of the population would be susceptible to infection should H2 influenza viruses reemerge. H2 influenza viruses continue to circulate in avian reservoirs worldwide, and these reservoirs are a potential source from which these viruses could emerge. Three reassortant cold-adapted (ca) H2 pandemic influenza vaccine candidates with hemagglutinin (HA) and neuraminidase (NA) genes derived from the wild...

  19. Knowledge discovery and sequence-based prediction of pandemic influenza using an integrated classification and association rule mining (CBA) algorithm.

    Kargarfard, Fatemeh; Sami, Ashkan; Ebrahimie, Esmaeil


    Pandemic influenza is a major concern worldwide. Availability of advanced technologies and the nucleotide sequences of a large number of pandemic and non-pandemic influenza viruses in 2009 provide a great opportunity to investigate the underlying rules of pandemic induction through data mining tools. Here, for the first time, an integrated classification and association rule mining algorithm (CBA) was used to discover the rules underpinning alteration of non-pandemic sequences to pandemic ones. We hypothesized that the extracted rules can lead to the development of an efficient expert system for prediction of influenza pandemics. To this end, we used a large dataset containing 5373 HA (hemagglutinin) segments of the 2009 H1N1 pandemic and non-pandemic influenza sequences. The analysis was carried out for both nucleotide and protein sequences. We found a number of new rules which potentially present the undiscovered antigenic sites at influenza structure. At the nucleotide level, alteration of thymine (T) at position 260 was the key discriminating feature in distinguishing non-pandemic from pandemic sequences. At the protein level, rules including I233K, M334L were the differentiating features. CBA efficiently classifies pandemic and non-pandemic sequences with high accuracy at both the nucleotide and protein level. Finding hotspots in influenza sequences is a significant finding as they represent the regions with low antibody reactivity. We argue that the virus breaks host immunity response by mutation at these spots. Based on the discovered rules, we developed the software, "Prediction of Pandemic Influenza" for discrimination of pandemic from non-pandemic sequences. This study opens a new vista in discovery of association rules between mutation points during evolution of pandemic influenza.

  20. Pandemic and Avian Influenza A Viruses in Humans: Epidemiology, Virology, Clinical Characteristics, and Treatment Strategy.

    Li, Hui; Cao, Bin


    The intermittent outbreak of pandemic influenza and emergence of novel avian influenza A virus is worldwide threat. Although most patients present with mild symptoms, some deteriorate to severe pneumonia and even death. Great progress in the understanding of the mechanism of disease pathogenesis and a series of vaccines has been promoted worldwide; however, incidence, morbidity, and mortality remains high. To step up vigilance and improve pandemic preparedness, this article elucidates the virology, epidemiology, pathogenesis, clinical characteristics, and treatment of human infections by influenza A viruses, with an emphasis on the influenza A(H1N1)pdm09, H5N1, and H7N9 subtypes.

  1. Simulation to assess the efficacy of US airport entry scrreening of passengers for pandemic influenza

    Mcmahon, Benjamin [Los Alamos National Laboratory


    We present our methodology and stochastic discrete-event simulation developed to model the screening of passengers for pandemic influenza at the US port-of-entry airports. Our model uniquely combines epidemiology modelling, evolving infected states and conditions of passengers over time, and operational considerations of screening in a single simulation. The simulation begins with international aircraft arrivals to the US. Passengers are then randomly assigned to one of three states -- not infected, infected with pandemic influenza and infected with other respiratory illness. Passengers then pass through various screening layers (i.e. pre-departure screening, en route screening, primary screening and secondary screening) and ultimately exit the system. We track the status of each passenger over time, with a special emphasis on false negatives (i.e. passengers infected with pandemic influenza, but are not identified as such) as these passengers pose a significant threat as they could unknowingly spread the pandemic influenza virus throughout our nation.

  2. A Coordinated Approach to Communicating Pediatric-Related Information on Pandemic Influenza at the Community Level



    The purpose of this document is to provide a suggested approach, based on input from pediatric stakeholders, to communicating pediatric-related information on pandemic influenza at the community level in a step-by-step manner.

  3. [Pandemic without drama. Influenza vaccination and Asian flu in Germany].

    Witte, Wilfried


    The history of the 1957/58 Asian flu in Germany is systematically presented for the first time. The focus is on flu vaccination, which is discussed as a yardstick of the perception of the pandemic. International expertise on influenza virology was predominantly based in Anglo-Saxon countries. German microbiologists issued no clear recommendation for preventative vaccination until 1960. Instead, quinine was relied upon as the traditional medicinal prophylaxis. Antibiotics were more frequently administered. In East Germany, little fuss was made over the Asian flu. In line with the authorities' social hygiene orientation, vaccination was accepted as a matter of principle. In the Federal Republic and West Berlin, the population rejected the vaccination largely. It was seen as a scandal that many employees were on sick leave because of the flu, thus adversely affecting the economy.

  4. Children hospitalized with influenza pneumonia AH1N1/2009 pandemic in the INSN

    Miranda-Choque, Edwin; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Infectólogo.; Ramírez, Carlos; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Infectólogo.; Candela-Herrera, Jorge; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Díaz, Javier; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Fernández, Ana; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Kolevic, Lenka; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Segura, Eddy R.; Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia. Lima, Perú. Escuela de Medicina, Univesidad Peruana de Ciencias Aplicadas. Lima, Perú. Médico Epidemiólogo Clínico.; Farfán-Ramos, Sonia; Hospital de Emergencias Pediátricas. Lima, Perú. Enfermera, especialista en Enfermería Pediátrica, Magister en Salud Pública y Comunitaria, Magister en Administración de Salud.


    ObjectiveTo determine the clinical and demographic characteristics of pneumonia with influenza virus AH1N1/2009 pandemic at the National Institute of Child. Methods. Retrospective case series in children hospitalized for influenza pneumonia pandemic AH1N1/2009 in a pediatric hospital. Reviewed the medical records between the months of June to September 2009. All cases had virological confirmation, we describe the clinical characteristics and conditions of severity. Results. A total of 74 ...

  5. Statistical estimates of absenteeism attributable to seasonal and pandemic influenza from the Canadian Labour Force Survey

    Zheng Hui


    Full Text Available Abstract Background As many respiratory viruses are responsible for influenza like symptoms, accurate measures of the disease burden are not available and estimates are generally based on statistical methods. The objective of this study was to estimate absenteeism rates and hours lost due to seasonal influenza and compare these estimates with estimates of absenteeism attributable to the two H1N1 pandemic waves that occurred in 2009. Methods Key absenteeism variables were extracted from Statistics Canada's monthly labour force survey (LFS. Absenteeism and the proportion of hours lost due to own illness or disability were modelled as a function of trend, seasonality and proxy variables for influenza activity from 1998 to 2009. Results Hours lost due to the H1N1/09 pandemic strain were elevated compared to seasonal influenza, accounting for a loss of 0.2% of potential hours worked annually. In comparison, an estimated 0.08% of hours worked annually were lost due to seasonal influenza illnesses. Absenteeism rates due to influenza were estimated at 12% per year for seasonal influenza over the 1997/98 to 2008/09 seasons, and 13% for the two H1N1/09 pandemic waves. Employees who took time off due to a seasonal influenza infection took an average of 14 hours off. For the pandemic strain, the average absence was 25 hours. Conclusions This study confirms that absenteeism due to seasonal influenza has typically ranged from 5% to 20%, with higher rates associated with multiple circulating strains. Absenteeism rates for the 2009 pandemic were similar to those occurring for seasonal influenza. Employees took more time off due to the pandemic strain than was typical for seasonal influenza.

  6. Cost effectiveness of vaccination against pandemic influenza in European countries : mathematical modelling analysis

    Lugner, A.K.; van Boven, Michiel; de Vries, Robin; Postma, M.J.; Wallinga, J.


    Objective To investigate whether a single optimal vaccination strategy exists across countries to deal with a future influenza pandemic by comparing the cost effectiveness of different strategies in various pandemic scenarios for three European countries. Design Economic and epidemic modelling study

  7. Pharmaceutical interventions for mitigating an influenza pandemic : modeling the risks and health-economic impacts

    Postma, Maarten J.; Milne, George; Nelson, E. Anthony S.; Pyenson, Bruce; Basili, Marcello; Coker, Richard; Oxford, John; Garrison, Louis P.


    Model-based analyses built on burden-of-disease and cost effectiveness theory predict that pharmaceutical interventions may efficiently mitigate both the epidemiologic and economic impact of an influenza pandemic. Pharmaceutical interventions typically encompass the application of (pre)pandemic infl

  8. Estimating the incidence reporting rates of new influenza pandemics at an early stage using travel data from the source country

    CHONG, K. C.; Fong, H. F.; ZEE, C. Y.


    SUMMARY During the surveillance of influenza pandemics, underreported data are a public health challenge that complicates the understanding of pandemic threats and can undermine mitigation efforts. We propose a method to estimate incidence reporting rates at early stages of new influenza pandemics using 2009 pandemic H1N1 as an example. Routine surveillance data and statistics of travellers arriving from Mexico were used. Our method incorporates changes in reporting rates such as linearly inc...

  9. Clinical and socioeconomic impact of seasonal and pandemic influenza in adults and the elderly.

    Gasparini, Roberto; Amicizia, Daniela; Lai, Piero Luigi; Panatto, Donatella


    Influenza epidemics and pandemics carry a heavy socioeconomic burden. Hospitalization and treatment are more often necessary in high-risk patients, such as the elderly. However, the impact of influenza is not negligible even in adults, mainly because of lost productivity. The World Health Organization estimates that seasonal influenza causes 250,000-500,000 deaths worldwide each year; however, mortality may be very high in pandemic periods. Many estimates of the costs of seasonal influenza have been made in various socioeconomic contexts. For instance, among the adult population in Italy, a cost of €940.39 per case has been estimated. In the US, the average annual influenza burden in 18-49-y-old adults without underlying medical conditions is judged to include approximately 32,000 hospitalizations and 680 deaths. Estimating the influenza burden is a useful aid to determining the best influenza vaccination strategy and preventive and clinical treatments.

  10. Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis

    Ramezanpour, Bahar; Pronker, Esther S.; Kreijtz, Joost H.C.M.; Osterhaus, Albert D.M.E.; Claassen, E.


    A quantitative method is presented to rank strengths, weaknesses, opportunities, and threats (SWOT) of modified vaccinia virus Ankara (MVA) as a platform for pre-pandemic and pandemic influenza vaccines. Analytic hierarchy process (AHP) was applied to achieve pairwise comparisons among SWOT factors in order to prioritize them. Key opinion leaders (KOLs) in the influenza vaccine field were interviewed to collect a unique dataset to evaluate the market potential of this platform. The purpose of this study, to evaluate commercial potential of the MVA platform for the development of novel generation pandemic influenza vaccines, is accomplished by using a SWOT and AHP combined analytic method. Application of the SWOT–AHP model indicates that its strengths are considered more important by KOLs than its weaknesses, opportunities, and threats. Particularly, the inherent immunogenicity capability of MVA without the requirement of an adjuvant is the most important factor to increase commercial attractiveness of this platform. Concerns regarding vector vaccines and anti-vector immunity are considered its most important weakness, which might lower public health value of this platform. Furthermore, evaluation of the results of this study emphasizes equally important role that threats and opportunities of this platform play. This study further highlights unmet needs in the influenza vaccine market, which could be addressed by the implementation of the MVA platform. Broad use of MVA in clinical trials shows great promise for this vector as vaccine platform for pre-pandemic and pandemic influenza and threats by other respiratory viruses. Moreover, from the results of the clinical trials seem that MVA is particularly attractive for development of vaccines against pathogens for which no, or only insufficiently effective vaccines, are available. PMID:26048779

  11. Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis.

    Ramezanpour, Bahar; Pronker, Esther S; Kreijtz, Joost H C M; Osterhaus, Albert D M E; Claassen, E


    A quantitative method is presented to rank strengths, weaknesses, opportunities, and threats (SWOT) of modified vaccinia virus Ankara (MVA) as a platform for pre-pandemic and pandemic influenza vaccines. Analytic hierarchy process (AHP) was applied to achieve pairwise comparisons among SWOT factors in order to prioritize them. Key opinion leaders (KOLs) in the influenza vaccine field were interviewed to collect a unique dataset to evaluate the market potential of this platform. The purpose of this study, to evaluate commercial potential of the MVA platform for the development of novel generation pandemic influenza vaccines, is accomplished by using a SWOT and AHP combined analytic method. Application of the SWOT-AHP model indicates that its strengths are considered more important by KOLs than its weaknesses, opportunities, and threats. Particularly, the inherent immunogenicity capability of MVA without the requirement of an adjuvant is the most important factor to increase commercial attractiveness of this platform. Concerns regarding vector vaccines and anti-vector immunity are considered its most important weakness, which might lower public health value of this platform. Furthermore, evaluation of the results of this study emphasizes equally important role that threats and opportunities of this platform play. This study further highlights unmet needs in the influenza vaccine market, which could be addressed by the implementation of the MVA platform. Broad use of MVA in clinical trials shows great promise for this vector as vaccine platform for pre-pandemic and pandemic influenza and threats by other respiratory viruses. Moreover, from the results of the clinical trials seem that MVA is particularly attractive for development of vaccines against pathogens for which no, or only insufficiently effective vaccines, are available.

  12. Influenza mortality in the United States, 2009 pandemic: burden, timing and age distribution.

    Ann M Nguyen

    Full Text Available BACKGROUND: In April 2009, the most recent pandemic of influenza A began. We present the first estimates of pandemic mortality based on the newly-released final data on deaths in 2009 and 2010 in the United States. METHODS: We obtained data on influenza and pneumonia deaths from the National Center for Health Statistics (NCHS. Age- and sex-specific death rates, and age-standardized death rates, were calculated. Using negative binomial Serfling-type methods, excess mortality was calculated separately by sex and age groups. RESULTS: In many age groups, observed pneumonia and influenza cause-specific mortality rates in October and November 2009 broke month-specific records since 1959 when the current series of detailed US mortality data began. Compared to the typical pattern of seasonal flu deaths, the 2009 pandemic age-specific mortality, as well as influenza-attributable (excess mortality, skewed much younger. We estimate 2,634 excess pneumonia and influenza deaths in 2009-10; the excess death rate in 2009 was 0.79 per 100,000. CONCLUSIONS: Pandemic influenza mortality skews younger than seasonal influenza. This can be explained by a protective effect due to antigenic cycling. When older cohorts have been previously exposed to a similar antigen, immune memory results in lower death rates at older ages. Age-targeted vaccination of younger people should be considered in future pandemics.

  13. The investigation of Risk factors of influenza pandemic H1N1

    koorosh Holakooyi Naeini


    Full Text Available Introduction: Influenza pandemic H1N1 is an acute respiratory infectious disease that is combination of two types of influenza virus type A (H1N1. This study aimed to identify risk factors affecting influenza pandemic H1N1. Methods: In this case-control study, the cases were 18 positive cases of pandemic influenza H1N1 and the controls were the patients who were admitted during the same time as the cases to sections of Orthopedics, Urology, Surgery and Women of the same hospital for reasons other than influenza. The data were collected through a form by two experienced nurses and then were fed into SPSS, and were analyzed using independent T-test and chi-square. Results: A significant relationship was observed between pandemic H1N1 influenza infection and a history of domestic travel, contact with confirmed patients, respiratory diseases, and diabetes (P0.05. Conclusion: People with underlying diseases, especially respiratory diseases, diabetes, heart disease and a secondary infection and cardiovascular disease most likely are susceptible to influenza pandemic H1N1.

  14. Improving pandemic H5N1 influenza vaccines by combining different vaccine platforms.

    Luke, Catherine J; Subbarao, Kanta


    A variety of platforms are being explored for the development of vaccines for pandemic influenza. Observations that traditional inactivated subvirion vaccines and live-attenuated vaccines against H5 and some H7 influenza viruses were poorly immunogenic spurred efforts to evaluate new approaches, including whole virus vaccines, higher doses of antigen, addition of adjuvants and combinations of different vaccine modalities in heterologous prime-boost regimens to potentiate immune responses. Results from clinical trials of prime-boost regimens have been very promising. Further studies are needed to determine optimal combinations of platforms, intervals between doses of vaccines and the logistics of deployment in pre-pandemic and early pandemic settings.

  15. Were equatorial regions less affected by the 2009 influenza pandemic? The Brazilian experience.

    Cynthia Schuck-Paim

    Full Text Available Although it is in the Tropics where nearly half of the world population lives and infectious disease burden is highest, little is known about the impact of influenza pandemics in this area. We investigated the mortality impact of the 2009 influenza pandemic relative to mortality rates from various outcomes in pre-pandemic years throughout a wide range of latitudes encompassing the entire tropical, and part of the subtropical, zone of the Southern Hemisphere (+5(°N to -35(°S by focusing on a country with relatively uniform health care, disease surveillance, immunization and mitigation policies: Brazil. To this end, we analyzed laboratory-confirmed deaths and vital statistics mortality beyond pre-pandemic levels for each Brazilian state. Pneumonia, influenza and respiratory mortality were significantly higher during the pandemic, affecting predominantly adults aged 25 to 65 years. Overall, there were 2,273 and 2,787 additional P&I- and respiratory deaths during the pandemic, corresponding to a 5.2% and 2.7% increase, respectively, over average pre-pandemic annual mortality. However, there was a marked spatial structure in mortality that was independent of socio-demographic indicators and inversely related with income: mortality was progressively lower towards equatorial regions, where low or no difference from pre-pandemic mortality levels was identified. Additionally, the onset of pandemic-associated mortality was progressively delayed in equatorial states. Unexpectedly, there was no additional mortality from circulatory causes. Comparing disease burden reliably across regions is critical in those areas marked by competing health priorities and limited resources. Our results suggest, however, that tropical regions of the Southern Hemisphere may have been disproportionally less affected by the pandemic, and that climate may have played a key role in this regard. These findings have a direct bearing on global estimates of pandemic burden and the

  16. Pandemic (H1N1 influenza in Diyarbakir, 2009

    Meliksah Ertem


    Full Text Available  Objective: This study was conducted to evaluate the pandemic (H1N1 influenza outbreak in 2009. Method: Influenza like illness (ILI cases were reported between the 36th to 53rd weeks of the pandemic, from all health centres. 731 nasopharyngeal swabs were collected from ILI cases. Results: The first H1N1 confirmed case was reported at the 36th week and an increasing trend continued. At the 43rd week the outbreak reached its maximum level and at the 53rd week the level had decreased to the level at the start. During the outbreak 31117 cases were reported as ILI and 635 cases were hospitalized (hospitalization rate was 2.0% and 17 H1N1 laboratory confirmed cases died (mortality rate 11.5/1.000.000. Symptoms of laboratory confirmed cases were similar to seasonal influenza. Coughing (90.9%, fever (84.5%, running nose (69.5%, headache (73.4%, diarrhoea (17.5% were the some of the symptoms in laboratory confirmed cases. The median interval between the onset of symptoms and hospital admission was 3.5 days (min: 1, max: 11 days and this was 7.5 days for the occurrence of death. Conclusion: During 36th to 53rd week an important outbreak of ILI was occurred. The mortality rate was not so high as expected but the infectivity was high. The delay for hospital admission may lead to higher mortality particularly for pregnant women.Key Words: Pandemic influenza; H1N1; case fatality rate; hospitalization rateDiyarbakır’da pandemik (H1N1 influenza, 2009Amaç: Bu çalışmada 2009 yılında -Türkiye’de pandemik influenza salgınını değerlendirmek amaçlanmıştır. Yöntem: Diyarbakır ’da 36 ve 53. haftalar arasında tüm sağlık kuruluşlarından influenza benzeri hastalık rapor edilmiştir. 731 nazofaringeal sürüntü alınmıştır. Bulgular: İlk H1N1 doğrulanmış vaka 36.haftada rapor edilmiştir ve vaka sayıları zaman içinde artış göstermiştir. 43. haftada salgın başlamış ve 53. haftada başlangıç düzeyine inmiştir.Salgın s

  17. The Relationship between Tuberculosis and Influenza Death during the Influenza (H1N1 Pandemic from 1918-19

    Welling Oei


    Full Text Available The epidemiological mechanisms behind the W-shaped age-specific influenza mortality during the Spanish influenza (H1N1 pandemic 1918-19 have yet to be fully clarified. The present study aimed to develop a formal hypothesis: tuberculosis (TB was associated with the W-shaped influenza mortality from 1918-19. Three pieces of epidemiological information were assessed: (i the epidemic records containing the age-specific numbers of cases and deaths of influenza from 1918-19, (ii an outbreak record of influenza in a Swiss TB sanatorium during the pandemic, and (iii the age-dependent TB mortality over time in the early 20th century. Analyzing the data (i, we found that the W-shaped pattern was not only seen in mortality but also in the age-specific case fatality ratio, suggesting the presence of underlying age-specific risk factor(s of influenza death among young adults. From the data (ii, TB was shown to be associated with influenza death (P=0.09, and there was no influenza death among non-TB controls. The data (iii were analyzed by employing the age-period-cohort model, revealing harvesting effect in the period function of TB mortality shortly after the 1918-19 pandemic. These findings suggest that it is worthwhile to further explore the role of TB in characterizing the age-specific risk of influenza death.

  18. Pandemic influenza preparedness: an ethical framework to guide decision-making

    Gibson Jennifer L


    Full Text Available Abstract Background Planning for the next pandemic influenza outbreak is underway in hospitals across the world. The global SARS experience has taught us that ethical frameworks to guide decision-making may help to reduce collateral damage and increase trust and solidarity within and between health care organisations. Good pandemic planning requires reflection on values because science alone cannot tell us how to prepare for a public health crisis. Discussion In this paper, we present an ethical framework for pandemic influenza planning. The ethical framework was developed with expertise from clinical, organisational and public health ethics and validated through a stakeholder engagement process. The ethical framework includes both substantive and procedural elements for ethical pandemic influenza planning. The incorporation of ethics into pandemic planning can be helped by senior hospital administrators sponsoring its use, by having stakeholders vet the framework, and by designing or identifying decision review processes. We discuss the merits and limits of an applied ethical framework for hospital decision-making, as well as the robustness of the framework. Summary The need for reflection on the ethical issues raised by the spectre of a pandemic influenza outbreak is great. Our efforts to address the normative aspects of pandemic planning in hospitals have generated interest from other hospitals and from the governmental sector. The framework will require re-evaluation and refinement and we hope that this paper will generate feedback on how to make it even more robust.

  19. Adoption of Preventive Measures and Attitudes toward the H1N1 Influenza Pandemic in Schools

    Pérez, Anna; Rodríguez, Tània; López, Maria José; Continente, Xavier; Nebot, Manel


    Background: This study describes the perceived impact of H1N1 influenza and the adoption of the recommended measures to address the pandemic in schools. Methods: A cross-sectional self-reported survey was conducted in 433 schools in Barcelona addressed to the school principal or the H1N1 influenza designated person. A descriptive analysis was…

  20. The Association of H1N1 Pandemic Influenza with Congenital Anomaly Prevalence in Europe

    Luteijn, Johannes Michiel; Addor, Marie-Claude; Arriola, Larraitz


    BACKGROUND: In the context of the European Surveillance of Congenital Anomalies (EUROCAT) surveillance response to the 2009 influenza pandemic, we sought to establish whether there was a detectable increase of congenital anomaly prevalence among pregnancies exposed to influenza seasons in general...

  1. Pandemic H1N1 influenza: zoonoses are a two-way street

    Influenza is a zoonotic viral disease representing a worldwide health and economic threat to humans and animals. Swine influenza was first recognized clinically in pigs in the Midwestern United States in 1918 concurrent with the Spanish flu human pandemic. Since the first report that flu was caused ...

  2. Acute Respiratory Infections in the Context of the Influenza A (H1N1 Pandemic

    Hilda María Delgado Acosta


    Full Text Available Background: acute respiratory infections are among the leading causes of morbidity and mortality worldwide. Objective: to characterize acute respiratory infections in the context of the influenza pandemic in Cienfuegos province. Methods: A case series study including 844 inpatients diagnosed with influenza-like illness, 806 suspected cases and 38 confirmed cases of pandemic influenza, was conducted. An analysis of the acute respiratory infections was performed, describing the pandemic in space and time. Suspected and confirmed cases were compared according to general variables, risk factors and interesting clinical features. Virus isolation and classification of confirmed cases considering source of infection and progress over time were showed. Data was collected from the Statistics Department of the Provincial Hygiene and Epidemiology Center and the inpatient database. Percentages, rates, the mean, standard deviation and Chi-square test with a 5 % margin of error were used.Results: acute respiratory infections morbidity increased since 2008, largely because of the impact of the pandemic and the increased clinical and epidemiological surveillance. Its association with risk factors such as pregnancy, chronic diseases and traveling abroad was demonstrated. Circulation of the pandemic influenza virus with displacement of seasonal viruses and prevalence of indigenous cases were observed. Conclusions: the characteristics of pandemic influenza in the province do not differ greatly from those described nationally and globally.

  3. The pandemic (H1N1 2009 influenza virus is resistant to mannose-binding lectin

    Ushirogawa Hiroshi


    Full Text Available Abstract Background Mannose-binding lectin (MBL is an important component of innate immunity because it promotes bacterial clearance and neutralization of human influenza A viruses. Since a majority of humans have no neutralizing antibody against the pandemic (H1N1 2009 influenza (pandemic 2009 virus, innate immunity may be crucial and MBL susceptibility may therefore influence viral pathogenesis. Results We examined MBL susceptibility of influenza A viruses and observed that the pandemic 2009 virus was resistant to MBL, whereas all seasonal influenza A viruses tested were susceptible. The mortality of mice infected with a seasonal H1N1 influenza virus was evidently enhanced on transient blockage of MBL activity by simultaneous inoculation of mannan, whereas mannan inoculation had no effect on mice infected with a pandemic 2009 virus. This indicates that MBL protects mice against infection with the seasonal virus but not against that with the pandemic 2009 virus. Conclusions These results indicate that the pandemic 2009 virus is not susceptible to MBL, an important component of innate immunity.

  4. Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules.

    Grødeland, Gunnveig; Bogen, Bjarne


    There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.

  5. Risk of fetal death after pandemic influenza infection or vaccination during pregnancy

    Håberg, Siri E; Trogstad, Lill; Gunnes, Nina; Wilcox, Allen J.; Gjessing, Håkon K.; Samuelsen, Sven Ove; Skrondal, Anders; Cappelen, Inger; Engeland, Anders; Aavitsland, Preben; Madsen, Steinar; Buajordet, Ingebjørg; Furu, Kari; Nafstad, Per; Vollset, Stein Emil; Berit, Feiring; Nøkleby, Hanne; Magnus, Per; Stoltenberg, Camilla


    Background During the 2009 influenza pandemic, pregnant women were at particular risk of serious influenza illness. This concern was further complicated by questions about vaccine safety in pregnant women raised by anecdotal reports of fetal deaths following vaccination. Methods We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios of fetal death, with gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. Results There were 117,347 eligible pregnancies in Norway in 2009–2010. Fetal mortality was 4.9/1000. 54% of pregnant women in their second or third trimester during the pandemic were vaccinated. Vaccination in pregnancy substantially reduced the risk of influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). A clinical diagnosis of influenza in the mother increased the risk of fetal death (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). Among pregnant women, the risk of fetal death was lower with vaccination, although this reduction was not statistically significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). Conclusions Pandemic influenza in pregnancy was associated with increased risk of fetal death. Vaccination during pregnancy reduced the risk of influenza diagnosis. Vaccination itself did not increase fetal mortality, and may have reduced the risk of influenza-related fetal death during the pandemic. PMID:23323868

  6. Pandemic influenza control in Europe and the constraints resulting from incoherent public health laws

    Martin Robyn


    Full Text Available Abstract Background With the emergence of influenza H1N1v the world is facing its first 21st century global pandemic. Severe Acute Respiratory Syndrome (SARS and avian influenza H5N1 prompted development of pandemic preparedness plans. National systems of public health law are essential for public health stewardship and for the implementation of public health policy1. International coherence will contribute to effective regional and global responses. However little research has been undertaken on how law works as a tool for disease control in Europe. With co-funding from the European Union, we investigated the extent to which laws across Europe support or constrain pandemic preparedness planning, and whether national differences are likely to constrain control efforts. Methods We undertook a survey of national public health laws across 32 European states using a questionnaire designed around a disease scenario based on pandemic influenza. Questionnaire results were reviewed in workshops, analysing how differences between national laws might support or hinder regional responses to pandemic influenza. Respondents examined the impact of national laws on the movements of information, goods, services and people across borders in a time of pandemic, the capacity for surveillance, case detection, case management and community control, the deployment of strategies of prevention, containment, mitigation and recovery and the identification of commonalities and disconnects across states. Results Results of this study show differences across Europe in the extent to which national pandemic policy and pandemic plans have been integrated with public health laws. We found significant differences in legislation and in the legitimacy of strategic plans. States differ in the range and the nature of intervention measures authorized by law, the extent to which borders could be closed to movement of persons and goods during a pandemic, and access to healthcare of non

  7. Signs of the 2009 influenza pandemic in the New York-Presbyterian Hospital electronic health records.

    Hossein Khiabanian

    Full Text Available BACKGROUND: In June of 2009, the World Health Organization declared the first influenza pandemic of the 21(st century, and by July, New York City's New York-Presbyterian Hospital (NYPH experienced a heavy burden of cases, attributable to a novel strain of the virus (H1N1pdm. METHODS AND RESULTS: We present the signs in the NYPH electronic health records (EHR that distinguished the 2009 pandemic from previous seasonal influenza outbreaks via various statistical analyses. These signs include (1 an increase in the number of patients diagnosed with influenza, (2 a preponderance of influenza diagnoses outside of the normal flu season, and (3 marked vaccine failure. The NYPH EHR also reveals distinct age distributions of patients affected by seasonal influenza and the pandemic strain, and via available longitudinal data, suggests that the two may be associated with distinct sets of comorbid conditions as well. In particular, we find significantly more pandemic flu patients with diagnoses associated with asthma and underlying lung disease. We further observe that the NYPH EHR is capable of tracking diseases at a resolution as high as particular zip codes in New York City. CONCLUSION: The NYPH EHR permits early detection of pandemic influenza and hypothesis generation via identification of those significantly associated illnesses. As data standards develop and databases expand, EHRs will contribute more and more to disease detection and the discovery of novel disease associations.

  8. Seasonal and pandemic influenza: the role of communication and preventive strategies.

    Boccia, A; Di Thiene, D; De Giusti, M; La Torre, G


    Appropriate, timely, and data-driven health information is a very important issue in preventive strategies against influenza. Intuitively, a link between willingness to be vaccinated against seasonal influenza and against pandemic influenza exists, given the similarities in decision-making for this vaccine. International and national literature reviews suggest that progress has been made in order to incorporate and disseminate crisis risk communication principles into public health practice, as such investments in public health could be important for building capacity and practice which aid in the realization of countermeasures in response to a future pandemic and epidemic situation. This study emphasizes the lack of perception by Health Care Workers (HCWs) of the importance of being immunized against seasonal and pandemic influenza and the doubts concerning safety. In the future, particular efforts are needed during vaccination campaigns, to provide more information to HCWs and the general population regarding role and safety of such vaccines.

  9. Investigating obesity as a risk factor for influenza-like illness during the 2009 H1N1 influenza pandemic using the Health Survey for England

    Murphy, R.; Fragaszy, E. B.; Hayward, A. C.; Warren-Gash, C.


    BACKGROUND: Following the 2009 H1N1 influenza pandemic, obesity was shown to be associated with severe influenza outcomes. It remains unclear whether obesity was a risk factor for milder influenza-like illness (ILI). OBJECTIVES: To determine whether obesity was associated with an increased risk of self-reported ILI during the 2009 H1N1 influenza pandemic using Health Survey for England (HSE) 2010 cross-sectional data. METHODS: This study used HSE data collected from English households between...

  10. Analysis of suspected adverse reactions following immunization against pandemic influenza

    Petrović Vladimir


    Full Text Available Introduction. The surveillance on adverse reaction following immunization was aimed at recording all adverse events possibly related with vaccines. During the implementation of immunization strategy against pandemic influenza A(H1N1 in 2009, the post-marketing comprehensive surveillance was suggested to be conducted due to limited clinical experience in applying this particular vaccine and because of the fact that some vaccines had been licensed only on the basis of the data regarding their quality. Material and Methods. The passive surveillance on adverse events following immunization was conducted simultaneously with immunization campaign against pandemic influenza in the Autonomous Province of Vojvodina. Reporting of adverse events was conducted by health care service through a specially designed questionnaire Results. In the period from December 17th 2009 to February 7th 2010, of the total number of 55720 people who were vaccinated, 50433 received one dose and 5287 received two doses of vaccine. The total number of doses administered was 61007. During the observed period, some adverse reactions were recorded in 37 people, the rate of occurrence of adverse reactions being 6.6 per 10.000 vaccinated. Since the majority of patients had several symptoms and signs, the number of recorded clinical manifestations was much higher (140 than the number of patients with reactions. The dominant symptoms and signs were fever (51.4%, weakness/fatigue (48.6%, headache (40.5% and myalgia (31.5%. The reactions in the majority of patients were mild and transient. Only two patients sought medical care and one was hospitalized. Since the immunization coverage was very small, it was not possible to record rare adverse events, whose expected incidence is, anyway, very low. Conclusion. Surveillance on adverse reaction following immunization represents an important component of immunization program, especially when new vaccines are introduced. Therefore, this form

  11. Establishment of pandemic influenza vaccine production capacity at Bio Farma, Indonesia.

    Suhardono, Mahendra; Ugiyadi, Dori; Nurnaeni, Ida; Emelia, Imelda


    In Indonesia, avian influenza A(H5N1) virus started to spread in humans in June 2005, with an alarming case-fatality rate of more than 80%. Considering that global influenza vaccine production capacity would barely have covered 10% of the world's pandemic vaccine needs, and that countries with no production facilities or prearranged contracts would be without access to a vaccine, the Government of Indonesia embarked on a programme to increase its readiness for a future influenza pandemic. This included the domestic production of influenza vaccine, which was entrusted to Bio Farma. This health security strategy consists of developing trivalent influenza vaccine production capacity in order to be able to convert immediately to monovalent production of up to 20 million pandemic doses for the Indonesian market upon receipt of the seed strain from the World Health Organization (WHO). For this purpose, a dedicated production facility is being constructed within the Bio Farma premises in Bandung. As an initial stage of influenza vaccine development, imported seasonal influenza bulk has been formulated and filled in the Bio Farma facility. Following three consecutive batches and successful clinical trials, the product was licensed by the Indonesian National Regulatory Authority and distributed commercially for the Hajj programme in 2009. With continued support from its technology transfer partners, Bio Farma is now advancing with the development of upstream processes to produce its own bulk for seasonal and pandemic use.

  12. Pandemia de influenza: la respuesta de México Influenza pandemic: Mexico's response

    Pablo Kuri-Morales


    Full Text Available En 1992 apareció en el sureste asiático un nuevo tipo de virus de la influenza, el cual ha ocasionado hasta la fecha más de 120 casos y un poco más de 60 defunciones en humanos en Camboya, Vietnam, Indonesia y Tailandia. Esta situación es considerada por los expertos como la probable génesis de una nueva pandemia de influenza, lo que podría traer graves consecuencias para la salud de la población, así como para la economía y el comercio mundial. Por lo anterior, la Organización Mundial de la Salud (OMS ha instado a los países miembros a desarrollar planes de preparación y respuesta para hacer frente a esta eventualidad. En el marco del Comité Nacional para la Seguridad en Salud, México ha diseñado el Plan Nacional de Preparación y Respuesta ante una Pandemia de Influenza con objeto de proteger a la población mediante acciones efectivas y oportunas. El Plan utiliza una escala de riesgo y define cinco líneas de acción: Coordinación, Vigilancia Epidemiológica, Atención Médica, Difusión y Movilización Social, y Reserva Estratégica. Si bien es imposible predecir cuándo se presentará la próxima pandemia y su impacto, es fundamental que las autoridades de salud nacionales, estatales y locales establezcan los mecanismos para poner en marcha los componentes del Plan en forma oportuna y garantizar con ello la salud de la población en caso de influenza pandémica.In 1992, a new type of influenza virus appeared in Southeast Asia. This new strain has caused to date, more than 120 cases and over 60 deaths in Cambodia, Vietnam, Indonesia and Thailand. This situation is seen by the experts as the possible genesis of a new influenza pandemic with the corresponding negative effects on the health of the population, international commerce and world economy. In order to face the coming challenge, the World Health Organization (WHO has asked member countries to develop national preparedness and response plans for an influenza pandemic

  13. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection


    The 2009 pandemic H1N1 influenza pandemic demonstrated the global health threat of reassortant influenza strains. Herein, we report a detailed analysis of plasmablast and monoclonal antibody responses induced by pandemic H1N1 infection in humans. Unlike antibodies elicited by annual influenza vaccinations, most neutralizing antibodies induced by pandemic H1N1 infection were broadly cross-reactive against epitopes in the hemagglutinin (HA) stalk and head domain of multiple influenza strains. T...

  14. Seroprevalence of seasonal and pandemic influenza a in Kuala Lumpur, Malaysia in 2008-2010.

    Sam, I-Ching; Shaw, Robert; Chan, Yoke-Fun; Hooi, Poh-Sim; Hurt, Aeron C; Barr, Ian G


    Relatively little is known about the burden of influenza in tropical countries. The seroprevalence of pandemic influenza A (H1N1) 2009, seasonal H1N1 and H3N2 was determined in Kuala Lumpur, Malaysia. Pre- and post-pandemic residual laboratory sera were tested by hemagglutination-inhibition. The seroprevalence of A(H1N1)pdm09 increased from 3.7% pre-pandemic to 21.9% post-pandemic, giving an overall cumulative incidence of 18.1% (95% CI, 13.8-22.5%), mainly due to increases in those 55 years. A(H1N1)pdm09 affected almost a third of those Kuala Lumpur. Pre-pandemic seroprevalence was 14.7% for seasonal H1N1 and 21.0% for H3N2, and these rates did not change significantly after the pandemic. Seasonal and pandemic influenza cause a considerable burden in tropical Malaysia, particularly in children and young adults.

  15. Prioritization of pandemic influenza vaccine: rationale and strategy for decision making.

    Schwartz, Benjamin; Orenstein, Walter A


    Few catastrophes can compare with the global impact of a severe influenza pandemic. The 1918-1919 pandemic was associated with more than 500,000 deaths in the USA and an estimated 20-40 million deaths worldwide, though some place the global total much higher. In an era when infectious disease mortality had been steadily decreasing, the 1918-1919 pandemic caused a large spike in overall population mortality, temporarily reversing decades of progress. The US Department of Health and Human Services, extrapolating from the 1918-1919 pandemic to the current US population size and demographics, has estimated that a comparable pandemic today would result in almost two million deaths. Vaccination is an important component of a pandemic response. Public health measures such as reduction of close contacts with others, improved hygiene, and respiratory protection with facemasks or respirators can reduce the risk of exposure and illness (Germann et al. 2006; Ferguson et al. 2006), but would not reduce susceptibility among the population. Prophylaxis with antiviral medications also may prevent illness but depends on the availability of large antiviral drug stockpiles and also does not provide long-term immunity. By contrast, immunization with a well-matched pandemic vaccine would provide active immunity and represent the most durable pandemic response. However, given current timelines for the development of a pandemic influenza vaccine and its production capacity, vaccine is likely not to be available in sufficient quantities to protect the entire population before pandemic outbreaks occur, and thus potentially limited stocks may need to be prioritized. This chapter reviews information on influenza vaccine production capacity, describes approaches used in the USA to set priorities for vaccination in the setting of limited supply, and presents a proposed strategy for prioritization.

  16. Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study

    Simonsen, L.; Spreeuwenberg, P.; Lustig, R.; Taylor, R.J.; Fleming, D.M.; Kroneman, M.; Kerkhove, M.D. Van; Mounts, A.W.; Paget, W.J.; Teams, G.L.C.


    BACKGROUND: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substanti

  17. Global mortality estimates for the 2009 influenza pandemic from the GLaMOR Project: a modeling study.

    Simonsen, L.; Spreeuwenberg, P.; Lustig, R.; Taylor, R.J.; Fleming, D.M.; Kroneman, M.; Kerkhove, M.D. van; Mounts, A.W.; Paget, W.J.


    Background: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substanti


    Paula, Stéfano Ivani de; Paula, Gustavo Ivani de; Cunegundes, Kelly Simone Almeida; Moraes-Pinto, Maria Isabel de


    This study evaluated the adherence to influenza vaccination among medical students in 2010 and 2011. From August to December 2011, a questionnaire was used to record the influenza vaccination in 2010 and 2011, reasons for acceptance of the influenza vaccine and knowledge of healthcare workers about the influenza vaccine recommendation. One hundred and forty-four students from the 2ndto the 6th years of the medical school were interviewed. A great adherence to pandemic influenza vaccine was noted in 2010, (91% of the students), with "self-protection" being the most common reason cited for vaccination. Other determinants for the vaccination during pandemic were "convenient access to vaccine" and "encouragement by peers and teachers in workplaces and at the university". However, there was a great decay in the acceptance to vaccine in the next influenza season (2011). Only 42% of the students received the vaccine. They claimed "lack of time" and "have forgotten to take the vaccine" as the main reasons. The "knowledge on the recommendation of influenza vaccine to healthcare workers" increased when the students come to attend the last year of the medical school, but that was an insufficient motivator for vaccination. Strategies to increase vaccination should be based on the abovementioned aspects for the adoption of effective measures in both, pandemic and seasonal periods.

  19. [The use of extracorporeal membrane oxygenation (ECMO) in the treatment of acute respiratory distress syndrome due to pandemic influenza].

    Knapik, Piotr; Przybylski, Roman; Nadziakiewicz, Paweł; Koba, Rafał; Maciejewski, Tomasz; Borowicz, Marcin; Włoczka, Grzegorz; Pawlak, Szymon; Zembala, Marian


    Pandemic influenza particularly often is associated with symptoms of acute respiratory failure, and in case of refractory hypoxemia patients may have indications for the extracorporeal membrane oxygenation (ECMO). The paper presents a case of a pandemic influenza virus infection, where classical indications for veno-venous ECMO occured. Practical aspects of this kind of treatment in the intensive care unit are discussed.

  20. Natality Decline and Miscarriages Associated With the 1918 Influenza Pandemic: The Scandinavian and United States Experiences

    Bloom-Feshbach, Kimberly; Simonsen, Lone; Viboud, Cecile;


    Background. Although pregnancy is a recognized risk factor for severe influenza infection, the effect of influenza on miscarriages and births remains unclear. We examined the relationship between influenza and birth rates during the 1918 pandemic in the United States, Denmark, Sweden, and Norway...... of peak pandemic exposure and depressions in birth rates, and identified pregnancy stages at risk of influenza-related miscarriage. Results. Birth rates declined in all study populations in spring 1919 by a mean of 2.2 births per 1000 persons, representing a 5%–15% drop below baseline levels (P .... Methods. We compiled monthly birth rates from 1911 through 1930 in 3 Scandinavian countries and the United States, identified periods of unusually low or high birth rates, and quantified births as “missing” or “in excess” of the normal expectation. Using monthly influenza data, we correlated the timing...

  1. Partial protection against 2009 pandemic influenza A (H1N1) of seasonal influenza vaccination and related regional factors: Updated systematic review and meta-analyses.

    Li, Zhi-yuan; Chen, Jin-yan; Zhang, Yan-ling; Fu, Wei-ming


    This updated systematic review and meta-analyses aims to systematically evaluate the cross-protection of seasonal influenza vaccines against the 2009 pandemic A (H1N1) influenza infection, and investigate the potential effect of the influenza strains circulating previous to the pandemic on the association between vaccine receipt and pandemic infection. In addition, subgroup analysis was performed based on the study locations and previous circulating influenza viruses. Relevant articles in English and Chinese from 2009 to October 2013 were systematically searched, and 21 eligible studies were included. For case-control studies, an insignificant 20% reduced risk for pandemic influenza infection based on combined national data (OR = 0.80; 95%CI: 0.60, 1.05) was calculated for people receiving seasonal influenza vaccination. However, for RCTs, an insignificant increase in the risk of seasonal influenza vaccines was observed (RR = 1.27; 95% CI: 0.46, 3.53). For the subgroup analysis, a significant 35% cross-protection was observed in the subgroup where influenza A outbreaks were detected before the 2009 pandemic. Moreover, the results indicated that seasonal influenza vaccination may reduce the risk of influenza-like illnesses (ILIs) (RR = 0.91; 95% CI: 0.84, 0.99). Our findings partially support the hypothesis that seasonal vaccines may offer moderate cross-protection for adults against laboratory-confirmed pandemic influenza A (H1N1) infection and ILIs. Further immunological studies are needed to understand the mechanism underlying these findings.

  2. People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior.

    Xu, Jianhua; Peng, Zongchao


    Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.

  3. Influenza Pandemic: Gaps in Pandemic Planning and Preparedness Need to Be Addressed. Testimony before the Committee on Homeland Security, House of Representatives. GAO-09-909T

    Steinhardt, Bernice


    As the current H1N1 outbreak underscores, an influenza pandemic remains a real threat to our nation. Over the past 3 years, the US Government Accountability Office (GAO) conducted a body of work, consisting of 12 reports and 4 testimonies, to help the nation better prepare for a possible pandemic. In February 2009, GAO synthesized the results of…

  4. Theoretical and practical exploration of vision building in human influenza pandemic prevention & control

    PengKong; YanKong; XuJiang; XiaohuaWang


    This article introduced the vision building concept about human influenza pandemic prevention and control. Different visions were built by creating different shapes of building blocks which also represented different organizations and physical facilities, respectively. The around-view reflection is required to be developed in the process of building so as to search for the ideal pattern. The correlation of all sectors and systems are established to combine different kinds of things, from one family to another, from communities, towns, counties, cities, rural areas, provinces to the state to handle trivial problems. These training objectives have been successfully accomplished, which has not only enriched the knowledge about prevention and control of influenza pandemic between different departments but also clarified the roles and responsibility. It lays the firm foundation for next cooperation between different departments, and make a bridge for the objective and choice of channel over human influenza pandemic prevention and control.

  5. Emerging Influenza Strains in the Last Two Decades: A Threat of a New Pandemic?

    Claudia Trombetta


    Full Text Available In the last 20 years, novel non-seasonal influenza viruses have emerged, most of which have originated from birds. Despite their apparent inability to cause pandemics, with the exception of H1N1 swine influenza virus, these viruses still constitute a constant threat to public health. While general concern has decreased after the peak of the H5N1 virus, in recent years several novel reassorted influenza viruses (e.g., H7N9, H9N2, H10N8 have jumped the host-species barrier and are under surveillance by the scientific community and public health systems. It is still unclear whether these viruses can actually cause pandemics or just isolated episodes. The purpose of this review is to provide an overview of old and novel potential pandemic strains of recent decades.

  6. School closures during the 2009 influenza pandemic: national and local experiences

    Cauchemez, Simon; Van Kerkhove, Maria; Archer, Brett; Cetron, Martin; Cowling, Benjamin; Grove, Peter; Hunt, Darren; Kojouharova, Mira; Kon, Predrag; Ungchusak, Kumnuan; Oshitani, Hitoshi; Pugliese, Andrea; Rizzo, Caterina; Saour, Guillaume; Sunagawa, Tomimase


    International audience; BACKGROUND: School closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event. Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic. Our intention is not to make a systematic review of country experiences; rather, it...

  7. Pharmaceutical interventions for mitigating an influenza pandemic: modeling the risks and health-economic impacts.

    Postma, Maarten J; Milne, George; Nelson, E Anthony S; Pyenson, Bruce; Basili, Marcello; Coker, Richard; Oxford, John; Garrison, Louis P


    Model-based analyses built on burden-of-disease and cost-effectiveness theory predict that pharmaceutical interventions may efficiently mitigate both the epidemiologic and economic impact of an influenza pandemic. Pharmaceutical interventions typically encompass the application of (pre)pandemic influenza vaccines, other vaccines (notably pneumococcal), antiviral treatments and other drug treatment (e.g., antibiotics to target potential complications of influenza). However, these models may be too limited to capture the full macro-economic impact of pandemic influenza. The aim of this article is to summarize current health-economic modeling approaches to recognize the strengths and weaknesses of these approaches, and to compare these with more recently proposed alternative methods. We conclude that it is useful, particularly for policy and planning purposes, to extend modeling concepts through the application of alternative approaches, including insurers' risk theories, human capital approaches and sectoral and full macro-economic modeling. This article builds on a roundtable meeting of the Pandemic Influenza Economic Impact Group that was held in Boston, MA, USA, in December 2008.

  8. An Avian Connection as a Catalyst to the 1918-1919 Influenza Pandemic


    Full Text Available The 1918 Influenza pandemic was one of the most virulent strains of influenza in history. This strain quickly dispatched previously held theories on influenza. World War One introduced new environmental stresses and speed of dissemination logistics never experienced by humans. In light of new phylogenic evidence the cause of this influenza outbreak is now being considered to have linkage to the avian influenza. Animals act as reservoirs for this influenza virus and research indicates the influenza virus often originates in the intestines of aquatic wildfowl. The virus is shed into the environment, which in turns infects domestic poultry, which in turn infects mammalian hosts. These animals, usually pigs, act as a transformer or converters; creating a strain that can more readily infect humans. Therefore swine can be infected with both avian and human influenza A viruses and serve as a source for infection for a number of species as the incidents of direct infection from birds to humans have been rare. Increased human habitation near poultry and swine raising facilities pose greater influenza outbreak risk. It was this combination of environmental factors that may have contributed to the greatest pandemic of recent times, and, moreover, similar conditions exist throughout Southeast Asia today.

  9. H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity.

    Morens, David M; Taubenberger, Jeffery K; Fauci, Anthony S


    ABSTRACT The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.

  10. Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base

    Wasserman Jeffrey


    Full Text Available Abstract Background In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. Methods Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic. Results The literature contained a dearth

  11. Evaluation of Three Live Attenuated H2 Pandemic Influenza Vaccine Candidates in Mice and Ferrets

    Chen, Grace L.; Lamirande, Elaine W.; Cheng, Xing; Torres-Velez, Fernando; Orandle, Marlene; Jin, Hong; Kemble, George


    ABSTRACT H2 influenza viruses have not circulated in humans since 1968, and therefore a significant portion of the population would be susceptible to infection should H2 influenza viruses reemerge. H2 influenza viruses continue to circulate in avian reservoirs worldwide, and these reservoirs are a potential source from which these viruses could emerge. Three reassortant cold-adapted (ca) H2 pandemic influenza vaccine candidates with hemagglutinin (HA) and neuraminidase (NA) genes derived from the wild-type A/Japan/305/1957 (H2N2) (Jap/57), A/mallard/6750/1978 (H2N2) (mal/78), or A/swine/MO/4296424/2006 (H2N3) (sw/06) viruses and the internal protein gene segments from the A/Ann Arbor/6/60 ca virus were generated by plasmid-based reverse genetics (Jap/57 ca, mal/78 ca, and sw/06 ca, respectively). The vaccine candidates exhibited the in vitro phenotypes of temperature sensitivity and cold adaptation and were restricted in replication in the respiratory tract of ferrets. In mice and ferrets, the vaccines elicited neutralizing antibodies and conferred protection against homologous wild-type virus challenge. Of the three candidates, the sw/06 ca vaccine elicited cross-reactive antibodies and provided significant protection against the greatest number of heterologous viruses. These observations suggest that the sw/06 ca vaccine should be further evaluated in a clinical trial as an H2 pandemic influenza vaccine candidate. IMPORTANCE Influenza pandemics arise when novel influenza viruses are introduced into a population with little prior immunity to the new virus and often result in higher rates of illness and death than annual seasonal influenza epidemics. An influenza H2 subtype virus caused a pandemic in 1957, and H2 viruses circulated in humans till 1968. H2 influenza viruses continue to circulate in birds, and the development of an H2 influenza vaccine candidate is therefore considered a priority in preparing for future pandemics. However, we cannot predict whether a

  12. Age distribution of cases of 2009 (H1N1 pandemic influenza in comparison with seasonal influenza.

    Drosos E Karageorgopoulos

    Full Text Available INTRODUCTION: Several aspects of the epidemiology of 2009 (H1N1 pandemic influenza have not been accurately determined. We sought to study whether the age distribution of cases differs in comparison with seasonal influenza. METHODS: We searched for official, publicly available data through the internet from different countries worldwide on the age distribution of cases of influenza during the 2009 (H1N1 pandemic influenza period and most recent seasonal influenza periods. Data had to be recorded through the same surveillance system for both compared periods. RESULTS: For 2009 pandemic influenza versus recent influenza seasons, in USA, visits for influenza-like illness to sentinel providers were more likely to involve the age groups of 5-24, 25-64 and 0-4 years compared with the reference group of >64 years [odds ratio (OR (95% confidence interval (CI: 2.43 (2.39-2.47, 1.66 (1.64-1.69, and 1.51 (1.48-1.54, respectively]. Pediatric deaths were less likely in the age groups of 2-4 and 65 years [OR (95% CI: 7.19 (6.67-7.75, 5.33 (4.90-5.79, 5.04 (4.70-5.41, 3.12 (2.89-3.36 and 1.89 (1.75-2.05, respectively]. In New Zealand, consultations for influenza-like illness by sentinel providers were more likely in the age groups of 65 years [OR (95% CI: 2.38 (1.74-3.26, 1.99 (1.62-2.45, 1.57 (1.30-1.89, 1.57 (1.30-1.88, 1.40 (1.17-1.69 and 1.39 (1.14-1.70, respectively]. CONCLUSIONS: The greatest increase in influenza cases during 2009 (H1N1 pandemic influenza period, in comparison with most recent seasonal influenza periods, was seen for school-aged children, adolescents, and younger adults.

  13. Influenza surveillance in the Pacific Island countries and territories during the 2009 pandemic: an observational study

    Kool Jacobus Leen


    Full Text Available Abstract Background Historically, Pacific island countries and territories (PICTs have been more severely affected by influenza pandemics than any other part of the world. We herein describe the emergence and epidemiologic characteristics of pandemic influenza H1N1 in PICTs from 2009 to 2010. Methods The World Health Organization gathered reports of influenza-like-illness and laboratory-confirmed pandemic H1N1 cases from all 23 Pacific island countries and territories, from April 2009 through August 2010. Data were gathered through weekly email reports from Pacific island countries and territories and through email or telephone follow-up. Results Pacific island countries and territories started detecting pandemic H1N1 cases in June 2009, firstly in French Polynesia, with the last new detection occurring in August 2009 in Tuvalu. Nineteen Pacific island countries and territories reported 1,972 confirmed cases, peaking in August 2009. No confirmed pandemic H1N1 cases were identified in Niue, Pitcairn and Tokelau; the latter instituted strict maritime quarantine. Influenza-like-illness surveillance showed trends similar to surveillance of confirmed cases. Seven Pacific island countries and territories reported 21 deaths of confirmed pandemic H1N1. Case-patients died of acute respiratory distress syndrome or multi-organ failure, or both. The most reported pre-existing conditions were obesity, lung disease, heart disease, and pregnancy. Pacific island countries and territories instituted a variety of mitigation measures, including arrival health screening. Multiple partners facilitated influenza preparedness planning and outbreak response. Conclusions Pandemic influenza spread rapidly throughout the Pacific despite enormous distances and relative isolation. Tokelau and Pitcairn may be the only jurisdictions to have remained pandemic-free. Despite being well-prepared, Pacific island countries and territories experienced significant morbidity and

  14. Estimating the incidence reporting rates of new influenza pandemics at an early stage using travel data from the source country.

    Chong, K C; Fong, H F; Zee, C Y


    During the surveillance of influenza pandemics, underreported data are a public health challenge that complicates the understanding of pandemic threats and can undermine mitigation efforts. We propose a method to estimate incidence reporting rates at early stages of new influenza pandemics using 2009 pandemic H1N1 as an example. Routine surveillance data and statistics of travellers arriving from Mexico were used. Our method incorporates changes in reporting rates such as linearly increasing trends due to the enhanced surveillance. From our results, the reporting rate was estimated at 0·46% during early stages of the pandemic in Mexico. We estimated cumulative incidence in the Mexican population to be 0·7% compared to 0·003% reported by officials in Mexico at the end of April. This method could be useful in estimation of actual cases during new influenza pandemics for policy makers to better determine appropriate control measures.

  15. Modeling uncertainties in workforce disruptions from influenza pandemics using dynamic input-output analysis.

    El Haimar, Amine; Santos, Joost R


    Influenza pandemic is a serious disaster that can pose significant disruptions to the workforce and associated economic sectors. This article examines the impact of influenza pandemic on workforce availability within an interdependent set of economic sectors. We introduce a simulation model based on the dynamic input-output model to capture the propagation of pandemic consequences through the National Capital Region (NCR). The analysis conducted in this article is based on the 2009 H1N1 pandemic data. Two metrics were used to assess the impacts of the influenza pandemic on the economic sectors: (i) inoperability, which measures the percentage gap between the as-planned output and the actual output of a sector, and (ii) economic loss, which quantifies the associated monetary value of the degraded output. The inoperability and economic loss metrics generate two different rankings of the critical economic sectors. Results show that most of the critical sectors in terms of inoperability are sectors that are related to hospitals and health-care providers. On the other hand, most of the sectors that are critically ranked in terms of economic loss are sectors with significant total production outputs in the NCR such as federal government agencies. Therefore, policy recommendations relating to potential mitigation and recovery strategies should take into account the balance between the inoperability and economic loss metrics.

  16. Research Preparedness Paves the Way to Respond to Pandemic H1N1 2009 Influenza Virus

    Michelle B French


    Full Text Available The international community has been preparing for an influenza pandemic because of the threat posed by H5N1 avian influenza. Over the past several years, Canada has dedicated funding to boost capacity for research, and public health and health care system readiness and response in the event of a pandemic. The current H1N1/09 influenza pandemic is now testing our readiness. From a research perspective, the present commentary discusses how have we prepared, along with the research gaps. We conclude that: sources of pandemics are not always predictable; investment in the past few years has paid off in a rapid response to pandemic H1N1/09 virus in Canada; and research to meet the challenges of infectious diseases has to be done on an ongoing long-term basis, and its funding has to be flexible, available and predictable to maintain capacity and expertise. In addition, new vaccine technologies are needed to develop and produce vaccines for public health emergencies in a timely fashion.

  17. Prenatal exposure to the 1957 influenza pandemic and non-affective psychosis in The Netherlands

    Selten, JP; Brown, AS; Moons, KGM; Slaets, JPJ; Susser, ES; Kahn, RS


    Second-trimester exposure to the 1957 A2 influenza pandemic is a controversial risk factor for schizophrenia. Two earlier studies of the Dutch psychiatric registry failed to find an increased risk for exposed subjects, but diagnostic misclassification within the spectrum of non-affective psychoses h

  18. The pandemic potential of avian influenza A(H7N9) virus: a review.

    Tanner, W D; Toth, D J A; Gundlapalli, A V


    In March 2013 the first cases of human avian influenza A(H7N9) were reported to the World Health Organization. Since that time, over 650 cases have been reported. Infections are associated with considerable morbidity and mortality, particularly within certain demographic groups. This rapid increase in cases over a brief time period is alarming and has raised concerns about the pandemic potential of the H7N9 virus. Three major factors influence the pandemic potential of an influenza virus: (1) its ability to cause human disease, (2) the immunity of the population to the virus, and (3) the transmission potential of the virus. This paper reviews what is currently known about each of these factors with respect to avian influenza A(H7N9). Currently, sustained human-to-human transmission of H7N9 has not been reported; however, population immunity to the virus is considered very low, and the virus has significant ability to cause human disease. Several statistical and geographical modelling studies have estimated and predicted the spread of the H7N9 virus in humans and avian species, and some have identified potential risk factors associated with disease transmission. Additionally, assessment tools have been developed to evaluate the pandemic potential of H7N9 and other influenza viruses. These tools could also hypothetically be used to monitor changes in the pandemic potential of a particular virus over time.

  19. Incorporating Research and Evaluation into Pandemic Influenza Vaccination Preparedness and Response


    Dr. Tom Shimabukuro, a medical officer at CDC, discusses Pandemic Influenza Vaccination Preparedness and Response.  Created: 3/27/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/27/2014.

  20. Pathogenesis Studies of the 2009 Pandemic Influenza Virus and Pseudorabies Virus From Wild Pigs In Swine

    Over the last ten years in the United States the epidemiology and ecology of swine flu and pseudorabies has been dynamic. Swine flu is caused by influenza A virus and the disease was first recognized in pigs concurrent with the 1918 Spanish flu pandemic in humans. Pigs displayed clinical signs simil...

  1. Coordination Costs for School-Located Influenza Vaccination Clinics, Maine, 2009 H1N1 Pandemic

    Asay, Garrett R. Beeler; Cho, Bo-Hyun; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.


    School nurses played a key role in Maine's school-located influenza vaccination (SLV) clinics during the 2009-2010 pandemic season. The objective of this study was to determine, from the school district perspective, the labor hours and costs associated with outside-clinic coordination activities (OCA). The authors defined OCA as labor hours spent…

  2. Healthcare workers' attitudes to working during pandemic influenza: a qualitative study

    Petts Judith I


    Full Text Available Abstract Background Healthcare workers (HCWs will play a key role in any response to pandemic influenza, and the UK healthcare system's ability to cope during an influenza pandemic will depend, to a large extent, on the number of HCWs who are able and willing to work through the crisis. UK emergency planning will be improved if planners have a better understanding of the reasons UK HCWs may have for their absenteeism, and what might motivate them to work during an influenza pandemic. This paper reports the results of a qualitative study that explored UK HCWs' views (n = 64 about working during an influenza pandemic, in order to identify factors that might influence their willingness and ability to work and to identify potential sources of any perceived duty on HCWs to work. Methods A qualitative study, using focus groups (n = 9 and interviews (n = 5. Results HCWs across a range of roles and grades tended to feel motivated by a sense of obligation to work through an influenza pandemic. A number of significant barriers that may prevent them from doing so were also identified. Perceived barriers to the ability to work included being ill oneself, transport difficulties, and childcare responsibilities. Perceived barriers to the willingness to work included: prioritising the wellbeing of family members; a lack of trust in, and goodwill towards, the NHS; a lack of information about the risks and what is expected of them during the crisis; fear of litigation; and the feeling that employers do not take the needs of staff seriously. Barriers to ability and barriers to willingness, however, are difficult to separate out. Conclusion Although our participants tended to feel a general obligation to work during an influenza pandemic, there are barriers to working, which, if generalisable, may significantly reduce the NHS workforce during a pandemic. The barriers identified are both barriers to willingness and to ability. This suggests that pandemic planning

  3. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A. (Sinai); (Scripps); (Vanderbilt)


    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  4. Protection of racial/ethnic minority populations during an influenza pandemic.

    Hutchins, Sonja S; Fiscella, Kevin; Levine, Robert S; Ompad, Danielle C; McDonald, Marian


    Racial/ethnic minority populations experience worse health outcomes than do other groups during and after disasters. Evidence for a differential impact from pandemic influenza includes both higher rates of underlying health conditions in minority populations, increasing their risk of influenza-related complications, and larger socioeconomic (e.g., access to health care), cultural, educational, and linguistic barriers to adoption of pandemic interventions. Implementation of pandemic interventions could be optimized by (1) culturally competent preparedness and response that address specific needs of racial/ethnic minority populations, (2) improvements in public health and community health safety net systems, (3) social policies that minimize economic burdens and improve compliance with isolation and quarantine, and (4) relevant, practical, and culturally and linguistically tailored communications.

  5. The influenza pandemic and Europe: the social impact and public health response

    John Paget


    Full Text Available Influenza is unpredictable. It is a virus that
    spreads globally and each season viruses emerge
    with different virological, clinical and epidemiological characteristics. Usually influenza affects 5-20% [1] of the population but sometimes a pandemic virus emerges which spreads on a worldwide scale and infects a larger proportion of the human population.
    On 11 June 2009 WHO announced that the world was confronted with a pandemic virus – pandemic (H1N1 2009 virus. This virus was first detected in two children in the United States in March 2009 but had its epidemiological origins in Mexico City in January-March 2009 [2]. The virus
    quickly spread to the US and Canada, and then further afield. In the European Union and EEA countries, there are currently 9453 cases and four deaths and globally there are now over 79,000 cases and 332 deaths (3 July 2009 [3].

  6. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

    van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs


    Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

  7. A vaccine manufacturer's approach to address medical needs related to seasonal and pandemic influenza viruses.

    Baras, Benoit; Bouveret, Nancy; Devaster, Jeanne-Marie; Fries, Louis; Gillard, Paul; Sänger, Roland; Hanon, Emmanuel


    Vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses. For the prevention of seasonal influenza, Fluarix and FluLaval have been marketed since 1987 and 1992, respectively. Both vaccines have consistently been shown to meet or exceed the regulatory criteria for immunogenicity against the three strains H1N1, H3N2 and B, have a good safety profile, and are recommended for vaccinating children and adults of all ages. For the prevention of pandemic influenza, GlaxoSmithKline (GSK) has obtained licensure of a pre-pandemic vaccine, Prepandrix. This split-virus H5N1 adjuvanted with AS03, a proprietary oil-in-water emulsion-based adjuvant system, has demonstrated broad immunity against drifted H5N1 strains and has been shown to be effective in preventing mortality and viral shedding in animal studies. The influenza vaccine portfolio of GSK addresses specific medical needs related to seasonal or pandemic influenza viruses, which remain an important public health threat worldwide.

  8. Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health.

    Kong, Weili; Wang, Feibing; Dong, Bin; Ou, Changbo; Meng, Demei; Liu, Jinhua; Fan, Zhen-Chuan


    Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens.

  9. Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico.

    Gerardo Chowell


    Full Text Available BACKGROUND: Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April-December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission. METHODS AND FINDINGS: We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April-December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April-May (Mexico City area, a second wave in June-July (southeastern states, and a geographically widespread third wave in August-December. The median age of laboratory confirmed ILI cases was ∼ 18 years overall and increased to ∼ 31 years during autumn (p<0.0001. The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5% among people over 60 years. The regional R estimates were 1.8-2.1, 1.6-1.9, and 1.2-1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%-37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school

  10. The response of the Liguria Region (Italy) to the pandemic influenza virus A/H1N1sv.

    Amicizia, D; Cremonesi, I; Carloni, R; Schiaffino, S


    Influenza is a cause of acute respiratory disease. It has a typical epidemic nature during the winter season, but may also assume a pandemic pattern when a completely new virus spreads among humans. Influenza places a heavy economic and healthcare burden on both the National Health Service and society. During the 2009/2010 influenza pandemic season, the Liguria Region drew upon the specific skills of the various sectors of the Department of Health and Social Services. In collaboration with the Department of Health Sciences of the University of Genova, the Regional Health Agency (RHA) and other public organizations, steps were taken to address the issues of technical and scientific updating and the coordination of all the departments of Local Healthcare Units in Liguria. The main activities conducted at the regional level provided an adequate response to the influenza pandemic. These activities focused on Local and National Influenza Surveillance Systems, the regional Pandemic Plan, vaccination strategies for seasonal and pandemic influenza, and the communication of data from monitoring programs (sentinel physicians--syndromic surveillance). The prevention of influenza transmission and containment of epidemics and pandemics require effective communication strategies that should target the whole population.

  11. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico.

    Mena, Ignacio; Nelson, Martha I; Quezada-Monroy, Francisco; Dutta, Jayeeta; Cortes-Fernández, Refugio; Lara-Puente, J Horacio; Castro-Peralta, Felipa; Cunha, Luis F; Trovão, Nídia S; Lozano-Dubernard, Bernardo; Rambaut, Andrew; van Bakel, Harm; García-Sastre, Adolfo


    Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade.

  12. Detection of Seasonal Influenza H1N1 and H3N2 Viruses using RT-PCR Assay during 2009 Pandemic Influenza in Golestan Province

    Zhand, S. (MSc


    Full Text Available Background and Objective: The emergence of a novel H1N1influenza A virus of animal origin with transmissibility from human to human poses pandemic concern. Current subtypes of Seasonal influenza A viruses spread in human are influenza A H1N1 influenza A H3N2 and influenza type B viruses. The aim of this study was to determine current strains of the H3N2 and new H1N1 subtypes of influenza A virus from patients suspected influenza infection in 2009 flu pandemic in Golestan province, Iran. Material and Methods: In this descriptive study, respiratory samples (n = 153 from patients with acute respiratory symptoms were collected in 2009 flu pandemic applied during 2009 pandemic influenza in Golestan province. After reverse transcription of extracted viral RNA, PCR was developed for both H1N1and H3N2subtypes using CDC specific primers. Results: The mean age of patients was 16.59. Of them 45.1% were male. Thirteen (8.49% were infected with seasonal influenza H1N1 and 25(16.33% with seasonal H3N2influenza. Conclusion: The rate of infection with seasonal H1N1and H3N2is similar to other studies reported from Iran, but lower than the rate reported from other parts of the world

  13. Pandemic influenza A (H1N1 2009 vaccine: An update

    M K Goel


    Full Text Available The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 coun-tries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009 virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.

  14. Responding to vaccine safety signals during pandemic influenza: a modeling study.

    Judith C Maro

    Full Text Available Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system.We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1 expected vaccination benefit from averted influenza; 2 expected vaccination risk from vaccine-associated febrile seizures; 3 expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4 expected change in vaccine-seeking behavior in future influenza seasons.Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3:1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior.The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.

  15. Meteorological Influence on the 2009 Influenza A (H1N1) Pandemic in Mainland China.

    Zhao, X.; Cai, J.; Feng, D.; Bai, Y.; Xu, B.


    Since May 2009, a novel influenza A (H1N1) pandemic has spread rapidly in mainland China from Mexico. Although there has been substantial analysis of this influenza, reliable work estimating its spatial dynamics and determinants remain scarce. The survival and transmission of this pandemic virus not only depends on its biological properties, but also a correlation with external environmental factors. In this study, we collected daily influenza A (H1N1) cases and corresponding annual meteorological factors in mainland China from May 2009 to April 2010. By analyzing these data at county-level, a similarity index, which considered the spatio-temporal characteristics of the disease, was proposed to evaluate the role and lag time of meteorological factors in the influenza transmission. The results indicated that the influenza spanned a large geographical area, following an overall trend from east to west across the country. The spatio-temporal transmission of the disease was affected by a series of meteorological variables, especially absolute humidity with a 3-week lag. These findings confirmed that the absolute humidity and other meteorological variables contributed to the local occurrence and dispersal of influenza A (H1N1). The impact of meteorological variables and their lag effects could be involved in the improvement of effective strategies to control and prevent disease outbreaks.

  16. A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice.

    Julia Steitz

    Full Text Available BACKGROUND: In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model. METHODS: We generated two adenovirus(Ad5-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA from the recently emerged swine influenza isolate A/California/04/2009 (H1N1pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNgamma Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus. CONCLUSIONS/SIGNIFICANCE: A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization.

  17. Prior population immunity reduces the expected impact of CTL-inducing vaccines for pandemic influenza control.

    Kirsty J Bolton

    Full Text Available Vaccines that trigger an influenza-specific cytotoxic T cell (CTL response may aid pandemic control by limiting the transmission of novel influenza A viruses (IAV. We consider interventions with hypothetical CTL-inducing vaccines in a range of epidemiologically plausible pandemic scenarios. We estimate the achievable reduction in the attack rate, and, by adopting a model linking epidemic progression to the emergence of IAV variants, the opportunity for antigenic drift. We demonstrate that CTL-inducing vaccines have limited utility for modifying population-level outcomes if influenza-specific T cells found widely in adults already suppress transmission and prove difficult to enhance. Administration of CTL-inducing vaccines that are efficacious in "influenza-experienced" and "influenza-naive" hosts can likely slow transmission sufficiently to mitigate a moderate IAV pandemic. However if neutralising cross-reactive antibody to an emerging IAV are common in influenza-experienced hosts, as for the swine-variant H3N2v, boosting CTL immunity may be ineffective at reducing population spread, indicating that CTL-inducing vaccines are best used against novel subtypes such as H7N9. Unless vaccines cannot readily suppress transmission from infected hosts with naive T cell pools, targeting influenza-naive hosts is preferable. Such strategies are of enhanced benefit if naive hosts are typically intensively mixing children and when a subset of experienced hosts have pre-existing neutralising cross-reactive antibody. We show that CTL-inducing vaccination campaigns may have greater power to suppress antigenic drift than previously suggested, and targeting adults may be the optimal strategy to achieve this when the vaccination campaign does not have the power to curtail the attack rate. Our results highlight the need to design interventions based on pre-existing cellular immunity and knowledge of the host determinants of vaccine efficacy, and provide a framework

  18. Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957

    Liu, Junfeng; Stevens, David J.; Lesley F Haire; Walker, Philip A.; Coombs, Peter J.; Russell, Rupert J.; Gamblin, Steven J.; John J Skehel


    The viruses that caused the three influenza pandemics of the twentieth century in 1918, 1957, and 1968 had distinct hemagglutinin receptor binding glycoproteins that had evolved the capacity to recognize human cell receptors. We have determined the structure of the H2 hemagglutinin from the second pandemic, the “Asian Influenza” of 1957. We compare it with the 1918 “Spanish Influenza” hemagglutinin, H1, and the 1968 “Hong Kong Influenza” hemagglutinin, H3, and show that despite its close over...

  19. Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

    Farooqui Amber


    Full Text Available Abstract Background Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA of viral genomes that might correlate with their different phenotypic behavior. Conclusions The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

  20. Seroprevalence study in Vojvodina (Serbia following 2009 pandemic influenza A(H1N1v

    Petrović Vladimir


    Full Text Available Introduction. The seroprevalence study was performed in Vojvodina during May and June 2010 in order to asses the effects of the 2009 pandemic influenza A(H1N1v epidemic on herd immunity. It was a part of the Serbian Ministry of Health funded nationwide study. Objective. Prevalence of antibodies against 2009 pandemic influenza A(H1N1v was determined in a 1% sample of the population monitored for influenza-like illness and acute respiratory infections in Vojvodina through sentinel surveillance system. Methods. The study sample involved a total of 1004 inhabitants of Vojvodina. The control group consisted of randomly selected and age-adjusted 1054 sera collected in the pre-pandemic period. Sera were tested by the reaction of hemagglutination inhibition using influenza A/California/7/2009 (H1N1 antigen in dilution from 1:8 to 1:256. Antibody titers ≥1:32 and ≥1:8 were considered protective and diagnostic, respectively. Results. The differences between control and study sera in all age groups were significant for both diagnostic ≥1/8 and protective titres ≥1/32 of hemagglutination inhibition antibodies (chi square test, p<0.001. The highest percentage of seropositive subjects was registered in the age group 15-19 years followed by children aged 5-14 years. Both diagnostic and protective titres were about twice higher in the vaccinated as compared to the non-vaccinated group. There were no statistically significant differences in seroprevalence between seven districts of Vojvodina. Conclusion. The 2009 pandemic influenza A(H1N1v epidemic significantly influenced the herd immunity in our population regardless of low immunization coverage with highest immunity levels in adolescents aged 15-19 years and with similar herd immunity levels in all the regions in the province six months after the outbreak.

  1. Early introduction and delayed dissemination of pandemic influenza, Gabon.

    Lekana-Douki, Sonia Etenna; Mouinga-Ondémé, Augustin; Nkoghe, Dieudonné; Drosten, Christian; Drexler, Jan Felix; Kazanji, Mirdad; Leroy, Eric M


    Active surveillance in health care centers in Gabon during 2009-2011 detected 72 clinical cases of pandemic (H1N1) 2009 (pH1N1). We found that pH1N1 virus was introduced in mid-2009 but spread throughout the country in 2010. Thus, Gabon was also affected by pH1N1.

  2. The politics of medicine and the global governance of pandemic influenza.

    Kamradt-Scott, Adam


    While still significant, the 2009 H1N1 (A) influenza pandemic was generally viewed as comparatively mild in contrast to past influenza pandemics. Even so, the conventional response of many governments to protect their populations against the threat from the H1N1 virus was to ensure adequate vaccine production and/or access to supplies of vaccines and antiviral medications. In this article, I examine the influence of biomedical knowledge (and the professionals that wield it) in determining the acceptable and rational limits of influenza public policy from 1918 to today. Particular attention is given to the role that medical practitioners have played in shaping post-World War II influenza policy and governance structures, together with the development, deployment, and political effect of more recent biomedical techniques-such as evidence-based medicine-in reinforcing the importance attached to influenza vaccines and antivirals. The article concludes by discussing how the intense focus on pharmaceutical-based solutions reflects a particular view of biomedicine that has had serious political implications in distorting global health governance arrangements, and I argue that only by unpacking these structures and revealing the political authority in play can alternative policy responses more appropriate to a wider proportion of humanity be considered.

  3. Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection

    Eun Lee


    Full Text Available Purpose : The purpose of this article is to describe the clinical and epidemiologic features and outcomes among children hospitalized with pandemic influenza A/H1N1 2009 infection. Methods : We retrospectively reviewed the charts of hospitalized pediatric patients (&lt;18 years diagnosed with pandemic influenza A/H1N1 2009 infection by reverse-transcriptase polymerase chain reaction at a tertiary hospital in Seoul, Korea, between September 2009 and February 2010. Results : A total of 72 children were hospitalized with pandemic influenza A/H1N1 2009 infection (median age, 6.0 years; range, 2 months to 18 years. A total of 40% had at least 1 underlying medical condition, including asthma (17%, malignancies (19%, and heart diseases (17%. Of the 72 patients, 54 (76% children admitted with H1N1 infection showed radiographic alterations compatible with pneumonia. There was no significant difference in pre-existing conditions between pandemic influenza A/H1N1 infected patients with or without pneumonia. Children with pandemic influenza A/ H1N1 pneumonia were more likely to have a lower lymphocyte ratio (P=0.02, higher platelet count (P=0.02, and higher level of serum glucose (P=0.003, and more commonly presented with dyspnea than did those without pneumonia (P=0.04. Conclusion : No significant differences in age, sex, or presence of preexisting conditions were found between children hospitalized with pandemic influenza A/H1N1 H1N1 influenza infection with pneumonia and those without pneumonia. Higher leukocyte count, higher glucose level, and a lower lymphocyte ratio were associated with the development of pandemic A/H1N1 2009 influenza pneumonia.

  4. Pandemic potential of avian influenza A (H7N9) viruses.

    Watanabe, Tokiko; Watanabe, Shinji; Maher, Eileen A; Neumann, Gabriele; Kawaoka, Yoshihiro


    Avian influenza viruses rarely infect humans, but the recently emerged avian H7N9 influenza viruses have caused sporadic infections in humans in China, resulting in 440 confirmed cases with 122 fatalities as of 16 May 2014. In addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with H7N9 viruses. These viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes that likely contribute to their ability to infect mammals. In this review, we summarize the characteristic features of the novel H7N9 viruses and assess their pandemic potential.

  5. An exploration of the effects of pandemic influenza on infant mortality in Toronto, 1917–1921

    Stacey Hallman


    Full Text Available This study investigates infant mortality from pandemic influenza in Toronto, Canada, from September to December 1918, through theRegistered Death Records of the Province of Ontario. A comparison of infant deaths in 1918 to surrounding years (1917–21 revealedthat although mortality rates remained relatively stable, there were changes in the mortality profile during the epidemic. Deaths frominfluenza did increase slightly, and the epidemic altered the expected sex ratio of infant deaths. Although communities may be greatly strained by an influenza epidemic, the infant mortality rate may be more representative of long-term social and environmental conditions rather than acute, intensive crises.


    Andrés G. Seguel


    Full Text Available The aim of the present paper is to present the symbolic features that are exposed by the concept of artefact in the context of a pandemic alarm, such as the A (H1N1 influenza. The symbolic qualities entailed by the notion of artefact are well-known within the Social Sciences: Sociology, Anthropology, Archaeology, and Linguistics. The artefact is basically not an object, but an action aimed at designing, simulating or creating a simile by means of material, technological or linguistic structures. The purpose of the present work is to unveil the symbolic dimensions that are activated by the A (H1N1 influenza as a Pandemic Artefact: a the assumption of separating information from matter; b the need for a material support to enable the exchange; c the sociological reflexivity of the artefact and its agency; d the arbitrariness of its social use, that detaches it from the design as intention.

  7. Pandemic potential of H7N9 influenza viruses

    Watanabe, Tokiko; Watanabe, Shinji; Maher, Eileen A.; Neumann, Gabriele; Kawaoka, Yoshihiro


    Avian influenza viruses rarely infect humans, but the recently emerged avian H7N9 influenza viruses have caused sporadic infections in humans in China, resulting in 440 confirmed cases with 122 fatalities as of May 16, 2014. In addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with H7N9 viruses. These viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid cha...

  8. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G


    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  9. Pandemic (H1N1 2009 influenza: Experience from a critical care unit in India

    Sahoo Jyoti


    Full Text Available This case series details our experience with seven patients with pandemic (H1N1 2009 influenza from an intensive care unit in India. All the patients had respiratory failure requiring ventilation except one; two patients developed pneumothorax. Of the seven patients, two died (28.5% and five recovered. Four patients had co-morbid conditions and one was morbidly obese; all the five patients were discharged alive.

  10. Facing the threat of influenza pandemic - roles of and implications to general practitioners

    Lee Albert


    Full Text Available Abstract The 2009 pandemic of H1N1 influenza, compounded with seasonal influenza, posed a global challenge. Despite the announcement of post-pandemic period on 10 August 2010 by theWHO, H1N1 (2009 virus would continue to circulate as a seasonal virus for some years and national health authorities should remain vigilant due to unpredictable behaviour of the virus. Majority of the world population is living in countries with inadequate resources to purchase vaccines and stockpile antiviral drugs. Basic hygienic measures such as wearing face masks and the hygienic practice of hand washing could reduce the spread of the respiratory viruses. However, the imminent issue is translating these measures into day-to-day practice. The experience from Severe Acute Respiratory Syndrome (SARS in Hong Kong has shown that general practitioners (GPs were willing to discharge their duties despite risks of getting infected themselves. SARS event has highlighted the inadequate interface between primary and secondary care and valuable health care resources were thus inappropriately matched to community needs. There are various ways for GPs to contribute in combating the influenza pandemic. They are prompt in detecting and monitoring epidemics and mini-epidemics of viral illnesses in the community. They can empower and raise the health literacy of the community such as advocating personal hygiene and other precautious measures. GPs could also assist in the development of protocols for primary care management of patients with flu-like illnesses and conduct clinical audits on the standards of preventive and treatment measures. GPs with adequate liaison with public health agencies would facilitate early diagnosis of patients with influenza. In this article, we summarise the primary care actions for phases 4-6 of the pandemic. We shall discuss the novel roles of GPs as alternative source of health care for patients who would otherwise be cared for in the secondary care

  11. A statistical method utilizing information of imported cases to estimate the transmissibility for an influenza pandemic

    Chong, Ka Chun; Zee, Benny Chung Ying; Wang, Maggie Haitian


    Background In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections connecting the originating country with other regions. It can be a complete and timely source for estimating the basic reproduction number (R 0 ), a key indicator of disease transmissibility. Method In this study, we developed a likelihood-based method using arrival times of infected c...

  12. Evolutionary pathways of the pandemic influenza A (H1N1 2009 in the UK.

    Monica Galiano

    Full Text Available The emergence of the influenza (H1N1 2009 virus provided a unique opportunity to study the evolution of a pandemic virus following its introduction into the human population. Virological and clinical surveillance in the UK were comprehensive during the first and second waves of the pandemic in 2009, with extensive laboratory confirmation of infection allowing a detailed sampling of representative circulating viruses. We sequenced the complete coding region of the haemagglutinin (HA segment of 685 H1N1 pandemic viruses selected without bias during two waves of pandemic in the UK (April-December 2009. Phylogenetic analysis showed that although temporal accumulation of amino acid changes was observed in the HA sequences, the overall diversity was less than that typically seen for seasonal influenza A H1N1 or H3N2. There was co-circulation of multiple variants as characterised by signature amino acid changes in the HA. A specific substitution (S203T became predominant both in UK and global isolates. No antigenic drift occurred during 2009 as viruses with greater than four-fold reduction in their haemagglutination inhibition (HI titre ("low reactors" were detected in a low proportion (3% and occurred sporadically. Although some limited antigenic divergence in viruses with four-fold reduction in HI titre might be related to the presence of 203T, additional studies are needed to test this hypothesis.

  13. 流感大流行带来的启示%The Inspiration from Pandemic Influenza



      人类历史上曾暴发过4次流感大流行,即1918年“西班牙流感”、1957年“亚洲流感”、1968年“香港流感”和2009年“北美流感”,每一次流感大流行都给全球公共卫生、社会经济等带来极大危害。本文从流感的流行史、流行的特点、死亡率等流行病学特征进行探讨,为全面认识流感,正确面对和科学防控流感大流行提供借鉴。%  Fore major pandemics were recorded in the history of human:“Spanish Influenza”in 1918,“Asian Influenza”in 1957,“Hong Kong influenza”in1968, and“Northern American influenza”in 2009. Each influenza pandemic has damaged the economic development and has influenced the global public health badly. In this review, we discussed the pandemic history of influenza, pandemic characters,mortality and other epidemiological characteristics for knowing influenza on all sides, facing influenza pandemic exactly, providing scientific reference on prevention and control of influenza pandemic.

  14. Death from 1918 pandemic influenza during the First World War: a perspective from personal and anecdotal evidence.

    Wever, Peter C; van Bergen, Leo


    The Meuse-Argonne offensive, a decisive battle during the First World War, is the largest frontline commitment in American military history involving 1.2 million U.S. troops. With over 26,000 deaths among American soldiers, the offensive is considered "America's deadliest battle". The Meuse-Argonne offensive coincided with the highly fatal second wave of the influenza pandemic in 1918. In Europe and in U.S. Army training camps, 1918 pandemic influenza killed around 45,000 American soldiers making it questionable which battle should be regarded "America's deadliest". The origin of the influenza pandemic has been inextricably linked with the men who occupied the military camps and trenches during the First World War. The disease had a profound impact, both for the military apparatus and for the individual soldier. It struck all the armies and might have claimed toward 100 000 fatalities among soldiers overall during the conflict while rendering millions ineffective. Yet, it remains unclear whether 1918 pandemic influenza had an impact on the course of the First World War. Still, even until this day, virological and bacteriological analysis of preserved archived remains of soldiers that succumbed to 1918 pandemic influenza has important implications for preparedness for future pandemics. These aspects are reviewed here in a context of citations, images, and documents illustrating the tragic events of 1918.

  15. Gradual changes in the age distribution of excess deaths in the years following the 1918 influenza pandemic in Copenhagen

    Saglanmak, Neslihan; Andreasen, Viggo; Simonsen, Lone


    Background: The 1918 influenza pandemic was associated with an unusual age pattern of mortality, with most deaths occurring among young adults. Few studies have addressed changes in the age distribution for influenza-related mortality in the pre-pandemic and post-pandemic period, which has...... on trends in the rate ratio of excess respiratory mortality in people under and over 65 years. Conclusions: The unusual elevation of excess respiratory mortality rates in young and middle-aged adults was confined to the first three years of A/H1N1 virus circulation 1918–1920; the rapid return to “epidemic...... in the recrudescent pandemic wave of 1919–1920 may suggest the emergence of an early influenza A/H1N1 drift variant. Subsequent drift events may have been associated with the particularly severe 1928–1929 epidemic in Denmark and elsewhere....

  16. Response to 2009 pandemic influenza a (H1N1) vaccine in HIV-infected patients and the influence of prior seasonal influenza vaccination

    D. Soonawala (Darius); G.F. Rimmelzwaan (Guus); L.B.S. Gelinck (Luc); L.G. Visser; F.P. Kroon (Frank)


    textabstractBackground: The immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition w

  17. Sublingual administration of bacteria-expressed influenza virus hemagglutinin 1 (HA1) induces protection against infection with 2009 pandemic H1N1 influenza virus.

    Shim, Byoung-Shik; Choi, Jung-Ah; Song, Ho-Hyun; Park, Sung-Moo; Cheon, In Su; Jang, Ji-Eun; Woo, Sun Je; Cho, Chung Hwan; Song, Min-Suk; Kim, Hyemi; Song, Kyung Joo; Lee, Jae Myun; Kim, Suhng Wook; Song, Dae Sub; Choi, Young Ki; Kim, Jae-Ouk; Nguyen, Huan Huu; Kim, Dong Wook; Bahk, Young Yil; Yun, Cheol-Heui; Song, Man Ki


    Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.

  18. Predictors of influenza in the adult population during seasonal and A(H1N1)pdm09 pandemic influenza periods.

    Gefenaite, G.; Tacken, M.; Kolthof, J.; Mulder, B.; Korevaar, J.C.; Stirbu-Wagner, I.; Bos, J.; Stolk, R.P.; Hak, E.


    We aimed to assess whether the characteristics of influenza-like illness (ILI) cases in the general population were similar during the seasonal and pandemic A(H1N1)pdm09 influenza periods. We conducted a study using a general population database, which included demographic (sex, age) and clinical (u

  19. Predictors of influenza in the adult population during seasonal and A(H1N1)pdm09 pandemic influenza periods

    Gefenaite, G.; Tacken, M.; Kolthof, J.; Mulder, B.; Korevaar, J. C.; Stirbu-Wagner, I.; Bos, J.; Stolk, R. P.; Hak, E.


    We aimed to assess whether the characteristics of influenza-like illness (ILI) cases in the general population were similar during the seasonal and pandemic A(H1N1)pdm09 influenza periods. We conducted a study using a general population database, which included demographic (sex, age) and clinical (u

  20. Biography, pandemic time and risk: Pregnant women reflecting on their experiences of the 2009 influenza pandemic.

    Lohm, Davina; Flowers, Paul; Stephenson, Niamh; Waller, Emily; Davis, Mark D M


    During the 2009 H1N1 pandemic, it was identified that women in the third trimester of pregnancy were particularly at risk of serious respiratory distress. At-risk women were advised to seek vaccination, avoid contact with anyone unwell, maintain hygiene routines and stop smoking. We examine this situation of emergent and intense risk produced at the intersection of individual biography and the historical event of a public health emergency. We examine how pregnant women took account of risk, how they negotiated incomplete and at times contradictory advice and shaped courses of action that assisted them to manage the emerging terrain of pandemic threat. Public health risk management advice was endorsed, although choosing vaccination was fraught. Social distancing, too, was seen as a valuable risk moderation strategy. However, time, and specifically the intersection of individual pregnancy timelines with the pandemic's timeline, was also seen as an important risk management resource. The implications of this mix of sanctioned and temporal risk management practices are discussed.

  1. Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant U.S. Military Women and Their Newborns


    Macdonald TM, Shakir S, Dryburgh M, Mantay BJ, McDonnell P, et al. Influenza H1N1 (swine flu ) vaccination : a safety surveillance feasibility study using...Naval Health Research Center Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant Women and Their Newborns Ava M.S. Conlin Anna...Safety of the Pandemic H1N1 Influenza Vaccine Among Pregnant U.S. Military Women and Their Newborns Ava Marie S. Conlin, DO, MPH, Anna T. Bukowinski

  2. The effect of risk perception on the 2009 H1N1 pandemic influenza dynamics.

    Piero Poletti

    Full Text Available BACKGROUND: The 2009 H1N1 pandemic influenza dynamics in Italy was characterized by a notable pattern: as it emerged from the analysis of influenza-like illness data, after an initial period (September-mid-October 2009 characterized by a slow exponential increase in the weekly incidence, a sudden and sharp increase of the growth rate was observed by mid-October. The aim here is to understand whether spontaneous behavioral changes in the population could be responsible for such a pattern of epidemic spread. METHODOLOGY/PRINCIPAL FINDINGS: In order to face this issue, a mathematical model of influenza transmission, accounting for spontaneous behavioral changes driven by cost/benefit considerations on the perceived risk of infection, is proposed and validated against empirical epidemiological data. The performed investigation revealed that an initial overestimation of the risk of infection in the general population, possibly induced by the high concern for the emergence of a new influenza pandemic, results in a pattern of spread compliant with the observed one. This finding is also supported by the analysis of antiviral drugs purchase over the epidemic period. Moreover, by assuming a generation time of 2.5 days, the initially diffuse misperception of the risk of infection led to a relatively low value of the reproductive number , which increased to in the subsequent phase of the pandemic. CONCLUSIONS/SIGNIFICANCE: This study highlights that spontaneous behavioral changes in the population, not accounted by the large majority of influenza transmission models, can not be neglected to correctly inform public health decisions. In fact, individual choices can drastically affect the epidemic spread, by altering timing, dynamics and overall number of cases.

  3. Social capital and health-protective behavior intentions in an influenza pandemic.

    Ying-Chih Chuang

    Full Text Available Health-protective behaviors, such as receiving a vaccine, wearing a face mask, and washing hands frequently, can reduce the risk of contracting influenza. However, little is known about how social capital may influence health-protective behavior in the general population. This study examined whether each of the social capital dimensions (bonding, bridging, and linking contributed to the intention to adopt any of the health-protective behaviors in an influenza pandemic. The data of this study were from the 2014 Taiwan Social Change Survey. A stratified, three-stage probability proportional-to-size sampling from across the nation, was conducted to select adults aged 20 years and older (N = 1,745. Bonding social capital was measured by the frequency of neighborly contact and support. Bridging social capital was measured based on association membership. Linking social capital was measured according to general government trust and trust in the government's capacity to counter an influenza pandemic. Binary logistic regressions were used to assess the multivariate associations between social capital and behavioral intention. The study results indicate that social capital may influence the response to influenza pandemic. Specifically, the intention to receive a vaccine and to wash hands more frequently were associated with the linking dimension and the bonding dimension of social capital, while the intention to wear a face mask was associated with all forms of social capital. The findings of this study suggest that government credibility and interpersonal networks may play a crucial role in health-protective behavior. This study provides new insights into how to improve the effectiveness of influenza prevention campaigns.

  4. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1.

    Yong-Dae Gwon

    Full Text Available An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA. However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV envelope-coated, baculovirus-based, virus-like-particle (VLP-forming DNA vaccine (termed AcHERV-VLP against pandemic influenza A/California/04/2009 (pH1N1. BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m. and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8, elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.

  5. One versus two doses: What is the best use of vaccine in an influenza pandemic?

    Laura Matrajt


    Full Text Available Avian influenza A (H7N9, emerged in China in April 2013, sparking fears of a new, highly pathogenic, influenza pandemic. In addition, avian influenza A (H5N1 continues to circulate and remains a threat. Currently, influenza H7N9 vaccines are being tested to be stockpiled along with H5N1 vaccines. These vaccines require two doses, 21 days apart, for maximal protection. We developed a mathematical model to evaluate two possible strategies for allocating limited vaccine supplies: a one-dose strategy, where a larger number of people are vaccinated with a single dose, or a two-dose strategy, where half as many people are vaccinated with two doses. We prove that there is a threshold in the level of protection obtained after the first dose, below which vaccinating with two doses results in a lower illness attack rate than with the one-dose strategy; but above the threshold, the one-dose strategy would be better. For reactive vaccination, we show that the optimal use of vaccine depends on several parameters, with the most important one being the level of protection obtained after the first dose. We describe how these vaccine dosing strategies can be integrated into effective pandemic control plans.

  6. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.

    Welsh, M D; Baird, P M; Guelbenzu-Gonzalo, M P; Hanna, A; Reid, S M; Essen, S; Russell, C; Thomas, S; Barrass, L; McNeilly, F; McKillen, J; Todd, D; Harkin, V; McDowell, S; Choudhury, B; Irvine, R M; Borobia, J; Grant, J; Brown, I H


    The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.

  7. Pandemic 2009 Influenza A (H1N1 Infection in Children

    Taner Özgür


    Full Text Available Introduction: The aim of this study is to share our experience of sixty-eight pediatric hospitalizations associated with influenza-like illness and pneumonia between November, 2009 and December, 2009.Materials and Methods: Clinical signs and symptoms, laboratory and radiological results, length of stay in hospital and intensive care unit, treatments and complications were compared in laboratory confirmed pandemic influenza A positive and negative cases.Results: There was no significant difference in gender distribution between the two groups. The number of positive cases in patients over 5 years of age were significantly higher than the same age group in negative patients (p=0.004. There were underlying health conditions in 78.8% of the positive cases and in 68.8% of the negative cases (p=0.57. The incidence of diarrhea in positive group was significantly higher than in the negative group (p=0.02. Low immunization rates of the seasonal influenza vaccine were remarkable in each group. There was no significant difference in vaccination rates between the two groups (p=0.99.Conclusions: The severity of the disease remained similar in patients with positive and negative groups. In both groups, the high ratio of those having an underlying disease was noteworthy. (Journal of Current Pediatrics 2011; 9: 53-9Key words: Pandemic 2009 influenza A, childhood, pneumonia

  8. Economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories

    Kelso, Joel K.; Halder, Nilimesh; Postma, Maarten J.; Milne, George J.


    Background: The threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza A (H5N1) is very real, and is reinforced by recent results showing that genetically modified A(H5N1) may be readily transmitted between ferrets. Public health authorities are hesitant in intro

  9. Systematic review of economic evaluations of preparedness strategies and interventions against influenza pandemics.

    Román Pérez Velasco

    Full Text Available BACKGROUND: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. METHODS: The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. RESULTS: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita, the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries. CONCLUSION: The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost

  10. Priority setting of ICU resources in an influenza pandemic: a qualitative study of the Canadian public's perspectives

    Silva Diego S


    Full Text Available Abstract Background Pandemic influenza may exacerbate existing scarcity of life-saving medical resources. As a result, decision-makers may be faced with making tough choices about who will receive care and who will have to wait or go without. Although previous studies have explored ethical issues in priority setting from the perspective of clinicians and policymakers, there has been little investigation into how the public views priority setting during a pandemic influenza, in particular related to intensive care resources. Methods To bridge this gap, we conducted three public town hall meetings across Canada to explore Canadian's perspectives on this ethical challenge. Town hall discussions group discussions were digitally recorded, transcribed, and analyzed using thematic analysis. Results Six interrelated themes emerged from the town hall discussions related to: ethical and empirical starting points for deliberation; criteria for setting priorities; pre-crisis planning; in-crisis decision-making; the need for public deliberation and input; and participants' deliberative struggle with the ethical issues. Conclusions Our findings underscore the importance of public consultation in pandemic planning for sustaining public trust in a public health emergency. Participants appreciated the empirical and ethical uncertainty of decision-making in an influenza pandemic and demonstrated nuanced ethical reasoning about priority setting of intensive care resources in an influenza pandemic. Policymakers may benefit from a better understanding the public's empirical and ethical 'starting points' in developing effective pandemic plans.

  11. Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established.

    Nigel J Dimmock

    Full Text Available Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1. Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes.

  12. General practice and pandemic influenza: a framework for planning and comparison of plans in five countries.

    Mahomed S Patel

    Full Text Available BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research.

  13. Influenza epidemiology in Italy two years after the 2009–2010 pandemic

    Gasparini, Roberto; Bonanni, Paolo; Amicizia, Daniela; Bella, Antonino; Donatelli, Isabella; Cristina, Maria Luisa; Panatto, Donatella; Lai, Piero Luigi


    Since 2000, a sentinel surveillance of influenza, INFLUNET, exists in Italy. It is coordinated by the Ministry of Health and is divided into two parts; one of these is coordinated by the National Institute of Health (NIH), the other by the Inter-University Centre for Research on Influenza and other Transmissible Infections (CIRI-IT). The influenza surveillance system performs its activity from the 42nd week of each year (mid-October) to the 17th week of the following year (late April). Only during the pandemic season (2009/2010) did surveillance continue uninterruptedly. Sentinel physicians – about 1,200 general practitioners and independent pediatricians – send in weekly reports of cases of influenza-like illness (ILI) among their patients (over 2% of the population of Italy) to these centers. In order to estimate the burden of pandemic and seasonal influenza, we examined the epidemiological data collected over the last 3 seasons (2009–2012). On the basis of the incidences of ILIs at different ages, we estimated that: 4,882,415; 5,519,917; and 4,660,601 cases occurred in Italy in 2009–2010, 2010–2011 and 2011–2012, respectively. Considering the ILIs, the most part of cases occurred in < 14 y old subjects and especially in 5–14 y old individuals, about 30% and 21% of cases respectively during 2009–2010 and 2010–2011 influenza seasons. In 2011–2012, our evaluation was of about 4.7 million of cases, and as in the previous season, the peak of cases regarded subjects < 14 y (about 29%). A/California/07/09 predominated in 2009–2010 and continued to circulate in 2010–2011. During 2010–2011 B/Brisbane/60/08 like viruses circulated and A/H3N2 influenza type was sporadically present. H3N2 (A/Perth/16/2009 and A/Victoria/361/2011) was the predominant influenza type-A virus that caused illness in the 2011–2012 season. Many strains of influenza viruses were present in the epidemiological scenario in 2009–2012. In the period 2009–2012, overall

  14. Knowledge and attitudes of university students toward pandemic influenza: a cross-sectional study from Turkey

    Hayran Osman


    Full Text Available Abstract Background During an influenza pandemic, higher education institutions with large populations of young adults can become serious outbreak centers. Since outbreak management is essential to disease control, we aimed to examine university students' knowledge of and attitudes toward the pandemic influenza A/H1N1 and vaccination and other preventive measures. Methods A cross-sectional study was conducted among 402 first year university students at Yeditepe University in Istanbul, Turkey between 1st and 30th of November 2009. Data regarding socio-demographic characteristics of the students, perceptions, level of knowledge and attitudes toward influenza pandemic and prevention measures were collected by means of a self-administered questionnaire. The questionnaire was distributed by the students affiliated with SANITAS, a university club of students in health related sciences. Results 25.1% (101/402 of the study group perceived their personal risk of influenza as "high", while 40.5% (163/402 perceived it as "moderate", 20.6% (107/402 viewed it as "low" and 7.7% (31/402 indicated that it was "unknown". The risk perception of males was significantly lower than that of females (p = 0.004 and the risk perception among the students of health sciences was significantly lower than that of students of other sciences (p = 0.037. Within the study group, 72.1% (290/402 indicated that their main information source regarding H1N1 was the mass media. Health sciences students tended to rely more on the internet as an information source than other students (p = 0.015. The vast majority (92.8%; 373/402 of those interviewed indicated that they would not be vaccinated. The major concerns regarding vaccination had to do with the safety and side effects of the vaccine. Most of the participants (343/402, 85.3% were carrying out one of prevention measures and the vast majority believed that hand washing, face mask and quarantina were effective measures for

  15. Reassortment patterns in Swine influenza viruses.

    Hossein Khiabanian

    Full Text Available Three human influenza pandemics occurred in the twentieth century, in 1918, 1957, and 1968. Influenza pandemic strains are the results of emerging viruses from non-human reservoirs to which humans have little or no immunity. At least two of these pandemic strains, in 1957 and in 1968, were the results of reassortments between human and avian viruses. Also, many cases of swine influenza viruses have reportedly infected humans, in particular, the recent H1N1 influenza virus of swine origin, isolated in Mexico and the United States. Pigs are documented to allow productive replication of human, avian, and swine influenza viruses. Thus it has been conjectured that pigs are the "mixing vessel" that create the avian-human reassortant strains, causing the human pandemics. Hence, studying the process and patterns of viral reassortment, especially in pigs, is a key to better understanding of human influenza pandemics. In the last few years, databases containing sequences of influenza A viruses, including swine viruses, collected since 1918 from diverse geographical locations, have been developed and made publicly available. In this paper, we study an ensemble of swine influenza viruses to analyze the reassortment phenomena through several statistical techniques. The reassortment patterns in swine viruses prove to be similar to the previous results found in human viruses, both in vitro and in vivo, that the surface glycoprotein coding segments reassort most often. Moreover, we find that one of the polymerase segments (PB1, reassorted in the strains responsible for the last two human pandemics, also reassorts frequently.

  16. The community impact of the 2009 influenza pandemic in the WHO European region: a comparison with historical seasonal data from 28 countries.

    Martirosyan, L.; Paget, W.J.; Jorgensen, P.; Brown, C.S.; Meerhoff, T.J.; Pereyaslov, D.; Mott, J.A.


    Background: The world has recently experienced the first influenza pandemic of the 21st century that lasted 14 months from June 2009 to August 2010. This study aimed to compare the timing, geographic spread and community impact during the winter wave of influenza pandemic A (H1N1) 2009 to historical

  17. Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009-2010

    Meijer, Adam; Jonges, Marcel; Abbink, Floor; Ang, Wim; van Beek, Janko; Beersma, Matthias; Bloembergen, Peter; Boucher, Charles; Claas, Eric; Donker, Ge; van Gageldonk-Lafeber, Rianne; Isken, Leslie; Kroes, Aloys; Leenders, Sander; van der Lubben, Mariken; Mascini, Ellen; Niesters, Bert; Oosterheert, Jan Jelrik; Osterhaus, Albert; Riesmeijer, Rob; Riezebos-Brilman, Annelies; Schutten, Martin; Sebens, Fre; Stelma, Foekje; Swaan, Corien; Timen, Aura; van 't Veen, Annemarie; van der Vries, Erhard; Wierik, Margreet Te; Koopmans, Marion; de Jong, A


    Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 200

  18. Estimating the costs of school closure for mitigating an influenza pandemic

    Adams Elisabeth J


    Full Text Available Abstract Background School closure is a key component of many countries' plans to mitigate the effect of an influenza pandemic. Although a number of studies have suggested that such a policy might reduce the incidence, there are no published studies of the cost of such policies. This study attempts to fill this knowledge gap Methods School closure is expected to lead to significant work absenteeism of working parents who are likely to be the main care givers to their dependent children at home. The cost of absenteeism due to school closure is calculated as the paid productivity loss of parental absenteeism during the period of school closure. The cost is estimated from societal perspective using a nationally representative survey. Results The results show that overall about 16% of the workforce is likely to be the main caregiver for dependent children and therefore likely to take absenteeism. This rises to 30% in the health and social care sector, as a large proportion of the workforce are women. The estimated costs of school closure are significant, at £0.2 bn – £1.2 bn per week. School closure is likely to significantly exacerbate the pressures on the health system through staff absenteeism. Conclusion The estimates of school closure associated absenteeism and the projected cost would be useful for pandemic planning for business continuity, and for cost effectiveness evaluation of different pandemic influenza mitigation strategies.

  19. Planning for the next influenza pandemic: using the science and art of logistics.

    Cupp, O Shawn; Predmore, Brad G


    The complexities and challenges for healthcare providers and their efforts to provide fundamental basic items to meet the logistical demands of an influenza pandemic are discussed in this article. The supply chain, planning, and alternatives for inevitable shortages are some of the considerations associated with this emergency mass critical care situation. The planning process and support for such events are discussed in detail with several recommendations obtained from the literature and the experience from recent mass casualty incidents (MCIs). The first step in this planning process is the development of specific triage requirements during an influenza pandemic. The second step is identification of logistical resources required during such a pandemic, which are then analyzed within the proposed logistics science and art model for planning purposes. Resources highlighted within the model include allocation and use of work force, bed space, intensive care unit assets, ventilators, personal protective equipment, and oxygen. The third step is using the model to discuss in detail possible workarounds, suitable substitutes, and resource allocation. An examination is also made of the ethics surrounding palliative care within the construction of an MCI and the factors that will inevitably determine rationing and prioritizing of these critical assets to palliative care patients.

  20. Structural Characterization of the Hemagglutinin Receptor Specificity from the 2009 H1N1 Influenza Pandemic

    Xu, Rui; McBride, Ryan; Nycholat, Corwin M.; Paulson, James C.; Wilson, Ian A. (Scripps)


    Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor-binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only for {alpha}2-6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For {alpha}2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with {alpha}2-6- and {alpha}2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for {alpha}2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus.

  1. Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.

    Alain Gagnon

    Full Text Available The worldwide spread of a novel influenza A (H1N1 virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

  2. Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.

    Gagnon, Alain; Miller, Matthew S; Hallman, Stacey A; Bourbeau, Robert; Herring, D Ann; Earn, David J D; Madrenas, Joaquín


    The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

  3. Mortality attributable to seasonal and pandemic influenza, Australia, 2003 to 2009, using a novel time series smoothing approach.

    David J Muscatello

    Full Text Available BACKGROUND: Official statistics under-estimate influenza deaths. Time series methods allow the estimation of influenza-attributable mortality. The methods often model background, non-influenza mortality using a cyclic, harmonic regression model based on the Serfling approach. This approach assumes that the seasonal pattern of non-influenza mortality is the same each year, which may not always be accurate. AIM: To estimate Australian seasonal and pandemic influenza-attributable mortality from 2003 to 2009, and to assess a more flexible influenza mortality estimation approach. METHODS: We used a semi-parametric generalized additive model (GAM to replace the conventional seasonal harmonic terms with a smoothing spline of time ('spline model' to estimate influenza-attributable respiratory, respiratory and circulatory, and all-cause mortality in persons aged <65 and ≥ 65 years. Influenza A(H1N1pdm09, seasonal influenza A and B virus laboratory detection time series were used as independent variables. Model fit and estimates were compared with those of a harmonic model. RESULTS: Compared with the harmonic model, the spline model improved model fit by up to 20%. In <65 year-olds, the estimated respiratory mortality attributable to pandemic influenza A(H1N1pdm09 was 0.5 (95% confidence interval (CI, 0.3, 0.7 per 100,000; similar to that of the years with the highest seasonal influenza A mortality, 2003 and 2007 (A/H3N2 years. In ≥ 65 year-olds, the highest annual seasonal influenza A mortality estimate was 25.8 (95% CI 22.2, 29.5 per 100,000 in 2003, five-fold higher than the non-statistically significant 2009 pandemic influenza estimate in that age group. Seasonal influenza B mortality estimates were negligible. CONCLUSIONS: The spline model achieved a better model fit. The study provides additional evidence that seasonal influenza, particularly A/H3N2, remains an important cause of mortality in Australia and that the epidemic of pandemic influenza

  4. Framing of Influenza A (H1N1) pandemic in a Singaporean newspaper.

    Basnyat, Iccha; Lee, Seow Ting


    This study seeks to understand how public health messages provided by the government in Singapore during an Influenza A (H1N1) pandemic were framed by the news media for the public. News articles were analyzed to explore how the global pandemic was framed as a local event, providing a unique exploration of the dynamic involving public health communication, news media and the state. Thematic analysis (n = 309) included the government-issued press releases disseminating public health information about H1N1 that were directly linked to news stories (n = 56) and news stories about H1N1 generated by the newspaper (n = 253). Four themes were found: (i) imported disease, (ii) war/battle metaphors, (iii) social responsibility and (iv) lockdown policies. Frame analysis revealed that the news coverage during the H1N1 pandemic reflected how the newspaper framed and mediated the information flow, amplified a positive tone for the government response, emphasized individual responsibility and utilized gain frames to construct local messages about the global H1N1 pandemic that reified Singapore as a nation-state.

  5. Hospital triage system for adult patients using an influenza-like illness scoring system during the 2009 pandemic--Mexico.

    Eduardo Rodriguez-Noriega

    Full Text Available BACKGROUND: Pandemic influenza A (H1N1 virus emerged during 2009. To help clinicians triage adults with acute respiratory illness, a scoring system for influenza-like illness (ILI was implemented at Hospital Civil de Guadalajara, Mexico. METHODS: A medical history, laboratory and radiology results were collected on emergency room (ER patients with acute respiratory illness to calculate an ILI-score. Patients were evaluated for admission by their ILI-score and clinicians' assessment of risk for developing complications. Nasal and throat swabs were collected from intermediate and high-risk patients for influenza testing by RT-PCR. The disposition and ILI-score of those oseltamivir-treated versus untreated, clinical characteristics of 2009 pandemic influenza A (H1N1 patients versus test-negative patients were compared by Pearson's Chi(2, Fisher's Exact, and Wilcoxon rank-sum tests. RESULTS: Of 1840 ER patients, 230 were initially hospitalized (mean ILI-score = 15, and the rest were discharged, including 286 ambulatory patients given oseltamivir (median ILI-score = 11, and 1324 untreated (median ILI-score = 5. Fourteen (1% untreated patients returned, and 3 were hospitalized on oseltamivir (median ILI-score = 19. Of 371 patients tested by RT-PCR, 104 (28% had pandemic influenza and 42 (11% had seasonal influenza A detected. Twenty (91% of 22 imaged hospitalized pandemic influenza patients had bilateral infiltrates compared to 23 (38% of 61 imaged hospital test-negative patients (p<0.001. One patient with confirmed pandemic influenza presented 6 days after symptom onset, required mechanical ventilation, and died. CONCLUSIONS: The triaging system that used an ILI-score complimented clinicians' judgment of who needed oseltamivir and inpatient care and helped hospital staff manage a surge in demand for services.

  6. Continued dominance of pandemic A(H1N1 2009 influenza in Victoria, Australia in 2010

    James E. Fielding


    Full Text Available The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95% were influenza A infections - 1001 (55% pandemic A(H1N1 2009, 4 (<1% A(H3N2 and 807 (45% not subtyped; 88 (5% were influenza B; and 14 (< 1% were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9% were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene.

  7. Key transmission parameters of an institutional outbreak during the 1918 influenza pandemic estimated by mathematical modelling

    Nelson Peter


    Full Text Available Abstract Aim To estimate the key transmission parameters associated with an outbreak of pandemic influenza in an institutional setting (New Zealand 1918. Methods Historical morbidity and mortality data were obtained from the report of the medical officer for a large military camp. A susceptible-exposed-infectious-recovered epidemiological model was solved numerically to find a range of best-fit estimates for key epidemic parameters and an incidence curve. Mortality data were subsequently modelled by performing a convolution of incidence distribution with a best-fit incidence-mortality lag distribution. Results Basic reproduction number (R0 values for three possible scenarios ranged between 1.3, and 3.1, and corresponding average latent period and infectious period estimates ranged between 0.7 and 1.3 days, and 0.2 and 0.3 days respectively. The mean and median best-estimate incidence-mortality lag periods were 6.9 and 6.6 days respectively. This delay is consistent with secondary bacterial pneumonia being a relatively important cause of death in this predominantly young male population. Conclusion These R0 estimates are broadly consistent with others made for the 1918 influenza pandemic and are not particularly large relative to some other infectious diseases. This finding suggests that if a novel influenza strain of similar virulence emerged then it could potentially be controlled through the prompt use of major public health measures.

  8. Examining the knowledge, attitudes and practices of domestic and international university students towards seasonal and pandemic influenza

    Seale Holly


    Full Text Available Abstract Background Prior to the availability of the specific pandemic vaccine, strategies to mitigate the impact of the disease typically involved antiviral treatment and “non-pharmaceutical” community interventions. However, compliance with these strategies is linked to risk perceptions, perceived severity and perceived effectiveness of the strategies. In 2010, we undertook a study to examine the knowledge, attitudes, risk perceptions, practices and barriers towards influenza and infection control strategies amongst domestic and international university students. Methods A study using qualitative methods that incorporated 20 semi-structured interviews was undertaken with domestic and international undergraduate and postgraduate university students based at one university in Sydney, Australia. Participants were invited to discuss their perceptions of influenza (seasonal vs. pandemic in terms of perceived severity and impact, and attitudes towards infection control measures including hand-washing and the use of social distancing, isolation or cough etiquette. Results While participants were generally knowledgeable about influenza transmission, they were unable to accurately define what ‘pandemic influenza’ meant. While avian flu or SARS were mistaken as examples of past pandemics, almost all participants were able to associate the recent “swine flu” situation as an example of a pandemic event. Not surprisingly, it was uncommon for participants to identify university students as being at risk of catching pandemic influenza. Amongst those interviewed, it was felt that ‘students’ were capable of fighting off any illness. The participant’s nominated hand washing as the most feasible and acceptable compared with social distancing and mask use. Conclusions Given the high levels of interaction that occurs in a university setting, it is really important that students are informed about disease transmission and about risk of infection

  9. Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility.

    Stefano Merler

    Full Text Available BACKGROUND: A common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated. METHODS: The level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40, was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model. RESULTS: By comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%. Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI. CONCLUSIONS: Our results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in

  10. Epidemiological characteristics of the influenza A(H1N1 2009 pandemic in the Western Pacific Region

    Lisa McCallum


    Full Text Available The first laboratory-confirmed cases of infection with pandemic influenza A(H1N1 2009 in the Western Pacific Region were reported on 28 April 2009. By 11 June 2009, the day the pandemic was declared by the World Health Organization, nine Western Pacific Region countries and areas had reported laboratory-confirmed pandemic influenza A(H1N1 2009 cases. From April 2009 to July 2010, more than 250 000 cases and 1800 deaths from laboratory-confirmed pandemic influenza A(H1N1 2009 were reported from 34 countries and areas in the Region. By age group region-wide, 8.6%, 41.9%, 48.3%, and 1.2% of cases were in the < 5 years, 5–14 years, 15–64 years, and 65+ years age groups, respectively; the overall crude case fatality ratio in the Western Pacific Region was 0.5%. The pandemic demonstrated that region-wide disease reporting was possible. Countries and areas of the Western Pacific Region should take this opportunity to strengthen the systems established during the pandemic to develop routine disease reporting.

  11. Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1

    Torun Fuat


    Full Text Available Abstract Background Both the health care workers (HCWs and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. Methods A cross-sectional questionnaire survey was conducted with health care workers (HCWs in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. Results A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105 reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1% of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Conclusions Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the

  12. Public health measures during an anticipated influenza pandemic: Factors influencing willingness to comply

    Melanie Taylor


    Full Text Available Melanie Taylor1, Beverley Raphael1, Margo Barr2, Kingsley Agho1, Garry Stevens1, Louisa Jorm11School of Medicine, University of Western Sydney, Sydney, Australia; 2Centre for Epidemiology and Research, New South Wales Department of Health, Sydney, AustraliaAbstract: This research assessed factors associated with willingness to comply with vaccination, isolation, and face mask wearing during an anticipated influenza pandemic. Data were collected from 2081 adults (16+ using a module of questions incorporated into the NSW Health Adult Population Health Survey. High levels of willingness to comply were reported with 73% either very or extremely willing to receive vaccination, 67% willing to isolate themselves, 58% willing to wear a face mask, and 48% willing to comply with all three behaviors. Further analysis indicated concern for self and family and higher levels of education were associated with high levels of willingness to comply. Younger people (16–24 were the least willing to comply; especially with wearing a face mask. Those with children reported higher levels of willingness to receive vaccination, and respondents who speak a language other than English at home were less willing to isolate themselves or comply with all behaviors. These findings provide a baseline measure of anticipated public compliance with key public health behaviors in the event of an influenza pandemic in the Australian population, and help to identify groups that may be more resistant to individual measures and may require additional attention in terms of risk communication strategies or health education.Keywords: risk perception, pandemic influenza, compliance, health behaviors

  13. Quantifying the risk of pandemic influenza virus evolution by mutation and re-assortment.

    Reperant, Leslie A; Grenfell, Bryan T; Osterhaus, Albert D M E


    Large outbreaks of zoonotic influenza A virus (IAV) infections may presage an influenza pandemic. However, the likelihood that an airborne-transmissible variant evolves upon zoonotic infection or co-infection with zoonotic and seasonal IAVs remains poorly understood, as does the relative importance of accumulating mutations versus re-assortment in this process. Using discrete-time probabilistic models, we determined quantitative probability ranges that transmissible variants with 1-5 mutations and transmissible re-assortants evolve after a given number of zoonotic IAV infections. The systematic exploration of a large population of model parameter values was designed to account for uncertainty and variability in influenza virus infection, epidemiological and evolutionary processes. The models suggested that immunocompromised individuals are at high risk of generating IAV variants with pandemic potential by accumulation of mutations. Yet, both immunocompetent and immunocompromised individuals could generate high viral loads of single and double mutants, which may facilitate their onward transmission and the subsequent accumulation of additional 1-2 mutations in newly-infected individuals. This may result in the evolution of a full transmissible genotype along short chains of contact transmission. Although co-infection with zoonotic and seasonal IAVs was shown to be a rare event, it consistently resulted in high viral loads of re-assortants, which may facilitate their onward transmission among humans. The prevention or limitation of zoonotic IAV infection in immunocompromised and contact individuals, including health care workers, as well as vaccination against seasonal IAVs-limiting the risk of co-infection-should be considered fundamental tools to thwart the evolution of a novel pandemic IAV by accumulation of mutations and re-assortment.

  14. Clinical characteristics of pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1 in Northern Bavaria, Germany

    Wieching Anna


    Full Text Available Abstract Background The 2009 pandemic influenza A (H1N1 (PIA virus infected large parts of the pediatric population with a wide clinical spectrum and an initially unknown complication rate. The aims of our study were to define clinical characteristics and outcome of pandemic influenza A (H1N1 2009-associated hospitalizations (PIAH in children Results Between July 2009 and March 2010, 94 PIAH (62% males occurred in children Conclusions Most PIAH demonstrated a benign course of disease. However, six children (6% needed treatment at an intensive care unit for severe complications.

  15. Safety and immunogenicity of Sinovac’s prototype pandemic influenza H5N1 vaccines: a review on clinical trials

    Qiu, Yuan‐Zheng; Yin, Wei‐Dong


    Abstract  Sinovac Biotech started to develop prototype pandemic influenza H5N1 vaccines in March 2004. On 2 April 2008, Sinovac’s inactivated, aluminium‐adjuvanted, whole‐virion prototype pandemic influenza A (H5N1) vaccine (PanFlu™) was granted production licensure by the China regulatory authority State Food and Drug Administration. The whole‐virion H5N1 vaccine was manufactured in embryonated hens’ eggs using the reassortant strain NIBRG‐14 (A/Vietnam/1194/2004‐A/PR/8/34) as vaccine virus....

  16. [Chile between pandemic: the influenza of 1918, globalization and the new medicine].

    López, Marcelo; Beltrán, Miriam


    In 1918 Chile met the deadly presence of the Spanish influenza pandemic twentieth century's most important. For many historians, this event is an important milestone in the historical process of the unification of the world through sickness and in which our country has been involved. In this context, this paper aims to examine how the flu broke into Chilean society and how that situation helped give new impetus to the modernization of the Chilean public health and the establishment in the 1920s to model new medicine or preventive medicine.

  17. Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship.

    Ward, Kate A; Armstrong, Paul; McAnulty, Jeremy M; Iwasenko, Jenna M; Dwyer, Dominic E


    To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.

  18. Pneumonia due to pandemic (H1N1) 2009 influenza virus and Klebsiella pneumoniae capsular serotype K16 in a patient with nasopharyngeal cancer.

    Lai, Chih-Cheng; Lee, Pei-Lin; Tan, Che-Kim; Huang, Yu-Tsung; Kao, Chiang-Lian; Wang, Jin-Town; Hsueh, Po-Ren


    Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and group A Streptoccocus, but no Klebsiella pneumoniae were responsible for bacterial coinfections during the 2009 and previous influenza pandemics. We hereby report a case with concurrent bacteremic pneumonia due to an unusual capsular serotype K16 K. pneumoniae and pandemic (H1N1) 2009 influenza in a patient with nasopharyngeal cancer. Such a coinfection has not previously been described.

  19. Burden of pediatric influenza A virus infection post swine-flu H1N1 pandemic in Egypt

    Adel Khattab; Malak Shaheen; Terez Kamel; Amel El Faramay; Safaa Abd El Rahman; Dalia Nabil; Mohamed Gouda


    Objective:To screen children with influenza like illness or with symptoms of acute respiratory tract infections for influenza A virus infection—post swine flu pandemic era—using rapid influenza diagnostic tests. Methods:During two years (2010&2011), 1 200 children with influenza like illness or acute respiratory tract infections (according to World Health Organization criteria) were recruited. Their ages ranged from 2-60 months. Nasopharyngeal aspirates specimens were collected from all children for rapid influenza A diagnostic test. Results: Influenza A virus rapid test was positive in 47.5%of the children;the majority (89.6%) were presented with lower respiratory tract infections. Respiratory rate and temperature were significantly higher among positive rapid influenza test patients. Conclusions:Influenza A virus infection is still a major cause of respiratory tract infections in Egyptian children. It should be considered in all cases with cough and febrile episodes and influenza like symptoms even post swine flu pandemic.

  20. Genetic Characteristics and Immunogenicity of Pandemic H1N1 Influenza Virus Isolate from Pig in Korea

    Moon, Hyoung Joon; Oh, Jin Sik; Na, Woonsung; Yeom, Minjoo; Han, Sang Yoon; Kim, Sung Jae; Park, Bong Kyun


    A pandemic influenza A (H1N1) virus strain was isolated from a pig farm in Korea in December 2009. The strain was propagated in and isolated from both the Madin-Darby canine kidney cell line and embryonated eggs. The partial and complete sequences of the strain were identical to those of A/California/04/2009, with >99% sequence similarity in the HA, NA, M, NS, NP, PA, PB1, and PB2 genes. The isolated strain was inactivated and used to prepare a swine influenza vaccine. This trial vaccine, containing the new isolate that has high sequence similarity with the pandemic influenza A (H1N1) virus, resulted in seroconversion in Guinea pigs and piglets. This strain could therefore be a potential vaccine candidate for swine influenza control in commercial farms.

  1. Assessment of local public health workers' willingness to respond to pandemic influenza through application of the extended parallel process model.

    Daniel J Barnett

    Full Text Available BACKGROUND: Local public health agencies play a central role in response to an influenza pandemic, and understanding the willingness of their employees to report to work is therefore a critically relevant concern for pandemic influenza planning efforts. Witte's Extended Parallel Process Model (EPPM has been found useful for understanding adaptive behavior in the face of unknown risk, and thus offers a framework for examining scenario-specific willingness to respond among local public health workers. We thus aim to use the EPPM as a lens for examining the influences of perceived threat and efficacy on local public health workers' response willingness to pandemic influenza. METHODOLOGY/PRINCIPAL FINDINGS: We administered an online, EPPM-based survey about attitudes/beliefs toward emergency response (Johns Hopkins approximately Public Health Infrastructure Response Survey Tool, to local public health employees in three states between November 2006-December 2007. A total of 1835 responses were collected for an overall response rate of 83%. With some regional variation, overall 16% of the workers in 2006-7 were not willing to "respond to a pandemic flu emergency regardless of its severity". Local health department employees with a perception of high threat and high efficacy--i.e., those fitting a 'concerned and confident' profile in the EPPM analysis--had the highest declared rates of willingness to respond to an influenza pandemic if required by their agency, which was 31.7 times higher than those fitting a 'low threat/low efficacy' EPPM profile. CONCLUSIONS/SIGNIFICANCE: In the context of pandemic influenza planning, the EPPM provides a useful framework to inform nuanced understanding of baseline levels of--and gaps in--local public health workers' response willingness. Within local health departments, 'concerned and confident' employees are most likely to be willing to respond. This finding may allow public health agencies to design, implement

  2. Skip the trip: air travelers' behavioral responses to pandemic influenza.

    Eli P Fenichel

    Full Text Available Theory suggests that human behavior has implications for disease spread. We examine the hypothesis that individuals engage in voluntary defensive behavior during an epidemic. We estimate the number of passengers missing previously purchased flights as a function of concern for swine flu or A/H1N1 influenza using 1.7 million detailed flight records, Google Trends, and the World Health Organization's FluNet data. We estimate that concern over "swine flu," as measured by Google Trends, accounted for 0.34% of missed flights during the epidemic. The Google Trends data correlates strongly with media attention, but poorly (at times negatively with reported cases in FluNet. Passengers show no response to reported cases. Passengers skipping their purchased trips forwent at least $50 M in travel related benefits. Responding to actual cases would have cut this estimate in half. Thus, people appear to respond to an epidemic by voluntarily engaging in self-protection behavior, but this behavior may not be responsive to objective measures of risk. Clearer risk communication could substantially reduce epidemic costs. People undertaking costly risk reduction behavior, for example, forgoing nonrefundable flights, suggests they may also make less costly behavior adjustments to avoid infection. Accounting for defensive behaviors may be important for forecasting epidemics, but linking behavior with epidemics likely requires consideration of risk communication.

  3. Interventions to reduce zoonotic and pandemic risks from avian influenza in Asia.

    Peiris, J S Malik; Cowling, Benjamin J; Wu, Joseph T; Feng, Luzhao; Guan, Yi; Yu, Hongjie; Leung, Gabriel M


    Novel influenza viruses continue to emerge, posing zoonotic and potentially pandemic threats, such as with avian influenza A H7N9. Although closure of live poultry markets (LPMs) in mainland China stopped H7N9 outbreaks temporarily, closures are difficult to sustain, in view of poultry production and marketing systems in China. In this Personal View, we summarise interventions taken in mainland China, and provide evidence for other more sustainable but effective interventions in the live poultry market systems that reduce risk of zoonotic influenza including rest days, and banning live poultry in markets overnight. Separation of live ducks and geese from land-based (ie, non-aquatic) poultry in LPM systems can reduce the risk of emergence of zoonotic and epizootic viruses at source. In view of evidence that H7N9 is now endemic in over half of the provinces in mainland China and will continue to cause recurrent zoonotic disease in the winter months, such interventions should receive high priority in China and other Asian countries at risk of H7N9 through cross-border poultry movements. Such generic measures are likely to reduce known and future threats of zoonotic influenza.

  4. Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

    Yu-Fen Tseng

    Full Text Available Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14, a reassortant virus between A/Vietnam/1194/2004 (H5N1 virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15 was generated and can grow over 10(8 TCID(50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes.

  5. Biopiracy and vaccines: Indonesia and the World Health Organization’s new Pandemic Influenza Plan

    Shawn Smallman


    Full Text Available Viral samples of avian influenza are essential to preparing pre-pandemic vaccines. In 2007, the conflicting interests of the developed and developing nations led Indonesia to briefly stop sharing viral samples. The result was a struggle in which the two blocs argued for different paradigms for viral sample sharing. The first paradigm, articulated by the developed world, depicted the issue as one of health security, in which international law mandated the sharing of viral samples. The second paradigm, advanced by the developing world, depicted viral sample sharing as a form of biopiracy, which violated countries’ sovereign control of their biological resources. Ultimately, the second paradigm proved more politically effective, enabling developing nations to achieve many of their goals through the WHO’s 2011 pandemic influenza plan. This paper examines how this plan was shaped by Indonesia’s argument that the global public good required a new approach to global health governance, in order to eliminate neocolonial power relationships.

  6. [The influenza pandemic 1968-1970: crisis management in separated Germany - "Vodka and Raspberry Tea"].

    Witte, W


    The Hong Kong Flu in the years 1968-1970 challenged both German health care systems. This article intends to analyse the patterns of reaction to the pandemic. Both German states faced the threat according to their respective ideological orientation. This applied to the two parts of Berlin - West and East - as well. In the GDR the control of influenza was centrally organized. When the pandemic passed away an influenza guiding document ("Führungsdokument") was made obligatory for the fight against the plague. In the FRG hospital treatment maintained predominance while the outpatient sector was administrated by physicians in private practice. In West- Berlin outpatient clinics were declined by the Association of Physicians ("Kassenärztliche Vereinigung"). In 1970 a first concept of surveillance was presented on the level of the state in West Germany. In the years 1968-1970 vaccinations were not common in both German states. The essay is based on the analysis of archival sources, monographs, scientific and newspaper articles.

  7. Toward unbiased assessment of treatment and prevention: modeling household transmission of pandemic influenza

    Chowell Gerardo


    Full Text Available Abstract Providing valid and reliable estimates of the transmissibility and severity of pandemic influenza in real time is key to guide public health policymaking. In particular, early estimates of the transmissibility are indispensable for determining the type and intensity of interventions. A recent study by House and colleagues in BMC Medicine devised a stochastic transmission model to estimate the unbiased risk of transmission within households, applying the method to datasets of the 2009 A/H1N1 influenza pandemic. Here, we discuss future challenges in household transmission studies and underscore the need to systematically collect epidemiological data to decipher the household transmission dynamics. We emphasize the need to consider three critical issues for future improvements: (i capturing age-dependent heterogeneity within households calls for intensive modeling efforts, (ii the timeline of observation during the course of an epidemic and the length of follow-up should be aligned with study objectives, and (iii the use of laboratory methods, especially molecular techniques, is encouraged to distinguish household transmissions from those arising in the community. See related article:

  8. Detection of pandemic strain of influenza virus (A/H1N1/pdm09 in pigs, West Africa: implications and considerations for prevention of future influenza pandemics at the source

    Oluwagbenga A. Adeola


    Full Text Available Background: Human and animal influenza are inextricably linked. In particular, the pig is uniquely important as a mixing vessel for genetic reassortment of influenza viruses, leading to emergence of novel strains which may cause human pandemics. Significant reduction in transmission of influenza viruses from humans, and other animals, to swine may therefore be crucial for preventing future influenza pandemics. This study investigated the presence of the 2009 pandemic influenza A/H1N1 virus, A(H1N1pdm09, in Nigerian and Ghanaian pigs, and also determined levels of acceptance of preventive measures which could significantly reduce the transmission of this virus from humans to pigs. Methods: Nasal swab specimens from 125 pigs in Ibadan, Nigeria, and Kumasi, Ghana, were tested for the presence of influenza A/California/04/2009 (H1N1 by quantitative antigen-detection ELISA. A semi-structured questionnaire was also administered to pig handlers in the two study areas and responses were analyzed to evaluate their compliance with seven measures for preventing human-to-swine transmission of influenza viruses. Results: The virus was detected among pigs in the two cities, with prevalence of 8% in Ibadan and 10% in Kumasi. Levels of compliance of pig handlers with relevant preventive measures were also found to be mostly below 25 and 40% in Ibadan and Kumasi, respectively. Conclusion: Detection of influenza A(H1N1pdm09 among pigs tested suggests the possibility of human-to-swine transmission, which may proceed even more rapidly, considering the very poor acceptance of basic preventive measures observed in this study. This is also the first report on detection of influenza A(H1N1pdm09 in Ghanaian pigs. We recommend improvement on personal hygiene among pig handlers, enforcement of sick leave particularly during the first few days of influenza-like illnesses, and training of pig handlers on recognition of influenza-like signs in humans and pigs. These could be

  9. A 'small-world-like' model for comparing interventions aimed at preventing and controlling influenza pandemics

    Sallé Anne-Violaine


    Full Text Available Abstract Background With an influenza pandemic seemingly imminent, we constructed a model simulating the spread of influenza within the community, in order to test the impact of various interventions. Methods The model includes an individual level, in which the risk of influenza virus infection and the dynamics of viral shedding are simulated according to age, treatment, and vaccination status; and a community level, in which meetings between individuals are simulated on randomly generated graphs. We used data on real pandemics to calibrate some parameters of the model. The reference scenario assumes no vaccination, no use of antiviral drugs, and no preexisting herd immunity. We explored the impact of interventions such as vaccination, treatment/prophylaxis with neuraminidase inhibitors, quarantine, and closure of schools or workplaces. Results In the reference scenario, 57% of realizations lead to an explosive outbreak, lasting a mean of 82 days (standard deviation (SD 12 days and affecting 46.8% of the population on average. Interventions aimed at reducing the number of meetings, combined with measures reducing individual transmissibility, would be partly effective: coverage of 70% of affected households, with treatment of the index patient, prophylaxis of household contacts, and confinement to home of all household members, would reduce the probability of an outbreak by 52%, and the remaining outbreaks would be limited to 17% of the population (range 0.8%–25%. Reactive vaccination of 70% of the susceptible population would significantly reduce the frequency, size, and mean duration of outbreaks, but the benefit would depend markedly on the interval between identification of the first case and the beginning of mass vaccination. The epidemic would affect 4% of the population if vaccination started immediately, 17% if there was a 14-day delay, and 36% if there was a 28-day delay. Closing schools when the number of infections in the community

  10. Social contact networks for the spread of pandemic influenza in children and teenagers

    Glass Robert J


    Full Text Available Abstract Background Influenza is a viral infection that primarily spreads via fluid droplets from an infected person's coughs and sneezes to others nearby. Social contact networks and the way people interact within them are thus important to its spread. We developed a method to characterize the social contact network for the potential transmission of influenza and then applied the method to school aged children and teenagers. Methods Surveys were administered to students in an elementary, middle and high-school in the United States. The social contact network of a person was conceptualized as a set of groups to which they belong (e.g., households, classes, clubs each composed of a sub-network of primary links representing the individuals within each group that they contact. The size of the group, number of primary links, time spent in the group, and level of contact along each primary link (near, talking, touching, or kissing were characterized. Public activities done by groups venturing into the community where random contacts occur (e.g., friends viewing a movie also were characterized. Results Students, groups and public activities were highly heterogeneous. Groups with high potential for the transmission of influenza were households, school classes, friends, and sports; households decreased and friends and sports increased in importance with grade level. Individual public activity events (such as dances were also important but lost their importance when averaged over time. Random contacts, primarily in school passing periods, were numerous but had much lower transmission potential compared to those with primary links within groups. Students are highly assortative, interacting mainly within age class. A small number of individual students are identified as likely "super-spreaders". Conclusion High-school students may form the local transmission backbone of the next pandemic. Closing schools and keeping students at home during a pandemic would

  11. Willingness to accept H1N1 pandemic influenza vaccine: A cross-sectional study of Hong Kong community nurses

    Wong Carmen


    Full Text Available Abstract Background The 2009 pandemic of influenza A (H1N1 infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1 infection. Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden. Our study aims to assess the willingness of nurses who work for the community nursing service (CNS in Hong Kong on their acceptance of influenza A (H1N1 influenza vaccination. Methods 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate. Results of the 267 respondents on their willingness to accept influenza A (H1N1 vaccine were analyzed. Results Twenty-seven percent of respondents were willing to accept influenza vaccination if vaccines were available. Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1 vaccination (OR = 4.03; 95% CI: 2.03-7.98. Conclusions Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1 vaccination is low. Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1 vaccination to protect vulnerable patient populations is needed.

  12. Importation and spread of pandemic influenza virus a(H1N1 in Autonomous Province of vojvodina in preepidemic period

    Ristić Mioljub


    Full Text Available Introduction. Influenza is the most frequently reported communicable disease, having epidemic and pandemic potential. The first influenza pandemic in this century started in Mexico and spread quickly throughout the world. This paper analyses importation of pandemic influenza cases and local transmission among population in the Autonomous Province of Vojvodina. Material and methods. According to the WHO guidelines and national recommendations, the influenza surveillance activities were conducted in Vojvodina in order to detect, isolate and treat affected international travelers and their close contacts. Patients whose pandemic influenza infection was laboratory confirmed were classified as confirmed cases, while those with symptoms who were epidemiologically linked with confirmed cases were classified as probable cases. Results. During the period from the 24th of June to 17th of August 2009, 123 pandemic influenza cases were recorded in Vojvodina. Infection was imported through international travelers and our citizens coming from countries affected by influenza outbreaks. Majority of cases had mild clinical picture. Most frequently reported symptoms were high fever (above 38oC (85.6%, and cough (61.6%. Difficulty in breathing was recorded in 20 (16.0% cases, while pneumonia developed in 4 (3.2% cases but none of the cases required mechanical ventilation. Conclusion. The imported cases of pandemic influenza in the pre-epidemic period led to limited local transmission in general population and caused a small outbreak among visitors of International music festival called EXIT.

  13. Assessing the State of Knowledge Regarding the Effectiveness of Interventions to Contain Pandemic Influenza Transmission: A Systematic Review and Narrative Synthesis

    Reisman, Jane; Krewski, Daniel


    Background Influenza pandemics occur when a novel influenza strain, to which humans are immunologically naïve, emerges to cause infection and illness on a global scale. Differences in the viral properties of pandemic strains, relative to seasonal ones, can alter the effectiveness of interventions typically implemented to control seasonal influenza burden. As a result, annual control activities may not be sufficient to contain an influenza pandemic. Purpose This study seeks to inform pandemic policy and planning initiatives by reviewing the effectiveness of previous interventions to reduce pandemic influenza transmission and infection. Results will inform the planning and design of more focused in-depth systematic reviews for specific types of interventions, thus providing the most comprehensive and current understanding of the potential for alternative interventions to mitigate the burden of pandemic influenza. Methods A systematic review and narrative synthesis of existing systematic reviews and meta-analyses examining intervention effectiveness in containing pandemic influenza transmission was conducted using information collected from five databases (PubMed, Medline, Cochrane, Embase, and Cinahl/EBSCO). Two independent reviewers conducted study screening and quality assessment, extracting data related to intervention impact and effectiveness. Results and Discussion Most included reviews were of moderate to high quality. Although the degree of statistical heterogeneity precluded meta-analysis, the present systematic review examines the wide variety of interventions that can impact influenza transmission in different ways. While it appears that pandemic influenza vaccination provides significant protection against infection, there was insufficient evidence to conclude that antiviral prophylaxis, seasonal influenza cross-protection, or a range of non-pharmaceutical strategies would provide appreciable protection when implemented in isolation. It is likely that an

  14. Factors associated with 2009 pandemic influenza A (H1N1 vaccination acceptance among university students from India during the post-pandemic phase

    Thejaswini Venkatesh


    Full Text Available Abstract Background There was a low adherence to influenza A (H1N1 vaccination program among university students and health care workers during the pandemic influenza in many parts of the world. Vaccination of high risk individuals is one of the recommendations of World Health Organization during the post-pandemic period. It is not documented about the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period. We aimed to analyze the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period in India. Methods Vaccine against H1N1 was made available to the students of Vellore Institute of Technology, India from September 2010. The data are based on a cross-sectional study conducted during October 2010 to January 2011 using a self-administered questionnaire with a representative sample of the student population (N = 802. Results Of the 802 respondents, only 102/802 (12.7% had been vaccinated and 105/802 (13% planned to do so in the future, while 595/802 (74% would probably or definitely not get vaccinated in the future. The highest coverage was among the female (65/102, 63.7% and non-compliance was higher among men in the group (384/595; 64.5% (p Conclusions Our study shows that the vaccination coverage among university students remains very low in the post-pandemic period and doubts about the safety and effectiveness of the vaccine are key elements in their rejection. Our results indicate a need to provide accessible information about the vaccine safety by scientific authorities and fill gaps and confusions in this regard.

  15. Technology transfer of an oil-in-water vaccine-adjuvant for strengthening pandemic influenza preparedness in Indonesia.

    Ventura, Roland; Brunner, Livia; Heriyanto, Bambang; de Boer, Otto; O'Hara, Michael; Huynh, Chuong; Suhardono, Mahendra; Collin, Nicolas


    With the current enzootic circulation of highly pathogenic avian influenza viruses, the ability to increase global pandemic influenza vaccine production capacity is of paramount importance. This has been highlighted by, and is one of the main pillars of, the WHO Global Action Plan for Influenza Vaccines (GAP). Such capacity expansion is especially relevant in developing countries. The Vaccine Formulation Laboratory at University of Lausanne is engaged in the technology transfer of an antigen-sparing oil-in-water adjuvant in order to empower developing countries vaccine manufacturers to increase pandemic influenza vaccine capacity. In a one-year project funded by United States Department of Health and Human Services, the Vaccine Formulation Laboratory transferred the process know-how and associated equipment for the pilot-scale manufacturing of an oil-in-water adjuvant to Bio Farma, Indonesia's state-owned vaccine manufacturer, for subsequent formulation with H5N1 pandemic influenza vaccines. This paper describes the experience acquired and lessons learnt from this technology transfer project.

  16. Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE multicentre case-control study.

    Marta Valenciano


    Full Text Available BACKGROUND: A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI laboratory-confirmed as pandemic influenza A (H1N1 (pH1N1. METHODS AND FINDINGS: Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year. We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902 adjusted pandemic VE (PIVE estimates were 71.9% (95% confidence interval [CI] 45.6-85.5 overall; 78.4% (95% CI 54.4-89.8 in patients <65 years; and 72.9% (95% CI 39.8-87.8 in individuals without chronic disease. The complete case (n = 1,502 adjusted PIVE were 66.0% (95% CI 23.9-84.8, 71.3% (95% CI 29.1-88.4, and 70.2% (95% CI 19.4-89.0, respectively. The adjusted PIVE was 66.0% (95% CI -69.9 to 93.2 if vaccinated 8-14 days before ILI onset. The adjusted 2009-2010 seasonal influenza VE was 9.9% (95% CI -65.2 to 50.9. CONCLUSIONS: Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the

  17. The Mx1 gene protects mice against the pandemic 1918 and highly lethal human H5N1 influenza viruses.

    Tumpey, Terrence M; Szretter, Kristy J; Van Hoeven, Neal; Katz, Jacqueline M; Kochs, Georg; Haller, Otto; García-Sastre, Adolfo; Staeheli, Peter


    Mice carrying a wild-type Mx1 gene (Mx1+/+) differ from standard laboratory mice (Mx1-/-) in being highly resistant to infection with common laboratory strains of influenza A virus. We report that Mx1 also protects mice against the pandemic human 1918 influenza virus and a highly lethal human H5N1 strain from Vietnam. Resistance to H5N1 of Mx1+/+ but not Mx1-/- mice was enhanced if the animals were treated with a single dose of exogenous alpha interferon before infection. Thus, the interferon-induced resistance factor Mx1 represents a key component of the murine innate immune system that mediates protection against epidemic and pandemic influenza viruses.

  18. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)


    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  19. Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: public health risk implications.

    Stincarelli, Maria; Arvia, Rosaria; De Marco, Maria Alessandra; Clausi, Valeria; Corcioli, Fabiana; Cotti, Claudia; Delogu, Mauro; Donatelli, Isabella; Azzi, Alberta; Giannecchini, Simone


    Exploring the reassortment ability of the 2009 pandemic H1N1 (A/H1N1pdm09) influenza virus with other circulating human or avian influenza viruses is the main concern related to the generation of more virulent or new variants having implications for public health. After different coinfection experiments in human A549 cells, by using the A/H1N1pdm09 virus plus one of human seasonal influenza viruses of H1N1 and H3N2 subtype or one of H11, H10, H9, H7 and H1 avian influenza viruses, several reassortant viruses were obtained. Among these, the HA of H1N1 was the main segment of human seasonal influenza virus reassorted in the A/H1N1pdm09 virus backbone. Conversely, HA and each of the three polymerase segments, alone or in combination, of the avian influenza viruses mainly reassorted in the A/H1N1pdm09 virus backbone. Of note, A/H1N1pdm09 viruses that reassorted with HA of H1N1 seasonal human or H11N6 avian viruses or carried different combination of avian origin polymerase segments, exerted a higher replication effectiveness than that of the parental viruses. These results confirm that reassortment of the A/H1N1pdm09 with circulating low pathogenic avian influenza viruses should not be misjudged in the prediction of the next pandemic.

  20. Pandemic influenza preparedness and health systems challenges in Asia: results from rapid analyses in 6 Asian countries

    Putthasri Weerasak


    Full Text Available Abstract Background Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. Methods The study relied on the Systemic Rapid Assessment (SYSRA toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. Results The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission

  1. Gauging U.S. Emergency Medical Services workers' willingness to respond to pandemic influenza using a threat- and efficacy-based assessment framework.

    Daniel J Barnett

    Full Text Available BACKGROUND: Emergency Medical Services workers' willingness to report to duty in an influenza pandemic is essential to healthcare system surge amidst a global threat. Application of Witte's Extended Parallel Process Model (EPPM has shown utility for revealing influences of perceived threat and efficacy on non-EMS public health providers' willingness to respond in an influenza pandemic. We thus propose using an EPPM-informed assessment of EMS workers' perspectives toward fulfilling their influenza pandemic response roles. METHODOLOGY/PRINCIPAL FINDINGS: We administered an EPPM-informed snapshot survey about attitudes and beliefs toward pandemic influenza response, to a nationally representative, stratified random sample of 1,537 U.S. EMS workers from May-June 2009 (overall response rate: 49%. Of the 586 respondents who met inclusion criteria (currently active EMS providers in primarily EMS response roles, 12% indicated they would not voluntarily report to duty in a pandemic influenza emergency if asked, 7% if required. A majority (52% indicated their unwillingness to report to work if risk of disease transmission to family existed. Confidence in personal safety at work (OR = 3.3 and a high threat/high efficacy ("concerned and confident" EPPM profile (OR = 4.7 distinguished those who were more likely to voluntarily report to duty. Although 96% of EMS workers indicated that they would probably or definitely report to work if they were guaranteed a pandemic influenza vaccine, only 59% had received an influenza immunization in the preceding 12 months. CONCLUSIONS/SIGNIFICANCE: EMS workers' response willingness gaps pose a substantial challenge to prehospital surge capacity in an influenza pandemic. "Concerned and confident" EMS workers are more than four times as likely to fulfill pandemic influenza response expectations. Confidence in workplace safety is a positively influential modifier of their response willingness. These findings can inform

  2. Preliminary study about sublingual administration of bacteria-expressed pandemic H1N1 influenza vaccine in miniature pigs.

    Kim, Hyekwon; Kim, Jeong-Ki; Song, Hohyun; Choi, Jungah; Shim, Byoungshik; Kang, Bokyu; Moon, Hyoungjoon; Yeom, Minjoo; Kim, Sang-Hyun; Song, Daesub; Song, Manki


    Sublingual (SL) administration of influenza vaccine would be non-invasive and effective way to give human populations protective immunity against the virus, especially when pandemic influenza outbreaks. In this study, the efficacy of pandemic influenza virus-based subunit vaccines was tested after sublingual (SL) adjuvant administration in pigs. Eight specific pathogen-free Yucatan pigs were divided into 4 groups: nonvaccinated but challenged (A) and vaccinated and challenged (B, C, and D). The vaccinated groups were subdivided by vaccine type and inoculation route: SL subunit vaccine (hemagglutinin antigen 1 [HA1] + wild-type cholera toxin [wtCT], B); IM subunit vaccine (HA1 + aluminum hydroxide, C); and IM inactivated vaccine (+ aluminum hydroxide, D). The vaccines were administered twice at a 2-week interval. All pigs were challenged with pandemic influenza virus (A/swine/GCVP-KS01/2009 [H1N1]) and monitored for clinical signs, serology, viral shedding, and histopathology. After vaccination, hemagglutination inhibition titre was higher in group D (320) than in the other vaccinated groups (40-80) at the time of challenge. The mobility and feed intake were reduced in group C. Both viral shedding and histopathological lesions were reduced in groups B and D. Although this study has limitation due to the limited number of pigs (2 pigs per a group), the preliminary data in this study provided the protective potential of SL administration of bacteria-expressed pandemic H1N1 influenza vaccine in pigs. There should be additional animal studies about effective adjuvant system and vaccine types for the use of SL influenza vaccination.

  3. EFSA Panel on Animal Health and Welfare (AHAW); Scientific Opinion on monitoring for the emergence of possible new pandemic strains of influenza in animals

    Bøtner, Anette; Capua, Ilaria; Gatherer, Derek

    Following the emergence in 2009 of the new pandemic H1N1 influenza virus, which contained gene segments from pig, bird and human influenza viruses, it was apparent that a better scientific understanding is required of influenza viruses to protect public and animal health. The latest scientific data...... an alert for the emergence of new human influenza strains of public health significance. In contrast, there is an incomplete view of the influenza virus strains circulating among pigs and birds at the global level. Interpretation of the origins and pandemic potential of influenza viruses do require...... knowledge of the influenza gene pools in both pigs and birds, as well as other animal species. It is recommended that there should be long term support for a passive monitoring network in pigs and birds in order to promote greater understanding of the evolution of influenza viruses at the global level...

  4. The feasibility of age-specific travel restrictions during influenza pandemics

    Lam Elson HY


    Full Text Available Abstract Background Epidemiological studies have shown that imposing travel restrictions to prevent or delay an influenza pandemic may not be feasible. To delay an epidemic substantially, an extremely high proportion of trips (~99% would have to be restricted in a homogeneously mixing population. Influenza is, however, strongly influenced by age-dependent transmission dynamics, and the effectiveness of age-specific travel restrictions, such as the selective restriction of travel by children, has yet to be examined. Methods A simple stochastic model was developed to describe the importation of infectious cases into a population and to model local chains of transmission seeded by imported cases. The probability of a local epidemic, and the time period until a major epidemic takes off, were used as outcome measures, and travel restriction policies in which children or adults were preferentially restricted were compared to age-blind restriction policies using an age-dependent next generation matrix parameterized for influenza H1N1-2009. Results Restricting children from travelling would yield greater reductions to the short-term risk of the epidemic being established locally than other policy options considered, and potentially could delay an epidemic for a few weeks. However, given a scenario with a total of 500 imported cases over a period of a few months, a substantial reduction in the probability of an epidemic in this time period is possible only if the transmission potential were low and assortativity (i.e. the proportion of contacts within-group were unrealistically high. In all other scenarios considered, age-structured travel restrictions would not prevent an epidemic and would not delay the epidemic for longer than a few weeks. Conclusions Selectively restricting children from traveling overseas during a pandemic may potentially delay its arrival for a few weeks, depending on the characteristics of the pandemic strain, but could have less

  5. Post-pandemic seroprevalence of pandemic influenza A (H1N1 2009 infection (swine flu among children <18 years in Germany.

    Rüdiger von Kries

    Full Text Available BACKGROUND: We determined antibodies to the pandemic influenza A (H1N1 2009 virus in children to assess: the incidence of (H1N1 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. METHODOLOGY/PRINCIPAL FINDINGS: Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1(st to July 31(st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (≥1∶10 was 27.1% (95% CI: 23.5-31.3 and 53.5% (95% CI: 50.9-56.2 compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5 in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0 in 5-17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5-28.8 reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6 of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5 of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1 2009. CONCLUSION: Serologically determined incidence of influenza A (H1N1 2009 infections in children indicates high infection rates with older children (5-17 years infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B

  6. Targets for the Induction of Protective Immunity Against Influenza A Viruses

    Guus F. Rimmelzwaan


    Full Text Available The current pandemic caused by the new influenza A(H1N1 virus of swine origin and the current pandemic threat caused by the highly pathogenic avian influenza A viruses of the H5N1 subtype have renewed the interest in the development of vaccines that can induce broad protective immunity. Preferably, vaccines not only provide protection against the homologous strains, but also against heterologous strains, even of another subtype. Here we describe viral targets and the arms of the immune response involved in protection against influenza virus infections such as antibodies directed against the hemagglutinin, neuraminidase and the M2 protein and cellular immune responses directed against the internal viral proteins.

  7. Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants.

    Ahmed, S Sohail; Schur, Peter H; MacDonald, Noni E; Steinman, Lawrence


    The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted A(H1N1) pandemic vaccine were used in more than 47 countries. The Canadian AS03-adjuvanted A(H1N1) pandemic vaccine was used with high coverage in Canada where an estimated 12 million doses were administered. As no similar narcolepsy association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic vaccine made using the Canadian inactivation/purification protocol, this suggests that the AS03 adjuvant alone may not be responsible for the narcolepsy association. To date, no narcolepsy association has been reported with the MF59®-adjuvanted A(H1N1) pandemic vaccine. This review article provides a brief background on narcolepsy, outlines the different types of vaccine preparations including the ones for influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between autoimmune diseases and natural infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why vaccine-associated narcolepsy may not be solely linked to the AS03 adjuvant but more likely be linked to how the specific influenza antigen component of the European AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic vaccine prepared with

  8. PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology.

    Julie L McAuley

    Full Text Available With the recent emergence of a novel pandemic strain, there is presently intense interest in understanding the molecular signatures of virulence of influenza viruses. PB1-F2 proteins from epidemiologically important influenza A virus strains were studied to determine their function and contribution to virulence. Using 27-mer peptides derived from the C-terminal sequence of PB1-F2 and chimeric viruses engineered on a common background, we demonstrated that induction of cell death through PB1-F2 is dependent upon BAK/BAX mediated cytochrome c release from mitochondria. This function was specific for the PB1-F2 protein of A/Puerto Rico/8/34 and was not seen using PB1-F2 peptides derived from past pandemic strains. However, PB1-F2 proteins from the three pandemic strains of the 20(th century and a highly pathogenic strain of the H5N1 subtype were shown to enhance the lung inflammatory response resulting in increased pathology. Recently circulating seasonal influenza A strains were not capable of this pro-inflammatory function, having lost the PB1-F2 protein's immunostimulatory activity through truncation or mutation during adaptation in humans. These data suggest that the PB1-F2 protein contributes to the virulence of pandemic strains when the PB1 gene segment is recently derived from the avian reservoir.

  9. [Effects of school closure during influenza A/H1N1 pandemic in 2009 in Japan].

    Uchida, Mitsuo; Kaneko, Minoru; Yamamoto, Hiroshi; Honda, Takayuki; Kawa, Shigeyuki


    Schools were closed worldwide during the 2009 influenza A/H1N1 pandemic to prevent the viral spread; however, to date, there has been insufficient evidence to conclude that the closures were beneficial. Therefore, in the present review, we evaluated the effects of school closure during the 2009 influenza A/H1N1 pandemic in Japan. A search of PubMed and Japanese journals identified 24 articles that evaluated the effects of school closure using the following methods: descriptive epidemiology, changes in absenteeism rate, a simulation model, and reproductive number. Almost all of the retrieved studies showed that school closure effectively reduced the number of new infections and thus subsequently suppressed the epidemic. On the other hand, two major sets of confounding variables were identified. First, the effect of school closure was confounded by the methods used to measure, viral infectivity, subject characteristics, increased immunization rates, nonpharmaceutical interventions, antiviral administration, student contact patterns during school closure, and individual household environments. Secondly, school closure implementation was affected by differences between proactive and reactive closures, differences between seasonal and pandemic influenza, decision factors regarding school closure, socioeconomic cost, and ethics of imposing restrictions on individuals. Therefore, a comprehensive, longitudinal study is necessary to clarify the effects of school closure during viral pandemics.

  10. Ten lessons for the next influenza pandemic-an English perspective: a personal reflection based on community surveillance data.

    Fleming, Douglas M; Durnall, Hayley


    We review experience in England of the swine flu pandemic between May 2009 and April 2010. The surveillance data from the Royal College of General Practitioners Weekly Returns Service and the linked virological data collected in the integrated program with the Health Protection Agency are used as a reference frame to consider issues emerging during the pandemic. Ten lessons are summarized. (1) Delay between illness onset in the first worldwide cases and virological diagnosis restricted opportunities for containment by regional prophylaxis. (2) Pandemic vaccines are unlikely to be available for effective prevention during the first wave of a pandemic. (3) Open, realistic and continuing communication with the public is important. (4) Surveillance programs should be continued through summer as well as winter. (5) Severity of illness should be incorporated in pandemic definition. (6) The reliability of diagnostic tests as used in routine clinical practice calls for further investigation. (7) Evidence from serological studies is not consistent with evidence based on health care requests made by sick persons and is thus of limited value in cost effectiveness studies. (8) Pregnancy is an important risk factor. (9) New strategies for administering vaccines need to be explored. (10) Acceptance by the public and by health professionals of influenza vaccination as the major plank on which the impact of influenza is controlled has still not been achieved.

  11. Modelling the spatial-temporal progression of the 2009 A/H1N1 influenza pandemic in Chile.

    Bürger, Raimund; Chowell, Gerardo; Mulet, Pep; Villada, Luis M


    A spatial-temporal transmission model of 2009 A/H1N1 pandemic influenza across Chile, a country that spans a large latitudinal range, is developed to characterize the spatial variation in peak timing of that pandemic as a function of local transmission rates, spatial connectivity assumptions for Chilean regions, and the putative location of introduction of the novel virus into the country. Specifically, a metapopulation SEIR (susceptible-exposed-infected-removed) compartmental model that tracks the transmission dynamics of influenza in 15 Chilean regions is calibrated. The model incorporates population mobility among neighboring regions and indirect mobility to and from other regions via the metropolitan central region ('hub region'). The stability of the disease-free equilibrium of this model is analyzed and compared with the corresponding stability in each region, concluding that stability may occur even with some regions having basic reproduction numbers above 1. The transmission model is used along with epidemiological data to explore potential factors that could have driven the spatial-temporal progression of the pandemic. Simulations and sensitivity analyses indicate that this relatively simple model is sufficient to characterize the south-north gradient in peak timing observed during the pandemic, and suggest that south Chile observed the initial spread of the pandemic virus, which is in line with a retrospective epidemiological study. The 'hub region' in our model significantly enhanced population mixing in a short time scale.

  12. Modeling the worldwide spread of pandemic influenza: baseline case and containment interventions.

    Vittoria Colizza


    Full Text Available BACKGROUND: The highly pathogenic H5N1 avian influenza virus, which is now widespread in Southeast Asia and which diffused recently in some areas of the Balkans region and Western Europe, has raised a public alert toward the potential occurrence of a new severe influenza pandemic. Here we study the worldwide spread of a pandemic and its possible containment at a global level taking into account all available information on air travel. METHODS AND FINDINGS: We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal. For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV drugs. We investigated the effect of the use of AV drugs in the event that therapeutic protocols can be carried out with maximal coverage for the populations in all countries. In view of the wide diversity of AV stockpiles in different regions of the world, we also studied scenarios in which only a limited number of countries are prepared (i.e., have considerable AV supplies. In particular, we compared different plans in which, on the one hand, only prepared and wealthy countries benefit from large AV resources, with, on the other hand, cooperative containment scenarios in which countries with large AV stockpiles make a small portion of their supplies available worldwide. CONCLUSIONS: We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit

  13. Student behavior during a school closure caused by pandemic influenza A/H1N1.

    Joel C Miller

    Full Text Available BACKGROUND: Many schools were temporarily closed in response to outbreaks of the recently emerged pandemic influenza A/H1N1 virus. The effectiveness of closing schools to reduce transmission depends largely on student/family behavior during the closure. We sought to improve our understanding of these behaviors. METHODOLOGY/PRINCIPAL FINDINGS: To characterize this behavior, we surveyed students in grades 9-12 and parents of students in grades 5-8 about student activities during a week long closure of a school during the first months after the disease emerged. We found significant interaction with the community and other students-though less interaction with other students than during school-with the level of interaction increasing with grade. CONCLUSIONS: Our results are useful for the future design of social distancing policies and to improving the ability of modeling studies to accurately predict their impact.

  14. Monitoring extravascular lung water in acute respiratory distress syndrome induced by probable 2009 pandemic influenza A (H1N1) virus: report of two cases

    LI Hong-liang; WANG Zong-yu; YAO Gai-qi; ZHU Xi


    @@ During the spring of 2009, a pandemic novel influenza A (H1N1) vims emerged and spread globally. As of January 3, 2009, more than 208 countries and overseas territories or communities have reported laboratory-confirmed cases of pandemic influenza H1N1 2009, including at least 12 799 death cases.1 Critical cases developed severe acute respiratory distress syndrome (ARDS) rapidly, which was refractory to conventional mechanical ventilation and rescue therapies.

  15. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania.

    Fox, Christopher B; Huynh, Chuong; O'Hara, Michael K; Onu, Adrian


    Many developing countries lack or have inadequate pandemic influenza vaccine manufacturing capacity. In the 2009 H1N1 pandemic, this led to delayed and inadequate vaccine coverage in the developing world. Thus, bolstering developing country influenza vaccine manufacturing capacity is urgently needed. The Cantacuzino Institute in Bucharest, Romania has been producing seasonal influenza vaccine since the 1970s, and has the capacity to produce ∼5 million doses of monovalent vaccine in the event of an influenza pandemic. Inclusion of an adjuvant in the vaccine could enable antigen dose sparing, expanding vaccine coverage and potentially allowing universal vaccination of the Romanian population and possibly neighboring countries. However, adjuvant formulation and manufacturing know-how are difficult to access. This manuscript describes the successful transfer of oil-in-water emulsion adjuvant manufacturing and quality control technologies from the Infectious Disease Research Institute in Seattle, USA to the Cantacuzino Institute. By describing the challenges and accomplishments of the project, it is hoped that the knowledge and experience gained will benefit other institutes involved in similar technology transfer projects designed to facilitate increased vaccine manufacturing capacity in developing countries.

  16. The 2009 H1N1 influenza pandemic and Minnesota's K-12 schools: public health lessons learned.

    Como-Sabetti, Kathryn; Livingston, Franci; Gahr, Pamala; Nagle, Kayla; Martin, Karen; Morin, Craig; Parilla, Elizabeth


    Prior to 2009, influenza pandemic planners had primarily planned for a virus that would originate in a location other than North America, giving public health officials in the United States time to determine its severity before widespread disease occurred here. Thus, response plans for schools focused on closure in the case of a severe pandemic and potential closure in the event of a moderate one. The 2009 H1N1 pandemic, however, presented a different scenario. The severity of 2009 H1N1 was initially unknown and later was determined to be mild to moderate. Thus, as the pandemic unfolded, state and national public health entities found themselves adapting their recommendations for school closure. This article reviews Minnesota's experience with 2009 H1N1, focusing on the pandemic among school-aged children during the spring (April to August 2009) and fall (September 2009 to April 2010), and it chronicles how outbreak surveillance policies and recommendations for K-12 schools changed over the course of the pandemic.

  17. Immune response after one or two doses of pandemic influenza A (H1N1) monovalent, AS03-adjuvanted vaccine in HIV infected adults

    Bybeck Nielsen, Allan; Nielsen, Henriette Schjønning; Nielsen, Lars;


    INTRODUCTION: Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients. METHOD......: Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n=60), one (n=31) or two (n=128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared.......7% and seroconversion rate of 86.7%. CONCLUSION: A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4-9 months. Two doses improved the immunogenicity further....

  18. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Nuriban Valero-Pacheco

    Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  19. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino


    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  20. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine

    Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C.; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino


    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans. PMID:26919288

  1. Serums and vaccines to fight the 1918-1919 influenza pandemic in Spain

    Porras Gallo, María Isabel


    Full Text Available Against the background of the renewed interest aroused in recent years by the influenza pandemic of 1918-1919, and the leading role now played by research analysing the process of innovation in medicine, this paper assesses the role played by serums and vaccines —the new resources of the medical science of the time— in the fight against the influenza outbreak of 1918-1919. The paper highlights the dependence on combined scientific, social, economic and professional factors, and also shows the main consequences arising from the fine-tuning and implementation of these therapeutic and prophylactic resources.

    En el marco de la renovada actualidad alcanzada por la pandemia de gripe de 1918-1919 en los últimos años y del protagonismo logrado por los estudios que analizan el proceso de innovación en Medicina, el presente trabajo analiza el papel representado por sueros y vacunas —los nuevos recursos de la ciencia médica del momento— en la lucha contra la gripe de 1918-1919. El estudio pone de relieve su dependencia de los factores científicos, sociales, económicos y profesionales que concurrieron, y muestra también las principales consecuencias derivadas de la puesta a punto y uso de los citados recursos terapéuticos y profilácticos.

  2. H5N1 Avian Influenza Pre-pandemic Vaccine Strains in China

    BO Hong; DONG Li Bo; ZHANG Ye; DONG Jie; ZOU Shu Mei; GAO Rong Bao; WANG Da Yan; SHU Yue Long


    ObjectiveTo prepare the 4 candidate vaccine strains of H5N1 avian influenza virus isolated in China. MethodsRecombinant viruses were rescued using reverse genetics. Neuraminidase (NA) and hemagglutinin (HA) segments of the A/Xinjiang/1/2006, A/Guangxi/1/2009, A/Hubei/1/2010, and A/Guangdong/1/2011 viruses were amplified by RT-PCR. Multibasic amino acid cleavage site of HA was removed and ligated into the pCIpolI vector for virus rescue. The recombinant viruses were evaluated by trypsin dependent assays. Their embryonate survival and antigenicity were compared with those of the respective wild-type viruses. ResultsThe 4 recombinant viruses showed similar antigenicity compared with wild-type viruses, chickenembryo survival and trypsin-dependent characteristics. ConclusionThe 4 recombinantviruses rescued using reverse genetics meet the criteria for classification of low pathogenic avian influenza strains, thus supporting the use of them for the development of seeds and production of pre-pandemic vaccines.

  3. Microdroplet sandwich real-time rt-PCR for detection of pandemic and seasonal influenza subtypes.

    Stephanie L Angione

    Full Text Available As demonstrated by the recent 2012/2013 flu epidemic, the continual emergence of new viral strains highlights the need for accurate medical diagnostics in multiple community settings. If rapid, robust, and sensitive diagnostics for influenza subtyping were available, it would help identify epidemics, facilitate appropriate antiviral usage, decrease inappropriate antibiotic usage, and eliminate the extra cost of unnecessary laboratory testing and treatment. Here, we describe a droplet sandwich platform that can detect influenza subtypes using real-time reverse-transcription polymerase chain reaction (rtRT-PCR. Using clinical samples collected during the 2010/11 season, we effectively differentiate between H1N1p (swine pandemic, H1N1s (seasonal, and H3N2 with an overall assay sensitivity was 96%, with 100% specificity for each subtype. Additionally, we demonstrate the ability to detect viral loads as low as 10(4 copies/mL, which is two orders of magnitude lower than viral loads in typical infected patients. This platform performs diagnostics in a miniaturized format without sacrificing any sensitivity, and can thus be easily developed into devices which are ideal for small clinics and pharmacies.

  4. The role of different social contexts in shaping influenza transmission during the 2009 pandemic

    Ajelli, Marco; Poletti, Piero; Melegaro, Alessia; Merler, Stefano


    Evaluating the relative importance of different social contexts in which infection transmission occurs is critical for identifying optimal intervention strategies. Nonetheless, an overall picture of influenza transmission in different social contexts has yet to emerge. Here we provide estimates of the fraction of infections generated in different social contexts during the 2009 H1N1 pandemic in Italy by making use of a highly detailed individual-based model accounting for time use data and parametrized on the basis of observed age-specific seroprevalence. We found that 41.6% (95%CI: 39-43.7%) of infections occurred in households, 26.7% (95%CI: 21-33.2) in schools, 3.3% (95%CI: 1.7-5%) in workplaces, and 28.4% (95%CI: 24.6-31.9%) in the general community. The above estimates strongly depend on the lower susceptibility to infection of individuals 19+ years old compared to younger ones, estimated to be 0.2 (95%CI 0.12-0.28). We also found that school closure over the weekends contributed to decrease the effective reproduction number of about 8% and significantly affected the pattern of transmission. These results highlight the pivotal role played by schools in the transmission of the 2009 H1N1 influenza. They may be relevant in the evaluation of intervention options and, hence, for informing policy decisions.

  5. Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1

    Wong Helen WC


    Full Text Available Abstract Background After the WHO issued the global alert for 2009 pandemic influenza A (H1N1, many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. Methods We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. Results Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. Conclusions Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.

  6. Awareness, attitudes, and practices related to the swine influenza pandemic among the Saudi public

    Al-Jumah Mohammad A


    Full Text Available Abstract Background During an infectious disease outbreak, it is critical to learn as much as possible about the concerns, knowledge, attitudes, and behavior of the public. Such information can be crucial to the improvement of communication efforts by public health officials and clinicians. The aim of this study was to identify awareness, attitudes, and practices related to influenza A (H1N1 among the Saudi public. Methods A cross-sectional study of 1,548 adult subjects recruited from various shopping malls in Riyadh and Jeddah was conducted. All of the subjects were interviewed using a questionnaire that tested their knowledge, attitudes, and use of precautionary measures in relation to the H1N1 influenza pandemic. Results More than half (54.3%, 840/1548 of the participants showed high concern, 43.7%(677/1548 showed a low level of knowledge, and 60.8%(941/1548 had taken minimal or no precautionary measures. After adjusting for other variables, education level was the only significant predictor of the level of concern (p Conclusions High concern did not translate into a higher compliance with precautionary recommendations, possibly due to the low level of knowledge about the disease among the public. Frequent communication between physicians and the public is recommended to help dispel myths about the disease and to spread better information about the role that the public can play in limiting the spread of the disease.

  7. The new school absentees reporting system for pandemic influenza A/H1N1 2009 infection in Japan.

    Takeshi Suzue

    Full Text Available OBJECTIVE: To evaluate the new Japanese School Absentees Reporting System for Infectious Disease (SARSID for pandemic influenza A/H1N1 2009 infection in comparison with the National epidemiological Surveillance of Infectious Disease (NESID. METHODS: We used data of 53,223 students (97.7% in Takamatsu city Japan. Data regarding school absentees in SARSID was compared with that in NESID from Oct 13, 2009 to Jan 12, 2010. RESULTS: Similar trends were observed both in SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought to be more sensitive than that in NESID. CONCLUSION: The epidemic trend for influenza among school-aged children could be easily and rapidly assessed by SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend of influenza.

  8. Seroincidence of Influenza Among HIV-infected and HIV-uninfected Men During the 2009 H1N1 Influenza Pandemic, Bangkok, Thailand.

    Garg, Shikha; Olsen, Sonja J; Fernandez, Stefan; Muangchana, Charung; Rungrojcharoenkit, Kamonthip; Prapasiri, Prabda; Katz, Jacqueline M; Curlin, Marcel E; Gibbons, Robert V; Holtz, Timothy H; Chitwarakorn, Anupong; Dawood, Fatimah S


    Among 368 Thai men who have sex with men with paired serum samples collected before and during the 2009 H1N1 influenza pandemic, we determined influenza A (H1N1)pdm09 seroconversion rates (≥4-fold rise in antibody titers by hemagglutination inhibition or microneutralization assays). Overall, 66 of 232 (28%) participants seroconverted after the first year of A(H1N1)pdm09 activity, and 83 of 234 (35%) participants seroconverted after the second year. Influenza A(H1N1)pdm09 seroconversion did not differ between human immunodeficiency virus (HIV)-infected (55 of 2157 [35%]) and HIV-uninfected (71 of 2211 [34%]) participants (P = .78). Influenza A(H1N1)pdm09 seroconversion occurred in approximately one third of our Thai study population and was similar among HIV-infected and HIV-uninfected participants.

  9. "With human health it's a global thing": Canadian perspectives on ethics in the global governance of an influenza pandemic.

    Thompson, Alison K; Smith, Maxwell J; McDougall, Christopher W; Bensimon, Cécile; Perez, Daniel Felipe


    We live in an era where our health is linked to that of others across the globe, and nothing brings this home better than the specter of a pandemic. This paper explores the findings of town hall meetings associated with the Canadian Program of Research on Ethics in a Pandemic (CanPREP), in which focus groups met to discuss issues related to the global governance of an influenza pandemic. Two competing discourses were found to be at work: the first was based upon an economic rationality and the second upon a humanitarian rationality. The implications for public support and the long-term sustainability of new global norms, networks, and regulations in global public health are discussed.

  10. The Mx1 Gene Protects Mice against the Pandemic 1918 and Highly Lethal Human H5N1 Influenza Viruses▿


    Mice carrying a wild-type Mx1 gene (Mx1+/+) differ from standard laboratory mice (Mx1−/−) in being highly resistant to infection with common laboratory strains of influenza A virus. We report that Mx1 also protects mice against the pandemic human 1918 influenza virus and a highly lethal human H5N1 strain from Vietnam. Resistance to H5N1 of Mx1+/+ but not Mx1−/− mice was enhanced if the animals were treated with a single dose of exogenous alpha interferon before infection. Thus, the interferon...

  11. Epidemiological survey on pandemic influenza A (H1N1) virus infection in Kurdistan province, Islamic Republic of Iran, 2009.

    Afrasiabian, S; Mohsenpour, B; Bagheri, K H; Barari, M; Ghaderi, E; Hashemi, R; Garibi, F


    This study evaluated the epidemiology of suspected cases of pandemic influenza A (H1N1) virus infection in 2009-2010 in Kurdistan province, a frontier province of the Islamic Republic of Iran. A questionnaire covering demographic characteristics, clinical presentation and outcome, and history of exposure and travel was completed by patients attending health centres and hospitals in the province. Nasal and throat swabs were analysed by RT-PCR. A total of 1059 suspected cases were assessed; H1N1 influenza A was confirmed in 157 (14.8%). The highest proportion of confirmed cases was 30.0%, among children aged Kurdistan.

  12. Correlation between emergency room visits for influenza-like illness during the influenza A (H1/N1) pandemic in children and adults.

    Bénet, Thomas; Cassier, Pierre; Voirin, Nicolas; Morélon-Daum, Sophie; Floret, Daniel; Gillet, Yves; Gueugniaud, Pierre-Yves; Vanhems, Philippe


    Surveillance of incident influenza-like illness (ILI) was implemented in two children and adult medical emergency departments during the influenza A (H1/N1) pandemic to assess correlations in the daily number of ILI-related emergency room visits (ERV) between these departments. A total of 7165 ILIs in children and 610 ILIs in adults were observed. We noticed a high linear correlation between the number of ERV involving ILI on day D in the pediatric department and the number of ERV because of ILI 2 days later in adults (R = 0·82, P ILI-related ERV might be anticipated based on the rate of pediatric ERV.

  13. The relative clinical impact of 2009 pandemic influenza A (H1N1) in the community compared to seasonal influenza in the Netherlands was most marked among 5-14 year olds.

    Gageldonk-Lafeber, A.B. van; Hooiveld, M.; Meijer, A.; Donker, G.A.; Veldman-Ariesen, M.J.; Hoek, W. van der; Sande, M.A.B. van der


    Background: So far, most pandemic influenza reports were based on case studies focusing on severe disease. For public health policy, it is essential to consider the overall impact of the pandemic, including mild diseases. Objectives: The aim of our study is to gain insight into the epidemiology of 2

  14. Evaluation of the spread of pandemic influenza A/H1N1 2009 among Japanese university students.

    Uchida, Mitsuo; Kaneko, Minoru; Tsukahara, Teruomi; Washizuka, Shinsuke; Kawa, Shigeyuki


    The pandemic influenza A/H1N1 2009 virus is commonly known to affect younger individuals. Several epidemiological studies have clarified the epidemic features of university students in Japan. In this study, we reviewed these studies in Japan in comparison with reports from other countries. The average cumulative incidence rate among university students was 9.6 %, with the major symptoms being cough, sore throat, and rhinorrhea. These epidemiological features were similar between Japan and other countries. Attitudes and behaviors toward pandemic influenza control measures were different before and improved during and after the epidemic. These features were also similar to those in other countries. On the other hand, the epidemic spread through club activities or social events, and transmission was attenuated after temporary closure of such groups in Japan. This transmission pattern was inconsistent among countries, which may have been due to differences in lifestyle and cultural habits. Based on these results, infection control measures of pandemic influenza for university organizations in Japan should be considered.

  15. Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection

    Yun, Tae Jin; Kwon, Gu Jin; Oh, Mi Kyeong; Woo, Sung Koo; Park, Seung Hoon; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo; Yim, Jae Joon; Kim, Jong Sung; Park, Chang Min [Seoul National University Hospital, Seoul (Korea, Republic of)


    To describe detailed clinical and radiological features of the pandemic H1N1 2009 influenza viral infection among healthy young males in a semiclosed institutionalized setting. A total of 18 patients confirmed with the pandemic H1N1 2009 influenza virus infection from July 18 to July 30, 2009 were enrolled in this study. Each patient underwent an evaluation to determine detailed clinical and radiological features. All patients presented with high fever (> 38.0..C), with accompanying symptoms of cough, rhinorrhea, sore throat, myalgia and diarrhea, and increased C-reactive protein (CRP) values with no leukocytosis nor elevated erythrocyte sedimentation rate (ESR). All patients, including one patient who progressed into acute respiratory distress syndrome, were treated with oseltamivir phosphate and quickly recovered from their symptoms. Chest radiographs showed abnormalities of small nodules and lobar consolidation in only two out of 18 patients. However, six of 12 patients who underwent thin-section CT examinations showed abnormal findings for small ground-glass opacities (GGOs) in addition to poorly-defined nodules with upper lobe predominance. In a population of healthy young adults, elevated CRP with normal ESR and white blood cell levels combined with GGOs and nodules on thin section CT scans may indicate early signs of infection by the pandemic H1N1 2009 influenza virus

  16. A new sentinel surveillance system for severe influenza in England shows a shift in age distribution of hospitalised cases in the post-pandemic period.

    Shelly Bolotin

    Full Text Available BACKGROUND: The World Health Organization and European Centre for Disease Prevention and Control have highlighted the importance of establishing systems to monitor severe influenza. Following the H1N1 (2009 influenza pandemic, a sentinel network of 23 Trusts, the UK Severe Influenza Surveillance System (USISS, was established to monitor hospitalisations due to confirmed seasonal influenza in England. This article presents the results of the first season of operation of USISS in 2010/11. METHODOLOGY/PRINCIPAL FINDINGS: A case was defined as a person hospitalised with confirmed influenza of any type. Weekly aggregate numbers of hospitalised influenza cases, broken down by flu type and level of care, were submitted by participating Trusts. Cases in 2010/11 were compared to cases during the 2009 pandemic in hospitals with available surveillance data for both time periods (n = 19. An unexpected resurgence in seasonal A/H1N1 (2009 influenza activity in England was observed in December 2010 with reports of severe disease. Reported cases over the period of 4 October 2010 to 13 February 2011 were mostly due to influenza A/H1N1 (2009. One thousand and seventy-one cases of influenza A/H1N1 (2009 occurred over this period compared to 409 at the same Trusts over the 2009/10 pandemic period (1 April 2009 to 6 January 2010. Median age of influenza A/H1N1 (2009 cases in 2010/11 was 35 years, compared with 20 years during the pandemic (p = <0.0001. CONCLUSIONS/SIGNIFICANCE: The Health Protection Agency successfully established a sentinel surveillance system for severe influenza in 2010/11, detecting a rise in influenza cases mirroring other surveillance indicators. The data indicate an upward shift in the age-distribution of influenza A/H1N1 (2009 during the 2010/11 influenza season as compared to the 2009/10 pandemic. Systems to enable the ongoing surveillance of severe influenza will be a key component in understanding and responding to the evolving

  17. Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008

    Liese Johannes G


    Full Text Available Abstract Background Data on complications in children with seasonal influenza virus infection are limited. We initiated a nation-wide three-year surveillance of children who were admitted to a paediatric intensive care unit (PICU with severe seasonal influenza. Methods From October 2005 to July 2008, active surveillance was performed using an established reporting system for rare diseases (ESPED including all paediatric hospitals in Germany. Cases to be reported were hospitalized children Results Twenty severe influenza-associated cases were reported from 14 PICUs during three pre-pandemic influenza seasons (2005-2008. The median age of the patients (12 males/8 females was 7.5 years (range 0.1-15 years. None had received vaccination against influenza. In 14 (70% patients, the infection had been caused by influenza A and in five (25% by influenza B; in one child (5% the influenza type was not reported. Patients spent a median of 19 (IQR 12-38 days in the hospital and a median of 11 days (IQR 6-18 days in the PICU; 10 (50% needed mechanical ventilation. Most frequent diagnoses were influenza-associated pneumonia (60%, bronchitis/bronchiolitis (30%, encephalitis/encephalopathy (25%, secondary bacterial pneumonia (25%, and ARDS (25%. Eleven (55% children had chronic underlying medical conditions, including 8 (40% with chronic pulmonary diseases. Two influenza A- associated deaths were reported: i an 8-year old boy with pneumococcal encephalopathy following influenza infection died from cerebral edema, ii a 14-year-old boy with asthma bronchiale, cardiac malformation and Addison's disease died from cardiac and respiratory failure. For nine (45% patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary, 3 other sequelae. Conclusions Influenza-associated pneumonia and secondary bacterial infections are relevant complications of seasonal influenza in Germany. The incidence of severe influenza cases in PICUs was relatively low

  18. Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay.

    Béatrice Labrosse

    Full Text Available BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007 and against pandemic A/H1N1 (A/California/04/2009 were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic.

  19. Population Effects of Influenza A(H1N1) Pandemic among Health Plan Members, San Diego, California, USA, October-December 2009.

    Bitar, Roger A


    Lacking population-specific data, activity of seasonal and pandemic influenza is usually tracked by counting the number of diagnoses and visits to medical facilities above a baseline. This type of data does not address the delivery of services in a specific population. To provide population-specific data, this retrospective study of patients with influenza-like illness, influenza, and pneumonia among members of a Kaiser Permanente health plan in San Diego, California, USA, during October-December 2009 was initiated. Population data included the number of outpatients accessing healthcare; the number of patients diagnosed with pneumonia; antimicrobial therapy administered; number of patients hospitalized with influenza, influenza-like illness, or pneumonia; level of care provided; and number of patients requiring specialized treatments (e.g., oxygen, ventilation, vasopressors). The rate of admissions specific to weeks and predictions of 2 epidemiologic models shows the strengths and weaknesses of those tools. Data collected in this study may improve planning for influenza pandemics.

  20. Oseltamivir for treatment and prevention of pandemic influenza A/H1N1 virus infection in households, Milwaukee, 2009

    Miller Joel C


    Full Text Available Abstract Background During an influenza pandemic, a substantial proportion of transmission is thought to occur in households. We used data on influenza progression in individuals and their contacts collected by the City of Milwaukee Health Department (MHD to study the transmission of pandemic influenza A/H1N1 virus in 362 households in Milwaukee, WI, and the effects of oseltamivir treatment and chemoprophylaxis. Methods 135 households had chronological information on symptoms and oseltamivir usage for all household members. The effect of oseltamivir treatment and other factors on the household secondary attack rate was estimated using univariate and multivariate logistic regression with households as the unit of analysis. The effect of oseltamivir treatment and other factors on the individual secondary attack rate was estimated using univariate and multivariate logistic regression with individual household contacts as the unit of analysis, and a generalized estimating equations approach was used to fit the model to allow for clustering within households. Results Oseltamivir index treatment on onset day or the following day (early treatment was associated with a 42% reduction (OR: 0.58, 95% CI: 0.19, 1.73 in the odds of one or more secondary infections in a household and a 50% reduction (OR: 0.5, 95% CI: 0.17, 1.46 in the odds of a secondary infection in individual contacts. The confidence bounds are wide due to a small sample of households with early oseltamivir index usage - in 29 such households, 5 had a secondary attack. Younger household contacts were at higher risk of infection (OR: 2.79, 95% CI: 1.50-5.20. Conclusions Early oseltamivir treatment may be beneficial in preventing H1N1pdm influenza transmission; this may have relevance to future control measures for influenza pandemics. Larger randomized trials are needed to confirm this finding statistically.

  1. From press release to news: mapping the framing of the 2009 H1N1 A influenza pandemic.

    Lee, Seow Ting; Basnyat, Iccha


    Pandemics challenge conventional assumptions about health promotion, message development, community engagement, and the role of news media. To understand the use of press releases in news coverage of pandemics, this study traces the development of framing devices from a government public health agency's press releases to news stories about the 2009 H1N1 A influenza pandemic. The communication management of the H1N1 pandemic, an international news event with local implications, by the Singapore government is a rich locus for understanding the dynamics of public relations, health communication, and journalism. A content analysis shows that the evolution of information from press release to news is marked by significant changes in media frames, including the expansion and diversification in dominant frames and emotion appeals, stronger thematic framing, more sources of information, conversion of loss frames into gain frames, and amplification of positive tone favoring the public health agency's position. Contrary to previous research that suggests that government information subsidies passed almost unchanged through media gatekeepers, the news coverage of the pandemic reflects journalists' selectivity in disseminating the government press releases and in mediating the information flow and frames from the press releases.

  2. Next generation syndromic surveillance: molecular epidemiology, electronic health records and the pandemic Influenza A (H1N1) virus.

    Rabadan, Raul; Calman, Neil; Hripcsak, George


    In the early phase of the 2009 A (H1N1) pandemic a marked increase in severity and a shift in the age distribution toward younger persons was found, with higher severity reported in patients with pre-existing medical conditions and pregnant women. Consistent with previous pandemics, the age and clinical history of the patients play a critical role in the morbidity and mortality associated with the pandemic virus. This is the first influenza pandemic in the information era, where enormous amounts of information will be available from the pathogen and the patient. Recent advances in molecular techniques have provided an enormous amount of information about pathogens in near real time and at relatively low cost. Electronic Health Records (EHRs) provide another enormously rich set of information about patients, which include patient preconditions, previous exposures, immunization history, presenting complaints, duration and severity of illness, treatment history, and geographic location. An infectious disease is a complex interplay between host and pathogen. The morbidity and mortality of a virus depend on the virus, the patient, and the environment. To evaluate and understand the severity of the pandemic virus and to identify the populations at risk of mild or severe, life-threatening illness, it is compulsory to integrate viral and patient information in a fast and accurate way. Both advances in biomedical informatics with the creation of EHRs and molecular techniques provide the framework to achieve these aims.

  3. Ethnicity, deprivation and mortality due to 2009 pandemic influenza A(H1N1) in England during the 2009/2010 pandemic and the first post-pandemic season.

    Zhao, H; Harris, R J; Ellis, J; Pebody, R G


    The relationship between risk of death following influenza A(H1N1)pdm09 infection and ethnicity and deprivation during the 2009/2010 pandemic period and the first post-pandemic season of 2010/2011 in England was examined. Poisson regression models were used to estimate the mortality risk, adjusted for age, gender, and place of residence. Those of non-White ethnicity experienced an increased mortality risk compared to White populations during the 2009/2010 pandemic [10·5/1000 vs. 6·0/1000 general population; adjusted risk ratio (RR) 1·84, 95% confidence interval (CI) 1·39-2·54] with the highest risk in those of Pakistani ethnicity. However, no significant difference between ethnicities was observed during the following 2010/2011 season. Persons living in areas with the highest level of deprivation had a significantly higher risk of death (RR 2·08, 95% CI 1·49-2·91) compared to the lowest level for both periods. These results highlight the importance of rapid identification of groups at higher risk of severe disease in the early stages of future pandemics to enable the implementation of optimal prevention and control measures for vulnerable populations.

  4. Oseltamivir compounding in the hospital pharmacy during the (H1N1 influenza pandemic

    Márcia Lúcia de Mário Marin


    Full Text Available AIMS: Pandemics impose large demands on the health care system. The supply of appropriate chemotherapeutic agents, namely oseltamivir solution, presented a serious challenge in the recent influenza pandemic. This study reports on the rational series of pharmacotechnical steps that were followed to appropriately handle bulk oseltamivir powder to meet the increased demand. METHODS: During a six-week period in August and September of 2009, a task force was created in the Central Pharmacy of Hospital das Clínicas to convert imported oseltamivir phosphate into ready-to-use solution for utilization by physicians and public health authorities. The protocol included dissolution, physico-chemical tests and the bottling of a liquid microdose formulation for emergency room and outpatient dispensing with adequate quality control during all phases. RESULTS: The successful production routine was based on a specially designed flowchart according to which a batch of 33210 g of oseltamivir powder was converted into 32175 solution units during the aforementioned period with a net loss of only 2.6%. The end products were bottles containing 50 ml of 15 mg/mL oseltamivir solution. The measured concentration was stable and accurate (97.5% - 102.0% of the nominal value. The drug was prescribed as both a prophylactic and therapeutic agent. DISCUSSION: Hospital pharmacies are conventionally engaged in the manipulation of medical prescriptions and specialty drugs. They are generally responsible for only small-scale equipment used for manufacturing and quality-control procedures. The compounding of oseltamivir was a unique effort dictated by exceptional circumstances. CONCLUSION: The shortage of oseltamivir solution for clinical use was solved by emergency operationalization of a semi-industrial process in which bulk powder was converted into practical vials for prompt delivery.

  5. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza.

    Gustavo Palacios

    (OR of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001. CONCLUSIONS/SIGNIFICANCE: The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management.

  6. Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

    Bragstad, Karoline; Martel, Cyril; Thomsen, Joakim S.;


    Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13-23. Background Alternative influenza vaccines...... immunised by particle-mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were......, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross-reactive immune responses against a recent 2005 H3N2 virus challenge. Conclusions DNA vaccines based on pandemic or recent seasonal influenza genes induced cross-reactive immunity against contemporary virus challenge as good...

  7. The Spanish flu in Uppsala, clinical and epidemiological impact of the influenza pandemic 1918–1919 on a Swedish county

    Jonas Holtenius


    Full Text Available Introduction and aim: The Spanish flu reached Sweden in June 1918, and at least one-third of the population (then 5.8 million became infected. Some 34,500 persons (5.9 per 1,000 people died from influenza during the first year of the pandemic (when acute pneumonia is included, the number of deaths rose to 7.1 per 1,000 people. In this historical look back at the pandemic, our aim was to review the epidemiological impact on the Swedish county of Uppsala, the clinical outcomes and the economic impact on the regional hospital; a relevant backgound to consider the impact of a future virulent pandemic. We also focused on how the pandemic was perceived by the medical community and by health care authorities. Methods: Health care reports, statistics, daily newspapers, medical journals, and records of patients treated for influenza at the Uppsala Academic Hospital from July 1918 to June 1919 were included in our review. Results: An influenza related mortality rate of 693 persons (5.1 per 1,000 people was reported in the Uppsala region from 1918–1919; from July 1918 to June 1919, 384 patients were treated for influenza at the Uppsala Academic Hospital. The first wave peaked in November 1918 with case fatality rates up to 30%; a second wave peaked in April 1919 with a lower rate of mortality. Of the patients treated, a total of 66 died. Of these, 60% were 20–29 years of age, and 85% were less than 40 years old. Autopsy reports revealed pneumonia in 89% of the cases; among these, 47% were hemorrhagic, 18% were bilateral, and 45% had additional extrapulmonary organ involvement. Signs of severe viral disease were documented, but secondary bacterial disease was the primary cause of death in the majority of cases. Conclusion: The epidemiologic and pathologic results were in accordance with other publications of this time period. The costs of running the hospital doubled from 1917 to 1920 and then reversed by 45%. Today, an influenza pandemic of the same

  8. The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

    Cuiling Xu

    Full Text Available BACKGROUND: Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1. METHODOLOGY/PRINCIPAL FINDINGS: Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China. CONCLUSIONS/SIGNIFICANCE: The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

  9. Neuraminidase and hemagglutinin matching patterns of a highly pathogenic avian and two pandemic H1N1 influenza A viruses.

    Yonghui Zhang

    Full Text Available BACKGROUND: Influenza A virus displays strong reassortment characteristics, which enable it to achieve adaptation in human infection. Surveying the reassortment and virulence of novel viruses is important in the prevention and control of an influenza pandemic. Meanwhile, studying the mechanism of reassortment may accelerate the development of anti-influenza strategies. METHODOLOGY/PRINCIPAL FINDINGS: The hemagglutinin (HA and neuraminidase (NA matching patterns of two pandemic H1N1 viruses (the 1918 and current 2009 strains and a highly pathogenic avian influenza A virus (H5N1 were studied using a pseudotyped particle (pp system. Our data showed that four of the six chimeric HA/NA combinations could produce infectious pps, and that some of the chimeric pps had greater infectivity than did their ancestors, raising the possibility of reassortment among these viruses. The NA of H5N1 (A/Anhui/1/2005 could hardly reassort with the HAs of the two H1N1 viruses. Many biological characteristics of HA and NA, including infectivity, hemagglutinating ability, and NA activity, are dependent on their matching pattern. CONCLUSIONS/SIGNIFICANCE: Our data suggest the existence of an interaction between HA and NA, and the HA NA matching pattern is critical for valid viral reassortment.

  10. Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway.

    Mohn, Kristin G-I; Cox, Rebecca Jane; Tunheim, Gro; Berdal, Jan Erik; Hauge, Anna Germundsson; Jul-Larsen, Åsne; Peters, Bjoern; Oftung, Fredrik; Jonassen, Christine Monceyron; Mjaaland, Siri


    Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza.

  11. Determinants of receiving the pandemic (H1N1 2009 vaccine and intention to receive the seasonal influenza vaccine in Taiwan.

    Ta-Chien Chan

    Full Text Available The paper examines the factors associated with both receiving pandemic (H1N1 2009 vaccines and individuals' intentions to get the next seasonal influenza vaccine in Taiwan.We conducted a representative nationwide survey with in-person household interviews during April-July 2010. Multivariate logistic regression incorporated socio-demographic background, household characteristics, health status, behaviors, and perceptions of influenza and vaccination.We completed interviews with 1,954 respondents. Among those, 548 (28.0% received the pandemic (H1N1 2009 vaccination, and 469 (24.0% intended to get the next seasonal influenza vaccine. Receipt of the H1N1 vaccine was more prevalent among schoolchildren, the elderly, those who had contact with more people in their daily lives, and those who had received influenza vaccinations in previous years. In comparison, the intention to receive the next seasonal influenza vaccine tended to be stronger among children, the elderly, and those who reported less healthy status or lived with children, who received a seasonal influenza vaccination before, and who worried more about a possible new pandemic.Children, the elderly, and those who had gotten seasonal flu shots before in Taiwan were more likely to both receive a pandemic H1N1 vaccination and intend to receive a seasonal influenza vaccine.

  12. University life and pandemic influenza: Attitudes and intended behaviour of staff and students towards pandemic (H1N1 2009

    MacIntyre C Raina


    Full Text Available Abstract Background In a pandemic young adults are more likely to be infected, increasing the potential for Universities to be explosive disease outbreak centres. Outbreak management is essential to reduce the impact in both the institution and the surrounding community. Through the use of an online survey, we aimed to measure the perceptions and responses of staff and students towards pandemic (H1N1 2009 at a major university in Sydney, Australia. Methods The survey was available online from 29 June to 30 September 2009. The sample included academic staff, general staff and students of the University. Results A total of 2882 surveys were completed. Nearly all respondents (99.6%, 2870/2882 were aware of the Australian pandemic situation and 64.2% (1851/2882 reported either "no anxiety" or "disinterest." Asian-born respondents were significantly (p Conclusions Responses to a pandemic are subject to change in its pre-, early and mid-outbreak stages. Lessons for these institutions in preparation for a second wave and future disease outbreaks include the need to promote positive public health behaviours amongst young people and students.

  13. Scaling in the Global Spreading Patterns of Pandemic Influenza A and the Role of Control: Empirical Statistics and Modeling

    Han, Xiao-Pu; Zhou, Chang-Song; Zhou, Tao; Zhu, Jun-Fang


    The pandemic of influenza A (H1N1) is a serious on-going global public crisis. Understanding its spreading dynamics is of fundamental importance for both public health and scientific researches. In this paper, we investigate the spreading patterns of influenza A and find the Zipf's law of the distributions of confirmed cases in different levels. Similar scaling properties are also observed for severe acute respiratory syndrome (SARS) and bird cases of avian influenza (H5N1). To explore the underlying mechanism, a model considering the control effects on both the local growth and transregional transmission is proposed, which shows that the strong control effects are responsible for the scaling properties. Although strict control measures for interregional travelers are helpful to delay the outbreak in the regions without local cases, our analysis suggests that the focus should be turned to local prevention after the outbreak of local cases. This work provides not only a deeper understanding of the generic mech...

  14. 2009年甲型H1N1流感大流行时空分布特征分析%Characterization of the Global Spatio-temporal Transmission of the 2009 Pandemic H1N1 Influenza

    蒋之犇; 白建军; 蔡俊; 李瑞云; 金震宇; 徐冰


    本文利用球面距离的Ripley'K函数,分析了全球2009年甲型H1N1流感大流行早期疫情的点空间分布模式.同时,通过对比2000-2008年甲型流感病例数据,分析不同纬度国家2009年甲型H1N1流感新增病例数的时间序列特征及其与国家入境人数的相关性.结果表明,2009年甲型H1N1流感大流行早期疫情呈聚类分布,其L函数值最大值区间与65个全球城市的最大值区间相同.78.5%的病例分布在全球城市周围600km半径内.时间序列特征总体上类似于历年甲型流感,但是北回归线以北部分国家在6、7月非甲型流感流行季节仍有大量病例出现.并且北回归线以北国家冬季暴发集中在第45周到第48周之间,早于历年甲型流感流行时间.进一步分析认为,全球城市是本次流感国际传播网络的关键节点.国际旅行是流感传播的重要途径,并在本次流感大流行前期主导着流感跨国传播方向.同时不同纬度的环境条件对2009年甲型H1N1流感大流行有重要影响.%In March of 2009, a novel swine-origin influenza A(H1N1) virus was first discovered in Mexico and quickly spread to over 200 countries in less than two years. However, limited research has been conducted on the characterization of the global spatio-temporal transmission of the pandemic. Applying Ripley 's K function based on the spherical distances, we analyzed spatial pattern of the outbreaks of the H1N1 pandemic from March 15, 2009 to June 9, 2009. Compared with other type A influenza occurred during 2000-2008, the 2009 H1N1 influenza showed generally similar temporal trend, but marked difference when we broke down the outbreak data of each country along the latitude. To look into the differences, we further associated the number of weekly cases of the H1N1 influenza with national arrivals through customs. Results show that the 2009 H1N1 influenza in early period was spatially clustered. The maximum value of the function L was

  15. Attack rates assessment of the 2009 pandemic H1N1 influenza A in children and their contacts: a systematic review and meta-analysis.

    Aharona Glatman-Freedman

    Full Text Available BACKGROUND: The recent H1N1 influenza A pandemic was marked by multiple reports of illness and hospitalization in children, suggesting that children may have played a major role in the propagation of the virus. A comprehensive detailed analysis of the attack rates among children as compared with their contacts in various settings is of great importance for understanding their unique role in influenza pandemics. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE (PubMed and Embase for published studies reporting outbreak investigations with direct measurements of attack rates of the 2009 pandemic H1N1 influenza A among children, and quantified how these compare with those of their contacts. We identified 50 articles suitable for review, which reported school, household, travel and social events. The selected reports and our meta-analysis indicated that children had significantly higher attack rates as compared to adults, and that this phenomenon was observed for both virologically confirmed and clinical cases, in various settings and locations around the world. The review also provided insight into some characteristics of transmission between children and their contacts in the various settings. CONCLUSION/SIGNIFICANCE: The consistently higher attack rates of the 2009 pandemic H1N1 influenza A among children, as compared to adults, as well as the magnitude of the difference is important for understanding the contribution of children to disease burden, for implementation of mitigation strategies directed towards children, as well as more precise mathematical modeling and simulation of future influenza pandemics.

  16. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase.

    Wu, Zhengliang L; Zhou, Hui; Ethen, Cheryl M; N Reinhold, Vernon


    The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and (3)H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme.

  17. Influenza epidemiology in Italy two years after the 2009-2010 pandemic: need to improve vaccination coverage.

    Gasparini, Roberto; Bonanni, Paolo; Amicizia, Daniela; Bella, Antonino; Donatelli, Isabella; Cristina, Maria Luisa; Panatto, Donatella; Lai, Piero Luigi


    Since 2000, a sentinel surveillance of influenza, INFLUNET, exists in Italy. It is coordinated by the Ministry of Health and is divided into two parts; one of these is coordinated by the National Institute of Health (NIH), the other by the Inter-University Centre for Research on Influenza and other Transmissible Infections (CIRI-IT). The influenza surveillance system performs its activity from the 42nd week of each year (mid-October) to the 17th week of the following year (late April). Only during the pandemic season (2009/2010) did surveillance continue uninterruptedly. Sentinel physicians - about 1,200 general practitioners and independent pediatricians - send in weekly reports of cases of influenza-like illness (ILI) among their patients (over 2% of the population of Italy) to these centers.   In order to estimate the burden of pandemic and seasonal influenza, we examined the epidemiological data collected over the last 3 seasons (2009-2012). On the basis of the incidences of ILIs at different ages, we estimated that: 4,882,415; 5,519,917; and 4,660,601 cases occurred in Italy in 2009-2010, 2010-2011 and 2011-2012, respectively. Considering the ILIs, the most part of cases occurred in < 14 y old subjects and especially in 5-14 y old individuals, about 30% and 21% of cases respectively during 2009-2010 and 2010-2011 influenza seasons. In 2011-2012, our evaluation was of about 4.7 million of cases, and as in the previous season, the peak of cases regarded subjects < 14 y (about 29%). A/California/07/09 predominated in 2009-2010 and continued to circulate in 2010-2011. During 2010-2011 B/Brisbane/60/08 like viruses circulated and A/H3N2 influenza type was sporadically present. H3N2 (A/Perth/16/2009 and A/Victoria/361/2011) was the predominant influenza type-A virus that caused illness in the 2011-2012 season. Many strains of influenza viruses were present in the epidemiological scenario in 2009-2012. In the period 2009-2012, overall vaccination coverage was low

  18. Ethical Reflections of Influenza Pandemic%流感大流行引发的伦理思考

    刘宇鹏; 刘姝; 张齐武; 李虹


    甲型H1N1流感大流行虽然已经过去,但却留下许多问题值得深思,如流行的严重程度远低于以往大流行,大流行的定义发生了变更、世界卫生组织与药厂是否存在利益关联.在流感大流行过程中,仍存在着资源分配不合理、疫情监测侵犯个人隐私、强制隔离剥夺人身自由等尚未解决的公共卫生伦理学问题,信息共享也尚需进一步加强.%The influenza A (H1N1) pandemic has already passed, but it left us many issues worthy of serious consideration, such as the severity of this pandemic is far lower than in the past, the definition of the pandemic changes and whether there are conflicts of interest between the WHO and the pharmaceutical companies.During the course of the pandemic, there are still many unresolved problems of public health ethics, such as unreasonable allocation of resources, invasion of personal privacy by the surveillance, deprivation of personal freedom by the forced isolation, and the sharing of information needs to be further strengthened.

  19. The Evaluations of Swine Flu Magnitudes in TV News: A Comparative Analysis of Paired Influenza Pandemics.

    Pan, Po-Lin; Meng, Juan


    This study examined how major TV news networks covered two flu pandemics in 1976 and 2009 in terms of news frames, mortality exemplars, mortality subject attributes, vaccination, evaluation approaches, and news sources. Results showed that the first pandemic was frequently framed with the medical/scientific and political/legal issues, while the second pandemic was emphasized with the health risk issue in TV news. Both flu pandemics were regularly reported with mortality exemplars, but the focus in the first pandemic was on the flu virus threat and vaccination side effects, while the vaccination shortage was frequently revealed in the second outbreak.

  20. Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines.

    Lee, In Hong; Kim, Hyun Soo; Seo, Sang Heui


    Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines. Inflammatory cytokine- and chemokine-encoding genes, including IL-1α, IL-6, CXCL9, CXCL10, and CXCL11, were upregulated in the infected porcine mast cells. Our results suggest that mast cells could be involved in enhancing influenza-virus-mediated disease in infected animals.

  1. ‘Spanish’ flu and army horses: what historians and biologists can learn from a history of animals with flu during the 1918–1919 influenza pandemic

    Floor Haalboom


    Full Text Available At the time of the 1918–1919 ‘Spanish’ influenza pandemic, influenza researchers did not just relate this disease to the human population, despite the focus of historians of medicine on its human aspects and meanings. In line with the use of historical reports of animals with influenza in present-day microbiological studies on influenza among different animal species, this article investigates understandings of animal influenza in the Netherlands during the 1918–1919 pandemic. The article adds to microbiological uses of the historical record by putting observations of animals with influenza in historical contexts, in particular the context of military dealings with influenza at the end of the First World War, and the social position of veterinary medicine. The case of the Dutch military horse veterinarian Emile Bemelmans, who argued that human and horse influenza were identical, illustrates that knowledge of these contexts is important to critically use historical sources reporting animals with influenza in present-day biological influenza research.

  2. Development and preclinical testing of HNVAC, a cell culture-based H1N1 pandemic influenza vaccine from India.

    Hegde, Nagendra R; Kumar, Deepak; Rao, P Panduranga; Kumari, P Krishna; Kaushik, Yashpal; Ravikrishnan, R; Prasad, Sai D; Ella, Krishna M


    Several limitations of the use of embryonated eggs and the threat of pandemics have highlighted the need for other platforms for the production of influenza vaccines. We report the indigenous development and pre-clinical testing of an MDCK-based H1N1 pandemic influenza vaccine HNVAC from India. The cell bank and virus seed were characterized extensively. The cells were characterized by PCR, electron microscopy, and karyotyping, and found to be of female canine epithelial origin. The virus was confirmed by neutralization, haemagglutination inhibition, neuraminidase inhibition, and PCR and nucleotide sequencing. Adventitious agent testing was performed by both in vitro and in vivo studies. The in vitro studies included culturing, haemadsorption, haemagglutination, PCR and RT-PCR, whereas in vivo studies included passage in embryonated eggs and in laboratory animals. Both cell bank and virus seed were free of adventitious agents. MDCK cell lysates as well as cellular DNA did not produce tumours in newborn or adult laboratory animals. The bioprocess parameters were standardized to recover antigen with minimal levels of process-related impurities. The vaccine bulk was tested for the presence of specific antigen, and quantified by single radial immunodiffusion. Finally, non-adjuvanted and aluminium hydroxide adjuvanted vaccine formulations were found to be safe in preclinical toxicity studies in mice, rats, guinea pigs and rabbits, and immunogenic in mice and rabbits. This is the first and only cell culture-based influenza vaccine platform developed in any developing country.

  3. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

    Cuevas, Maria Teresa; Pozo, Francisco; Guerra, Susana; García-Barreno, Blanca; Martinez-Orellana, Pamela; Pérez-Breña, Pilar; Montoya, Maria; Melero, Jose Antonio; Pizarro, Manuel; Ortin, Juan; Casas, Inmaculada; Nieto, Amelia


    Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32). PMID:23326447

  4. Assessing Google flu trends performance in the United States during the 2009 influenza virus A (H1N1 pandemic.

    Samantha Cook

    Full Text Available BACKGROUND: Google Flu Trends (GFT uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1 pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet. For each GFT model we calculated the correlation and RMSE (root mean square error between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009-Dec 2009. We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (r = 0.95 and 0.29, respectively. The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications. CONCLUSIONS: Internet search behavior changed during pH1N1, particularly in the categories "influenza complications" and "term for influenza." The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1

  5. Avian and pandemic human influenza policy in South-East Asia: the interface between economic and public health imperatives.

    Pongcharoensuk, Petcharat; Adisasmito, Wiku; Sat, Le Minh; Silkavute, Pornpit; Muchlisoh, Lilis; Cong Hoat, Pham; Coker, Richard


    The aim of this study was to analyse the contemporary policies regarding avian and human pandemic influenza control in three South-East Asia countries: Thailand, Indonesia and Vietnam. An analysis of poultry vaccination policy was used to explore the broader policy of influenza A H5N1 control in the region. The policy of antiviral stockpiling with oseltamivir, a scarce regional resource, was used to explore human pandemic influenza preparedness policy. Several policy analysis theories were applied to analyse the debate on the use of vaccination for poultry and stockpiling of antiviral drugs in each country case study. We conducted a comparative analysis across emergent themes. The study found that whilst Indonesia and Vietnam introduced poultry vaccination programmes, Thailand rejected this policy approach. By contrast, all three countries adopted similar strategic policies for antiviral stockpiling in preparation. In relation to highly pathogenic avian influenza, economic imperatives are of critical importance. Whilst Thailand's poultry industry is large and principally an export economy, Vietnam's and Indonesia's are for domestic consumption. The introduction of a poultry vaccination policy in Thailand would have threatened its potential to trade and had a major impact on its economy. Powerful domestic stakeholders in Vietnam and Indonesia, by contrast, were concerned less about international trade and more about maintaining a healthy domestic poultry population. Evidence on vaccination was drawn upon differently depending upon strategic economic positioning either to support or oppose the policy. With influenza A H5N1 endemic in some countries of the region, these policy differences raise questions around regional coherence of policies and the pursuit of an agreed overarching goal, be that eradication or mitigation. Moreover, whilst economic imperatives have been critically important in guiding policy formulation in the agriculture sector, questions arise

  6. Applying the Lessons of SARS to Pandemic Influenza: An Evidence-based Approach to Mitigating the Stress Experienced by Healthcare Workers

    Maunder, Robert G.; Peladeau, Nathalie; Leszcz, Molyn; Romano, Donna; Savage, Diane; Rose, Marci; Adam, Mary Anne; Schulman, Rabbi Bernard


    We describe an evidence-based approach to enhancing the resilience of healthcare workers in preparation for an influenza pandemic, based on evidence about the stress associated with working in healthcare during the SARS outbreak. SARS was associated with significant long-term stress in healthcare workers, but not with increased mental illness. Reducing pandemic-related stress may best be accomplished through interventions designed to enhance resilience in psychologically healthy people. Appli...

  7. Effective detection of the 2009 H1N1 influenza pandemic in U.S. Veterans Affairs medical centers using a national electronic biosurveillance system.

    Patricia Schirmer

    Full Text Available BACKGROUND: The 2008-09 influenza season was the time in which the Department of Veterans Affairs (VA utilized an electronic biosurveillance system for tracking and monitoring of influenza trends. The system, known as ESSENCE or Electronic Surveillance System for the Early Notification of Community-based Epidemics, was monitored for the influenza season as well as for a rise in influenza cases at the start of the H1N1 2009 influenza pandemic. We also describe trends noted in influenza-like illness (ILI outpatient encounter data in VA medical centers during the 2008-09 influenza season, before and after the recognition of pandemic H1N1 2009 influenza virus. METHODOLOGY/PRINCIPAL FINDINGS: We determined prevalence of ILI coded visits using VA's ESSENCE for 2008-09 seasonal influenza (Sept. 28, 2008-April 25, 2009 corresponding to CDC 2008-2009 flu season weeks 40-16 and the early period of pandemic H1N1 2009 (April 26, 2009-July 31, 2009 corresponding to CDC 2008-2009 flu season weeks 17-30. Differences in diagnostic ICD-9-CM code frequencies were analyzed using Chi-square and odds ratios. There were 649,574 ILI encounters captured representing 633,893 patients. The prevalence of VA ILI visits mirrored the CDC's Outpatient ILI Surveillance Network (ILINet data with peaks in late December, early February, and late April/early May, mirroring the ILINet data; however, the peaks seen in the VA were smaller. Of 31 ILI codes, 6 decreased and 11 increased significantly during the early period of pandemic H1N1 2009. The ILI codes that significantly increased were more likely to be symptom codes. Although influenza with respiratory manifestation (487.1 was the most common code used among 150 confirmed pandemic H1N1 2009 cases, overall it significantly decreased since the start of the pandemic. CONCLUSIONS/SIGNIFICANCE: VA ESSENCE effectively detected and tracked changing ILI trends during pandemic H1N1 2009 and represents an important temporal alerting

  8. Response to the 2009-H1N1 influenza pandemic in the Mekong Basin: surveys of country health leaders

    Dausey David J


    Full Text Available Abstract Background Soon after the 2009-H1N1 virus emerged as the first influenza pandemic in 41 years, countries had an early opportunity to test their preparedness plans, protocols and procedures, including their cooperation with other countries in responding to the global pandemic threat. The Mekong Basin Disease Surveillance cooperation (MBDS comprises six countries - Cambodia, China (Yunnan and Guangxi Provinces, Lao People's Democratic Republic, Myanmar, Thailand and Vietnam - that formally organized themselves in 2001 to cooperate in disease surveillance and control. The pandemic presented an opportunity to assess their responses in light of their individual and joint planning. We conducted two surveys of the MBDS leadership from each country, early during the pandemic and shortly after it ended. Results On average, participants rated their country's pandemic response performance as good in both 2009 and 2010. Post-pandemic (2010, perceived performance quality was best for facility-based interventions (overall mean of 4.2 on a scale from 1 = poor to 5 = excellent, followed by surveillance and information sharing (4.1, risk communications (3.9 and disease prevention and control in communities (3.7. Performance was consistently rated as good or excellent for use of hotlines for case reporting (2010 mean of 4.4 and of selected facility-based interventions (each with a 2010 mean of 4.4: using hospital admission criteria, preparing or using isolation areas, using PPE for healthcare workers and using antiviral drugs for treatment. In at least half the countries, the post-pandemic ratings were lower than initial 2009 assessments for performance related to surveillance, facility-based interventions and risk communications. Conclusions MBDS health leaders perceived their pandemic responses effective in areas previously considered problematic. Most felt that MBDS cooperation helped drive and thus added value to their efforts. Surveillance capacity

  9. Age Distribution of Influenza Like Illness Cases during Post-Pandemic A(H3N2): Comparison with the Twelve Previous Seasons, in France

    Turbelin, Clément; Souty, Cécile; Pelat, Camille; Hanslik, Thomas; Sarazin, Marianne; Blanchon, Thierry; Falchi, Alessandra


    In France, the 2011–2012 influenza epidemic was characterized by the circulation of antigenically drifted influenza A(H3N2) viruses and by an increased disease severity and mortality among the elderly, with respect to the A(H1N1)pdm09 pandemic and post-pandemic outbreaks. Whether the epidemiology of influenza in France differed between the 2011–2012 epidemic and the previous outbreaks is unclear. Here, we analyse the age distribution of influenza like illness (ILI) cases attended in general practice during the 2011–2012 epidemic, and compare it with that of the twelve previous epidemic seasons. Influenza like illness data were obtained through a nationwide surveillance system based on sentinel general practitioners. Vaccine effectiveness was also estimated. The estimated number of ILI cases attended in general practice during the 2011–2012 was lower than that of the past twelve epidemics. The age distribution was characteristic of previous A(H3N2)-dominated outbreaks: school-age children were relatively spared compared to epidemics (co-)dominated by A(H1N1) and/or B viruses (including the 2009 pandemic and post-pandemic outbreaks), while the proportion of adults over 30 year-old was higher. The estimated vaccine effectiveness (54%, 95% CI (48, 60)) was in the lower range for A(H3N2) epidemics. In conclusion, the age distribution of ILI cases attended in general practice seems to be not different between the A(H3N2) pre-pandemic and post-pandemic epidemics. Future researches including a more important number of ILI epidemics and confirmed virological data of influenza and other respiratory pathogens are necessary to confirm these results. PMID:23755294

  10. Transmission characteristics of the 2009 H1N1 influenza pandemic: comparison of 8 Southern hemisphere countries.

    Lulla Opatowski


    Full Text Available While in Northern hemisphere countries, the pandemic H1N1 virus (H1N1pdm was introduced outside of the typical influenza season, Southern hemisphere countries experienced a single wave of transmission during their 2009 winter season. This provides a unique opportunity to compare the spread of a single virus in different countries and study the factors influencing its transmission. Here, we estimate and compare transmission characteristics of H1N1pdm for eight Southern hemisphere countries/states: Argentina, Australia, Bolivia, Brazil, Chile, New Zealand, South Africa and Victoria (Australia. Weekly incidence of cases and age-distribution of cumulative cases were extracted from public reports of countries' surveillance systems. Estimates of the reproduction numbers, R(0, empirically derived from the country-epidemics' early exponential phase, were positively associated with the proportion of children in the populations (p = 0.004. To explore the role of demography in explaining differences in transmission intensity, we then fitted a dynamic age-structured model of influenza transmission to available incidence data for each country independently, and for all the countries simultaneously. Posterior median estimates of R₀ ranged 1.2-1.8 for the country-specific fits, and 1.29-1.47 for the global fits. Corresponding estimates for overall attack-rate were in the range 20-50%. All model fits indicated a significant decrease in susceptibility to infection with age. These results confirm the transmissibility of the 2009 H1N1 pandemic virus was relatively low compared with past pandemics. The pattern of age-dependent susceptibility found confirms that older populations had substantial--though partial--pre-existing immunity, presumably due to exposure to heterologous influenza strains. Our analysis indicates that between-country-differences in transmission were at least partly due to differences in population demography.

  11. Influenza in hospitalized children in Ireland in the pandemic period and the 2010/2011 season: risk factors for paediatric intensive-care-unit admission.

    Rebolledo, J


    SUMMARY Influenza causes significant morbidity and mortality in children. This study\\'s objectives were to describe influenza A(H1N1)pdm09 during the pandemic, to compare it with circulating influenza in 2010\\/2011, and to identify risk factors for severe influenza defined as requiring admission to a paediatric intensive care unit (PICU). Children hospitalized with influenza during the pandemic were older, and more likely to have received antiviral therapy than children hospitalized during the 2010\\/2011 season. In 2010\\/2011, only one child admitted to a PICU with underlying medical conditions had been vaccinated. The risk of severe illness in the pandemic was higher in females and those with underlying conditions. In 2010\\/2011, infection with influenza A(H1N1)pdm09 compared to other influenza viruses was a significant risk factor for severe disease. An incremental relationship was found between the number of underlying conditions and PICU admission. These findings highlight the importance of improving low vaccination uptake and increasing the use of antivirals in vulnerable children.

  12. Emergency Physicians’ Adherence to Center for Disease Control and Prevention Guidance During the 2009 Influenza A H1N1 Pandemic

    Yu-Hsiang Hsieh


    Full Text Available Introduction: Little is known regarding compliance with management guidelines for epidemicinfluenza in adult emergency department (ED settings during the 2009 novel influenza A(H1N1 epidemic, especially in relation to the Centers for Disease Control and Prevention (CDCguidance.Methods: We investigated all patients with a clinical diagnosis of influenza at an inner-citytertiary academic adult ED with an annual census of approximately 60,000 visits from May 2008to December 2009. We aimed to determine patterns of presentation and management for adultpatients with an ED diagnosis of influenza during the H1N1 pandemic, using seasonal influenza(pre-H1N1 as reference and to determine the ED provider’s adherence to American College ofEmergency Physicians and CDC guidance during the 2009 H1N1 influenza pandemic. Adherenceto key elements of CDC 2009 H1N1 guidance was defined as (1 the proportion of admittedpatients who were recommended to receive testing or treatment who actually received testingfor influenza or treatment with antivirals; and (2 the proportion of high-risk patients who weresupposed to be treated who actually were treated with antivirals.Results: Among 339 patients with clinically diagnosed influenza, 88% occurred during the H1N1pandemic. Patients were similarly managed during both phases. Median length of visit (pre-H1N1:385 min, H1N1: 355 min, P > 0.05 and admission rates (pre-H1N1: 8%, H1N1: 11%, P > 0.05were similar between the 2 groups. 28% of patients in the pre-H1N1 group and 16% of patientsin the H1N1 group were prescribed antibiotics during their ED visits (P > 0.05. There were 34admitted patients during the pandemic;, 30 (88% of them received influenza testing in the ED,and 22 (65% were prescribed antivirals in the ED. Noticeably, 19 (56% of the 34 admittedpatients, including 6 with a positive influenza test, received antibiotic treatment during their ED stay.Conclusion: During the recent H1N1 pandemic, most admitted patients

  13. Determinants of non-vaccination against pandemic 2009 H1N1 influenza in pregnant women: a prospective cohort study.

    Romain Freund

    Full Text Available BACKGROUND: In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9% women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3-12.7], North African origin, aOR = 2.5[1.3-4.7] and Asian origin, aOR = 2.1[1.7-2.6] compared to French and European origin and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0-2.6], intermediate professionals, aOR = 1.3[1.0-1.6], employees and manual workers, aOR = 2.5[1.4-4.4] compared to managers and intellectual professionals. The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4-0.8] and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4-0.8]. Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. CONCLUSIONS/SIGNIFICANCE: In this cohort of pregnant women, vaccine coverage against pandemic

  14. Enhanced surveillance of initial cases of pandemic H1N1 2009 influenza in Ireland, April-July 2009.

    Martin, J


    From 28 April to 18 July 2009 there were 156 cases of pandemic H1N1 2009 influenza confirmed in Ireland. During this time, Ireland was in containment phase, and detailed case-based epidemiological information was gathered on all cases presenting in the community and acute health care setting. Active case finding was performed among contacts of cases. Eighty percent of cases were in people less than 35 years of age and 86% were imported. The most frequent symptoms were fever, sore throat, myalgia and dry cough. Nine people were hospitalized, no fatalities occurred.

  15. Persistence of the 2009 pandemic influenza A (H1N1) virus on N95 respirators.

    Coulliette, A D; Perry, K A; Edwards, J R; Noble-Wang, J A


    In the United States, the 2009 pandemic influenza A (H1N1) virus (pH1N1) infected almost 20% of the population and caused >200,000 hospitalizations and >10,000 deaths from April 2009 to April 2010. On 24 April 2009, the CDC posted interim guidance on infection control measures in health care settings explicitly for pH1N1 and recommended using filtering face respirators (FFRs) when in close contact with a suspected- or confirmed-to-be-infected individual, particularly when performing aerosol-generating procedures. The persistence and infectivity of pH1N1 were evaluated on FFRs, specifically N95 respirators, under various conditions of absolute humidity (AH) (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, and 14.6 × 10(5) mPa), sample matrices (2% fetal bovine serum [FBS], 5 mg/ml mucin, and viral medium), and times (4, 12, 24, 48, 72, and 144 h). pH1N1 was distributed onto N95 coupons (3.8 to 4.2 cm(2)) and extracted by a vortex-centrifugation-filtration process, and the ability of the remaining virus to replicate was quantified using an enzyme-linked immunosorbent assay (ELISA) to determine the log10 concentration of the infectious virus per coupon. Overall, pH1N1 remained infectious for 6 days, with an approximately 1-log10 loss of virus concentrations over this time period. Time and AH both affected virus survival. We found significantly higher (P ≤ 0.01) reductions in virus concentrations at time points beyond 24 to 72 h (-0.52-log10 reduction) and 144 h (-0.74) at AHs of 6.5 × 10(5) mPa (-0.53) and 14.6 × 10(5) mPa (-0.47). This research supports discarding respirators after close contact with a person with suspected or confirmed influenza infection due to the virus's demonstrated ability to persist and remain infectious.

  16. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    Pan, Yang [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Sasaki, Tadahiro [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Inoue, Yuji [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yasugi, Mayo [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Du, Anariwa [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Boonsathorn, Naphatsawan [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Ibrahim, Madiha S. [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour (Egypt); and others


    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  17. The immunogenicity of the intradermal injection of seasonal trivalent influenza vaccine containing influenza A(H1N1)pdm09 in COPD patients soon after a pandemic.

    Chuaychoo, Benjamas; Kositanont, Uraiwan; Rittayamai, Nuttapol; Niyomthong, Parichat; Songserm, Thaweesak; Maranetra, Khun Nanta; Rattanasaengloet, Kanokwan; Nana, Arth


    The antibody responses of a reduced-dose intradermal seasonal influenza vaccination have never been studied in COPD patients soon after a pandemic. A total of 149 COPD patients (60 y of age or older) were randomized to receive trivalent influenza vaccine (Sanofi-Pasteur, France) either 9 µg of hemagglutinin (HA) per strain split into 2-site intradermal (ID) injections via the Mantoux technique or one intramuscular (IM) injection of 15 µg of HA per strain. The geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates for influenza A(H3N2) and B administered through the ID injection (n = 75) were similar to those obtained with the IM injection (n = 74) 4 weeks post-vaccination. The antibody responses for influenza A(H1N1)pdm09 administered through the ID injection were lower than those obtained with the IM injection, but all of these responses met the 3 criteria proposed by the Committee for Proprietary Medicinal Products (CPMP) for annual re-licensure. The seroprotection rates 4 weeks post-vaccination for influenza A(H1N1)pdm09 were 64.0% (95%CI 52.7-74.0%) in the ID group vs. 78.4% (95% CI 67.6-86.3%) in the IM group (p = 0.053). Influenza-related acute respiratory illness (ARI), diagnosed as a 4-fold rise in HI titers with a convalescent titer > 1:40, and/or the RT-PCR between the ID group (5.3%) and the IM group (8.1%) were not significantly different. The reduced-dose intradermal influenza vaccine may expand vaccine coverage in cases of vaccine shortage.

  18. Possible pandemic threat from new reassortment of influenza A(H7N9) virus in China.

    Meng, Z; Han, R; Hu, Y; Yuan, Z; Jiang, S; Zhang, X; Xu, J


    Avian influenza A(H7N9) virus re-emerged in China in December 2013, after a decrease in the number of new cases during the preceding six months. Reassortment between influenza A(H7N9) and local H9N2 strains has spread from China's south-east coast to other regions. Three new reassortments of A(H7N9) virus were identified by phylogenetic analysis: between A(H7N9) and Zhejiang-derived strains, Guangdong/Hong Kong-derived strains or Hunan-derived A(H9N2) strains. Our findings suggest there is a possible risk that a pandemic could develop.

  19. 流感大流行期间孕妇的防治%Prevention and treatment for pregnant women during the pandemic of influenza

    周祖木; 蔡彩萍; 魏承毓


    流行性感冒(流感)可引起世界性大流行,已成为全球重大的公共卫生问题.孕妇为流感的高危人群,故在流感大流行时加强这一人群的保护尤为重要.此文就近年来国内外流感对孕妇及其胎儿的影响以及采取的防治措施等研究进展进行了综述.%Influenza results in worldwide pandemics and has been a global public health problem.Pregnant women are at risk for influenza.A responding plan for a future influenza pandemic should include comideratiom specific to pregnant women.This article reviews the recent development effects of influenza in pregnant worflen and fetus.and the use of prophylaxis and treatment.

  20. Seasonal influenza vaccine and protection against pandemic (H1N1 2009-associated illness among US military personnel.

    Matthew C Johns

    Full Text Available INTRODUCTION: A novel A/H1N1 virus is the cause of the present influenza pandemic; vaccination is a key countermeasure, however, few data assessing prior seasonal vaccine effectiveness (VE against the pandemic strain of H1N1 (pH1N1 virus are available. MATERIALS AND METHODS: Surveillance of influenza-related medical encounter data of active duty military service members stationed in the United States during the period of April-October 2009 with comparison of pH1N1-confirmed cases and location and date-matched controls. Crude odds ratios (OR and VE estimates for immunized versus non-immunized were calculated as well as adjusted OR (AOR controlling for sex, age group, and history of prior influenza vaccination. Separate stratified VE analyses by vaccine type (trivalent inactivated [TIV] or live attenuated [LAIV], age groups and hospitalization status were also performed. For the period of April 20 to October 15, 2009, a total of 1,205 cases of pH1N1-confirmed cases were reported, 966 (80% among males and over one-half (58% under 25 years of age. Overall VE for service members was found to be 45% (95% CI, 33 to 55%. Immunization with prior season's TIV (VE = 44%, 95% CI, 32 to 54% as well as LAIV (VE = 24%, 95% CI, 6 to 38% were both found to be associated with protection. Of significance, VE against a severe disease outcome was higher (VE = 62%, 95% CI, 14 to 84% than against milder outcomes (VE = 42%, 95% CI, 29 to 53%. CONCLUSION: A moderate association with protection against clinically apparent, laboratory-confirmed Pandemic (H1N1 2009-associated illness was found for immunization with either TIV or LAIV 2008-09 seasonal influenza vaccines. This association with protection was found to be especially apparent for severe disease as compared to milder outcome, as well as in the youngest and older populations. Prior vaccination with seasonal influenza vaccines in 2004-08 was also independently associated with protection.

  1. Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study.

    Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe


    We assessed the perception and attitudes of university staff, including medical school and other science specialties, toward the 2009 A/H1N1 influenza pandemic and influenza vaccination program. A cross-sectional online survey was conducted among 4,529 university personnel on October 19-20, 2009. Seven hundred (15%) employees participated in the study. Only 18% were willing to be vaccinated, men more than women (29% versus 9%, P < 0.001), and professors/researchers more than administrative/technical staff (30% vs. 6%, P < 0.001). Intention to be vaccinated was insufficient. Additional efforts are needed to improve information dissemination among university staff. Medical university personnel should receive more information to increase vaccine coverage and protect them as well as patients.

  2. A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America

    Greninger, Alexander L.; Chen, Eunice C.; Sittler, Taylor; Scheinerman, Alex; Roubinian, Nareg; Yu, Guixia; Kim, Edward; Pillai, Dylan R.; Guyard, Cyril; Mazzulli, Tony; Isa, Pavel; Arias, Carlos F.; Hackett, John; Schochetman, Gerald; Miller, Steve; Tang, Patrick; Chiu, Charles Y.


    Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings. PMID:20976137

  3. A metagenomic analysis of pandemic influenza A (2009 H1N1 infection in patients from North America.

    Alexander L Greninger

    Full Text Available Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17, the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%, with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.

  4. Molecular and phylogenetic analysis of influenza A H1N1 pandemic viruses in Cuba, May 2009 to August 2010.

    Ramos, Alexander Piñón; Herrera, Belsy Acosta; Ramírez, Odalys Valdés; García, Amely Arencibia; Jiménez, Mayra Muné; Valdés, Clara Savón; Fernández, Angel Goyenechea; González, Grehete; Fernández, Suset I Oropesa; Báez, Guelsys González; Espinosa, Bárbara Hernández


    The influenza A(H1N1)pdm09 virus was detected in Cuba in May 2009. The introduction of a new virus with increased transmissibility into a population makes surveillance of the pandemic strain to the molecular level necessary. The aim of the present study was the molecular and phylogenetic analysis of pandemic influenza A(H1N1)pdm09 strains that circulated in Cuba between May 2009 and August 2010. Seventy clinical samples were included in the study. Nucleotide sequences from the hemagglutinin HA1 region segment were obtained directly from clinical samples. Genetic distances were calculated using MEGA v.5.05. A phylogenetic tree was constructed using MrBayes v.3.1.2 software. Potential N-glycosylation sites were predicted using NetNGlyc server 1.0. The 48 Cuban sequences of influenza A(H1N1)pdm09 obtained were similar to the A/California/07/2009 (H1N1) vaccine strain. Most of the Cuban strains belonged to clade 7. Cuban viruses showed amino acid changes, some of them located at three antigenic sites: Ca, Sa, and Sb. Two dominant mutations were detected: P83S (100%) and S203T (85.7%). Glycosylation site analysis revealed the gain of one site at position 162 in 13 sequences. The findings in this study contribute to our understanding of the progress of the influenza A(H1N1)pdm09 virus, since this virus is at the starting point of its evolution in humans.

  5. "Will they just pack up and leave?" – attitudes and intended behaviour of hospital health care workers during an influenza pandemic

    Po Kieren


    Full Text Available Abstract Background There is a general consensus that another influenza pandemic is inevitable. Although health care workers (HCWs are essential to the health system response, there are few studies exploring HCW attitudes to pandemic influenza. The aim of this study was to explore HCWs knowledge, attitudes and intended behaviour towards pandemic influenza. Methods Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation. Results Respondents were categorized into four main groups by occupation: Nursing (47.5%, Medical (26.0%, Allied (15.3% and Ancillary (11.2%. Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n = 873 but less than half were able to correctly define it (43.9%, n = 473. Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. The main determinants of variation in our study were occupational factors, demographics and health beliefs. Non-clinical staff were significantly most likely to be unsure of their intentions (OR 1.43, p Conclusion We identified two issues that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans. Other issues included a high level of confidence in dietary measures to protect against influenza, and a belief among ancillary workers that antibiotics would be protective. All

  6. Pandemic influenza A (H1N1 2009: epidemiological analysis of cases in a tropical/semi-arid region of Brazil

    Roberto da Justa Pires Neto


    Full Text Available Introduction The year 2009 marked the beginning of a pandemic caused by a new variant of influenza A (H1N1. After spreading through North America, the pandemic influenza virus (H1N1 2009 spread rapidly throughout the world. The aim of this study was to describe the clinical and epidemiological characteristics of cases of pandemic influenza in a tropical/semi-arid region of Brazil. Methods A retrospective study analyzed all suspected cases of pandemic influenza (H1N1 2009 reported in the Ceará State through the National Information System for Notifiable Diseases during the pandemic period between 28 April, 2009 and November 25, 2010. Results A total of 616 suspected cases were notified, 58 (9.4% in the containment phase and 558 (90.6% in the mitigation phase. Most cases were of affected young people resident in the City of Fortaleza, the largest urban center in the State of Ceará. The most frequent symptoms presented by the cases with confirmed infection were fever, cough, myalgia, arthralgia, and nasal congestion. Mortality rate was 0.0009/1,000 inhabitants and lethality was 5.6%. Deaths were observed only in the mitigation phase. Mortality rates were similar for both sexes but were higher in the age group under 5 years. Conclusions The study suggests that the influenza A (H1N1 pandemic in this tropical/semi-arid region had a lower magnitude when compared to states in the Southern and Southeastern regions of Brazil.

  7. Whole genome characterization of human influenza A(H1N1)pdm09 viruses isolated from Kenya during the 2009 pandemic.

    Gachara, George; Symekher, Samuel; Otieno, Michael; Magana, Japheth; Opot, Benjamin; Bulimo, Wallace


    An influenza pandemic caused by a novel influenza virus A(H1N1)pdm09 spread worldwide in 2009 and is estimated to have caused between 151,700 and 575,400 deaths globally. While whole genome data on new virus enables a deeper insight in the pathogenesis, epidemiology, and drug sensitivities of the circulating viruses, there are relatively limited complete genetic sequences available for this virus from African countries. We describe herein the full genome analysis of influenza A(H1N1)pdm09 viruses isolated in Kenya between June 2009 and August 2010. A total of 40 influenza A(H1N1)pdm09 viruses isolated during the pandemic were selected. The segments from each isolate were amplified and directly sequenced. The resulting sequences of individual gene segments were concatenated and used for subsequent analysis. These were used to infer phylogenetic relationships and also to reconstruct the time of most recent ancestor, time of introduction into the country, rates of substitution and to estimate a time-resolved phylogeny. The Kenyan complete genome sequences clustered with globally distributed clade 2 and clade 7 sequences but local clade 2 viruses did not circulate beyond the introductory foci while clade 7 viruses disseminated country wide. The time of the most recent common ancestor was estimated between April and June 2009, and distinct clusters circulated during the pandemic. The complete genome had an estimated rate of nucleotide substitution of 4.9×10(-3) substitutions/site/year and greater diversity in surface expressed proteins was observed. We show that two clades of influenza A(H1N1)pdm09 virus were introduced into Kenya from the UK and the pandemic was sustained as a result of importations. Several closely related but distinct clusters co-circulated locally during the peak pandemic phase but only one cluster dominated in the late phase of the pandemic suggesting that it possessed greater adaptability.

  8. Hedging against antiviral resistance during the next influenza pandemic using small stockpiles of an alternative chemotherapy.

    Joseph T Wu


    Full Text Available BACKGROUND: The effectiveness of single-drug antiviral interventions to reduce morbidity and mortality during the next influenza pandemic will be substantially weakened if transmissible strains emerge which are resistant to the stockpiled antiviral drugs. We developed a mathematical model to test the hypothesis that a small stockpile of a secondary antiviral drug could be used to mitigate the adverse consequences of the emergence of resistant strains. METHODS AND FINDINGS: We used a multistrain stochastic transmission model of influenza to show that the spread of antiviral resistance can be significantly reduced by deploying a small stockpile (1% population coverage of a secondary drug during the early phase of local epidemics. We considered two strategies for the use of the secondary stockpile: early combination chemotherapy (ECC; individuals are treated with both drugs in combination while both are available; and sequential multidrug chemotherapy (SMC; individuals are treated only with the secondary drug until it is exhausted, then treated with the primary drug. We investigated all potentially important regions of unknown parameter space and found that both ECC and SMC reduced the cumulative attack rate (AR and the resistant attack rate (RAR unless the probability of emergence of resistance to the primary drug p(A was so low (less than 1 in 10,000 that resistance was unlikely to be a problem or so high (more than 1 in 20 that resistance emerged as soon as primary drug monotherapy began. For example, when the basic reproductive number was 1.8 and 40% of symptomatic individuals were treated with antivirals, AR and RAR were 67% and 38% under monotherapy if p(A = 0.01. If the probability of resistance emergence for the secondary drug was also 0.01, then SMC reduced AR and RAR to 57% and 2%. The effectiveness of ECC was similar if combination chemotherapy reduced the probabilities of resistance emergence by at least ten times. We extended our model

  9. Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic

    Xu, Rui; McBride, Ryan; Paulson, James C.; Basler, Christopher F.; Wilson, Ian A. (Sinai); (Scripps)


    The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 {angstrom} resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

  10. Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein.

    Benjamin Mänz


    Full Text Available The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP of pandemic strains A/Brevig Mission/1/1918 (1918 and A/Hamburg/4/2009 (pH1N1 that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1/04 (H5N1 resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.

  11. Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey

    Blumental Sophie


    Full Text Available Abstract Background During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. Methods From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR and probable (positive influenza A antigen or culture pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. Results During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%, concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002 and a higher mortality rate (4% vs 0%, p = 0.06. Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. Conclusion Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

  12. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses.

    Pan, Yang; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Inoue, Yuji; Yasugi, Mayo; Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha; Du, Anariwa; Boonsathorn, Naphatsawan; Ibrahim, Madiha S; Daidoji, Tomo; Nakaya, Takaaki; Ono, Ken-ichiro; Okuno, Yoshinobu; Ikuta, Kazuyoshi; Watanabe, Yohei


    Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  13. Relapse of minimal change disease following infection with the 2009 pandemic influenza (H1N1) virus.

    Kim, Seo Rin; Lee, Soo Bong; Kim, Il Young; Lee, Dong Won; Rhee, Harin; Seong, Eun Young; Song, Sang Heon; Kwak, Ihm Soo


    We report a case of relapse of minimal change disease following infection with the influenza A (H1N1) virus responsible for the 2009 pandemic. A 22-year-old man who had been diagnosed with minimal change disease presented with systemic edema. He had achieved complete remission with an oral steroid (prednisolone 1 mg/kg/day) by the 17th day of administration. On the 27th day of prednisolone administration, he presented with a new onset of generalized edema after several days of productive coughing. His urine showed proteinuria (4+) with a protein/creatinine ratio (PCR) of 2852.1 mg/g. His nasal swab sample was positive for the 2009 pandemic influenza (H1N1) virus by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). He received oseltamivir (150 mg/day) for 5 days. A day after completing the oseltamivir therapy, his proteinuria returned to a normal range; urinalysis was negative for protein with PCR 79.2 mg/g. One month later, the patient remained normal with no proteinuria.

  14. Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.

    Irina Isakova-Sivak

    Full Text Available H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2 master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1 or A/Tokyo/3/67 (clade 2 showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.

  15. African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates

    Matsuoka, Yumiko; Suguitan, Amorsolo; Orandle, Marlene; Paskel, Myeisha; Boonnak, Kobporn; Gardner, Donald J.; Feldmann, Friederike; Feldmann, Heinz; Marino, Michael; Jin, Hong; Kemble, George


    ABSTRACT Live attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of the wt viruses replicated efficiently, while replication of the ca vaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2 ca vaccines. Protection from wt virus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication of ca vaccine candidates. IMPORTANCE Ferrets and mice are commonly used for preclinical evaluation of influenza

  16. Pandemic influenza A (H1N1 vaccination among libyan health care personnel: A cross-sectional retrospective study

    Nagiat Tayeb Hwisa


    Full Text Available Context: Vaccination rate among health-care personnel′s (HCPs are not promising notwithstanding the World Health Organization campaigns over three decades resulting in compromising patient safety. The H1N1 virus, which caused a world-wide pandemic earlier has now transformed into a seasonal flu virus. Aims: The aim of this study was to analyze the incidence of 2009-10 pandemic influenza A (H1N1 vaccination among Libyan HCPs in four hospitals of Al-Zawia, Libya. Materials and Methods: A questionnaire, which listed eight sections of parameters distributed among 310 HCPs to assess the vaccination rate and resulting adverse effects. Statistical Analysis: The data were analyzed using descriptive statistics, Pearson′s χ2-test and Student′s t-test where appropriate. Results: The overall pandemic A (H1N1 vaccination among all HCPs was only 107 (39.9% out of 268 respondents. The distribution of respondents based on physicians, other staff and sex were found significant (P < 0.05. The common barriers of H1N1 vaccination being lack of awareness fear of adverse effects, allergies and religious beliefs. The major adverse effect observed was erythema in 95.56% of physicians and 87.1% in other staff. About 2% of HCPs have reported arthralgia. No significant differences existed between the responses of general variables and adverse effects. The glycoprotein 120 and squalene were found responsible for the reported adverse effects. 37 (82.22% vaccinated medical HCPs have advised their patients to get vaccinated. Conclusions: Due to recurrence of H1N1 influenza in recent times, vaccination campaigns should be promoted immediately to address the knowledge gap of HCPs for intervention by regulatory and health organizations in Libya. The health belief model could be applied to improve vaccination among HCPs.

  17. Clinical features of initial cases of 2009 pandemic influenza A (H1N1) in Macau, China

    ZHOU Bao-tong; FAN Yun-ming; LI Tak-ming; LIU Xiao-qing


    Background The first case of pandemic influenza A (H1N1) virus infection in Macau Special Administrative Region (SAR) of the People's Republic of China was documented on June 18, 2009. Subsequently, persons with suspected infection or of contact with suspected cases received screening. All the confirmed cases were hospitalized and treated with oseltamivir. Their clinical features were observed. This may help for better management for later patients and be of benefit to the government of Macau SAR to adjust its strategy to combat the pandemic influenza A (H1N1) virus infection more efficiently.Methods From June to July 2009, the initial 72 cases of influenza A (H1N1) in Macau were hospitalized in Common Hospital Centre S. Januario (CHCSJ). The infection was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The clinical features of the disease were closely observed and documented. Oseltamivir was given to all patients within 48 hours after the onset of disease and maintained for 5 days.Results The mean age of the 72 patients was 21 years old. Forty of them were men and 32 were women. The median incubation of the virus was 2 days (1 to 7 days). The most common symptoms were fever (97.2%) and cough (77.8%).The rate of gastrointestinal symptoms including nausea, vomiting, and diarrhea was 2.8%. Fever typically lasted for 3days (1 to 9 days). The median time from the onset to positive results of real-time RT-PCR was 6 days (3 to 13 days).After treatment with oseltamivir, most patients became afebrile within 48 hours. Only one aged patient with a history of glaucoma and hypothyroidism was found to have lung infiltration on chest X-ray.Conclusions The initial cases of pandemic influenza A (H1N1) virus infection in Macau SAR showed that most of the infected persons had a mild course. The virus could be detected by real-time RT-PCR within a median of 6 days from the onset. Oseltamivir was effective.

  18. Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11).

    Mereckiene, J; Cotter, S; Nicoll, A; Lopalco, P; Noori, T; Weber, Jt; D'Ancona, F; Levy-Bruhl, D; Dematte, L; Giambi, C; Valentiner-Branth, P; Stankiewicz, I; Appelgren, E; O Flanagan, D


    Since 2008, annual surveys of influenza vaccination policies, practices and coverage have been undertaken in 29 European Union (EU)/ European Economic Area (EEA) countries. After 2009, this monitored the impact of European Council recommendation to increase vaccination coverage to 75% among risk groups. This paper summarises the results of three seasonal influenza seasons: 2008/09, 2009/10 and 2010/11. In 2008/09, 27/29 countries completed the survey; in 2009/10 and 2010/11, 28/29 completed it. All or almost all countries recommended vaccination of older people (defined as those aged ≥50, ≥55, ≥59, ≥60 or ≥65 years), and people aged ≥6 months with clinical risk and healthcare workers. A total of 23 countries provided vaccination coverage data for older people, but only 7 and 10 had data for the clinical risk groups and healthcare workers, respectively. The number of countries recommending vaccination for some or all pregnant women increased from 10 in 2008/09 to 22 in 2010/11. Only three countries could report coverage among pregnant women. Seasonal influenza vaccination coverage during and after the pandemic season in older people and clinical groups remained unchanged in countries with higher coverage. However, small decreases were seen in most countries during this period. The results of the surveys indicate that most EU/EEA countries recommend influenza vaccination for the main target groups; however, only a few countries have achieved the target of 75% coverage among risk groups. Coverage among healthcare workers remained low.

  19. Lessons learned from the global surveillance of pandemic influenza, the different communication strategies and the impact on Europe’s public health response.

    Velden, J. van der; Paget, W.J.


    After the first case of Mexican flu was reported in early spring 2009, a wave of reported cases went quickly through the (scientific) media. Pandemic influenza A(H1N1) activity was reported in all continents, but most countries were affected during summer 2009 in Latin America, Oceania and Asia, fol

  20. 5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication

    García-Sastre Adolfo


    Full Text Available Abstract Background Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I has recently been shown to induce antiviral state. Results In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5'PPP-RNA, a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication in vivo in mice. Conclusions Our findings suggest that 5'PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status.

  1. Recombinant human interferon reduces titer of the 1918 pandemic and H5N1 influenza viruses in a guinea pig model

    Although H5N1 subtype influenza viruses have yet to acquire the ability to transmit efficiently among humans, the geographic expansion, genetic diversity and persistence of H5N1 viruses in birds indicates that pandemic potential of these viruses remains high. Vaccination remains the primary means f...

  2. Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: A multinational self-controlled case series in Europe

    S.A. Romio (Silvana); D.M. Weibel (Daniel); J.P. Dieleman (Jeanne); H.K. Olberg (Henning); C.S. de Vries (Corinne); C. Sammon (Cormac); N.J. Andrews (Nick); H. Svanström (Henrik); D. Mølgaard-Nielsen (Ditte); A. Hviid (Anders); M. Lapeyre-Mestre (Maryse); A. Sommet (Agnès); C. Saussier (Christel); A. Castot (Anne); H. Heijbel (Harald); L. Arnheim-Dahlström (Lisen); P. Sparen (Pär); M. Mosseveld (Mees); M.J. Schuemie (Martijn); N.A.T. van der Maas (Nicoline); B.C. Jacobs (Bart); T. Leino (Tuija); T. Kilpi (Terhi); J. Storsaeter (Jann); K. Johansen (Kari); P Kramarz (Piotr); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)


    textabstractBackground: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following

  3. Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers in the major teaching hospital of Sicily (Italy).

    Amodio, Emanuele; Anastasi, Giovanna; Marsala, Maria Grazia Laura; Torregrossa, Maria Valeria; Romano, Nino; Firenze, Alberto


    The aim of the study was to investigate factors involved in vaccination acceptance among healthcare workers (HCWs) and adverse reactions rates associated with pandemic influenza vaccination. The study was carried out in the major teaching hospital of Sicily from November 2009 to February 2010 on 2267 HCWs. A total of 407 (18%) HCWs were vaccinated against the 2009 pandemic influenza A (H1N1). A logistic regression analysis indicates an increased risk of non-vaccination against pandemic influenza in females (OR=1.6; 95% CI=1.3-2.1) compared to males, in nurses/technicians/administrative workers (OR=1.7; 95% CI=1.3-2.2) compared to doctors/biologists, and in HCWs who were non-vaccinated against seasonal influenza in 2008-2009 (OR=4.9; 95% CI=3.7-6.5) compared to vaccinated HCWs. Overall, 302 (74.2%) out of 407 questionnaires distributed to vaccinated HCWs were returned within the observation period. One hundred fifty-two workers (50.3%) experienced at least one adverse reaction (30.1%, local reactions; 6.6% systemic reactions and 13.6% both of them). The most frequent side effect of vaccination was pain at the injection site (43.4%). Twelve (3.9%) out of 302 HCWs stated they experienced influenza-like illness episodes during the follow-up period. The use of an adjuvanted vaccine against pandemic influenza A (H1N1) appears to be an effective and safe preventive strategy, showing a prevalence of both local and systemic adverse reactions not very different from that seen after vaccination with non-adjuvanted seasonal influenza vaccine. Despite this finding, vaccination coverage among HCWs remains very low, suggesting the need to implement educational campaigns directed to groups with lower coverage rates.

  4. Early Characterization of the Severity and Transmissibility of Pandemic Influenza Using Clinical Episode Data from Multiple Populations.

    Pete Riley


    Full Text Available The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0 and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics.

  5. 太阳黑子活动与流感大流行关系的探讨%Discussion on the relationship between sunspot activity and influenza pandemic

    曲江文; 聂绍发


    目的 探讨流感大流行与太阳黑子活动周期的关系,为阐明流感大流行的原因和起源提供科学的依据.方法 采用描述性分析、χ2检验以及非条件Logistic回归的方法对1700-2009年的太阳黑子活动与流感大流行的资料进行分析.结果 1700-2009年以来发生的16次流感大流行或者可能的流感大流行中,有13次发生在太阳黑子极值年或前、后一年;太阳黑子极值年或前、后一年流感大流行的发生率(7.65%)高于其他年份的发生率(2.14%),差异有统计学意义(χ2=4.75,P<0.05).太阳黑子极值年或前、后一年与流感大流行的非条件Logistic回归结果表明,OR=4.160(95% CI=1.161~14.903).结论 太阳黑子极值年或前、后一年是流感大流行的一个重要的危险因素.%Objective Through studying the relationship between influenza pandemic and sunspot cycle, we aim to provide scientific basis for the cause and origin of influenza pandemics. Methods Descriptive analysis, chi-square test and non-conditional Logistic regression were used to analyze sunspot number and influenza pandemic data from 1700 to 2009.Results Among 16 influenza pandemics or possible influenza pandemics from 1700 to 2009, 13 of them occurred in Sunspot extremum +/- one year. Incidence rate of influenza pandemic in Sunspot extremum +/- one year (7.65%)wasmuch higher than those in other years (2. 14%), and the difference had a statistical significance (x2=4.75,P<0.05). Non-conditional Logistic regression analysis showed odds ratio value was 4. 160 (95% CI = 1.161~14.903). Conclusions Sunspot extremum +/- one year is an important risk factor for influenza pandemic.

  6. 2009 pandemic influenza A (H1N1 virus outbreak and response--Rwanda, October, 2009-May, 2010.

    Justin Wane

    Full Text Available BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1pdm09 (pH1N1 was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL. Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532 of specimens tested influenza positive; of these 96% (n = 510 were influenza A and 4% (n = 22 were influenza B. Of cases testing influenza A positive, 96.8% (n = 494, 3% (n = 15, and 0.2% (n = 1 were A(H1N1pdm09, Seasonal A(H3 and Seasonal A(non-subtyped, respectively. Among laboratory-confirmed cases, 263 (53.2% were children <15 years and 275 (52% were female. In total, 58 (12% cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days. All cases recovered and there were no deaths. Overall, 339 (68% confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532 were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532, asthma 0.8% (4/532, cardiac disease 1.5% (8/532, pregnancy 0.6% (3/532, diabetes mellitus 0.4% (2/532, and chronic malnutrition 0.8% (4/532. CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to

  7. Aptamers that bind to the hemagglutinin of the recent pandemic influenza virus H1N1 and efficiently inhibit agglutination.

    Gopinath, Subash C B; Kumar, Penmetcha K R


    Influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza A viruses. In this study we have selected RNA aptamers (D-12 and D-26) that specifically target the HA protein of the recent pandemic influenza virus pdmH1N1 (A/California/07/2009). Among the selected aptamers the D-26 aptamer showed higher affinity for the HA of pdmH1N1 and was able to distinguish HA derived from other sub-types of influenza A viruses. The affinity of the D-26 aptamer was further improved upon incorporation of 2'-fluoropyrimidines to a level of 67 fM. Furthermore, the high affinity D-12 and D-26 aptamers were tested for their ability to interfere with HA-glycan interactions using a chicken red blood cell (RBC) agglutination assay. At a concentration of 200 nM the D-26 aptamer completely abolished the agglutination of RBCs, whereas D-12 only did so at 400 nM. These studies suggest that the selected aptamer D-26 not only has a higher affinity and specificity for the HA of pdmH1N1 but also has a better ability to efficiently interfere with HA-glycan interactions compared with the D-12 aptamer. The D-26 aptamer warrants further study regarding its application in developing topical virucidal products against the pdmH1N1 virus and also in surveillance of the pdmH1N1 influenza virus.

  8. Vaccination for 2009 pandemic H1N1 influenza A did not induce conserved epitope-specific memory CD8 T cell responses in HIV+ northern Thai children.

    Chawansuntati, Kriangkrai; Aurpibul, Linda; Wipasa, Jiraprapa


    The influenza virus causes severe illness in susceptible populations, including children and people living with human immunodeficiency virus (HIV). Here, we investigated cell-mediated immune responses (CMI) against influenza CD8 T cell conserved epitopes in HIV-infected (HIV+) northern Thai children following the 2009 pandemic H1N1 influenza A vaccination. Sixty HIV+ children were vaccinated with two doses of the 2009 pandemic influenza vaccine and their CD8T cell responses were assessed. We found no significant differences in the increase of cytokines-producing and CD107a-expressing CD8+ T cells or CD8+ memory T cells in response to pooled conserved epitopes stimulation in vitro between children with different serologic responses to the vaccine at all time points of the study. Our results suggest that the 2009 pandemic H1N1 vaccine did not induce the conserved epitope-specific immune responses in HIV+ children. Vaccine design and vaccination strategy against influenza in these populations warrant further studies.

  9. Influenza pandemic (H1N1 2009 activity during summer 2009: Effectiveness of the 2008-9 trivalent vaccine against pandemic influenza in Spain Actividad de la gripe pandémica (H1N1 2009 durante el verano de 2009: Efectividad de la vacuna trivalente 2008-9 frente a la gripe pandémica en España

    Amparo Larrauri


    Full Text Available Introduction: The Spanish influenza surveillance system (SISS maintained its activity during the summer of 2009 to monitor the influenza pandemic. Objectives: To describe pandemic influenza activity from May to September 2009 and to estimate the effectiveness of the 2008-9 seasonal influenza vaccine against laboratory-confirmed pandemic (H1N1 2009 influenza. Methods: Data from the SISS were used to identify the trend of pandemic (H1N1 2009 influenza outside the influenza season. For the effectiveness study, we compared the vaccination status of notified cases [influenza-like illnesses (ILI laboratory confirmed as pandemic influenza] with that of the test-negative controls. Results: The first laboratory-confirmed case of the pandemic virus was notified in the system in week 20/2009. The ILI rate increased gradually in the study period, exceeding basic activity in week 38. The proportion of pandemic (H1N1 2009 influenza viruses detected by the system represented 14% in week 20/2009 and rapidly increased to 90% in week 34. The adjusted vaccine effectiveness of the 2008-9 seasonal vaccine against laboratory-confirmed pandemic influenza was 12% (-30; 41. Conclusions: The SISS became an essential tool for pandemic monitoring in Spain. The improved SISS will provide more accurate information on influenza activity in future seasonal or pandemic waves. Using surveillance data, we could not demonstrate the effectiveness of the seasonal 2008-9 vaccine against laboratory-confirmed pandemic influenza.Introducción: El Sistema de Vigilancia de Gripe en España (SVGE continuó y reforzó su actividad durante el verano de 2009 con el objetivo de vigilar la evolución de la pandemia en España. Objetivos: Describir la actividad de la gripe pandémica en España de mayo a septiembre de 2009 y estimar la efectividad de la vacuna antigripal estacional 2008-2009 frente a casos confirmados de gripe pandémica (H1N1 2009. Métodos: Se utilizaron datos del SVGE para

  10. Reconstruction of epidemic curves for pandemic influenza A (H1N1 2009 at city and sub-city levels

    Wong Ngai Sze


    Full Text Available Abstract To better describe the epidemiology of influenza at local level, the time course of pandemic influenza A (H1N1 2009 in the city of Hong Kong was reconstructed from notification data after decomposition procedure and time series analysis. GIS (geographic information system methodology was incorporated for assessing spatial variation. Between May and September 2009, a total of 24415 cases were successfully geocoded, out of 25473 (95.8% reports in the original dataset. The reconstructed epidemic curve was characterized by a small initial peak, a nadir followed by rapid rise to the ultimate plateau. The full course of the epidemic had lasted for about 6 months. Despite the small geographic area of only 1000 Km2, distinctive spatial variation was observed in the configuration of the curves across 6 geographic regions. With the relatively uniform physical and climatic environment within Hong Kong, the temporo-spatial variability of influenza spread could only be explained by the heterogeneous population structure and mobility patterns. Our study illustrated how an epidemic curve could be reconstructed using regularly collected surveillance data, which would be useful in informing intervention at local levels.

  11. Pandemic H1N1 2009 virus in Norwegian pigs naïve to influenza A viruses

    Germundsson, A.; Gjerset, B.; Hjulsager, Charlotte Kristiane;

    In March-April 2009, a novel pandemic influenza A (H1N1) virus (pH1N1-09v) emerged in the human population. The first case of pH1N1v infection in pigs was reported from Canada in May 2009. In Norway, pH1N1v infection was recorded in a swine herd on the 10th of October of 2009. Here, we report...... showed clinical signs or iii) with a history of close contact with or close proximity to infected herds. In addition, blood samples were collected from nucleus and multiplier breeding herds. Detection of pH1N1-09v was initially performed using a real-time RT-PCR targeted to detect influenza A virus....... Positive samples were tested by a pH1N1-09v specific real-time RT-PCR. Blood samples were tested for presence of antibodies against influenza A virus by ELISA (IDVET) and positive samples in the ELISA were tested by haemagglutinin inhibition test using A/California/07/09 as antigen. From the onset...

  12. Lack of Group X Secreted Phospholipase A2 Increases Survival Following Pandemic H1N1 Influenza Infection

    Kelvin, Alyson A.; Degousee, Norbert; Banner, David; Stefanski, Eva; Leon, Alberto J.; Angoulvant, Denis; Paquette, Stéphane G.; Huang, Stephen S. H.; Danesh, Ali; Robbins, Clinton S.; Noyan, Hossein; Husain, Mansoor; Lambeau, Gerard; Gelb, Michael H.; Kelvin, David J.; Rubin, Barry B.


    The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of (Reviewer 2 Minor Comment 2) GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX−/−) model and found that survival after infection was significantly greater in GX−/− mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX−/− mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX−/− mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its (Reviewer 2 Minor Comment 2) inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza. PMID:24725934

  13. Burden of the 1999-2008 seasonal influenza epidemics in Italy: comparison with the H1N1v (A/California/07/09) pandemic.

    Lai, Piero Luigi; Panatto, Donatella; Ansaldi, Filippo; Canepa, Paola; Amicizia, Daniela; Patria, Antonio Giuseppe; Gasparini, Roberto


    Despite preventive efforts, seasonal influenza epidemics are responsible for substantial morbidity and mortality every year worldwide, including developed countries. The A/H1N1v pandemic imposed a considerable healthcare and economic burden. In order to obtain an accurate estimate of the economic burden of influenza, and hence to guide policymakers effectively, systematic studies are necessary. To this end, data from epidemiological surveillance are essential. To estimate the impact of the 1999-2008 seasonal influenza epidemics and the H1N1v pandemic, we analyzed data from the Italian Influenza Surveillance System (CIRI NET). In the period 1999-2008, the Italian surveillance network consisted of sentinel general practitioners and pediatricians, who reported cases of Influenza-Like Illness (ILI) and Acute Respiratory Infections (ARI ) observed during their clinical practice from mid-October to late April each year; reports were sent to the Center for Research on Influenza and other Viral Infections (CIRI -IV). CIRI -IV receives data from 9 of the 20 Italian regions: Liguria, Abruzzo, Calabria, Friuli Venezia Giulia, Lombardy, Puglia, Sicily, Tuscany and Umbria. Previous estimates of influenza case costs were used in economic evaluations. Clinical-epidemiological and virological surveillance of the seasonal epidemics from 1999-2008 showed that the highest epidemic period was 2004-2005, when a new variant of the H3N2 influenza virus subtype emerged (A/California/07/04). Indeed, the highest peak of morbidity in the decade occurred in February 2005 (12.6 per 1,000 inhabitants). In 1999-2008, H1N1 subtype strains circulated and co-circulated with strains belonging to the H3N2 subtype and B type. Regarding B viruses in 2001-02, viruses belonged to the B/Victoria/02/07 lineage re-emerged, and in subsequent years co-circulated with viruses belonging to the B/Yamagata/lineage. The estimated costs of seasonal epidemics from 1999-2008 in Italy ranged from €15 to €20

  14. 应对流感大流行威胁急需的一项对策%A Much Needed Countermeasure to the Threat of New Influenza Pandemic



    本文总结了近年来世界卫生组织先后两次预测流感大流行失败的教训。但是,致人大量死亡的流感大流行今后肯定还会再发生。这就要求科学必须找到引起流感大流行的根源。由于人类生存在宇宙中间,所以人类必然要受到各种重要的宇宙现象的影响。本文总结了新星爆发以及宇宙线大的地面增强事件(GLE)和流感流行的关系,得出结论:这种流感大流行都是由宇宙线环境大的增强引起的。从而提出了科学预警流感大流行的对策,即立即加强对宇宙线环境的监测。具体内容有四点:立即加强对新星的监测,立即加强对特殊天体ηCar星的监测、立即加强对宇宙线大G%The paper sums up the serious lessons of that WHO twice failed successively in predicting influenza pandemic in recent years,i.e.WHO's influenza experts neglected the ecological environment conditions influencing influenza epidemics.Although WHO has not been able to predict influenza pandemic,yet a new high-mortality influenza pandemic must occur in future,perhaps in the near future.So the science should try to find the root cause of influenza pandemics.In view of the idea that mankind lives not only on the Earth,but also in the cosmos and so mankind must be influenced by various important cosmic phenomena.This paper summaries the relationship between novae explosions,the large ground level enhancements(GLE) of cosmic rays and influenza epidemics and thus concludes that influenza pandemics are caused by the large enhancements of cosmic ray environment.Therefore,by increasing monitoring of the cosmic ray environment,we could scientifically predict the impending high-mortality influenza pandemic.Specifically,four main points need to be addressed:1.immediately increase monitoring of novae.2.increase monitoring of starηCar.3.increase monitoring of large GLE of cosmic of data from the last several years to

  15. Impact of seasonal influenza vaccination on pandemic influenza%季节性流感疫苗接种对大流行流感的影响研究



    Canadian studies have found that receipt of seasonal influenza vaccine increased the risk of infection with 2009 pandemic influenza A ( H1N1 ) , and Australian studies have not confirmed this finding. Ferret experiments have suggested protection against pandemic influenza A ( H1N1 ) from prior seasonal influenza infections but not from prior seasonal vaccination. Modelling studies suggest that influenza infection leads to heterosubtypic temporary immunity. These observations can explain the discrepant findings in Canada and Australia. In Australia there was no recent prior circulation of seasonal influenza and thus no temporary immunity to pandemic influenza. There was no association of seasonal influenza vaccine with pandemic influenza infection. In Canada seasonal influenza preceded circulation of pandemic influenza. An unvaccinated proportion of the population developed temporary immunity to pandemic influenza from seasonal infection but a vaccinated proportion of the population did not get seasonal infection and hence did not develop temporary immunity to pandemic influenza. It may therefore have appeared as if seasonal vaccination increased the risk of infection with 2009 pandemic influenza A( H1N1).%加拿大研究发现,季节性流感疫苗接种增加2009年大流行甲型流感(H1N1)感染的危险性,而澳大利亚研究未能证实这个发现.雪貂实验结果表明,以前的季节性流感感染能防御大流行甲型流感(H1N1),但以前的季节性流感疫苗接种则不能.模型研究显示,流感感染可导致对不同亚型的暂时性免疫.这些观察可以解释加拿大和澳大利亚的不一致发现.澳大利亚近期没有季节性流感流行,因而对大流行流感没有暂时性免疫.季节性流感疫苗与大流行流感感染无关.加拿大大流行流感流行前有季节性流感流行,未接种疫苗的人群由于罹患季节性流感而获得对大流行流感的暂时性免疫,但接种疫苗的人群未罹患季

  16. Public-Private Partnerships: Critical to Combatting the Next Pandemic Influenza in the State of Kansas


    Influenza A (H5N1), also known as Avian Flu or Bird Flu because it primarily affects chickens, turkeys, guinea fowls, migratory waterfowl, and other avian...Wikipedia: H1N1 2011) Influenza A H5N1: (also called ―Avian Flu‖ or ― Bird Flu ‖) ―influenza caused by viruses adapted to birds. Of the greatest concern is...1999. Biohazard. New York: Delta. CIDRAP. 2011. Avian influenza ( bird flu ): Implications for human disease.

  17. Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

    Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik


    Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.

  18. Detection of the Pandemic H1N1/2009 Influenza A Virus by a Highly Sensitive Quantitative Real-time Reverse-transcription Polymerase Chain Reaction Assay

    Zhu Yang; Guoliang Mao; Yujun Liu; Yuan-Chuan Chen; Chengjing Liu; Jun Luo; Xihan Li


    A quantitative real time reverse-transcription polymerase chain reaction (qRT-PCR) assay with specific primers recommended by the World Health Organization (WHO) has been widely used successfully for detection and monitoring of the pandemic H1N 1/2009 influenza A virus.In this study,we report the design and characterization of a novel set of primers to be used in a qRT-PCR assay for detecting the pandemic H1N1/2009 virus.The newly designed primers target three regions that are highly conserved among the hemagglutinin (HA) genes of the pandemic H1N1/2009 viruses and are different from those targeted by the WHO-recommended primers.The qRT-PCR assays with the newly designed primers are highly specific,and as specific as the WHO-recommended primers for detecting pandemic H1N1/2009 viruses and other influenza viruses including influenza B viruses and influenza A viruses of human,swine,and raccoon dog origin.Furthermore,the qRT-PCR assays with the newly designed primers appeared to be at least 10-fold more sensitive than those with the WHO-recommended primers as the detection limits of the assays with our primers and the WHO-recommended primers were 2.5 and 25 copies of target RNA per reaction,respectively.When tested with 83 clinical samples,32 were detected to be positive using the qRT-PCR assays with our designed primers,while only 25 were positive by the assays with the WHO-recommended primers.These results suggest that the qRT-PCR system with the newly designed primers represent a highly sensitive assay for diagnosis of the pandemic H1N1/2009 virus infection.

  19. Isolation and quarantine during pandemic (H1N1) 2009 influenza in NSW: the operational experience of public health units.

    Binns, Philippa L; Sheppeard, Vicky; Staff, Michael P


    During the DELAY and CONTAIN phases of pandemic (H1N1) 2009 influenza in NSW, public health units needed to rapidly surge operations to manage the 3070 potential cases and 1894 contacts notified to them. The Incident Control System, NetEpi (the web-based multi-user access database), training to up-skill surge staff, and electronic communication were all integral to the outbreak response. Ongoing identification and training of surge staff would assist a timely and effective response to future large scale outbreaks. Investing and incorporating information technology tools into routine public health unit business to assist with communication, outbreak management and reporting will improve familiarity and capability within the network to respond to public health emergencies.

  20. Epidemiological aspects of influenza A related to climatic conditions during and after a pandemic period in the city of Salvador, northeastern Brazil

    Rosangela de Castro Silva


    Full Text Available During the influenza pandemic of 2009, the A(H1N1pdm09, A/H3N2 seasonal and influenza B viruses were observed to be co-circulating with other respiratory viruses. To observe the epidemiological pattern of the influenza virus between May 2009-August 2011, 467 nasopharyngeal aspirates were collected from children less than five years of age in the city of Salvador. In addition, data on weather conditions were obtained. Indirect immunofluorescence, real-time transcription reverse polymerase chain reaction (RT-PCR, and sequencing assays were performed for influenza virus detection. Of all 467 samples, 34 (7% specimens were positive for influenza A and of these, viral characterisation identified Flu A/H3N2 in 25/34 (74% and A(H1N1pdm09 in 9/34 (26%. Influenza B accounted for a small proportion (0.8% and the other respiratory viruses for 27.2% (127/467. No deaths were registered and no pattern of seasonality or expected climatic conditions could be established. These observations are important for predicting the evolution of epidemics and in implementing future anti-pandemic measures.

  1. Boosted influenza-specific T cell responses after H5N1 pandemic live attenuated influenza virus (pLAIV vaccination

    Yanchun ePeng


    Full Text Available Background: In a phase I clinical trial, a H5N1 pandemic live attenuated influenza virus (pLAIV VN2004 vaccine bearing avian influenza H5N1 HA and NA genes on the A/Ann Arbor cold-adapted vaccine backbone displayed very restricted replication. We evaluated T cell responses to H5N1 pLAIV vaccination and assessed pre-existing T cell responses to to determine whether they were associated with restricted replication of the H5N1 pLAIV. Method: ELISPOT assays were performed using pools of overlapping peptides spanning the entire H5N1 proteome and the hemagglutinin (HA proteins of relevant seasonal H1N1 and H3N2 viruses. We tested stored PBMCs from 21 study subjects who received two doses of the H5N1 pLAIV. The PBMCs were collected 1 day before and 7 days after the first and second pLAIV vaccine doses, respectively. Result: T cell responses to conserved internal proteins M and NP were significantly boosted by vaccination (p=0.036. In addition, H5N1 pLAIV appeared to preferentially stimulate and boost pre-existing seasonal influenza virus HA-specific T cell responses that showed low cross-reactivity with the H5 HA. We confirmed this observation by T cell cloning and identified a novel HA-specific epitope. However, we did not find any evidence that pre-existing T cells prevented pLAIV replication and take. Conclusion: We found that cross-reactive T cell responses could be boosted by pLAIV regardless of the induction of antibody. The impact of the original antigenic sin phenomenon in a subset of volunteers, with preferential expansion of seasonal influenza-specific but not H5N1-specific T cell responses merits further investigation.

  2. National surveillance of pandemic influenza A(H1N1) infection-related admissions to intensive care units during the 2009-10 winter peak in Denmark: two complementary approaches

    Gubbels, S; Perner, A; Valentiner-Branth, Palle


    Surveillance of 2009 pandemic influenza A(H1N1) in Denmark was enhanced during the 2009–10 winter season with a system monitoring the burden of the pandemic on intensive care units (ICUs), in order to inform policymakers and detect shortages in ICUs in a timely manner. Between week 46 of 2009...

  3. Phase 1 study of pandemic H1 DNA vaccine in healthy adults.

    Michelle C Crank

    Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza NCT00973895.

  4. Surveillance of hospitalizations with pandemic A(H1N1 2009 influenza infection in Queensland, Australia

    Frances Birrell


    Full Text Available Objective : To describe the demographic and clinical characteristics of patients hospitalized with pandemic A(H1N1 2009 infection in Queensland, Australia between 25 May and 3 October 2009 and to examine the relationship between timing of antiviral treatment and severity of illness.Method: Using data from the Queensland Health EpiLog information system, descriptive analysis and logistic regression modelling were used to describe and model factors which influence patient outcomes (death, admission to intensive care unit and/or special care unit. Data on patients admitted to hospital in Queensland with confirmed pandemic A(H1N1 2009 infection were included in this analysis.Results: 1236 patients with pandemic A(H1N1 2009 infection were admitted to hospitals in Queensland during the study period. Of the total group: 15% were admitted to an intensive care unit or special care unit; 3% died; 34% were under the age of 18 years and 8% were 65 years of age or older; and 55% had at least one underlying medical condition. Among the 842 patients for whom data were available regarding the use of antiviral drugs, antiviral treatment was initiated in 737 (87.5% patients with treatment commencing at a median of one day (range 1–33 days after onset of illness. Admission to an intensive care unit or special care unit (ICU/SCU or death was significantly associated with increased age, lack of timeliness of antiviral treatment, chronic renal disease and morbid obesity.Discussion: Early antiviral treatment was significantly associated with lower likelihood of ICU/SCU admission or death. Early antiviral treatment for influenza cases may therefore have important public health implications.

  5. Estimating the economic impact of pandemic influenza: An application of the computable general equilibrium model to the U.K.

    Smith, Richard D; Keogh-Brown, Marcus R; Barnett, Tony


    There is concern regarding the impact that a global infectious disease pandemic might have, especially the economic impact in the current financial climate. However, preparedness planning concentrates more upon population health and maintaining a functioning health sector than on the wider economic impact. We developed a single country Computable General Equilibrium model to estimate the economic impact of pandemic influenza (PI) and associated policies. While the context for this development was the United Kingdom, there are lessons to be drawn for application of this methodology, as well as indicative results, to other contexts. Disease scenarios were constructed from an epidemiological model which estimated case fatality rates (mild, moderate and severe) as 0.06%, 0.18% and 0.35%. A clinical attack rate of 35% was also used to produce influenza scenarios, together with preparedness policies, including antivirals and school closure, and the possible prophylactic absence of workers. U.K. cost estimates (in Sterling) are presented, together with relative percentage impacts applicable to similar large economies. Percentage/cost estimates suggest PI would reduce GDP by 0.3% (£ 3.5 bn), 0.4% (£ 5 bn) and 0.6% (£ 7.4 bn) respectively for the three disease scenarios. However, the impact of PI itself is smaller than disease mitigation policies: combining school closure with prophylactic absenteeism yields percentage/cost effects of 1.1% (£ 14.7 bn), 1.3% (£ 16.3 bn) and 1.4% (£ 18.5 bn) respectively for the three scenarios. Sensitivity analysis shows little variability with changes in disease parameters but notable changes with variations in school closure and prophylactic absenteeism. The most severe sensitivity scenario results in a 2.9% (£ 37.4 bn), 3.2% (£ 41.4 bn) and 3.7% (£ 47.5 bn) loss to GDP respectively for the three scenarios.

  6. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  7. Assortativity and the Probability of Epidemic Extinction: A Case Study of Pandemic Influenza A (H1N1-2009

    Hiroshi Nishiura


    Full Text Available Unlike local transmission of pandemic influenza A (H1N1-2009, which was frequently driven by school children, most cases identified in long-distance intranational and international travelers have been adults. The present study examines the relationship between the probability of temporary extinction and the age-dependent next-generation matrix, focusing on the impact of assortativity. Preferred mixing captures as a good approximation the assortativity of a heterogeneously mixing population. We show that the contribution of a nonmaintenance host (i.e., a host type which cannot sustain transmission on its own to the risk of a major epidemic is greatly diminished as mixing patterns become more assortative, and in such a scenario, a higher proportion of non-maintenance hosts among index cases elevates the probability of extinction. Despite the presence of various other epidemiological factors that undoubtedly influenced the delay between first importations and the subsequent epidemic, these results suggest that the dominance of adults among imported cases represents one of the possible factors explaining the delays in geographic spread observed during the recent pandemic.

  8. Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010.

    O'Flanagan, D; Barret, A S; Foley, M; Cotter, S; Bonner, C; Crowe, C; Lynch, B; Sweeney, B; Johnson, H; McCoy, B; Purcell, E


    In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset from 1 April 2009 to 31 December 2010 were identified through active case finding. Narcolepsy history was gathered from medical records. Pandemic vaccination status was obtained from vaccination databases. Two independent experts classified cases using the Brighton case definition. Date of onset was defined as date of first healthcare contact for narcolepsy symptoms. Incidence of narcolepsy in vaccinated and non-vaccinated individuals was compared. Of 32 narcolepsy cases identified, 28 occurred in children/adolescents and for 24 first healthcare contact was between April 2009 and December 2010. Narcolepsy incidence was 5.7 (95% confidence interval (CI): 3.4–8.9) per 100,000 children/adolescents vaccinated with Pandemrix and 0.4 (95% CI: 0.1–1.0) per 100,000 unvaccinated children/adolescents (relative risk: 13.9; absolute attributable risk: 5.3 cases per 100,000 vaccinated children/adolescents). This study confirms the crude association between Pandemrix vaccination and narcolepsy as observed in Finland and Sweden. The vaccine is no longer in use in Ireland. Further studies are needed to explore the immunogenetic mechanism of narcolepsy.

  9. Assessing the congruence between perceived connectivity and network centrality measures specific to pandemic influenza preparedness in Alberta

    Shiell Alan


    Full Text Available Abstract Background Recent research has suggested that perceived organizational connectivity may serve as an important measure of public health preparedness. Presumably, organizations with higher perceived connectivity also have a greater number of actual organizational ties. Using network analysis, we evaluate this presumption by assessing the correlation between perceived organizational connectivity and reported inter-organizational connections. Methods During late 2007-early 2008, representatives from organizations involved in the delivery of public health systems in Alberta were asked to complete an online questionnaire on public health preparedness. Organizational jurisdictional information was collected. Items from Dorn and colleagues connectivity scale (2007 were used to measure perceived organizational connectivity. Inter-organizational network data on formal connections in the area of pandemic influenza preparedness were collected using a roster approach. These data were imported into UCINET to calculate in- and out-degree centrality scores for each organization. One-way ANOVA tests assessed if perceived connectivity and in- and out-degree centrality varied among jurisdictions. Pearson correlation coefficients were used to assess the correlation of perceived connectivity and in- and out-degree centrality. Results Significant mean differences among jurisdictions were observed for in-degree (F(3,116 = 26.60, p F(3,116 = 5.24, p r(123 = 0.22, p r(123 = -0.07, p > 0.05. Conclusions The results suggest in terms of pandemic preparedness that perceived connectivity may serve as a partial proxy measure of formal out-degree network connectivity.

  10. Serological response to the 2009 pandemic influenza A (H1N1 virus for disease diagnosis and estimating the infection rate in Thai population.

    Hatairat Lerdsamran

    Full Text Available BACKGROUND: Individuals infected with the 2009 pandemic virus A(H1N1 developed serological response which can be measured by hemagglutination-inhibition (HI and microneutralization (microNT assays. METHODOLOGY/PRINCIPAL FINDINGS: MicroNT and HI assays for specific antibody to the 2009 pandemic virus were conducted in serum samples collected at the end of the first epidemic wave from various groups of Thai people: laboratory confirmed cases, blood donors and health care workers (HCW in Bangkok and neighboring province, general population in the North and the South, as well as archival sera collected at pre- and post-vaccination from vaccinees who received influenza vaccine of the 2006 season. This study demonstrated that goose erythrocytes yielded comparable HI antibody titer as compared to turkey erythrocytes. In contrast to the standard protocol, our investigation found out the necessity to eliminate nonspecific inhibitor present in the test sera by receptor destroying enzyme (RDE prior to performing microNT assay. The investigation in pre-pandemic serum samples showed that HI antibody was more specific to the 2009 pandemic virus than NT antibody. Based on data from pre-pandemic sera together with those from the laboratory confirmed cases, HI antibody titers ≥ 40 for adults and ≥ 20 for children could be used as the cut-off level to differentiate between the individuals with or without past infection by the 2009 pandemic virus. CONCLUSIONS/SIGNIFICANCE: Based on the cut-off criteria, the infection rates of 7 and 12.8% were estimated in blood donors and HCW, respectively after the first wave of the 2009 influenza pandemic. Among general population, the infection rate of 58.6% was found in children versus 3.1% in adults.

  11. Seasonal influenza vaccination may mitigate the potential impact of an H5N1 pandemic

    QIN Cheng-feng; QIN E-de


    @@ Seasonal influenza is a highly contagious, acute respiratory illness that affects people of all ages. The major pathogens, influenza A viruses, are classified into serologically defined antigenic subtypes of the hemagglutinin (HA) and neuraminidase (NA). Of 16 identified HA and 9 NA subtypes, only H1N1 and H3N2 subtypes are now circulating among humans.

  12. Burden of influenza, healthcare seeking behaviour and hygiene measures during the A(H1N12009 pandemic in France: a population based study

    Van Cauteren Dieter


    Full Text Available Abstract Background Influenza surveillance systems do not allow the identification of the true burden of illness caused by influenza in the community because they are restricted to consulting cases. A study was conducted to estimate the incidence and the burden of self-defined influenza, and to describe healthcare seeking behavior for self-defined influenza during the A(H1N12009 pandemic in the French population. Methods We conducted a random-based retrospective cross-sectional telephone survey between May 2009 and April 2010 among a random sample of the French population. Results For the 10 076 people included, 107 episodes of self-defined influenza were reported. The annual incidence of self-defined influenza was estimated at 13 942 cases per 100 000 inhabitants (CI95% 10 947 – 16 961, 62.1% (CI95% 50.5 – 72.5 of cases consulted a physician and 11.3% (CI95% 5.5 - 21.7 used a face mask. Following recommendations, 37.5% (CI95% 35.5 – 39.5 of people in the survey reported washing their hands more often during the pandemic season, and there was a positive association with being vaccinated against A(H1N12009 influenza, being a women, being a child ( Conclusions Self-defined influenza causes a significant burden of illness in the French population and is a frequent cause for consultation. These results allow a more accurate interpretation of influenza surveillance data and an opportunity to adapt future health education messages.

  13. [Attitudes and side effects related to pandemic influenza A (H1N1) vaccination in healthcare personnel].

    Ormen, Bahar; Türker, Nesrin; Vardar, Ilknur; Kaptan, Figen; El, Sibel; Ural, Serap; Kaya, Fatih; Coşkun, Nejat Ali


    The aims of this study were to evaluate the attitudes towards H1N1 vaccination and to determine the safety and side effects following 2009 pandemic influenza A (H1N1) vaccination. Pandemic influenza vaccine had been administered to the healthcare personnel in our research and training hospital in December 2009. The rate being vaccinated was established as 40% (800/2000). Four months following vaccination, the opinions about vaccination were asked to the healthcare workers, and also side effects were questioned to the vaccinated group. Two different questionnaires (for vaccinated and unvaccinated subjects) were delivered to the volunteers who agreed to participate in the study. Demographic features, reasons related to being vaccinated or not, were questioned. The vaccinated group was also questioned for the presence of chronic diseases, previous vaccinations (pandemic/seasonal influenza), local or systemic reactions that develop after vaccination. A total of 332 volunteers participated in the questionnaire. Of them 247 (74.4%) were vaccinated and 85 (25.6%) were unvaccinated. Male/female ratio of the participants was 1.2, and 55.7% of them were older than 30-year-old. Most of the participants (82.8%) were highly educated (high school and faculty-graduated). Vaccination rates were found statistically significant in advanced age group compared to young adults (p= 0.042); in male gender compared to females (p= 0.001) and in parents compared to subjects who didn't have children (p= 0.021). Vaccination rates were observed to be higher (57.5%) in non-medical staff (cleaning employers, administrative personnel, etc.) than the physicians (29.1%) and nurses (13.4%), and the rate was also high (54.7%) in personnel who worked in intensive care units, emergency department and administrative units than the personnel who worked in the clinics of internal medicine (22.3%) and surgery (23.1%) (p= 0.001). The most important causes of rejecting vaccination were being afraid of the

  14. Impact of influenza in the post-pandemic phase: Clinical features in hospitalized patients with influenza A (H1N1) pdm09 and H3N2 viruses, during 2013 in Santa Fe, Argentina.

    Kusznierz, Gabriela; Carolina, Cudós; Manuel, Rudi Juan; Sergio, Lejona; Lucila, Ortellao; Julio, Befani; Mirta, Villani; Pedro, Morana; Graciana, Morera; Andrea, Uboldi; Elsa, Zerbini


    It is important to characterize the clinical and epidemiological pattern of the influenza A (H1N1) pdm09 virus and compare it with influenza A (H3N2) virus, as surveyed in just a few studies, in order to contribute to the implementation and strengthening of influenza control and prevention strategies. The aims in this study were to describe influenza clinical and epidemiological characteristics in hospitalized patients, caused by influenza A (H1N1)pdm09 and influenza A (H3N2) viruses during 2013, in Santa Fe, Argentina. A retrospective study was conducted over 2013 among hospitalized patients with laboratory-confirmed influenza diagnosis. In contrast to patients with influenza A (H3N2) (20.5%), a higher proportion of hospitalizations associated with influenza H1N1pdm were reported among adults aged 35-65 years (42.8%). Of all patients, 73.6% had an underlying medical condition. Hospitalized patients with H1N1pdm were subject to 2.6 (95%CI, 1.0-6.8) times higher risk of severity, than those hospitalized with influenza A (H3N2). This results demonstrate the impact in the post-pandemic era of H1N1pdm virus, with increased risk of severe disease, in relation to H3N2 virus, both viruses co-circulating during 2013.

  15. Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

    Qiang Shao

    Full Text Available The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50 and cytopathic effect (CPE inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731 and A/California/04/2009 H1N1 (CA04 replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8, A/WSN/1933 H1N1 (WSN, A/Swine/Beijing/26/2008 H1N1 (SW26, A/Chicken/Shandong/LY/2008 H9N2 (LY08, and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07 viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

  16. Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

    Shao, Qiang; Guo, Qiang; Xu, Wen ping; Li, Zandong; Zhao, Tong tong


    The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50) and cytopathic effect (CPE) inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731) and A/California/04/2009 H1N1 (CA04) replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8), A/WSN/1933 H1N1 (WSN), A/Swine/Beijing/26/2008 H1N1 (SW26), A/Chicken/Shandong/LY/2008 H9N2 (LY08), and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07) viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

  17. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

    Fabiani, Massimo; Bella, Antonino; Rota, Maria C; Clagnan, Elena; Gallo, Tolinda; D'Amato, Maurizio; Pezzotti, Patrizio; Ferrara, Lorenza; Demicheli, Vittorio; Martinelli, Domenico; Prato, Rosa; Rizzo, Caterina


    Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during

  18. Tracking oseltamivir-resistance in New Zealand influenza viruses during a medicine reclassification in 2007, a resistant-virus importation in 2008 and the 2009 pandemic

    Q Sue Huang


    Full Text Available Introduction: Oseltamivir (Tamiflu® is an important pharmaceutical intervention against the influenza virus. The importance of surveillance for resistance to oseltamivir has been highlighted by two global events: the emergence of an oseltamivir-resistant seasonal influenza A(H1N1 virus in 2008, and emergence of the influenza A(H1N1pdm09 virus in 2009. Oseltamivir is a prescription medicine in New Zealand, but more timely access has been provided since 2007 by allowing pharmacies to directly dispense oseltamivir to patients with influenza-like illness.Objective: To determine the frequency of oseltamivir-resistance in the context of a medicine reclassification in 2007, the importation of an oseltamivir-resistant seasonal influenza virus in 2008, and the emergence of a pandemic in 2009.Methods: A total of 1795 influenza viruses were tested for oseltamivir-resistance using a fluorometric neuraminidase inhibition assay. Viruses were collected as part of a sentinel influenza surveillance programme between the years 2006 and 2010.Results: All influenza B, influenza A(H3N2 and influenza A(H1N1pdm09 viruses tested between 2006 and 2010 were shown to be sensitive to oseltamivir. Seasonal influenza A(H1N1 viruses from 2008 and 2009 were resistant to oseltamivir. Sequencing of the neuraminidase gene showed that the resistant viruses contained an H275Y mutation, and S247N was also identified in the neuraminidase gene of one seasonal influenza A(H1N1 virus that exhibited enhanced resistance.Discussion: No evidence was found to suggest that increased access to oseltamivir has promoted resistance. A probable importation event was documented for the global 2008 oseltamivir-resistant seasonal A(H1N1 virus nine months after it was first reported in Europe in January 2008.

  19. The Influenza A(H1N1)v Pandemic: An Exploratory System Dynamics Approach

    Pruyt, E.; Hamarat, C.


    This paper presents a small exploratory System Dynamics model related to the dynamics of the 2009 flu pandemic, also known as the Mexican flu, swine flu, or A(H1N1)v. The model was developed in May 2009 in order to quickly foster understanding about the possible dynamics of this new flu variant and

  20. Serological report of pandemic and seasonal human influenza virus infection in dogs in southern China.

    Yin, Xin; Zhao, Fu-Rong; Zhou, Dong-Hui; Wei, Ping; Chang, Hui-Yun


    From January to July 2012, we looked for evidence of subclinical A (H1N1) pdm09 and seasonal human influenza viruses infections in healthy dogs in China. Sera from a total of 1920 dogs were collected from Guangdong, Guangxi, Fujian and Jiangxi provinces. We also examined archived sera from 66 dogs and cats that were collected during 2008 from these provinces. Using hemagglutination inhibition (HI) and microneutralization (MN) assays, we found that only the dogs sampled in 2012 had elevated antibodies (≥ 1:32) against A(H1N1)pdm09 virus and seasonal human influenza viruses: Of the 1920 dog sera, 20.5 % (n = 393) had elevated antibodies against influenza A(H1N1) pdm09 by the HI assay, 1.1 % (n = 22), and 4.7 % (n = 91) of the 1920 dogs sera had elevated antibodies against human seasonal H1N1 influenza virus and human seasonal H3N2 influenza virus by the HI assay. Compared with dogs that were raised on farms, dogs that were raised as pets were more likely to have elevated antibodies against A(H1N1)pdm09 and seasonal human influenza viruses. Seropositivity was highest among pet dogs, which likely had more diverse and frequent exposures to humans than farm dogs. These findings will help us better understand which influenza A viruses are present in dogs and will contribute to the prevention and control of influenza A virus. Moreover, further in-depth study is necessary for us to understand what roles dogs play in the ecology of influenza A.

  1. Transmission of 2009 pandemic influenza A (H1N1) at a Public University--Delaware, April-May 2009.

    Guh, Alice; Reed, Carrie; Gould, L Hannah; Kutty, Preeta; Iuliano, Danielle; Mitchell, Tarissa; Dee, Deborah; Desai, Mitesh; Siebold, Joseph; Silverman, Paul; Massoudi, Mehran; Lynch, Michael; Sotir, Mark; Armstrong, Gregory; Swerdlow, David


    We investigated the first documented university outbreak of the 2009 pandemic influenza A(H1N1) to identify factors associated with disease transmission. An online student survey was administered to assess risk factors for influenza-like illness (ILI), defined as fever with cough or sore throat. Of 6049 survey respondents, 567 (9%) experienced ILI during 27 March to 9 May 2009. Studying with an ill contact (adjusted risk ratios [aRR], 1.29; 95% confidence intervals [CI], 1.01-1.65) and caring for an ill contact (aRR, 1.51; CI, 1.14-2.01) any time during 27 March to 9 May were predictors for ILI. Respondents reported that 680 (6%) of 11,411 housemates were ill; living with an ill housemate was a predictor for ILI (RR, 1.38; CI, 1.04-1.83). Close contact or prolonged exposures to ill persons were likely associated with experiencing ILI. Self-protective measures should be promoted in university populations to mitigate transmission.

  2. The avian influenza H9N2 at avian-human interface: A possible risk for the future pandemics

    Shaghayegh RahimiRad


    Full Text Available The avian influenza subtype H9N2 is considered a low pathogenic virus which is endemic in domestic poultry of a majority of Asian countries. Many reports of seropositivity in occupationally poultry-exposed workers and a number of confirmed human infections with an H9N2 subtype of avian influenza have been documented up to now. Recently, the human infections with both H7N9 and H10N8 viruses highlighted that H9N2 has a great potential for taking a part in the emergence of new human-infecting viruses. This review aimed at discussing the great potential of H9N2 virus which is circulating at avian-human interface, for cross-species transmission, contribution in the production of new reassortants and emergence of new pandemic subtypes. An intensified surveillance is needed for controlling the future risks which would be created by H9N2 circulation at avian-human interfaces.

  3. Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells.

    Rachael L Gerlach

    Full Text Available Replication, cell tropism and the magnitude of the host's antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host responses during infection of well-differentiated, primary human bronchial epithelial cells (wd-NHBE may differ between seasonal (H1N1 A/BN/59/07 and H1N1pdm isolates from a fatal (A/KY/180/10 and nonfatal (A/KY/136/09 case. For each virus, the level of infectious virus and host response to infection (gene expression and apical/basal cytokine/chemokine profiles were measured in wd-NHBE at 8, 24, 36, 48 and 72 hours post-infection (hpi. At 24 and 36 hpi, KY/180 showed a significant, ten-fold higher titer as compared to the other two isolates. Apical cytokine/chemokine levels of IL-6, IL-8 and GRO were similar in wd-NHBE cells infected by each of these viruses. At 24 and 36 hpi, NHBE cells had greater levels of pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, and CCL5, when infected by pandemic viruses as compared with seasonal. Polarization of IL-6 in wd-NHBE cells was greatest at 36 hpi for all isolates. Differential polarized secretion was suggested for CCL5 across isolates. Despite differences in viral titer across isolates, no significant differences were observed in KY/180 and KY/136 gene expression intensity profiles. Microarray profiles of wd-NHBE cells diverged at 36 hpi with 1647 genes commonly shared by wd-NHBE cells infected by pandemic, but not seasonal isolates. Significant differences were observed in cytokine signaling, apoptosis, and cytoskeletal arrangement pathways. Our studies revealed differences in temporal dynamics and basal levels of cytokine/chemokine responses of wd-NHBE cells infected with each isolate; however, wd-NHBE cell gene intensity profiles were not significantly

  4. Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City

    Garcia-Garcia, Lourdes; Valdespino-Gómez, Jose Luis; Lazcano-Ponce, Eduardo; Jimenez-Corona, Aida; Higuera-Iglesias, Anjarath; Cruz-Hervert, Pablo; Cano-Arellano, Bulmaro; Garcia-Anaya, Antonio; Ferreira-Guerrero, Elizabeth; Baez-Saldaña, Renata; Ferreyra-Reyes, Leticia; Ponce-de-León-Rosales, Samuel; Alpuche-Aranda, Celia; Rodriguez-López, Mario Henry; Perez-Padilla, Rogelio; Hernandez-Avila, Mauricio


    Objective To evaluate the association of 2008-9 seasonal trivalent inactivated vaccine with cases of influenza A/H1N1 during the epidemic in Mexico. Design Frequency matched case-control study. Setting Specialty hospital in Mexico City, March to May 2009. Participants 60 patients with laboratory confirmed influenza A/H1N1 and 180 controls with other diseases (not influenza-like illness or pneumonia) living in Mexico City or the State of Mexico and matched for age and socioeconomic status. Main outcome measures Odds ratio and effectiveness of trivalent inactivated vaccine against influenza A/H1N1. Results Cases were more likely than controls to be admitted to hospital, undergo invasive mechanical ventilation, and die. Controls were more likely than cases to have chronic conditions that conferred a higher risk of influenza related complications. In the multivariate model, influenza A/H1N1 was independently associated with trivalent inactivated vaccine (odds ratio 0.27, 95% confidence interval 0.11 to 0.66) and underlying conditions (0.15, 0.08 to 0.30). Vaccine effectiveness was 73% (95% confidence interval 34% to 89%). None of the eight vaccinated cases died. Conclusions Preliminary evidence suggests some protection from the 2008-9 trivalent inactivated vaccine against pandemic influenza A/H1N1 2009, particularly severe forms of the disease, diagnosed in a specialty hospital during the influenza epidemic in Mexico City. PMID:19808768

  5. Clinico-epidemiological profile, pandemic influenza a h1n1/2009 and seasonal influenza, august 2009-march 2013, Himachal Pradesh, India

    Vinod Kumar Mehta


    Full Text Available Background: Novel influenza A (H1N1 virus emerged in April, 2009, spread rapidly to become pandemic by June, 2009. Objective: To study the clinco-epidemiological profile of pH1N1and seasonal influenza (SI from 2009 to 2013. Materials and Methods : Retrospective, hospital-based study was done by reviewing medical records for collecting demographic and clinical profile of the study samples. Result: Out of 969 samples, positivity and case fatality for pH1N1 and SI was 9.39 and 20.87% vs 11.76 and 7.89%, respectively. Among pH1N1and SI, sex distribution, mean age, and age group involved were 54.95% females, 37.10 years, and 20-29 years (23.08% vs 43.86% females, 40.32 years, and 20-29 years (22.81%, respectively. Mortality shift was observed from younger to older and healthier, 75% to comorbid, 100% from 2009-2010 to 2012-13 for pH1N1. Conclusion: We observed seasonal variation, cocirculation, similar clinical features, decreased virulence, and community spread with respect to pH1N1 and SI from 2009-2013.

  6. Multiple estimates of transmissibility for the 2009 influenza pandemic based on influenza-like-illness data from small US military populations.

    Pete Riley

    Full Text Available Rapidly characterizing the amplitude and variability in transmissibility of novel human influenza strains as they emerge is a key public health priority. However, comparison of early estimates of the basic reproduction number during the 2009 pandemic were challenging because of inconsistent data sources and methods. Here, we define and analyze influenza-like-illness (ILI case data from 2009-2010 for the 50 largest spatially distinct US military installations (military population defined by zip code, MPZ. We used publicly available data from non-military sources to show that patterns of ILI incidence in many of these MPZs closely followed the pattern of their enclosing civilian population. After characterizing the broad patterns of incidence (e.g. single-peak, double-peak, we defined a parsimonious SIR-like model with two possible values for intrinsic transmissibility across three epochs. We fitted the parameters of this model to data from all 50 MPZs, finding them to be reasonably well clustered with a median (mean value of 1.39 (1.57 and standard deviation of 0.41. An increasing temporal trend in transmissibility ([Formula: see text], p-value: 0.013 during the period of our study was robust to the removal of high transmissibility outliers and to the removal of the smaller 20 MPZs. Our results demonstrate the utility of rapidly available - and consistent - data from multiple populations.


    S. V. Stepaniuk


    Full Text Available Influenza viruses A play an important role in the structure of the incidence of people with acute respiratory viral infection, which make up 90% from all other infectious diseases. According to the World Health Organization, only severe flu worldwide suffer annually 3.5 million, of which 45–60% are children. An economic loss from seasonal flu epidemic is in average about 85% of economic losses from infectious diseases in general. The experience of fighting the flu, accumulated over the years, has shown that to develop and deliver effective preventive measures necessary to build a system of permanent monitoring for influenza virus circulation, based on use of laboratory methods for accurate and rapid dentification and characterization of circulating strains of influenza virus A. Among the methods of laboratory diagnosis of influenza, the most effective is a method of polymerase chain reaction. Data on the evelopment of diagnostic test kits in the format of two-stage multiplex RTPCR-analysis for detection and genotyping of pandemic influenza virus A (H1N12009 are given. The results of laboratory and experimental research of «DIA Influenza H1N1» test system showed that it is effective and specific for detection of California pandemic influenza virus A (H1N12009 strains and can be used to diagnose disease caused by this strain of virus. Clinical trial of the course of the State registration by Ministry of Health of Ukraine have shown sensitivity and specificity of «DIA Influenza H1N1» test systems up to 100%.

  8. Limiting Severe Outcomes and Impact on Intensive Care Units of Moderate-Intermediate 2009 Pandemic Influenza: Role of Infectious Diseases Units

    Sergio Carbonara; Giuseppe Bruno; Giuseppe Di Ciaula; Anna Donata Pantaleo; Gioacchino Angarano; Laura Monno


    PURPOSE: The rate of severe outcomes of patients with 2009 pandemic (A/H1N1) influenza (2009pI) hospitalized in non-intensive care units (ICUs) has not been defined thus far. This study aims to assess the efficacy of the management of patients with influenza-like illness (ILI) of moderate intermediate severity in an infectious diseases unit (IDU) during the first wave of 2009pI and its influence on the burden of ICUs. METHODS: All patients hospitalized from October 27, 2009, to February 5, 20...

  9. Fatal acute myocarditis and fulminant hepatic failure in an infant with pandemic human influenza A, H1N1 (2009 virus infection

    Mortada H.F. El-Shabrawi


    Full Text Available We report the clinical presentation of a 10 month-old infant who succumbed with acute myocarditis and fulminant hepatic failure associated with a virologically confirmed human influenza A, H1N1 (2009 virus infection. To date, this is the first pediatric patient presenting with this fatal combination of complications during the current H1N1 pandemic. Therefore, we recommend meticulous assessment and follow up of the cardiac status, liver enzymes and coagulation profile in all pediatric patients with severe H1N1 influenza infection.

  10. Estimating the value of containment strategies in delaying the arrival time of an influenza pandemic: A case study of travel restriction and patient isolation

    Wang, Lin; Huang, Tianyi; Li, Xiang; 10.1103/PhysRevE.86.032901


    With a simple phenomenological metapopulation model, which characterizes the invasion process of an influenza pandemic from a source to a subpopulation at risk, we compare the efficiency of inter- and intra-population interventions in delaying the arrival of an influenza pandemic. We take travel restriction and patient isolation as examples, since in reality they are typical control measures implemented at the inter- and intra-population levels, respectively. We find that the intra-population interventions, e.g., patient isolation, perform better than the inter-population strategies such as travel restriction if the response time is small. However, intra-population strategies are sensitive to the increase of the response time, which might be inevitable due to socioeconomic reasons in practice and will largely discount the efficiency.

  11. Estimating the value of containment strategies in delaying the arrival time of an influenza pandemic: a case study of travel restriction and patient isolation.

    Wang, Lin; Zhang, Yan; Huang, Tianyi; Li, Xiang


    With a simple phenomenological metapopulation model, which characterizes the invasion process of an influenza pandemic from a source to a subpopulation at risk, we compare the efficiency of inter- and intrapopulation interventions in delaying the arrival of an influenza pandemic. We take travel restriction and patient isolation as examples, since in reality they are typical control measures implemented at the inter- and intrapopulation levels, respectively. We find that the intrapopulation interventions, e.g., patient isolation, perform better than the interpopulation strategies such as travel restriction if the response time is small. However, intrapopulation strategies are sensitive to the increase of the response time, which might be inevitable due to socioeconomic reasons in practice and will largely discount the efficiency.

  12. [Management of the pandemic influenza (H1N1) 2009 in Germany - results from an evaluation of the public health authorities].

    Bradt, K; Schütz-Langermann, A; Zeck, G; Winkel, I


    In 2009, the health-care system was faced with numerous challenges resulting from the emergence and the worldwide spread of a new influenza virus. Public health authorities played a fundamental role in the management of the pandemic. The Advisory Committee for Infectious Disease Protection of the German Medical Association for Public Health Authorities (BVÖGD e.V.) requested the local public health authorities in Germany to take part in a written evaluation of the management of the new influenza pandemic in February 2010, before the official end of the influenza pandemic. The purpose of this timely analysis was to identify areas in need of improvement in preparation for similar incidents that may occur in the future. The survey showed that the communication between the various parties involved, the prompt and appropriate transmission of information, as well as the control over the overwhelming onslaught of information need to be optimised. The participants also found the practicability of the official recommendations to be lacking. The wide scale increase in workload, as seen on a national basis, required to deal with the pandemic indicates that the public health services have only very limited resources for handling crisis situations, and this must be taken into consideration when planning for coping with such matters in the future. The findings of the study participants for the national management of a pandemic coincide in most aspects with the results of other evaluations. Distinct differences in the assessment of policies were noticeable when comparing the experiences in the various German states (Bundesländer). A detailed analysis of the points at issue is necessary before possible best practice models can be developed.

  13. A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity.

    Kevin J McHugh

    Full Text Available Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and co-infection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300. Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia.

  14. Fatal acute myocarditis and fulminant hepatic failure in an infant with pandemic human influenza A, H1N1 (2009) virus infection

    Mortada H.F. El-Shabrawi; Bazaraa, Hafez M; Hanan Zekri; Hanaa I. Rady


    We report the clinical presentation of a 10 month-old infant who succumbed with acute myocarditis and fulminant hepatic failure associated with a virologically confirmed human influenza A, H1N1 (2009) virus infection. To date, this is the first pediatric patient presenting with this fatal combination of complications during the current H1N1 pandemic. Therefore, we recommend meticulous assessment and follow up of the cardiac status, liver enzymes and coagulation profile in all pediatric patien...

  15. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding

    S. Chutinimitkul (Salin); S. Herfst (Sander); J. Steel (John); A.C. Lowen (Anice); J. Ye (Jian); D.A.J. van Riel (Debby); E.J.A. Schrauwen (Eefje); T.M. Bestebroer (Theo); B.F. Koel (Björn); D.F. Burke (David); K.H. Sutherland-Cash (Kyle); C.S. Whittleson (Chris); C.A. Russell (Colin); D.J. Wales (David); D.J. Smith (Derek); M. Jonges (Marcel); A. Meijer (Adam); M. Koopmans (Matty); G.F. Rimmelzwaan (Guus); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert); A. García-Sastre (Adolfo); D.R. Perez (Daniel); R.A.M. Fouchier (Ron)


    textabstractThe clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by rever

  16. Factors Affecting the Acceptance of Pandemic Influenza A H1N1 Vaccine amongst Essential Service Providers: A Cross Sectional Study

    Charlotte Roberts


    Full Text Available Although mentioned in the UK pandemic plan, essential service providers were not among the priority groups. They may be important targets of future influenza pandemic vaccination campaigns. Therefore, we conducted a cross-sectional survey among 380 employees from West Midlands police headquarters and 15 operational command units in the West Midlands Area during December 2009–February 2010 to identify factors affecting intention to accept the pandemic influenza A (H1N1 vaccine. One hundred and ninety nine (52.4% employees completed the questionnaire. 39.7% were willing to accept the vaccine. The most common reasons for intention to accept were worry about catching Swine Flu (n = 42, 53.2% and about infecting others (n = 40, 50.6%. The most common reason for declination was worry about side effects (n = 45, 57.0%. The most important factor predicting vaccine uptake was previous receipt of seasonal vaccine (OR 7.9 (95% CI 3.4, 18.5. Employees aged <40 years, males, current smokers, and those who perceived a greater threat and severity of swine flu were also more likely to agree to the vaccine. The findings of this study could be used to improve future pandemic immunization strategies. Targeted education programs should be used to address misconceptions; the single most important factor which might lead to a large improvement in uptake is to allay concern about side effects.

  17. The European Union faces up to the threat of a pandemic: meeting at the DGV on the influenza A (H5N1) of the ad hoc group on communicable diseases Luxembourg 14 January 1998.

    Desenclos, J-C.; Manigat, R


    The transmission of an avian influenza H5N1 virus to a child in Hong Kong in May 1997 followed by the occurrence of 17 other human cases with a high case fatality rate (6/18, 33%) suggested that an influenza pandemic could be imminent and led many Europea

  18. Event-based biosurveillance of respiratory disease in Mexico, 2007-2009: connection to the 2009 influenza A(H1N1) pandemic?

    Nelson, N P; Brownstein, J S; Hartley, D M


    The emergence of the 2009 pandemic influenza A(H1N1) virus in North America and its subsequent global spread highlights the public health need for early warning of infectious disease outbreaks. Event-based biosurveillance, based on local- and regional-level Internet media reports, is one approach to early warning as well as to situational awareness. This study analyses media reports in Mexico collected by the Argus biosurveillance system between 1 October 2007 and 31 May 2009. Results from Mexico are compared with the United States and Canadian media reports obtained from the HealthMap system. A significant increase in reporting frequency of respiratory disease in Mexico during the 2008-9 influenza season relative to that of 2007-8 was observed (p<0.0001). The timing of events, based on media reports, suggests that respiratory disease was prevalent in parts of Mexico, and was reported as unusual, much earlier than the microbiological identification of the pandemic virus. Such observations suggest that abnormal respiratory disease frequency and severity was occurring in Mexico throughout the winter of 2008-2009, though its connection to the emergence of the 2009 pandemic influenza A(H1N1) virus remains unclear.

  19. A PB1 T296R substitution enhance polymerase activity and confer a virulent phenotype to a 2009 pandemic H1N1 influenza virus in mice.

    Yu, Zhijun; Cheng, Kaihui; Sun, Weiyang; Zhang, Xinghai; Li, Yuanguo; Wang, Tiecheng; Wang, Hualei; Zhang, Qianyi; Xin, Yue; Xue, Li; Zhang, Kun; Huang, Jing; Yang, Songtao; Qin, Chuan; Wilker, Peter R; Yue, Donghui; Chen, Hualan; Gao, Yuwei; Xia, Xianzhu


    While the 2009 pandemic H1N1 virus has become established in the human population as a seasonal influenza virus, continued adaptation may alter viral virulence. Here, we passaged a 2009 pandemic H1N1 virus (A/Changchun/01/2009) in mice. Serial passage in mice generated viral variants with increased virulence. Adapted variants displayed enhanced replication kinetics in vitro and vivo. Analysis of the variants genomes revealed 6 amino acid changes in the PB1 (T296R), PA (I94V), HA (H3 numbering; N159D, D225G, and R226Q), and NP (D375N). Using reverse genetics, we found that a PB1-T296R substitution found in all adapted viral variants enhanced viral replication kinetics in vitro and vivo, increased viral polymerase activity in human cells, and was sufficient for enhanced virulence of the 2009 pandemic H1N1 virus in mice. Therefore, we defined a novel influenza pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals.

  20. [Incidence of avian flu worldwide and in the Russian Federation. Improvement of surveillance and control of influenza during preparation for potential pandemic].

    Onishchenko, G G


    necessary to organize medical monitoring of sea ships, aircraft and train crews, arriving from the countries where influenza H5N1 cases were detected, in case of need to arrange raids to outlets and markets to detect poultry and poultry products brought from these countries. In Russia it is necessary to prepare a reserve of vaccine strains of viruses--potential causative agent of pandemic, including H5N1 and H7N7, that can start to vaccine reproduction immediately in case of pandemic.

  1. Comparative analysis of epidemiological and clinical features in hospitalized children with acute respiratory infection caused by novel swine-origin influenza virus and seasonal influenza virus A in Chongqing from 2009 to 2011%重庆单中心2009至2011年急性呼吸道感染住院患儿2种甲型流感病毒检出情况及临床特征分析

    谢晓虹; 金玲; 彭才静; 王丽佳; 邓昱; 刘恩梅


    Objective To describe the epidemiological and clinical features in hospitalized children with acute respiratory infection caused by novel swine-origin influenza virus and seasonal influenza virus A in Chongqing. Methods A total of 1 074 nasopharyngeal aspirates were collected in hospitalized children with acute respiratory tract infection enrolled in the department of respiratory medicine in Children's Hospital of Chongqing Medical University from June 2009 to May 2011. The RNA of S-OIVs /seasonal IVA in the sample was examined using real time PCR. Clinical data were recorded and analyzed. Results The presence of IVA was detected in 105(9. 8%)samples of 1 074 cases,including S-OIVs in 15(1. 4%)samples and seasonal IVA in the rest of samples(8. 4%). No differences in gender,age and average inpatient hospital stay were found between patients with S-OIVs infection and seasonal IVA infection. ①The prevalence of S-OIVs was 73. 3%(11/15)in summer of 2009,and the incidence of seasonal IVA infection was higher in the summer of 2009(26/95,27. 4%),summer of 2010(22/95,23. 2%)and spring of 2011 (25/95,26. 3%). The incidence of both two viruses infection was lower in autumn and winter of 2009-2010. ②The rate of severe pneumonia in patients with S-OIVs and seasonal IVA infection was 1/15(6. 7%)and 14/90(15. 6%). There were no significant differences in clinical manifestation,white cell counts,CRP level between S-OIVs and seasonal IVA positive cases. 14 of 90 seasonal IVA positive cases were with severe pneumonia and 1 of 15 S-OIVs positive cases was with severe bronchiolitis. ③Five samples were found with single S-OIVs infection among 15 S-OIVs positive cases,other respiratory viruses were detected in 9 samples. Twenty one samples were found to be single seasonal IVA postive among 90 seasonal IVA positive cases,other respiratory viruses were detected in 42 samples. ④Multivariate logistic regression analysis showed that underling heart medical condition (OR=13. 60

  2. Knowledge and attitudes of health care workers from intensive care units regarding nosocomial transmission of influenza: a study on the immediate pre-pandemic period

    CR Fortaleza


    Full Text Available The transmission of influenza in health care settings is a major threat to patients, especially those with severe diseases. The attitude of health care workers (HCWs may influence the transmission of countless infections. The current study aimed to quantify knowledge and identify attitudes of HCWs involved in intensive care units (ICUs regarding the risk of nosocomial influenza transmission. A questionnaire was applied through interviews to HCWs who worked in one of the five ICUs from a teaching hospital. Questions about influenza were deliberately dispersed among others that assessed several infectious agents. Forty-two HCWs were interviewed: nine physicians, ten nurses and 23 nursing technicians or auxiliaries. Among the 42 HCWs, 98% were aware of the potential transmission of influenza virus in the ICUs, but only 31% would indicate droplet precautions for patients with suspected infection. Moreover, only 31% of them had been vaccinated against influenza in the last campaign (2008. Nursing technicians or auxiliaries were more likely to have been vaccinated, both by univariate and multivariable analysis. When asked about absenteeism, only 10% of the study subjects stated that they would not go to work if they had an influenza-like illness. Those findings suggest that, in non-pandemic periods, influenza control in hospitals requires strategies that combine continuous education with changes in organizational culture.

  3. Outbreak of H3N2 influenza at a US military base in Djibouti during the H1N1 pandemic of 2009.

    Michael T Cosby

    Full Text Available BACKGROUND: Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. OBJECTIVE: We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1pdm09]. METHODS: Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR methodology and sequenced genetic material was phylogenetically compared to other published strains. RESULTS: rt-RT-PCR and DNA sequencing revealed that 25 (78% of the 32 clinical samples collected were seasonal H3N2 and only 2 (6% were A(H1N1pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. CONCLUSIONS: This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed.

  4. New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

    Robert H E Friesen

    Full Text Available BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach

  5. Secondary attack rate of pandemic influenza A(H1N1) 2009 in Western Australian households, 29 May-7 August 2009.

    Carcione, D; Giele, C M; Goggin, L S; Kwan, K S; Smith, D W; Dowse, G K; Mak, D B; Effler, P


    Understanding household transmission of the pandemic influenza A(H1N1)2009 virus, including risk factors for transmission, is important for refining public health strategies to reduce the burden of the disease. During the influenza season of 2009 we investigated transmission of the emerging virus in 595 households in which the index case was the first symptomatic case of influenza A(H1N1)2009. Secondary cases were defined as household contacts with influenza-like illness (ILI) or laboratory-confirmed influenza A(H1N1)2009, occurring at least one day after but within seven days following symptom onset in the index case. ILI developed in 231 of the 1,589 household contacts, a secondary attack rate of 14.5% (95% confidence interval (CI): 12.9–16.4). At least one secondary case occurred in 166 of the 595 households (a household transmission rate of 27.9%; 95% CI: 24.5–31.6).Of these, 127 (76.5%) households reported one secondary case and 39 (23.5%) households reported two or more secondary cases. Secondary attack rates were highest in children younger than five years (p=0.001), and young children were also more efficient transmitters (p=0.01). Individual risk was not associated with household size. Prophylactic antiviral therapy was associated with reduced transmission (p=0.03). The secondary attack rate of ILI in households with a confirmed pandemic influenza A(H1N1)2009 index case was comparable to that described previously for seasonal influenza.

  6. 流感大流行期间家庭支持策略研究%Support and strategies for family fighting against pandemic influenza

    文博; 段艳红; 何素芹


    Objective To proposes some suggestions for the family and social support by investigating the familial coping measures,cognition and psychological demand about pandemic influenza. Methods The cognition,preparation and psychological demand of family about pandemic influenza were investigated with questionnaire through convenience sampling and internet. Results There were altogether five questions about basic knowledge of pandemic influenza in the questionnaire, the average correct rates were less than 50%. The investigation of how to get the information about influenza H1N1 showed that television was considered as the most popular way to know about the information about influenza, the number accounted for 70. 9% ;followed by the newspapers(43.4% ) and network(41.1% ). 86. 3% of people believed that the pandemic will give their family pressure,and 83.4% of people thought that it was necessary to carry out the psychological counseling in order to relieve the panic. Conclusion Families' understanding and preparation for the pandemic influenza at present isn't enough to cope with the pandemic influenza. Families need to get multifold support of the government,society,media and units to cope with pandemic influenza.%目的 了解家庭应对流感大流行的措施、认知程度和需求状况,对预防流感提出家庭和社会支持建议.方法 通过偶遇抽样问卷调查和网络问卷调查法对家庭在流感大流行期间的认知状况、准备状况和心理需求进行研究.结果 问卷中关于流感大流行基本知识的题目有5道,平均正确率均低于50%.在获取关于甲型H1N1流感信息方面,调查人群中希望获得流感相关信息最多的途径为电视(70.9%);其次为报纸(43.4%)和网络(41.1%).86.3%的人认为流感会给家庭带来压力,83.4%的人认为十分有必要或有必要对民众进行心理疏导以缓解恐慌情绪.结论 家庭目前对于流感大流行的认识和准备还远远不足以

  7. Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts.

    Yuma Iwai

    Full Text Available The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in 2009 and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. The threat of influenza A thus remains a serious global health issue and novel drugs that target these viruses are highly desirable. Influenza A possesses an endonuclease within its RNA polymerase which comprises PA, PB1 and PB2 subunits. To identify potential new anti-influenza compounds in our current study, we screened 33 different types of phytochemicals using a PA endonuclease inhibition assay in vitro and an anti-influenza A virus assay. The marchantins are macrocyclic bisbibenzyls found in liverworts, and plagiochin A and perrottetin F are marchantin-related phytochemicals. We found from our screen that marchantin A, B, E, plagiochin A and perrottetin F inhibit influenza PA endonuclease activity in vitro. These compounds have a 3,4-dihydroxyphenethyl group in common, indicating the importance of this moiety for the inhibition of PA endonuclease. Docking simulations of marchantin E with PA endonuclease suggest a putative "fitting and chelating model" as the mechanism underlying PA endonuclease inhibition. The docking amino acids are well conserved between influenza A and B. In a cultured cell system, marchantin E was further found to inhibit the growth of both H3N2 and H1N1 influenza A viruses, and marchantin A, E and perrotein F showed inhibitory properties towards the growth of influenza B. These marchantins also decreased the viral infectivity titer, with marchantin E showing the strongest activity in this assay. We additionally identified a chemical group that is conserved among different anti-influenza chemicals including marchantins, green tea catechins and dihydroxy phenethylphenylphthalimides. Our present results indicate that marchantins are candidate anti-influenza drugs and demonstrate the utility of the PA endonuclease assay in

  8. Influenza A (H1N1-2009) pandemic in Singapore--public health control measures implemented and lessons learnt.

    Tay, Joanne; Ng, Yeuk Fan; Cutter, Jeffery L; James, Lyn


    We describe the public health control measures implemented in Singapore to limit the spread of influenza A (H1N1-2009) and mitigate its social effects. We also discuss the key learning points from this experience. Singapore's public health control measures were broadly divided into 2 phases: containment and mitigation. Containment strategies included the triage of febrile patients at frontline healthcare settings, admission and isolation of confirmed cases, mandatory Quarantine Orders (QO) for close contacts, and temperature screening at border entry points. After sustained community transmission became established, containment shifted to mitigation. Hospitals only admitted H1N1-2009 cases based on clinical indications, not for isolation. Mild cases were managed in the community. Contact tracing and QOs tapered off, and border temperature screening ended. The 5 key lessons learnt were: (1) Be prepared, but retain flexibility in implementing control measures; (2) Surveillance, good scientific information and operational research can increase a system's ability to manage risk during a public health crisis; (3) Integrated systems-level responses are essential for a coherent public health response; (4) Effective handling of manpower surges requires creative strategies; and (5) Communication must be strategic, timely, concise and clear. Singapore's effective response to the H1N1-2009 pandemic, founded on experience in managing the 2003 SARS epidemic, was a whole-of-government approach towards pandemic preparedness planning. Documenting the measures taken and lessons learnt provides a learning opportunity for both doctors and policy makers, and can help fortify Singapore's ability to respond to future major disease outbreaks.

  9. A review of adult mortality due to 2009 pandemic (H1N1 influenza A in California.

    Janice K Louie

    Full Text Available BACKGROUND: While children and young adults had the highest attack rates due to 2009 pandemic (H1N1 influenza A (2009 H1N1, studies of hospitalized cases noted high fatality in older adults. We analyzed California public health surveillance data to better characterize the populations at risk for dying due to 2009 H1N1. METHODS AND FINDINGS: A case was an adult ≥20 years who died with influenza-like symptoms and laboratory results indicative of 2009 H1N1. Demographic and clinical data were abstracted from medical records using a standardized case report form. From April 3, 2009-August 10, 2010, 541 fatal cases ≥20 years with 2009 H1N1 were reported. Influenza fatality rates per 100,000 population were highest in persons 50-59 years (3.5; annualized rate = 2.6 and 60-69 years (2.3; annualized rate = 1.7 compared to younger and older age groups (0.4-1.9; annualized rates = 0.3-1.4. Of 486 cases hospitalized prior to death, 441 (91% required intensive care unit (ICU admission. ICU admission rates per 100,000 population were highest in adults 50-59 years (8.6. ICU case-fatality ratios among adults ranged from 24-42%, with the highest ratios in persons 70-79 years. A total of 425 (80% cases had co-morbid conditions associated with severe seasonal influenza. The prevalence of most co-morbid conditions increased with increasing age, but obesity, pregnancy and obstructive sleep apnea decreased with age. Rapid testing was positive in 97 (35% of 276 tested. Of 482 cases with available data, 384 (80% received antiviral treatment, including 49 (15% of 328 within 48 hours of symptom onset. CONCLUSIONS: Adults aged 50-59 years had the highest fatality due to 2009 H1N1; older adults may have been spared due to pre-existing immunity. However, once infected and hospitalized in intensive care, case-fatality ratios were high for all adults, especially in those over 60 years. Vaccination of adults older than 50 years should be encouraged.

  10. Satisfaction and public health cost of a statewide influenza nurse triage line in response to pandemic H1N1 influenza.

    Alicen B Spaulding

    Full Text Available BACKGROUND: The 2009 H1N1 pandemic strained healthcare systems. There was a need for supportive services, rapid antiviral access, and minimization of unnecessary healthcare contacts particularly face-to-face interactions. In response, the Minnesota Department of Health (MDH launched a telephone-based nurse triage line (NTL called the Minnesota FluLine coordinating all major MN healthcare systems with NTLs to form a single toll-free number triage service. Callers were evaluated for symptoms of influenza-like illness (ILI and were prescribed an antiviral if indicated, using nurse administered protocols. METHODS: To determine caller outcomes, associated healthcare seeking, and satisfaction a telephone survey of Minnesota FluLine callers was conducted using a 5% random sample of those who completed the protocol and those who did not. RESULTS: Of 6,122 callers with ILI who began the nurse protocol administered by the contract NTL, 1,221 people were contacted for the survey and 325 agreed to participate; response rate was 26%. Of those who completed the nurse protocol 73% said they would have sought healthcare without the Minnesota FluLine, 89% reported the service was moderately or very helpful, and 91% reported being satisfied or very satisfied. Of those not completing the protocol, 50% reported the service was moderately or very helpful and 50% reported being satisfied or very satisfied. 72% of qualitative responses to open-ended questions were positive regarding the MN FluLine. Cost to MDH for operating the Minnesota FluLine service was $331,226 to service 27,391 callers ($12.09/call. DISCUSSION: The Minnesota FluLine diverted patients with mild ILI symptoms away from acute care visits at low cost and had a high rate of satisfaction among callers. Early intervention likely prevented morbidity and possibly additional cases. NTLs are powerful and flexible tools for pandemic response and should be considered as an important tool for future emergency

  11. Effect of human rhinovirus infection in pediatric patients with influenza-like illness on the 2009 pandemic influenza A(H1N1) virus

    Sun Yu; Zhu Ru'nan; Zhao Linqing; Deng Jie; Wang Fang; Ding Yaxin; Yuan Yi


    Background Some research groups have hypothesized that human rhinoviruses (HRVs) delayed the circulation of the 2009 pandemic influenza A(H1N1) virus (A(H1N1)pdm09) at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A(H1N1)pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A(H1N1)pdm09 and seasonal influenza A virus (FLU A) was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR (rRT-PCR) assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A(H1N1)pdm09 was observed.The percentage of positive cases for A(H1N1)pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September (2.2%) and October (3.3%),revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 (1.8%) were HRV-positive,which was significantly lower than that reported previously in Beijing (15.4% to 19.2%) (P <0.01).Overall,6 samples were positive for both A(H1N1)pdm09 and HRV,which represented a positive relative frequency of 1.60% and 2.08% HRV,considering the A(H1N1)pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 (95% CI 0.32; 2.44,P=0.80).Conclusions HRVs and A (H1N1)pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A(H1N1)pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A(H1N1)pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.

  12. Cross-protection against lethal H5N1 challenge in ferrets with an adjuvanted pandemic influenza vaccine.

    Benoît Baras

    Full Text Available BACKGROUND: Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007 The Lancet 370:580-589, for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets. METHODOLOGY AND PRINCIPAL FINDINGS: All ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing >or=1.7 microg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74% responders and clade 2 viruses (14/23 (61% responders, and 96% (22/23 of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission. CONCLUSION: These protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness.

  13. Internet-based surveillance of Influenza-like-illness in the UK during the 2009 H1N1 influenza pandemic

    Ealden Toby


    Full Text Available Abstract Background Internet-based surveillance systems to monitor influenza-like illness (ILI have advantages over traditional (physician-based reporting systems, as they can potentially monitor a wider range of cases (i.e. including those that do not seek care. However, the requirement for participants to have internet access and to actively participate calls into question the representativeness of the data. Such systems have been in place in a number of European countries over the last few years, and in July 2009 this was extended to the UK. Here we present results of this survey with the aim of assessing the reliability of the data, and to evaluate methods to correct for possible biases. Methods Internet-based monitoring of ILI was launched near the peak of the first wave of the UK H1N1v influenza pandemic. We compared the recorded ILI incidence with physician-recorded incidence and an estimate of the true number of cases over the course of the epidemic. We also compared overall attack rates. The effect of using different ILI definitions and alternative denominator assumptions on incidence estimates was explored. Results The crude incidence measured by the internet-based system appears to be influenced by individuals who participated only once in the survey and who appeared more likely to be ill. This distorted the overall incidence trend. Concentrating on individuals who reported more than once results in a time series of ILI incidence that matches the trend of case estimates reasonably closely, with a correlation of 0.713 (P-value: 0.0001, 95% CI: 0.435, 0.867. Indeed, the internet-based system appears to give a better estimate of the relative height of the two waves of the UK pandemic than the physician-recorded incidence. The overall attack rate is, however, higher than other estimates, at about 16% when compared with a model-based estimate of 6%. Conclusion Internet-based monitoring of ILI can capture the trends in case numbers if

  14. Polymyositis following Pandemic Influenza A (H1N1 and 2009-10 Seasonal Trivalent Vaccines

    Clodoveo Ferri


    Full Text Available Sporadic associations between inflammatory myopathies with vaccinations were described in the literature, raising the possible trigger value of vaccines in the development of these autoimmune disorders. Here, we reported the clinical history of 3 patients who developed polymyositis complicated by interstitial lung disease (2 cases and dermatomyositis (1 case, after influenza A (H1N1 vaccination.

  15. Department of Defense Influenza and Other Respiratory Disease Surveillance during the 2009 Pandemic


    NMRCD partnerships with Bolivia and Ecuador ; AFRIMS surveillance in Vietnam; NAMRU-3 develop- ment of a veterinary and human influenza surveillance...Korea, Microbiology Section, Unit 15244, Box 459, APO AP 96205, USA. 11Naval Medical Research Unit Number 2, Kompleks Pergudangan DEPKES R.I., JI

  16. Recombinant HA1 produced in E. coli forms functional oligomers and generates strain-specific SRID potency antibodies for pandemic influenza vaccines.

    Khurana, Surender; Larkin, Christopher; Verma, Swati; Joshi, Manju B; Fontana, Juan; Steven, Alasdair C; King, Lisa R; Manischewitz, Jody; McCormick, William; Gupta, Rajesh K; Golding, Hana


    Vaccine production and initiation of mass vaccination is a key factor in rapid response to new influenza pandemic. During the 2009-2010 H1N1 pandemic, several bottlenecks were identified, including the delayed availability of vaccine potency reagents. Currently, antisera for the single-radial immunodiffusion (SRID) potency assay are generated in sheep immunized repeatedly with HA released and purified after bromelain-treatment of influenza virus grown in eggs. This approach was a major bottleneck for pandemic H1N1 (H1N1pdm09) potency reagent development in 2009. Alternative approaches are needed to make HA immunogens for generation of SRID reagents in the shortest possible time. In this study, we found that properly folded recombinant HA1 globular domain (rHA1) from several type A viruses including H1N1pdm09 and two H5N1 viruses could be produced efficiently using a bacterial expression system and subsequent purification. The rHA1 proteins were shown to form functional oligomers of trimers, similar to virus derived HA, and elicited high titer of neutralizing antibodies in rabbits and sheep. Importantly, the immune sera formed precipitation rings with reference antigens in the SRID assay in a dose-dependent manner. The HA contents in multiple H1N1 vaccine products from different manufacturers (and in several lots) as determined with the rHA1-generated sheep sera were similar to the values obtained with a traditionally generated sheep serum from NIBSC. We conclude that bacterially expressed recombinant HA1 proteins can be produced rapidly and used to generate SRID potency reagents shortly after new influenza strains with pandemic potential are identified.

  17. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1 disease.

    Oliver W Morgan

    Full Text Available BACKGROUND: Severe illness due to 2009 pandemic A(H1N1 infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1, independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP to increase the risk of influenza-related complications. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1 influenza occurring between April-July, 2009, with a cohort of the U.S. population estimated from the 2003-2006 National Health and Nutrition Examination Survey (NHANES; pregnant women and children or=20 year olds, hospitalization was associated with being morbidly obese (BMI>or=40 for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4-9.9 and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3-17.2. Among 2-19 year olds, hospitalization was associated with being underweight (BMIor=20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5-6.6 and morbid obesity (OR = 7.6, 95%CI 2.1-27.9. CONCLUSIONS/SIGNIFICANCE: Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.

  18. Mutations in polymerase genes enhanced the virulence of 2009 pandemic H1N1 influenza virus in mice.

    Wenfei Zhu

    Full Text Available Influenza A virus can infect a wide variety of animal species with illness ranging from mild to severe, and is a continual cause for concern. Genetic mutations that occur either naturally or during viral adaptation in a poorly susceptible host are key mechanisms underlying the evolution and virulence of influenza A virus. Here, the variants containing PA-A36T or PB2-H357N observed in the mouse-adapted descendants of 2009 pandemic H1N1 virus (pH1N1, A/Sichuan/1/2009 (SC, were characterized. Both mutations enhanced polymerase activity in mammalian cells. These effects were confirmed using recombinant SC virus containing polymerase genes with wild type (WT or mutant PA or PB2. The PA-A36T mutant showed enhanced growth property compared to the WT in both human A549 cells and porcine PK15 cells in vitro, without significant effect on viral propagation in murine LA-4 cells and pathogenicity in mice; however, it did enhance the lung virus titer. PB2-H357N variant demonstrated growth ability comparable to the WT in A549 cells, but replicated well in PK15, LA-4 cells and in mice with an enhanced pathogenic phenotype. Despite such mutations are rare in nature, they could be observed in avian H5 and H7 subtype viruses which were currently recognized to pose potential threat to human. Our findings indicated that pH1N1 may adapt well in mammals when acquiring these mutations. Therefore, future molecular epidemiological surveillance should include scrutiny of both markers because of their potential impact on pathogenesis.

  19. Prediction of clinical factors associated with pandemic influenza A (H1N1 2009 in Pakistan.

    Nadia Nisar

    Full Text Available BACKGROUND: Influenza is a viral infection that can lead to serious complications and death(s in vulnerable groups if not diagnosed and managed in a timely manner. This study was conducted to improve the accuracy of predicting influenza through various clinical and statistical models. METHODOLOGY: A retrospective cross sectional analysis was done on demographic and epidemiological data collected from March 2009 to March 2010. Patients were classified as ILI or SARI using WHO case definitions. Respiratory specimens were tested by RT-PCR. Clinical symptoms and co-morbid conditions were analyzed using binary logistic regression models. RESULTS: In the first approach, analysis compared children (≤12 and adults (>12. Of 1,243 cases, 262 (21% tested positive for A(H1N1pdm09 and the proportion of children (≤12 and adults (>12 were 27% and 73% respectively. Four symptoms predicted influenza in children: fever (OR 2.849, 95% CI 1.931-8.722, cough (OR 1.99, 95% CI 1.512-3.643, diarrhea (OR 2.100, 95% CI 2.040-3.25 and respiratory disease (OR 3.269, 95% CI 2.128-12.624. In adults, the strongest clinical predictor was fever (OR 2.80, 95% CI 1.025-3.135 followed by cough (OR 1.431, 95% CI 1.032-2.815. In the second instance, patients were separated into two groups: SARI 326 (26% and ILI 917 (74% cases. Male to female ratio was 1.41∶1.12 for SARI and 2∶1.5 for ILI cases. Chi-square test showed that fever, cough and sore throat were significant factors for A(H1N1pdm09 infections (p = 0.008. CONCLUSION: Studies in a primary care setting should be encouraged focused on patients with influenza-like illness to develop sensitive clinical case definition that will help to improve accuracy of detecting influenza infections. Formulation of a standard "one size fits all" case definition that best correlates with influenza infections can help guide decisions for additional diagnostic testing and also discourage unjustified antibiotic prescription and usage

  20. Persistence of the 2009 pandemic influenza A (H1N1 virus in water and on non-porous surface.

    Amélie Dublineau

    Full Text Available Knowledge of influenza A virus survival in different environmental conditions is a key element for the implementation of hygiene and personal protection measures by health authorities. As it is dependent on virus isolates even within the same subtype, we studied the survival of the 2009 H1N1 pandemic (H1N1pdm virus in water and on non-porous surface. The H1N1pdm virus was subjected to various environmental parameters over time and tested for infectivity. In water, at low and medium salinity levels and 4°C, virus survived at least 200 days. Increasing temperature and salinity had a strong negative effect on the survival of the virus which remained infectious no more than 1 day at 35°C and 270 parts per thousand (ppt of salt. Based on modeled data, the H1N1pdm virus retained its infectivity on smooth non-porous surface for at least 7 days at 35°C and up to 66 days at 4°C. The H1N1pdm virus has thus the ability to persist in water and on glass surface for extended periods of time, even at 35°C. Additional experiments suggest that external viral structures in direct contact with the environment are mostly involved in loss of virus infectivity.

  1. Influenza-like illness in acute myocardial infarction patients during the winter wave of the influenza A H1N1 pandemic in London: a case–control study

    Warren-Gash, Charlotte; Geretti, Anna Maria; Hamilton, George; Rakhit, Roby D; Smeeth, Liam; Hayward, Andrew C


    Objective To investigate recent respiratory and influenza-like illnesses (ILIs) in acute myocardial infarction patients compared with patients hospitalised for acute non-vascular surgical conditions during the second wave of the 2009 influenza A H1N1 pandemic. Design Case–control study. Setting Coronary care unit, acute cardiology and acute surgical admission wards in a major teaching hospital in London, UK. Participants 134 participants (70 cases and 64 controls) aged ≥40 years hospitalised for acute myocardial infarction and acute surgical conditions between 21 September 2009 and 28 February 2010, frequency-matched for gender, 5-year age-band and admission week. Primary exposure ILI (defined as feeling feverish with either a cough or sore throat) within the last month. Secondary exposures Acute respiratory illness within the last month not meeting ILI criteria; nasopharyngeal and throat swab positive for influenza virus. Results 29 of 134 (21.6%) participants reported respiratory illness within the last month, of whom 13 (9.7%) had illnesses meeting ILI criteria. The most frequently reported category for timing of respiratory symptom onset was 8–14 days before admission (31% of illnesses). Cases were more likely than controls to report ILI—adjusted OR 3.17 (95% CI 0.61 to 16.47)—as well as other key respiratory symptoms, and were less likely to have received influenza vaccination—adjusted OR 0.46 (95% CI 0.19 to 1.12)—although the differences were not statistically significant. No swabs were positive for influenza virus. Conclusions Point estimates suggested that recent ILI was more common in patients hospitalised with acute myocardial infarction than with acute surgical conditions during the second wave of the influenza A H1N1 pandemic, and influenza vaccination was associated with cardioprotection, although the findings were not statistically significant. The study was underpowered, partly because the age groups typically affected by acute

  2. Comparison of CATs, CURB-65 and PMEWS as triage tools in pandemic influenza admissions to UK hospitals: case control analysis using retrospective data.

    Myles, Puja R; Nguyen-Van-Tam, Jonathan S; Lim, Wei Shen; Nicholson, Karl G; Brett, Stephen J; Enstone, Joanne E; McMenamin, James; Openshaw, Peter J M; Read, Robert C; Taylor, Bruce L; Bannister, Barbara; Semple, Malcolm G


    Triage tools have an important role in pandemics to identify those most likely to benefit from higher levels of care. We compared Community Assessment Tools (CATs), the CURB-65 score, and the Pandemic Medical Early Warning Score (PMEWS); to predict higher levels of care (high dependency--Level 2 or intensive care--Level 3) and/or death in patients at or shortly after admission to hospital with A/H1N1 2009 pandemic influenza. This was a case-control analysis using retrospectively collected data from the FLU-CIN cohort (1040 adults, 480 children) with PCR-confirmed A/H1N1 2009 influenza. Area under receiver operator curves (AUROC), sensitivity, specificity, positive predictive values and negative predictive values were calculated. CATs best predicted Level 2/3 admissions in both adults [AUROC (95% CI): CATs 0.77 (0.73, 0.80); CURB-65 0.68 (0.64, 0.72); PMEWS 0.68 (0.64, 0.73), ptools for predicting need for higher levels of care and/or mortality in patients of all ages.

  3. Molecular characterization of a novel reassortant H1N2 influenza virus containing genes from the 2009 pandemic human H1N1 virus in swine from eastern China.

    Peng, Xiuming; Wu, Haibo; Xu, Lihua; Peng, Xiaorong; Cheng, Linfang; Jin, Changzhong; Xie, Tiansheng; Lu, Xiangyun; Wu, Nanping


    Pandemic outbreaks of H1N1 swine influenza virus have been reported since 2009. Reassortant H1N2 viruses that contain genes from the pandemic H1N1 virus have been isolated in Italy and the United States. However, there is limited information regarding the molecular characteristics of reassortant H1N2 swine influenza viruses in eastern China. Active influenza surveillance programs in Zhejiang Province identified a novel H1N2 influenza virus isolated from pigs displaying clinical signs of influenza virus infection. Whole-genome sequencing was performed and this strain was compared with other influenza viruses available in GenBank. Phylogenetic analysis suggested that the novel strain contained genes from the 2009 pandemic human H1N1 and swine H3N2 viruses. BALB/c mice were infected with the isolated virus to assess its virulence in mice. While the novel H1N2 isolate replicated well in mice, it was found to be less virulent. These results provide additional evidence that swine serve as intermediate hosts or 'mixing vessels' for novel influenza viruses. They also emphasize the importance of surveillance in the swine population for use as an early warning system for influenza outbreaks in swine and human populations.

  4. [Human influenza].

    Stock, Ingo


    Human influenza is one of the most common human infectious diseases, contributing to approximately one million deaths every year. In Germany, each year between 5.000 and 20.000 individuals die from severe influenza infections. In several countries, the morbidity and mortality of influenza is greatly underestimated. This is reflected by general low immunization rates. The emergence of avian influenza against the background of the scenario of a human influenza pandemic has revived public interest in the disease. According to the World Health Organisation, it is only the question on the beginning of a new influenza pandemic. The virus type of the new pandemic is still uncertain and it is also unclear, if a pandemic spread of the virus may be prevented by consistent controlling of avian influenza.

  5. Potency of a vaccine prepared from A/swine/Hokkaido/2/1981 (H1N1 against A/Narita/1/2009 (H1N1 pandemic influenza virus strain

    Okamatsu Masatoshi


    Full Text Available Abstract Background The pandemic 2009 (H1N1 influenza virus has spread throughout the world and is now causing seasonal influenza. To prepare for the emergence of pandemic influenza, we have established a library of virus strains isolated from birds, pigs, and humans in global surveillance studies. Methods Inactivated whole virus particle (WV and ether-split (ES vaccines were prepared from an influenza virus strain, A/swine/Hokkaido/2/1981 (H1N1, from the library and from A/Narita/1/2009 (H1N1 pandemic strain. Each of the vaccines was injected subcutaneously into mice and their potencies were evaluated by challenge with A/Narita/1/2009 (H1N1 virus strain in mice. Results A/swine/Hokkaido/2/81 (H1N1, which was isolated from the lung of a diseased piglet, was selected on the basis of their antigenicity and growth capacity in embryonated chicken eggs. Two injections of the WV vaccine induced an immune response in mice, decreasing the impact of disease caused by the challenge with A/Narita/1/2009 (H1N1, as did the vaccine prepared from the homologous strain. Conclusion The WV vaccine prepared from an influenza virus in the library is useful as an emergency vaccine in the early phase of pandemic influenza.

  6. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B


    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  7. Caveolin-1 influences human influenza A virus (H1N1 multiplication in cell culture

    Hemgård Gun-Viol


    Full Text Available Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1 as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1 strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1 virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK, a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

  8. The public's acceptance of novel vaccines during a pandemic: a focus group study and its application to influenza H1N1.

    Henrich, N; Holmes, B


    As influenza H1N1 spreads around the world, health officials are considering the development and use of a new vaccine to protect the public and help control the outbreak. Acceptance of novel vaccines during health crises, however, is influenced by perceptions of a range of risks, including the risk of infection, risk of becoming severely ill or dying if infected, as well as the risk of serious side and long-term effects of the vaccine. A study on 11 focus groups was conducted with the public in Vancouver, Canada in 2006 and 2007 to explore how people assess these risks and how these assessments relate to their willingness to use novel vaccines in a pandemic. Concerns about using new vaccines during a pandemic differ from concerns about using established products in a non-crisis situation. Participants were hesitant to use novel vaccines because of a low perception of the early risk of infection in a pandemic, coupled with the many uncertainties that surround new vaccines and the emerging infectious disease, and owing to the concern that unsafe pharmaceuticals may be rushed to market during a health crisis. Understanding the public´s assessment of the risks related to, and willingness to use, novel vaccines during a pandemic can help officials promote disease-control measures in ways that improve the likelihood of acceptance by the public and may increase uptake of an H1N1 vaccine.

  9. The public's acceptance of novel vaccines during a pandemic: A focus group study and its application to influenza H1N1

    Natalie Henrich


    Full Text Available

    As influenza H1N1 spreads around the world, health officials are considering the development and use of a new vaccine to protect the public and help control the outbreak. Acceptance of novel vaccines during health crises, however, is influenced by perceptions of a range of risks, including risk of infection, risk of becoming severely ill or dying if infected, and risk of serious side- and long-term effects of the vaccine. Eleven focus groups were conducted with the public in Vancouver, Canada in 2006 and 2007 to explore how people assess these risks and how these assessments relate to willingness to use novel vaccines in a pandemic. Concerns about using new vaccines during a pandemic differ from concerns about using established products in a non-crisis situation. Participants were hesitant to use the novel vaccines because of a low perception of risk of infection early in a pandemic coupled with the many uncertainties that surround new vaccines and the emerging infectious disease, and concern that unsafe pharmaceuticals may be rushed to market during the health crisis. Understanding adults|[rsquo]| assessment of risks related to, and willingness to use, novel vaccines during a pandemic can help officials promote disease-control measures in ways that improve the likelihood of acceptance by the public and may increase uptake of an H1N1 vaccine.

  10. A Meta-analysis of Point-of-care Laboratory Tests in the Diagnosis of Novel 2009 Swine-lineage Pandemic Influenza A(H1N1)

    Babin, Steven M.; Hsieh, Yu-Hsiang; Rothman, Richard E.; Gaydos, Charlotte A.


    This paper reviews fourteen published studies describing performance characteristics, including sensitivity and specificity, of commercially-available rapid, point-of-care (POC) influenza tests in patients affected by an outbreak of a novel swine-related influenza A (H1N1) that was declared a pandemic in 2009. Although these POC tests weren’t intended to be specific for this pandemic influenza strain, the non-specialized skills required and the timeliness of results make these POC tests potentially valuable for clinical and public health use. Pooled sensitivity and specificity for the POC tests studied were 68% and 81%, respectively, but published values were not homogeneous with sensitivities and specificities ranging from 10–88% and 51–100%, respectively. Pooled positive and negative likelihood ratios were 5.94 and 0.42, respectively. These results support current recommendations for use of rapid POC tests when H1N1 is suspected, recognizing that positive results are more reliable than negative results in determining infection, especially when disease prevalence is high. PMID:21396538

  11. Integrated network analysis reveals a novel role for the cell cycle in 2009 pandemic influenza virus-induced inflammation in macaque lungs

    Shoemaker Jason E


    Full Text Available Abstract Background Annually, influenza A viruses circulate the world causing wide-spread sickness, economic loss, and death. One way to better defend against influenza virus-induced disease may be to develop novel host-based therapies, targeted at mitigating viral pathogenesis through the management of virus-dysregulated host functions. However, mechanisms that govern aberrant host responses to influenza virus infection remain incompletely understood. We previously showed that the pandemic H1N1 virus influenza A/California/04/2009 (H1N1; CA04 has enhanced pathogenicity in the lungs of cynomolgus macaques relative to a seasonal influenza virus isolate (A/Kawasaki/UTK-4/2009 (H1N1; KUTK4. Results Here, we used microarrays to identify host gene sequences that were highly differentially expressed (DE in CA04-infected macaque lungs, and we employed a novel strategy – combining functional and pathway enrichment analyses, transcription factor binding site enrichment analysis and protein-protein interaction data – to create a CA04 differentially regulated host response network. This network describes enhanced viral RNA sensing, immune cell signaling and cell cycle arrest in CA04-infected lungs, and highlights a novel, putative role for the MYC-associated zinc finger (MAZ transcription factor in regulating these processes. Conclusions Our findings suggest that the enhanced pathology is the result of a prolonged immune response, despite successful virus clearance. Most interesting, we identify a mechanism which normally suppresses immune cell signaling and inflammation is ineffective in the pH1N1 virus infection; a dyregulatory event also associated with arthritis. This dysregulation offers several opportunities for developing strain-independent, immunomodulatory therapies to protect against future pandemics.

  12. In ovo and in vitro susceptibility of American alligators (Alligator mississippiensis) to avian influenza virus infection.

    Temple, Bradley L; Finger, John W; Jones, Cheryl A; Gabbard, Jon D; Jelesijevic, Tomislav; Uhl, Elizabeth W; Hogan, Robert J; Glenn, Travis C; Tompkins, S Mark


    Avian influenza has emerged as one of the most ubiquitous viruses within our biosphere. Wild aquatic birds are believed to be the primary reservoir of all influenza viruses; however, the spillover of H5N1 highly pathogenic avian influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked increased interest in identifying and understanding which and how many species can be infected. Moreover, novel influenza virus sequences were recently isolated from New World bats. Crocodilians have a slow rate of molecular evolution and are the sister group to birds; thus they are a logical reptilian group to explore susceptibility to influenza virus infection and they provide a link between birds and mammals. A primary American alligator (Alligator mississippiensis) cell line, and embryos, were infected with four, low pathogenic avian influenza (LPAI) strains to assess susceptibility to infection. Embryonated alligator eggs supported virus replication, as evidenced by the influenza virus M gene and infectious virus detected in allantoic fluid and by virus antigen staining in embryo tissues. Primary alligator cells were also inoculated with the LPAI viruses and showed susceptibility based upon antigen staining; however, the requirement for trypsin to support replication in cell culture limited replication. To assess influenza virus replication in culture, primary alligator cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that replicate independent of trypsin. Both viruses replicated efficiently in culture, even at the 30 C temperature preferred by the alligator cells. This research demonstrates the ability of wild-type influenza viruses to infect and replicate within two crocodilian substrates and suggests the need for further research to assess crocodilians as a species potentially susceptible to influenza virus infection.

  13. Effectiveness of trivalent and pandemic influenza vaccines in England and Wales 2008-2010: results from a cohort study in general practice.

    Hardelid, Pia; Fleming, Douglas M; Andrews, Nick; Barley, Michele; Durnall, Hayley; Mangtani, Punam; Pebody, Richard


    Estimation of influenza vaccine effectiveness (VE) is complicated by various degrees of mismatch between circulating and vaccine strains each season. We carried out a cohort study to estimate VE of trivalent (TIV) and pandemic influenza vaccines (PIV) in preventing various respiratory outcomes among general practice (GP) patients in England and Wales between 2008 and 2010. Dates of consultations for influenza-like illness (ILI), acute respiratory tract infection (ARTI), lower respiratory tract infection (LRTI) and nasopharyngeal swabs were obtained from the patient-level electronic records of the 100 practices enrolled in a national GP network. Dates of vaccination with TIV and PIV were also extracted. Confounders including age, time period and consultation frequency were adjusted for through Poisson regression models. In the winter of 2008/9, adjusted VE of TIV in preventing ILI was 22.3% (95% CI 13.5%, 30.2%). During the 2009/10 winter VE for PIV in preventing ILI was 21.0% (5.3%, 34.0%). The VE for PIV in preventing PCR-confirmed influenza A/H1N1 (2009) was 63.7% (-6.1%, 87.6%). TIV during the period of influenza circulation of 2008/9 and PIV in the winter of 2009/10 were effective in preventing GP consultations for ILI. The cohort study design could be used each season to estimate VE; however, residual confounding by indication could still present issues, despite adjustment for propensity to consult.

  14. Properly folded bacterially expressed H1N1 hemagglutinin globular head and ectodomain vaccines protect ferrets against H1N1 pandemic influenza virus.

    Surender Khurana

    Full Text Available BACKGROUND: In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "Spanish Flu". The traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant technology can be used to express the hemagglutinin (HA of the emerging new influenza strain in a variety of systems including mammalian, insect, and bacterial cells. In this study, two forms of HA proteins derived from the currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1-330 and HA (1-480, were expressed and purified from E. coli under controlled redox refolding conditions that favoured proper protein folding. However, only the recombinant HA1 (1-330 protein formed oligomers, including functional trimers that bound receptor and caused agglutination of human red blood cells. These proteins were used to vaccinate ferrets prior to challenge with the A/California/07/2009 virus. Both proteins induced neutralizing antibodies, and reduced viral loads in nasal washes. However, the HA1 (1-330 protein that had higher content of multimeric forms provided better protection from fever and weight loss at a lower vaccine dose compared with HA (1-480. Protein yield for the HA1 (1-330 ranged around 40 mg/Liter, while the HA (1-480 yield was 0.4-0.8 mg/Liter. CONCLUSIONS/SIGNIFICANCE: This is the first study that describes production in bacterial system of properly folded functional globular HA1 domain trimers, lacking the HA2 transmembrane protein, that elicit potent neutralizing antibody responses following vaccination and protect ferrets from in vivo challenge. The combination of bacterial expression system with established quality control methods could provide a mechanism for rapid large

  15. A hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern France during the Great War provided the conditions for the emergence of the "Spanish" influenza pandemic of 1918-1919.

    Oxford, J S; Lambkin, R; Sefton, A; Daniels, R; Elliot, A; Brown, R; Gill, D


    The Great Influenza Pandemic of 1918-1919 was a cataclysmic outbreak of infection wherein over 50 million people died worldwide within 18 months. The question of the origin is important because most influenza surveillance at present is focussed on S.E. Asia. Two later pandemic viruses in 1957 and 1968 arose in this region. However we present evidence that early outbreaks of a new disease with rapid onset and spreadability, high mortality in young soldiers in the British base camp at Etaples in Northern France in the winter of 1917 is, at least to date, the most likely focus of origin of the pandemic. Pathologists working at Etaples and Aldershot barracks later agreed that these early outbreaks in army camps were the same disease as the infection wave of influenza in 1918. The Etaples camp had the necessary mixture of factors for emergence of pandemic influenza including overcrowding (with 100,000 soldiers daily changing), live pigs, and nearby live geese, duck and chicken markets, horses and an additional factor 24 gases (some of them mutagenic) used in large 100 ton quantities to contaminate soldiers and the landscape. The final trigger for the ensuing pandemic was the return of millions of soldiers to their homelands around the entire world in the autumn of 1918.

  16. Perceptions and behaviors related to hand hygiene for the prevention of H1N1 influenza transmission among Korean university students during the peak pandemic period

    Kim Seon-Ung


    Full Text Available Abstract Background This study was performed to better assess the perceptions, motivating factors, and behaviors associated with the use of hand washing to prevent H1N1 influenza transmission during the peak pandemic period in Korea. Methods A cross-sectional survey questionnaire was completed by 942 students at a university campus in Suwon, Korea, between December 1 and 8, 2009. The survey included questions regarding individual perceptions, motivating factors, and behaviors associated with hand washing for the prevention of H1N1 influenza transmission. Results Compared to one year prior, 30.3% of participants reported increasing their hand washing frequency. Female students were more likely to practice more frequent hand washing. Women also perceived the effectiveness of hand washing to be lower, and illness severity and personal susceptibility to H1N1 infection to be higher. Study participants who were female (OR: 1.79-3.90 who perceived of hand washing to be effective (OR: 1.34-12.15 and illness severity to be greater (OR: 1.00-3.12 washed their hands more frequently. Conclusions Korean students increased their frequency of hand hygiene practices during the pandemic, with significant gender differences existing in the attitudes and behaviors related to the use of hand hygiene as a means of disease prevention. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission.