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Sample records for ah1n1 influenza viruses

  1. Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

    PubMed

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

    2014-03-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas. PMID:24565026

  2. Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

    PubMed

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

    2014-03-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.

  3. Influenza A(H1N1)pdm09 virus in pigs, Togo, 2013

    PubMed Central

    Ducatez, Mariette F.; Awoume, Félix; Webby, Richard J.

    2015-01-01

    We collected 325 nasal swabs from freshly slaughtered previously healthy pigs from October 2012 through January 2014 in a slaughterhouse near Lomé in Togo. Influenza A virus genome was detected by RT-PCR in 2.5% to 12.3% of the pooled samples, and results of hemagglutinin subtyping RT-PCR assays showed the virus in all the positive pools to be A(H1N1)pdm09. Virus was isolated on MDCK cells from a representative specimen, A/swine/Togo/ONA32/2013(H1N1). The isolate was fully sequenced and harbored 8 genes similar to A(H1N1)pdm09 virus genes circulating in humans in 2012–2013, suggesting human-to-swine transmission of the pathogen. PMID:25778544

  4. Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

    PubMed

    Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

    2016-04-01

    In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model.

  5. Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

    PubMed

    Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

    2016-04-01

    In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. PMID:26829383

  6. Oseltamivir-Resistant Influenza A(H1N1)pdm09 Viruses, United States, 2013–14

    PubMed Central

    Okomo-Adhiambo, Margaret; Fry, Alicia M.; Su, Su; Nguyen, Ha T.; Elal, Anwar Abd; Negron, Elizabeth; Hand, Julie; Garten, Rebecca J.; Barnes, John; Xiyan, Xu; Villanueva, Julie M.

    2015-01-01

    We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013–14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance–conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses. PMID:25532050

  7. Cluster analysis of the origins of the new influenza A(H1N1) virus.

    PubMed

    Solovyov, A; Palacios, G; Briese, T; Lipkin, W I; Rabadan, R

    2009-05-28

    In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia. PMID:19480812

  8. An update on swine-origin influenza virus A/H1N1: a review.

    PubMed

    Schnitzler, Sebastian U; Schnitzler, Paul

    2009-12-01

    Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1.

  9. Efficacy of Inactivated Swine Influenza Virus Vaccines Against the 2009 A/H1N1 Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species. Although its hemagglutinin gene is related to North Ameri...

  10. [Direct immunofluorescence assay performance in diagnosis of the Influenza A(H1N1) virus].

    PubMed

    Pianciola, Luis; González, Gladys; Mazzeo, Melina; Navello, Mariano; Quidel, Natalia; Bulgheroni, María Fernanda

    2010-06-01

    By 25 April 2009, less than one month after the first human with Influenza A(H1N1) virus was detected in Mexico, the disease had already spread to more than 40 countries, with over 10,000 cases reported. Due to its unpredictability, this type of virus requires appropriate, reliable, and safe diagnostic methods that are also accessible to clinical laboratories. Through the analysis of 291 samples taken from patients with suspected Influenza A(H1N1) virus infection in Neuquén, Argentina, this study compares the two diagnostic methods used simultaneously: direct immunofluorescence assay (DFA) and real-time polymerase chain reaction (RT-PCR). DFA had a sensitivity of 44.4%, a specificity of 99.6%, a positive predictive value of 95.2%, and a negative predictive value of 90.7%. Positive results obtained with this method can be considered true positives. A negative result does not rule out the presence of the virus. In this case, the sample should be examined by RT-PCR. Out of a total of 291 samples, there were 45 positive results with RT-PCR and 21 positive results with DFA.

  11. Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

    PubMed Central

    Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

    2015-01-01

    ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

  12. Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008

    PubMed Central

    Dijkstra, Frederika; Jonges, Marcel; van Beek, Ruud; Donker, Gé A; Schellevis, François G; Koopmans, Marion; van der Sande, Marianne A.B; Osterhaus, Albert D.M.E; Boucher, Charles A.B; Rimmelzwaan, Guus F; Meijer, Adam

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively. Results: Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivir resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses. Conclusion: In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter. PMID:22253652

  13. [Effect of Yinghua Pinggan granule against influenza A/H1N1 virus in vivo].

    PubMed

    Peng, Xue-qian; He, Yu; Zhou, Hui-fen; Zhang, Yu-yan; Yang, Jie-hong; Chen, Jun-kui; Lu, Yi-yu; Wan, Hai-tong

    2015-10-01

    To study the effect of Yinghua Pinggan granule (YHPG) against influenza A/H1N1 virus in vivo and on the immunologic function of infected mice. The intranasal influenza virus infection was adopted in ICR mouse to establish the influenza virus pneumonia model. At the 3rd and 7th day after the infection, the lung index and pathologic changes in lung tissues of mice were detected. Realtime PCR and flow cytometry were employed to observe the virus load in lung tissues and the levels of CD4+, CD8+, and CD4+/CD8+ in peripheral blood. The result showed that at the 3rd and 7th day after the infection, YHPG (15, 30 g x kg(-1)) can significant decrease in the lung index and virus load in lung tissues of mice infected with influenza virus, alleviate the pathologic changes in lung tissues, significantly increase the levels of CD4+ and CD4+/CD8+ ratio and reduce the levels of CD8+ in whole blood. This indicated that YHPG can inhibit the influenza virus replication, alleviate pulmonary damage and adjust the weak immunologic function of infected mice, with a certain therapeutic effect on mice infected by H1N1 virus in vivo.

  14. Impact of influenza A(H1N1)pdm09 virus on circulation dynamics of seasonal influenza strains in Kenya.

    PubMed

    Majanja, Janet; Njoroge, Rose N; Achilla, Rachel; Wurapa, Eyako K; Wadegu, Meshack; Mukunzi, Silvanos; Mwangi, Josephat; Njiri, James; Gachara, George; Bulimo, Wallace

    2013-05-01

    We describe virus variations from patients with influenza-like illness before and after the appearance of influenza A(H1N1)pdm09 in Kenya during January 2008-July 2011. A total of 11,592 nasopharyngeal swabs were collected from consenting patients. Seasonal influenza B, A/H1N1, A/H3N2, A/H5N1, and influenza A(H1N1)pdm09 viruses were detected by real-time reverse transcription-polymerase chain reaction. Of patients enrolled, 2073 (17.9%) had influenza. A total of 1,524 (73.4%) of 2,073 samples were positive for influenza A virus and 549 (26.6%) were positive for influenza B virus. Influenza B virus predominated in 2008 and seasonal A(H1N1) virus predominated in the first half of 2009. Influenza A(H1N1)pdm09 virus predominated in the second half of 2009. Influenza A/H3N2 virus predominated in 2010, and co-circulation of influenza A(H1N1)pdm09 virus and influenza B virus predominated the first half of 2011. The reduction and displacement of seasonal A(H1N1) virus was the most obvious effect of the arrival of influenza A(H1N1)pdm09 virus. The decision of the World Health Organization to replace seasonal A(H1N1) virus with the pandemic virus strain for the southern hemisphere vaccine was appropriate for Kenya.

  15. Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection

    PubMed Central

    Tse, Herman; To, Kelvin K. W.; Wen, Xi; Chen, Honglin; Chan, Kwok-Hung; Tsoi, Hoi-Wah; Li, Iris W. S.; Yuen, Kwok-Yung

    2011-01-01

    Background Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. Methodology/Principal Findings Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. Conclusion Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. PMID:21980333

  16. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    PubMed

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  17. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    PubMed

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará. PMID:27598244

  18. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases

    PubMed Central

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; de Melo, Maria Elisabeth Lisboa; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; da Silva, Luciene Alexandre Bié; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-01-01

    Abstract We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará. PMID:27598244

  19. Multiyear Persistence of 2 Pandemic A/H1N1 Influenza Virus Lineages in West Africa

    PubMed Central

    Nelson, Martha I.; Njouom, Richard; Viboud, Cecile; Niang, Mbayame N. D.; Kadjo, Hervé; Ampofo, William; Adebayo, Adedeji; Tarnagda, Zekiba; Miller, Mark A.; Holmes, Edward C.; Diop, Ousmane M.

    2014-01-01

    Our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in Africa. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009–2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. The potential for novel influenza virus lineages to evolve within Africa warrants intensified influenza surveillance in Africa and other understudied areas. PMID:24446525

  20. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.

    PubMed

    Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi

    2010-04-01

    The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the

  1. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.

    PubMed

    Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi

    2010-04-01

    The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the

  2. Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

    PubMed Central

    Wan, Hongquan; Yang, Hua; Shore, David A.; Garten, Rebecca J.; Couzens, Laura; Gao, Jin; Jiang, Lianlian; Carney, Paul J.; Villanueva, Julie; Stevens, James; Eichelberger, Maryna C.

    2015-01-01

    A(H1N1)pdm09 influenza A viruses predominated in the 2013–2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses. PMID:25668439

  3. The new pandemic influenza A/(H1N1)pdm09 virus: is it really "new"?

    PubMed

    Baldo, V; Bertoncello, C; Cocchio, S; Fonzo, M; Pillon, P; Buja, A; Baldovin, T

    2016-01-01

    In June 2009, the World Health Organization (WHO) issued a pandemic alert concerning the spread of an influenza A (H1N1) virus that showed distinctive genetic characteristics vis-à-vis both seasonal influenza strains and vaccine strains. The main mutation occurred in the gene coding for hemagglutinin (HA). Mathematical models were developed to calculate the transmissibility of the virus; the results indicated a significant overlap with the transmissibility of previous pandemic strains and seasonal strains. The remarkable feature of A/(H1N1)pdm09, compared with seasonal strains, is its high fatality rate and its higher incidence among younger people. Data provided by the WHO on the number of deaths caused by A/(H1N1)pdm09 only include laboratory-confirmed cases. Some authors suggest that these data could underestimate the magnitude of the event, as laboratory confirmation is not obtained in all cases. It is important to bear in mind that the A/(H1N1)pdm09 virus is still circulating in the population. It is therefore essential to maintain its epidemiological and virological surveillance. PMID:27346935

  4. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza. PMID:2066386

  5. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza.

  6. Productive Infection of Human Skeletal Muscle Cells by Pandemic and Seasonal Influenza A(H1N1) Viruses

    PubMed Central

    Desdouits, Marion; Munier, Sandie; Prevost, Marie-Christine; Jeannin, Patricia; Butler-Browne, Gillian; Ozden, Simona; Gessain, Antoine; Van Der Werf, Sylvie; Naffakh, Nadia; Ceccaldi, Pierre-Emmanuel

    2013-01-01

    Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients. PMID:24223983

  7. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    PubMed

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection.

  8. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    PubMed

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection. PMID:25022686

  9. Simultaneous discrimination and detection of influenza A(H1N1)pdm09 and seasonal influenza A viruses using a rapid immunogold biosensor.

    PubMed

    Apiwat, Chayachon; Wiriyachaiporn, Natpapas; Maneeprakorn, Weerakanya; Dharakul, Tararaj; Thepthai, Charin; Puthavathana, Pilaipan; Siritantikorn, Sontana; Horthongkham, Navin

    2014-07-01

    A rapid immunogold biosensor for the simultaneous discrimination of influenza A(H1N1)pdm09 and seasonal influenza A viruses was developed successfully. Monoclonal antibodies (mAbs) that were specific for the hemagglutinin protein of the A(H1N1)pdm09 virus were produced, and the best mAb pairs were selected. Using an mAb that was specific for the influenza A nucleoprotein, a rapid immunogold biosensor for the discrimination and detection of A(H1N1)pdm09/seasonal influenza viruses was developed. When tested with 72 virus isolates, the system achieved 100 % detection of the A(H1N1)pdm09 virus without cross-reactivity against seasonal influenza A (H1, H3 subtypes) and B viruses, parainfluenza viruses, respiratory syncytial viruses, and adenoviruses. The detection limits for A(H1N1)pdm09 and seasonal strains were 5 × 10(2)-7.5 × 10(3) and 1 × 10(3)-7.5 × 10(5) TCID50/mL, respectively. When tested with 49 clinical specimens, the specificity was high (100 %). The sensitivity for the detection of A(H1N1)pdm09 and seasonal strains was 90 % and 100 %, respectively, which correlated with the results of real-time reverse transcription polymerase chain reaction as a reference method. The ability of the system to detect and discriminate the A(H1N1)pdm09 strain from the seasonal strains suggests that this method may be beneficial for investigation of outbreaks and diagnostic applications. Furthermore, this method might be a useful platform for developing a rapid diagnostic system for the simultaneous discrimination of other influenza virus subtypes during future outbreaks. PMID:24402634

  10. Reassortant swine influenza viruses isolated in Japan contain genes from pandemic A(H1N1) 2009.

    PubMed

    Kanehira, Katsushi; Takemae, Nobuhiro; Uchida, Yuko; Hikono, Hirokazu; Saito, Takehiko

    2014-06-01

    In 2013, three reassortant swine influenza viruses (SIVs)-two H1N2 and one H3N2-were isolated from symptomatic pigs in Japan; each contained genes from the pandemic A(H1N1) 2009 virus and endemic SIVs. Phylogenetic analysis revealed that the two H1N2 viruses, A/swine/Gunma/1/2013 and A/swine/Ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) H1 and nucleoprotein (NP) genes derived from a classical swine H1 HA lineage uniquely circulating among Japanese SIVs; (ii) neuraminidase (NA) genes from human-like H1N2 swine viruses; and (iii) other genes from pandemic A(H1N1) 2009 viruses. The H3N2 virus, A/swine/Miyazaki/2/2013, comprised genes from two sources: (i) hemagglutinin (HA) and NA genes derived from human and human-like H3N2 swine viruses and (ii) other genes from pandemic A(H1N1) 2009 viruses. Phylogenetic analysis also indicated that each of the reassortants may have arisen independently in Japanese pigs. A/swine/Miyazaki/2/2013 were found to have strong antigenic reactivities with antisera generated for some seasonal human-lineage viruses isolated during or before 2003, whereas A/swine/Miyazaki/2/2013 reactivities with antisera against viruses isolated after 2004 were clearly weaker. In addition, antisera against some strains of seasonal human-lineage H1 viruses did not react with either A/swine/Gunma/1/2013 or A/swine/Ibaraki/1/2013. These findings indicate that emergence and spread of these reassortant SIVs is a potential public health risk.

  11. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses.

    PubMed

    Butler, Jeff; Hooper, Kathryn A; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G; McCaw, James M; Bloom, Jesse D; Hurt, Aeron C

    2014-04-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide. PMID:24699865

  12. Prevalence of Influenza A(H1N1)pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013

    PubMed Central

    Khodadad, Nastaran; Moattari, Afagh; Shamsi Shahr Abadi, Mahmoud; Kadivar, Mohammad Rahim; Sarvari, Jamal; Tavakoli, Forough; Pirbonyeh, Neda; Emami, Amir

    2015-01-01

    Background: Oseltamivir has been used as a drug of choice for the prophylaxis and treatment of human influenza A(H1N1)pdm09 infection across the world. However, the most frequently identified oseltamivir resistant virus, influenza A(H1N1)pdm09, exhibit the H275Y substitution in NA gene. Objectives: This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran. Patients and Methods: Throat swab samples were collected from 200 patients with influenza-like disease from December 2012 until February 2013. A total of 77 influenza A(H1N1)pdm09 positive strains were identified by real-time polymerase chain reaction (PCR). Oseltamivir resistance was detected using quantal assay and nested-PCR method. The NA gene sequencing was conducted to detect oseltamivir-resistant mutants and establish the phylogeny of the prevalent influenza variants. Results: Our results revealed that A(H1N1)pdm09 viruses present in these samples were susceptible to oseltamivir, and contained 5 site specific mutations (V13G, V106I, V241I, N248D, and N369K) in NA gene. These mutations correlated with increasing expression and enzymatic activity of NA protein in the influenza A(H1N1)pdm09 viruses, which were closely related to a main influenza A(H1N1)pdm09 cluster isolated around the world. Conclusions: A(H1N1)pdm09 viruses, identified in this study in Shiraz, Iran, contained 5 site specific mutations and were susceptible to oseltamivir. PMID:26464773

  13. Enhanced Pneumonia With Pandemic 2009 A/H1N1 Swine Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. Swine influenza A viruses (SIV) in the major swine producing regions of North America consist of multiple subtypes of endemic H1N1, H1N2, and H3N2 derived from swine, avian and human influenza viruses with a triple reassortant internal gene (TRIG) constellation (1). Genetic drift and r...

  14. Comparison of biological and physical properties of human and animal A(H1N1) influenza viruses.

    PubMed

    Fiszon, B; Hannoun, C; Garcia-Sastre, A; Villar, E; Cabezas, J A

    1989-01-01

    The study of biological properties of influenza virus strains belonging to the same subtype A(H1N1) and closely antigenically related, but isolated from different animal species (man, pig and duck), demonstrated that avian strains were more resistant than those isolated from mammals to high temperature and low pH, as shown by titration of residual infectivity in cell cultures (MDCK) and by sialidase assay. The difference in behaviour could be correlated to biological adaptation of the virus to its host. Avian body temperature is 40 degrees C and influenza virus, in ducks, is enterotropic and therefore capable of passing through the low pH values in the upper digestive tract of the animal. These results do not contradict the hypothesis of a possible filiation between avian and mammalian orthomyxoviruses.

  15. The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection

    PubMed Central

    2013-01-01

    Background Most illnesses caused by pandemic influenza A (H1N1) pdm09 virus (A/H1N1) infection are acute and self-limiting among children. However, in some children, disease progression is rapid and may require hospitalization and transfer to a pediatric intensive care unit (PICU). We investigated factors associated with rapid disease progression among children admitted to hospital for A/H1N1 infection, particularly findings on initial chest radiographs. Methods In this retrospective study, we investigated the records of children who had received a laboratory or clinical diagnosis of A/H1N1 infection and were admitted to the largest children’s hospital in Japan between May 2009 and March 2010. The medical records were reviewed for age, underlying diseases, vital signs on admission, initial chest radiographic findings, and clinical outcomes. According to chest radiographic findings, patients were classified into 4 groups, as follows: [1] normal (n = 46), [2] hilar and/or peribronchial markings alone (n = 64), [3] consolidation (n = 64), and [4] other findings (n = 29). Factors associated with clinical outcomes were analyzed using logistic regression. Results Two hundreds and three patients (median 6.8 years) were enrolled in this study. Fifteen percent (31/203) of patients were admitted to PICU. Among 31 patients, 39% (12/31) of patients required mechanical ventilation (MV). When the initial chest radiographic findings were compared between patients with consolidation (n = 64) and those without consolidation (n = 139), a higher percentage of patients with consolidation were admitted to PICU (29.7% vs.8.6%, P < 0.001) and required MV (17.2% vs. 0.7%, P < 0.001). These findings remain significant when the data were analyzed with the logistic regression (P < 0.001, P < 0.001, respectively). Conclusions Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection. PMID

  16. A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June-July 2009.

    PubMed

    de Silva, U C; Warachit, J; Waicharoen, S; Chittaganpitch, M

    2009-08-01

    As the influenza A(H1N1)v pandemic unfolds globally, it is vital to monitor closely for signals of change in the current patterns of transmission. We estimate the basic reproduction ratio for A(H1N1)v virus in Thailand and propose a method to keep track of the actual case count notwithstanding the exponential growth rate. PMID:19660247

  17. In vitro antiviral activity of hypothiocyanite against A/H1N1/2009 pandemic influenza virus.

    PubMed

    Cegolon, L; Salata, C; Piccoli, E; Juarez, V; Palu', G; Mastrangelo, G; Calistri, A

    2014-01-01

    Influenza virus spreads via small particle aerosols, droplets and fomites, and since it can survive for a short time on surfaces, can be introduced into the nasal mucosa before it loses infectivity. The hypothiocyanite ion (OSCN-), product of the lactoperoxidase/H2O2/SCN- system of central airways, is emerging as an important molecule for innate defense mechanism against bacteria, fungi and viruses. Here we demonstrated that OSCN(-) displays virucidal activity in vitro against the A/H1N1 2009 pandemic influenza virus. The concentration required to inhibit viral replication by 50% was 2 μM when virus were challenged directly with OSCN- before cell inoculation. These values were even lower when inoculated cells were maintained in contact with enzyme free-OSCN- in the culture medium. The last experimental conditions better reflect those of tracheobronchial mucosa, where HOSCN/OSCN- is retained in the air-liquid interface and inactivates both the viruses approaching the epithelium from outside and those released from the inoculated cells after the replication cycle. Importantly no OSCN- cytotoxicity was observed in the cellular system employed. The lack of toxicity in humans and the absence of damage on surfaces of fomites suggest a potential use of OSCN- to avoid mucosal and environmental transmission of influenza virus. Since hypothiocyanite is normally present in human airways a low risk of viral resistance is envisaged. In vivo confirmatory studies are needed to evaluate the appropriate dose, regimen and formulation.

  18. Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

    PubMed Central

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E.; Losso, Marcelo H.; Wentworth, Deborah; Cozzi-Lepri, Alessandro; Herman-Lamin, Kathy; Cholewinska, Grazyna; David, Daniel; Kuetter, Stefan; Ternesgen, Zelalem; Uyeki, Timothy M.; Lane, H. Clifford; Lundgren, Jens; Neaton, James D.

    2014-01-01

    Background Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. Methods and Findings Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. Conclusions Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic

  19. Point of Care Strategy for Rapid Diagnosis of Novel A/H1N1 Influenza Virus

    PubMed Central

    Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Gazin, Celine; Drancourt, Michel; La Scola, Bernard; Raoult, Didier; Charrel, Remi N.

    2010-01-01

    Background Within months of the emergence of the novel A/H1N1 pandemic influenza virus (nA/H1N1v), systematic screening for the surveillance of the pandemic was abandoned in France and in some other countries. At the end of June 2009, we implemented, for the public hospitals of Marseille, a Point Of Care (POC) strategy for rapid diagnosis of the novel A/H1N1 influenza virus, in order to maintain local surveillance and to evaluate locally the kinetics of the pandemic. Methodology/Principal Findings Two POC laboratories, located in strategic places, were organized to receive and test samples 24 h/24. POC strategy consisted of receiving and processing naso-pharyngeal specimens in preparation for the rapid influenza diagnostic test (RIDT) and real-time RT-PCR assay (rtRT-PCR). This strategy had the theoretical capacity of processing up to 36 samples per 24 h. When the flow of samples was too high, the rtRT-PCR test was abandoned in the POC laboratories and transferred to the core virology laboratory. Confirmatory diagnosis was performed in the core virology laboratory twice a day using two distinct rtRT-PCR techniques that detect either influenza A virus or nA/N1N1v. Over a period of three months, 1974 samples were received in the POC laboratories, of which 111 were positive for nA/H1N1v. Specificity and sensitivity of RIDT were 100%, and 57.7% respectively. Positive results obtained using RIDT were transmitted to clinical practitioners in less than 2 hours. POC processed rtRT-PCR results were available within 7 hours, and rtRT-PCR confirmation within 24 hours. Conclusions/Significance The POC strategy is of benefit, in all cases (with or without rtRT-PCR assay), because it provides continuous reception/processing of samples and reduction of the time to provide consolidated results to the clinical practitioners. We believe that implementation of the POC strategy for the largest number of suspect cases may improve the quality of patient care and our knowledge of the

  20. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1) Virus Impairs the Human T Cell Response

    PubMed Central

    Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus. PMID:24187568

  1. PD-L1 expression induced by the 2009 pandemic influenza A(H1N1) virus impairs the human T cell response.

    PubMed

    Valero-Pacheco, Nuriban; Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8⁺ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8⁺ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus.

  2. Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy

    PubMed Central

    2010-01-01

    A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population. PMID:20738882

  3. Sudden death of a patient with pandemic influenza (A/H1N1pdm) virus infection by acute respiratory distress syndrome.

    PubMed

    Takiyama, Akihiro; Wang, Lei; Tanino, Mishie; Kimura, Taichi; Kawagishi, Naoki; Kunieda, Yasuyuki; Katano, Harutaka; Nakajima, Noriko; Hasegawa, Hideki; Takagi, Tomoyuki; Nishihara, Hiroshi; Sata, Tetsutaro; Tanaka, Shinya

    2010-01-01

    We describe an autopsy case of a patient with pandemic influenza (A/H1N1pdm) virus infection in Japan, who developed rapidly progressive viral pneumonia exhibiting diffuse alveolar damage. A 41-year-old female visited our hospital with a fever of 38.7C. She was a public health nurse with no underlying disease and had had contact with a group of elementary school students who had been infected with the influenza (A/H1N1pdm) virus 1 week earlier. She was prescribed oseltamivir and returned to the hotel where she was staying alone. The next day, she was found dead in her hotel room. At autopsy, both lungs were voluminous and microscopic examination revealed acute-stage, severe diffuse alveolar damage with remarkable mononuclear cell infiltration and hyaline membrane formation in the lungs. CD8-positive T lymphocytes were dominantly observed. Immunohistochemically, influenza A viral protein was confirmed in the damaged type II pneumocytes and also in the infiltrated macrophages. Real-time RT-PCR analysis of both pre- and post-mortem pharyngeal swabs confirmed a novel influenza (A/H1N1pdm) virus infection. This is the second autopsy case of influenza (A/H1N1pdm) virus infection in Japan, and the findings indicated that the patient died due to an exceptionally rapid progression of viral pneumonia. This case indicates that patients with influenza (A/H1N1pdm) virus infection should be carefully monitor for acute respiratory distress syndrome. PMID:20093769

  4. Reduced replication capacity of influenza A(H1N1)pdm09 virus during the 2010-2011 winter season in Tottori, Japan.

    PubMed

    Tsuneki, Akeno; Itagaki, Asao; Tsuchie, Hideaki; Tokuhara, Misato; Okada, Takayoshi; Narai, Sakae; Kasagi, Masaaki; Tanaka, Kiyoshi; Kageyama, Seiji

    2013-11-01

    A novel swine-origin influenza A(H1N1)pdm09 virus has been circulating in humans since March-April, 2009. The 2009-2010 epidemic involved predominantly a single subtype of A(H1N1)pdm09 (at 96%, 46/48) in the sentinel sites of this study. However, A(H1N1)pdm09 started to circulate together with other type/subtype (49%, 33/68) at the first peak in the next epidemic season in 2010-2011: A(H1N1)pdm09/A(H3N2) (9%, 6/68), A(H1N1)pdm09/B (35%, 24/68), and A(H1N1)pdm09/A(H3N2)/B (4%, 3/68). Single infection of A(H1N1)pdm09 became a rare event (8%, 5/65) at the second peak of the same season in 2010-2011 compared with that at the first peak (50%, 34/68). Concurrently with this decline, single infections of others, A(H3N2) or B, became evident (6%, 4/65; 14%, 9/65, respectively). Triple infections were more common (29%, 19/65) at the second peak than at the first peak (4%). The A(H1N1)pdm09 detected in 2010-2011 produced less virus upon 72 hr of incubation in vitro after the inoculations at 10(4) and 3,300 copies/ml (2.3 × 10(9) and 2.3 × 10(9) copies/ml on average) than that in 2009-2010 (3.7 × 10(9) and 1.3 × 10(10) copies/ml on average; P<0.05 by ANOVA test), respectively. As described above, the replication capacity of A(H1N1)pdm09 seems to have deteriorated in the 2010-2011 season presumably due to substantial herd immunity and allowed the existence of other type/subtype. These results suggest that assessment of replication capacity is indispensable for analysis of influenza epidemics.

  5. Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic.

    PubMed

    Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S

    2016-09-01

    Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

  6. Guillain-Barre syndrome, influenzalike illnesses, and influenza vaccination during seasons with and without circulating A/H1N1 viruses.

    PubMed

    Grimaldi-Bensouda, Lamiae; Alpérovitch, Annick; Besson, Gérard; Vial, Christophe; Cuisset, Jean-Marie; Papeix, Caroline; Lyon-Caen, Olivier; Benichou, Jacques; Rossignol, Michel

    2011-08-01

    The role of influenzalike illnesses and influenza vaccination in the development of Guillain-Barré syndrome (GBS), particularly the role of A/H1N1 epidemics and A/H1N1 vaccination, is debated. Data on all incident GBS cases meeting the Brighton Collaboration criteria that were diagnosed at 25 neurology centers in France were prospectively collected between March 2007 and June 2010, covering 3 influenzavirus seasons, including the 2009-2010 A/H1N1 outbreak. A total of 457 general practitioners provided a registry of patients from which 1,080 controls were matched by age, gender, index date (calendar month), and region to 145 cases. Causal relations were assessed by multivariate case-control analysis with adjustment for risk factors (personal and family history of autoimmune disorders, among others), while matching on age, gender, and calendar time. Influenza (seasonal or A/H1N1) or influenzalike symptoms in the 2 months preceding the index date was associated with GBS, with a matched odds ratio of 2.3 (95% confidence interval (CI): 0.7, 8.2). The difference in the rates of GBS occurring between influenza virus circulation periods and noncirculation periods was highly statistically significant (P = 0.004). Adjusted odds ratios for GBS occurrence within 6 weeks after seasonal and A/H1N1 vaccination were 1.3 (95% CI: 0.4, 4.1) and 0.9 (95% CI: 0.1, 7.6), respectively. Study results confirm that influenza virus is a likely risk factor for GBS. Conversely, no new concerns have arisen regarding influenza vaccination.

  7. Biological characteristics of influenza A(H1N1)pdm09 virus circulating in West Siberia during pandemic and post-pandemic periods.

    PubMed

    Prokop'eva, E A; Kurskaya, O G; Saifutdinova, S G; Glushchenko, A V; Shestopalova, L V; Shestopalov, A M; Shkurupii, V A

    2014-03-01

    We studied biological characteristics of influenza A(H1N1)pdm09 virus circulating in Siberia during the 2009 pandemic and the post-pandemic period of 2011. BALB/c mice were chosen as the experimental model. Virus titers in the lungs were evaluated on days 1, 3, 6 and blood serum titers on day 15 after infection with different strains. Blood sera of convalescents after influenza of 2010-2011 epidemic season were analyzed. Influenza A(H1N1)pdm09 virus strains isolated during the post-pandemic period of 2011 were characterized by low epidemic activity and virulence in comparison with the strains isolated during 2009 pandemic period, which indicates completion of the pandemic cycle.

  8. Whole genome characterization of human influenza A(H1N1)pdm09 viruses isolated from Kenya during the 2009 pandemic.

    PubMed

    Gachara, George; Symekher, Samuel; Otieno, Michael; Magana, Japheth; Opot, Benjamin; Bulimo, Wallace

    2016-06-01

    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.

  9. Serum antibody response to matrix protein 2 following natural infection with 2009 pandemic influenza A(H1N1) virus in humans.

    PubMed

    Zhong, Weimin; Reed, Carrie; Blair, Patrick J; Katz, Jacqueline M; Hancock, Kathy

    2014-04-01

    Natural infection-induced humoral immunity to matrix protein 2 (M2) of influenza A viruses in humans is not fully understood. Evidence suggests that anti-M2 antibody responses following influenza A virus infection are weak and/or transient. We show that the seroprevalence of anti-M2 antibodies increased with age in 317 serum samples from healthy individuals in the United States in 2007-2008. Infection with 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) elicited a recall serum antibody response to M2 protein of A(H1N1)pdm09 in 47% of the affected 118 individuals tested. Anti-M2 antibody responses were more robust among individuals with preexisting antibodies to M2 protein. Moreover, the antibodies induced as a result of infection with A(H1N1)pdm09 were cross-reactive with M2 protein of seasonal influenza A viruses. These results emphasize the need to further investigate the possible roles of anti-M2 antibodies in human influenza A virus infection. PMID:24325965

  10. Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

    PubMed

    Russo, Mara L; Pontoriero, Andrea V; Benedetti, Estefania; Czech, Andrea; Avaro, Martin; Periolo, Natalia; Campos, Ana M; Savy, Vilma L; Baumeister, Elsa G

    2014-12-01

    This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed

  11. Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age.

    PubMed

    Fielding, James E; Kelly, Heath A; Mercer, Geoffry N; Glass, Kathryn

    2014-03-01

    Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.

  12. Production impact of influenza A(H1N1)pdm09 virus infection on fattening pigs in Norway.

    PubMed

    Er, Chiek; Skjerve, Eystein; Brun, Edgar; Hofmo, Peer Ola; Framstad, Tore; Lium, Bjørn

    2016-02-01

    Newly emerged influenza A(H1N1)pdm09 virus infection in Norwegian pigs, although often observed in a subclinical form, can lower the pig's growth performance by reducing feed efficiency in terms of a poorer feed conversion ratio. Infected pigs would consume more feed and require protracted production time to reach market weight. In our observational longitudinal study, growth performance data from 728 control pigs and 193 infected pigs with known viral shedding time points were analyzed using mixed linear regression models to give estimates of the marginal effects of infection. Gaussian curves describing the variability of the estimates at the individual pig level formed the fundamental inputs to our stochastic models. The models were constructed to simulate the summed negative effects of the infection at the batch level of 150 fattening pigs growing from 33 to 100 kg. Other inputs of variability and uncertainty were 1) batch transmission points, 2) pig infection points to reflect the disease transmission dynamics of the virus, and 3) final prevalence of infected pigs in the batch. Monte Carlo random sampling gave 5,000 estimates on the outputs of the marginal effects for each pig. These results were summed up to provide estimates for a batch size of 150 pigs. This figure was adjusted by our final prevalence distribution function, which was also derived from the longitudinal study with 12 cohorts of infected pigs. For a 150-fattening-pig herd randomly selected from the population, the marginal effects of the infection were 1) 835 kg (fifth percentile) to 1,350 kg (95th percentile) increased feed intake and 2) 194 (fifth percentile) to 334 (95th percentile) pig days in excess of expected figures for an uninfected batch. A batch infected during growth phase 3 (81 to 100 kg BW) gave the worst results since the longitudinal study showed that a pig infected during growth phase 3 required more feed and a greater protracted production time compared to younger infected

  13. Assessing Antigenic Drift of Seasonal Influenza A(H3N2) and A(H1N1)pdm09 Viruses.

    PubMed

    Tewawong, Nipaporn; Prachayangprecha, Slinporn; Vichiwattana, Preeyaporn; Korkong, Sumeth; Klinfueng, Sirapa; Vongpunsawad, Sompong; Thongmee, Thanunrat; Theamboonlers, Apiradee; Poovorawan, Yong

    2015-01-01

    Under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (HA) have continually evolved to escape antibody recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2) and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. We amplified and sequenced the HA gene of 120 A(H3N2) and 81 A(H1N1)pdm09 influenza virus samples obtained from respiratory specimens and calculated the perfect-match vaccine efficacy using the pepitope model, which quantitated the antigenic drift in the dominant epitope of HA. Phylogenetic analysis of the A(H3N2) HA1 genes classified most strains into genetic clades 1, 3A, 3B, and 3C. The A(H3N2) strains from the 2013 and 2014 seasons showed very low to moderate vaccine efficacy and demonstrated antigenic drift from epitopes C and A to epitope B. Meanwhile, most A(H1N1)pdm09 strains from the 2012-2014 seasons belonged to genetic clades 6A, 6B, and 6C and displayed the dominant epitope mutations at epitopes B and E. Finally, the vaccine efficacy for A(H1N1)pdm09 (79.6-93.4%) was generally higher than that of A(H3N2). These findings further confirmed the accelerating antigenic drift of the circulating influenza A(H3N2) in recent years.

  14. [Detection of conservative and variable epitopes of the pandemic influenza virus A(H1N1)pdm09 hemagglutinin using monoclonal antibodies].

    PubMed

    Masalova, O V; Chichev, E V; Fediakina, I T; Mukasheva, E A; Klimova, R R; Shchelkanov, M Iu; Burtseva, E I; Ivanova, V T; Kushch, A A; L'vov, D K

    2014-01-01

    The goal of this work was to analyze the antigenic structure of the hemagglutinin (HA) of the pandemic influenza virus A(H1N1)pdm09 using monoclonal antibodies (MAbs) and to develop a sandwich ELISA for identification of pandemic strains. Competitive ELISA demonstrated that 6 MAbs against HA of the pandemic influenza A/ IIV-Moscow/01/2009 (H1N1)pdm09 virus identified six epitopes. Binding of MAbs with 22 strains circulating in Russian Federation during 2009-2012 was analyzed in the hemagglutination-inhibition test (HI). The MAbs differed considerably in their ability to decrease the HI activity of these strains. MAb 5F7 identified all examined strains; MAbs 3A3 and 10G2 reacted with the majority of them. A highly sensitive sandwich ELISA was constructed based on these three MAbs that can differentiate the pandemic influenza strains from the seasonal influenza virus. The constancy of the HA epitope that reacts with MAb 5F7 provides its use for identification of the pandemic influenza strains in HI test. MAbs 3D9, 6A3 and 1E7 are directed against the variable HA epitopes, being sensitive to several amino acid changes in Sa, Sb, and Ca2 antigenic sites and in receptor binding site. These MAbs can be used to detect differences in HA structure and to study the antigenic drift of the pandemic influenza virus A(H1N1)pdm09.

  15. Inactivated Seasonal Influenza Vaccines Increase Serum Antibodies to the Neuraminidase of Pandemic Influenza A(H1N1) 2009 Virus in an Age-Dependent Manner

    PubMed Central

    Marcelin, Glendie; Bland, Hilliary M.; Negovetich, Nicholas J.; Sandbulte, Matthew R.; Ellebedy, Ali H.; Webb, Ashley D.; Griffin, Yolanda S.; DeBeauchamp, Jennifer L.; McElhaney, Janet E.; Webby, Richard J.

    2010-01-01

    Levels of preexisting antibodies to the hemagglutinin of pandemic influenza A(H1N1) 2009 (hereafter pandemic H1N1) virus positively correlate with age. The impact of contemporary seasonal influenza vaccines on establishing immunity to other pandemic H1N1 proteins is unknown. We measured serum antibodies to the neuraminidase (NA) of pandemic H1N1 in adults prior to and after vaccination with seasonal trivalent inactivated influenza vaccines. Serum antibodies to pandemic H1N1 NA were observed in all age groups; however, vaccination elevated levels of pandemic H1N1 NA antibodies predominately in elderly individuals (age,⩾60 years). Therefore, contemporary seasonal vaccines likely contribute to reduction of pandemic H1N1-associated disease in older individuals. PMID:20979454

  16. In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses.

    PubMed

    Sleeman, Katrina; Mishin, Vasiliy P; Deyde, Varough M; Furuta, Yousuke; Klimov, Alexander I; Gubareva, Larisa V

    2010-06-01

    Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 muM (0.5 microg/ml) (50% effective concentrations [EC(50)s] of 0.19 to 22.48 muM and 0.03 to 3.53 microg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 muM (0.5 microg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs.

  17. The Association between Serum Biomarkers and Disease Outcome in Influenza A(H1N1)pdm09 Virus Infection: Results of Two International Observational Cohort Studies

    PubMed Central

    Davey, Richard T.; Lynfield, Ruth; Dwyer, Dominic E.; Losso, Marcello H.; Cozzi-Lepri, Alessandro; Wentworth, Deborah; Lane, H. Clifford; Dewar, Robin; Rupert, Adam; Metcalf, Julia A.; Pett, Sarah L.; Uyeki, Timothy M.; Bruguera, Jose Maria; Angus, Brian; Cummins, Nathan; Lundgren, Jens; Neaton, James D.

    2013-01-01

    Background Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. Methods Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified. Results In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3rd versus 1st tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3rd versus 1st tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only. Conclusions In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or

  18. Reassortment and mutations associated with emergence and spread of oseltamivir-resistant seasonal influenza A/H1N1 viruses in 2005-2009.

    PubMed

    Yang, Ji-Rong; Lin, Yu-Cheng; Huang, Yuan-Pin; Su, Chun-Hui; Lo, Je; Ho, Yu-Lin; Yao, Ching-Yuan; Hsu, Li-Ching; Wu, Ho-Sheng; Liu, Ming-Tsan

    2011-01-01

    A dramatic increase in the frequency of the H275Y mutation in the neuraminidase (NA), conferring resistance to oseltamivir, has been detected in human seasonal influenza A/H1N1 viruses since the influenza season of 2007-2008. The resistant viruses emerged in the ratio of 14.3% and quickly reached 100% in Taiwan from September to December 2008. To explore the mechanisms responsible for emergence and spread of the resistant viruses, we analyzed the complete genome sequences of 25 viruses collected during 2005-2009 in Taiwan, which were chosen from various clade viruses, 1, 2A, 2B-1, 2B-2, 2C-1 and 2C-2 by the classification of hemagglutinin (HA) sequences. Our data revealed that the dominant variant, clade 2B-1, in the 2007-2008 influenza emerged through an intra-subtype 4+4 reassortment between clade 1 and 2 viruses. The dominant variant acquired additional substitutions, including A206T in HA, H275Y and D354G in NA, L30R and H41P in PB1-F2, and V411I and P453S in basic polymerase 2 (PB2) proteins and subsequently caused the 2008-2009 influenza epidemic in Taiwan, accompanying the widespread oseltamivir-resistant viruses. We also characterized another 3+5 reassortant virus which became double resistant to oseltamivir and amantadine. Comparison of oseltamivir-resistant influenza A/H1N1 viruses belonging to various clades in our study highlighted that both reassortment and mutations were associated with emergence and spread of these viruses and the specific mutation, H275Y, conferring to antiviral resistance, was acquired in a hitch-hiking mechanism during the viral evolutionary processes. PMID:21483816

  19. Serologic evidence of influenza A(H1N1)pdm09 virus in northern sea otters

    USGS Publications Warehouse

    Li, Zhu-Nan; Ip, Hon S.; Frost, Jessica F.; White, C. LeAnn; Murray, Michael J.; Carney, Paul J.; Sun, Xiang-Jie; Stevens, James; Levine, Min Z.; Katz, Jacqueline M.

    2014-01-01

    Sporadic epizootics of pneumonia among marine mammals have been associated with multiple animal-origin influenza A virus subtypes (1–6); seals are the only known nonhuman host for influenza B viruses (7). Recently, we reported serologic evidence of influenza A virus infection in free-ranging northern sea otters (Enhydra lutris kenyoni) captured off the coast of Washington, USA, in August 2011 (8). To investigate further which influenza A virus subtype infected these otters, we tested serum samples from these otters by ELISA for antibody-binding activity against 12 recombinant hemagglutinins (rHAs) from 7 influenza A hemagglutinin (HA) subtypes and 2 lineages of influenza B virus (Technical Appendix Table 1). Estimated ages for the otters were 2–19 years (Technical Appendix Table 2); we also tested archived serum samples from sea otters of similar ages collected from a study conducted during 2001–2002 along the Washington coast (9).

  20. Protection by face masks against influenza A(H1N1)pdm09 virus on trans-Pacific passenger aircraft, 2009.

    PubMed

    Zhang, Lijie; Peng, Zhibin; Ou, Jianming; Zeng, Guang; Fontaine, Robert E; Liu, Mingbin; Cui, Fuqiang; Hong, Rongtao; Zhou, Hang; Huai, Yang; Chuang, Shuk-Kwan; Leung, Yiu-Hong; Feng, Yunxia; Luo, Yuan; Shen, Tao; Zhu, Bao-Ping; Widdowson, Marc-Alain; Yu, Hongjie

    2013-01-01

    In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0-0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect.

  1. Mutation Analysis of 2009 Pandemic Influenza A(H1N1) Viruses Collected in Japan during the Peak Phase of the Pandemic

    PubMed Central

    Morlighem, Jean-Étienne; Aoki, Shintaro; Kishima, Mami; Hanami, Mitsue; Ogawa, Chihiro; Jalloh, Amadu; Takahashi, Yukari; Kawai, Yuki; Saga, Satomi; Hayashi, Eiji; Ban, Toshiaki; Izumi, Shinyu; Wada, Akira; Mano, Masayuki; Fukunaga, Megumu; Kijima, Yoshiyuki; Shiomi, Masashi; Inoue, Kaoru; Hata, Takeshi; Koretsune, Yukihiro; Kudo, Koichiro; Himeno, Yuji; Hirai, Aizan; Takahashi, Kazuo; Sakai-Tagawa, Yuko; Iwatsuki-Horimoto, Kiyoko; Kawaoka, Yoshihiro; Hayashizaki, Yoshihide; Ishikawa, Toshihisa

    2011-01-01

    Background Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges. Methodology A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations. Results and Conclusions Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo. PMID:21572517

  2. The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces.

    PubMed

    Oxford, John; Berezin, Eitan N; Courvalin, Patrice; Dwyer, Dominic E; Exner, Martin; Jana, Laura A; Kaku, Mitsuo; Lee, Christopher; Letlape, Kgosi; Low, Donald E; Madani, Tariq Ahmed; Rubino, Joseph R; Saini, Narendra; Schoub, Barry D; Signorelli, Carlo; Tierno, Philip M; Zhong, Xuhui

    2014-04-01

    We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.

  3. The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces.

    PubMed

    Oxford, John; Berezin, Eitan N; Courvalin, Patrice; Dwyer, Dominic E; Exner, Martin; Jana, Laura A; Kaku, Mitsuo; Lee, Christopher; Letlape, Kgosi; Low, Donald E; Madani, Tariq Ahmed; Rubino, Joseph R; Saini, Narendra; Schoub, Barry D; Signorelli, Carlo; Tierno, Philip M; Zhong, Xuhui

    2014-04-01

    We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission. PMID:24679569

  4. Amino acid substitution D222N from fatal influenza infection affects receptor-binding properties of the influenza A(H1N1)pdm09 virus.

    PubMed

    Matos-Patrón, Adriana; Byrd-Leotis, Lauren; Steinhauer, David A; Barclay, Wendy S; Ayora-Talavera, Guadalupe

    2015-10-01

    We have analyzed the receptor binding profile of A(H1N1)pdm09 recombinant influenza viruses containing the amino acid substitution D222N which has been associated with a fatal case of infection. This mutation was investigated in conjunction with a secondary mutation, S185N. Using human tracheobronchial epithelial cells (HTBE), we found that single mutation D222N affects the binding and replication of the virus during initial stages of infection, with limited but preferred tropism to non-ciliated cells expressing α2,6-SA. However, in conjunction with the S185N change, the (D222N, S185N) virus shows a remarkable increase in binding and replication efficiency, with tropism for both ciliated and non-ciliated cells. Glycan microarray analysis demonstrated correlation between the binding profile and the cell tropism observed in the HTBE cells. These findings suggest that viruses with D222N required compensatory mutations such as S185N to maintain viral fitness, and in combination, affect the pathogenicity of the virus and the clinical outcome.

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

    PubMed

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

    2011-09-01

    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.

  6. Punctuated Evolution of Influenza Virus Neuraminidase (A/H1N1) under Opposing Migration and Vaccination Pressures

    PubMed Central

    Phillips, J. C.

    2014-01-01

    Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Here we focus first on the simpler problem of the much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. Our thermodynamic panorama shows that very small amino acid changes can be monitored very accurately across many historic (1945–2011) Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the fractal differential hydropathicity scale based on protein self-organized criticality (SOC). Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in common influenza severity in the last century. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses directly from amino acid sequences alone. An engineered strain of NA1 is described which could well be significantly less virulent than current circulating strains. PMID:25143953

  7. Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets.

    PubMed

    Bosch, Berend Jan; Bodewes, Rogier; de Vries, Robert P; Kreijtz, Joost H C M; Bartelink, Willem; van Amerongen, Geert; Rimmelzwaan, Guus F; de Haan, Cornelis A M; Osterhaus, Albert D M E; Rottier, Peter J M

    2010-10-01

    The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA(3)) and NA (sNA(4)) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-microg doses of these antigens elicited strong antibody responses, which were adjuvant dependent. Interestingly, coadministration of both antigens strongly enhanced the HA-specific but not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA(3) dramatically reduced virus replication (e.g., by lowering pulmonary titers by about 5 log(10) units), immunization with sNA(4) markedly decreased the clinical effects of infection, such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly, and safely produced in high quantities. In particular, our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.

  8. Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

    PubMed Central

    Harvey, William T.; Benton, Donald J.; Gregory, Victoria; Hall, James P. J.; Daniels, Rodney S.; Bedford, Trevor; Haydon, Daniel T.; Hay, Alan J.; McCauley, John W.; Reeve, Richard

    2016-01-01

    Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. PMID:27057693

  9. Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses.

    PubMed

    Harvey, William T; Benton, Donald J; Gregory, Victoria; Hall, James P J; Daniels, Rodney S; Bedford, Trevor; Haydon, Daniel T; Hay, Alan J; McCauley, John W; Reeve, Richard

    2016-04-01

    Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997-2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. PMID:27057693

  10. Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses.

    PubMed

    Harvey, William T; Benton, Donald J; Gregory, Victoria; Hall, James P J; Daniels, Rodney S; Bedford, Trevor; Haydon, Daniel T; Hay, Alan J; McCauley, John W; Reeve, Richard

    2016-04-01

    Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997-2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens.

  11. Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus

    PubMed Central

    Rith, Sareth; Chin, Savuth; Sar, Borann; Y, Phalla; Horm, Srey Viseth; Ly, Sovann; Buchy, Philippe; Dussart, Philippe; Horwood, Paul F.

    2015-01-01

    Background Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. Study design We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. Results Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 104/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. Conclusions It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. PMID:26590689

  12. Pathogenesis and transmission of the novel swine-origin influenza virus A/H1N1 after experimental infection of pigs.

    PubMed

    Lange, Elke; Kalthoff, Donata; Blohm, Ulrike; Teifke, Jens P; Breithaupt, Angele; Maresch, Christina; Starick, Elke; Fereidouni, Sasan; Hoffmann, Bernd; Mettenleiter, Thomas C; Beer, Martin; Vahlenkamp, Thomas W

    2009-09-01

    Influenza virus A/H1N1, which is currently causing a pandemic, contains gene segments with ancestors in the North American and Eurasian swine lineages. To get insights into virus replication dynamics, clinical symptoms and virus transmission in pigs, we infected animals intranasally with influenza virus A/Regensburg/D6/09/H1N1. Virus excretion in the inoculated pigs was detected in nasal swabs from 1 day post-infection (p.i.) onwards and the pigs developed generally mild symptoms, including fever, sneezing, nasal discharge and diarrhoea. Contact pigs became infected, shed virus and developed clinical symptoms similar to those in the inoculated animals. Plasma samples of all animals remained negative for virus RNA. Nucleoprotein- and haemagglutinin H1-specific antibodies could be detected by ELISA 7 days p.i. CD4(+) T cells became activated immediately after infection and both CD4(+) and CD8(+) T-cell populations expanded from 3 to 7 days p.i., coinciding with clinical signs. Contact chickens remained uninfected, as judged by the absence of virus excretion, clinical signs and seroconversion.

  13. Proteinquakes in the Evolution of Influenza Virus Hemagglutinin (A/H1N1) under Opposing Migration and Vaccination Pressures

    PubMed Central

    Phillips, J. C.

    2015-01-01

    Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Here we show that, while HA evolution is much more complex than NA evolution, it still shows abrupt punctuation changes linked to punctuation changes of NA. HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions. HA proteinquakes based on shifting sialic acid interactions are required for optimal balance between the receptor-binding and receptor-destroying activities of HA and NA for efficient virus replication. Our comprehensive results present a historical (1945–2011) panorama of HA evolution over thousands of strains and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains. PMID:25654090

  14. Influenza vaccine effectiveness estimates in Croatia in 2010-2011: a season with predominant circulation of A(H1N1)pdm09 influenza virus.

    PubMed

    Kurečić Filipović, S; Gjenero-Margan, I; Kissling, E; Kaić, B; Cvitković, A

    2015-09-01

    This is a retrospective study using the test-negative case-control method to estimate seasonal 2010-2011 influenza vaccine effectiveness (VE) in Croatia. Of patients consulting a physician for influenza-like illness (ILI) and for whom a swab was taken, we compared RT-PCR influenza-positive and RT-PCR influenza-negative patients. We used a structured questionnaire and physicians' records to obtain information on vaccination status and potential confounders. We conducted a complete case analysis using logistic regression to measure adjusted VE overall, against A(H1N1)pdm09 and in age groups. Out of 785 interviewed patients, 495 eligible patients were included in the study, after applying exclusion criteria [217 cases, of which 92·6% were A(H1N1)pdm09 positive, 278 controls]. Crude VE was 31·9% [95% confidence interval (CI) -40·9 to 67·1] and adjusted VE was 20·7% (95% CI -71·4 to 63·3), with higher VE in youngest and oldest age groups. Results from this first VE study in Croatia suggest a low to moderate VE for the 2010-2011 season. Studies year on year are needed with a greater sample size to provide more precise estimates, and also by age group and risk groups for vaccination.

  15. Characteristic amino acid changes of influenza A(H1N1)pdm09 virus PA protein enhance A(H7N9) viral polymerase activity.

    PubMed

    Liu, Jun; Huang, Feng; Zhang, Junsong; Tan, Likai; Lu, Gen; Zhang, Xu; Zhang, Hui

    2016-06-01

    Human coinfection with a novel H7N9 influenza virus and the 2009 pandemic A(H1N1) influenza virus, H1N1pdm09, has recently been reported in China. Because reassortment can occur during coinfection, it is necessary to clarify the effects of gene reassortment between these two viruses. Among the viral ribonucleoprotein complex (vRNP) genes, only the PA gene of H1N1pdm09 enhances the avian influenza viral polymerase activity. Based on a phylogenetic analysis, we show a special evolutionary feature of the H1N1pdm09 PA gene, which clustered with those of the novel H7N9 virus and related H9N2 viruses, rather than in the outgroup as the H1N1pdm09 genes do on the phylogenetic trees of other vRNP genes. Using a minigenome system of the novel H7N9 virus, we further demonstrate that replacement of its PA gene significantly enhanced its polymerase activity, whereas replacement of the other vRNP genes reduced its polymerase activity. We also show that the residues of PA evolutionarily conserved between H1N1pdm09 and the novel H7N9 virus are associated with attenuated or neutral polymerase activity. The mutations associated with the increased activity of the novel H7N9 polymerase are characteristic of the H1N1pdm09 gene, and are located almost adjacent to the surface of the PA protein. Our results suggest that the novel H7N9 virus has more effective PB1, PB2, and NP genes than H1N1pdm09, and that H1N1pdm09-like PA mutations enhance the novel H7N9 polymerase function.

  16. Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates

    PubMed Central

    Belanov, Sergei S.; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E.

    2015-01-01

    Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009–2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009–2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates. PMID:26615216

  17. Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates.

    PubMed

    Belanov, Sergei S; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E

    2015-11-27

    Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates.

  18. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    PubMed Central

    Faverio, Paola; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage. PMID:25383078

  19. Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults

    PubMed Central

    Atmar, Robert L.; Franco, Luis M.; Quarles, John M.; Niño, Diane; Wells, Janet M.; Arden, Nancy; Cheung, Sheree; Belmont, John W.

    2012-01-01

    Background. A new influenza A/H1N1 (pH1N1) virus emerged in April 2009, proceeded to spread worldwide, and was designated as an influenza pandemic. A/H1N1 viruses had circulated in 1918–1957 and 1977–2009 and were in the annual vaccine during 1977–2009. Methods. Serum antibody to the pH1N1 and seasonal A/H1N1 viruses was measured in 579 healthy adults at enrollment (fall 2009) and after surveillance for illness (spring 2010). Subjects reporting with moderate to severe acute respiratory illness had illness and virus quantitation for 1 week; evaluations for missed illnesses were conducted over holiday periods and at the spring 2010 visit. Results. After excluding 66 subjects who received pH1N1 vaccine, 513 remained. Seventy-seven had reported with moderate to severe illnesses; 31 were infected with pH1N1 virus, and 30 with a rhinovirus. Determining etiology from clinical findings was not possible, but fever and prominent myalgias favored influenza and prominent rhinorrhea favored rhinovirus. Tests of fall and spring antibody indicated pH1N1 infection of 23% had occurred, with the rate decreasing with increasing anti-pH1N1 antibody; a similar pattern was seen for influenza-associated illness. A reducing frequency of pH1N1 infections was also seen with increasing antibody to the recent seasonal A/H1N1 virus (A/Brisbane/59/07). Preexisting antibody to pH1N1 virus, responses to a single vaccine dose, a low infection-to-illness ratio, and a short duration of illness and virus shedding among those with influenza indicated presence of considerable preexisting immunity to pH1N1 in the population. Conclusions. The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses. PMID:22075792

  20. Protein profiling of nasopharyngeal aspirates of hospitalized and outpatients revealed cytokines associated with severe influenza A(H1N1)pdm09 virus infections: A pilot study.

    PubMed

    Fu, Yu; Gaelings, Lana; Jalovaara, Petri; Kakkola, Laura; Kinnunen, Mervi T; Kallio-Kokko, Hannimari; Valkonen, Miia; Kantele, Anu; Kainov, Denis E

    2016-10-01

    Influenza A viruses (IAV) mutate rapidly and cause seasonal epidemics and occasional pandemics, which result in substantial number of patient visits to the doctors and even hospitalizations. We aimed here to identify inflammatory proteins, which levels correlated to clinical severity of the disease. For this we analysed 102 cytokines and growth factors in human nasopharyngeal aspirate (NPA) samples of 27 hospitalized and 27 outpatients diagnosed with influenza A(H1N1)pdm09 virus infection. We found that the relative levels of monocyte differentiation antigen CD14, lipocalin-2 (LCN2), C-C-motif chemokine 20 (CCL20), CD147, urokinase plasminogen activator surface receptor (uPAR), pro-epidermal growth factor (EGF), trefoil factor 3 (TFF3), and macrophage migration inhibitory factor (MIF) were significantly lower (p<0.008), whereas levels of retinol-binding protein 4 (RBP4), C-X-C motif chemokine 5 (CXCL5), interleukin-8 (IL-8), complement factor D (CFD), adiponectin, and chitinase-3-like 1 (CHI3L1) were significantly higher (p<0.008) in NPA samples of hospitalized than non-hospitalized patients. While changes in CD14, LCN2, CCL20, uPAR, EGF, MIF, CXCL5, IL-8, adiponectin and CHI3L1 levels have already been correlated with severity of IAV infection in mice and humans, our study is the first to describe association of CD147, RBP4, TFF3, and CFD with hospitalization of IAV-infected patients. Thus, we identified local innate immune profiles, which were associated with the clinical severity of influenza infections. PMID:27442005

  1. Screening of random peptide library of hemagglutinin from pandemic 2009 A(H1N1) influenza virus reveals unexpected antigenically important regions.

    PubMed

    Xu, Wanghui; Han, Lu; Lin, Zhanglin

    2011-01-01

    The antigenic structure of the membrane protein hemagglutinin (HA) from the 2009 A(H1N1) influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS) against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify "hot spots" or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins. PMID:21437206

  2. Recrudescent Wave of A/H1N1pdm09 Influenza Viruses in Winter 2012-2013 in Kashmir, India.

    PubMed

    Koul, Parvaiz; Khan, Umar; Bhat, Khursheed; Saha, Siddhartha; Broor, Shobha; Lal, Renu; Chadha, Mandeep

    2013-01-01

    Some parts of world, including India observed a recrudescent wave of influenza A/H1N1pdm09 in 2012. We undertook a study to examine the circulating influenza strains, their clinical association and antigenic characteristics to understand the recrudescent wave of A/H1N1pdm09 from November 26, 2012 to Feb 28, 2013 in Kashmir, India. Of the 751 patients (545 outpatient and 206 hospitalized) presenting with acute respiratory infection at a tertiary care hospital in Srinagar; 184 (24.5%) tested positive for influenza. Further type and subtype analysis revealed that 106 (58%) were influenza A (H1N1pdm09 =105, H3N2=1) and 78 (42%) were influenza B. The influenza positive cases had a higher frequency of chills, nasal discharge, sore throat, body aches and headache, compared to influenza negative cases. Of the 206 patients hospitalized for pneumonia/acute respiratory distress syndrome or an exacerbation of an underlying lung disease, 34 (16.5%) tested positive for influenza (22 for H1N1pdm09, 11 for influenza B). All influenza-positive patients received oseltamivir and while most patients responded well to antiviral therapy and supportive care, 6 patients (4 with H1N1pdm09 and 2 with influenza B) patients died of progressive respiratory failure and multi-organ dysfunction. Following a period of minimal circulation, H1N1pdm09 re-emerged in Kashmir in 2012-2013, causing serious illness and fatalities. As such the healthcare administrators and policy planners need to be wary and monitor the situation closely.

  3. Enhanced influenza surveillance on Réunion Island (southern hemisphere) in the context of the emergence of influenza A(H1N1)v.

    PubMed

    D'Ortenzio, E; Do, C; Renault, P; Weber, F; Filleul, L

    2009-06-11

    With the winter season on the southern hemisphere that starts in Reunion Island in June seasonal influenza activity usually increases shortly afterwards. The new influenza A(H1N1)v virus is rapidly spreading worldwide and may reach the island during the coming winter season. We have therefore enhanced influenza surveillance to detect the introduction of influenza A(H1N1)v, monitor its spread and impact on public health and characterise potential viral changes, particularly if seasonal influenza A(H1N1), resistant to oseltamivir, co-circulates with A(H1N1)v. PMID:19531342

  4. Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus

    PubMed Central

    2013-01-01

    Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can

  5. Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus.

    PubMed

    Wilson, Jason R; Guo, Zhu; Tzeng, Wen-Pin; Garten, Rebecca J; Xiyan, Xu; Blanchard, Elisabeth G; Blanchfield, Kristy; Stevens, James; Katz, Jacqueline M; York, Ian A

    2015-11-01

    Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift.

  6. Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus.

    PubMed

    Wilson, Jason R; Guo, Zhu; Tzeng, Wen-Pin; Garten, Rebecca J; Xiyan, Xu; Blanchard, Elisabeth G; Blanchfield, Kristy; Stevens, James; Katz, Jacqueline M; York, Ian A

    2015-11-01

    Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift. PMID:26318247

  7. [Comparison of the influenza epidemics in Russia caused by the pandemic virus A(H1N1)pdm09 within the period from 2009 to 2013].

    PubMed

    Karpova, L S; Sominina, A A; Burtseva, E I; Pelikh, M Yu; Feodoritova, E L; Popovtseva, N M; Stolyarov, T P; Kiselev, O I

    2015-01-01

    Comparative analysis of the three past epidemics with the participation of the pandemic influenza A(H1N1)pdm09 was conducted according to the results of the epidemiological trials of two WHO National influenza centers for the morbidity, hospitalization, and mortality of the influenza in 59 cities of Russia for the period from 2009 to 2013. The first wave of the pandemic of 2009 was the most severe. Compared with this wave, during the next epidemics of 2011 and 2013, the involvement of urban population in the epidemic was reduced, as well as the morbidity in the people 15-64 years old and schoolchildren 7-14 years old. The duration of the epidemic among the adult population, the mortality rate of the total population, and the mortality rates in all age groups were also decreased. Vice versa, the incidence in the children of preschool age and the elderly people and the duration of the epidemic among children (especially preschool children) were increased. The share of patients 65 years and older, children 0-2 years old, and patients with pathology of the cardiovascular systems among the deceased patients increased to 33.6%.

  8. Molecular genetic analysis of the Influenza A(H1N1)pdm09 virus from lethal and recovered cases in Russia from 2009 to 2014: Deletions in the nucleoprotein.

    PubMed

    Yatsyshina, Svetlana; Renteeva, Anna; Deviatkin, Andrei; Vorobyeva, Nadezhda; Minenko, Angrey; Valdokhina, Anna; Elkina, Mariya; Kuleshov, Konstantin; Shipulin, German

    2015-08-01

    Influenza A(H1N1)pdm09 virus caused about 2000 laboratory confirmed lethal cases in Russia during 2009-2010 and 1302, 135 and 29 cases in the 2010-2011, 2012-2013 and 2013-2014 seasons respectively. The on average short duration (7.8±5 days) of lethal cases of Influenza A(H1N1)pdm09 infections in Russia suggests primary viral rather than secondary bacterial pneumonia. Hemorrhagic syndrome was recorded in 36.6% of patients. An examination of 221 lung samples from lethal influenza cases for the presence of bacterial DNA that could cause pneumonia did not reveal bacterial superinfections in 86% of cases. Molecular-genetic analyses of Influenza A(H1N1)pdm09 viruses from lethal and recovered cases were performed. Amino acids G and N at position 222 of the influenza virus hemagglutinin, which increase the affinity for the lower respiratory tract receptors, were detected more often in the lungs of patients who died than in respiratory swabs collected from recovered patients (p<0.0001 and p=0.007). Viruses harboring various mutations (222D/G/N/S) was significantly associated with lung samples compared with respiratory swabs from recovered patients (p<0.0001). Amino acid 222E, which increases the affinity for upper respiratory tract receptors, was found more frequently in recovered patients than in patients with lethal disease (27% versus 3%, p=0.005). Phylogenetic analysis identified an isolated cluster of viruses in the 2009-2010 season that harbored amino acid 222E, which could explain the high transmissibility of the virus at the beginning of the pandemic. Bayesian skyline plot implied a decline in the effective population size of Influenza A(H1N1)pdm09 viruses in Russia from 2010-2011 to 2011-2012, followed by an increase in 2012-2013; this trend was accompanied by the increased genetic diversity of the hemagglutinin antigenic sites. Mutations of viral RNA leading to oseltamivir resistance were found in 2.8% of tested patients during only 2010-2011 season. Deletions

  9. Polymeric LabChip Real-Time PCR as a Point-of-Care-Potential Diagnostic Tool for Rapid Detection of Influenza A/H1N1 Virus in Human Clinical Specimens

    PubMed Central

    Song, Hyun-Ok; Kim, Je-Hyoung; Ryu, Ho-Sun; Lee, Dong-Hoon; Kim, Sun-Jin; Kim, Deog-Joong; Suh, In Bum; Choi, Du Young; In, Kwang-Ho; Kim, Sung-Woo; Park, Hyun

    2012-01-01

    It is clinically important to be able to detect influenza A/H1N1 virus using a fast, portable, and accurate system that has high specificity and sensitivity. To achieve this goal, it is necessary to develop a highly specific primer set that recognizes only influenza A viral genes and a rapid real-time PCR system that can detect even a single copy of the viral gene. In this study, we developed and validated a novel fluidic chip-type real-time PCR (LabChip real-time PCR) system that is sensitive and specific for the detection of influenza A/H1N1, including the pandemic influenza strain A/H1N1 of 2009. This LabChip real-time PCR system has several remarkable features: (1) It allows rapid quantitative analysis, requiring only 15 min to perform 30 cycles of real-time PCR. (2) It is portable, with a weight of only 5.5 kg. (3) The reaction cost is low, since it uses disposable plastic chips. (4) Its high efficiency is equivalent to that of commercially available tube-type real-time PCR systems. The developed disposable LabChip is an economic, heat-transferable, light-transparent, and easy-to-fabricate polymeric chip compared to conventional silicon- or glass-based labchip. In addition, our LabChip has large surface-to-volume ratios in micro channels that are required for overcoming time consumed for temperature control during real-time PCR. The efficiency of the LabChip real-time PCR system was confirmed using novel primer sets specifically targeted to the hemagglutinin (HA) gene of influenza A/H1N1 and clinical specimens. Eighty-five human clinical swab samples were tested using the LabChip real-time PCR. The results demonstrated 100% sensitivity and specificity, showing 72 positive and 13 negative cases. These results were identical to those from a tube-type real-time PCR system. This indicates that the novel LabChip real-time PCR may be an ultra-fast, quantitative, point-of-care-potential diagnostic tool for influenza A/H1N1 with a high sensitivity and specificity

  10. Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study

    PubMed Central

    2012-01-01

    Background Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Methods Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Results Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated

  11. An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

    PubMed Central

    Aguilar-Yáñez, José M.; Portillo-Lara, Roberto; Mendoza-Ochoa, Gonzalo I.; García-Echauri, Sergio A.; López-Pacheco, Felipe; Bulnes-Abundis, David; Salgado-Gallegos, Johari; Lara-Mayorga, Itzel M.; Webb-Vargas, Yenny; León-Angel, Felipe O.; Rivero-Aranda, Ramón E.; Oropeza-Almazán, Yuriana; Ruiz-Palacios, Guillermo M.; Zertuche-Guerra, Manuel I.; DuBois, Rebecca M.; White, Stephen W.; Schultz-Cherry, Stacey; Russell, Charles J.; Alvarez, Mario M.

    2010-01-01

    Background The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. Methodology/Principal Findings We expressed the globular HA receptor binding domain, referred to here as HA63–286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63–286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. Conclusions/Significance Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy. PMID:20661476

  12. Predominance of HA-222D/G Polymorphism in Influenza A(H1N1)pdm09 Viruses Associated with Fatal and Severe Outcomes Recently Circulating in Germany

    PubMed Central

    Wedde, Marianne; Wählisch, Stephanie; Wolff, Thorsten; Schweiger, Brunhilde

    2013-01-01

    Influenza A(H1N1)pdm09 viruses cause sporadically very severe disease including fatal clinical outcomes associated with pneumonia, viremia and myocarditis. A mutation characterized by the substitution of aspartic acid (wild-type) to glycine at position 222 within the haemagglutinin gene (HA-D222G) was recorded during the 2009 H1N1 pandemic in Germany and other countries with significant frequency in fatal and severe cases. Additionally, A(H1N1)pdm09 viruses exhibiting the polymorphism HA-222D/G/N were detected both in the respiratory tract and in blood. Specimens from mild, fatal and severe cases were collected to study the heterogeneity of HA-222 in A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2011. In order to enable rapid and large scale analysis we designed a pyrosequencing (PSQ) assay. In 2009/2010, the 222D wild-type of A(H1N1)pdm09 viruses predominated in fatal and severe outcomes. Moreover, co-circulating virus mutants exhibiting a D222G or D222E substitution (8/6%) as well as HA-222 quasispecies were identified (10%). Both the 222D/G and the 222D/G/N/V/Y polymorphisms were confirmed by TA cloning. PSQ analyses of viruses associated with mild outcomes revealed mainly the wild-type 222D and no D222G change in both seasons. However, an increase of variants with 222D/G polymorphism (60%) was characteristic for A(H1N1)pdm09 viruses causing fatal and severe cases in the season 2010/2011. Pure 222G viruses were not observed. Our results support the hypothesis that the D222G change may result from adaptation of viral receptor specificity to the lower respiratory tract. This could explain why transmission of the 222G variant is less frequent among humans. Thus, amino acid changes at HA position 222 may be the result of viral intra-host evolution leading to the generation of variants with an altered viral tropism. PMID:23451145

  13. Newly emerging mutations in the matrix genes of the human influenza A(H1N1)pdm09 and A(H3N2) viruses reduce the detection sensitivity of real-time reverse transcription-PCR.

    PubMed

    Yang, Ji-Rong; Kuo, Chuan-Yi; Huang, Hsiang-Yi; Wu, Fu-Ting; Huang, Yi-Lung; Cheng, Chieh-Yu; Su, Yu-Ting; Chang, Feng-Yee; Wu, Ho-Sheng; Liu, Ming-Tsan

    2014-01-01

    New variants of the influenza A(H1N1)pdm09 and A(H3N2) viruses were detected in Taiwan between 2012 and 2013. Some of these variants were not detected in clinical specimens using a common real-time reverse transcription-PCR (RT-PCR) assay that targeted the conserved regions of the viral matrix (M) genes. An analysis of the M gene sequences of the new variants revealed that several newly emerging mutations were located in the regions where the primers or probes of the real-time RT-PCR assay bind; these included three mutations (G225A, T228C, and G238A) in the A(H1N1)pdm09 virus, as well as one mutation (C163T) in the A(H3N2) virus. These accumulated mismatch mutations, together with the previously identified C154T mutation of the A(H1N1)pdm09 virus and the C153T and G189T mutations of the A(H3N2) virus, result in a reduced detection sensitivity for the real-time RT-PCR assay. To overcome the loss of assay sensitivity due to mismatch mutations, we established a real-time RT-PCR assay using degenerate nucleotide bases in both the primers and probe and successfully increased the sensitivity of the assay to detect circulating variants of the human influenza A viruses. Our observations highlight the importance of the simultaneous use of different gene-targeting real-time RT-PCR assays for the clinical diagnosis of influenza.

  14. Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany.

    PubMed

    Wedde, Marianne; Biere, Barbara; Wolff, Thorsten; Schweiger, Brunhilde

    2015-10-01

    This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants.

  15. Liver Biochemistry During the Course of Influenza A/H1N1 Infection

    PubMed Central

    Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

    2013-01-01

    Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus.

  16. Rapid spread of influenza A(H1N1)pdm09 viruses with a new set of specific mutations in the internal genes in the beginning of 2015/2016 epidemic season in Moscow and Saint Petersburg (Russian Federation).

    PubMed

    Komissarov, Andrey; Fadeev, Artem; Sergeeva, Maria; Petrov, Sergey; Sintsova, Kseniya; Egorova, Anna; Pisareva, Maria; Buzitskaya, Zhanna; Musaeva, Tamila; Danilenko, Daria; Konovalova, Nadezhda; Petrova, Polina; Stolyarov, Kirill; Smorodintseva, Elizaveta; Burtseva, Elena; Krasnoslobodtsev, Kirill; Kirillova, Elena; Karpova, Lyudmila; Eropkin, Mikhail; Sominina, Anna; Grudinin, Mikhail

    2016-07-01

    A dramatic increase of influenza activity in Russia since week 3 of 2016 significantly differs from previous seasons in terms of the incidence of influenza and acute respiratory infection (ARI) and in number of lethal cases. We performed antigenic analysis of 108 and whole-genome sequencing of 77 influenza A(H1N1)pdm09 viruses from Moscow and Saint Petersburg. Most of the viruses were antigenically related to the vaccine strain. Whole-genome analysis revealed a composition of specific mutations in the internal genes (D2E and M83I in NEP, E125D in NS1, M105T in NP, Q208K in M1, and N204S in PA-X) that probably emerged before the beginning of 2015/2016 epidemic season.

  17. International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE.

    PubMed

    Laurie, Karen L; Engelhardt, Othmar G; Wood, John; Heath, Alan; Katz, Jacqueline M; Peiris, Malik; Hoschler, Katja; Hungnes, Olav; Zhang, Wenqing; Van Kerkhove, Maria D

    2015-08-01

    The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.

  18. Live attenuated influenza A virus vaccine protects against heterologous challenge with A(H1N1)pdm09 without inducing vaccine associated enhanced respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus (IAV) vaccines that provide broad cross-protection against antigenic variants are necessary to prevent infection and shedding of the wide array of IAV cocirculating in swine. Whole inactivated virus (WIV) vaccines provide only partial protection against IAV with substantial antigen...

  19. The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A(H1N1) virus.

    PubMed

    Kim, Jin Il; Hwang, Min-Woong; Lee, Ilseob; Park, Sehee; Lee, Sangmoo; Bae, Joon-Yong; Heo, Jun; Kim, Donghwan; Jang, Seok-Il; Park, Mee Sook; Kwon, Hyung-Joo; Song, Jin-Won; Park, Man-Seong

    2014-06-20

    By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface.

  20. Characterization of an influenza A virus in Mexican swine that is related to the A/H1N1/2009 pandemic clade.

    PubMed

    Escalera-Zamudio, Marina; Cobián-Güemes, Georgina; de los Dolores Soto-del Río, María; Isa, Pavel; Sánchez-Betancourt, Iván; Parissi-Crivelli, Aurora; Martínez-Cázares, María Teresa; Romero, Pedro; Velázquez-Salinas, Lauro; Huerta-Lozano, Belem; Nelson, Martha; Montero, Hilda; Vinuesa, Pablo; López, Susana; Arias, Carlos F

    2012-11-10

    In the spring of 2009, swine-origin influenza H1N1pdm09 viruses caused the first influenza pandemic of this century. We characterized the influenza viruses that circulated early during the outbreak in Mexico, including one newly sequenced swine H1N1pdm09 virus and three newly sequenced human H1N1pdm09 viruses that circulated in the outbreak of respiratory disease in La Gloria, Veracruz. Phylogenetic analysis revealed that the swine isolate (A/swine/Mexico/4/2009) collected in April 2009 is positioned in a branch that is basal to the rest of the H1N1pdm09 clade in two (NP and PA) of the eight single-gene trees. In addition, the concatenated HA-NA and the complete whole-genome trees also showed a basal position for A/swine/Mexico/4/2009. Furthermore, this swine virus was found to share molecular traits with non-H1N1pdm09 H1N1 viral lineages. These results suggest that this isolate could potentially be the first one detected from a sister lineage closely related to the H1N1pdm09 viruses.

  1. Evolution of oseltamivir resistance mutations in Influenza A(H1N1) and A(H3N2) viruses during selection in experimentally infected mice.

    PubMed

    Pizzorno, Andrés; Abed, Yacine; Plante, Pier-Luc; Carbonneau, Julie; Baz, Mariana; Hamelin, Marie-Ève; Corbeil, Jacques; Boivin, Guy

    2014-11-01

    The evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. Herein, we assessed the evolution of neuraminidase (NA) and hemagglutinin (HA) genes of influenza A/WSN/33 (H1N1) and A/Victoria/3/75 (H3N2) viruses recovered from the lungs of experimentally infected BALB/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body weight/day) of oseltamivir over two generations. The traditional phenotypic and genotypic methods as well as deep-sequencing analysis were used to characterize the potential selection of mutations and population dynamics of oseltamivir-resistant variants. No oseltamivir-resistant NA or HA changes were detected in the recovered A/WSN/33 viruses. However, we observed a positive selection of the I222T NA substitution in the recovered A/Victoria/3/75 viruses, with a frequency increasing over time and with an oseltamivir concentration from 4% in the initial pretherapy inoculum up to 28% after two lung passages. Although the presence of mixed I222T viral populations in mouse lungs only led to a minimal increase in oseltamivir 50% enzyme-inhibitory concentrations (IC50s) (by a mean of 5.7-fold) compared to that of the baseline virus, the expressed recombinant A/Victoria/3/75 I222T NA protein displayed a 16-fold increase in the oseltamivir IC50 level compared to that of the recombinant wild type (WT). In conclusion, the combination of serial in vivo passages under neuraminidase inhibitor (NAI) pressure and temporal deep-sequencing analysis enabled, for the first time, the identification and selection of the oseltamivir-resistant I222T NA mutation in an influenza H3N2 virus. Additional in vivo selection experiments with other antivirals and drug combinations might provide important information on the evolution of antiviral resistance in influenza viruses.

  2. Association between Hemagglutinin Stem-Reactive Antibodies and Influenza A/H1N1 Virus Infection during the 2009 Pandemic

    PubMed Central

    Hoa, Le Nguyen Minh; Mai, Le Quynh; Bryant, Juliet E.; Thai, Pham Quang; Hang, Nguyen Le Khanh; Yen, Nguyen Thi Thu; Duong, Tran Nhu; Thoang, Dang Dinh; Horby, Peter; Werheim, Heiman F. L.

    2016-01-01

    ABSTRACT The discovery of influenza virus broadly neutralizing (BrN) antibodies prompted efforts to develop universal vaccines. Influenza virus stem-reactive (SR) broadly neutralizing antibodies have been detected by screening antibody phage display libraries. However, studies of SR BrN antibodies in human serum, and their association with natural infection, are limited. To address this, pre- and postpandemic sera from a prospective community cohort study in Vietnam were assessed for antibodies that inhibit SR BrN monoclonal antibody (MAb) (C179) binding to H1N1 pandemic 2009 virus (H1N1pdm09). Of 270 households, 33 with at least one confirmed H1N1pdm09 illness or at least two seroconverters were included. The included households comprised 71 infected and 41 noninfected participants. Sera were tested as 2-fold dilutions between 1:5 and 1:40. Fifty percent C179 inhibition (IC50) titers did not exceed 10, although both IC50 titers and percent C179 inhibition by sera diluted 1:5 or 1:10 correlated with hemagglutination inhibition (HI) and microneutralization (MN) titers (all P < 0.001). Thirteen (12%) participants had detectable prepandemic IC50 titers, but only one reached a titer of 10. This proportion increased to 44% after the pandemic, when 39 participants had a titer of 10, and 67% of infected compared to 44% of noninfected had detectable IC50 titers (P < 0.001). The low levels of SR antibodies in prepandemic sera were not associated with subsequent H1N1pdm09 infection (P = 0.241), and the higher levels induced by H1N1pdm09 infection returned to prepandemic levels within 2 years. The findings indicate that natural infection induces only low titers of SR antibodies that are not sustained. IMPORTANCE Universal influenza vaccines could have substantial health and economic benefits. The focus of universal vaccine research has been to induce antibodies that prevent infection by diverse influenza virus strains. These so-called broadly neutralizing antibodies are

  3. Rapid research response to the 2009 A(H1N1)pdm09 influenza pandemic (Revised)

    PubMed Central

    2013-01-01

    Background When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus. Findings and conclusions Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request. PMID:23641940

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

    PubMed

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

    2010-12-01

    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.

  5. Effect of test system on the ability of monoclonal antibodies to detect antigenic drift in influenza A(H1N1) virus haemagglutinins.

    PubMed

    Kendal, A P; Phillips, D J; Webster, R G; Galland, G G; Reimer, C B

    1981-06-01

    Results of analysing antigenic variation in the haemagglutinin (HA) molecule of naturally occurring influenza A (H1N1) viruses from 1977 to 1979 with monoclonal antibodies were found to be dependent in some instances on the test system used. In several instances A/USSR/90/77 HA-specific monoclonal antibodies had sharply reduced haemagglutination-inhibition (HI) titres with variant virus although they bound to the variant and A/USSR/90/77 HAs with similar efficiencies as judged by titration in a sensitive and accurate solid-phase immunofluorimetric assay. In another instance, the converse situation was observed: monoclonal antibodies having a reduced efficiency of binding to the HA of a variant virus nevertheless had comparable HI titres with the variant and with A/USSR/90/77. The chemical basis and epidemiological significance of these observations remain to be elucidated. Nevertheless, the finding that the reaction of monoclonal antibodies can, in some cases, be markedly dependent on the test system employed is of significance for the efficient design and correct interpretation of immunochemical studies which employ monoclonal antibodies to investigate the basis for variation in influenza strains.

  6. Influenza A/H1N1_09: Australia and New Zealand's winter of discontent.

    PubMed

    Kotsimbos, Tom; Waterer, Grant; Jenkins, Christine; Kelly, Paul M; Cheng, Allen; Hancox, Robert J; Holmes, Mark; Wood-Baker, Richard; Bowler, Simon; Irving, Louis; Thompson, Philip

    2010-02-15

    Influenza A/H1N1_09 emerged in Mexico at the end of the Northern Hemisphere winter. Within weeks, the focus shifted to the Southern Hemisphere as the introduction of the novel virus coincided with the beginning of the influenza season. Intensive public health and health services planning had occurred in Australia and New Zealand as preparation for an influenza pandemic before 2009. However, this first pandemic wave was quite different to what had been expected. Key elements of the pandemic and response are outlined from the perspective of clinicians working at the frontline of patient care. In particular, they examine why past influenza pandemics and recent history are poor predictors of the current pandemic, the discordance between potential for transmission and disease severity, the broad clinical spectrum of H1N1_09 infection, clinical and health service management issues, and the relationship between health care and government policy. Finally, they address the need for the respiratory community to show leadership in times of crisis. Lessons learned in Australia and New Zealand during 2009 have important messages for similarly resourced countries in the Northern Hemisphere in the coming months as they face their own influenza season.

  7. The influenza A(H1N1) epidemic in Mexico. Lessons learned

    PubMed Central

    Córdova-Villalobos, José A; Sarti, Elsa; Arzoz-Padrés, Jacqueline; Manuell-Lee, Gabriel; Méndez, Josefina Romero; Kuri-Morales, Pablo

    2009-01-01

    Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health. PMID:19785747

  8. Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

    PubMed Central

    Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cécile; Simonsen, Lone; Tamerius, James; Miller, Mark A.; Borja-Aburto, Víctor H.

    2011-01-01

    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

  9. Host Adaptation and the Alteration of Viral Properties of the First Influenza A/H1N1pdm09 Virus Isolated in Japan

    PubMed Central

    Ainai, Akira; Hasegawa, Hideki; Obuchi, Masatsugu; Odagiri, Takato; Ujike, Makoto; Shirakura, Masayuki; Nobusawa, Eri; Tashiro, Masato; Asanuma, Hideki

    2015-01-01

    A/Narita/1/2009 (A/N) was the first H1N1 virus from the 2009 pandemic (H1pdm) to be isolated in Japan. To better understand and predict the possible development of this virus strain, the effect of passaging A/N was investigated in Madin-Darby canine kidney cells, chicken eggs and mice. A/N that had been continuously passaged in cells, eggs, or mice obtained the ability to grow efficiently in each host. Moreover, A/N grown in mice had both a high level of pathogenicity in mice and an increased growth rate in cells and eggs. Changes in growth and pathogenicity were accompanied by amino acid substitutions in viral hemagglutinin (HA) and PB2. In addition, the adapted viruses exhibited a reduced ability to react with ferret antisera against A/N. In conclusion, prolonged passaging allowed influenza A/N to adapt to different hosts, as indicated by a high increase in proliferative capacity that was accompanied by an antigenic alteration leading to amino acid substitutions. PMID:26079133

  10. Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?

    PubMed Central

    Ilyushina, Natalia A.; Ducatez, Mariette F.; Rehg, Jerold E.; Marathe, Bindumadhav M.; Marjuki, Henju; Bovin, Nicolai V.; Webster, Robert G.; Webby, Richard J.

    2010-01-01

    Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10:90, 50:50, and 90:10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations (hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37°C, and the hemagglutinin change affected binding of the virus to α2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated. PMID:21116343

  11. French Experience of 2009 A/H1N1v Influenza in Pregnant Women

    PubMed Central

    Dubar, Grégory; Azria, Elie; Tesnière, Antoine; Dupont, Hervé; Le Ray, Camille; Baugnon, Thomas; Matheron, Sophie; Luton, Dominique; Richard, Jean-Christophe; Launay, Odile; Tsatsaris, Vassilis; Goffinet, François; Mignon, Alexandre

    2010-01-01

    Background The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. Methodology/Principal Findings A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2–11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9–12.1 and 61.2, 95% CI; 14.4–261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. Conclusions This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of

  12. Influenza A(H1N1)pdm09 during air travel

    PubMed Central

    Neatherlin, John; Cramer, Elaine H.; Dubray, Christine; Marienau, Karen J.; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K.; Kirking, Hannah L.; Schembri, Christopher; Katz, Jacqueline M.; Cohen, Nicole J.; Fishbein, Daniel B.

    2015-01-01

    Summary The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1–7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241

  13. Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders

    PubMed Central

    Chen, Huazhong; Liu, Shelan; Liu, Jun; Chai, Chengliang; Mao, Haiyan; Yu, Zhao; Tang, Yuming; Zhu, Geqin; Chen, Haixiao X.; Zhu, Chengchu; Shao, Hui; Tan, Shuguang; Wang, Qianli; Bi, Yuhai; Zou, Zhen; Liu, Guang; Jin, Tao; Jiang, Chengyu; Gao, George F.; Peiris, Malik

    2016-01-01

    A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another. PMID:26982379

  14. Key role of regulated upon activation normal T-cell expressed and secreted, nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells.

    PubMed

    Phung, Thuy Thi Bich; Sugamata, Ryuichi; Uno, Kazuko; Aratani, Yasuaki; Ozato, Keiko; Kawachi, Shoji; Thanh Nguyen, Liem; Nakayama, Toshinori; Suzuki, Kazuo

    2011-12-01

    Influenza virus infection causes severe respiratory disease such as that due to avian influenza (H5N1). Influenza A viruses proliferate in human epithelial cells, which produce inflammatory cytokines/chemokines as a "cytokine storm" attenuated with the viral nonstructural protein 1 (NS1). Cytokine/chemokine production in A549 epithelial cells infected with influenza A/H1N1 virus (PR-8) or nonstructural protein 1 (NS1) plasmid was examined in vitro. Because tumor necrosis factor-α (TNF-α) and regulated upon activation normal T-cell expressed and secreted (RANTES) are predominantly produced from cells infected with PR-8 virus, the effects of mRNA knockdown of these cytokines were investigated. Small interfering (si)TNF-α down-regulated RANTES expression and secretion of RANTES, interleukin (IL)-8, and monocyte chemotactic protein-1 (MCP-1). In addition, siRANTES suppressed interferon (IFN)-γ expression and secretion of RANTES, IL-8, and MCP-1, suggesting that TNF-α stimulates production of RANTES, IL-8, MCP-1, and IFN-γ, and RANTES also increased IL-8, MCP-1, and IFN-γ. Furthermore, administration of TNF-α promoted increased secretion of RANTES, IL-8, and MCP-1. Administration of RANTES enhanced IL-6, IL-8, and MCP-1 production without PR-8 infection. These results strongly suggest that, as an initial step, TNF-α regulates RANTES production, followed by increase of IL-6, IL-8, and MCP-1 and IFNs concentrations. At a later stage, cells transfected with viral NS1 plasmid showed production of a large amount of IL-8 and MCP-1 in the presence of the H(2)O(2)-myeloperoxidse (MPO) system, suggesting that NS1 of PR-8 may induce a "cytokine storm" from epithelial cells in the presence of an H(2)O(2)-MPO system.

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

    PubMed Central

    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

    2010-01-01

    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

  16. Substantial Morbidity and Mortality Associated with Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity

    PubMed Central

    Dávila, Javier; Chowell, Gerardo; Borja-Aburto, Víctor H.; Viboud, Cécile; Grajales Muñiz, Concepciòn; Miller, Mark

    2014-01-01

    Background: A recrudescent wave of pandemic influenza A/H1N1 is underway in Mexico in winter 2013-14, following a mild 2012-13 A/H3N2 influenza season. Mexico previously experienced several waves of pandemic A/H1N1 activity in spring, summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older ages. Here we describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak, relative to previous seasons dominated by the A/H1N1 pandemic virus. The analysis is intended to guide public health intervention strategies in near real time. Methods: We analyzed demographic and geographic data on hospitalizations with severe acute respiratory infection (SARI), laboratory-confirmed A/H1N1 influenza hospitalizations, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-October 2013 to 31-Jan 2014. We characterized the age and regional patterns of influenza activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also estimated the reproduction number (R) based on the growth rate of daily case incidence by date of symptoms onset. Results: A total of 7,886 SARI hospitalizations and 529 inpatient-deaths (3.2%) were reported between 01-October 2013 and 31-January 2014 (resulting in 3.2 laboratory-confirmed A/H1N1 hospitalizations per 100,00 and 0.52 laboratory-confirmed A/H1N1-positive deaths per 100,000). The progression of daily SARI hospitalizations in 2013-14 exceeded that observed during the 2011-2012 A/H1N1 epidemic. The mean age of laboratory-confirmed A/H1N1 patients in 2013-14 was 41.1 y (SD=20.3) for hospitalizations and 49.2 y (SD=16.7) for deaths. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 y and lower among younger age groups for the ongoing 2013-2014 epidemic, compared to the 2011-12 A/H1N1 epidemic (Chi-square test, P

  17. The early diversification of influenza A/H1N1pdm

    PubMed Central

    Nelson, Martha; Spiro, David; Wentworth, David; Fan, Jiang; Beck, Eric; St. George, Kirsten; Ghedin, Elodie; Halpin, Rebecca; Bera, Jayati; Hine, Erin; Proudfoot, Kathleen; Stockwell, Tim; Lin, Xudong; Griesemer, Sara; Bose, Michael; Jurgens, Lisa; Kumar, Swati; Viboud, Cecile; Holmes, Edward; Henrickson, Kelly

    2009-01-01

    Background Since its initial detection in April 2009, the A/H1N1pdm influenza virus has spread rapidly in humans, with over 5,700 human deaths. However, little is known about the evolutionary dynamics of H1N1pdm and its geographic and temporal diversification. Methods Phylogenetic analysis was conducted upon the concatenated coding regions of whole-genome sequences from 290 H1N1pdm isolates sampled globally between April 1 – July 9, 2009, including relatively large samples from the US states of Wisconsin and New York. Results At least 7 phylogenetically distinct viral clades have disseminated globally and co-circulated in localities that experienced multiple introductions of H1N1pdm. The epidemics in New York and Wisconsin were dominated by two different clades, both phylogenetically distinct from the viruses first identified in California and Mexico, suggesting an important role for founder effects in determining local viral population structures. Conclusions Determining the global diversity of H1N1pdm is central to understanding the evolution and spatial spread of the current pandemic, and to predict its future impact on human populations. Our results indicate that H1N1pdm has already diversified into distinct viral lineages with defined spatial patterns. PMID:20029664

  18. Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016.

    PubMed

    Chambers, Catharine; Skowronski, Danuta M; Sabaiduc, Suzana; Winter, Anne Luise; Dickinson, James A; De Serres, Gaston; Gubbay, Jonathan B; Drews, Steven J; Martineau, Christine; Eshaghi, Alireza; Krajden, Mel; Bastien, Nathalie; Li, Yan

    2016-01-01

    Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses.

  19. A case of central diabetes insipidus following probable type A/H1N1 influenza infection.

    PubMed

    Kobayashi, Takaaki; Miwa, Takashi; Odawara, Masato

    2011-01-01

    The major causes of central diabetes insipidus (CDI) are neoplastic or infiltrative lesions of the hypothalamus or pituitary gland, severe head injuries, or pituitary or hypothalamic surgery. Lymphocytic infundibuloneurophysitis (LINH) is associated with autoimmune inflammatory disease of the pituitary gland, but the exact etiology is unknown. CDI caused by viral infections has been rarely reported. Here, we describe the case of a 22-year-old man who was in good health until 2 months prior to admission, presented with acute development of polyuria and polydipsia, and showed increased urinary volume up to 9000 mL/day. The patient showed elevated serum osmolality and low urine osmolality, with a low level of antidiuretic hormone. Endocrinological findings revealed CDI, but his arterial pituitary function appeared normal. Magnetic resonance imaging revealed significant enlargement of the pituitary stalk. We suspected CDI due to LINH based on non-transsphenoidal biopsy findings. He was diagnosed as type A influenza,and given oral therapeutic agents. However, acute onset of polyuria and polydipsia occurred 10 days after the influenza diagnosis. The available epidemiological information regarding the outbreak of influenza around that time strongly suggested that the patient was infected with the A/H1N1 influenza virus, although this virus had not been detected on polymerase chain reaction testing. In the present case, the autoimmune mechanism of LINH may have been associated with novel influenza A/H1N1 virus infection.

  20. Behavioural response in educated young adults towards influenza A(H1N1)pdm09.

    PubMed

    Chen, S C; Hsieh, N H; You, S H; Wang, C H; Liao, C M

    2015-07-01

    The purpose of this paper was to determine how contact behaviour change influences the indoor transmission of influenza A(H1N1)pdm09 among school children. We incorporated transmission rate matrices constructed from questionnaire responses into an epidemiological model to simulate contact behaviour change during an influenza epidemic. We constructed a dose-response model describing the relationships between contact rate, viral load, and respiratory symptom scores using published experimental human infection data for A(H1N1)pdm09. Findings showed that that mean numbers of contacts were 5.66 ± 6.23 and 1.96 ± 2.76 d-1 in the 13-19 and 40-59 years age groups, respectively. We found that the basic reproduction number (R 0) was <1 during weekends in pandemic periods, implying that school closures or class suspensions are probably an effective social distancing policy to control pandemic influenza transmission. We conclude that human contact behaviour change is a potentially influential factor on influenza infection rates. For substantiation of this effect, we recommend a future study with more comprehensive control measures.

  1. Recombinant equine herpesvirus 1 (EHV-1) vaccine protects pigs against challenge with influenza A(H1N1)pmd09.

    PubMed

    Said, Abdelrahman; Lange, Elke; Beer, Martin; Damiani, Armando; Osterrieder, Nikolaus

    2013-05-01

    Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs but also a threat to human health. The pandemic influenza A(H1N1)pdm09 virus likely originated in swine through reassortment between a North American triple reassortant and Eurasian avian-like SIV. The North American triple reassortant virus harbors genes from avian, human and swine influenza viruses. An effective vaccine may protect the pork industry from economic losses and curb the development of new virus variants that may threaten public health. In the present study, we evaluated the efficacy of a recombinant equine herpesvirus type 1 (EHV-1) vaccine (rH_H1) expressing the hemagglutinin H1 of A(H1N1)pdm09 in the natural host. Our data shows that the engineered rH_H1 vaccine induces influenza virus-specific antibody responses in pigs and is able to protect at least partially against challenge infection: no clinical signs of disease were detected and virus replication was reduced as evidenced by decreased nasal virus shedding and faster virus clearance. Taken together, our results indicate that recombinant EHV-1 encoding H1 of A(H1N1)pdm09 may be a promising alternative for protection of pigs against infection with A(H1N1)pdm09 or other influenza viruses.

  2. Predicting AH1N1 2009 influenza epidemic in Southeast Europe

    PubMed Central

    Smoljanović, Mladen; Smoljanović, Ankica; Mlikotić, Marijana

    2011-01-01

    Aim To use the data on the AH1N1 2009 influenza epidemic in the Southern hemisphere countries to predict the course and size of the upcoming influenza epidemic in South-Eastern Europe (SEE) countries and other regions of the World with temperate climate. Method We used a comparative epidemiological method to evaluate accessible electronic data on laboratory-confirmed deaths from AH1N1 2009 influenza in the seasons 2009/2010 and 2010/2011. The studied SEE countries were Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Hungary, Kosovo, Macedonia, Montenegro, Romania, Serbia, and Slovenia, while Southern hemisphere countries were Argentina, Australia, Chile, New Zealand, Paraguay, Uruguay, and South Africa. Results In influenza season 2009/2010, Southern hemisphere countries with temperate climate reported 1187 laboratory-confirmed influenza AH1N1 2009 deaths (mortality rate 0.84/100 000; 95% confidence interval [CI], 0.50-1.24). SEE countries with similar climatic conditions reported 659 deaths and similar mortality rates (0.86/100 000, 95% CI, 0.83-1.10). In the whole Europe without the Commonwealth of Independent States countries (CIS, former Soviet Union), there were 3213 deaths (0.60/100 000; 95% CI, 0.65-0.93). In 2010/2011, Southern hemisphere countries reported 94 laboratory-confirmed deaths (mortality rate 0.07/100 000; 95% CI, 0.02-0.28) or only 7.9% of the previous season. SEE countries by the end of the 11th epidemiological week of 2010/2011 season reported 489 laboratory-confirmed deaths, with a mortality rate of 0.64/100 000 (95% CI, 0.26-0.96) or 74.2% of the previous season, which was significantly higher than in the Southern hemisphere countries (χ21 = 609.1, P < 0.001). In Europe without CIS countries, there were 1836 deaths, with a mortality rate of 0.34/100 000 (χ2 = 153.3, P < 0.001 vs SEE countries). Conclusion In the 2009/2010 season, SEE countries and Southern hemisphere countries had similar influenza

  3. New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

    PubMed

    Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

    2015-06-01

    Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time.

  4. Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza Pandemic in Peru

    PubMed Central

    Chowell, Gerardo; Viboud, Cécile; Munayco, Cesar V.; Gómez, Jorge; Simonsen, Lone; Miller, Mark A.; Tamerius, James; Fiestas, Victor; Halsey, Eric S.; Laguna-Torres, Victor A.

    2011-01-01

    Background Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. Methods We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. Results The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. Conclusions Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school

  5. Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report

    PubMed Central

    2011-01-01

    Background Immunocompromised patients, such as systemic lupus erythematosus (SLE) sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. Case Presentation In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU) discharge. Conclusions To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement. PMID:22206235

  6. Public sources of information and information needs for pandemic influenza A(H1N1).

    PubMed

    Wong, Li Ping; Sam, I-Ching

    2010-12-01

    Providing health information during disease outbreaks is a fundamental component of outbreak control strategies. This study aimed to explore sources of influenza A(H1N1)-related information, specific information needs and preferences of the lay public during the peak of the outbreak. A cross-sectional, population-based, computer-assisted telephone interview of 1,050 respondents was conducted in Malaysia between July 11 and September 12, 2009. Newspaper, television and family were three main sources of information about A(H1N1). There were substantial ethnic differences; the Malays were significantly more likely to identify television as main source, while newspapers and family were identified as the main sources by the Chinese and Indians, respectively. Overall, the two main information needs identified were prevention and treatment. The Malays expressed lesser need for overall information than other ethnic groups. The three most preferred sources of information were television, newspapers and healthcare providers. There were significant positive correlations between amount of information received with knowledge (r = 0.149), perceived susceptibility to infection (r = 0.177), and other behavioral responses. Health information dissemination should be dedicated to meeting the information needs of diverse sociodemographic and ethnic groups. The findings highlight the importance of providing information that increases awareness and behavioral changes in disease prevention yet reduce fear.

  7. Transmission and control in an institutional pandemic influenza A(H1N1) 2009 outbreak.

    PubMed

    Arinaminpathy, N; Raphaely, N; Saldana, L; Hodgekiss, C; Dandridge, J; Knox, K; McCarthy, N D

    2012-06-01

    A pandemic influenza A(H1N1) 2009 outbreak in a summer school affected 117/276 (42%) students. Residential social contact was associated with risk of infection, and there was no evidence for transmission associated with the classroom setting. Although the summer school had new admissions each week, which provided susceptible students the outbreak was controlled using routine infection control measures (isolation of cases, basic hygiene measures and avoidance of particularly high-risk social events) and prompt treatment of cases. This was in the absence of chemoprophylaxis or vaccination and without altering the basic educational activities of the school. Modelling of the outbreak allowed estimation of the impact of interventions on transmission. These models and follow-up surveillance supported the effectiveness of routine infection control measures to stop the spread of influenza even in this high-risk setting for transmission. PMID:21859502

  8. Socioeconomic Factors Influencing Hospitalized Patients with Pneumonia Due to Influenza A(H1N1)pdm09 in Mexico

    PubMed Central

    Manabe, Toshie; Higuera Iglesias, Anjarath Lorena; Vazquez Manriquez, Maria Eugenia; Martinez Valadez, Eduarda Leticia; Ramos, Leticia Alfaro; Izumi, Shinyu; Takasaki, Jin; Kudo, Koichiro

    2012-01-01

    Background In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. Methodology and Principal Findings A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. Conclusions Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These

  9. Recrudescent wave of pandemic A/H1N1 influenza in Mexico, winter 2011-2012: Age shift and severity

    PubMed Central

    Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cecile; Simonsen, Lone; Grajales Muñiz, Concepcion; Rascón Pacheco, Ramón Alberto; González León, Margot; Borja Aburto, Víctor Hugo

    2012-01-01

    reproduction number of the winter 2011-12 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009. Conclusions We have documented a substantial and ongoing increase in the number of ARI hospitalizations during the period December 2011-February 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths, relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is reminiscent of historical pandemics and indicates either a gradual drift in the A/H1N1 virus, and/or a build-up of immunity among younger populations. PMID:22485199

  10. Knowledge, attitudes and perceptions of health professionals in relation to A/H1N1 influenza and its vaccine

    PubMed Central

    López-Picado, Amanda; Apiñaniz, Antxon; Ramos, Amaia Latorre; Miranda-Serrano, Erika; Cobos, Raquel; Parraza-Díez, Naiara; Amezua, Patricia; Martinez-Cengotitabengoa, Mónica; Aizpuru, Felipe

    2012-01-01

    Objective To determine the intention of health professionals, doctors and nurses, concerning whether or not to be vaccinated against A/H1N1 influenza virus, and their perception of the severity of this pandemic compared with seasonal flu. Material and Methods A cross-sectional study was carried out based on an questionnaire e-mailed to health professionals in public healthcare centres in Vitoria between 6 and 16 November 2009; the percentage of respondents who wanted to be vaccinated and who perceived the pandemic flu to carry a high risk of death were calculated. Results A total of 115 people completed the questionnaire of whom 61.7% (n=71) were doctors and 38.3% (n=44) were nurses. Of these, 33.3% (n=23) of doctors and 13.6% (n=6) of nurses intended to be vaccinated (p=0.019). Even among those who considered themselves to be at a high risk, 70.6% (n=48) of doctors and 31.7% (n=13) of nurses participating in the study (p=0.001) planned to have the vaccination. Conclusions Most health professionals, and in particular nurses, had no intention to be vaccinated against A/H1N1 influenza virus at the beginning of the vaccination campaign. PMID:22461846

  11. Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

    PubMed Central

    Casado, Itziar; Martínez-Baz, Iván; Burgui, Rosana; Irisarri, Fátima; Arriazu, Maite; Elía, Fernando; Navascués, Ana; Ezpeleta, Carmen; Aldaz, Pablo; Castilla, Jesús

    2014-01-01

    Background 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(H1N1)pdm09 in the pandemic and post-pandemic seasons. Methods 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(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. Results In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 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). Conclusion 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. PMID:25254376

  12. Transmission by super-spreading event of pandemic A/H1N1 2009 influenza during road and train travel.

    PubMed

    Pestre, Vincent; Morel, Bruno; Encrenaz, Nathalie; Brunon, Amandine; Lucht, Frédéric; Pozzetto, Bruno; Berthelot, Philippe

    2012-03-01

    The investigation of clustered cases of pandemic A/H1N1 2009 influenza virus infection (21 children, 3 adults) during a summer camp, led to the identification of transportation as the circumstance of transmission. Results suggest that super-spreading of flu can occur in a confined space without sufficient air renewal.

  13. Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic

    PubMed Central

    Freidl, Gudrun S.; van den Ham, Henk-Jan; Boni, Maciej F.; de Bruin, Erwin; Koopmans, Marion P.G.

    2016-01-01

    Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses. PMID:26853924

  14. Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009 A/H1N1 Influenza Vaccination

    PubMed Central

    Fell, Deshayne B.; Wilson, Kumanan; Ducharme, Robin; Hawken, Steven; Sprague, Ann E.; Kwong, Jeffrey C.; Smith, Graeme; Wen, Shi Wu; Walker, Mark C.

    2016-01-01

    Background Infants are at high risk for influenza illness, but are ineligible for vaccination before 6 months. Transfer of maternal antibodies to the fetus has been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical effectiveness is unknown. Our objective was to evaluate the association between 2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza and pneumonia. Methods We linked a population-based birth cohort to administrative databases to measure rates of influenza and pneumonia diagnosed during ambulatory physician visits, hospitalizations and emergency department visits during one year of follow-up. We estimated incidence rate ratios and 95% confidence intervals (95% CI) using Poisson regression, comparing infants born to A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants, adjusted for confounding using high-dimensional propensity scores. Results Among 117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women. Crude rates of influenza during the pandemic (per 100,000 infant-days) for vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27–3.76 and 3.60, 95% CI: 2.51–5.14, respectively), as were crude rates of influenza and pneumonia combined. We did not observe any significant differences in rates of study outcomes between study groups during the second wave of the 2009 A/H1N1 pandemic, nor during any post-pandemic time period. Conclusion We observed no difference in rates of study outcomes among infants born to A/H1N1-vaccinated mothers relative to unexposed infants born during the second A/H1N1 pandemic wave; however, due to late availability of the pandemic vaccine, the available follow-up time during the pandemic time period was very limited. PMID:27486858

  15. Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

    PubMed

    Helanterä, I; Anttila, V-J; Lappalainen, M; Lempinen, M; Isoniemi, H

    2015-09-01

    Seasonal influenza vaccination is recommended for patients with end-stage renal disease (ESRD), despite suggested inferior efficacy among these patients. We characterize an outbreak of influenza A(H1N1) in a kidney transplant unit. Altogether 23 patients were treated on the ward for postoperative care after kidney transplantation during the outbreak. After the first positive case, all patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal influenza vaccination, of whom 2/17 tested positive for influenza (one asymptomatic, one with mild cough). Five of six unvaccinated patients were diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure and were treated with ventilator support in the ICU, but all died due to acute respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis and recovered fully. The risk of influenza infection and mortality was significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7-507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed patients early after kidney transplantation. None of the vaccinated patients developed serious disease, supporting the role of vaccination also for ESRD patients.

  16. Timeliness of contact tracing among flight passengers for influenza A/H1N1 2009

    PubMed Central

    2011-01-01

    Background During the initial containment phase of influenza A/H1N1 2009, close contacts of cases were traced to provide antiviral prophylaxis within 48 h after exposure and to alert them on signs of disease for early diagnosis and treatment. Passengers seated on the same row, two rows in front or behind a patient infectious for influenza, during a flight of ≥ 4 h were considered close contacts. This study evaluates the timeliness of flight-contact tracing (CT) as performed following national and international CT requests addressed to the Center of Infectious Disease Control (CIb/RIVM), and implemented by the Municipal Health Services of Schiphol Airport. Methods Elapsed days between date of flight arrival and the date passenger lists became available (contact details identified - CI) was used as proxy for timeliness of CT. In a retrospective study, dates of flight arrival, onset of illness, laboratory diagnosis, CT request and identification of contacts details through passenger lists, following CT requests to the RIVM for flights landed at Schiphol Airport were collected and analyzed. Results 24 requests for CT were identified. Three of these were declined as over 4 days had elapsed since flight arrival. In 17 out of 21 requests, contact details were obtained within 7 days after arrival (81%). The average delay between arrival and CI was 3,9 days (range 2-7), mainly caused by delay in diagnosis of the index patient after arrival (2,6 days). In four flights (19%), contacts were not identified or only after > 7 days. CI involving Dutch airlines was faster than non-Dutch airlines (P < 0,05). Passenger locator cards did not improve timeliness of CI. In only three flights contact details were identified within 2 days after arrival. Conclusion CT for influenza A/H1N1 2009 among flight passengers was not successful for timely provision of prophylaxis. CT had little additional value for alerting passengers for disease symptoms, as this information already was provided

  17. New Influenza A/H1N1 (“Swine Flu”): information needs of airport passengers and staff

    PubMed Central

    Dickmann, P.; Rubin, G. J.; Gaber, W.; Wessely, S.; Wicker, S.; Serve, H.; Gottschalk, R.

    2010-01-01

    Please cite this paper as: Dickmann et al. (2010) New Influenza A/H1N1 (“Swine Flu”): information needs of airport passengers and staff. . Influenza and Other Respiratory Viruses 5(1), 39–46. Background  Airports are the entrances of infectious diseases. Particularly at the beginning of an outbreak, information and communication play an important role to enable the early detection of signs or symptoms and to encourage passengers to adopt appropriate preventive behaviour to limit the spread of the disease. Objectives  To determine the adequacy of the information provided to airport passengers and staff in meeting their information needs in relation to their concerns. Methods  At the start of the influenza A/H1N1 epidemic (29–30 April 2009), qualitative semi‐structured interviews (N = 101) were conducted at Frankfurt International Airport with passengers who were either returning from or going to Mexico and with airport staff who had close contact with these passengers. Interviews focused on knowledge about swine flu, information needs and fear or concern about the outbreak. Results  The results showed that a desire for more information was associated with higher concern – the least concerned participants did not want any additional information, while the most concerned participants reported a range of information needs. Airport staff in contact with passengers travelling from the epicentre of the outbreak showed the highest levels of fear or concern, coupled with a desire to be adequately briefed by their employer. Conclusions  Our results suggest that information strategies should address not only the exposed or potentially exposed but also groups that feel at risk. Identifying what information these different passenger and staff groups wish to receive will be an important task in any future infectious disease outbreak. PMID:21138539

  18. Gene signatures related to HAI response following influenza A/H1N1 vaccine in older individuals.

    PubMed

    Ovsyannikova, Inna G; Oberg, Ann L; Kennedy, Richard B; Zimmermann, Michael T; Haralambieva, Iana H; Goergen, Krista M; Grill, Diane E; Poland, Gregory A

    2016-05-01

    To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses. PMID:27441275

  19. Mortality Burden of the A/H1N1 Pandemic in Mexico: A Comparison of Deaths and Years of Life Lost to Seasonal Influenza

    PubMed Central

    Charu, Vivek; Chowell, Gerardo; Palacio Mejia, Lina Sofia; Echevarría-Zuno, Santiago; Borja-Aburto, Víctor H.; Simonsen, Lone; Miller, Mark A.

    2011-01-01

    Background. The mortality burden of the 2009 A/H1N1 influenza pandemic remains controversial, in part because of delays in reporting of vital statistics that are traditionally used to measure influenza-related excess mortality. Here, we compare excess mortality rates and years of life lost (YLL) for pandemic and seasonal influenza in Mexico and evaluate laboratory-confirmed death reports. Methods. Monthly age- and cause-specific death rates from January 2000 through April 2010 and population-based surveillance of influenza virus activity were used to estimate excess mortality and YLL in Mexico. Age-stratified laboratory-confirmed A/H1N1 death reports were obtained from an active surveillance system covering 40% of the population. Results. The A/H1N1 pandemic was associated with 11.1 excess all-cause deaths per 100 000 population and 445 000 YLL during the 3 waves of virus activity in Mexico, April–December 2009. The pandemic mortality burden was 0.6–2.6 times that of a typical influenza season and lower than that of the severe 2003–2004 influenza epidemic. Individuals aged 5–19 and 20–59 years were disproportionately affected relative to their experience with seasonal influenza. Laboratory-confirmed deaths captured 1 of 7 pandemic excess deaths overall but only 1 of 41 deaths in persons >60 years of age in 2009. A recrudescence of excess mortality was observed in older persons during winter 2010, in a period when influenza and respiratory syncytial virus cocirculated. Conclusions. Mexico experienced higher 2009 A/H1N1 pandemic mortality burden than other countries for which estimates are available. Further analyses of detailed vital statistics are required to assess geographical variation in the mortality patterns of this pandemic. PMID:21976464

  20. Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016.

    PubMed

    Chambers, Catharine; Skowronski, Danuta M; Sabaiduc, Suzana; Winter, Anne Luise; Dickinson, James A; De Serres, Gaston; Gubbay, Jonathan B; Drews, Steven J; Martineau, Christine; Eshaghi, Alireza; Krajden, Mel; Bastien, Nathalie; Li, Yan

    2016-01-01

    Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses. PMID:27020673

  1. The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability

    PubMed Central

    Castelán-Vega, Juan A; Magaña-Hernández, Anastasia; Jiménez-Alberto, Alicia; Ribas-Aparicio, Rosa María

    2014-01-01

    The last influenza A pandemic provided an excellent opportunity to study the adaptation of the influenza A(H1N1)pdm09 virus to the human host. Particularly, due to the availability of sequences taken from isolates since the beginning of the pandemic until date, we could monitor amino acid changes that occurred in the hemagglutinin (HA) as the virus spread worldwide and became the dominant H1N1 strain. HA is crucial to viral infection because it binds to sialidated cell-receptors and mediates fusion of cell and viral membranes; because antibodies that bind to HA may block virus entry to the cell, this protein is subjected to high selective pressure. Multiple alignment analysis of sequences of the HA from isolates taken since 2009 to date allowed us to find amino acid changes that were positively selected as the pandemic progressed. We found nine changes that became prevalent: HA1 subunits D104N, K166Q, S188T, S206T, A259T, and K285E; and HA2 subunits E47K, S124N, and E172K. Most of these changes were located in areas involved in inter- and intrachain interactions, while only two (K166Q and S188T) were located in known antigenic sites. We conclude that selective pressure on HA was aimed to improve its functionality and hence virus fitness, rather than at avoidance of immune recognition. PMID:25328411

  2. A Large Proportion of the Mexican Population Remained Susceptible to A(H1N1)pdm09 Infection One Year after the Emergence of 2009 Influenza Pandemic

    PubMed Central

    Veguilla, Vic; López-Gatell, Hugo; López-Martínez, Irma; Aparicio-Antonio, Rodrigo; Barrera-Badillo, Gisela; Rojo-Medina, Julieta; Gross, Felicia Liaini; Jefferson, Stacie N.; Katz, Jacqueline M.; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M.

    2016-01-01

    Background The 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors. Methods We evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005–2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population. Results Sera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged ≤19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI. Conclusions Despite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011–2012 and

  3. Hospitalization Fatality Risk of Influenza A(H1N1)pdm09: A Systematic Review and Meta-Analysis

    PubMed Central

    Wong, Jessica Y.; Kelly, Heath; Cheung, Chung-Mei M.; Shiu, Eunice Y.; Wu, Peng; Ni, Michael Y.; Ip, Dennis K. M.; Cowling, Benjamin J.

    2015-01-01

    During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%–3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting. PMID:26188191

  4. Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk

    PubMed Central

    Skowronski, Danuta M.; Hamelin, Marie-Eve; De Serres, Gaston; Janjua, Naveed Z.; Li, Guiyun; Sabaiduc, Suzana; Bouhy, Xavier; Couture, Christian; Leung, Anders; Kobasa, Darwyn; Embury-Hyatt, Carissa; de Bruin, Erwin; Balshaw, Robert; Lavigne, Sophie; Petric, Martin; Koopmans, Marion; Boivin, Guy

    2014-01-01

    During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in

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

    PubMed

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

    2016-02-01

    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.

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

    PubMed

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

    2016-02-01

    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. PMID:26776260

  7. Risk of Guillain–Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany†

    PubMed Central

    Prestel, Jürgen; Volkers, Peter; Mentzer, Dirk; Lehmann, Helmar C; Hartung, Hans-Peter; Keller-Stanislawski, Brigitte

    2014-01-01

    Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24817531

  8. Prospective cohort study of the safety of an influenza A(H1N1) vaccine in pregnant Chinese women.

    PubMed

    Ma, Fubao; Zhang, Longhua; Jiang, Renjie; Zhang, Jinlin; Wang, Huaqing; Gao, Xiaozhi; Li, Xiuhong; Liu, Yuanbao

    2014-09-01

    To monitor and evaluate the safety of the influenza A(H1N1) vaccine in pregnant women and its influence on the fetus and neonate, we performed a prospective study in which 122 pregnant Chinese women who received the influenza A(H1N1) vaccine and 104 pregnant women who did not receive any vaccine (serving as controls) were observed. The results indicated that the seroconversion rate in the vaccinated group was 90.4% (95% confidence interval [CI], 82.6% to 95.5%). The rate of adverse events following immunization in the pregnant women who received the influenza A(H1N1) vaccine was 3.3%. The spontaneous abortion rates in the vaccinated group and the unvaccinated group were 0.8% and 1.9%, respectively (exact probability test, P = 0.470), the prolonged-pregnancy rates were 8.2% and 4.8%, respectively (χ(2) = 1.041, P = 0.308), the low-birth-weight rates were 1.6% and 0.95%, respectively (exact probability test, P = 1.000), and the spontaneous-labor rates were 70.5% and 75%, respectively (χ(2) = 0.573, P = 0.449). All newborns who have an Apgar score of ≥7 are considered healthy; Apgar scores of ≥9 were observed in 38.5% and 57.7% of newborns in the vaccinated group and the unvaccinated group, respectively (χ(2) = 8.274, P = 0.004). From these results, we conclude that the influenza A(H1N1) vaccine is safe for pregnant women and has no observed adverse effects on fetal growth. (This study has been registered at ClinicalTrials.gov under registration no. NCT01842997.).

  9. Enhanced Pneumonia and Proinflammatory Cytokine Response in Pigs Challenged with Pandemic 2009 A/H1N1 Influenza Virus Following Vaccination with an Inactivated delta-Cluster H1N2 Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endemic strains of swine influenza A virus (IAV) in North America consist of the subtypes H1N1, H1N2, and H3N2. These circulating strains contain the triple reassortant internal gene (TRIG) cassette resulting from incorporation of genes from swine, avian, and human IAV’s. Genetic drift and reassortm...

  10. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination

    PubMed Central

    Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31–50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  11. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination.

    PubMed

    Jürchott, Karsten; Schulz, Axel Ronald; Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas; Babel, Nina; Thiel, Andreas; Neumann, Avidan Uriel

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31-50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  12. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination.

    PubMed

    Jürchott, Karsten; Schulz, Axel Ronald; Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas; Babel, Nina; Thiel, Andreas; Neumann, Avidan Uriel

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31-50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  13. Two waves of pandemic influenza A(H1N1) 2009 in Wales--the possible impact of media coverage on consultation rates, April-December 2009.

    PubMed

    Keramarou, M; Cottrell, S; Evans, M R; Moore, C; Stiff, R E; Elliott, C; Thomas, D R; Lyons, M; Salmon, R L

    2011-01-01

    In the United Kingdom, the influenza A(H1N1) 2009 pandemic had a distinct two-wave pattern of general practice consultations for influenza-like illness (ILI). We describe the epidemiology of the influenza pandemic in Wales between April and December 2009 using integrated data from a number of independent sources: GP surveillance, community virology surveillance, hospital admissions and deaths, and media enquiries monitoring. The first wave peaked in late July at 100 consultations per 100,000 general practice population and attracted intensive media coverage. The positivity rate for the A(H1N1)2009 influenza did not exceed 25% and only 44 hospitalisations and one death were recorded. By contrast, the second wave peaked in late October and although characterised by lower ILI consultation rates (65 consultations per 100,000 general practice population) and low profile media activity, was associated with much higher positivity rates for pandemic influenza A(H1N1)2009 (60%) and substantially more hospital admissions (n=379) and deaths (n=26). The large number of ILI-related consultations during the first wave in Wales probably reflected the intensive media activity rather than influenza virus circulating in the community. Data from community surveillance schemes may therefore have considerably overestimated the true incidence of influenza. This has implications for the future interpretation of ILI surveillance data and their use in policy making, and underlines the importance of using integrated epidemiological, virological and hospital surveillance data to monitor influenza activity. PMID:21262184

  14. Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

    PubMed

    Tsuge, Mitsuru; Oka, Takashi; Yamashita, Nobuko; Saito, Yukie; Fujii, Yosuke; Nagaoka, Yoshiharu; Yashiro, Masato; Tsukahara, Hirokazu; Morishima, Tsuneo

    2014-02-01

    Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

  15. Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic

    PubMed Central

    Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc

    2016-01-01

    ABSTRACT Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of

  16. Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

    PubMed Central

    Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark

    2014-01-01

    Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307

  17. Influenza A(H1N1)pdm09 resistance and cross-decreased susceptibility to oseltamivir and zanamivir antiviral drugs.

    PubMed

    Correia, Vanessa; Santos, Luis A; Gíria, Marta; Almeida-Santos, Maria M; Rebelo-de-Andrade, Helena

    2015-01-01

    Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.

  18. Segregation of Virulent Influenza A(H1N1) Variants in the Lower Respiratory Tract of Critically Ill Patients during the 2010–2011 Seasonal Epidemic

    PubMed Central

    Piralla, Antonio; Pariani, Elena; Rovida, Francesca; Campanini, Giulia; Muzzi, Alba; Emmi, Vincenzo; Iotti, Giorgio A.; Pesenti, Antonio; Conaldi, Pier Giulio; Zanetti, Alessandro; Baldanti, Fausto

    2011-01-01

    Background Since its appearance in 2009, the pandemic influenza A(H1N1) virus circulated worldwide causing several severe infections. Methods Respiratory samples from patients with 2009 influenza A(H1N1) and acute respiratory distress attending 24 intensive care units (ICUs) as well as from patients with lower respiratory tract infections not requiring ICU admission and community upper respiratory tract infections in the Lombardy region (10 million inhabitants) of Italy during the 2010–2011 winter-spring season, were analyzed. Results In patients with severe ILI, the viral load was higher in bronchoalveolar lavage (BAL) with respect to nasal swab (NS), (p<0.001) suggesting a higher virus replication in the lower respiratory tract. Four distinct virus clusters (referred to as cluster A to D) circulated simultaneously. Most (72.7%, n = 48) of the 66 patients infected with viruses belonging to cluster A had a severe (n = 26) or moderate ILI (n = 22). Amino acid mutations (V26I, I116M, A186T, D187Y, D222G/N, M257I, S263F, I286L/M, and N473D) were observed only in patients with severe ILI. D222G/N variants were detected exclusively in BAL samples. Conclusions Multiple virus clusters co-circulated during the 2010–2011 winter-spring season. Severe or moderate ILI were associated with specific 2009 influenza A(H1N1) variants, which replicated preferentially in the lower respiratory tract. PMID:22194826

  19. Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

    PubMed

    Maestri, Alvino; Sortica, Vinicius Albuquerque; Tovo-Rodrigues, Luciana; Santos, Mirleide Cordeiro; Barbagelata, Luana; Moraes, Milene Raiol; Alencar de Mello, Wyller; Gusmão, Leonor; Sousa, Rita Catarina Medeiros; Emanuel Batista Dos Santos, Sidney

    2015-01-01

    Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus. PMID:26436774

  20. A continuous peptide epitope reacting with pandemic influenza AH1N1 predicted by bioinformatic approaches.

    PubMed

    Carrillo-Vazquez, Jonathan P; Correa-Basurto, José; García-Machorro, Jazmin; Campos-Rodríguez, Rafael; Moreau, Violaine; Rosas-Trigueros, Jorge L; Reyes-López, Cesar A; Rojas-López, Marlon; Zamorano-Carrillo, Absalom

    2015-09-01

    Computational identification of potential epitopes with an immunogenic capacity challenges immunological research. Several methods show considerable success, and together with experimental studies, the efficiency of the algorithms to identify potential peptides with biological activity has improved. Herein, an epitope was designed by combining bioinformatics, docking, and molecular dynamics simulations. The hemagglutinin protein of the H1N1 influenza pandemic strain served as a template, owing to the interest of obtaining a scheme of immunization. Afterward, we performed enzyme-linked immunosorbent assay (ELISA) using the epitope to analyze if any antibodies in human sera before and after the influenza outbreak in 2009 recognize this peptide. Also, a plaque reduction neutralization test induced by virus-neutralizing antibodies and the IgG determination showed the biological activity of this computationally designed peptide. The results of the ELISAs demonstrated that the serum of both prepandemic and pandemic recognized the epitope. Moreover, the plaque reduction neutralization test evidenced the capacity of the designed peptide to neutralize influenza virus in Madin-Darby canine cells.

  1. A continuous peptide epitope reacting with pandemic influenza AH1N1 predicted by bioinformatic approaches.

    PubMed

    Carrillo-Vazquez, Jonathan P; Correa-Basurto, José; García-Machorro, Jazmin; Campos-Rodríguez, Rafael; Moreau, Violaine; Rosas-Trigueros, Jorge L; Reyes-López, Cesar A; Rojas-López, Marlon; Zamorano-Carrillo, Absalom

    2015-09-01

    Computational identification of potential epitopes with an immunogenic capacity challenges immunological research. Several methods show considerable success, and together with experimental studies, the efficiency of the algorithms to identify potential peptides with biological activity has improved. Herein, an epitope was designed by combining bioinformatics, docking, and molecular dynamics simulations. The hemagglutinin protein of the H1N1 influenza pandemic strain served as a template, owing to the interest of obtaining a scheme of immunization. Afterward, we performed enzyme-linked immunosorbent assay (ELISA) using the epitope to analyze if any antibodies in human sera before and after the influenza outbreak in 2009 recognize this peptide. Also, a plaque reduction neutralization test induced by virus-neutralizing antibodies and the IgG determination showed the biological activity of this computationally designed peptide. The results of the ELISAs demonstrated that the serum of both prepandemic and pandemic recognized the epitope. Moreover, the plaque reduction neutralization test evidenced the capacity of the designed peptide to neutralize influenza virus in Madin-Darby canine cells. PMID:25788327

  2. Psychological response of family members of patients hospitalised for influenza A/H1N1 in Oaxaca, Mexico

    PubMed Central

    2010-01-01

    Background The A/H1N1 pandemic originated in Mexico in April 2009, amid high uncertainty, social and economic disruption, and media reports of panic. The aim of this research project was to evaluate the psychological response of family primary caregivers of patients hospitalised in the Intensive Care Unit (ICU) with suspected influenza A/H1N1 to establish whether there was empirical evidence of high adverse psychological response, and to identify risk factors for such a response. If such evidence was found, a secondary aim was to develop a specific early intervention of psychological support for these individuals, to reduce distress and possibly lessen the likelihood of post-traumatic stress disorder (PTSD) in the longer term. Methods Psychological assessment questionnaires were administered to the family primary caregivers of patients hospitalised in the ICU in the General Hospital of Zone 1 of the Mexican Institute for Social Security (IMSS), Oaxaca, Mexico with suspected influenza A/H1N1, during the month of November 2009. The main outcome measures were ratings of reported perceived stress (PSS-10), depression (CES-D), and death anxiety (DAQ). Data were subjected to simple and multiple linear regression analysis to identify risk factors for adverse psychological response. Results Elevated levels of perceived stress and depression, compared to population normative data, and moderate levels of death anxiety were noted. Levels of depression were similar to those found in comparable studies of family members of ICU patients admitted for other conditions. Multiple regression analysis indicated that increasing age and non-spousal family relationship were significantly associated with depression and perceived stress. Female gender, increasing age, and higher levels of education were significantly associated with high death anxiety. Comparisons with data collected in previous studies in the same hospital ICU with groups affected by a range of other medical conditions

  3. Overview of the winter wave of 2009 pandemic influenza A(H1N1)v in Vojvodina, Serbia

    PubMed Central

    Petrović, Vladimir; Šeguljev, Zorica; Ćosić, Gorana; Ristić, Mioljub; Nedeljković, Jasminka; Dragnić, Nataša; Ukropina, Snežana

    2011-01-01

    Aim To analyze the epidemiological data for pandemic influenza A(H1N1)v in the Autonomous Province of Vojvodina, Serbia, during the season of 2009/2010 and to assess whether including severe acute respiratory illness (SARI) hospitalization data to the surveillance system gives a more complete picture of the impact of influenza during the pandemic. Methods From September 2009 to September 2010, the Institute of Public Health of Vojvodina conducted sentinel surveillance of influenza-like illnesses and acute respiratory infections in all hospitalized patients with SARI and virological surveillance of population of Vojvodina according to the European Centers for Disease Control technical document. Results The pandemic influenza outbreak in the province started in October 2009 (week 44) in students who had returned from a school-organized trip to Prague, Bratislava, and Vienna. The highest incidence rate was 1090 per 100 000 inhabitants, found in the week 50. The most affected age group were children 5-14 years old. A total of 1591 patients with severe illness were admitted to regional hospitals, with a case fatality rate of 2%, representing a hospitalization rate of 78.3 per 100 000 inhabitants and a mortality rate of 1.6 per 100 000. Most frequently hospitalized were 15-19 years old patients, male patients, and patients with pneumonia (P < 0.001). The highest case fatality rate was found among patients with acute respiratory distress syndrome (P < 0.001). Nasal/throat swabs were obtained for polymerase chain reaction test from 315 hospitalized patients and 20 non-hospitalized patients, and 145 (46%) and 15 (75%) specimens, respectively, tested positive on A(H1N1)v. Conclusion Sentinel influenza-like illness and SARI surveillance, both followed with virological surveillance, seem to be the optimal method to monitor the full scope of the influenza pandemic (from mild to severe influenza) in Vojvodina. PMID:21495196

  4. Performance of the Directigen EZ Flu A+B rapid influenza diagnostic test to detect pandemic influenza A/H1N1 2009.

    PubMed

    Boyanton, Bobby L; Almradi, Amro; Mehta, Tejal; Robinson-Dunn, Barbara

    2014-04-01

    The Directigen EZ Flu A+B rapid influenza diagnostic test, as compared to real-time reverse transcriptase polymerase chain reaction, demonstrated suboptimal performance to detect pandemic influenza A/H1N1 2009. Age- and viral load-stratified test sensitivity ranged from 33.3 to 84.6% and 0 to 100%, respectively.

  5. Pandemic influenza A(H1N1) 2009 vaccines in the European Union.

    PubMed

    Johansen, K; Nicoll, A; Ciancio, B C; Kramarz, P

    2009-01-01

    Pandemic vaccines from four manufacturers are now available for use within the European Union (EU). Use of these vaccines will protect individuals and reduce the impact on health services to more manageable levels. The majority of the severely ill will be from known risk groups and the best strategy will be to start vaccinating in line with the recommendation from the European Union Health Security Committee prioritizing adults and children with chronic conditions, pregnant women and healthcare workers. The composition of authorized vaccines is reviewed in this article. The vaccine strain in all authorized pandemic vaccines worldwide is based on the same initial isolate of influenza A/California/7/2009 (H1N1)v but the vaccines differ in conditions for virus propagation, antigen preparation, antigen content and whether they are adjuvanted or not. The vaccines are likely to be effective since no significant genetic or antigenic drift has occurred and there are already mechanisms for estimating clinical effectiveness. Influenza vaccines have good safety records and no safety concerns have so far been encountered with any of the vaccines developed. However, special mechanisms have been devised for the early detection and rigorous investigation of possible significant side effects in Europe through post-marketing surveillance and analysis. Delivery of the vaccines to the risk groups will pose difficulties where those with chronic illnesses are not readily identifiable to the healthcare services. There is considerable scope for European added value through Member States with excess vaccines making them available to other states. PMID:19883538

  6. HIV-1 and Its gp120 Inhibits the Influenza A(H1N1)pdm09 Life Cycle in an IFITM3-Dependent Fashion

    PubMed Central

    Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q.; Abrantes, Juliana L.; Costa, Eduardo; Temerozo, Jairo R.; Siqueira, Marilda M.; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L.

    2014-01-01

    HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010. PMID:24978204

  7. Permissive changes in the neuraminidase play a dominant role in improving the viral fitness of oseltamivir-resistant seasonal influenza A(H1N1) strains.

    PubMed

    Abed, Yacine; Pizzorno, Andrés; Bouhy, Xavier; Boivin, Guy

    2015-02-01

    Permissive neuraminidase (NA) substitutions such as R222Q, V234M and D344N have facilitated the emergence and worldwide spread of oseltamivir-resistant influenza A/Brisbane/59/2007 (H1N1)-H275Y viruses. However, the potential contribution of genetic changes in other viral segments on viral fitness remains poorly investigated. A series of recombinant A(H1N1)pdm09 and A/WSN/33 7:1 reassortants containing the wild-type (WT) A/Brisbane/59/2007 NA gene or its single (H275Y) and double (H275Y/Q222R, H275Y/M234V and H275Y/N344D) variants were generated and their replicative properties were assessed in vitro. The Q222R reversion substitution significantly reduced viral titers when evaluated in both A(H1N1)pdm09 and A/WSN/33 backgrounds. The permissive role of the R222Q was further confirmed using A/WSN/33 7:1 reassortants containing the NA gene of the oseltamivir-susceptible or oseltamivir-resistant influenza A/Mississippi/03/2001 strains. Therefore, NA permissive substitutions play a dominant role for improving viral replication of oseltamivir-resistant A (H1N1)-H275Y viruses in vitro.

  8. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza.

    PubMed

    Cheng, Zhongshan; Zhou, Jie; To, Kelvin Kai-Wang; Chu, Hin; Li, Cun; Wang, Dong; Yang, Dong; Zheng, Shufa; Hao, Ke; Bossé, Yohan; Obeidat, Ma'en; Brandsma, Corry-Anke; Song, You-Qiang; Chen, Yu; Zheng, Bo-Jian; Li, Lanjuan; Yuen, Kwok-Yung

    2015-10-15

    The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18-3.77; P = .01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.

  9. Mortality, Severe Acute Respiratory Infection, and Influenza-Like Illness Associated with Influenza A(H1N1)pdm09 in Argentina, 2009

    PubMed Central

    Azziz-Baumgartner, Eduardo; Cabrera, Ana María; Chang, Loretta; Calli, Rogelio; Kusznierz, Gabriela; Baez, Clarisa; Yedlin, Pablo; Zamora, Ana María; Cuezzo, Romina; Sarrouf, Elena Beatriz; Uboldi, Andrea; Herrmann, Juan; Zerbini, Elsa; Uez, Osvaldo; Rico Cordeiro, Pedro Osvaldo; Chavez, Pollyanna; Han, George; Antman, Julián; Coronado, Fatima; Bresee, Joseph; Kosacoff, Marina; Widdowson, Marc-Alain; Echenique, Horacio

    2012-01-01

    Introduction While there is much information about the burden of influenza A(H1N1)pdm09 in North America, little data exist on its burden in South America. Methods During April to December 2009, we actively searched for persons with severe acute respiratory infection and influenza-like illness (ILI) in three sentinel cities. A proportion of case-patients provided swabs for influenza testing. We estimated the number of case-patients that would have tested positive for influenza by multiplying the number of untested case-patients by the proportion who tested positive. We estimated rates by dividing the estimated number of case-patients by the census population after adjusting for the proportion of case-patients with missing illness onset information and ILI case-patients who visited physicians multiple times for one illness event. Results We estimated that the influenza A(H1N1)pdm09 mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years. A(H1N1)pdm09 hospitalization rates per 100,000 py ranged between 26.9 among children aged <5 years to 41.8 among persons aged ≥65 years. Influenza A(H1N1)pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to 17.1 among persons aged 45–64 years. While 9 (53%) of 17 influenza A(H1N1)pdm09 decedents with available data had obesity and 7 (17%) of 40 had diabetes, less than 4% of surviving influenza A(H1N1)pdm09 case-patients had these pre-existing conditions (p≤0.001). Conclusion Influenza A(H1N1)pdm09 caused a similar burden of disease in Argentina as in other countries. Such disease burden suggests the potential value of timely influenza vaccinations. PMID:23118877

  10. [Influenza A/H1N1 pandemic: central European experience and perspective of prevention and control of this disease].

    PubMed

    Snacken, R

    2009-01-01

    When the influenza pandemic A/H1N1 emerged in 2009, European countries activated their national pandemic plan that were initiated in 2005 when ECDC was established in Stockholm. This agency from the European Commission played its role to strengthen capacities of Member States. ECDC essentially focused attention on surveillance and its reinforcement, epidemic intelligence and guidance. Nevertheless, main challenges remain to be met: continuous adjustment of assumptions, weaknesses in national plans (e.g. no stockpile of antibiotics), paucity of investment in scientific research, no control of transmission from human to animal, persistence of the impact of the pandemic in the subsequent years and eventually the worrying unpreparedness of developing countries that paid a huge toll during previous pandemics.

  11. Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high-dose oseltamivir exposure.

    PubMed

    Watcharananan, S P; Suwatanapongched, T; Wacharawanichkul, P; Chantratitaya, W; Mavichak, V; Mossad, S B

    2010-04-01

    We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients. PMID:20102550

  12. Neurologic complications of influenza A(H1N1)pdm09

    PubMed Central

    Khandaker, Gulam; Zurynski, Yvonne; Buttery, Jim; Marshall, Helen; Richmond, Peter C.; Dale, Russell C.; Royle, Jenny; Gold, Michael; Snelling, Tom; Whitehead, Bruce; Jones, Cheryl; Heron, Leon; McCaskill, Mary; Macartney, Kristine; Elliott, Elizabeth J.

    2012-01-01

    Objective: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1′09) in children hospitalized with influenza. Methods: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1′09. Results: A total of 506 children with pH1N1′09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5–12.6 years) compared with 3.7 years (0.01–14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). Conclusions: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms. PMID:22993280

  13. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

    PubMed

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course. PMID:26379185

  14. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity

    PubMed Central

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10−8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course. PMID:26379185

  15. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

    PubMed

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  16. The 2009 A/H1N1 pandemic influenza and the nursing home.

    PubMed

    Gravenstein, Stefan; Pop-Vicas, Aurora; Ambrozaitis, Arvydas

    2010-12-01

    Seasonal and pandemic influenza clinically remain remarkably similar in long-term care populations. Clinicians cannot distinguish clinical influenza, whether seasonal or pandemic H1N1, from other respiratory viral infections in individual patients. Part of the difficulty in the clinical diagnosis relates to fewer clinical features that might help with diagnostic differentiation, such as fever. However, the nursing home provides an epidemiologic context that can prove helpful to clinicians who inquire--by considering illness patterns among others in the facility, both staff and residents. This can lead to more timely diagnosis and treatment in the resident, and prophylaxis--an opportunity to protect the remaining residents and staff. Check out the treatment guidelines posted on the CDC website to be sure to select the best agents, because antiviral resistance patterns have been rapidly changing. PMID:21214077

  17. The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile

    PubMed Central

    2012-01-01

    of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes. PMID:23148597

  18. 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.

    PubMed

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

    2014-05-01

    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

  19. Macrophage activation syndrome induced by A/H1N1 influenza in cystic fibrosis.

    PubMed

    Casciaro, Rosaria; Cresta, Federico; Favilli, Federica; Naselli, Aldo; De Alessandri, Alessandra; Minicucci, Laura

    2014-02-01

    Bacterial respiratory infections have an important impact on the development and progression of pulmonary disease in cystic fibrosis (CF). Viral infections are possible triggers of acute deterioration in the clinical status of CF patients. Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic disease characterized by pancytopenia, hepatitis, hyperferritinemia, coagulopathy, and neurologic symptoms. This syndrome is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. Here, we report the case of a boy affected by CF who developed MAS triggered by pandemic H1N1 influenza; good clinical response was obtained through high dose prednisone treatment. PMID:23401277

  20. [Fatal pneumonitis due to oseltamivir-resistant new influenza A(H1N1) in the case of an intensive care patient].

    PubMed

    Aardema, Heleen; Tulleken, Jaap E; van den Biggelaar, Ries J M; Wolters, Bert A; de Jager, Corine M; Boucher, Charles A B; Riezebos-Brilman, Annelies

    2010-01-01

    A 58-year-old man was submitted to our intensive care ward with respiratory failure due to pneumonitis. He had previously been treated for non-Hodgkin lymphoma by autologous stem cell transplantation, as a result of which bone marrow function was reduced. Further analysis showed infection with new influenza A(H1N1); typing revealed an oseltamivir-resistant subpopulation (H275Y). The patient was treated with oseltamivir and intravenously with zanamivir, but died of respiratory disease progression. This is the first published case of oseltamivir-resistant new influenza A(H1N1) infection in the Netherlands. PMID:20482913

  1. [Comparative analysis of A(H1N1) influenza epidemiological dynamics in Chile].

    PubMed

    Canals L, Mauricio

    2010-09-01

    In order to increase awareness of the pandemic and to streamline control measures before any new outbreak of influenza we analyze the behavior of the cases of Chile and from 9 countries with more cases in 2009. Reproductive numbers, doubling times and estimations of susceptible and infected at the end of the epidemic were estimated. Epidemic curves to the situation in Chile under different initial conditions were adjusted and simulations for different reproductive numbers and notification scenarios were performed. The reproductive numbers varied between 1.37 and 1.82, with doubling times of between 5 and 8 days at 30 days of the epidemic. According to this, the proportions of infected by the end of the epidemic vary between 58% and 78.5%. The transmission coefficient ranged from 2 to 132 new cases per day x 10(6) susceptible individuals. The adjustments showed that the onset of the epidemic probably had more cases than reported. All estimates suggest that there must have been a large number of susceptible and therefore can not be explained as small outbreaks in 2009. A large number of susceptible individuals may still exist who are at risk from a possible new outbreak.

  2. High Vaccination Coverage among Children during Influenza A(H1N1)pdm09 as a Potential Factor of Herd Immunity

    PubMed Central

    Matsuoka, Toshihiko; Sato, Tomoki; Akita, Tomoyuki; Yanagida, Jiturou; Ohge, Hiroki; Kuwabara, Masao; Tanaka, Junko

    2016-01-01

    The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1)pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010) on influenza A(H1N1)pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1)pdm09 and the pandemic vaccine effectiveness (VE) were estimated. The response rate was 53.5% (178,669/333,892). Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1)pdm09 was 2.18 (95% confidence interval (CI): 2.13–2.23) and the VE was 43.9% (CI: 42.8–44.9). The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7–15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak. PMID:27763532

  3. Molecular modeling studies demonstrate key mutations that could affect the ligand recognition by influenza AH1N1 neuraminidase.

    PubMed

    Ramírez-Salinas, Gema L; García-Machorro, J; Quiliano, Miguel; Zimic, Mirko; Briz, Verónica; Rojas-Hernández, Saul; Correa-Basurto, J

    2015-11-01

    The goal of this study was to identify neuraminidase (NA) residue mutants from human influenza AH1N1 using sequences from 1918 to 2012. Multiple alignment studies of complete NA sequences (5732) were performed. Subsequently, the crystallographic structure of the 1918 influenza (PDB ID: 3BEQ-A) was used as a wild-type structure and three-dimensional (3-D) template for homology modeling of the mutated selected NA sequences. The 3-D mutated NAs were refined using molecular dynamics (MD) simulations (50 ns). The refined 3-D models were used to perform docking studies using oseltamivir. Multiple sequence alignment studies showed seven representative mutations (A232V, K262R, V263I, T264V, S367L, S369N, and S369K). MD simulations applied to 3-D NAs showed that each NA had different active-site shapes according to structural surface visualization and docking results. Moreover, Cartesian principal component analyses (cPCA) show structural differences among these NA structures caused by mutations. These theoretical results suggest that the selected mutations that are located outside of the active site of NA could affect oseltamivir recognition and could be associated with resistance to oseltamivir.

  4. Molecular modeling studies demonstrate key mutations that could affect the ligand recognition by influenza AH1N1 neuraminidase.

    PubMed

    Ramírez-Salinas, Gema L; García-Machorro, J; Quiliano, Miguel; Zimic, Mirko; Briz, Verónica; Rojas-Hernández, Saul; Correa-Basurto, J

    2015-11-01

    The goal of this study was to identify neuraminidase (NA) residue mutants from human influenza AH1N1 using sequences from 1918 to 2012. Multiple alignment studies of complete NA sequences (5732) were performed. Subsequently, the crystallographic structure of the 1918 influenza (PDB ID: 3BEQ-A) was used as a wild-type structure and three-dimensional (3-D) template for homology modeling of the mutated selected NA sequences. The 3-D mutated NAs were refined using molecular dynamics (MD) simulations (50 ns). The refined 3-D models were used to perform docking studies using oseltamivir. Multiple sequence alignment studies showed seven representative mutations (A232V, K262R, V263I, T264V, S367L, S369N, and S369K). MD simulations applied to 3-D NAs showed that each NA had different active-site shapes according to structural surface visualization and docking results. Moreover, Cartesian principal component analyses (cPCA) show structural differences among these NA structures caused by mutations. These theoretical results suggest that the selected mutations that are located outside of the active site of NA could affect oseltamivir recognition and could be associated with resistance to oseltamivir. PMID:26499499

  5. Immunogenicity and Efficacy of A/H1N1pdm Vaccine Among Subjects With Severe Motor and Intellectual Disability in the 2010/11 Influenza Season

    PubMed Central

    Hara, Megumi; Hanaoka, Tomoyuki; Maeda, Kazuhiro; Kase, Tetsuo; Ohfuji, Satoko; Fukushima, Wakaba; Hirota, Yoshio

    2016-01-01

    Background While the immunogenicity and effectiveness of seasonal influenza vaccines among subjects with severe motor and intellectual disability (SMID) are known to be diminished, the efficacy of the A/H1N1pdm vaccine has not been evaluated. Methods We prospectively evaluated 103 subjects with SMID (mean age, 41.7 years) who received trivalent inactivated influenza vaccine during the 2010/11 influenza season. The hemagglutination inhibition (HI) antibody titer was measured in serum samples collected pre-vaccination (S0), post-vaccination (S1), and end-of-season (S2) to evaluate subjects’ immunogenicity capacity. Vaccine efficacy was assessed based on antibody efficacy and achievement proportion. Results The proportions of seroprotection and seroconversion, and the geometric mean titer (GMT) ratio (GMT at S1/GMT at S0) for A/H1N1pdm were 46.0%, 16.0%, and 1.8, respectively—values which did not meet the European Medicines Evaluation Agency criteria. The achievement proportion was 26%. During follow-up, 11 of 43 subjects with acute respiratory illness were diagnosed with type A influenza according to a rapid influenza diagnostic test (RIDT), and A/H1N1pdm strains were isolated from the throat swabs of 5 of those 11 subjects. When either or both RIDT-diagnosed influenza or serologically diagnosed influenza (HI titer at S2/HI titer at S1 ≥2) were defined as probable influenza, subjects with A/H1N1pdm seroprotection were found to have a lower incidence of probable influenza (odds ratio, 0.31; antibody efficacy, 69%; vaccine efficacy, 18%). Conclusions In the present seasonal assessment, antibody efficacy was moderate against A/H1N1pdm among SMID subjects, but vaccine efficacy was low due to the reduced immunogenicity of SMID subjects. PMID:26780860

  6. Epidemiological Characterization of a Fourth Wave of Pandemic A/H1N1 Influenza in Mexico, Winter 2011–2012: Age Shift and Severity

    PubMed Central

    Borja-Aburto, Víctor H.; Chowell, Gerardo; Viboud, Cécile; Simonsen, Lone; Miller, Mark A.; Grajales-Muñiz, Concepción; González-Bonilla, Cesar R.; Diaz-Quiñonez, Jose A; Echevarría-Zuno, Santiago

    2012-01-01

    Background and Aims A substantial recrudescent wave of pandemic influenza A/H1N1 affected the Mexican population from December 1, 2011–March 20, 2012 following a 2-year period of sporadic transmission. Methods We analyzed demographic and geographic data on all hospitalizations with severe acute respiratory infection (SARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by a Mexican social security medical system during April 1, 2009– March 20, 2012. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset. Results A total of 7569 SARI hospitalizations and 443 in-patient deaths (5.9%) were reported between December 1, 2011, and March 20, 2012 (1115 A/H1N1-positive inpatients and 154 A/H1N1-positive deaths). The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among subjects ≥60 years of age (χ2 test, p <0.0001) and lower among younger age groups (χ2 test, p <0.04) for the 2011–2012 pandemic wave compared to the earlier waves in 2009. The reproduction number of the winter 2011–2012 wave in central Mexico was estimated at 1.2–1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009. Conclusions We documented a substantial increase in the number of SARI hospitalizations during the period December 2011–March 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is consistent with a build-up of immunity among younger populations. PMID:23079035

  7. Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010

    PubMed Central

    Rossetto, Érika Valeska; Luna, Expedito José de Albuquerque

    2015-01-01

    ABSTRACT Objective: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. Methods: A descriptive study of cases reported in Sistema de Informação de Agravos de Notificação (SINAN), 2009-2010. Results: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. Conclusion: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus. PMID:26154537

  8. Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs.

    PubMed

    Tanaka, Seiji; Saikusa, Tomoko; Katafuchi, Yuno; Ushijima, Kosuke; Ohtsu, Yasushi; Tsumura, Naoki; Ito, Yuhei

    2015-09-11

    A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.

  9. WHO recommendations for the viruses used in the 2013-2014 Northern Hemisphere influenza vaccine: Epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013.

    PubMed

    Barr, Ian G; Russell, Colin; Besselaar, Terry G; Cox, Nancy J; Daniels, Rod S; Donis, Ruben; Engelhardt, Othmar G; Grohmann, Gary; Itamura, Shigeyuki; Kelso, Anne; McCauley, John; Odagiri, Takato; Schultz-Cherry, Stacey; Shu, Yuelong; Smith, Derek; Tashiro, Masato; Wang, Dayan; Webby, Richard; Xu, Xiyan; Ye, Zhiping; Zhang, Wenqing

    2014-08-20

    In February the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winter in the Northern Hemisphere. These recommendations are based on data collected by National Influenza Centres (NICs) through the WHO Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations of the 2013-2014 Northern Hemisphere influenza vaccine composition.

  10. Using High-Throughput Sequencing to Leverage Surveillance of Genetic Diversity and Oseltamivir Resistance: A Pilot Study during the 2009 Influenza A(H1N1) Pandemic

    PubMed Central

    Téllez-Sosa, Juan; Rodríguez, Mario Henry; Gómez-Barreto, Rosa E.; Valdovinos-Torres, Humberto; Hidalgo, Ana Cecilia; Cruz-Hervert, Pablo; Luna, René Santos; Carrillo-Valenzo, Erik; Ramos, Celso; García-García, Lourdes; Martínez-Barnetche, Jesús

    2013-01-01

    Background Influenza viruses display a high mutation rate and complex evolutionary patterns. Next-generation sequencing (NGS) has been widely used for qualitative and semi-quantitative assessment of genetic diversity in complex biological samples. The “deep sequencing” approach, enabled by the enormous throughput of current NGS platforms, allows the identification of rare genetic viral variants in targeted genetic regions, but is usually limited to a small number of samples. Methodology and Principal Findings We designed a proof-of-principle study to test whether redistributing sequencing throughput from a high depth-small sample number towards a low depth-large sample number approach is feasible and contributes to influenza epidemiological surveillance. Using 454-Roche sequencing, we sequenced at a rather low depth, a 307 bp amplicon of the neuraminidase gene of the Influenza A(H1N1) pandemic (A(H1N1)pdm) virus from cDNA amplicons pooled in 48 barcoded libraries obtained from nasal swab samples of infected patients (n  =  299) taken from May to November, 2009 pandemic period in Mexico. This approach revealed that during the transition from the first (May-July) to second wave (September-November) of the pandemic, the initial genetic variants were replaced by the N248D mutation in the NA gene, and enabled the establishment of temporal and geographic associations with genetic diversity and the identification of mutations associated with oseltamivir resistance. Conclusions NGS sequencing of a short amplicon from the NA gene at low sequencing depth allowed genetic screening of a large number of samples, providing insights to viral genetic diversity dynamics and the identification of genetic variants associated with oseltamivir resistance. Further research is needed to explain the observed replacement of the genetic variants seen during the second wave. As sequencing throughput rises and library multiplexing and automation improves, we foresee that the approach

  11. General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic

    PubMed Central

    2010-01-01

    Background Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress. Method Between September 1st and 30th, 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28. Results More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008). Conclusions A significant proportion of

  12. Impact of antiviral treatment and hospital admission delay on risk of death associated with 2009 A/H1N1 pandemic influenza in Mexico

    PubMed Central

    2012-01-01

    Background Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics. In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico. Methods We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system

  13. Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran

    PubMed Central

    Sharifirad, Gholamreza; Yarmohammadi, Parastoo; Sharifabad, Mohammad Ali Morowati; Rahaei, Zohreh

    2014-01-01

    Introduction: Influenza A/H1N1 pandemic has recently threatened the health of world's population more than ever. Non-pharmaceutical measures are important to prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective influenza pandemic management requires understanding of the factors influencing preventive behavioral. This study reports on predictors of students’ preventive behaviors for pandemic influenza A/H1N1 using variables based on the protection motivation theory (PMT). Materials and Methods: In a cross-sectional study, multiple-stage randomized sampling was used to select 300 female students in Isfahan who completed a questionnaire in December 2009. Data were collected using a self-report questionnaire based on PMT. The statistical analysis of the data included bivariate correlations, Mann-Whitney, Kruskal-Wallis, and linear regression. Results: The mean age of participants was 15.62 (SE = 1.1) years old. Majority of participants were aware regarding pandemic influenza A/H1N1 (87.3%, 262 out of 300). Results showed that, protection motivation was highly significant relationship with preventive behavior and predicted 34% of its variance. We found all of the variables with the exception of perceived susceptibility, perceived severity, and response cost were related with protection motivation and explained 22% of its variance. Conclusion: Promotion of students’ self-efficacy, and intention to protect themselves from a health threat should be priorities of any programs aimed at promoting preventive behaviors among students. It is also concluded that the protection motivation theory may be used in developing countries, like Iran, as a framework for prevention interventions in an attempt to improve the preventive behaviors of students. PMID:24741647

  14. Dependence of the results of ecological-epidemic investigation of influenza A(H1N1) on immunity

    NASA Astrophysics Data System (ADS)

    Fathudinova, Mohinav; Alimova, Barno; Rahimova, Halima

    2016-07-01

    This report presents the results of ecology-epidemical and immunological researches influ-enza virus A (H1 N1) and acute respiratory infection in Dushanbe from 2011 till 2015. The received results epidemiological and immunological analysis showed us, that last years has been changed not only characteristics of influenza epidemic, but it can not be notice the low-er of intensively of the collective immunity to actual versions influenza viruses A and B

  15. Serum activin A and B, and follistatin in critically ill patients with influenza A(H1N1) infection

    PubMed Central

    2014-01-01

    Background Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients. Methods A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7. Results Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P < 0.05 for all). Conclusions Higher than normal values of these proteins were common in patients with H1N1 infection but we found no association with the severity of their respiratory failure. PMID:24885241

  16. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

    PubMed

    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

    2015-05-01

    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

  17. The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

    PubMed Central

    Haralambieva, Iana H.; Painter, Scott D.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Goergen, Krista M.; Oberg, Ann L.; Poland, Gregory A.

    2015-01-01

    Background Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly. Methods We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles – TREC content, peripheral white blood cell telomerase – TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination. Results TERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively). Conclusion Our data suggest that influenza-specific humoral immunity

  18. Polymorphisms at Residue 222 of the Hemagglutinin of Pandemic Influenza A(H1N1)pdm09: Association of Quasi-Species to Morbidity and Mortality in Different Risk Categories

    PubMed Central

    Resende, Paola Cristina; Motta, Fernando C.; Oliveira, Maria de Lourdes A.; Gregianini, Tatiana S.; Fernandes, Sandra B.; Cury, Ana Luisa F.; do Carmo D. Rosa, Maria; Souza, Thiago Moreno L.; Siqueira, Marilda M.

    2014-01-01

    The D222G substitution in the hemagglutinin (HA) gene of the pandemic influenza A(H1N1)pdm09 virus has been identified as a potential virulence marker, because this change allows for virus invasion deeper into the respiratory tract. In this study, we analyzed D, G and N polymorphisms at residue 222 by pyrosequencing (PSQ). We initially analyzed 401 samples from Brazilian patients. These were categorized with respect to clinical conditions due to influenza infection (mild, serious or fatal) and sub-stratified by risky factors. The frequency of mixed population of virus, with more than one polymorphism at residue 222, was significantly higher in serious (10.6%) and fatal (46.7%) influenza cases, whereas those who showed mild influenza infections were all infected by D222 wild-type. Mixtures of quasi-species showed a significant association of mortality, especially for those with risk factors, in special pregnant women. These results not only reinforce the association between D222G substitution and influenza A(H1N1)pdm09-associated morbidity and mortality, but also add the perspective that a worse clinical prognosis is most likely correlated with mixtures of quasi-species at this HA residue. Therefore, quasi-species may have a critical and underestimated role in influenza-related clinical outcomes. PMID:24667815

  19. A spatial-temporal transmission model and early intervention policies of 2009 A/H1N1 influenza in South Korea.

    PubMed

    Lee, Jonggul; Jung, Eunok

    2015-09-01

    We developed a spatial-temporal model of the 2009 A/H1N1 influenza pandemic in the Seoul metropolitan area (SMA), which is located in the north-west of South Korea and is the second-most complex metropolitan area worldwide. This multi-patch influenza model consists of a SEIAR influenza transmission model and flow model between two districts. This model is based on the daily confirmed cases of A/H1N1 influenza collected by the Korea Center for Disease Control and Prevention from April 27 to September 15, 2009 and the daily commuting data from 33 districts of SMA reported in the 2010 Population and Housing Census (PHC). We analyzed the spread patterns of 2009 influenza in the SMA by the reproductive numbers and geographic information systems. During the early period of novel influenza pandemics, when pharmaceutical interventions are lacking, non-pharmaceutical public health interventions will be the most critical strategies for impeding the spread of influenza and delaying an epidemic. Using the spatial-temporal model developed herein, we also investigated the impact of non-pharmaceutical public health interventions, isolation and/or commuting restrictions, on the incidence reduction in various scenarios. Our model provides scientific evidence for predicting the spread of disease and preparedness for a future pandemic.

  20. Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1

    PubMed Central

    Greatorex, Jane S.; Page, Rosanna F.; Curran, Martin D.; Digard, Paul; Enstone, Joanne E.; Wreghitt, Tim; Powell, Penny P.; Sexton, Darren W.; Vivancos, Roberto; Nguyen-Van-Tam, Jonathan S.

    2010-01-01

    Background In the event of an influenza pandemic, the majority of people infected will be nursed at home. It is therefore important to determine simple methods for limiting the spread of the virus within the home. The purpose of this work was to test a representative range of common household cleaning agents for their effectiveness at killing or reducing the viability of influenza A virus. Methodology/Principal Findings Plaque assays provided a robust and reproducible method for determining virus viability after disinfection, while a National Standard influenza virus RT-PCR assay (VSOP 25, www.hpa-standardmethods.org.uk) was adapted to detect viral genome, and a British Standard (BS:EN 14476:2005) was modified to determine virus killing. Conclusions/Significance Active ingredients in a number of the cleaning agents, wipes, and tissues tested were able to rapidly render influenza virus nonviable, as determined by plaque assay. Commercially available wipes with a claimed antiviral or antibacterial effect killed or reduced virus infectivity, while nonmicrobiocidal wipes and those containing only low concentrations (<5%) of surfactants showed lower anti-influenza activity. Importantly, however, our findings indicate that it is possible to use common, low-technology agents such as 1% bleach, 10% malt vinegar, or 0.01% washing-up liquid to rapidly and completely inactivate influenza virus. Thus, in the context of the ongoing pandemic, and especially in low-resource settings, the public does not need to source specialized cleaning products, but can rapidly disinfect potentially contaminated surfaces with agents readily available in most homes. PMID:20126543

  1. Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study.

    PubMed

    Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe

    2015-01-01

    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. PMID:25715115

  2. Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study

    PubMed Central

    Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe

    2015-01-01

    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. PMID:25715115

  3. Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control

    PubMed Central

    Greatorex, Jane S.; Digard, Paul; Curran, Martin D.; Moynihan, Robert; Wensley, Harrison; Wreghitt, Tim; Varsani, Harsha; Garcia, Fayna; Enstone, Joanne; Nguyen-Van-Tam, Jonathan S.

    2011-01-01

    Background The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. Methodology and Principal Findings Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. Conclusions/Significance The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals. PMID:22132172

  4. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin

    PubMed Central

    Wilson, Jason R.; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O.; Katz, Jacqueline M.; York, Ian A.

    2016-01-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72–130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Importance Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely-related viruses. In spite of this limited range of protection, recent findings indicate individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help put bounds on the

  5. Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013-14: Results from the InNHOVE network.

    PubMed

    Rondy, M; Castilla, J; Launay, O; Costanzo, S; Ezpeleta, C; Galtier, F; de Gaetano Donati, K; Moren, A

    2016-05-01

    We conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: -1.9;85.4), 39.4% (95%CI: -32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18-64, 65-79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: -145.3;65.4), 25.6% (95%CI: -36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18-64, 65-79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013-14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. PMID:27065000

  6. Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013-14: Results from the InNHOVE network.

    PubMed

    Rondy, M; Castilla, J; Launay, O; Costanzo, S; Ezpeleta, C; Galtier, F; de Gaetano Donati, K; Moren, A

    2016-05-01

    We conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: -1.9;85.4), 39.4% (95%CI: -32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18-64, 65-79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: -145.3;65.4), 25.6% (95%CI: -36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18-64, 65-79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013-14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups.

  7. Use of Cumulative Incidence of Novel Influenza A/H1N1 in Foreign Travelers to Estimate Lower Bounds on Cumulative Incidence in Mexico

    PubMed Central

    Lipsitch, Marc; Lajous, Martin; O'Hagan, Justin J.; Cohen, Ted; Miller, Joel C.; Goldstein, Edward; Danon, Leon; Wallinga, Jacco; Riley, Steven; Dowell, Scott F.; Reed, Carrie; McCarron, Meg

    2009-01-01

    Background An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1. Methods and Results We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude. Conclusions We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases. PMID:19742302

  8. Sensitivity of the Quidel Sofia Fluorescent Immunoassay Compared With 2 Nucleic Acid Assays and Viral Culture to Detect Pandemic Influenza A(H1N1)pdm09.

    PubMed

    Arbefeville, Sophie S; Fickle, Ann R; Ferrieri, Patricia

    2015-01-01

    To confirm a diagnosis of influenza at the point of care, healthcare professionals may rely on rapid influenza diagnostic tests (RIDTs). RIDTs have low to moderate sensitivity compared with viral culture or real-time reverse-transcription polymerase chain reaction (rRT-PCR). With the resurgence of the influenza A (Flu A; subtype H1N1) pandemic 2009 (pdm09) strain in the years 2013 and 2014, we evaluated the accuracy of the United State Food and Drug Administration (FDA)-approved Sofia Influenza A+B Fluorescent Immunoassay to detect epidemic Flu A(H1N1)pdm09 in specimens from the upper-respiratory tract. During a 3-month period, we collected 40 specimens that tested positive via PCR and/or culture for Flu A of the H1N1 pdm09 subtype. Of the 40 specimens, 27 tested positive (67.5%) via Sofia assay for Flu A. Of the 13 specimens with a negative result via Sofia testing, 4 had coinfection, as detected by the GenMark Diagnostics eSensor Respiratory Viral Panel. This sensitivity of the RIDT Sofia assay to detect Flu A(H1N1) pdm09 was comparable to previously reported sensitivities ranging from 10% to 75% for older RIDTs.

  9. Molecular epidemiology and phylogenetic analysis of HA gene of influenza A(H1N1)pdm09 strain during 2010-2014 in Dalian, North China.

    PubMed

    Han, Yan; Sun, Nan; Lv, Qiu-Yue; Liu, Dan-Hong; Liu, Da-Peng

    2016-10-01

    The objective of the present study was to evaluate the epidemiology of influenza A(H1N1)pdm09 and its hemagglutinin (HA) molecular and phylogenetic analysis during 2010-2014 in Dalian, North China. A total of 3717 influenza-like illness (ILI) cases were tested by real-time PCR and 493 were found to be positive. Out of these 493 cases, 121 were subtype influenza A(H1N1)pdm09, of which 14 cases were reported in 2010-2011, 29 in 2012-2013, and 78 in 2013-2014. HA coding regions of 45 isolates were compared to that of the vaccine strain A/California/7/09(H1N1), and a number of variations were detected. P83S, S185T, S203T, R223Q, and I321V mutations were observed in all of the Dalian isolates. Furthermore, a high proportion >71 % of the strains possessed the variation D97N and K283E. Phylogenetic analysis confirmed the close match of the majority of circulating strains with the vaccine strains. However, it also reveals a trend of strains to accumulate amino acid variations and form new phylogenetic groups. PMID:27251702

  10. Molecular epidemiology and phylogenetic analysis of HA gene of influenza A(H1N1)pdm09 strain during 2010-2014 in Dalian, North China.

    PubMed

    Han, Yan; Sun, Nan; Lv, Qiu-Yue; Liu, Dan-Hong; Liu, Da-Peng

    2016-10-01

    The objective of the present study was to evaluate the epidemiology of influenza A(H1N1)pdm09 and its hemagglutinin (HA) molecular and phylogenetic analysis during 2010-2014 in Dalian, North China. A total of 3717 influenza-like illness (ILI) cases were tested by real-time PCR and 493 were found to be positive. Out of these 493 cases, 121 were subtype influenza A(H1N1)pdm09, of which 14 cases were reported in 2010-2011, 29 in 2012-2013, and 78 in 2013-2014. HA coding regions of 45 isolates were compared to that of the vaccine strain A/California/7/09(H1N1), and a number of variations were detected. P83S, S185T, S203T, R223Q, and I321V mutations were observed in all of the Dalian isolates. Furthermore, a high proportion >71 % of the strains possessed the variation D97N and K283E. Phylogenetic analysis confirmed the close match of the majority of circulating strains with the vaccine strains. However, it also reveals a trend of strains to accumulate amino acid variations and form new phylogenetic groups.

  11. Monitoring pandemic influenza A(H1N1) vaccination coverage in Germany 2009/10 - results from thirteen consecutive cross-sectional surveys.

    PubMed

    Walter, Dietmar; Böhmer, Merle M; Heiden, Matthias an der; Reiter, Sabine; Krause, Gérard; Wichmann, Ole

    2011-05-23

    To monitor pandemic influenza A(H1N1) vaccine uptake during the vaccination campaign in Germany 2009/10, thirteen consecutive cross-sectional telephone-surveys were performed between November 2009 and April 2010. In total 13,010 household-interviews were conducted. Vaccination coverage in persons >14 years of age remained low, both in the general population (8.1%; 95%CI: 7.4-8.8) and in specific target groups such as healthcare workers and individuals with underlying chronic diseases (12.8%; 95%CI: 11.4-14.4). Previous vaccination against seasonal influenza was a main factor independently associated with pandemic influenza vaccination (Odds ratio=8.8; 95%CI: 7.2-10.8). The campaign failed to reach people at risk who were not used to receive their annual seasonal influenza shot.

  12. Transmission of the First Influenza A(H1N1)pdm09 Pandemic Wave in Australia Was Driven by Undetected Infections: Pandemic Response Implications

    PubMed Central

    Fielding, James E.; Kelly, Heath A.; Glass, Kathryn

    2015-01-01

    Background During the first wave of influenza A(H1N1)pdm09 in Victoria, Australia the rapid increase in notified cases and the high proportion with relatively mild symptoms suggested that community transmission was established before cases were identified. This lead to the hypothesis that those with low-level infections were the main drivers of the pandemic. Methods A deterministic susceptible-infected-recovered model was constructed to describe the first pandemic wave in a population structured by disease severity levels of asymptomatic, low-level symptoms, moderate symptoms and severe symptoms requiring hospitalisation. The model incorporated mixing, infectivity and duration of infectiousness parameters to calculate subgroup-specific reproduction numbers for each severity level. Results With stratum-specific effective reproduction numbers of 1.82 and 1.32 respectively, those with low-level symptoms, and those with asymptomatic infections were responsible for most of the transmission. The effective reproduction numbers for infections resulting in moderate symptoms and hospitalisation were less than one. Sensitivity analyses confirmed the importance of parameters relating to asymptomatic individuals and those with low-level symptoms. Conclusions Transmission of influenza A(H1N1)pdm09 was largely driven by those invisible to the health system. This has implications for control measures–such as distribution of antivirals to cases and contacts and quarantine/isolation–that rely on detection of infected cases. Pandemic plans need to incorporate milder scenarios, with a graded approach to implementation of control measures. PMID:26692335

  13. Autoimmune disorders after immunisation with Influenza A/H1N1 vaccines with and without adjuvant: EudraVigilance data and literature review.

    PubMed

    Isai, Alina; Durand, Julie; Le Meur, Steven; Hidalgo-Simon, Ana; Kurz, Xavier

    2012-11-19

    All suspected autoimmune disorders (AID) reported as adverse reactions to EudraVigilance from 1 October 2009 to 31 December 2010 for adjuvanted (Celtura™, Fluval P™, Focetria™ and Pandemrix™) and non-adjuvanted (Cantgrip™, Celvapan™ and Panenza™) pandemic Influenza A/H1N1 vaccines were analysed to determine whether adjuvanted vaccines were associated with higher reporting of AID than non-adjuvanted ones. AID were identified based on the corresponding MedDRA High Level Group Term. Reports of type 1 diabetes mellitus and multiple sclerosis were also included in the analysis. Causality was assessed based on WHO causality assessment for adverse events following immunisation and Brighton Collaboration criteria for Guillain-Barré syndrome (GBS), idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis. Of the 50,221 adverse reactions received in EudraVigilance for A/H1N1 vaccines (adjuvanted: 46,173, non-adjuvanted: 4048), 314 were AID (adjuvanted: 276, non-adjuvanted: 38). GBS was the AID with the highest number of reports (125, adjuvanted: 109, non-adjuvanted: 16). Reporting ratios as calculated by the percentages of AID amongst all reported adverse reactions were 0.60% (95% CI: 0.53-0.67) and 0.94% (95% CI: 0.64-1.24) for adjuvanted and non-adjuvanted vaccines, and were 0.26% (95% CI: 0.22-0.31) and 0.37% (95% CI: 0.18-0.56) in a restricted analysis based on diagnostic certainty, causal relationship and plausible temporal association. Reporting rates for all reports of AID using the estimated number of vaccinees as denominator were 6.87 (95% CI: 6.06-7.68) and 9.98 (95% CI: 6.81-13.16) per million for adjuvanted and non-adjuvanted vaccines, and 3.01 (95% CI: 2.47-3.55) and 3.94 (95% CI: 1.95-5.94) per million in the restricted analysis. These results do not suggest a difference in the reporting of AID between adjuvanted and non-adjuvanted A/H1N1 vaccines. In a literature review performed on 31 August 2011, GBS was also the AID the

  14. Unequal access to vaccines in the WHO European Region during the A(H1N1) influenza pandemic in 2009.

    PubMed

    Jorgensen, Pernille; Wasley, Annemarie; Mereckiene, Jolita; Cotter, Suzanne; Weber, J Todd; Brown, Caroline Sarah

    2013-08-28

    In a severe pandemic, rapid production and deployment of vaccines will potentially be critical in mitigating the impact on populations and essential services. We compared access to vaccines and timing of delivery relative to identification of A(H1N1)pdm09 and the geographic progression of the pandemic in the WHO European Region in order to identify gaps in provision. Information on vaccine procurement and donations was collected through a web-based survey conducted in all 53 member states of the Region. Among the 51 countries responding to the survey, the majority (84%) implemented vaccination campaigns against A(H1N1)pdm09. However, time of vaccine receipt and number of doses varied substantially across the region, with delayed access in many countries especially in those in the lowest income range. Improving access to influenza vaccines in low resource countries and solving issues of product liability should help reduce inequalities and operational challenges arising during a future public health crisis. PMID:23845820

  15. Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience.

    PubMed

    Cuesta, Julita Gil; Aavitsland, Preben; Englund, Hélène; Gudlaugsson, Ólafur; Hauge, Siri Helene; Lyytikäinen, Outi; Sigmundsdóttir, Guðrún; Tegnell, Anders; Virtanen, Mikko; Krause, Tyra Grove

    2016-04-21

    During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.

  16. Why were Turks unwilling to accept the A/H1N1 influenza-pandemic vaccination? People's beliefs and perceptions about the swine flu outbreak and vaccine in the later stage of the epidemic.

    PubMed

    Gaygısız, Ümmügülsüm; Gaygısız, Esma; Özkan, Türker; Lajunen, Timo

    2010-12-16

    This study investigated the acceptability of the A/H1N1 influenza vaccination and related factors among 1137 adults in the later stage of the A/H1N1 outbreak in Turkey. Having already been vaccinated or intending to get vaccinated were related to trust in the vaccine effectiveness, perceived risk of the side effects, and benefits of getting vaccinated. Perceived long term consequences of the A/H1N1 infection, perceptions of the A/H1N1 information in media, and barriers for getting vaccinated were related to intention whereas anticipated epidemic situation in Turkey, being chronically ill, and being not married were related to having already been vaccinated.

  17. Decreased Serologic Response in Vaccinated Military Recruits during 2011 Correspond to Genetic Drift in Concurrent Circulating Pandemic A/H1N1 Viruses

    PubMed Central

    Faix, Dennis J.; Hawksworth, Anthony W.; Myers, Christopher A.; Hansen, Christian J.; Ortiguerra, Ryan G.; Halpin, Rebecca; Wentworth, David; Pacha, Laura A.; Schwartz, Erica G.; Garcia, Shawn M. S.; Eick-Cost, Angelia A.; Clagett, Christopher D.; Khurana, Surender; Golding, Hana; Blair, Patrick J.

    2012-01-01

    Background Population-based febrile respiratory illness surveillance conducted by the Department of Defense contributes to an estimate of vaccine effectiveness. Between January and March 2011, 64 cases of 2009 A/H1N1 (pH1N1), including one fatality, were confirmed in immunized recruits at Fort Jackson, South Carolina, suggesting insufficient efficacy for the pH1N1 component of the live attenuated influenza vaccine (LAIV). Methodology/Principal Findings To test serologic protection, serum samples were collected at least 30 days post-vaccination from recruits at Fort Jackson (LAIV), Parris Island (LAIV and trivalent inactivated vaccine [TIV]) at Cape May, New Jersey (TIV) and responses measured against pre-vaccination sera. A subset of 78 LAIV and 64 TIV sera pairs from recruits who reported neither influenza vaccination in the prior year nor fever during training were tested by microneutralization (MN) and hemagglutination inhibition (HI) assays. MN results demonstrated that seroconversion in paired sera was greater in those who received TIV versus LAIV (74% and 37%). Additionally, the fold change associated with TIV vaccination was significantly different between circulating (2011) versus the vaccine strain (2009) of pH1N1 viruses (ANOVA p value = 0.0006). HI analyses revealed similar trends. Surface plasmon resonance (SPR) analysis revealed that the quantity, IgG/IgM ratios, and affinity of anti-HA antibodies were significantly greater in TIV vaccinees. Finally, sequence analysis of the HA1 gene in concurrent circulating 2011 pH1N1 isolates from Fort Jackson exhibited modest amino acid divergence from the vaccine strain. Conclusions/Significance Among military recruits in 2011, serum antibody response differed by vaccine type (LAIV vs. TIV) and pH1N1 virus year (2009 vs. 2011). We hypothesize that antigen drift in circulating pH1N1 viruses contributed to reduce vaccine effectiveness at Fort Jackson. Our findings have wider implications regarding vaccine

  18. The Comparative Clinical Course of Pregnant and Non-Pregnant Women Hospitalised with Influenza A(H1N1)pdm09 Infection

    PubMed Central

    Brett, Stephen J.; Enstone, Joanne E.; Read, Robert C.; Openshaw, Peter J. M.; Semple, Malcolm G.; Lim, Wei Shen; Taylor, Bruce L.; McMenamin, James; Nicholson, Karl G.; Bannister, Barbara; Nguyen-Van-Tam, Jonathan S.

    2012-01-01

    Introduction The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy. Methods A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15–44 years, using univariate and multivariable techniques. Results Of the 395 women aged 15–44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30–0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20–0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46–1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died. Conclusions Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups. PMID:22870239

  19. Use of a large general practice syndromic surveillance system to monitor the progress of the influenza A(H1N1) pandemic 2009 in the UK.

    PubMed

    Harcourt, S E; Smith, G E; Elliot, A J; Pebody, R; Charlett, A; Ibbotson, S; Regan, M; Hippisley-Cox, J

    2012-01-01

    The Health Protection Agency/QSurveillance national surveillance system utilizes QSurveillance®, a recently developed general practitioner database covering over 23 million people in the UK. We describe the spread of the first wave of the influenza A(H1N1) pandemic 2009 using data on consultations for influenza-like illness (ILI), respiratory illness and prescribing for influenza from 3400 contributing general practices. Daily data, provided from 27 April 2009 to 28 January 2010, were used to give a timely overview for those managing the pandemic nationally and locally. The first wave particularly affected London and the West Midlands with a peak in ILI in week 30. Children aged between 1 and 15 years had consistently high consultation rates for ILI. Daily ILI rates were used for modelling national weekly case estimates. The system enabled the 'real-time' monitoring of the pandemic to a small geographical area, linking morbidity and prescribing for influenza and other respiratory illnesses. PMID:21473803

  20. The Lao Experience in Deploying Influenza A(H1N1)pdm09 Vaccine: Lessons Made Relevant in Preparing for Present Day Pandemic Threats

    PubMed Central

    Xeuatvongsa, Anonh; Mirza, Sara; Winter, Christian; Feldon, Keith; Vongphrachanh, Phengta; Phonekeo, Darouny; Denny, Justin; Khanthamaly, Viengphone; Kounnavong, Bounheuang; Lylianou, Doualy; Phousavath, Sisouphane; Norasingh, Sisouveth; Boutta, Nao; Olsen, Sonja; Bresee, Joseph; Moen, Ann; Corwin, Andrew

    2015-01-01

    The Lao PDR, as did most countries of the Mekong Region, embarked on a pandemic vaccine initiative to counter the threat posed by influenza A(H1N1)pdm09. Overall, estimated vaccine coverage of the Lao population was 14%, with uptake in targeted health care workers and pregnant women 99% and 41%, respectively. Adverse Events Following Immunization accounted for only 6% of survey driven, reported vaccination experiences, with no severe consequences or deaths. Public acceptability of the vaccine campaign was high (98%). Challenges to vaccine deployment included: 1) no previous experience in fielding a seasonal influenza vaccine, 2) safety and efficacy concerns, and 3) late arrival of vaccine 10 months into the pandemic. The Lao success in surmounting these hurdles was in large measure attributed to the oversight assigned the National Immunization Program, and national sensitivities in responding to the avian influenza A(H5N1) crisis in the years leading up to the pandemic. The Lao “lessons learned” from pandemic vaccine deployment are made even more relevant four years on, given the many avian influenza strains circulating in the region, all with pandemic potential. PMID:25923779

  1. Use of intravenous peramivir for treatment of severe influenza A(H1N1)pdm09.

    PubMed

    Louie, Janice K; Yang, Samuel; Yen, Cynthia; Acosta, Meileen; Schechter, Robert; Uyeki, Timothy M

    2012-01-01

    Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety.

  2. [A survey about determinants of 2009 pandemic influenza A(H1N1) vaccination among French general practionners patients. Motivac study].

    PubMed

    Partouche, Henri; Benainous, Olivier; Barthe, Juliette; Pierret, Janine; Rigal, Laurent; Michaloux, Maud; Gilberg, Serge

    2011-12-01

    The influenza A/H1N1 2009 immunization campaign did not have the accession of the French population resulting in a very low rate of immunization coverage. We conducted a cross-sectional study in spring 2010 to identify factors that led general practitionners (GPs) and their adult patients to be vaccinated or not; 43 GPs in France, included 668 patients; 29 GPs (67%) and 108 patients (16.5%) have been vaccinated; among 238 patients under vaccine priority indication 17% were vaccinated; 48% of patients thought they could receive effective treatment for influenza, 36% felt that the vaccine protected against influenza but 27% thought it did not meet usual safety criteria. A higher level of education, the belief of an effective protection with vaccination, the positive GP's opinion and behavior (OR 4,21 IC95% [1.4-14]; p=0.012), the receipt of an invitation to immunization (OR 7, 1 IC95% [1.73-58.4] and the active seek of information (OR 8.05, IC95% [2.8-27]) were significantly associated with vaccination. Regarding this immunization campaign few patients n=87 (13.7%) did trust the state heath agency. Our study confirms the distrust of the vaccine and suggests the decisive role of the GPs to achieve adequate levels of immunization coverage.

  3. Risk perception and information-seeking behaviour during the 2009/10 influenza A(H1N1)pdm09 pandemic in Germany.

    PubMed

    Walter, D; Bohmer, Mm; Reiter, S; Krause, G; Wichmann, O

    2012-01-01

    During the influenza A(H1N1)pdm09 pandemic in 2009/10, a total of 13 consecutive surveys were carried out of the general population in Germany to monitor knowledge, attitude and behaviour concerning the disease and vaccination against pandemic influenza in real time. In total, 13,010 persons aged 14 years or older were interviewed by computer-assisted telephone techniques between November 2009 and April 2010. During the peak of the pandemic, only 18% of participants stated that they perceived the risk of pandemic influenza as high; this proportion fell to 10% in January 2010. There was a significant difference in information-seeking behaviour among population subgroups concerning the disease and vaccine uptake. However, in all subgroups, conventional media sources such as television, radio and newspapers were more frequently used than the Internet. While the majority of participants (78%) felt sufficiently informed to make a decision for or against vaccination, overall vaccination coverage remained low. Among those who decided against vaccination, fear of adverse events and perception that the available vaccines were not sufficiently evaluated were the most frequently stated reasons. Such mistrust in the vaccines and the perceived low risk of the disease were the main barriers that contributed to the low vaccination coverage in Germany during the pandemic. PMID:22490383

  4. Initial surveillance of 2009 influenza A(H1N1) pandemic in the European Union and European Economic Area, April-September 2009.

    PubMed

    Devaux, I; Kreidl, P; Penttinen, P; Salminen, Mika; Zucs, P; Ammon, A

    2010-12-01

    European Union (EU) and European Economic Area (EEA) countries reported surveillance data on 2009 pandemic influenza A(H1N1) cases to the European Centre for Disease Prevention and Control (ECDC) through the Early Warning and Response System (EWRS) during the early phase of the 2009 pandemic. We describe the main epidemiological findings and their implications in respect to the second wave of the 2009 influenza pandemic. Two reporting systems were in place (aggregate and case-based) from June to September 2009 to monitor the evolution of the pandemic. The notification rate was assessed through aggregate reports. Individual data were analysed retrospectively to describe the population affected. The reporting peak of the first wave of the 2009 pandemic influenza was reached in the first week of August. Transmission was travel-related in the early stage and community transmission within EU/EEA countries was reported from June 2009. Seventy eight per cent of affected individuals were less than 30 years old. The proportions of cases with complications and underlying conditions were 3% and 7%, respectively. The most frequent underlying medical conditions were chronic lung (37%) and cardio-vascular diseases (15%). Complication and hospitalisation were both associated with underlying conditions regardless of age. The information from the first wave of the pandemic produced a basis to determine risk groups and vaccination strategies before the start of the winter wave. Public health recommendations should be guided by early capture of profiles of affected populations through monitoring of infectious diseases. PMID:21163182

  5. Two doses of pandemic influenza A(H1N1) vaccine: tolerability in healthy young children in the Netherlands.

    PubMed

    van't Klooster, Tessa M; Kemmeren, Jeanet M; de Melker, Hester E; Vermeer-de Bondt, Patricia E; van der Maas, Nicoline A T

    2011-10-01

    During the 2009 influenza pandemic, children aged 6 months up to and including 4 years, without chronic illness, were vaccinated with two doses of Pandemrix(®) through mass vaccination in the Netherlands. During the vaccination campaign a warning was issued about fever after the second dose of Pandemrix(®). Therefore, we investigated the tolerability of both doses Pandemrix(®) in these children. Among parents of children eligible for vaccination, 1500 questionnaires were distributed during both, the first and second mass vaccination session. We asked for the occurrence, time interval, and duration of local reactions and systemic adverse events (AEs). The responses were 36.7% and 29.5% after each dose, respectively. Local reactions were reported in 40.4% and 39.3%, most frequently, pain at the injection site. After the first and second dose, 29.6% and 30.7% of all children experienced fever (mean temperature 38.8{degree sign}C). Other systemic AEs were reported in 41.6% and 42.9% of the children. No differences were seen between the first and second dose for all reported AEs except for pallor. One child was hospitalized after the first dose, but a causal relation to the vaccination was considered improbable. In conclusion, fever was frequently reported in children 6 months up to and including 4 years of age after the first and second dose of Pandemrix(®). However, for almost all AEs, including fever, no dose effect was observed. Reported AEs were mostly mild and all were transient.

  6. Risk Factors for Death from Influenza A(H1N1)pdm09, State of São Paulo, Brazil, 2009

    PubMed Central

    Ribeiro, Ana Freitas; Pellini, Alessandra Cristina Guedes; Kitagawa, Beatriz Yuko; Marques, Daniel; Madalosso, Geraldine; de Cassia Nogueira Figueira, Gerrita; Fred, João; Albernaz, Ricardo Kerti Mangabeira; Carvalhanas, Telma Regina Marques Pinto; Zanetta, Dirce Maria Trevisan

    2015-01-01

    This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28th and August 29th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza. PMID:25774804

  7. Epidemiological Characterization of Influenza A(H1N1)pdm09 Cases from 2009 to 2010 in Baguio City, the Philippines

    PubMed Central

    Pamaran, Rochelle R.; Kamigaki, Taro; Hewe, Teresita T.; Flores, Korrine Madeleine C.; Mercado, Edelwisa S.; Alday, Portia P.; Tan, Alvin G.; Oshitani, Hitoshi; Olveda, Remigio M.; Tallo, Veronica L.

    2013-01-01

    Background Baguio City, Philippines experienced its first influenza A(H1N1)pdm09 [A(H1)pdm09] case in May 2009. In spite of numerous reports describing the epidemiological and clinical features of A(H1)pdm09 cases, there are no studies about A(H1)pdm09 epidemiology in the Philippines, where year-round influenza activity was observed. Objectives We aimed to investigate the epidemiological and clinical features of A(H1)pdm09 in pandemic and post-pandemic periods. Methods Data were collected under enhanced surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) from January 2009 to December 2010. RT-PCR was used to detect A(H1)pdm09, following the protocol of the United States Centers for Disease Control and Prevention. The reproduction number was computed as a simple exponential growth rate. Differences in proportional and categorical data were examined using chi-square test or Fishers’ exact test. Results and Conclusions The outbreak was observed from week 25 to 35 in 2009 and from week 24 to 37 in 2010. The highest proportion of cases was among children aged 5–14 years. The number of ILI outpatients was 2.3-fold higher in 2009 than in 2010, while the number of inpatients was 1.8-fold higher in 2009. No significant difference in gender was observed during the two periods. The clinical condition of all patients was generally mild and self-limiting, with only 2 mortalities among inpatients in 2009. The basic reproduction number was estimated as 1.16 in 2009 and 1.05 in 2010 in the assumption of mean generation time as 2.6 days. School children played a significant role in facilitating influenza transmission. PMID:24244578

  8. The E119D neuraminidase mutation identified in a multidrug-resistant influenza A(H1N1)pdm09 isolate severely alters viral fitness in vitro and in animal models.

    PubMed

    Abed, Yacine; Bouhy, Xavier; L'Huillier, Arnaud G; Rhéaume, Chantal; Pizzorno, Andrés; Retamal, Miguel; Fage, Clément; Dubé, Karen; Joly, Marie-Hélène; Beaulieu, Edith; Mallett, Corey; Kaiser, Laurent; Boivin, Guy

    2016-08-01

    We recently isolated an influenza A(H1N1)pdm09 E119D/H275Y neuraminidase (NA) variant from an immunocompromised patient who received oseltamivir and zanamivir therapies. This variant demonstrated cross resistance to zanamivir, oseltamivir, peramivir and laninamivir. In this study, the viral fitness of the recombinant wild-type (WT), E119D and E119D/H275Y A(H1N1)pdm09 viruses was evaluated in vitro and in experimentally-infected C57BL/6 mice and guinea pigs. In replication kinetics experiments, viral titers obtained with the E119D and E119D/H275Y recombinants were up to 2- and 4-log lower compared to the WT virus in MDCK and ST6GalI-MDCK cells, respectively. Enzymatic studies revealed that the E119D mutation significantly decreased the surface NA activity. In experimentally-infected mice, a 50% mortality rate was recorded in the group infected with the WT recombinant virus whereas no mortality was observed in the E119D and E119D/H275Y groups. Mean lung viral titers on day 5 post-inoculation for the WT (1.2 ± 0.57 × 10(8) PFU/ml) were significantly higher than those of the E119D (9.75 ± 0.41 × 10(5) PFU/ml, P < 0.01) and the E119D/H275Y (1.47 ± 0.61 × 10(6) PFU/ml, P < 0.01) groups. In guinea pigs, comparable seroconversion rates and viral titers in nasal washes (NW) were obtained for the WT and mutant index and contact groups. However, the D119E reversion was observed in most NW samples of the E119D and E119D/H275Y animals. In conclusion, the E119D NA mutation that could emerge in A(H1N1)pdm09 viruses during zanamivir therapy has a significant impact on viral fitness and such mutant is unlikely to be highly transmissible. PMID:27185624

  9. Improving the Evidence Base for Decision Making During a Pandemic: The Example of 2009 Influenza A/H1N1

    PubMed Central

    Finelli, Lyn; Heffernan, Richard T.; Leung, Gabriel M.; Redd, Stephen C.

    2011-01-01

    This article synthesizes and extends discussions held during an international meeting on “Surveillance for Decision Making: The Example of 2009 Pandemic Influenza A/H1N1,” held at the Center for Communicable Disease Dynamics (CCDD), Harvard School of Public Health, on June 14 and 15, 2010. The meeting involved local, national, and global health authorities and academics representing 7 countries on 4 continents. We define the needs for surveillance in terms of the key decisions that must be made in response to a pandemic: how large a response to mount and which control measures to implement, for whom, and when. In doing so, we specify the quantitative evidence required to make informed decisions. We then describe the sources of surveillance and other population-based data that can presently—or in the future—form the basis for such evidence, and the interpretive tools needed to process raw surveillance data. We describe other inputs to decision making besides epidemiologic and surveillance data, and we conclude with key lessons of the 2009 pandemic for designing and planning surveillance in the future. PMID:21612363

  10. Efficiency of Points of Dispensing for Influenza A(H1N1)pdm09 Vaccination, Los Angeles County, California, USA, 2009

    PubMed Central

    Dean, Brandon; Teutsch, Steven; Borse, Rebekah H.; Meltzer, Martin I.; Bagwell, DeeAnn; Plough, Alonzo; Fielding, Jonathan

    2014-01-01

    During October 23–December 8, 2009, the Los Angeles County Department of Public Health used points of dispensing (PODs) to improve access to and increase the number of vaccinations against influenza A(H1N1)pdm09. We assessed the efficiency of these units and access to vaccines among ethnic groups. An average of 251 persons per hour (SE 65) were vaccinated at the PODs; a 10% increase in use of live-attenuated monovalent vaccines reduced that rate by 23 persons per hour (SE 7). Vaccination rates were highest for Asians (257/10,000 persons), followed by Hispanics (114/10,000), whites (75/100,000), and African Americans (37/10,000). Average distance traveled to a POD was highest for whites (6.6 miles; SD 6.5) and lowest for Hispanics (4.7 miles; SD ±5.3). Placing PODs in areas of high population density could be an effective strategy to reach large numbers of persons for mass vaccination, but additional PODs may be needed to improve coverage for specific populations. PMID:24656212

  11. Research Updates: Experimental Evaluation of 2009 Pandemic A/H1N1 in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: In March 2009, a novel pandemic A/H1N1 emerged in the human population in North America (2). The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before be...

  12. [The 24 May, 2009 isolation of the first A/IIV-Moscow/01/2009 (H1N1)swl strain similar to swine A(H1N1) influenza virus from the first Moscow case detected on May 21, 2009, and its deposit in the state collection of viruses (SCV No. 2452 dated May 24, 2009)].

    PubMed

    L'vov, D K; Burtseva, E I; Prilipov, A G; Bazarova, M V; Kolobukhina, L V; Merkulova, L N; Malyshev, N A; Deriabin, P G; Fediakina, I T; Sadykova, G K; Usachev, E V; Shchelkanov, M Iu; Shevchenko, E S; Trushakova, S V; Ivanova, V T; Beliakova, N V; Oskerko, T A; Aliper, T I

    2009-01-01

    The paper presents the results of the first isolation of the new influenza virus in Moscow and the Russian Federation, which was similar to the swine A/IIV-Moscow/01/2009(H1N1)swl strain isolated on May 24, 2009 from a Russian arrived in Moscow from the USA on May 19, 2009. The antigenic, biological, and molecular genetic properties of this virus were studied. The virus was isolated on MDCK and chick embryos, the hemagglutination titers being 1:8-1:16 AE; the infectious titers being 6.51g of the tissue cytopathogenic infective dose (TCID50) and 7.01g of the common infective dose (CID50). The virus was sensitive to arbidol, ribavirin, oseltamivir, and resistant to rimantadine. The complete virus genome was sequenced; the data were accepted to the Gen Bank on May 28, 2009 under GQ219584-GQ219590 and GQ202724. The significant gene substitution of neuraminidase Asp for Gly in position 451, which has been undetectable in any other strain published in the Gen Bank by the present time is unique only to A/IIV-Moscow/01/2009 (H1N1)swl. The virus has been deposited in the State Collection of Viruses, D. I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, under No. 2452 dated May 24, 2009.

  13. Predictors of clinical outcome in a national hospitalised cohort across both waves of the influenza A/H1N1 pandemic 2009–2010 in the UK

    PubMed Central

    Myles, Puja R; Semple, Malcolm G; Lim, Wei Shen; Openshaw, Peter J M; Gadd, Elaine M; Read, Robert C; Taylor, Bruce L; Brett, Stephen J; McMenamin, James; Enstone, Joanne E; Armstrong, Colin; Bannister, Barbara; Nicholson, Karl G

    2012-01-01

    Background Although generally mild, the 2009–2010 influenza A/H1N1 pandemic caused two major surges in hospital admissions in the UK. The characteristics of patients admitted during successive waves are described. Methods Data were systematically obtained on 1520 patients admitted to 75 UK hospitals between May 2009 and January 2010. Multivariable analyses identified factors predictive of severe outcome. Results Patients aged 5–54 years were over-represented compared with winter seasonal admissions for acute respiratory infection, as were non-white ethnic groups (first wave only). In the second wave patients were less likely to be school age than in the first wave, but their condition was more likely to be severe on presentation to hospital and they were more likely to have delayed admission. Overall, 45% had comorbid conditions, 16.5% required high dependency (level 2) or critical (level 3) care and 5.3% died. As in 1918–1919, the likelihood of severe outcome by age followed a W-shaped distribution. Pre-admission antiviral drug use decreased from 13.3% to 10% between the first and second waves (p=0.048), while antibiotic prescribing increased from 13.6% to 21.6% (p<0.001). Independent predictors of severe outcome were age 55–64 years, chronic lung disease (non-asthma, non-chronic obstructive pulmonary disease), neurological disease, recorded obesity, delayed admission (≥5 days after illness onset), pneumonia, C-reactive protein ≥100 mg/litre, and the need for supplemental oxygen or intravenous fluid replacement on admission. Conclusions There were demographic, ethnic and clinical differences between patients admitted with pandemic H1N1 infection and those hospitalised during seasonal influenza activity. Despite national policies favouring use of antiviral drugs, few patients received these before admission and many were given antibiotics. PMID:22407890

  14. Pre- and postpandemic estimates of 2009 pandemic influenza A(H1N1) seroprotection to inform surveillance-based incidence, by age, during the 2013-2014 epidemic in Canada.

    PubMed

    Skowronski, Danuta M; Chambers, Catharine; Sabaiduc, Suzana; Janjua, Naveed Z; Li, Guiyun; Petric, Martin; Krajden, Mel; Purych, Dale; Li, Yan; De Serres, Gaston

    2015-01-01

    To understand the epidemic resurgence of influenza due to the 2009 pandemic influenza A(H1N1) strain (A[H1N1]pdm09) during the 2013-2014 influenza season, we compared age-related cross-sectional estimates of seroprotection before the pandemic (during 2009) and after the pandemic (during 2010 and 2013) to subsequent surveillance-based, laboratory-confirmed incidence of influenza due to A(H1N1)pdm09 in British Columbia, Canada. Prepandemic seroprotection was negligible except for very old adults (defined as adults aged ≥ 80 years), among whom 80% had seroprotection. Conversely, postpandemic seroprotection followed a U-shaped distribution, with detection in approximately 35%-45% of working-aged adults but in ≥ 70% of very old adults and young children, excluding children aged <5 years in 2013, among whom seroprotection again decreased to <20%. The incidence was 5-fold higher during 2013-2014, compared with 2010-2011, and was highest among children aged <5 years and working-aged adults, reflecting a mirror image of the age-based seroprotection data.

  15. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated to hereditary neuropathy with liability to pressure palsies (HNPP) and revealed after influenza AH1N1 vaccination.

    PubMed

    Remiche, Gauthier; Abramowicz, Marc; Mavroudakis, Nicolas

    2013-12-01

    Neurological complications of AH1N1 vaccination such as Guillain-Barré syndrome were described in the previous years. Several reports suggest that hereditary neuropathies may be a predisposing factor for immune-mediated neuropathies. We report the case of a 54-year-old female who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 5 weeks after AH1N1 vaccination. She had no previous neurological history, but neurophysiological features led us to suspect an underlying hereditary neuropathy. PMP22 gene analysis showed a typical deletion, confirming the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP). We observed a significant clinical and neurophysiological improvement of the neuropathy after intravenous immunoglobulin treatment. This is, to our knowledge, the first reported case of CIDP potentially triggered by AH1N1 vaccination. This and previous observations suggest that genetic-determined neuropathies could predispose to the occurrence of immune-mediated neuropathies. One must recall the possibility of a superimposed hereditary neuropathy like HNPP in patients with a clinical presentation of CIDP, especially when positive family history or unexpected neurophysiological features are present.

  16. Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons — An Analysis Based on a Dynamic Transmission Model

    PubMed Central

    Shubin, Mikhail; Lebedev, Artem; Lyytikäinen, Outi; Auranen, Kari

    2016-01-01

    The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 – 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 – 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic. PMID:27010206

  17. Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons - An Analysis Based on a Dynamic Transmission Model.

    PubMed

    Shubin, Mikhail; Lebedev, Artem; Lyytikäinen, Outi; Auranen, Kari

    2016-03-01

    The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 - 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 - 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic. PMID:27010206

  18. Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons - An Analysis Based on a Dynamic Transmission Model.

    PubMed

    Shubin, Mikhail; Lebedev, Artem; Lyytikäinen, Outi; Auranen, Kari

    2016-03-01

    The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 - 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 - 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic.

  19. Potentially-toxic and essential elements profile of AH1N1 patients in Mexico City

    PubMed Central

    Moya, Mireya; Bautista, Edgar G.; Velázquez-González, Antonio; Vázquez-Gutiérrez, Felipe; Tzintzun, Guadalupe; García-Arreola, María Elena; Castillejos, Manuel; Hernández, Andrés

    2013-01-01

    During spring of 2009, a new influenza virus AH1N1 spread in the world causing acute respiratory illness and death, resulting in the first influenza pandemic since 1968. Blood levels of potentially-toxic and essential elements of 40 pneumonia and confirmed AH1N1 were evaluated against two different groups of controls, both not infected with the pandemic strain. Significant concentrations of potentially-toxic elements (lead, mercury, cadmium, chromium, arsenic) along with deficiency of selenium or increased Zn/Cu ratios characterized AH1N1 cases under study when evaluated versus controlled cases. Deficiency of selenium is progressively observed from controls I (influenza like illness) through controls II (pneumonia) and finally pneumonia -AH1N1 infected patients. Cases with blood Se levels greater than the recommended for an optimal cut-off to activate glutathione peroxidase (12.5 μg/dL) recovered from illness and survived. Evaluation of this essential element in critical pneumonia patients at the National Institutes is under evaluation as a clinical trial. PMID:23422930

  20. Concurrent and cross-season protection of inactivated influenza vaccine against A(H1N1)pdm09 illness among young children: 2012-2013 case-control evaluation of influenza vaccine effectiveness.

    PubMed

    Fu, Chuanxi; Xu, Jianxiong; Lin, Jinyan; Wang, Ming; Li, Kuibiao; Ge, Jing; Thompson, Mark G

    2015-06-01

    In 2012-2013, we examined 1729 laboratory-confirmed A(H1N1)pdm09 influenza cases matched 1:1 with healthy controls and estimated influenza vaccine effectiveness (VE) for trivalent inactivated influenza vaccine (IIV3) to be 67% (95% confidence interval=58-74%) for ages 8 months to 6 years old. Among children aged 8-35 months old, VE for fully vaccinated children (73%, 60-81%) was significantly higher than VE for partially vaccinated children (55%, 33-70%). Significant cross-season protection from prior IIV3 was noted, including VE of 31% (8-48%) from IIV3 received in 2010-2011 against influenza illness in 2012--2013 without subsequent boosting doses.

  1. Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15.

    PubMed

    Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Rizzo, Caterina; Gherasim, Alin; Horváth, Judit Krisztina; Domegan, Lisa; Pitigoi, Daniela; Machado, Ausenda; Paradowska-Stankiewicz, Iwona Anna; Bella, Antonino; Larrauri, Amparo; Ferenczi, Annamária; Lazar, Mihaela; Pechirra, Pedro; Korczyńska, Monika Roberta; Pozo, Francisco; Moren, Alain

    2016-01-01

    Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and  ≥60  years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and  ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains.

  2. Combination effects of peramivir and favipiravir against oseltamivir-resistant 2009 pandemic influenza A(H1N1) infection in mice.

    PubMed

    Park, Sehee; Kim, Jin Il; Lee, Ilseob; Lee, Sangmoo; Hwang, Min-Woong; Bae, Joon-Yong; Heo, Jun; Kim, Donghwan; Jang, Seok-Il; Kim, Hyejin; Cheong, Hee Jin; Song, Jin-Won; Song, Ki-Joon; Baek, Luck Ju; Park, Man-Seong

    2014-01-01

    Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.

  3. Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

    PubMed Central

    Lee, Sangmoo; Hwang, Min-Woong; Bae, Joon-Yong; Heo, Jun; Kim, Donghwan; Jang, Seok-Il; Kim, Hyejin; Cheong, Hee Jin; Song, Jin-Won; Song, Ki-Joon; Baek, Luck Ju; Park, Man-Seong

    2014-01-01

    Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection. PMID:24992479

  4. Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia De Lange syndrome.

    PubMed

    Esposito, Susanna; Selicorni, Angelo; Daleno, Cristina; Valzano, Antonia; Cerutti, Marta; Galeone, Carlotta; Consolo, Silvia; Menni, Francesca; Principi, Nicola

    2011-06-01

    In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.

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

    PubMed

    Bitar, Roger A

    2016-02-01

    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.

  6. [Database linkage for surveillance of the influenza A(H1N1)pdm09 pandemic in Brazil, 2009-2010].

    PubMed

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-07-21

    Based on database linkage, the objective of this study was to describe the epidemiological profile of notified cases and deaths from the new viral subtype of influenza during the influenza pandemic. Secondary data were used from the SINAN (Information System for Notifiable Diseases) and SIM (Mortality Information System) for the years 2009 and 2010. Linkage identified 5,973 deaths of cases notified as pandemic influenza. Of these, 2,170 (36.33%) had been classified in the SINAN as confirmed pandemic influenza, 215 (3.6%) as due to other infectious agents, and 3,340 (55.92%) as ruled out. After linkage, some cases in the SINAN database that were closed as death from influenza (n = 658) or death from other causes (n = 847) could not be located in the SIM database. Database linkage can improve the surveillance system and monitoring of morbidity and mortality. We recommend strengthening influenza surveillance in Brazil using linkage of Ministry of Health databases.

  7. Long-term effect of the influenza A/H1N1 pandemic: attitudes and preventive behaviours one year after the pandemic.

    PubMed

    Garcia-Continente, Xavier; Serral, Gemma; López, María José; Pérez, Anna; Nebot, Manel

    2013-08-01

    This study aimed to describe changes in attitudes and behaviours regarding influenza A infection 1 year after the end of the pandemic. A cross-sectional study was performed based on two population-based telephone surveys including 1027 (February, 2010) and 1000 (February, 2011) participants in Spain. The percentages of the respondents who reported that they had adopted preventive measures to avoid Influenza infection declined 1 year after the pandemic. Influenza-related consultations decreased, whereas confidence in vaccination increased. Despite the decrease observed in adopting preventive measures, some behaviours were still being adopted long time after the pandemic in general population. PMID:23748851

  8. Early spread of the 2009 influenza A(H1N1) pandemic in the United Kingdom--use of local syndromic data, May-August 2009.

    PubMed

    Smith, S; Smith, G E; Olowokure, B; Ibbotson, S; Foord, D; Maguire, H; Pebody, R; Charlett, A; Hippisley-Cox, J; Elliot, A J

    2011-01-20

    Following the confirmation of the first two cases of pandemic influenza on 27 April 2009 in the United Kingdom (UK), syndromic surveillance data from the Health Protection Agency (HPA)/QSurveillance and HPA/NHS Direct systems were used to monitor the possible spread of pandemic influenza at local level during the first phase of the outbreak. During the early weeks, syndromic indicators sensitive to influenza activity monitored through the two schemes remained low and the majority of cases were travel-related. The first evidence of community spread was seen in the West Midlands region following a school-based outbreak in central Birmingham. During the first phase several Primary Care Trusts had periods of exceptional influenza activity two to three weeks ahead of the rest of the region. Community transmission in London began slightly later than in the West Midlands but the rates of influenza-like illness recorded by general practitioners (GPs) were ultimately higher. Influenza activity in the West Midlands and London regions peaked a week before the remainder of the UK. Data from the HPA/NHS Direct and HPA/QSurveillance systems were mapped at local level and used alongside laboratory data and local intelligence to assist in the identification of hotspots, to direct limited public health resources and to monitor the progression of the outbreak. This work has demonstrated the utility of local syndromic surveillance data in the detection of increased transmission and in the epidemiological investigation of the pandemic and has prompted future spatio-temporal work.

  9. [Database linkage for surveillance of the influenza A(H1N1)pdm09 pandemic in Brazil, 2009-2010].

    PubMed

    Rossetto, Erika Valeska; Luna, Expedito José de Albuquerque

    2016-07-21

    Based on database linkage, the objective of this study was to describe the epidemiological profile of notified cases and deaths from the new viral subtype of influenza during the influenza pandemic. Secondary data were used from the SINAN (Information System for Notifiable Diseases) and SIM (Mortality Information System) for the years 2009 and 2010. Linkage identified 5,973 deaths of cases notified as pandemic influenza. Of these, 2,170 (36.33%) had been classified in the SINAN as confirmed pandemic influenza, 215 (3.6%) as due to other infectious agents, and 3,340 (55.92%) as ruled out. After linkage, some cases in the SINAN database that were closed as death from influenza (n = 658) or death from other causes (n = 847) could not be located in the SIM database. Database linkage can improve the surveillance system and monitoring of morbidity and mortality. We recommend strengthening influenza surveillance in Brazil using linkage of Ministry of Health databases. PMID:27462844

  10. Early spread of the 2009 influenza A(H1N1) pandemic in the United Kingdom--use of local syndromic data, May-August 2009.

    PubMed

    Smith, S; Smith, G E; Olowokure, B; Ibbotson, S; Foord, D; Maguire, H; Pebody, R; Charlett, A; Hippisley-Cox, J; Elliot, A J

    2011-01-01

    Following the confirmation of the first two cases of pandemic influenza on 27 April 2009 in the United Kingdom (UK), syndromic surveillance data from the Health Protection Agency (HPA)/QSurveillance and HPA/NHS Direct systems were used to monitor the possible spread of pandemic influenza at local level during the first phase of the outbreak. During the early weeks, syndromic indicators sensitive to influenza activity monitored through the two schemes remained low and the majority of cases were travel-related. The first evidence of community spread was seen in the West Midlands region following a school-based outbreak in central Birmingham. During the first phase several Primary Care Trusts had periods of exceptional influenza activity two to three weeks ahead of the rest of the region. Community transmission in London began slightly later than in the West Midlands but the rates of influenza-like illness recorded by general practitioners (GPs) were ultimately higher. Influenza activity in the West Midlands and London regions peaked a week before the remainder of the UK. Data from the HPA/NHS Direct and HPA/QSurveillance systems were mapped at local level and used alongside laboratory data and local intelligence to assist in the identification of hotspots, to direct limited public health resources and to monitor the progression of the outbreak. This work has demonstrated the utility of local syndromic surveillance data in the detection of increased transmission and in the epidemiological investigation of the pandemic and has prompted future spatio-temporal work. PMID:21262185

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

    PubMed

    Girmenia, Corrado; Mercanti, Caterina; Federico, Vincenzo; Rea, Massimiliano; De Vellis, Annalisa; Valle, Veronica; Micozzi, Alessandra; Latagliata, Roberto; Breccia, Massimo; Morano, Salvatore Giacomo; Brunetti, Gregorio Antonio; Sali, Michela; Delogu, Giovanni; Foà, Robin; Alimena, Giuliana; Gentile, Giuseppe

    2011-01-01

    Data derived from epidemiologic surveillance adopted at our center in hematologic and stem cell transplant patients during the 2009 influenza A (H1N1)v pandemic are reported. Of the 52 patients with influenza-like disease we observed, 37 underwent a real-time PCR evaluation and 21 had a confirmed diagnosis. Of the RT-PCR-confirmed cases, 23.8% were children (age <18 years) and 9.5% were >65 years; 47.6% presented with a pulmonary infiltrate and 33.3% with respiratory failure. Pulmonary involvement was observed more frequently in patients with comorbidities. All patients received a course of oseltamivir therapy starting an average of 1 day (range <1-2) after the onset of symptoms. No patient was transferred to the intensive care unit. The viral disease had a generally favorable outcome despite the high frequency of pulmonary involvement. A prompt clinical evaluation with an early antiviral and supportive therapy may have played a beneficial role in the outcome. PMID:21411983

  12. Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

    PubMed

    Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik

    2016-01-01

    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.

  13. Compliance to oseltamivir among two populations in Oxfordshire, United Kingdom affected by influenza A(H1N1)pdm09, November 2009--a waste water epidemiology study.

    PubMed

    Singer, Andrew C; Järhult, Josef D; Grabic, Roman; Khan, Ghazanfar A; Fedorova, Ganna; Fick, Jerker; Lindberg, Richard H; Bowes, Michael J; Olsen, Björn; Söderström, Hanna

    2013-01-01

    Antiviral provision remains the focus of many pandemic preparedness plans, however, there is considerable uncertainty regarding antiviral compliance rates. Here we employ a waste water epidemiology approach to estimate oseltamivir (Tamiflu®) compliance. Oseltamivir carboxylate (oseltamivir's active metabolite) was recovered from two waste water treatment plant (WWTP) catchments within the United Kingdom at the peak of the autumnal wave of the 2009 Influenza A (H1N1)pdm09 pandemic. Predictions of oseltamivir consumption from detected levels were compared with two sources of national government statistics to derive compliance rates. Scenario and sensitivity analysis indicated between 3-4 and 120-154 people were using oseltamivir during the study period in the two WWTP catchments and a compliance rate between 45-60%. With approximately half the collected antivirals going unused, there is a clear need to alter public health messages to improve compliance. We argue that a near real-time understanding of drug compliance at the scale of the waste water treatment plant (hundreds to millions of people) can potentially help public health messages become more timely, targeted, and demographically sensitive, while potentially leading to less mis- and un-used antiviral, less wastage and ultimately a more robust and efficacious pandemic preparedness plan.

  14. Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave (May–September 2009)

    PubMed Central

    Openshaw, P J M; Hashim, A; Gadd, E M; Lim, W S; Semple, M G; Read, R C; Taylor, B L; Brett, S J; McMenamin, J; Enstone, J E; Armstrong, C; Nicholson, K G

    2010-01-01

    Background During the first wave of pandemic H1N1 influenza in 2009, most cases outside North America occurred in the UK. The clinical characteristics of UK patients hospitalised with pandemic H1N1 infection and risk factors for severe outcome are described. Methods A case note-based investigation was performed of patients admitted with confirmed pandemic H1N1 infection. Results From 27 April to 30 September 2009, 631 cases from 55 hospitals were investigated. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically-confirmed pneumonia and a raised C-reactive protein (CRP) level (≥100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people. Conclusions Pandemic H1N1 infection causes disease requiring hospitalisation of previously fit individuals as well as those with underlying conditions. An abnormal chest x-ray or a raised CRP level, especially in patients who are recorded as obese or who have pulmonary conditions other than asthma or COPD, indicate a potentially serious outcome. These findings support the use of pandemic vaccine in pregnant women, children <5 years of age and those with chronic lung disease. PMID:20627925

  15. Public perceptions of the transmission of pandemic influenza A/H1N1 2009 from pigs and pork products in Australia.

    PubMed

    Dhand, Navneet K; Hernandez-Jover, Marta; Taylor, Melanie; Holyoake, Patricia

    2011-02-01

    A cross-sectional study was conducted at the height of the pandemic influenza H1N1/09 outbreak in Australia in 2009. The objectives of the study were to evaluate public perceptions about transmission and prevention of the disease, to understand their concerns and preparedness to cope with the disease, and to investigate drivers influencing their behaviour. A questionnaire was designed and administered to 510 customers visiting 15 butcher shops in the Greater Sydney region between 26th June and 2nd August 2009. Data were analysed to estimate the proportion of people with certain perceptions and to evaluate the influence of these perceptions on two binary outcome variables: (1) whether or not people believed that avoiding pork would protect them from contracting H1N1/09, and (2) whether or not they actually made some changes to pork consumption after the outbreak. A majority of the respondents had perceptions based on fact about transmission and prevention of H1N1/09. As many as 96.8% of the respondents believed that washing their hands frequently was likely to protect them from contracting H1N1/09. Similarly, most believed that they could contract H1N1/09 by travelling on public transport with a sick person present (94.1%), by shaking hands with a sick person (89.2%), or by attending a community gathering (73.7%). Women were more likely than men to have factual perceptions about protective behaviours. Misconceptions regarding transmission of the disease were evident, with 21.7% believing that avoiding eating pork could protect them against H1N1/09, 11.1% believing that they could contract H1N1/09 by drinking tap water, 22.8% by handling uncooked pork meat and 15.6% by eating cooked pork. Approximately one third of respondents believed that working in a pig farm or an abattoir increased their likelihood of contracting H1N1/09 (36.9% and 32.3%, respectively). Younger people (<35 years old) were more likely to have these misconceptions than older people. Reduction in

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

    PubMed

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

    2015-12-01

    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.

  17. "Trivalent influenza vaccination of healthy adults 3 years after the onset of swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v constituent?".

    PubMed

    Allwinn, R; Bickel, M; Lassmann, C; Wicker, S; Friedrichs, I

    2013-04-01

    Influenza vaccination is advised annually to reduce the burden of influenza disease. For sufficient vaccine campaigns also a continuous adoption of influenza vaccines are necessary, due to particularly high genetic variability of influenza A virus. Therefore, we evaluate the effectiveness of the trivalent influenza vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune response was investigated in paired sera from 92 healthcare workers with the hemagglutination inhibition assay (HI). Protective antibody levels (HI titer ≥40) were found after vaccination for influenza A/California/07/2009(H1N1): 84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47] and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the currently circulating virus strains. However, the highest seroprevalence rate was found against influenza B; pre- and post-vaccination titers as well, which may be due to comparatively high virus preservation. Remarkable, lowest seropositivity was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.

  18. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies

    PubMed Central

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6–35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3–17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6–35 months and 3–17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158. PMID:26176592

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

    PubMed

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

    2013-08-01

    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. Surveillance of perceptions, knowledge, attitudes and behaviors of the Italian adult population (18-69 years) during the 2009-2010 A/H1N1 influenza pandemic.

    PubMed

    Ferrante, Gianluigi; Baldissera, Sandro; Moghadam, Pirous Fateh; Carrozzi, Giuliano; Trinito, Massimo Oddone; Salmaso, Stefania

    2011-03-01

    Monitoring perceptions, knowledge, attitudes and behaviors of populations during pandemic flu outbreaks is important as it allows communication strategies to be adjusted to meet emerging needs and assessment to be made of the effects of recommendations for prevention. The ongoing Italian Behavioral Risk Factor Surveillance System (PASSI) offered the setting for investigating people's opinions and behaviors regarding the A/H1N1 pandemic. PASSI surveillance is carried out in 126/148 Italian Local Health Units (LHU) through monthly telephone interviews administered by public health staff to a random sample of the resident population 18-69 years. In fall 2009 additional questions exploring issues related to the A/H1N1 flu were added to the standard questionnaire. The pandemic module was administered on a voluntary basis by the 70 participating LHUs from November 2nd, 2009 to February 7th, 2010; 4 047 interviews were collected. Overall 33% of respondents considered it likely that they would catch flu, 26% stated they were worried, 16% reported having limited some daily activities out of home and 22% said they would accept vaccination if offered. All these indicators showed a decreasing trend across the four-month period of observation. The most trusted sources of information were family doctors (81%). Willingness to be vaccinated was associated with worry about pandemic, age, sex, having a chronic disease and timing of the interview. The surveillance allowed us to gather relevant information, crucial for devising appropriate public health interventions. In future disease outbreaks, systems monitoring people's perceptions and behaviors should be included in the preparedness and response plans.

  1. Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa in 2011

    PubMed Central

    Hsiao, Marvin; Martin, Darren Patrick

    2015-01-01

    Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional

  2. Global migration of influenza A viruses in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence of the 2009 A/H1N1 pandemic virus underscores the importance of understanding how influenza A viruses evolve in swine on a global scale. To reveal the frequency, patterns and drivers of the spread of swine influenza virus globally, we conducted the largest phylogenetic analysis of swin...

  3. Detection of Novel Reassortant Influenza A (H3N2) and H1N1 2009 Pandemic Viruses in Swine in Hanoi, Vietnam.

    PubMed

    Baudon, E; Poon, L L; Dao, T D; Pham, N T; Cowling, B J; Peyre, M; Nguyen, K V; Peiris, M

    2015-09-01

    From May to September 2013, monthly samples were collected from swine in a Vietnamese slaughterhouse for influenza virus isolation and serological testing. A(H1N1)pdm09 viruses and a novel H3N2 originating from reassortment between A(H1N1)pdm09 and novel viruses of the North American triple reassortant lineage were isolated. Serological results showed low seroprevalence for the novel H3N2 virus and higher seroprevalence for A(H1N1)pdm09 viruses. In addition, serology suggested that other swine influenza viruses are also circulating in Vietnamese swine.

  4. A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

    PubMed

    Lind, Alexander; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Nilsson, Anna-Lena; Bomfim, Izaura Lima; Fink, Katharina; Lernmark, Åke

    2014-05-01

    Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1

  5. A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

    PubMed

    Lind, Alexander; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Nilsson, Anna-Lena; Bomfim, Izaura Lima; Fink, Katharina; Lernmark, Åke

    2014-05-01

    Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1

  6. 'Rhyme or reason?' Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009-2010.

    PubMed

    Lundgren, Britta

    2015-12-01

    During the swine flu pandemic of 2009-2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or 'big pharma capitalism' are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants. PMID:26077985

  7. ‘Rhyme or reason?’ Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009–2010

    PubMed Central

    Lundgren, Britta

    2015-01-01

    During the swine flu pandemic of 2009–2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or ‘big pharma capitalism’ are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants. PMID:26077985

  8. 'Rhyme or reason?' Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009-2010.

    PubMed

    Lundgren, Britta

    2015-12-01

    During the swine flu pandemic of 2009-2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or 'big pharma capitalism' are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants.

  9. Safety and Immunogenicity of a Monovalent 2009 Influenza A/H1N1v Vaccine Adjuvanted With AS03A or Unadjuvanted in HIV-Infected Adults: A Randomized, Controlled Trial

    PubMed Central

    Desaint, Corinne; Durier, Christine; Loulergue, Pierre; Duval, Xavier; Jacomet, Christine; Pialoux, Gilles; Ghosn, Jade; Raffi, François; Rey, David; Ajana, Faiza; Colin de Verdière, Nathalie; Reynes, Jacques; Foubert, Valérie; Roman, François; Devaster, Jeanne-Marie; Delfraissy, Jean-François; Aboulker, Jean-Pierre

    2011-01-01

    Background. Human immunodeficiency virus (HIV)–infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. Methods. We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03A-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. Results. A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. Conclusions. In HIV-1–infected adults, the AS03A-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection. PMID:21628666

  10. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients

    PubMed Central

    Caglioti, Claudia; Selleri, Marina; Rozera, Gabriella; Giombini, Emanuela; Zaccaro, Paola; Valli, Maria Beatrice; Capobianchi, Maria Rosaria

    2016-01-01

    In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8–42.3) X 10−4 vs 30.6 (27.4–33.6) X 10−4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients. PMID

  11. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.

    PubMed

    Caglioti, Claudia; Selleri, Marina; Rozera, Gabriella; Giombini, Emanuela; Zaccaro, Paola; Valli, Maria Beatrice; Capobianchi, Maria Rosaria

    2016-01-01

    In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8-42.3) X 10-4 vs 30.6 (27.4-33.6) X 10-4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients. PMID:27186639

  12. Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia

    PubMed Central

    El Moussi, Awatef; Pozo, Francisco; Ben Hadj Kacem, Mohamed Ali; Ledesma, Juan; Cuevas, Maria Teresa; Casas, Inmaculada; Slim, Amine

    2013-01-01

    Background The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. Objective The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. Method We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. Results The 2008–09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010–11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). Conclusion This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases. PMID:24069267

  13. Interaction of nanodiamonds materials with influenza viruses

    NASA Astrophysics Data System (ADS)

    Ivanova, V. T.; Ivanova, M. V.; Spitsyn, B. V.; Garina, K. O.; Trushakova, S. V.; Manykin, A. A.; Korzhenevsky, A. P.; Burseva, E. I.

    2012-02-01

    The perspectives of the application of modern materials contained nanodiamonds (ND) are considered in this study. The interaction between detonation paniculate ND, soot and influenza A and B viruses, fragments of cDNA were analyzed at the normal conditions. It was shown that these sorbents can interact with the following viruses: reference epidemic strains of influenza A(H1N1), A(H1N1)v, A(H3N2) and B viruses circulated in the word in 2000-2010. The allantoises, concentrated viruses, cDNA can be absorbed by ND sorbents and getting removed from water solutions within 20 min. ND sorbents can be used for the preparation of antivirus filters for water solution and for future diagnostic systems in virology.

  14. Oral administration of a Spirulina extract enriched for Braun-type lipoproteins protects mice against influenza A(H1N1) virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies indicate that Immulina, a commercial extract of Arthrospira (Spirulina) platensis, is a potent activator of innate immune cells and that Braun-type lipoproteins (a principal toll-like receptor (TLR) 2 ligand) are the main active components within this product. In the present study, ...

  15. Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

    PubMed

    Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

    2016-03-01

    This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

  16. The epidemiology and spread of drug resistant human influenza viruses.

    PubMed

    Hurt, Aeron C

    2014-10-01

    Significant changes in the circulation of antiviral-resistant influenza viruses have occurred over the last decade. The emergence and continued circulation of adamantane-resistant A(H3N2) and A(H1N1)pdm09 viruses mean that the adamantanes are no longer recommended for use. Resistance to the newer class of drugs, the neuraminidase inhibitors, is typically associated with poorer viral replication and transmission. But 'permissive' mutations, that compensated for impairment of viral function in A(H1N1) viruses during 2007/2008, enabled them to acquire the H275Y NA resistance mutation without fitness loss, resulting in their rapid global spread. Permissive mutations now appear to be present in A(H1N1)pdm09 viruses thereby increasing the risk that oseltamivir-resistant A(H1N1)pdm09 viruses may also spread globally, a concerning scenario given that oseltamivir is the most widely used influenza antiviral.

  17. Global circulation patterns of seasonal influenza viruses vary with antigenic drift

    NASA Astrophysics Data System (ADS)

    Bedford, Trevor; Riley, Steven; Barr, Ian G.; Broor, Shobha; Chadha, Mandeep; Cox, Nancy J.; Daniels, Rodney S.; Gunasekaran, C. Palani; Hurt, Aeron C.; Kelso, Anne; Klimov, Alexander; Lewis, Nicola S.; Li, Xiyan; McCauley, John W.; Odagiri, Takato; Potdar, Varsha; Rambaut, Andrew; Shu, Yuelong; Skepner, Eugene; Smith, Derek J.; Suchard, Marc A.; Tashiro, Masato; Wang, Dayan; Xu, Xiyan; Lemey, Philippe; Russell, Colin A.

    2015-07-01

    Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.

  18. Global circulation patterns of seasonal influenza viruses vary with antigenic drift.

    PubMed

    Bedford, Trevor; Riley, Steven; Barr, Ian G; Broor, Shobha; Chadha, Mandeep; Cox, Nancy J; Daniels, Rodney S; Gunasekaran, C Palani; Hurt, Aeron C; Kelso, Anne; Klimov, Alexander; Lewis, Nicola S; Li, Xiyan; McCauley, John W; Odagiri, Takato; Potdar, Varsha; Rambaut, Andrew; Shu, Yuelong; Skepner, Eugene; Smith, Derek J; Suchard, Marc A; Tashiro, Masato; Wang, Dayan; Xu, Xiyan; Lemey, Philippe; Russell, Colin A

    2015-07-01

    Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.

  19. 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.

    PubMed

    Hillaire, Marine L B; Vogelzang-van Trierum, Stella E; Kreijtz, Joost H C M; de Mutsert, Gerrie; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2013-03-01

    Virus-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 of human CD8(+) T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8(+) T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8(+) T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.

  20. Influenza A Viruses of Human Origin in Swine, Brazil.

    PubMed

    Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-08-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  1. Influenza A Viruses of Human Origin in Swine, Brazil

    PubMed Central

    Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-01-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  2. Influenza A Viruses of Human Origin in Swine, Brazil.

    PubMed

    Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-08-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.

  3. Clinical and socioeconomic impact of different types and subtypes of seasonal influenza viruses in children during influenza seasons 2007/2008 and 2008/2009

    PubMed Central

    2011-01-01

    Background There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness. Methods Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households. Results Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05). Conclusions Disease due to influenza A

  4. The challenges of global case reporting during pandemic A(H1N1) 2009.

    PubMed

    Williams, Stephanie; Fitzner, Julia; Merianos, Angela; Mounts, Anthony

    2014-01-01

    During the 2009 A(H1N1) influenza pandemic, the World Health Organization (WHO) asked all Member States to provide case-based data on at least the first 100 laboratory-confirmed influenza cases to generate an early understanding of the pandemic and provide appropriate guidance to affected countries. In reviewing the pandemic surveillance strategy, we evaluated the utility of case-based data collection and the challenges in interpreting these data at the global level. To do this, we assessed compliance with the surveillance recommendation and data completeness of submitted case records and described the epidemiological characteristics of up to the first 110 reported cases from each country, aggregated into regions. From April 2009 to August 2011, WHO received over 18 000 case records from 84 countries. Data reached WHO at different time intervals, in different formats and without information on collection methods. Just over half of the 18 000 records gave the date of symptom onset, which made it difficult to assess whether the cases were among the earliest to be confirmed. Descriptive epidemiological analyses were limited to summarizing age, sex and hospitalization ratios. Centralized analysis of case-based data had little value in describing key features of the pandemic. Results were difficult to interpret and would have been misleading if viewed in isolation. A better approach would be to identify critical questions, standardize data elements and methods of investigation, and create efficient channels for communication between countries and the international public health community. Regular exchange of routine surveillance data will help to consolidate these essential channels of communication.

  5. A historical perspective of influenza A(H1N2) virus.

    PubMed

    Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

    2014-01-01

    The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.

  6. Experimental Inoculation of Pigs with Pandemic H1N1 2009 Virus and HI Cross-Reactivity with Contemporary Swine Influenza Virus Antisera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In March-April 2009, a novel A/H1N1 emerged in the human population in North America. The gene constellation of the virus was demonstrated to be a combination from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before been identified in swine or other species...

  7. Analysis of Coinfections with A/H1N1 Strain Variants among Pigs in Poland by Multitemperature Single-Strand Conformational Polymorphism.

    PubMed

    Lepek, Krzysztof; Pajak, Beata; Rabalski, Lukasz; Urbaniak, Kinga; Kucharczyk, Krzysztof; Markowska-Daniel, Iwona; Szewczyk, Boguslaw

    2015-01-01

    Monitoring and control of infections are key parts of surveillance systems and epidemiological risk prevention. In the case of influenza A viruses (IAVs), which show high variability, a wide range of hosts, and a potential of reassortment between different strains, it is essential to study not only people, but also animals living in the immediate surroundings. If understated, the animals might become a source of newly formed infectious strains with a pandemic potential. Special attention should be focused on pigs, because of the receptors specific for virus strains originating from different species, localized in their respiratory tract. Pigs are prone to mixed infections and may constitute a reservoir of potentially dangerous IAV strains resulting from genetic reassortment. It has been reported that a quadruple reassortant, A(H1N1)pdm09, can be easily transmitted from humans to pigs and serve as a donor of genetic segments for new strains capable of infecting humans. Therefore, it is highly desirable to develop a simple, cost-effective, and rapid method for evaluation of IAV genetic variability. We describe a method based on multitemperature single-strand conformational polymorphism (MSSCP), using a fragment of the hemagglutinin (HA) gene, for detection of coinfections and differentiation of genetic variants of the virus, difficult to identify by conventional diagnostic. PMID:25961024

  8. The genomic and epidemiological dynamics of human influenza A virus

    PubMed Central

    Rambaut, Andrew; Pybus, Oliver G.; Nelson, Martha I.; Viboud, Cecile; Taubenberger, Jeffery K.; Holmes, Edward C.

    2008-01-01

    The evolutionary interaction between influenza A virus and the human immune system, manifest as ‘antigenic drift’ of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome-scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/H3N2 and A/H1N1 subtypes co-circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/H3N2 and A/H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/H1N1, indicative of weaker antigenic drift. These results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions. PMID:18418375

  9. The serial intervals of seasonal and pandemic influenza viruses in households in Bangkok, Thailand.

    PubMed

    Levy, Jens W; Cowling, Benjamin J; Simmerman, James M; Olsen, Sonja J; Fang, Vicky J; Suntarattiwong, Piyarat; Jarman, Richard G; Klick, Brendan; Chotipitayasunondh, Tawee

    2013-06-15

    The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11-14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies.

  10. The serial intervals of seasonal and pandemic influenza viruses in households in Bangkok, Thailand.

    PubMed

    Levy, Jens W; Cowling, Benjamin J; Simmerman, James M; Olsen, Sonja J; Fang, Vicky J; Suntarattiwong, Piyarat; Jarman, Richard G; Klick, Brendan; Chotipitayasunondh, Tawee

    2013-06-15

    The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11-14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies. PMID:23629874

  11. Amantadine-resistant influenza A viruses isolated in South Korea from 2003 to 2009.

    PubMed

    Choi, Woo-Young; Kim, SuJin; Lee, NamJoo; Kwon, Meehwa; Yang, InSeok; Kim, Min-Ji; Cheong, Seul-Gi; Kwon, Donghyok; Lee, Joo-Yeon; Oh, Hee-Bok; Kang, Chun

    2009-11-01

    To investigate the frequency of amantadine resistance among influenza A viruses isolated in Korea during the 2003-2009 seasons, 369 (16.8%) 2199 A/H1N1 viruses and 780 (14.8%) of 5263 A/H3N2 viruses were randomly selected. The M2 and HA1 genes of each isolate were amplified by reverse transcription-polymerase chain reaction and followed by nucleotide sequencing. The results showed that the resistance rate to amantadine among A/H1N1 viruses increased significantly from 2004-2005 (33.3%) to 2007-2008 (97.8%) and then decreased dramatically in 2008-2009 (1.9%). The A/H1N1 isolates recently detected in 2008-2009 turned amantadine-sensitive containing two new substitutions at specific sites (S141N, G185A) in HA1. Compared with A/H1N1 viruses, the amantadine resistance among the A/H3N2 viruses increased from 2003-2004 (9.7%) to 2005-2006 (96.7%) and decreased in 2006-2007 (57.4%). During 2006-2007, both of amantadine-resistant and -sensitive A/H3N2 viruses co-circulated but clustered in different branches phylogenetically. All of A/H3N2 isolates tested during 2007-2009 appeared to cluster in the same group being resistant to amantadine.

  12. Multiple Reassortment Events in the Evolutionary History of H1N1 Influenza A Virus Since 1918

    PubMed Central

    Nelson, Martha I.; Viboud, Cécile; Simonsen, Lone; Bennett, Ryan T.; Griesemer, Sara B.; St. George, Kirsten; Taylor, Jill; Spiro, David J.; Sengamalay, Naomi A.; Ghedin, Elodie; Taubenberger, Jeffery K.; Holmes, Edward C.

    2008-01-01

    The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized. PMID:18463694

  13. Pandemic (H1N1) 2009 Influenza Virus Infection in A Survivor Who Has Recovered from Severe H7N9 Virus Infection, China

    PubMed Central

    Chen, Shan-Hui; Wu, Meng-Na; Qian, Yan-Hua; Ma, Guang-Yuan; Wang, Guo-Lin; Yang, Yang; Zhao, Teng; Lu, Bing; Ma, Mai-Juan; Cao, Wu-Chun

    2016-01-01

    We firstly report a patient who presented with severe complications after infection with influenza A(H1N1) pdm2009, more than 1 year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination. PMID:27757100

  14. Global circulation patterns of seasonal influenza viruses vary with antigenic drift

    PubMed Central

    Bedford, Trevor; Riley, Steven; Barr, Ian G.; Broor, Shobha; Chadha, Mandeep; Cox, Nancy J.; Daniels, Rodney S.; Gunasekaran, C. Palani; Hurt, Aeron C.; Kelso, Anne; Lewis, Nicola S.; Li, Xiyan; McCauley, John W.; Odagiri, Takato; Potdar, Varsha; Rambaut, Andrew; Shu, Yuelong; Skepner, Eugene; Smith, Derek J.; Suchard, Marc A.; Tashiro, Masato; Wang, Dayan; Xu, Xiyan; Lemey, Philippe; Russell, Colin A.

    2015-01-01

    Understanding the spatio-temporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well-characterized1-7 but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here, based on analyses of 9,604 hemagglutinin sequences of human seasonal influenza viruses from 2000–2012, we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses. While genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast (E-SE) Asia, genetic variants of A/H1N1 and B viruses persisted across multiple seasons and exhibited complex global dynamics with E-SE Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as likely drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology and human behavior. PMID:26053121

  15. Experimental Challenge with Two Isolates of 2009 A/H1N1 in Weaned Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. The gene constellation of the 2009 pandemic H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species (1). Although the hemagglutinin gene is relate...

  16. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know?

    PubMed

    Minodier, Laetitia; Charrel, Remi N; Ceccaldi, Pierre-Emmanuel; van der Werf, Sylvie; Blanchon, Thierry; Hanslik, Thomas; Falchi, Alessandra

    2015-12-12

    This review provides for the first time an assessment of the current understanding about the occurrence and the clinical significance of gastrointestinal (GI) symptoms in influenza patients, and their correlation with the presence of human influenza viruses in stools of patients with confirmed influenza virus infection. Studies exploring how human influenza viruses spread to the patient's GI tract after a primary respiratory infection have been summarized. We conducted a systematic search of published peer-reviewed literature up to June 2015 with regard to the above-mentioned aspects, focusing on human influenza viruses (A(H1N1), A(H1N1)pdm09, A(H3N2), and B). Forty-four studies were included in this systematic review and meta-analysis. The pooled prevalence of any digestive symptoms ranged from 30.9% (95% CI, 9.8 to 57.5; I(2) = 97.5%) for A(H1N1)pdm09 to 2.8% (95% CI, 0.6 to 6.5; I(2) = 75.4%) for A(H1N1). The pooled prevalence of influenza viruses in stool was 20.6% (95% CI, 8.9 to 35.5; I(2) = 96.8%), but their correlation with GI symptoms has rarely been explored. The presence of viral RNA in stools because of haematogenous dissemination to organs via infected lymphocytes is likely, but the potential to cause direct intestinal infection and faecal-oral transmission warrants further investigation. This review highlights the gaps in our knowledge, and the high degree of uncertainty about the prevalence and significance of GI symptoms in patients with influenza and their correlation with viral RNA positivity in stool because of the high level of heterogeneity among studies.

  17. Effect of vaccines and antivirals during the major 2009 A(H1N1) pandemic wave in Norway--and the influence of vaccination timing.

    PubMed

    Blasio, Birgitte Freiesleben de; Iversen, Bjørn G; Tomba, Gianpaolo Scalia

    2012-01-01

    To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7-29.8%), with highest disease rates among children 0-14 years (43-44%). Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11-12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%. In conclusion, vaccination timing was a critical factor in relation to the spread of the 2009 A(H1N1) influenza. Our results also corroborate the central role of children for the transmission of A(H1N1) pandemic influenza. PMID:22253862

  18. Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study

    PubMed Central

    Trotta, Francesco; Da Cas, Roberto; Spila Alegiani, Stefania; Gramegna, Maria; Venegoni, Mauro; Zocchetti, Carlo

    2014-01-01

    Objective To assess the risk of maternal, fetal, and neonatal outcomes associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during pregnancy. Design Historical cohort study. Setting Singleton pregnancies of the resident population of the Lombardy region of Italy. Participants All deliveries between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic vaccine, pregnancy, and birth outcomes were retrieved from regional databases. Vaccinated and non-vaccinated women were compared in a propensity score matched analysis to estimate risks of adverse outcomes. Main outcome measures Main maternal outcomes included type of delivery, admission to intensive care unit, eclampsia, and gestational diabetes; fetal and neonatal outcomes included perinatal deaths, small for gestational age births, and congenital malformations. Results Among the 86 171 eligible pregnancies, 6246 women were vaccinated (3615 (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No difference was observed in terms of spontaneous deliveries (adjusted odds ratio 1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated and non-vaccinated women. A slight increase in congenital malformations, although not statistically significant, was present in the exposed cohort (1.14, 0.99 to 1.31). Conclusions Our findings add relevant information about the safety of the MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly explain the increased risk of some maternal outcomes. Meta-analysis of published studies should be conducted to further clarify the risk of infrequent outcomes, such as specific congenital malformations. PMID:24874845

  19. Review on the impact of pregnancy and obesity on influenza virus infection

    PubMed Central

    Karlsson, Erik A.; Marcelin, Glendie; Webby, Richard J.; Schultz‐Cherry, Stacey

    2012-01-01

    Please cite this paper as: Karlsson et al. (2012) Review on the impact of pregnancy and obesity on influenza virus infection. Influenza and Other Respiratory Viruses 6(6), 449–460. A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness. PMID:22335790

  20. Serological report of pandemic and seasonal human influenza virus infection in dogs in southern China.

    PubMed

    Yin, Xin; Zhao, Fu-Rong; Zhou, Dong-Hui; Wei, Ping; Chang, Hui-Yun

    2014-11-01

    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. Detection of Nonhemagglutinating Influenza A(H3) Viruses by Enzyme-Linked Immunosorbent Assay in Quantitative Influenza Virus Culture

    PubMed Central

    Els, C.; Sprong, L.; van Beek, R.; van der Vries, E.; Osterhaus, A. D. M. E.; Rimmelzwaan, G. F.

    2014-01-01

    To assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. Typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutinin (HA). This readout method is no longer adequate, since an increasing number of currently circulating influenza A virus H3 subtype (A[H3]) viruses display a reduced capacity to agglutinate erythrocytes. Here, we report the magnitude of this problem by analyzing the frequency of HA-deficient A(H3) viruses detected in The Netherlands from 1999 to 2012. Furthermore, we report the development and validation of an alternative method for monitoring the production of progeny influenza virus in quantitative virus cultures, which is independent of the capacity to agglutinate erythrocytes. This method is based on the detection of viral nucleoprotein (NP) in virus culture plates by enzyme-linked immunosorbent assay (ELISA), and it produced results similar to those of the hemagglutination assay using strains with good HA activity, including A/Brisbane/059/07 (H1N1), A/Victoria/210/09 (H3N2), other seasonal A(H1N1), A(H1N1)pdm09, and the majority of A(H3) virus strains isolated in 2009. In contrast, many A(H3) viruses that have circulated since 2010 failed to display HA activity, and infectious virus titers were determined only by detecting NP. The virus culture ELISA described here will enable efficacy testing of new antiviral compounds in clinical trials during seasons in which nonhemagglutinating influenza A viruses circulate. PMID:24622097

  2. Detection of nonhemagglutinating influenza a(h3) viruses by enzyme-linked immunosorbent assay in quantitative influenza virus culture.

    PubMed

    van Baalen, C A; Els, C; Sprong, L; van Beek, R; van der Vries, E; Osterhaus, A D M E; Rimmelzwaan, G F

    2014-05-01

    To assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. Typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutinin (HA). This readout method is no longer adequate, since an increasing number of currently circulating influenza A virus H3 subtype (A[H3]) viruses display a reduced capacity to agglutinate erythrocytes. Here, we report the magnitude of this problem by analyzing the frequency of HA-deficient A(H3) viruses detected in The Netherlands from 1999 to 2012. Furthermore, we report the development and validation of an alternative method for monitoring the production of progeny influenza virus in quantitative virus cultures, which is independent of the capacity to agglutinate erythrocytes. This method is based on the detection of viral nucleoprotein (NP) in virus culture plates by enzyme-linked immunosorbent assay (ELISA), and it produced results similar to those of the hemagglutination assay using strains with good HA activity, including A/Brisbane/059/07 (H1N1), A/Victoria/210/09 (H3N2), other seasonal A(H1N1), A(H1N1)pdm09, and the majority of A(H3) virus strains isolated in 2009. In contrast, many A(H3) viruses that have circulated since 2010 failed to display HA activity, and infectious virus titers were determined only by detecting NP. The virus culture ELISA described here will enable efficacy testing of new antiviral compounds in clinical trials during seasons in which nonhemagglutinating influenza A viruses circulate.

  3. Effects of oral intake of plasmacytoid dendritic cells-stimulative lactic acid bacterial strain on pathogenesis of influenza-like illness and immunological response to influenza virus.

    PubMed

    Sugimura, Tetsu; Takahashi, Hitoshi; Jounai, Kenta; Ohshio, Konomi; Kanayama, Masaya; Tazumi, Kyoko; Tanihata, Yoko; Miura, Yutaka; Fujiwara, Daisuke; Yamamoto, Norio

    2015-09-14

    Lactococcus lactis ssp. lactis JCM5805 has been shown to be a rare lactic acid bacterium that can activate plasmacytoid dendritic cells in both murine and human species. In this study, we carried out a randomised placebo-controlled double-blind experiment to evaluate its effect on the pathogenesis of influenza-like illness during the winter season. A total of 213 volunteers were divided into two groups, which received either yogurt made with L. lactis JCM5805 or a placebo beverage daily for 10 weeks. In the JCM5805 group, the cumulative incidence days of 'cough' and 'feverishness', which are defined as major symptoms of an influenza-like illness, were significantly decreased compared with the placebo group. In addition, peripheral blood mononuclear cells prepared from volunteers were cultured in the presence of inactivated human influenza virus A/H1N1 (A/PR/8/34). IFN-α elicited by A/H1N1 tended to be higher in the JCM5805 group compared with the placebo group, and an IFN-α-inducible antiviral factor, interferon-stimulated gene 15 (ISG15), elicited by A/H1N1 was significantly higher in the JCM5805 group compared with the placebo group after the intake period. These results suggest that intake of JCM5805 is able to prevent the pathogenesis of an influenza-like illness via enhancement of an IFN-α-mediated response to the influenza virus.

  4. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    PubMed

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.

  5. Genetic and Antigenic Typing of Seasonal Influenza Virus Breakthrough Cases from a 2008-2009 Vaccine Efficacy Trial

    PubMed Central

    Durviaux, Serge; Treanor, John; Beran, Jiri; Duval, Xavier; Esen, Meral; Feldman, Gregory; Frey, Sharon E.; Launay, Odile; Leroux-Roels, Geert; McElhaney, Janet E.; Nowakowski, Andrzej; Ruiz-Palacios, Guillermo M.; van Essen, Gerrit A.; Oostvogels, Lidia; Devaster, Jeanne-Marie

    2014-01-01

    Estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. This study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (HA) gene-encoded HA1 domain is a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza virus vaccine efficacy trial involving >43,000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380 viruses), A(H1N1) (29 viruses), B(Yamagata) (23 viruses), and B(Victoria) (66 viruses) from 603 PCR- or culture-confirmed specimens. Unlike the B strains, most A(H3N2) (377 viruses) and all A(H1N1) viruses were classified as homologous to the respective vaccine strains based on their HA1 domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48% (182/380) of A(H3N2) and 86% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses classified as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR is a sensitive diagnostic method for confirming influenza virus cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity; hence, it may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine strain for estimating vaccine efficacy in a prospective clinical trial. PMID:24371255

  6. Antigenic and genetic variation in the hemagglutinins of H1N1 and H3N2 human influenza a viruses in the Shanghai area from 2005 to 2008.

    PubMed

    Ren, Xiao-wei; Ju, Li-wen; Yang, Ji-xing; Lv, Xi-hong; Jiang, Lu-fang; Zhao, Nai-qing; Jiang, Qing-wu

    2011-07-01

    Continued rapid evolution of the influenza A virus is responsible for annual epidemics and occasional pandemics in the Shanghai area. In the present study, the representative strains of A/H1N1 and A/H3N2 influenza viruses isolated in the Shanghai area from 2005 to 2008 were antigenically and genetically characterized. The antigenic cartography method was carried out to visualize the hemagglutination-inhibition data. Antigenic differences were detected between circulating A/H1N1 strains isolated from 2005 to 2006 and the epidemic A/H1N1 strains isolated in 2008, which were found to be associated with the amino acid substitution K140E in HA1. The present vaccine strain A/Brisbane/59/2007 is considered to be capable of providing sufficient immunity against most of the circulating A/H1N1 viruses isolated in 2008 from the Shanghai population. The study showed that there were significant antigenic differences between the epidemic A/H3N2 strains isolated in 2007 and 2008, suggesting that antigenic drift had occurred in the A/H3N2 strains isolated in 2008. The P194L mutation was thought to be responsible for the antigenic evolution of influenza A/H3N2 viruses isolated from Shanghai in 2008. Evidence of antigenic drift suggests that the influenza A/H3N2 vaccine component needs to be updated.

  7. Use of influenza A viruses expressing reporter genes to assess the frequency of double infections in vitro.

    PubMed

    Bodewes, R; Nieuwkoop, N J; Verburgh, R J; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

    2012-08-01

    Exchange of gene segments between mammalian and avian influenza A viruses may lead to the emergence of potential pandemic influenza viruses. Since co-infection of single cells with two viruses is a prerequisite for reassortment to take place, we assessed frequencies of double-infection in vitro using influenza A/H5N1 and A/H1N1 viruses expressing the reporter genes eGFP or mCherry. Double-infected A549 and Madin-Darby canine kidney cells were detected by confocal microscopy and flow cytometry. PMID:22535774

  8. Measured voluntary avoidance behaviour during the 2009 A/H1N1 epidemic

    PubMed Central

    Bayham, Jude; Kuminoff, Nicolai V.; Gunn, Quentin; Fenichel, Eli P.

    2015-01-01

    Managing infectious disease is among the foremost challenges for public health policy. Interpersonal contacts play a critical role in infectious disease transmission, and recent advances in epidemiological theory suggest a central role for adaptive human behaviour with respect to changing contact patterns. However, theoretical studies cannot answer the following question: are individual responses to disease of sufficient magnitude to shape epidemiological dynamics and infectious disease risk? We provide empirical evidence that Americans voluntarily reduced their time spent in public places during the 2009 A/H1N1 swine flu, and that these behavioural shifts were of a magnitude capable of reducing the total number of cases. We simulate 10 years of epidemics (2003–2012) based on mixing patterns derived from individual time-use data to show that the mixing patterns in 2009 yield the lowest number of total infections relative to if the epidemic had occurred in any of the other nine years. The World Health Organization and other public health bodies have emphasized an important role for ‘distancing’ or non-pharmaceutical interventions. Our empirical results suggest that neglect for voluntary avoidance behaviour in epidemic models may overestimate the public health benefits of public social distancing policies. PMID:26511046

  9. Measured voluntary avoidance behaviour during the 2009 A/H1N1 epidemic.

    PubMed

    Bayham, Jude; Kuminoff, Nicolai V; Gunn, Quentin; Fenichel, Eli P

    2015-11-01

    Managing infectious disease is among the foremost challenges for public health policy. Interpersonal contacts play a critical role in infectious disease transmission, and recent advances in epidemiological theory suggest a central role for adaptive human behaviour with respect to changing contact patterns. However, theoretical studies cannot answer the following question: are individual responses to disease of sufficient magnitude to shape epidemiological dynamics and infectious disease risk? We provide empirical evidence that Americans voluntarily reduced their time spent in public places during the 2009 A/H1N1 swine flu, and that these behavioural shifts were of a magnitude capable of reducing the total number of cases. We simulate 10 years of epidemics (2003-2012) based on mixing patterns derived from individual time-use data to show that the mixing patterns in 2009 yield the lowest number of total infections relative to if the epidemic had occurred in any of the other nine years. The World Health Organization and other public health bodies have emphasized an important role for 'distancing' or non-pharmaceutical interventions. Our empirical results suggest that neglect for voluntary avoidance behaviour in epidemic models may overestimate the public health benefits of public social distancing policies. PMID:26511046

  10. Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan.

    PubMed

    Dapat, Clyde; Kondo, Hiroki; Dapat, Isolde C; Baranovich, Tatiana; Suzuki, Yasushi; Shobugawa, Yugo; Saito, Kousuke; Saito, Reiko; Suzuki, Hiroshi

    2013-09-01

    Two new influenza virus neuraminidase inhibitors (NAIs), peramivir and laninamivir, were approved in 2010 which resulted to four NAIs that were used during the 2010-2011 influenza season in Japan. This study aims to monitor the susceptibility of influenza virus isolates in 2009-2010 and 2010-2011 influenza seasons in Japan to the four NAIs using the fluorescence-based 50% inhibitory concentration (IC₅₀) method. Outliers were identified using box-and-whisker plot analysis and full NA gene sequencing was performed to determine the mutations that are associated with reduction of susceptibility to NAIs. A total of 117 influenza A(H1N1)pdm09, 59 A(H3N2), and 18 type B viruses were tested before NAI treatment and eight A(H1N1)pdm09 and 1 type B viruses were examined from patients after NAI treatment in the two seasons. NA inhibition assay showed type A influenza viruses were more susceptible to NAIs than type B viruses. The peramivir and laninamivir IC₅₀ values of both type A and B viruses were significantly lower than the oseltamivir and zanamivir IC₅₀ values. Among influenza A(H1N1)pdm09 viruses, the prevalence of H274Y viruses increased from 0% in the 2009-2010 season to 3% in the 2010-2011 season. These H274Y viruses were resistant to oseltamivir and peramivir with 200-300 fold increase in IC₅₀ values but remained sensitive to zanamivir and laninamivir. Other mutations in NA, such as I222T and M241I were identified among the outliers. Among influenza A(H3N2) viruses, two outliers were identified with D151G and T148I mutations, which exhibited a reduction in susceptibility to oseltamivir and zanamivir, respectively. Among type B viruses, no outliers were identified to the four NAIs. For paired samples that were collected before and after drug treatment, three (3/11; 27.3%) H274Y viruses were identified among A(H1N1)pdm09 viruses after oseltamivir treatment but no outliers were found in the laninamivir-treatment group (n=3). Despite widespread use of

  11. A/H1N1 Vaccine Intentions in College Students: An Application of the Theory of Planned Behavior

    ERIC Educational Resources Information Center

    Agarwal, Vinita

    2014-01-01

    Objective: To test the applicability of the Theory of Planned Behavior (TPB) in college students who have not previously received the A/H1N1 vaccine. Participants: Undergraduate communication students at a metropolitan southern university. Methods: In January-March 2010, students from voluntarily participating communication classes completed a…

  12. Molecular and phylogenetic analysis of influenza A H1N1 pandemic viruses in Cuba, May 2009 to August 2010.

    PubMed

    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

    2013-07-01

    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.

  13. Preexisting Antibody-Dependent Cellular Cytotoxicity-Activating Antibody Responses Are Stable Longitudinally and Cross-reactive Responses Are Not Boosted by Recent Influenza Exposure.

    PubMed

    Valkenburg, Sophie A; Zhang, Yanyu; Chan, Ka Y; Leung, Kathy; Wu, Joseph T; Poon, Leo L M

    2016-10-15

    Cross-reactive influenza virus-specific antibody-dependent cellular cytotoxicity (ADCC)-activating antibodies are readily detected in healthy adults. However, little is known about the kinetics of these ADCC responses. We used retrospective serial blood samples from healthy donors to investigate this topic. All donors had ADCC responses against 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) and avian influenza A(H7N9) virus hemagglutinins (HAs) despite being seronegative for these viruses in standard hemagglutination inhibition and microneutralization serological assays. A(H1N1)pdm09 exposure did not boost ADCC responses specific for H7 HA antigens. H7 HA ADCC responses were variable longitudinally within donors, suggesting that these cross-reactive antibodies are unstable. We found no correlation between ADCC responses to the H7 HA and either influenza virus-specific immunoglobulin G1 concentration or age. PMID:27493238

  14. Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir.

    PubMed

    Takashita, Emi; Ejima, Miho; Ogawa, Rie; Fujisaki, Seiichiro; Neumann, Gabriele; Furuta, Yousuke; Kawaoka, Yoshihiro; Tashiro, Masato; Odagiri, Takato

    2016-08-01

    Favipiravir, a viral RNA-dependent RNA polymerase inhibitor, has recently been approved in Japan for influenza pandemic preparedness. Here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. In this assay, the antiviral activity of favipiravir is determined by inhibition of virus-induced cytopathic effect, which can be measured by using a colorimetric cell proliferation assay. To demonstrate the robustness of the assay, we compared the favipiravir susceptibilities of neuraminidase (NA) inhibitor-resistant influenza A(H1N1)pdm09, A(H3N2), A(H7N9) and B viruses and their sensitive counterparts. No significant differences in the favipiravir susceptibilities were found between NA inhibitor-resistant and sensitive viruses. We, then, examined the antiviral susceptibility of 57 pairs of influenza viruses isolated from patients pre- and post-administration of favipiravir in phase 3 clinical trials. We found that there were no viruses with statistically significant reduced susceptibility to favipiravir or NA inhibitors, although two of 20 paired A(H1N1)pdm09, one of 17 paired A(H3N2) and one of 20 paired B viruses possessed amino acid substitutions in the RNA-dependent RNA polymerase subunits, PB1, PB2 and PA, after favipiravir administration. This is the first report on the antiviral susceptibility of influenza viruses isolated from patients after favipiravir treatment.

  15. On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic

    PubMed Central

    Hsieh, Ying-Hen; Huang, Hsiang-Min; Lan, Yu-Ching

    2016-01-01

    Background It has been observed that, historically, strains of pandemic influenza led to succeeding seasonal waves, albeit with decidedly different patterns. Recent studies suggest that the 2009 A(H1N1)pdm09 pandemic has had an impact on the circulation patterns of seasonal influenza strains in the post-pandemic years. In this work we aim to investigate this issue and also to compare the relative transmissibility of these waves of differing strains using Taiwan influenza surveillance data before, during and after the pandemic. Methods We make use of the Taiwan Center for Disease Control and Prevention influenza surveillance data on laboratory-confirmed subtyping of samples and a mathematical model to determine the waves of circulating (and co-circulating) H1, H3 and B virus strains in Taiwan during 2008–2014; or namely, short before, during and after the 2009 pandemic. We further pinpoint the turning points and relative transmissibility of each wave, in order to ascertain whether any temporal pattern exists. Results/Findings For two consecutive years following the 2009 pandemic, A(H1N1)pdm09 circulated in Taiwan (as in most of Northern Hemisphere), sometimes co-circulating with AH3. From the evolution point of view, A(H1N1)pdm09 and AH3 were able to sustain their circulation patterns to the end of 2010. In fact, A(H1N1)pdm09 virus circulated in six separate waves in Taiwan between summer of 2009 and spring of 2014. Since 2009, a wave of A(H1N1)pmd09 occurred every fall/winter influenza season during our study period except 2011–2012 season, when mainly influenza strain B circulated. In comparing transmissibility, while the estimated per capita weekly growth rates for cumulative case numbers (and the reproduction number) seem to be lower for most of the influenza B waves (0.06~0.26; range of 95% CIs: 0.05~0.32) when compared to those of influenza A, the wave of influenza B from week 8 to week 38 of 2010 immediately following the fall/winter wave of 2009 A(H1N1

  16. A human-like H1N2 influenza virus detected during an outbreak of acute respiratory disease in swine in Brazil.

    PubMed

    Schaefer, Rejane; Rech, Raquel Rubia; Gava, Danielle; Cantão, Mauricio Egídio; da Silva, Marcia Cristina; Silveira, Simone; Zanella, Janice Reis Ciacci

    2015-01-01

    Passive monitoring for detection of influenza A viruses (IAVs) in pigs has been carried out in Brazil since 2009, detecting mostly the A(H1N1)pdm09 influenza virus. Since then, outbreaks of acute respiratory disease suggestive of influenza A virus infection have been observed frequently in Brazilian pig herds. During a 2010-2011 influenza monitoring, a novel H1N2 influenza virus was detected in nursery pigs showing respiratory signs. The pathologic changes were cranioventral acute necrotizing bronchiolitis to subacute proliferative and purulent bronchointerstitial pneumonia. Lung tissue samples were positive for both influenza A virus and A(H1N1)pdm09 influenza virus based on RT-qPCR of the matrix gene. Two IAVs were isolated in SPF chicken eggs. HI analysis of both swine H1N2 influenza viruses showed reactivity to the H1δ cluster. DNA sequencing was performed for all eight viral gene segments of two virus isolates. According to the phylogenetic analysis, the HA and NA genes clustered with influenza viruses of the human lineage (H1-δ cluster, N2), whereas the six internal gene segments clustered with the A(H1N1)pdm09 group. This is the first report of a reassortant human-like H1N2 influenza virus derived from pandemic H1N1 virus causing an outbreak of respiratory disease in pigs in Brazil. The emergence of a reassortant IAV demands the close monitoring of pigs through the full-genome sequencing of virus isolates in order to enhance genetic information about IAVs circulating in pigs.

  17. Multiplex RT-PCR and indirect immunofluorescence assays for detection and subtyping of human influenza virus in Tunisia.

    PubMed

    Ben M'hadheb, Manel; Harrabi, Myriam; Souii, Amira; Jrad-Battikh, Nadia; Gharbi, Jawhar

    2015-03-01

    Influenza viruses are negative stranded segmented RNA viruses belonging to Orthomyxoviridae family. They are classified into three types A, B, and C. Type A influenza viruses are classified into subtypes according to the antigenic characters of the surface glycoproteins: hemagglutinin (H) and neuraminidase (N). The aim of the present study is to develop a fast and reliable multiplex RT-PCR technique for detecting simultaneously the subtypes A/H1N1 and A/H3N2 of influenza virus. Our study included 398 patients (mean age 30.33 ± 19.92 years) with flu or flu-like syndromes, consulting physicians affiliated with collaborating teams. A multiplex RT-PCR detecting A/H1N1 and A/H3N2 influenza viruses and an examination by indirect immunofluorescence (IFI) were performed. In the optimized conditions, we diagnosed by IFI a viral infection in 90 patients (22.6 %): 85 cases of influenza type A, four cases of influenza type B, and only one case of coinfection with types A and B. An evaluation of the technique was performed on 19 clinical specimens positive in IFI, and we detected eight cases of A/H3N2, five cases of A/H1N1, one case of influenza virus type A which is not an H1N1 nor H3N2, and five negative cases. Multiplex RT-PCR is a sensitive technique allowing an effective and fast diagnosis of respiratory infections caused by influenza viruses in which the optimization often collides with problems of sensibility.

  18. The sorption of influenza viruses and antibiotics on carbon nanotubes and polyaniline nanocomposites

    NASA Astrophysics Data System (ADS)

    Ivanova, V. T.; Katrukha, G. S.; Timofeeva, A. V.; Ilyna, M. V.; Kurochkina, Y. E.; Baratova, L. A.; Sapurina, I. Yu; Ivanov, V. F.

    2011-04-01

    The decontamination of the solutions from micropatogens and drug delivery are the important problems of modern life. It was shown that carbon nanotubes, polyaniline and their composites can interact with antibiotics-polypeptides and some viruses (pandemic strain of influenza viruses A(H1N1)v circulated in Russia in 2009-2010. During a short time drug and viruses can be absorbed by polyaniline and removed from aqueous solutions at the normal conditions. Polyaniline composites can be useful for the preparation of drug delivery and virus control filters and also in biotechnology for the improvement the methods of antibiotics purification.

  19. [Comparison of detection sensitivity in rapid-diagnosis influenza virus kits].

    PubMed

    Tokuno, Osamu; Fujiwara, Miki; Nakajoh, Yoshimi; Yamanouchi, Sumika; Adachi, Masayo; Ikeda, Akiko; Kitayama, Shigeo; Takahashi, Toshio; Kase, Tetsuo; Kinoshita, Shouhiro; Kumagai, Shunichi

    2009-09-01

    Rapid-diagnosis kits able to detect influenza A and B virus by immunochromatography developed by different manufacturers, while useful in early diagnosis, may vary widely in detection sensitivity. We compared sensitivity results for eight virus-detection kits in current use--Quick Chaser FluA, B (Mizuho Medy), Espline Influenza A & B-N (Fujirebio), Capilia Flu A + B (Nippon Beckton Dickinson & Alfesa Pharma), Poctem Influenza A/B (Otsuka Pharma & Sysmex), BD Flu Examan (Nippon Beckton Dickinson), Quick Ex-Flu "Seiken" (Denka Seiken), Quick Vue Rapid SP Influ (DP Pharma Biomedical), and Rapid Testa FLU stick (Daiichi Pure Chemicals)--against influenza virus stocks, contained five vaccination strains (one A/H1N1, two A/H3N2, and two B) and six clinical strains (two A/H1N1, two A/H3N2, and two B). Minimum detection concentrations giving immunologically positive signals in serial dilution and RNA copies in positive dilution in real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were assayed for all kits and virus stock combinations. RNA log10 copy numbers/mL in dilutions within detection limits yielded 5.68-7.02, 6.37-7,17, and 6.5-8.13 for A/H1N1, A/H3N2, and B. Statistically significant differences in sensitivity were observed between some kit combinations. Detection sensitivity tended to be relatively higher for influenza A than B virus. This is assumed due to different principles in kit methods, such as monoclonal antibodies, specimen-extraction conditions, and other unknown factors.

  20. Detailed Report on 2014/15 Influenza Virus Characteristics, and Estimates on Influenza Virus Vaccine Effectiveness from Austria’s Sentinel Physician Surveillance Network

    PubMed Central

    2016-01-01

    Background Influenza vaccine effectiveness (VE) is influenced by the antigenic similarity between vaccine- and circulating strains. Material and Methods This paper presents data obtained by the Austrian sentinel surveillance system on the evolution of influenza viruses during the season 2014/15 and its impact on influenza vaccine effectiveness in primary care in Austria as estimated by a test-negative case control design. VE estimates were performed for each influenza virus type/subtype, stratified by underlying diseases and adjusted for age, sex and calendar week of infection. Results Detailed genetic and antigenic analyses showed that circulating A(H3N2) viruses were genetically distinct from the 2014/15 A(H3N2) vaccine component indicating a profound vaccine mismatch. The Influenza A(H1N1)pdm09 viruses were antigenically conserved and matched the respective vaccine component. Influenza B viruses were lineage-matched B/Yamagata viruses with a clade-level variation. Consistent with substantial vaccine mismatch for the A(H3N2) viruses a crude overall VE of only 47% was estimated, whereas the VE estimates for A(H1N1)pdm09 were 84% and for influenza B viruses 70%. Increased VE estimates were obtained after stratification by underlying diseases and adjustment for the covariates sex and age, whereby the adjustment for the calendar week of infection was the covariate exerting the highest influence on adjusted VE estimates. Conclusion In summary, VE data obtained in this study underscore the importance to perform VE estimates in the context of detailed characterization of the contributing viruses and also demonstrate that the calendar week of influenza virus infection is the most important confounder of VE estimates. PMID:26975056

  1. Social capital and immunization against the 2009 A(H1N1) pandemic in the American States.

    PubMed

    Rönnerstrand, B

    2014-08-01

    The objective of this paper was to investigate the association between contextual social capital and immunization coverage rates. A cross-sectional, ecologic study design was used. Three different estimations of contextual social capital in American states have been used. Data on immunization coverage rates at state level comes from Centers for Disease Control and Prevention. Correlation coefficients were calculated to investigate the bivariate association between the independent variable social capital and the dependent variable 2009 A(H1N1) immunization coverage rates. A multivariate OLS regression model was used to investigate the association between contextual social capital and immunization, under control for state-level health care spending per capita, state population, population per square mile, and median age in the American States. Results show that Social capital was strongly correlated with 2009 A(H1N1) immunization acceptance among American States. In a multivariate regression analysis, the association remains strong and significant also when controlling state-level confounders. In conclusion, social capital, at least in a U.S. context, is shown to be associated with the state-level uptake of vaccination against the 2009 A(H1N1) pandemic.

  2. [Deployment of a mobile RT-PCR laboratory molecular biology to deal with the A(H1N1) challenge in Kaboul].

    PubMed

    Maslin, J; Ducher, P; Fourel, D; Causse Le Dorze, P

    2010-11-01

    Since October 2009, the fear of swine flu spread in Afghanistan and severe cases were observed among NATO soldiers. Two patients were hospitalized in an Intensive Care Unit. To face this new challenge, the French Health Service decided the deployment of a mobile RT-PCR laboratory molecular biology in the Kabul International Military Hospital. We describe the implementation of the mobile RT-PCR laboratory for the diagnosis of A(H1N1). The analysis of the first nasopharyngeal samples confirmed the presence of this virus in Afghanistan. The peak of positive cases was observed in mid-November 2009, and some cluster cases were observed among units deployed on the field.

  3. Single dose vaccination of the ASO3-adjuvanted A(H1N1)pdm09 monovalent vaccine in health care workers elicits homologous and cross-reactive cellular and humoral responses to H1N1 strains.

    PubMed

    Lartey, Sarah; Pathirana, Rishi D; Zhou, Fan; Jul-Larsen, Åsne; Montomoli, Emanuele; Wood, John; Cox, Rebecca Jane

    2015-01-01

    Healthcare workers (HCW) were prioritized for vaccination during the 2009 influenza A(H1N1)pdm09 pandemic. We conducted a clinical trial in October 2009 where 237 HCWs were immunized with a AS03-adjuvanted A(H1N1)pdm09 monovalent vaccine. In the current study, we analyzed the homologous and cross-reactive H1N1 humoral responses using prototype vaccine strains dating back to 1977 by the haemagglutinin inhibition (HI), single radial hemolysis SRH), antibody secreting cell (ASC) and memory B cell (MBC) assays. The cellular responses were assessed by interferon-γ (IFN-γ) ELISPOT and by intracellular staining (ICS) for the Th1 cytokines IFN-γ, interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). All assays were performed using blood samples obtained prior to (day 0) and 7, 14 and 21 d post-pandemic vaccination, except for ASC (day 7) and ICS (days 0 and 21). Vaccination elicited rapid HI, SRH and ASC responses against A(H1N1)pdm09 which cross reacted with seasonal H1N1 strains. MBC responses were detected against the homologous and seasonal H1N1 strains before vaccination and were boosted 2 weeks post-vaccination. An increase in cellular responses as determined by IFN-γ ELISPOT and ICS were observed 1-3 weeks after vaccination. Collectively, our data show that the AS03-adjuvanted A(H1N1)pdm09 vaccine induced rapid cellular and humoral responses against the vaccine strain and the response cross-reacted against prototype H1N1 strains dating back to 1977.

  4. Antiviral activity of acidic polysaccharides from Coccomyxa gloeobotrydiformi, a green alga, against an in vitro human influenza A virus infection.

    PubMed

    Komatsu, Takayuki; Kido, Nobuo; Sugiyama, Tsuyoshi; Yokochi, Takashi

    2013-02-01

    The extracts prepared from green algae are reported to possess a variety of biological activities including antioxidant, antitumor and antiviral activities. The acidic polysaccharide fraction from a green alga Coccomyxa gloeobotrydiformi (CmAPS) was isolated and the antiviral action on an in vitro infection of influenza A virus was examined. CmAPS inhibited the growth and yield of all influenza A virus strains tested, such as A/H1N1, A/H2N2, A/H3N2 and A/H1N1 pandemic strains. The 50% inhibitory concentration of CmAPS on the infection of human influenza A virus strains ranged from 26 to 70 µg/mL and the antiviral activity of CmAPS against influenza A/USSR90/77 (H1N1) was the strongest. The antiviral activity of CmAPS was not due to the cytotoxicity against host cells. The antiviral activity of CmAPS required its presence in the inoculation of virus onto MDCK cells. Pretreatment and post-treatment with CmAPS was ineffective for the antiviral activity. CmAPS inhibited influenza A virus-induced erythrocyte hemagglutination and hemolysis. Taken together, CmAPS was suggested to exhibit the anti-influenza virus activity through preventing the interaction of virus and host cells. The detailed antiviral activity of CmAPS is discussed.

  5. Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010

    PubMed Central

    Baggett, Henry C.; Chittaganpitch, Malinee; Thamthitiwat, Somsak; Prapasiri, Prabda; Naorat, Sathapana; Sawatwong, Pongpun; Ditsungnoen, Darunee; Olsen, Sonja J.; Simmerman, James M.; Srisaengchai, Prasong; Chantra, Somrak; Peruski, Leonard F.; Sawanpanyalert, Pathom; Maloney, Susan A.; Akarasewi, Pasakorn

    2012-01-01

    Background Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010. Methods We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. Results Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). Conclusions Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children. PMID:23139802

  6. Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice.

    PubMed

    Vollmer, Almut H; Gebre, Makda S; Barnard, Dale L

    2016-09-01

    Assessment of influenza virus disease progression and efficacy of antiviral therapy in the widely used mouse models relies mostly on body weight loss and lung virus titers as markers of disease. However, both parameters have their shortcomings. Therefore, the aim of our study was to find non-invasive markers in the murine model of severe influenza that could detect disease early and predict disease outcome. BALB/c mice were lethally infected with influenza A(H1N1)pdm09 virus and serum samples were collected at various time points. Enzyme-linked immunosorbent assays were performed to quantify amounts of serum amyloid A (SAA), C-reactive protein, complement 3, transferrin, corticosterone, prostaglandin E2, H2O2, and alpha-2,6-sialyltransferase. We found that SAA was the most promising candidate with levels acutely and temporarily elevated by several hundred-fold 3 days post virus inoculation. Upon treatment with oseltamivir phosphate, levels of SAA were significantly decreased. High levels of SAA were associated with poor disease prognosis, whereas body weight loss was not as a reliable predictor of disease outcome. SAA levels were also transiently increased in BALB/c mice infected with influenza A(H3N2) and influenza B virus, as well as in C57BL/2, Swiss-Webster, and DBA.2 mice infected with influenza A(H1N1)pdm09 virus. High levels of SAA often, but not always, were associated with disease outcome in these other influenza virus mouse models. Therefore, SAA represents a valid biomarker for influenza disease detection in all tested mouse strains but its prognostic value is limited to BALB/c mice infected with influenza A(H1N1)pdm09 virus. PMID:27523492

  7. The evolutionary dynamics of influenza A and B viruses in the tropical city of Managua, Nicaragua

    PubMed Central

    Nelson, Martha I.; Balmaseda, Angel; Kuan, Guillermina; Saborio, Saira; Lin, Xudong; Halpin, Rebecca A.; Stockwell, Timothy B.; Wentworth, David E.; Harris, Eva; Gordon, Aubree

    2014-01-01

    Despite mounting evidence of the high disease burden of influenza in tropical regions, relatively little viral sequence data is available from tropical countries in the Western hemisphere. To understand the evolutionary dynamics of influenza A and B viruses in Managua, Nicaragua, we performed a phylogenetic analysis of 1,956 influenza viruses, including 335 collected for this study during 2007–2010 from a population-based cohort in Managua. North America was consistently identified as the most significant source of influenza virus diversity in Managua, although South America and Mexico were important viral sources during the 2009 A/H1N1 pandemic. The low number of viral introductions of Central American origin may reflect differences in the seasonality of influenza in Nicaragua versus neighboring countries, and underscores the need for additional data in this understudied region. PMID:24959982

  8. [Genetic Diversity and Evolution of the M Gene of Human Influenza A Viruses from 2009 to 2013 in Hangzhou, China].

    PubMed

    Shao, Tiejuan; Li, Jun; Pu, Xiaoying; Yu, Xinfen; Kou, Yu; Zhou, Yinyan; Qian, Xin

    2015-03-01

    We investigated the genetic diversity and evolution of the M gene of human influenza A viruses in Hangzhou (Zhejiang province, China) from 2009 to 2013, including subtypes of A(H1N1) pdm09 strains and seasonal A(H3N2) strains. Subtypes of analyzed viruses were identified by cell culture and real-time reverse transcription-polymerase chain reaction, followed by cloning, sequencing and phylogenetic analyses of the M gene. Assessment of 5675 throat swabs revealed a positive rate for the influenza virus of 20.46%, and 827 cases were diagnosed as. infections due to influenza A viruses. Seventy-six influenza-A strains were selected randomly from nine stages during six phases of a virus epidemic. Sequences of the M gene showed high homology among six epidemics with identities of amino-acid sequences of 98.98-100%. All strains contained the adamantine-resistant mutation S31N in its M2 protein. Two of the A(H1N1)pdm09 strains had double mutants of V27A/S31N or V271/S31N. One of the seasonal A(H3N2) viruses had another form of double-mutant R45H/S31N. Evolutionary rate of the M gene was much lower than that of the HA gene and NA gene. Compared with A(H3N2) strains, higher positive pressure on the M1 and M2 proteins of A(H1N1) pdm09 viruses was observed. Separate analyses of M1 and M2 proteins revealed very different selection pressures. Knowledge of the genetic diversity and evolution of the M gene of human influenza-A viruses will be valuable for the control and prevention of diseases.

  9. New Small Molecule Entry Inhibitors Targeting Hemagglutinin-Mediated Influenza A Virus Fusion

    PubMed Central

    Antanasijevic, Aleksandar; Wang, Minxiu; Li, Bing; Mills, Debra M.; Ames, Jessica A.; Nash, Peter J.; Williams, John D.; Peet, Norton P.; Moir, Donald T.; Prichard, Mark N.; Keith, Kathy A.; Barnard, Dale L.; Caffrey, Michael; Rong, Lijun; Bowlin, Terry L.

    2014-01-01

    Influenza viruses are a major public health threat worldwide, and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. Using pseudotype virus-based high-throughput screens, we have identified several new small molecules capable of inhibiting influenza virus entry. We prioritized two novel inhibitors, MBX2329 and MBX2546, with aminoalkyl phenol ether and sulfonamide scaffolds, respectively, that specifically inhibit HA-mediated viral entry. The two compounds (i) are potent (50% inhibitory concentration [IC50] of 0.3 to 5.9 μM); (ii) are selective (50% cytotoxicity concentration [CC50] of >100 μM), with selectivity index (SI) values of >20 to 200 for different influenza virus strains; (iii) inhibit a wide spectrum of influenza A viruses, which includes the 2009 pandemic influenza virus A/H1N1/2009, highly pathogenic avian influenza (HPAI) virus A/H5N1, and oseltamivir-resistant A/H1N1 strains; (iv) exhibit large volumes of synergy with oseltamivir (36 and 331 μM2 % at 95% confidence); and (v) have chemically tractable structures. Mechanism-of-action studies suggest that both MBX2329 and MBX2546 bind to HA in a nonoverlapping manner. Additional results from HA-mediated hemolysis of chicken red blood cells (cRBCs), competition assays with monoclonal antibody (MAb) C179, and mutational analysis suggest that the compounds bind in the stem region of the HA trimer and inhibit HA-mediated fusion. Therefore, MBX2329 and MBX2546 represent new starting points for chemical optimization and have the potential to provide valuable future therapeutic options and research tools to study the HA-mediated entry process. PMID:24198411

  10. Global transmission of influenza viruses from humans to swine

    PubMed Central

    Gramer, Marie R.; Vincent, Amy L.; Holmes, Edward C.

    2012-01-01

    To determine the extent to which influenza viruses jump between human and swine hosts, we undertook a large-scale phylogenetic analysis of pandemic A/H1N1/09 (H1N1pdm09) influenza virus genome sequence data. From this, we identified at least 49 human-to-swine transmission events that occurred globally during 2009–2011, thereby highlighting the ability of the H1N1pdm09 virus to transmit repeatedly from humans to swine, even following adaptive evolution in humans. Similarly, we identified at least 23 separate introductions of human seasonal (non-pandemic) H1 and H3 influenza viruses into swine globally since 1990. Overall, these results reveal the frequency with which swine are exposed to human influenza viruses, indicate that humans make a substantial contribution to the genetic diversity of influenza viruses in swine, and emphasize the need to improve biosecurity measures at the human–swine interface, including influenza vaccination of swine workers. PMID:22791604

  11. In Vitro Characterization of A-315675, a Highly Potent Inhibitor of A and B Strain Influenza Virus Neuraminidases and Influenza Virus Replication

    PubMed Central

    Kati, Warren M.; Montgomery, Debra; Carrick, Robert; Gubareva, Larisa; Maring, Clarence; McDaniel, Keith; Steffy, Kevin; Molla, Akhteruzzaman; Hayden, Frederick; Kempf, Dale; Kohlbrenner, William

    2002-01-01

    A-315675 is a novel, pyrrolidine-based compound that was evaluated in this study for its ability to inhibit A and B strain influenza virus neuraminidases in enzyme assays and influenza virus replication in cell culture. A-315675 effectively inhibited influenza A N1, N2, and N9 and B strain neuraminidases with inhibitor constant (Ki) values between 0.024 and 0.31 nM. These values were comparable to or lower than the Ki values measured for oseltamivir carboxylate (GS4071), zanamivir, and BCX-1812, except for the N1 enzymes that were found to be the most sensitive to BCX-1812. The time-dependent inhibition of neuraminidase catalytic activity observed with A-315675 is likely due to its very low rate of dissociation from the active site of neuraminidase. The half times for dissociation of A-315675 from B/Memphis/3/89 and A/Tokyo/3/67 (H3N2) influenza virus neuraminidases of 10 to 12 h are significantly slower than the half times measured for oseltamivir carboxylate (33 to 60 min). A-315675 inhibited the replication of several laboratory strains of influenza virus in cell culture with potencies that were comparable or superior to those for oseltamivir carboxylate and BCX-1812, except for the A/H1N1 viruses that were found to be two- to fourfold more susceptible to BCX-1812. A-315675 and oseltamivir carboxylate exhibited comparable potencies against a panel of A/H1N1 and A/H3N2 influenza virus clinical isolates, but A-315675 was found to be significantly more potent than oseltamivir carboxylate against the B strain isolates. The favorable in vitro results relative to other clinically effective agents provide strong support for the further investigation of A-315675 as a potential therapy for influenza virus infections. PMID:11897583

  12. A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

    PubMed

    Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

    2014-01-01

    During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens. PMID:24480060

  13. A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

    PubMed

    Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

    2014-01-23

    During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens.

  14. Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

    PubMed

    Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

    2013-04-01

    The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

  15. [Internal epidemic influenza virus proteins: isolation and investigation].

    PubMed

    Ivanova, V T; Rakutina, R O; Kordiukova, L V; Manykin, A A; Fedorova, N V; Ksenofontov, A L; Slepushkin, A N

    2006-01-01

    The internal influenza virus proteins M1 and RNP free from surface protein impurities were isolated from subviral particles (virions free from HA and NA ectomenes). The spikeless particles had no propensity to aggregate in the solution at pH 5.0 as compared with native viruses. The subviral particles of B/Hong Kong/330/01 influenza virus, which belonged to B/Victoria/2/87-lineage, were obtained by proteolytic treatment with the enzyme bromelain under the same conditions as in cases of influenza B viruses of B/Jamagata/16/88 lineage. A chromatographic analysis of the tryptic hydrolyzates obtained for matrix (M1) proteins of A(H1N1) and A(H3N2) influenza viruses revealed differences that were greatest between the protein M1 molecules isolated from influenza viruses of different subtypes of hemagglutinine. These findings suggest there are variations in the structure of this conservative internal viral protein M1 during evolution.

  16. A(H1N1) vaccination recruits T lymphocytes to the choroid plexus for the promotion of hippocampal neurogenesis and working memory in pregnant mice.

    PubMed

    Qi, Fangfang; Yang, Junhua; Xia, Yucen; Yuan, Qunfang; Guo, Kaihua; Zou, Juntao; Yao, Zhibin

    2016-03-01

    We previously demonstrated that A(H1N1) influenza vaccine (AIV) promoted hippocampal neurogenesis and working memory in pregnant mice. However, the underlying mechanism of flu vaccination in neurogenesis and memory has remained unclear. In this study, we found that T lymphocytes were recruited from the periphery to the choroid plexus (CP) of the lateral and third (3rd) ventricles in pregnant mice vaccinated with AIV (Pre+AIV). Intracerebroventricular delivery of anti-TCR antibodies markedly decreased neurogenesis and the working memory of the Pre+AIV mice. Similarly, intravenous delivery of anti-CD4 antibodies to the periphery also down-regulated neurogenesis. Furthermore, AIV vaccination caused microglia to skew toward an M2-like phenotype (increased Arginase-1 and Ym1 mRNA levels), and elevated levels of brain-derived growth factor (BDNF) and insulin-like growth factor-1 (IGF-1) were found in the hippocampus, whereas these effects were offset by anti-TCR antibody treatment. Additionally, in the CP, the expression level of adhesion molecules and chemokines, which assist leukocytes in permeating into the brain, were also elevated after AIV vaccination of pregnant mice. Collectively, the results suggested that the infiltrative T lymphocytes in the CP contribute to the increase in hippocampal neurogenesis and working memory caused by flu vaccination, involving activation of the brain's CP, M2 microglial polarization and neurotrophic factor expression.

  17. Effect of Statin Use on Influenza Vaccine Effectiveness

    PubMed Central

    McLean, Huong Q.; Chow, Brian D. W.; VanWormer, Jeffrey J.; King, Jennifer P.; Belongia, Edward A.

    2016-01-01

    Background. Recent studies suggest that statin use may reduce influenza vaccine effectiveness (VE), but laboratory-confirmed influenza was not assessed. Methods. Patients ≥45 years old presenting with acute respiratory illness were prospectively enrolled during the 2004–2005 through 2014–2015 influenza seasons. Vaccination and statin use were extracted from electronic records. Respiratory samples were tested for influenza virus. Results. The analysis included 3285 adults: 1217 statin nonusers (37%), 903 unvaccinated statin nonusers (27%), 847 vaccinated statin users (26%), and 318 unvaccinated statin users (10%). Statin use modified VE and the risk of influenza A(H3N2) virus infection (P = .002) but not 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) or influenza B virus infection (P = .2 and .4, respectively). VE against influenza A(H3N2) was 45% (95% confidence interval [CI], 27%–59%) among statin nonusers and −21% (95% CI, −84% to 20%) among statin users. Vaccinated statin users had significant protection against influenza A(H1N1)pdm09 (VE, 68%; 95% CI, 19%–87%) and influenza B (VE, 48%; 95% CI, 1%–73%). Statin use did not significantly modify VE when stratified by prior season vaccination. In validation analyses, the use of other cardiovascular medications did not modify influenza VE. Conclusions. Statin use was associated with reduced VE against influenza A(H3N2) but not influenza A(H1N1)pdm09 or influenza B. Further research is needed to assess biologic plausibility and confirm these results. PMID:27471318

  18. Isolation and phylogenetic analysis of avian-origin European H1N1 swine influenza viruses in Jiangsu, China.

    PubMed

    Zhao, Guo; Pan, Jinjin; Gu, Xiaobing; Lu, Xinlun; Li, Qunhui; Zhu, Jie; Chen, Chaoyang; Duan, Zhiqiang; Xu, Quangang; Wang, Xiaobo; Hu, Shunlin; Liu, Wenbo; Peng, Daxin; Liu, Xiaowen; Wang, Xiaoquan; Liu, Xiufan

    2012-04-01

    Isolates of the A(H1N1)pdm2009 virus were first identified in asymptomatic swine in Jiangsu province, China in January 2010, indicating that the virus has retro-infected swine after circulating through humans in mainland China. The purpose of this study was to determine whether the avian-origin European H1N1 swine influenza virus (SIV) and the A(H1N1)pdm2009 virus are cocirculating in swine in Jiangsu province of China. From May 2010 to May 2011, 1,030 nasal swab samples were collected from healthy swine in Jiangsu province of China and were tested for influenza A H1N1 using reverse transcription-PCR. Fragments of the complete genomes of viruses from the samples that were positive for influenza A H1N1 were sequenced and analysed. A total of 32 avian-origin European H1N1 SIVs were isolated, and no A(H1N1)pdm2009 viruses were identified; full-length genomes of 18 strains were sequenced. The eight gene segments of some of the isolated H1N1 viruses have 99.1-99.8% sequence identity with the human A/Jiangsu/ALS1/2011(H1N1) isolates in the same region. Our study indicates that the avian-origin European H1N1 SIVs remain endemic in swine and have retro-infected humans after circulating through swine, which may present a risk factor for public health.

  19. Determinants of Refusal of A/H1N1 Pandemic Vaccination in a High Risk Population: A Qualitative Approach

    PubMed Central

    d'Alessandro, Eugenie; Hubert, Dominique; Launay, Odile; Bassinet, Laurence; Lortholary, Olivier; Jaffre, Yannick; Sermet-Gaudelus, Isabelle

    2012-01-01

    Background Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine. Methodology/Principal Findings We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated. The two groups differed quite substantially in their perceptions of vaccine- and disease-related risks. Those who refused the vaccine were motivated mainly by the fears it aroused and did not explicitly consider the 2009 A/H1N1 flu a potentially severe disease. People who were vaccinated explained their choice, first and foremost, as intended to prevent the flu's potential consequences on respiratory cystic fibrosis disease. Moreover, they considered vaccination to be an indirect collective prevention tool. Patients who refused the vaccine mentioned multiple, contradictory information sources and did not appear to consider the recommendation of their local health care provider as predominant. On the contrary, those who were vaccinated stated that they had based their decision solely on the clear and unequivocal advice of their health care provider. Conclusions/Significance These results of our survey led us to formulate three main recommendations for improving adhesion to new pandemic vaccines. (1) it appears necessary to reinforce patient education about the disease and its specific risks, but also general population information about community immunity. (2) it is essential to disseminate a clear and effective message about the safety of novel vaccines. (3) this message should be conveyed by local health care providers, who should be involved in implementing immunization. PMID:22506011

  20. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013.

    PubMed

    Meijer, Adam; Rebelo-de-Andrade, Helena; Correia, Vanessa; Besselaar, Terry; Drager-Dayal, Renu; Fry, Alicia; Gregory, Vicky; Gubareva, Larisa; Kageyama, Tsutomu; Lackenby, Angie; Lo, Janice; Odagiri, Takato; Pereyaslov, Dmitriy; Siqueira, Marilda M; Takashita, Emi; Tashiro, Masato; Wang, Dayan; Wong, Sun; Zhang, Wenqing; Daniels, Rod S; Hurt, Aeron C

    2014-10-01

    Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) is sporadic, often follows exposure to NAIs, but occasionally occurs in the absence of NAI pressure. The emergence and global spread in 2007/2008 of A(H1N1) influenza viruses showing clinical resistance to oseltamivir due to neuraminidase (NA) H275Y substitution, in the absence of drug pressure, warrants continued vigilance and monitoring for similar viruses. Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) tested 11,387 viruses collected by WHO-recognized National Influenza Centres (NIC) between May 2012 and May 2013 to determine 50% inhibitory concentration (IC50) data for oseltamivir, zanamivir, peramivir and laninamivir. The data were evaluated using normalized IC50 fold-changes rather than raw IC50 data. Nearly 90% of the 11,387 viruses were from three WHO regions: Western Pacific, the Americas and Europe. Only 0.2% (n=27) showed highly reduced inhibition (HRI) against at least one of the four NAIs, usually oseltamivir, while 0.3% (n=39) showed reduced inhibition (RI). NA sequence data, available from the WHO CCs and from sequence databases (n=3661), were screened for amino acid substitutions associated with reduced NAI susceptibility. Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=18), A(H3N2) with NA E119V (n=3) or NA R292K (n=1) and B/Victoria-lineage with NA H273Y (n=2); amino acid position numbering is A subtype and B type specific. Overall, approximately 99% of circulating viruses tested during the 2012-2013 period were sensitive to all four NAIs. Consequently, these drugs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections.

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

    PubMed Central

    Bodewes, Rogier; Osterhaus, Albert D.M.E; Rimmelzwaan, Guus F.

    2010-01-01

    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. PMID:21994606

  2. [Pandemic influenza 2009 in Russia. Characteristics of the isolation and biological properties of viruses].

    PubMed

    Danilenko, D M; Konovalova, N I; Eropkin, M Yu; Gudkova, T M; Grigoryeva, V A; Ivanova, A V; Shchekanova, S M; Smirnova, T D; Kiselev, O I

    2011-01-01

    Research Institute of Influenza, Ministry of Health and Social Development of Russia, Saint Petersburg The characteristics of the isolation of pandemic influenza A(H1N1)v viruses were studied on chick embryos (CE) and MDCK cell culture. The materials (nasal swabs and autopsies) were collected in different regions Russia in the period from 20 July to 30 December 2009. The paper gives the data of the antigenic analysis of isolates, their capacity to multiply in different species-specific and tissue cell cultures. The viruses isolated on CE were shown to have higher hemagglutination titers and to be more stable. Isolation from the autopsies was effective only on CE. All the test cell lines other than MDCK were insensitive to the isolated pandemic influenza strains. The antigenic analysis showed no significant antigenic drift of the viruses isolated during the first wave of the pandemic in the Russian Federation.

  3. Bioluminescence-based neuraminidase inhibition assay for monitoring influenza virus drug susceptibility in clinical specimens.

    PubMed

    Marjuki, Henju; Mishin, Vasiliy P; Sleeman, Katrina; Okomo-Adhiambo, Margaret; Sheu, Tiffany G; Guo, Lizheng; Xu, Xiyan; Gubareva, Larisa V

    2013-11-01

    The QFlu prototype bioluminescence-based neuraminidase (NA) inhibition (NI) assay kit was designed to detect NA inhibitor (NAI)-resistant influenza viruses at point of care. Here, we evaluated its suitability for drug susceptibility assessment at a surveillance laboratory. A comprehensive panel of reference viruses (n = 14) and a set of 90 seasonal influenza virus A and B isolates were included for testing with oseltamivir and/or zanamivir in the QFlu assay using the manufacturer-recommended protocol and a modified version attuned to surveillance requirements. The 50% inhibitory concentrations (IC50s) generated were compared with those of NI assays currently used for monitoring influenza drug susceptibility, the fluorescent (FL) and chemiluminescent (CL) assays. To provide proof of principle, clinical specimens (n = 235) confirmed by real-time reverse transcription (RT)-PCR to contain influenza virus A(H1N1)pdm09 and prescreened for the oseltamivir resistance marker H275Y using pyrosequencing were subsequently tested in the QFlu assay. All three NI assays were able to discriminate the reference NA variants and their matching wild-type viruses based on the difference in their IC50s. Unless the antigenic types were first identified, certain NA variants (e.g., H3N2 with E119V) could be detected among seasonal viruses using the FL assays only. Notably, the QFlu assay identified oseltamivir-resistant A(H1N1)pdm09 viruses carrying the H275Y marker directly in clinical specimens, which is not feasible with the other two phenotypic assays, which required prior virus culturing in cells. Furthermore, The QFlu assay allows detection of the influenza virus A and B isolates carrying established and potential NA inhibitor resistance markers and may become a useful tool for monitoring drug resistance in clinical specimens. PMID:23917311

  4. An Evaluation of Community Assessment Tools (CATs) in Predicting Use of Clinical Interventions and Severe Outcomes during the A(H1N1)pdm09 Pandemic

    PubMed Central

    Nicholson, Karl G.; Lim, Wei Shen; Read, Robert C.; Taylor, Bruce L.; Brett, Stephen J.; Openshaw, Peter J. M.; Enstone, Joanne E.; McMenamin, James; Bannister, Barbara; Nguyen-Van-Tam, Jonathan S.

    2013-01-01

    During severe influenza pandemics healthcare demand can exceed clinical capacity to provide normal standards of care. Community Assessment Tools (CATs) could provide a framework for triage decisions for hospital referral and admission. CATs have been developed based on evidence that supports the recognition of severe influenza and pneumonia in the community (including resource limited settings) for adults, children and infants, and serious feverish illness in children. CATs use six objective criteria and one subjective criterion, any one or more of which should prompt urgent referral and admission to hospital. A retrospective evaluation of the ability of CATs to predict use of hospital-based interventions and patient outcomes in a pandemic was made using the first recorded routine clinical assessment on or shortly after admission from 1520 unselected patients (800 female, 480 children <16 years) admitted with PCR confirmed A(H1N1)pdm09 infection (the FLU-CIN cohort). Outcome measures included: any use of supplemental oxygen; mechanical ventilation; intravenous antibiotics; length of stay; intensive or high dependency care; death; and “severe outcome” (combined: use of intensive or high dependency care or death during admission). Unadjusted and multivariable analyses were conducted for children (age <16 years) and adults. Each CATs criterion independently identified both use of clinical interventions that would in normal circumstances only be provided in hospital and patient outcome measures. “Peripheral oxygen saturation ≤92% breathing air, or being on oxygen” performed well in predicting use of resources and outcomes for both adults and children; supporting routine measurement of peripheral oxygen saturation when assessing severity of disease. In multivariable analyses the single subjective criterion in CATs “other cause for clinical concern” independently predicted death in children and in adults predicted length of stay, mechanical ventilation and

  5. Campus quarantine (Fengxiao) for curbing emergent infectious diseases: lessons from mitigating A/H1N1 in Xi'an, China.

    PubMed

    Tang, Sanyi; Xiao, Yanni; Yuan, Lin; Cheke, Robert A; Wu, Jianhong

    2012-02-21

    During the 2009 A/H1N1 influenza pandemic, very strict interventions including campus quarantine (Fengxiao) (restrictions on the movements of university personnel) were taken in mainland China to slow down the initial spread of the disease from the university network to a wider community. The decision for implementation and/or relaxation of Fengxiao depends on the assessment of the level of infection within the university network compared with that in the wider community and on the degree of interruption of normal academic activities and the associated social/economic costs. However, the most important consideration influencing the decision is whether the initiation and termination of Fengxiao can alter the pattern of disease spread in the entire community for effective prevention and control of the emerging disease. Here we formulate and analyze a dynamic model to evaluate the effectiveness of Fengxiao as a social distance measure for curbing the outbreak in major cities of China. Using data from the initial laboratory-confirmed cases admitted to the 8th Hospital of Xi'an (the capital city of the Shaanxi Province), we estimated the reproduction number for the period under consideration in the range 1.273-1.784 and concluded that the population's mobility, combined with the suspension of the Fengxiao strategy, was a key factor contributing to a subsequent epidemic wave. Fengxiao in China is a reversal of the usual strategy of school closures adopted in many other countries, but the lessons learnt from it may be useful for disease management in other countries where restrictions on the movements across a facility boundary and close monitoring of the infection within the facility are feasible in the long term. PMID:22079943

  6. Beliefs and knowledge about vaccination against AH1N1pdm09 infection and uptake factors among Chinese parents.

    PubMed

    Wu, Cynthia Sau Ting; Kwong, Enid Wai Yung; Wong, Ho Ting; Lo, Suet Hang; Wong, Anthony Siu Wo

    2014-02-01

    Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R2 of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children.

  7. Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico

    PubMed Central

    Comas‐García, Andreu; García‐Sepúlveda, Christian A.; Méndez‐de Lira, José J.; Aranda‐Romo, Saray; Hernández‐Salinas, Alba E.; Noyola, Daniel E.

    2010-01-01

    Please cite this paper as: Comas‐García et al. (2011) Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico. Influenza and Other Respiratory Viruses 5(2), 76–82. Background  Acute respiratory infections are a leading cause of morbidity and mortality worldwide. Starting in 2009, pandemic influenza A(H1N1) 2009 virus has become one of the leading respiratory pathogens worldwide. However, the overall impact of this virus as a cause of mortality has not been clearly defined. Objectives  To determine the impact of pandemic influenza A(H1N1) 2009 on mortality in a Mexican population. Methods  We assessed the impact of pandemic influenza virus on mortality during the first and second outbreaks in San Luis Potosí, Mexico, and compared it to mortality associated with seasonal influenza and respiratory syncytial virus (RSV) during the previous winter seasons. Results  We estimated that, on average, 8·1% of all deaths that occurred during the 2003–2009 seasons were attributable to influenza and RSV. During the first pandemic influenza A(H1N1) 2009 outbreak, there was an increase in mortality in persons 5–59 years of age, but not during the second outbreak (Fall of 2009). Overall, pandemic influenza A (H1N1) 2009 outbreaks had similar effects on mortality to those associated with seasonal influenza virus epidemics. Conclusions  The impact of influenza A(H1N1) 2009 virus on mortality during the first year of the pandemic was similar to that observed for seasonal influenza. The establishment of real‐time surveillance systems capable of integrating virological, morbidity, and mortality data may result in the timely identification of outbreaks so as to allow for the institution of appropriate control measures to reduce the impact of emerging pathogens on the population. PMID:21306570

  8. Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

    PubMed Central

    Watson, Simon J.; Langat, Pinky; Reid, Scott M.; Lam, Tommy Tsan-Yuk; Cotten, Matthew; Kelly, Michael; Van Reeth, Kristien; Qiu, Yu; Simon, Gaëlle; Bonin, Emilie; Foni, Emanuela; Chiapponi, Chiara; Larsen, Lars; Hjulsager, Charlotte; Markowska-Daniel, Iwona; Urbaniak, Kinga; Dürrwald, Ralf; Schlegel, Michael; Huovilainen, Anita; Davidson, Irit; Dán, Ádám; Loeffen, Willie; Edwards, Stephanie; Bublot, Michel; Vila, Thais; Maldonado, Jaime; Valls, Laura; Brown, Ian H.; Pybus, Oliver G.

    2015-01-01

    ABSTRACT The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like (“avian-like”) genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level. IMPORTANCE The influenza A(H1N1)pdm09 virus contains a reassortant genome with segments derived from separate virus lineages that evolved in different regions of the world. In particular, its neuraminidase and matrix segments were derived from the Eurasian avian virus-like (“avian-like”) lineage that emerged in European swine in the 1970s. However, while large-scale genomic characterization of swine has been reported for southern

  9. [Influenza virus].

    PubMed

    Juozapaitis, Mindaugas; Antoniukas, Linas

    2007-01-01

    Every year, especially during the cold season, many people catch an acute respiratory disease, namely flu. It is easy to catch this disease; therefore, it spreads very rapidly and often becomes an epidemic or a global pandemic. Airway inflammation and other body ailments, which form in a very short period, torment the patient several weeks. After that, the symptoms of the disease usually disappear as quickly as they emerged. The great epidemics of flu have rather unique characteristics; therefore, it is possible to identify descriptions of such epidemics in historic sources. Already in the 4th century bc, Hippocrates himself wrote about one of them. It is known now that flu epidemics emerge rather frequently, but there are no regular intervals between those events. The epidemics can differ in their consequences, but usually they cause an increased mortality of elderly people. The great flu epidemics of the last century took millions of human lives. In 1918-19, during "The Spanish" pandemic of flu, there were around 40-50 millions of deaths all over the world; "Pandemic of Asia" in 1957 took up to one million lives, etc. Influenza virus can cause various disorders of the respiratory system: from mild inflammations of upper airways to acute pneumonia that finally results in the patient's death. Scientist Richard E. Shope, who investigated swine flu in 1920, had a suspicion that the cause of this disease might be a virus. Already in 1933, scientists from the National Institute for Medical Research in London - Wilson Smith, Sir Christopher Andrewes, and Sir Patrick Laidlaw - for the first time isolated the virus, which caused human flu. Then scientific community started the exhaustive research of influenza virus, and the great interest in this virus and its unique features is still active even today.

  10. A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade

    PubMed Central

    Oh, Ding Yuan; Hurt, Aeron C.

    2014-01-01

    Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013), the adamantanes and the neuraminidase inhibitors (NAIs). During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1) viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future. PMID:24800107

  11. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013-2014.

    PubMed

    Takashita, Emi; Meijer, Adam; Lackenby, Angie; Gubareva, Larisa; Rebelo-de-Andrade, Helena; Besselaar, Terry; Fry, Alicia; Gregory, Vicky; Leang, Sook-Kwan; Huang, Weijuan; Lo, Janice; Pereyaslov, Dmitriy; Siqueira, Marilda M; Wang, Dayan; Mak, Gannon C; Zhang, Wenqing; Daniels, Rod S; Hurt, Aeron C; Tashiro, Masato

    2015-05-01

    Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) tested 10,641 viruses collected by WHO-recognized National Influenza Centres between May 2013 and May 2014 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. In addition, neuraminidase (NA) sequence data, available from the WHO CCs and from sequence databases (n=3206), were screened for amino acid substitutions associated with reduced NAI susceptibility. Ninety-five per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 2% (n=172) showed highly reduced inhibition (HRI) against at least one of the four NAIs, commonly oseltamivir, while 0.3% (n=32) showed reduced inhibition (RI). Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=169), A(H3N2) with NA E119V (n=1), B/Victoria-lineage with NA E117G (n=1) and B/Yamagata-lineage with NA H273Y (n=1); amino acid position numbering is A subtype and B type specific. Although approximately 98% of circulating viruses tested during the 2013-2014 period were sensitive to all four NAIs, a large community cluster of A(H1N1)pdm09 viruses with the NA H275Y substitution from patients with no previous exposure to antivirals was detected in Hokkaido, Japan. Significant numbers of A(H1N1)pdm09 NA H275Y viruses were also detected in China and the United States: phylogenetic analyses showed that the Chinese viruses were similar to those from Japan, while the United States viruses clustered separately from those of the Hokkaido outbreak, indicative of multiple resistance-emergence events. Consequently, global surveillance of influenza antiviral susceptibility should be continued from a public health perspective.

  12. Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance

    PubMed Central

    McKimm‐Breschkin, Jennifer L.

    2012-01-01

    Please cite this paper as: McKimm‐Breschkin (2012) Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 25–36. There are two major classes of antivirals available for the treatment and prevention of influenza, the M2 inhibitors and the neuraminidase inhibitors (NAIs). The M2 inhibitors are cheap, but they are only effective against influenza A viruses, and resistance arises rapidly. The current influenza A H3N2 and pandemic A(H1N1)pdm09 viruses are already resistant to the M2 inhibitors as are many H5N1 viruses. There are four NAIs licensed in some parts of the world, zanamivir, oseltamivir, peramivir, and a long‐acting NAI, laninamivir. This review focuses on resistance to the NAIs. Because of differences in their chemistry and subtle differences in NA structures, resistance can be both NAI‐ and subtype specific. This results in different drug resistance profiles, for example, the H274Y mutation confers resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 NAs. Mutations at E119, D198, I222, R292, and N294 can also reduce NAI sensitivity. In the winter of 2007–2008, an oseltamivir‐resistant seasonal influenza A(H1N1) strain with an H274Y mutation emerged in the northern hemisphere and spread rapidly around the world. In contrast to earlier evidence of such resistant viruses being unfit, this mutant virus remained fully transmissible and pathogenic and became the major seasonal A(H1N1) virus globally within a year. This resistant A(H1N1) virus was displaced by the sensitive A(H1N1)pdm09 virus. Approximately 0·5–1·0% of community A(H1N1)pdm09 isolates are currently resistant to oseltamivir. It is now apparent that variation in non‐active site amino acids can affect the fitness of the enzyme and compensate for mutations that confer high‐level oseltamivir resistance resulting in minimal impact on enzyme function. PMID:23279894

  13. In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011-2012 season in Japan.

    PubMed

    Ikematsu, Hideyuki; Kawai, Naoki; Iwaki, Norio; Kashiwagi, Seizaburo

    2014-02-01

    The neuraminidase inhibitors oseltamivir phosphate (Tamiflu®), zanamivir (Relenza®), laninamivir octanoate (Inavir®), and peramivir (Rapiacta®) have been available for the treatment of influenza in Japan since 2010. To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC₅₀) of each drug for influenza virus isolates from the 2011-2012 influenza season. Specimens were obtained from patients prior to treatment. Viral isolation was done using Madine-Darby canine kidney cells, and the type and subtype of influenza A(H1N1)pdm09, A(H3N2), or influenza B were determined by RT-PCR using type- and subtype-specific primers. The IC₅₀ was determined by a neuraminidase inhibition assay using a fluorescent substrate. The lineage of influenza B virus was determined by direct sequencing of the hemagglutinin gene. Influenza A(H3N2) and influenza B viruses were isolated in 283 and 42 patients, respectively, while no influenza A(H1N1)pdm09 virus was isolated. No isolate showed an IC₅₀ value exceeding 50 nM for any of the neuraminidase inhibitors. IC50 values for A(H3N2) were similar between the 2010-2011 and 2011-2012 seasons. In contrast, the IC₅₀ values for influenza B viruses in the 2011-2012 season to the four drugs were significantly lower than those found in the 2010-2011 season. These results indicate that the currently epidemic influenza viruses are susceptible to all four neuraminidase inhibitors, with no trend for IC₅₀ values to increase in Japan at present.

  14. Adverse events with the influenza A(H1N1) vaccine Pandemrix® at healthcare professionals in Portugal.

    PubMed

    Marques, Joana Isabel; Ribeiro Vaz, Inês; Santos, Cristina; Polónia, Jorge

    2013-01-01

    Introdução: Os profissionais de saúde foram um grupo prioritário para vacinação contra a pandemia da Gripe A (H1N1), Pandemrix®. Assim, monitorizar os eventos adversos relacionados com esta vacina neste grupo específico poderá originar informação valiosa relacionada com o perfil de segurança da vacina. O nosso objetivo foi identificar os eventos adversos após imunização com a vacina Pandemrix® em profissionais de saúde. Material e Métodos: Foi desenhado um questionário de monitorização dos eventos adversos ocorridos com a vacina Pandemrix®. O questionário foi distribuído aos profissionais de saúde a trabalhar em três centros hospitalares da região norte do País, vacinados no período de 26 de Outubro de 2009 a 31 de janeiro de 2009. Resultados: Dos 2358 profissionais de saúde que aceitaram participar no estudo, 864 (37%) devolveram o questionário preenchido. Destes, 73% experienciaram pelo menos um evento adverso após imunização, mas só 8% experienciaram um evento inesperado. Os eventos adversos mais frequentemente reportados foram os esperados e muito comuns: reações locais no local de administração (57%), mialgia (31%), fadiga (incluindo astenia) (24%) e dor de cabeça (19%). Não foram reportados casos de eventos de maior gravidade para a saúde, tais como morte ou risco de vida. O género feminino e a existência de doença de base foram fatores de risco independentes para o desenvolvimento de pelo menos um evento adverso após imunização com a Pandemrix®. Conclusões: O nosso trabalho sugere um perfil de segurança aceitável da vacina pandémica Pandermix® em profissionais de saúde. Tanto a frequência como a severidade dos eventos adversos não se verificaram superiores ao esperado.

  15. Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain.

    PubMed

    Antón, A; Marcos, M A; Torner, N; Isanta, R; Camps, M; Martínez, A; Domínguez, A; Jané, M; Jiménez de Anta, M T; Pumarola, T

    2016-06-01

    Most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (RV) is not widely considered. The aim of the present study is to describe the circulation of RV in the general population during six consecutive seasons from 2006 to 2012 in Catalonia, Spain. Cell culture, immunofluorescence and PCR-based assays were used for the RV laboratory-confirmation and influenza subtyping. Phylogenetic and molecular characterizations of viral haemagglutinin, partial neuraminidase and matrix 2 proteins were performed from a representative sampling of influenza viruses. A total of 6315 nasopharyngeal samples were collected, of which 64% were laboratory-confirmed, mainly as influenza A viruses and rhinoviruses. Results show the significant burden of viral aetiological agents in acute respiratory infection, particularly in the youngest cases. The study of influenza strains reveals their continuous evolution through either progressive mutations or by segment reassortments. Moreover, the predominant influenza B lineage was different from that included in the recommended vaccine in half of the studied seasons, supporting the formulation and use of a quadrivalent influenza vaccine. Regarding neuraminidase inhibitors resistance, with the exception of the 2007/08 H275Y seasonal A(H1N1) strains, no other circulating influenza strains carrying known resistance genetic markers were found. Moreover, all circulating A(H1N1)pdm09 and A(H3N2) strains finally became genetically resistant to adamantanes. A wide knowledge of the seasonality patterns of the RV in the general population is well-appreciated, but it is a challenge due to the unpredictable circulation of RV, highlighting the value of local and global RV surveillance. PMID:26939538

  16. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    PubMed

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614

  17. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012

    PubMed Central

    Grgić, Helena; Costa, Marcio; Friendship, Robert M.; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614

  18. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    PubMed

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  19. Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus

    PubMed Central

    Martínez-Baz, Iván; Navascués, Ana; Pozo, Francisco; Chamorro, Judith; Albeniz, Esther; Casado, Itziar; Reina, Gabriel; Cenoz, Manuel García; Ezpeleta, Carmen; Castilla, Jesús

    2015-01-01

    Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratory-confirmed influenza B cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. We have evaluated the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season, which was dominated by a vaccine-matched influenza B virus. In the population covered by the Navarra Health Service, all hospitalized patients with influenza-like illness (ILI) and all ILI patients attended by a sentinel network of general practitioners were swabbed for influenza testing, and all were included in a test-negative case-control analysis. VE was calculated as (1-odds ratio)×100. Among 744 patients tested, 382 (51%) were positive for influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2). The overall estimate of VE in preventing laboratory-confirmed influenza was 63% (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74% (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza B and 43% (−45 to 78) against influenza A. The VE against virus B was 87% (52 to 96) in hospitalized patients and 56% in outpatients (−5 to 81). Adjusted comparison of vaccination status between inpatient and outpatient cases with influenza B did not show statistically significant differences (odds ratio: 1.13; p = 0.878). These results suggest a high protective effect of the vaccine in the 2012–2013 season, with no differences found for the effect between outpatient and hospitalized cases. PMID:25996366

  20. Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland.

    PubMed

    Bednarska, K; Hallmann-Szelińska, E; Kondratiuk, K; Brydak, L B

    2016-01-01

    Morbidity rates of influenza could be greatly reduced due to vaccination. However, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. Their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. In Poland, the 2014/2015 influenza epidemic started in week 5 (January/February) of 2015 and continued until week 17 (April) of 2015. The influenza activity was moderate with the highest incidence of influence-like illness at week 10/2015 (March). During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Among the 2416 tested specimens, 22.6 % of influenza cases were positive for A/H3N2/, while A/H1N1/pdm09 constituted 14.6 % cases. Influenza A viruses were detected in co-circulation with influenza B viruses; the latter amounted to 34.1 % of all influenza detections. Other detected causes of influenza-like illness consisted of respiratory syncytial virus (RSV), being predominant, and, sporadically, human coronavirus, parainfluenza 1-3, rhinovirus, and adenovirus. Despite low vaccine effectiveness of solely one component, A/H3N2/, the vaccine could mitigate or shorten the length of influenza infection and reduce the number of severe outcomes and mortality. Thus, vaccination against influenza remains the most effective way to prevent illness and possibly fatal outcomes. PMID:26956457

  1. Type- and subtype-specific detection of influenza viruses in clinical specimens by rapid culture assay.

    PubMed

    Ziegler, T; Hall, H; Sánchez-Fauquier, A; Gamble, W C; Cox, N J

    1995-02-01

    A rapid culture assay which allows for the simultaneous typing and subtyping of currently circulating influenza A(H1N1), A(H3N2), and B viruses in clinical specimens was developed. Pools of monoclonal antibodies (MAbs) against influenza A and B viruses and MAbs HA1-71 and HA2-76, obtained by immunizing mice with the denatured hemagglutinin subfragments HA1 and HA2 of influenza virus A/Victoria/3/75, were used for immunoperoxidase staining of antigens in infected MDCK cells. MAb HA1-71 reacted exclusively with influenza A viruses of the H3 subtype, while MAb HA2-76 reacted with subtypes H1, H3, H4, H6, H8, H9, H10, H11, and H12, as determined with 78 human, 4 swine, and 10 avian influenza virus reference strains subtyped by the hemagglutination inhibition test. To determine if the technique can be used as a rapid diagnostic test, 263 known influenza virus-positive frozen nasal or throat swabs were inoculated into MDCK cells. After an overnight incubation, the cells were fixed and viral antigens were detected by immunoperoxidase staining. Influenza A viruses of the H1 and H3 subtypes were detected in 31 and 113 specimens, respectively. The subtypes of 10 influenza A virus-positive specimens could not be determined because they contained too little virus. Influenza B viruses were detected in 84 specimens, and 25 specimens were negative. We conclude that this assay is a rapid, convenient, non-labor-intensive, and relatively inexpensive test for detecting, typing, and subtyping influenza viruses in clinical specimens. PMID:7714186

  2. Avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) is type A influenza, which is adapted to an avian host. Although avian influenza has been isolated from numerous avian species, the primary natural hosts for the virus are dabbling ducks, shorebirds, and gulls. The virus can be found world-wide in these species and in o...

  3. The East Jakarta Project: surveillance for highly pathogenic avian influenza A(H5N1) and seasonal influenza viruses in patients seeking care for respiratory disease, Jakarta, Indonesia, October 2011-September 2012.

    PubMed

    Storms, A D; Kusriastuti, R; Misriyah, S; Praptiningsih, C Y; Amalya, M; Lafond, K E; Samaan, G; Triada, R; Iuliano, A D; Ester, M; Sidjabat, R; Chittenden, K; Vogel, R; Widdowson, M A; Mahoney, F; Uyeki, T M

    2015-12-01

    Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription-polymerase chain reaction. During October 2011-September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December-May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season.

  4. "Prepandemic" immunization for novel influenza viruses, "swine flu" vaccine, Guillain-Barré syndrome, and the detection of rare severe adverse events.

    PubMed

    Evans, David; Cauchemez, Simon; Hayden, Frederick G

    2009-08-01

    The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against "swine" influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or "priming" of populations in the so-called "prepandemic" (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide-scale application of vaccines in the interpandemic period. For example, wide-scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against "swine flu" and its well-documented association with Guillain-Barré syndrome as a case study illustration of a suspected vaccine-associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting.

  5. Influenza and other respiratory viruses in three Central American countries

    PubMed Central

    Laguna‐Torres, Victor A.; Sánchez‐Largaespada, José F.; Lorenzana, Ivette; Forshey, Brett; Aguilar, Patricia; Jimenez, Mirna; Parrales, Eduardo; Rodriguez, Francisco; García, Josefina; Jimenez, Ileana; Rivera, Maribel; Perez, Juan; Sovero, Merly; Rios, Jane; Gamero, María E.; Halsey, Eric S.; Kochel, Tadeusz J.

    2010-01-01

    Please cite this paper as: Laguna‐Torres et al. (2011) Influenza and other respiratory viruses in three Central American countries. Influenza and Other Respiratory Viruses 5(2), 123–134. Background  Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. Aims  To analyze viral etiologic agents associated with influenza‐like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & Methods  Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. Results  A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. Discussion  When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). Conclusion  Genetic analysis of influenza

  6. Serological and molecular prevalence of swine influenza virus on farms in northwestern Mexico.

    PubMed

    López-Robles, Guadalupe; Montalvo-Corral, Maricela; Burgara-Estrella, Alexel; Hernández, Jesús

    2014-08-01

    The aim of this study was to provide an overview of the epidemiological status of swine influenza viruses in pigs from northwestern Mexico in 2008-2009. A serological and molecular survey was conducted in 150 pigs from 15 commercial farms in Sonora, Mexico (northwestern region of Mexico). The serological data showed that 55% of the sera were positive for the H1N1 subtype, 59% for the H3N2 subtype, and 38% for both subtypes. Overall, 16.6% (25/150) of the samples were positive for type A influenza by qRT-PCR. The phylogenetic analysis of the H1 viruses circulating in northwestern Mexico were grouped into cluster α, from five other clusters previously described. The influenza virus H1 circulating in northwestern Mexico showed 97-100% identity at the nucleotide level among them, 89% identity with other North American strains, 88% with strains from central Mexico, and 85% with the pandemic A/H1N1p2009 virus. Meanwhile, a closer relationship with some influenza viruses from North America (97% nucleotide identity) was found for H3 subtype. In conclusion, our results demonstrated a high circulation of strains similar to those observed in the North American linage among commercial farms in northwestern Mexico, involving of a different lineage virus different to the influenza pandemic of 2009.

  7. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

    PubMed

    To, Kelvin K W; Mok, Ka-Yi; Chan, Andy S F; Cheung, Nam N; Wang, Pui; Lui, Yin-Ming; Chan, Jasper F W; Chen, Honglin; Chan, Kwok-Hung; Kao, Richard Y T; Yuen, Kwok-Yung

    2016-08-01

    Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo. PMID:27259985

  8. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

    PubMed

    To, Kelvin K W; Mok, Ka-Yi; Chan, Andy S F; Cheung, Nam N; Wang, Pui; Lui, Yin-Ming; Chan, Jasper F W; Chen, Honglin; Chan, Kwok-Hung; Kao, Richard Y T; Yuen, Kwok-Yung

    2016-08-01

    Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.

  9. Epidemiology and Surveillance of Influenza Viruses in Uganda between 2008 and 2014

    PubMed Central

    Wabwire-Mangen, Fred; Mimbe, Derrick E.; Erima, Bernard; Mworozi, Edison A.; Millard, Monica; Kibuuka, Hannah; Bwogi, Josephine; Kiconco, Jocelyn; Tugume, Titus; Mulei, Sophia; Ikomera, Christine; Tsui, Sharon; Malinzi, Stephen; Kasasa, Simon; Coldren, Rodney; Byarugaba, Denis K.

    2016-01-01

    Introduction Influenza surveillance was conducted in Uganda from October 2008 to December 2014 to identify and understand the epidemiology of circulating influenza strains in out-patient clinic attendees with influenza-like illness and inform control strategies. Methodology Surveillance was conducted at five hospital-based sentinel sites. Nasopharyngeal and/or oropharyngeal samples, epidemiological and clinical data were collected from enrolled patients. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to identify and subtype influenza strains. Data were double-entered into an Epi Info 3.5.3 database and exported to STATA 13.0 software for analysis. Results Of the 6,628 patient samples tested, influenza virus infection was detected in 10.4% (n = 687/6,628) of the specimens. Several trends were observed: influenza circulates throughout the year with two peaks; the major one from September to November and a minor one from March to June. The predominant strains of influenza varied over the years: Seasonal Influenza A(H3) virus was predominant from 2008 to 2009 and from 2012 to 2014; Influenza A(H1N1)pdm01 was dominant in 2010; and Influenza B virus was dominant in 2011. The peaks generally coincided with times of higher humidity, lower temperature, and higher rainfall. Conclusion Influenza circulated throughout the year in Uganda with two major peaks of outbreaks with similar strains circulating elsewhere in the region. Data on the circulating strains of influenza and its patterns of occurrence provided critical insights to informing the design and timing of influenza vaccines for influenza prevention in tropical regions of sub-Saharan Africa. PMID:27755572

  10. Population susceptibility to North American and Eurasian swine influenza viruses in England, at three time points between 2004 and 2011.

    PubMed

    Hoschler, K; Thompson, C; Casas, I; Ellis, J; Galiano, M; Andrews, N; Zambon, M

    2013-01-01

    Age-stratified sera collected in 2004, 2008 and 2010 in England were evaluated for antibody to swine influenza A(H3N2) and A(H1N1) viruses from the United States or Europe as a measure of population susceptibility to the emergence of novel viruses. Children under 11 years of age had little or no measurable antibody to recent swine H3N2 viruses despite their high levels of antibody to recent H3N2 seasonal human strains. Adolescents and young adults (born 1968–1999) had higher antibody levels to swine H3N2 viruses. Antibody levels to swine H3N2 influenza show little correlation with exposure to recent seasonal H3N2 (A/Perth/16/2009) strains, but with antibody to older H3N2 strains represented by A/Wuhan/359/1995. Children had the highest seropositivity to influenza A(H1N1)pdm09 virus, and young adults had the lowest antibody levels to A/Perth/16/2009. No age group showed substantial antibody levels to A/Aragon/RR3218/2008, a European swine H1N1 virus belonging to the Eurasian lineage. After vaccination with contemporary trivalent vaccine we observed evidence of boosted reactivity to swine H3N2 viruses in children and adults, while only a limited boosting effect on antibody levels to A/Aragon/RR3218/2008 was observed in both groups. Overall, our results suggest that different vaccination strategies may be necessary according to age if swine viruses emerge as a significant pandemic threat.

  11. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015.

    PubMed

    Hurt, Aeron C; Besselaar, Terry G; Daniels, Rod S; Ermetal, Burcu; Fry, Alicia; Gubareva, Larisa; Huang, Weijuan; Lackenby, Angie; Lee, Raphael T C; Lo, Janice; Maurer-Stroh, Sebastian; Nguyen, Ha T; Pereyaslov, Dmitriy; Rebelo-de-Andrade, Helena; Siqueira, Marilda M; Takashita, Emi; Tashiro, Masato; Tilmanis, Danielle; Wang, Dayan; Zhang, Wenqing; Meijer, Adam

    2016-08-01

    The World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza (WHO CCs) tested 13,312 viruses collected by WHO recognized National Influenza Centres between May 2014 and May 2015 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Ninety-four per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.5% (n = 68) of viruses showed either highly reduced inhibition (HRI) or reduced inhibition (RI) (n = 56) against at least one of the four NAIs. Of the twelve viruses with HRI, six were A(H1N1)pdm09 viruses, three were A(H3N2) viruses and three were B/Yamagata-lineage viruses. The overall frequency of viruses with RI or HRI by the NAIs was lower than that observed in 2013-14 (1.9%), but similar to the 2012-13 period (0.6%). Based on the current analysis, the NAIs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections.

  12. Characteristics of patients with influenza-like illness, severe acture respiratory illness, and laboratory-confirmed influenza at a major children's hospital in Angola, 2009-2011.

    PubMed

    Cardoso, Yolanda; Oliveira, Erika; Vasconcelos, Jocelyne; Cohen, Adam L; Francisco, Moises

    2012-12-15

    There are no published data on influenza trends in Angola, where pneumonia is a leading cause of death among young children. This study aims to describe the seasonal trends, types, and subtypes of influenza virus recovered from patients with respiratory illness who were admitted to the major children's hospital in Angola from May 2009 through April 2011. Nasal and oral swabs were collected from patients seen in the outpatient clinic with influenza-like illness (ILI) or hospitalized with severe acute respiratory illness (SARI) and tested for influenza virus by polymerase chain reaction assays. Of 691 samples collected, 334 (48%) were from case patients with ILI, and 357 (52%) were from case patients with SARI. Most (86%) of these children were <5 years of age. Thirty-nine samples (47% SARI, 53% outpatient) tested positive for influenza virus, including 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09; n = 9), influenza A virus subtype H3, likely H3N2 (n = 12), and influenza B virus (n = 18). The proportion of specimens positive for influenza virus was 5% for ILI cases and 6% for SARI cases. After the peak of A(H1N1)pdm09 infection from May through September of 2009, additional peaks of ILI and SARI were seen, especially during February-April 2010. Influenza virus causes a small but preventable number of pneumonia cases among children in Angola.

  13. Low-dimensional clustering reveals new influenza strains before they become dominant

    NASA Astrophysics Data System (ADS)

    He, Jiankui; Deem, Michael

    2010-03-01

    Influenza A virus has been circulating in the human population and has caused three pandemics in the last century (1918 H1N1, 1957 H2N2, 1968 H3N2). The newly appeared 2009 A(H1N1) has been classified by the World Health Organization (WHO) as the fourth pandemic virus strain. We here consider an approach for early detection of new dominant strains. We first construct a network model and apply it to the evolution of the 2009 A(H1N1) virus. By clustering the sequence data, we found two main clusters. We then define a metric to detect the emergence of dominant strains. We show on historical H3N2 data that this method is able to find a cluster around an incipient dominant strain before it becomes dominant. For example, for H3N2 as of 30 March 2009, we see the cluster for the new A/BritishColumbia/RV1222/2009 strain. Turning to H1N1 and the 2009 A(H1N1), we do not see evidence for antigenically novel 2009 A(H1N1) strains as of August 2009. This strain detection tool combines a projection operator with a density estimation.

  14. Detection of Influenza Virus with Specific Subtype by Using Localized Surface Plasmons Excited on a Flat Metal Surface

    NASA Astrophysics Data System (ADS)

    Ning, Jun; Nagata, Kotaro; Ainai, Akira; Hasegawa, Hideki; Kano, Hiroshi

    2013-08-01

    We report on a method to determine subtype of influenza viruses by using surface plasmons localized in microscopic region on a flat metal surface. In this method, refractive index variation arisen from interactions between viruses and their monoclonal antibodies is measured. The developed sensor shows stability of refractive index in the order of 10-4 against sample exchange. In our experiment, A/H1N1 viruses are distinguished from A/H3N2 viruses by using monoclonal antibodies immobilized on the metal surface. Since the measurement probe has the volume of ˜6 al, the method has potential to handle multiple subtypes in the measurement of a sample with ultra small volume.

  15. Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity

    PubMed Central

    DeFeo, Christopher J.; Alvarado-Facundo, Esmeralda; Vassell, Russell

    2015-01-01

    ABSTRACT Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well

  16. Surveillance of human influenza A(H3N2) virus from 1999 to 2009 in southern Italy.

    PubMed

    DE Donno, A; Idolo, A; Quattrocchi, M; Zizza, A; Gabutti, G; Romano, A; Grima, P; Donatelli, I; Guido, M

    2014-05-01

    The aim of this study was to evaluate the presence of influenza virus co-infections in humans and changes in the genetic variability of A(H3N2) virus strains in southern Italy from 1999 to 2009. A partial sequence of the haemagglutinin (HA) gene by human influenza H3N2 strains identified in oropharyngeal swabs from patients with influenza-like illness was analysed by DNA sequencing and a phylogenetic analysis was performed. During the seasons 1999-2000, 2002-2003, 2004-2005 and 2008-2009, the influenza viruses circulating belonged to subtype H3N2. However, A(H1N1) subtype virus and B type were respectively prevalent during the 2000-2001, 2006-2007, 2007-2008 and 2001-2002, 2003-2004, 2005-2006 seasons. The HA sequences appeared to be closely related to the sequence of the influenza A vaccine strain. Only the 2002-2003 season was characterized by co-circulation of two viral lineages: A/New York/55/01(H3N2)-like virus of the previous season and A/Fujian/411/02(H3N2)-like virus, a new H3 variant. In this study, over the decade analysed, no significant change was seen in the sequences of the HA gene of H3 viruses isolated.

  17. Strain-specific antiviral activity of iminosugars against human influenza A viruses

    PubMed Central

    Hussain, S.; Miller, J. L.; Harvey, D. J.; Gu, Y.; Rosenthal, P. B.; Zitzmann, N.; McCauley, J. W.

    2015-01-01

    Objectives Drugs that target host cell processes can be employed to complement drugs that specifically target viruses, and iminosugar compounds that inhibit host α-glucosidases have been reported to show antiviral activity against multiple viruses. Here the effect and mechanism of two iminosugar α-glucosidase inhibitors, N-butyl-deoxynojirimycin (NB-DNJ) and N-nonyl-deoxynojirimycin (NN-DNJ), on human influenza A viruses was examined. Methods The viruses examined were a recently circulating seasonal influenza A(H3N2) virus strain A/Brisbane/10/2007, an older H3N2 strain A/Udorn/307/72, and A/Lviv/N6/2009, a strain representative of the currently circulating pandemic influenza A(H1N1)pdm09 virus. Results The inhibitors had the strongest effect on Brisbane/10 and NN-DNJ was more potent than NB-DNJ. Both compounds showed antiviral activity in cell culture against three human influenza A viruses in a strain-specific manner. Consistent with its action as an α-glucosidase inhibitor, NN-DNJ treatment resulted in an altered glycan processing of influenza haemagglutinin (HA) and neuraminidase (NA), confirmed by MS. NN-DNJ treatment was found to reduce the cell surface expression of the H3 subtype HA. The level of sialidase activity of NA was reduced in infected cells, but the addition of exogenous sialidase to the cells did not complement the NN-DNJ-mediated inhibition of virus replication. Using reassortant viruses, the drug susceptibility profile was determined to correlate with the origin of the HA. Conclusions NN-DNJ inhibits influenza A virus replication in a strain-specific manner that is dependent on the HA. PMID:25223974

  18. Influenza A virus reassortment.

    PubMed

    Steel, John; Lowen, Anice C

    2014-01-01

    Reassortment is the process by which influenza viruses swap gene segments. This genetic exchange is possible due to the segmented nature of the viral genome and occurs when two differing influenza viruses co-infect a cell. The viral diversity generated through reassortment is vast and plays an important role in the evolution of influenza viruses. Herein we review recent insights into the contribution of reassortment to the natural history and epidemiology of influenza A viruses, gained through population scale phylogenic analyses. We describe methods currently used to study reassortment in the laboratory, and we summarize recent progress made using these experimental approaches to further our understanding of influenza virus reassortment and the contexts in which it occurs.

  19. Real-time numerical forecast of global epidemic spreading: case study of 2009 A/H1N1pdm

    PubMed Central

    2012-01-01

    Background Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches. Methods We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability. Results Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model. Conclusions Our results show that large-scale models can be used to provide valuable real-time forecasts of

  20. SNPer: an R library for quantitative variant analysis on single nucleotide polymorphisms among influenza virus populations.

    PubMed

    Sangket, Unitsa; Vijasika, Sukanya; Noh, Hasnee; Chantratita, Wasun; Klungthong, Chonticha; Yoon, In Kyu; Fernandez, Stefan; Rutvisuttinunt, Wiriya

    2015-01-01

    Influenza virus (IFV) can evolve rapidly leading to genetic drifts and shifts resulting in human and animal influenza epidemics and pandemics. The genetic shift that gave rise to the 2009 influenza A/H1N1 pandemic originated from a triple gene reassortment of avian, swine and human IFVs. More minor genetic alterations in genetic drift can lead to influenza drug resistance such as the H274Y mutation associated with oseltamivir resistance. Hence, a rapid tool to detect IFV mutations and the potential emergence of new virulent strains can better prepare us for seasonal influenza outbreaks as well as potential pandemics. Furthermore, identification of specific mutations by closely examining single nucleotide polymorphisms (SNPs) in IFV sequences is essential to classify potential genetic markers associated with potentially dangerous IFV phenotypes. In this study, we developed a novel R library called "SNPer" to analyze quantitative variants in SNPs among IFV subpopulations. The computational SNPer program was applied to three different subpopulations of published IFV genomic information. SNPer queried SNPs data and grouped the SNPs into (1) universal SNPs, (2) likely common SNPs, and (3) unique SNPs. SNPer outperformed manual visualization in terms of time and labor. SNPer took only three seconds with no errors in SNP comparison events compared with 40 hours with errors using manual visualization. The SNPer tool can accelerate the capacity to capture new and potentially dangerous IFV strains to mitigate future influenza outbreaks. PMID:25876137

  1. Current status of live attenuated influenza virus vaccine in the US.

    PubMed

    Belshe, Robert B

    2004-07-01

    The efficacy and effectiveness of cold adapted live attenuated (CAIV-T, FluMist intranasal influenza vaccine is reviewed. CAIV-T consists of approximately 10(7) TCID50 per dose of each influenza A/H1N1, influenza A/H3N2, and influenza B vaccine strain. The exact strains are updated each year to antigenically match the antigens recommended by national health authorities for inclusion in the vaccine. In one year in which the vaccine strain did not well match the epidemic strain, the live attenuated vaccine induced a broad immune response that cross-reacted significantly with the drifted strain. The efficacy of CAIV-T in adults was demonstrated with challenge studies and the effectiveness of the vaccine for reducing febrile upper respiratory illness, days of missed work, and days of antibiotic use was demonstrated in a large field trial. In young children, protective efficacy against culture confirmed influenza was demonstrated in a field trial with overall protective efficacy of 92% during a two year study. Vaccine was also highly protective against a strain not contained in the vaccine, with 86% protective efficacy demonstrated against this significantly drifted virus. Effectiveness measures, including protection against febrile otitis media and visits to the doctor were demonstrated. Live attenuated vaccine provides a significant new tool to help prevent influenza.

  2. Vaccine-associated enhanced respiratory disease does not interfere with the adaptive immune response following challenge with pandemic A/H1N1 2009

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. The implications of sequential prime and challenge with mismatched influenza A viruses is a concern in mammals including humans. We evaluated the ability of pigs affected with vaccine associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the hetero...

  3. No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination

    PubMed Central

    Lamb, Favelle; Ploner, Alexander; Fink, Katharina; Maeurer, Markus; Bergman, Peter; Piehl, Fredrik; Weibel, Daniel; Sparén, Pär; Dahlström, Lisen Arnheim

    2016-01-01

    Objectives To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. Methods Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy. Results In total, 72 narcolepsy cases and 251 controls were included (range 3–69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6–8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6–8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3–2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2–0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0–170.2) and ADHD (OR = 35.3 95% CI 3.4–369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication. Conclusion The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. PMID:27120092

  4. Human infections with influenza A(H3N2) variant virus in the United States, 2011-2012.

    PubMed

    Epperson, Scott; Jhung, Michael; Richards, Shawn; Quinlisk, Patricia; Ball, Lauren; Moll, Mària; Boulton, Rachelle; Haddy, Loretta; Biggerstaff, Matthew; Brammer, Lynnette; Trock, Susan; Burns, Erin; Gomez, Thomas; Wong, Karen K; Katz, Jackie; Lindstrom, Stephen; Klimov, Alexander; Bresee, Joseph S; Jernigan, Daniel B; Cox, Nancy; Finelli, Lyn

    2013-07-01

    BACKGROUND. During August 2011-April 2012, 13 human infections with influenza A(H3N2) variant (H3N2v) virus were identified in the United States; 8 occurred in the prior 2 years. This virus differs from previous variant influenza viruses in that it contains the matrix (M) gene from the Influenza A(H1N1)pdm09 pandemic influenza virus. METHODS. A case was defined as a person with laboratory-confirmed H3N2v virus infection. Cases and contacts were interviewed to determine exposure to swine and other animals and to assess potential person-to-person transmission. RESULTS. Median age of cases was 4 years, and 12 of 13 (92%) were children. Pig exposure was identified in 7 (54%) cases. Six of 7 cases with swine exposure (86%) touched pigs, and 1 (14%) was close to pigs without known direct contact. Six cases had no swine exposure, including 2 clusters of suspected person-to-person transmission. All cases had fever; 12 (92%) had respiratory symptoms, and 3 (23%) were hospitalized for influenza. All 13 cases recovered. CONCLUSIONS. H3N2v virus infections were identified at a high rate from August 2011 to April 2012, and cases without swine exposure were identified in influenza-like illness outbreaks, indicating that limited person-to-person transmission likely occurred. Variant influenza viruses rarely result in sustained person-to-person transmission; however, the potential for this H3N2v virus to transmit efficiently is of concern. With minimal preexisting immunity in children and the limited cross-protective effect from seasonal influenza vaccine, the majority of children are susceptible to infection with this novel influenza virus.

  5. [Influenza in Poland in 2001].

    PubMed

    Kuszewski, Krzysztof; Brydak, Lidia B; Machała, Magdalena

    2003-01-01

    In 2001 the number of cases of influenza and influenza-like illness (ILI) registered in Poland amounted to 576,449. This is 36.1% of the number of cases recorded in 2000. The highest influenza incidence was found in Dolnoślaskie voivodship (3013.4 per 100,000), Mazowieckie voivodship (2688.5 per 100,000) and Zachodniopomorskie voivodship (2132.2 per 100,000). In children aged 0 to 14 years the number of influenza and ILI cases amounted to 275,358 (incidence was 3851.4 per 100,000) and this is 47.8% of the total number of cases recorded in 2001. The number of patients referred to hospitals amounted to 678 and 26 persons died. One influenza strain A(H1N1) was isolated from the patient aged 10. Immunofluorescence tests carried out in over 900 specimens did not confirm infection with influenza virus. Sero-surveys performed in the epidemic season 2001/2002 showed that the levels of antihemagglutinin antibodies were comparable for three antigens: A(H1N1), A(H3N2) and B. The highest antibody titers were recorded in the age group 15-25. Since May 2001 Poland is a member of the European Influenza Surveillance Scheme. PMID:12926309

  6. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  7. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  8. Influenza B vaccine lineage selection—An optimized trivalent vaccine

    PubMed Central

    Mosterín Höpping, Ana; Fonville, Judith M.; Russell, Colin A.; James, Sarah; Smith, Derek J.

    2016-01-01

    Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines. PMID:26896685

  9. Influenza B vaccine lineage selection--an optimized trivalent vaccine.

    PubMed

    Mosterín Höpping, Ana; Fonville, Judith M; Russell, Colin A; James, Sarah; Smith, Derek J

    2016-03-18

    Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines.

  10. Natural Products as Promising Therapeutics for Treatment of Influenza Disease.

    PubMed

    Sencanski, Milan; Radosevic, Draginja; Perovic, Vladimir; Gemovic, Branislava; Stanojevic, Maja; Veljkovic, Nevena; Glisic, Sanja

    2015-01-01

    The influenza virus represents a permanent global health threat because it circulates not only within but also between numerous host populations, thereby frequently causing unexpected outbreaks in animals and humans with a generally unpredictable course of disease and epidemiology. Conventional influenza therapy is directed against the viral neuraminidase protein, which promotes virus release from infected cells, and the viral ion channel M2, which facilitates viral uncoating. However, these drugs, albeit effective, have a major drawback: their targets are of a highly variable sequence. As a consequence, the virus can readily acquire resistance by mutating the drug targets. Indeed, most seasonal A/H1N1 viruses and the 2009 H1N1 virus are resistant to M2 inhibitors, and a significant proportion of the seasonal A/H1N1 viruses are resistant to the neuraminidase inhibitor oseltamivir. Development of new effective drugs for treatment of disease during the regular influenza seasons and the possible influenza pandemic represents an important goal. The results presented here point out natural products as a promising source of low toxic and widely accessible drug candidates for treatment of the influenza disease. Natural products combined with new therapeutic targets and drug repurposing techniques, which accelerate development of new drugs, serve as an important platform for development of new influenza therapeutics.

  11. Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses

    PubMed Central

    Carolan, Louise A.; Rockman, Steve; Borg, Kathryn; Guarnaccia, Teagan; Reading, Patrick; Mosse, Jennifer; Kelso, Anne; Barr, Ian

    2015-01-01

    ABSTRACT The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p40, alpha interferon (IFN-α), IFN-β, and tumor necrosis factor alpha (TNF-α) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-γ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. IMPORTANCE Both influenza A and B viruses cocirculate in the human population, and annual influenza seasons are typically dominated by an influenza A virus subtype or an influenza B virus lineage

  12. The 2009 H1N1 Pandemic Influenza in Korea

    PubMed Central

    2016-01-01

    In late March of 2009, an outbreak of influenza in Mexico, was eventually identified as H1N1 influenza A. In June 2009, the World Health Organization raised a pandemic alert to the highest level. More than 214 countries have reported confirmed cases of pandemic H1N1 influenza A. In Korea, the first case of pandemic influenza A/H1N1 infection was reported on May 2, 2009. Between May 2009 and August 2010, 750,000 cases of pandemic influenza A/H1N1 were confirmed by laboratory test. The H1N1-related death toll was estimated to reach 252 individuals. Almost one billion cases of influenza occurs globally every year, resulting in 300,000 to 500,000 deaths. Influenza vaccination induces virus-neutralizing antibodies, mainly against hemagglutinin, which provide protection from invading virus. New quadrivalent inactivated influenza vaccine generates similar immune responses against the three influenza strains contained in two types of trivalent vaccines and superior responses against the additional B strain. PMID:27066083

  13. A review of simulation modelling approaches used for the spread of zoonotic influenza viruses in animal and human populations.

    PubMed

    Dorjee, S; Poljak, Z; Revie, C W; Bridgland, J; McNab, B; Leger, E; Sanchez, J

    2013-09-01

    Increasing incidences of emerging and re-emerging diseases that are mostly zoonotic (e.g. severe acute respiratory syndrome, avian influenza H5N1, pandemic influenza) has led to the need for a multidisciplinary approach to tackling these threats to public and animal health. Accordingly, a global movement of 'One-Health/One-Medicine' has been launched to foster collaborative efforts amongst animal and human health officials and researchers to address these problems. Historical evidence points to the fact that pandemics caused by influenza A viruses remain a major zoonotic threat to mankind. Recently, a range of mathematical and computer simulation modelling methods and tools have increasingly been applied to improve our understanding of disease transmission dynamics, contingency planning and to support policy decisions on disease outbreak management. This review provides an overview of methods, approaches and software used for modelling the spread of zoonotic influenza viruses in animals and humans, particularly those related to the animal-human interface. Modelling parameters used in these studies are summarized to provide references for future work. This review highlights the limited application of modelling research to influenza in animals and at the animal-human interface, in marked contrast to the large volume of its research in human populations. Although swine are widely recognized as a potential host for generating novel influenza viruses, and that some of these viruses, including pandemic influenza A/H1N1 2009, have been shown to be readily transmissible between humans and swine, only one study was found related to the modelling of influenza spread at the swine-human interface. Significant gaps in the knowledge of frequency of novel viral strains evolution in pigs, farm-level natural history of influenza infection, incidences of influenza transmission between farms and between swine and humans are clearly evident. Therefore, there is a need to direct

  14. [Influenza surveillance in nine consecutive seasons, 2003-2012: results from National Influenza Reference Laboratory, Istanbul Faculty Of Medicine, Turkey].

    PubMed

    Akçay Ciblak, Meral; Kanturvardar Tütenyurd, Melis; Asar, Serkan; Tulunoğlu, Merve; Fındıkçı, Nurcihan; Badur, Selim

    2012-10-01

    Influenza is a public health problem that affects 5-20% of the world population annually causing high morbidity and mortality especially in risk groups. In addition to determining prevention and treatment strategies with vaccines and antivirals, surveillance data plays an important role in combat against influenza. Surveillance provides valuable data on characteristics of influenza activity, on types, sub-types, antigenic properties and antiviral resistance profile of circulating viruses in a given region. The first influenza surveillance was initiated as a pilot study in 2003 by now named National Influenza Reference Laboratory, Istanbul Faculty of Medicine. Surveillance was launched at national level by Ministry of Health in 2004 and two National Influenza Laboratories, one in Istanbul and the other in Ankara, have been conducting surveillance in Turkey. Surveillance data obtained for nine consecutive years, 2003-2012, by National Influenza Reference Laboratory in Istanbul Faculty of Medicine have been summarized in this report. During 2003-2012 influenza surveillance seasons, a total of 11.077 nasal swabs collected in viral transport medium were sent to the National Influenza Reference Laboratory, Istanbul for analysis. Immun-capture ELISA followed by MDCK cell culture was used for detection of influenza viruses before 2009 and real-time RT-PCR was used thereafter. Antigenic characterizations were done by hemagglutination inhibition assay with the reactives supplied by World Health Organization. Analysis of the results showed that influenza B viruses have entered the circulation in 2005-2006 seasons, and have contributed to the epidemics at increasing rates every year except in the 2009 pandemic season. Influenza B Victoria and Yamagata lineages were cocirculating for two seasons. For other seasons either lineage was in circulation. Antigenic characterization revealed that circulating B viruses matched the vaccine composition either partially or totally for only

  15. Optimisation of a micro-neutralisation assay and its application in antigenic characterisation of influenza viruses

    PubMed Central

    Lin, Yipu; Gu, Yan; Wharton, Stephen A; Whittaker, Lynne; Gregory, Victoria; Li, Xiaoyan; Metin, Simon; Cattle, Nicholas; Daniels, Rodney S; Hay, Alan J; McCauley, John W

    2015-01-01

    Objectives The identification of antigenic variants and the selection of influenza viruses for vaccine production are based largely on antigenic characterisation of the haemagglutinin (HA) of circulating viruses using the haemagglutination inhibition (HI) assay. However, in addition to evolution related to escape from host immunity, variants emerging as a result of propagation in different cell substrates can complicate the interpretation of HI results. The objective was to develop further a micro-neutralisation (MN) assay to complement the HI assay in antigenic characterisation of influenza viruses to assess the emergence of new antigenic variants and reinforce the selection of vaccine viruses. Design and setting A 96-well-plate plaque reduction MN assay based on the measurement of infected cell population using a simple imaging technique. Sample Representative influenza A (H1N1) pdm09, A(H3N2) and B viruses isolated between 2004 and 2013 Main outcome measures and results Improvements to the plaque reduction MN assay included selection of the most suitable cell line according to virus type or subtype, and optimisation of experimental design and data quantitation. Comparisons of the results of MN and HI assays showed the importance of complementary data in determining the true antigenic relationships among recent human influenza A(H1N1)pdm09, A(H3N2) and type B viruses. Conclusions Our study demonstrates that the improved MN assay has certain advantages over the HI assay: it is not significantly influenced by the cell-selected amino acid substitutions in the neuraminidase (NA) of A(H3N2) viruses, and it is particularly useful for antigenic characterisation of viruses which either grow to low HA titre and/or undergo an abortive infection resulting in an inability to form plaques in cultured cells. PMID:26073976

  16. Introductions and Evolution of Human-Origin Seasonal Influenza A Viruses in Multinational Swine Populations

    PubMed Central

    Wentworth, David E.; Culhane, Marie R.; Vincent, Amy L.; Viboud, Cecile; LaPointe, Matthew P.; Lin, Xudong; Holmes, Edward C.; Detmer, Susan E.

    2014-01-01

    ABSTRACT The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influenza viruses collected from North American swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal A/H3N2 virus origin. A molecular clock analysis indicates that this virus—A/sw/Saskatchewan/02903/2009(H3N2)—has likely circulated undetected in swine for at least 7 years. For historical context, we performed a comprehensive phylogenetic analysis of an additional 1,404 whole-genome sequences from swine influenza A viruses collected globally during 1931 to 2013. Human-to-swine transmission occurred frequently over this time period, with 20 discrete introductions of human seasonal influenza A viruses showing sustained onward transmission in swine for at least 1 year since 1965. Notably, human-origin hemagglutinin (H1 and H3) and neuraminidase (particularly N2) segments were detected in swine at a much higher rate than the six internal gene segments, suggesting an association between the acquisition of swine-origin internal genes via reassortment and the adaptation of human influenza viruses to new swine hosts. Further understanding of the fitness constraints on the adaptation of human viruses to swine, and vice versa, at a genomic level is central to understanding the complex multihost ecology of influenza and the disease threats that swine and humans pose to each other. IMPORTANCE The swine origin of the 2009 A/H1N1 pandemic virus underscored the importance of understanding how influenza A virus evolves in these animals hosts. While the importance of reassortment in generating genetically diverse influenza viruses in swine is well documented, the role of human-to-swine transmission has not been as

  17. Effectiveness of seasonal influenza vaccinations against laboratory-confirmed influenza-associated infections among Singapore military personnel in 2010–2013

    PubMed Central

    Ho, Hin Peow; Zhao, Xiahong; Pang, Junxiong; Chen, Mark I-C; Lee, Vernon J M; Ang, Li Wei; Lin, Raymond V Tzer Pin; Gao, Christine Q; Hsu, Li Yang; Cook, Alex R

    2014-01-01

    Background Limited information is available about seasonal influenza vaccine effectiveness (VE) in tropical communities. Objectives Virus subtype-specific VE was determined for all military service personnel in the recruit camp and three other non-recruit camp in Singapore's Armed Forces from 1 June 2009 to 30 June 2012. Methods Consenting servicemen underwent nasal washes, which were tested with RT-PCR and subtyped. The test positive case and test negative control design was used to estimate the VE. To estimate the overall effect of the programme on new recruits, we used an ecological time series approach. Results A total of 7016 consultations were collected. The crude estimates for the VE of the triavalent vaccine against both influenza A(H1N1)pdm09 and influenza B were 84% (95% CI 78–88%, 79–86%, respectively). Vaccine efficacy against influenza A(H3N2) was markedly lower (VE 33%, 95% CI −4% to 57%). An estimated 70% (RR = 0·30; 95% CI 0·11–0·84), 39% (RR = 0·61;0·25–1·43) and 75% (RR = 0·25; 95% CI 0·11–0·50) reduction in the risk of influenza A(H1N1)pdm09, influenza A(H3N2) and influenza B infections, respectively, in the recruit camp during the post-vaccination period compared with during the pre-vaccination period was observed. Conclusions Overall, the blanket influenza vaccine programme in Singapore's Armed Forces has had a moderate to high degree of protection against influenza A(H1N1)pdm09 and influenza B, but not against influenza A(H3N2). Blanket influenza vaccination is recommended for all military personnel. PMID:24828687

  18. Predicting the Mutating Distribution at Antigenic Sites of the Influenza Virus

    PubMed Central

    Xu, Hongyang; Yang, Yiyan; Wang, Shuning; Zhu, Ruixin; Qiu, Tianyi; Qiu, Jingxuan; Zhang, Qingchen; Jin, Li; He, Yungang; Tang, Kailin; Cao, Zhiwei

    2016-01-01

    Mutations of the influenza virus lead to antigenic changes that cause recurrent epidemics and vaccine resistance. Preventive measures would benefit greatly from the ability to predict the potential distribution of new antigenic sites in future strains. By leveraging the extensive historical records of HA sequences for 90 years, we designed a computational model to simulate the dynamic evolution of antigenic sites in A/H1N1. With templates of antigenic sequences, the model can effectively predict the potential distribution of future antigenic mutants. Validation on 10932 HA sequences from the last 16 years showing that the mutated antigenic sites of over 94% of reported strains fell in our predicted profile. Meanwhile, our model can successfully capture 96% of antigenic sites in those dominant epitopes. Similar results are observed on the complete set of H3N2 historical data, supporting the general applicability of our model to multiple sub-types of influenza. Our results suggest that the mutational profile of future antigenic sites can be predicted based on historical evolutionary traces despite the widespread, random mutations in influenza. Coupled with closely monitored sequence data from influenza surveillance networks, our method can help to forecast changes in viral antigenicity for seasonal flu and inform public health interventions. PMID:26837263

  19. Quadrivalent Ann Arbor strain live-attenuated influenza vaccine.

    PubMed

    Toback, Seth L; Levin, Myron J; Block, Stan L; Belshe, Robert B; Ambrose, Christopher S; Falloon, Judith

    2012-11-01

    Influenza B is responsible for significant morbidity in children and adults worldwide. For more than 25 years, two antigenically distinct lineages of influenza B viruses, B/Yamagata and B/Victoria, have cocirculated globally. Current influenza vaccine formulations are trivalent and contain two influenza subtype A strains (A/H1N1 and A/H3N2) but only one B strain. In a half of recent influenza seasons, the predominant circulating influenza B lineage was different from that contained in trivalent influenza vaccines. A quadrivalent live-attenuated influenza vaccine (Q/LAIV) that contains two B strains, one from each lineage, has been developed to help provide broad protection against influenza B. Q/LAIV was recently approved for use in the USA in eligible individuals 2-49 years of age. This review summarizes clinical trial data in support of Q/LAIV.

  20. Swine Influenza/Variant Influenza Viruses

    MedlinePlus

    ... Humans Key Facts about Human Infections with Variant Viruses Interim Guidance for Clinicians on Human Infections Background, Risk Assessment & Reporting Reported Infections with Variant Influenza Viruses in the United States since 2005 Prevention Treatment ...

  1. MDCK-SIAT1 cells show improved isolation rates for recent human influenza viruses compared to conventional MDCK cells.

    PubMed

    Oh, Ding Yuan; Barr, Ian G; Mosse, Jenny A; Laurie, Karen L

    2008-07-01

    The ability to isolate and propagate influenza virus is an essential tool for the yearly surveillance of circulating virus strains and to ensure accurate clinical diagnosis for appropriate treatment. The suitability of MDCK-SIAT1 cells, engineered to express increased levels of alpha-2,6-linked sialic acid receptors, as an alternative to conventional MDCK cells for isolation of circulating influenza virus was assessed. A greater number of influenza A (H1N1 and H3N2) and B viruses from stored human clinical specimens collected between 2005 and 2007 were isolated following inoculation in MDCK-SIAT1 cells than in MDCK cells. In addition, a higher titer of virus was recovered following culture in MDCK-SIAT1 cells. All A(H1N1) viruses recovered from MDCK-SIAT1 cells were able to agglutinate both turkey and guinea pig red blood cells (RBC), while half of the A(H3N2) viruses recovered after passage in MDCK-SIAT1 cells lost the ability to agglutinate turkey RBC. Importantly, the HA-1 domain of the hemagglutinin gene was genetically stable after passaging in MDCK-SIAT1 cells, a feature not always seen following MDCK cell or embryonated chicken egg passage of human influenza virus. These data indicate that the MDCK-SIAT1 cell line is superior to conventional MDCK cells for isolation of human influenza virus from clinical specimens and may be used routinely for the isolation and propagation of current human influenza viruses for surveillance, diagnostic, and research purposes.

  2. Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant region of hepatitis B core antigen: Broad protective efficacy of particles carrying four copies of M2e.

    PubMed

    Tsybalova, Liudmila M; Stepanova, Liudmila A; Kuprianov, Victor V; Blokhina, Elena A; Potapchuk, Marina V; Korotkov, Alexander V; Gorshkov, Andrey N; Kasyanenko, Marina A; Ravin, Nikolai V; Kiselev, Oleg I

    2015-06-26

    A long-term objective when designing influenza vaccines is to create one with broad cross-reactivity that will provide effective control over influenza, no matter which strain has caused the disease. Here we summarize the results from an investigation into the immunogenic and protective capacities inherent in variations of a recombinant protein, HBc/4M2e. This protein contains four copies of the ectodomain from the influenza virus protein M2 (M2e) fused within the immunodominant loop of the hepatitis B virus core antigen (HBc). Variations of this basic design include preparations containing M2e from the consensus human influenza virus; the M2e from the highly pathogenic avian A/H5N1 virus and a combination of two copies from human and two copies from avian influenza viruses. Intramuscular delivery in mice with preparations containing four identical copies of M2e induced high IgG titers in blood sera and bronchoalveolar lavages. It also provoked the formation of memory T-cells and antibodies were retained in the blood sera for a significant period of time post immunization. Furthermore, these preparations prevented the death of 75-100% of animals, which were challenged with lethal doses of virus. This resulted in a 1.2-3.5 log10 decrease in viral replication within the lungs. Moreover, HBc particles carrying only "human" or "avian" M2e displayed cross-reactivity in relation to human (A/H1N1, A/H2N2 and A/H3N2) or A/H5N1 and A(H1N1)pdm09 viruses, respectively; however, with the particles carrying both "human" and "avian" M2e this effect was much weaker, especially in relation to influenza virus A/H5N1. It is apparent from this work that to quickly produce vaccine for a pandemic it would be necessary to have several variations of a recombinant protein, containing four copies of M2e (each one against a group of likely influenza virus strains) with these relevant constructs housed within a comprehensive collection Escherichia coli-producers and maintained ready for use.

  3. Serum antibody responses in naturally occurring influenza A virus infection determined by enzyme-linked immunosorbent assay, hemagglutination inhibition, and complement fixation.

    PubMed

    Madore, H P; Reichman, R C; Dolin, R

    1983-12-01

    Serum antibody responses to influenza A virus infection were examined in 388 normal subjects during a trial of chemoprophylaxis in an outbreak of influenza A in 1980-1981 in which both A/H1N1 and A/H3N2 viruses circulated. Paired serum specimens obtained over a 6-week period were tested for antibodies to both A/H1N1 and A/H3N2 viruses by conventional hemagglutination inhibition, complement fixation, and an enzyme-linked immunosorbent assay (ELISA). Antibody responses detected by ELISA were determined by calculation of the area generated between titration curves of paired sera (area method), as well as by a conventional endpoint dilution method (endpoint method). Forty-two significant antibody rises were detected; 42 by ELISA (area method), 33 by ELISA (endpoint method), 32 by hemagglutination inhibition, and 13 by complement fixation. ELISA (area method) detected rises more frequently than either ELISA (endpoint method) (P less than 0.01), hemagglutination inhibition (P less than 0.005), or complement fixation (P less than 0.001). Another sensitive assay, the microneutralization test, detected significantly fewer rises (33, P less than 0.025) than the ELISA (area method). In the 42 subjects with ELISA (area method) rises, corroborating evidence of influenza A infection by other techniques (virus isolation, microneutralization, hemagglutination inhibition, or complement fixation tests) were available for 39 (93%). ELISA (area method) rises were subtype specific in all serum pairs in which other documentation of subtype-specific infection was available (38 of 38). Thus, ELISA (area method) was the single most sensitive assay for detection of serum antibody rises in this setting and possessed a high degree of subtype specificity.

  4. Outbreak of influenza A (H3N2) variant virus infection among attendees of an agricultural fair, Pennsylvania, USA, 2011.

    PubMed

    Wong, Karen K; Greenbaum, Adena; Moll, Maria E; Lando, James; Moore, Erin L; Ganatra, Rahul; Biggerstaff, Matthew; Lam, Eugene; Smith, Erica E; Storms, Aaron D; Miller, Jeffrey R; Dato, Virginia; Nalluswami, Kumar; Nambiar, Atmaram; Silvestri, Sharon A; Lute, James R; Ostroff, Stephen; Hancock, Kathy; Branch, Alicia; Trock, Susan C; Klimov, Alexander; Shu, Bo; Brammer, Lynnette; Epperson, Scott; Finelli, Lyn; Jhung, Michael A

    2012-12-01

    During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection developed in a child who attended an agricultural fair in Pennsylvania, USA; the virus resulted from reassortment of a swine influenza virus with influenza A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort study among members of an agricultural club who attended the fair. Probable and confirmed cases of A(H3N2)v virus infection were defined by serology and genomic sequencing results, respectively. We identified 82 suspected, 4 probable, and 3 confirmed case-patients who attended the fair. Among 127 cohort study members, the risk for suspected case status increased as swine exposure increased from none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2-53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8-116.3). Fairs may be venues for zoonotic transmission of viruses with epidemic potential; thus, health officials should investigate respiratory illness outbreaks associated with agricultural events.

  5. First-year results of the Global Influenza Hospital Surveillance Network: 2012–2013 Northern hemisphere influenza season

    PubMed Central

    2014-01-01

    Background The Global Influenza Hospital Surveillance Network (GIHSN) was developed to improve understanding of severe influenza infection, as represented by hospitalized cases. The GIHSN is composed of coordinating sites, mainly affiliated with health authorities, each of which supervises and compiles data from one to seven hospitals. This report describes the distribution of influenza viruses A(H1N1), A(H3N2), B/Victoria, and B/Yamagata resulting in hospitalization during 2012–2013, the network’s first year. Methods In 2012–2013, the GIHSN included 21 hospitals (five in Spain, five in France, four in the Russian Federation, and seven in Turkey). All hospitals used a reference protocol and core questionnaire to collect data, and data were consolidated at five coordinating sites. Influenza infection was confirmed by reverse-transcription polymerase chain reaction. Hospitalized patients admitted within 7 days of onset of influenza-like illness were included in the analysis. Results Of 5034 patients included with polymerase chain reaction results, 1545 (30.7%) were positive for influenza. Influenza A(H1N1), A(H3N2), and both B lineages co-circulated, although distributions varied greatly between coordinating sites and over time. All age groups were affected. A(H1N1) was the most common influenza strain isolated among hospitalized adults 18–64 years of age at four of five coordinating sites, whereas A(H3N2) and B viruses were isolated more often than A(H1N1) in adults ≥65 years of age at all five coordinating sites. A total of 16 deaths and 20 intensive care unit admissions were recorded among patients with influenza. Conclusions Influenza strains resulting in hospitalization varied greatly between coordinating sites and over time. These first-year results of the GIHSN are relevant, useful, and timely. Due to its broad regional representativeness and sustainable framework, this growing network should contribute substantially to understanding the

  6. Immunopathogenesis of 2009 pandemic influenza.

    PubMed

    Almansa, Raquel; Bermejo-Martín, Jesús F; de Lejarazu Leonardo, Raúl Ortiz

    2012-10-01

    Three years after the pandemic, major advances have been made in our understanding of the innate and adaptive immune responses to the influenza A(H1N1)pdm09 virus and those responses' contribution to the immunopathology associated with this infection. Severe disease is characterized by early secretion of proinflammatory and immunomodulatory cytokines. This cytokine secretion persisted in patients with severe viral pneumonia and was directly associated with the degree of viral replication in the respiratory tract. Cytokines play important roles in the antiviral defense, but persistent hypercytokinemia may cause inflammatory tissue damage and participate in the genesis of the respiratory failure observed in these patients. An absence of pre-existing protective antibodies was the rule for both mild and severe cases. A role for pathogenic immunocomplexes has been proposed for this disease. Defective T cell responses characterize severe cases of infection caused by the influenza A(H1N1)pdm09 virus. Immune alterations associated with accompanying conditions such as obesity, pregnancy or chronic obstructive pulmonary disease may interfere with the normal development of the specific response to the virus. The role of host immunogenetic factors associated with disease severity is also discussed in this review. In conclusion, currently available information suggests a complex immunological dysfunction/alteration that characterizes the severe cases of 2009 pandemic influenza. The potential benefits of prophylactic/therapeutic interventions aimed at preventing/correcting such dysfunction warrant investigation. PMID:23116788

  7. Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1) 2009 virus infected patients in Spain, 2009-2010.

    PubMed

    González-Candelas, Fernando; Astray, Jenaro; Alonso, Jordi; Castro, Ady; Cantón, Rafael; Galán, Juan Carlos; Garin, Olatz; Sáez, Marc; Soldevila, Nuria; Baricot, Maretva; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martín, Vicente; Mayoral, José María; Pumarola, Tomás; Quintana, José María; Tamames, Sonia; Domínguez, Angela

    2012-01-01

    The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.

  8. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    SciTech Connect

    Mai, Binh Khanh; Li, Mai Suan

    2011-07-08

    Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  9. Accuracy of rapid influenza detection test in diagnosis of influenza A and B viruses in children less than 59 months old.

    PubMed

    Nitsch-Osuch, Aneta; Wozniak-Kosek, Agnieszka; Korzeniewski, Krzysztof; Zycinska, Katarzyna; Wardyn, Kazimierz; Brydak, Lidia B

    2013-01-01

    Influenza burden among children is underestimated. Rapid influenza diagnostic tests (RIDTs) may be helpful in the early diagnosis of the disease, but their results should be interpreted cautiously. The aim of our study was to estimate the accuracy of the rapid influenza detection test BD Directigen™ EZ Flu A+B (Becton, Dickinson and Company, Sparks, MD) used among children with influenza-like illness (ILI) consulted in the ambulatory care clinics. A total number of 150 patients were enrolled into the study. The inclusion criteria were: age of the child less than 59 months, presentation of ILI according to CDC definition (fever >37.8 °C, cough, and/or sore throat in the absence of another known cause of illness), and duration of symptoms shorter than 96 h. In all patients two nasal and one pharyngeal swab were obtained and tested by RIDT, RT-PCR, and real time RT-PCR. For or influenza A(H1N1)pdm09, virus sensitivity of RIDT was 62.2 % (95 %CI 53.4-66.5 %), specificity 97.1 % (95 %CI 93.4-99 %), positive predictive value (PPV) 90.3 % (95 %CI 77.5-96.5 %), and negative predictive value (NPV) 85.7 % (95 %CI 82.4-87.3 %). For influenza B, virus sensitivity was 36.8 % (95 %CI 23.3-41.1 %), specificity 99.2 % (95 %CI 97.3-99.9 %), PPV 87.5 % (95 %CI 55.4-97.7 %), and NPV 91.5 % (95 % CI 89.7-92.1 %). We conclude that the RIDT immunoassay is a specific, but moderately sensitive, method in the diagnosis of influenza type A and is of low sensitivity in the diagnosis of influenza B infections in infants and children.

  10. Nosocomial outbreak of the pandemic Influenza A (H1N1) 2009 in critical hematologic patients during seasonal influenza 2010-2011: detection of oseltamivir resistant variant viruses

    PubMed Central

    2013-01-01

    Background The pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus infection caused illness and death among people worldwide, particularly in hematologic/oncologic patients because influenza infected individuals can shed virus for prolonged periods, thus increasing the chances for the development of drug-resistant strains such as oseltamivir-resistant (OST-r) variant. Methods The aim of our study was to retrospectively evaluate the clinical importance of OST-r variant in circulating strains of the pandemic H1N1pdm09 virus. By means of RT-PCR and Sanger sequencing we analysed the presence of OST-r variant in 76 H1N1pdm09 laboratory-confirmed cases, hospitalized at the hematologic/oncologic ward at Spedali Civili of Brescia –Italy. Results Out of 76 hospitalized hematologic/oncologic patients, 23 patients (30.2%) were infected by H1N1pdm09 virus. Further investigation revealed that 3 patients were positive for the OST-r variant carrying the H275Y mutation. All the 23 infected patients were immuno-compromised, and were under treatment or had been treated previously with oseltamivir. Three patients died (13%) after admission to intensive care unit and only one of them developed H275Y mutation. Conclusions Our retrospective observational study shows that pandemic influenza A (H1N1) 2009 virus can cause significant morbidity and even mortality in hematologic/oncologic patients and confirms the high rate of nosocomial transmission of pandemic H1N1pdm09 virus in these critical subjects. Indeed, the reduction in host defences in these hospitalized patients favoured the prolonged use of antiviral therapy and permitted the development of OST-r strain. Strategies as diagnostic vigilance, early isolation of patients and seasonal influenza A(H1N1) vaccination may prevent transmission of influenza in high risk individuals. PMID:23496867

  11. Sequence Analysis of In Vivo Defective Interfering-Like RNA of Influenza A H1N1 Pandemic Virus

    PubMed Central

    Saira, Kazima; Lin, Xudong; DePasse, Jay V.; Halpin, Rebecca; Twaddle, Alan; Stockwell, Timothy; Angus, Brian; Cozzi-Lepri, Alessandro; Delfino, Marina; Dugan, Vivien; Dwyer, Dominic E.; Freiberg, Matthew; Horban, Andrzej; Losso, Marcelo; Lynfield, Ruth; Wentworth, Deborah N.; Holmes, Edward C.; Davey, Richard; Wentworth, David E.

    2013-01-01

    Influenza virus defective interfering (DI) particles are naturally occurring noninfectious virions typically generated during in vitro serial passages in cell culture of the virus at a high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach, we characterize several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus. The distribution of these in vivo-derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The lengths of the in vivo-derived DI-like segments also are similar to those of known in vitro DIs, and the in vivo-derived DI-like segments share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established. PMID:23678180

  12. Virus-Vectored Influenza Virus Vaccines

    PubMed Central

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  13. Emergence of influenza A (H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015.

    PubMed

    Parida, Manmohan; Dash, Paban Kumar; Kumar, Jyoti S; Joshi, Gaurav; Tandel, Kundan; Sharma, Shashi; Srivastava, Ambuj; Agarwal, Ankita; Saha, Amrita; Saraswat, Shweta; Karothia, Divyanshi; Malviya, Vatsala

    2016-01-01

    To investigate the aetiology of the 2015 A(H1N1)pdm09 influenza outbreak in India, 1,083 nasopharyngeal swabs from suspect patients were screened for influenza A(H1N1)pdm09 in the state of Madhya Pradesh. Of 412 positive specimens, six were further characterised by phylogenetic analysis of haemagglutinin (HA) sequences revealing that they belonged to genogroup 6B. A new mutation (E164G) was observed in HA2 of two sequences. Neuraminidase genes in two of 12 isolates from fatal cases on prior oseltamivir treatment harboured the H275Y mutation. PMID:26876980

  14. Emergence of influenza A (H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015.

    PubMed

    Parida, Manmohan; Dash, Paban Kumar; Kumar, Jyoti S; Joshi, Gaurav; Tandel, Kundan; Sharma, Shashi; Srivastava, Ambuj; Agarwal, Ankita; Saha, Amrita; Saraswat, Shweta; Karothia, Divyanshi; Malviya, Vatsala

    2016-01-01

    To investigate the aetiology of the 2015 A(H1N1)pdm09 influenza outbreak in India, 1,083 nasopharyngeal swabs from suspect patients were screened for influenza A(H1N1)pdm09 in the state of Madhya Pradesh. Of 412 positive specimens, six were further characterised by phylogenetic analysis of haemagglutinin (HA) sequences revealing that they belonged to genogroup 6B. A new mutation (E164G) was observed in HA2 of two sequences. Neuraminidase genes in two of 12 isolates from fatal cases on prior oseltamivir treatment harboured the H275Y mutation.

  15. [Analysis of HA and NA Genes of Influenza A H1N1 Virus in Yunnan Province during 2009-2014].

    PubMed

    Li, Juan; Zhao, Xiaonan; Cao, Yihui; Ning, Deming; Fu, Xiaoqing; Xu, Wen

    2015-11-01

    To analyze influenza pathogen spectrum in Yunnan province during 2009-2014 years, and analyze HA and NA genes of influenza A H1N1. Analysis was made on the monitoring date of influenza cases in Yunnan province in recent 6 years, 23 strains of influenza virus of HA and NA gene was sequenced and analyzed by MEGA 5 software to construct phylogenetic tree. 4 times of influenza AH1N1 epidemic peak were monitored from 2009-2014 years in Yunnan Province, as the nucleic acid detection results of influenza A H1N1 accounted for 28.8% of the total. The sequencing result showed that HA and NA gene were divided into 3 groups, one was detected with H275Y mutation strains. Influenza A H1N1 is one of the important subtypes in Yunnan province and their genes have divided into three branches during the period of 2009-2014 years, the vast majority of influenza a H1N1 are still sensitive to neuraminidase inhibitors.

  16. [Influenza surveillance in five consecutive seasons during post pandemic period: results from National Influenza Center, Turkey].

    PubMed

    Altaş, Ayşe Başak; Bayrakdar, Fatma; Korukluoğlu, Gülay

    2016-07-01

    Influenza surveillance provides data about the characteristics of influenza activity, types, sub-types and antigenic properties of the influenza viruses in circulation in a region. Surveillance also provides for the preparation against potential influenza pandemics with the identification of the genetic properties of viruses and the mutant strains that could pose a threat. In this study, data in the scope of national influenza surveillance carried out by National Influenza Center, Turkey for five consecutive influenza seasons between 2010-2015, following the A(H1N1)pdm09 virus pandemic, have been presented and evaluated. A total of 15.149 respiratory samples, including 8.894 sentinel and 6.255 non-sentinel specimens, during 2010-2015 influenza seasons, within the periods between September and May, were evaluated in our center. All samples were tested using real-time reverse transcriptase PCR (rRT-PCR) for the presence of influenza virus types and subtypes. Within the sentinel influenza surveillance, the samples that were detected negative for influenza viruses, have also been tested for the other respiratory viruses (respiratory syncytial virus, rhinoviruses, paramyxoviruses, coronaviruses) using the same technique. Further analysis, including virus isolation by cell culture inoculation and antigenic characterization by hemagglutination inhibiton test were performed for the samples found positive for influenza A and B viruses. Selected representative virus isolates have been sent to WHO reference laboratory for the sequence analysis. In the study, influenza virus positivity rates detected for all of the samples (sentinel+non-sentinel) were as follows; 34% (779/2316) in 2010-11 season; 25% (388/1554) in 2011-12; 20% (696/3541) in 2012-13; 23% (615/2678) in 2013-14; and 26% (1332/5060) in 2014-15. When all the samples were considered for influenza A and B viruses, the positivity rates for the seasons of 2010-11; 2011-12; 2012-13; 2013-14; 2014-15 were determined as

  17. [Influenza surveillance in five consecutive seasons during post pandemic period: results from National Influenza Center, Turkey].

    PubMed

    Altaş, Ayşe Başak; Bayrakdar, Fatma; Korukluoğlu, Gülay

    2016-07-01

    Influenza surveillance provides data about the characteristics of influenza activity, types, sub-types and antigenic properties of the influenza viruses in circulation in a region. Surveillance also provides for the preparation against potential influenza pandemics with the identification of the genetic properties of viruses and the mutant strains that could pose a threat. In this study, data in the scope of national influenza surveillance carried out by National Influenza Center, Turkey for five consecutive influenza seasons between 2010-2015, following the A(H1N1)pdm09 virus pandemic, have been presented and evaluated. A total of 15.149 respiratory samples, including 8.894 sentinel and 6.255 non-sentinel specimens, during 2010-2015 influenza seasons, within the periods between September and May, were evaluated in our center. All samples were tested using real-time reverse transcriptase PCR (rRT-PCR) for the presence of influenza virus types and subtypes. Within the sentinel influenza surveillance, the samples that were detected negative for influenza viruses, have also been tested for the other respiratory viruses (respiratory syncytial virus, rhinoviruses, paramyxoviruses, coronaviruses) using the same technique. Further analysis, including virus isolation by cell culture inoculation and antigenic characterization by hemagglutination inhibiton test were performed for the samples found positive for influenza A and B viruses. Selected representative virus isolates have been sent to WHO reference laboratory for the sequence analysis. In the study, influenza virus positivity rates detected for all of the samples (sentinel+non-sentinel) were as follows; 34% (779/2316) in 2010-11 season; 25% (388/1554) in 2011-12; 20% (696/3541) in 2012-13; 23% (615/2678) in 2013-14; and 26% (1332/5060) in 2014-15. When all the samples were considered for influenza A and B viruses, the positivity rates for the seasons of 2010-11; 2011-12; 2012-13; 2013-14; 2014-15 were determined as

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

    PubMed

    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

    2011-09-28

    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

  19. Is the onset of influenza in the community age-related?

    PubMed

    Fleming, D M; Durnall, H; Warburton, F; Ellis, J S; Zambon, M C

    2016-08-01

    We studied the spread of influenza in the community between 1993 and 2009 using primary-care surveillance data to investigate if the onset of influenza was age-related. Virus detections [A(H3N2), B, A(H1N1)] and clinical incidence of influenza-like illness (ILI) in 12·3 million person-years in the long-running Royal College of General Practitioners-linked clinical-virological surveillance programme in England & Wales were examined. The number of days between symptom onset and the all-age peak ILI incidence were compared by age group for each influenza type/subtype. We found that virus detection and ILI incidence increase, peak and decrease were in unison. The mean interval between symptom onset to peak ILI incidence in virus detections (all ages) was: A(H3N2) 20·5 [95% confidence interval (CI) 19·7-21·6] days; B, 18·8 (95% CI 15·8·0-21·7) days; and A(H1N1) 17·0 (95% CI 15·6-18·4) days. Differences by age group were examined using the Kruskal-Wallis test. For A(H3N2) and A(H1N1) viruses the interval was similar in each age group. For influenza B there were highly significant differences by age group (P = 0·0001). Clinical incidence rates of ILI reported in the 8 weeks preceding the period of influenza virus activity were used to estimate a baseline incidence and threshold value (upper 95% CI of estimate) which was used as a marker of epidemic progress. Differences between the age groups in the week in which the threshold was reached were small and not localized to any age group. In conclusion we found no evidence to suggest that influenza A(H3N2) and A(H1N1) occurs in the community in one age group before another. For influenza B, virus detection was earlier in children aged 5-14 years than in persons aged ⩾25 years. PMID:27350234

  20. Age-specific genetic and antigenic variations of influenza A viruses in Hong Kong, 2013–2014

    PubMed Central

    Cao, Peihua; Wong, Chit-Ming; Chan, Kwok-Hung; Wang, Xiling; Chan, King-Pan; Peiris, Joseph Sriyal Malik; Poon, Leo Lit-Man; Yang, Lin

    2016-01-01

    Age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. We implemented a systematic surveillance program in two tertiary hospitals in Hong Kong Island, to collect 112 A(H1N1)pdm09 and 254 A(H3N2) positive specimens from 2013 to 2014. Of these, 56 and 72 were identified as genetic variants of the WHO recommended vaccine composition strains, respectively. A subset of these genetic variants was selected for hemagglutination-inhibition (HI) tests, but none appeared to be antigenic variants of the vaccine composition strains. We also found that genetic and antigenicity variations were similar across sex and age groups of ≤18 yrs, 18 to 65 yrs, and ≥65 yrs. Our findings suggest that none of the age groups led other age groups in genetic evolution of influenza virus A strains. Future studies from different regions and longer study periods are needed to further investigate the age and sex heterogeneity of influenza viruses. PMID:27453320

  1. Age-specific genetic and antigenic variations of influenza A viruses in Hong Kong, 2013-2014.

    PubMed

    Cao, Peihua; Wong, Chit-Ming; Chan, Kwok-Hung; Wang, Xiling; Chan, King-Pan; Peiris, Joseph Sriyal Malik; Poon, Leo Lit-Man; Yang, Lin

    2016-01-01

    Age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. We implemented a systematic surveillance program in two tertiary hospitals in Hong Kong Island, to collect 112 A(H1N1)pdm09 and 254 A(H3N2) positive specimens from 2013 to 2014. Of these, 56 and 72 were identified as genetic variants of the WHO recommended vaccine composition strains, respectively. A subset of these genetic variants was selected for hemagglutination-inhibition (HI) tests, but none appeared to be antigenic variants of the vaccine composition strains. We also found that genetic and antigenicity variations were similar across sex and age groups of ≤18 yrs, 18 to 65 yrs, and ≥65 yrs. Our findings suggest that none of the age groups led other age groups in genetic evolution of influenza virus A strains. Future studies from different regions and longer study periods are needed to further investigate the age and sex heterogeneity of influenza viruses. PMID:27453320

  2. Review: influenza virus in pigs.

    PubMed

    Crisci, Elisa; Mussá, Tufária; Fraile, Lorenzo; Montoya, Maria

    2013-10-01

    Influenza virus disease still remains one of the major threats to human health, involving a wide range of animal species and pigs play an important role in influenza ecology. Pigs were labeled as "mixing vessels" since they are susceptible to infection with avian, human and swine influenza viruses and genetic reassortment between these viruses can occur. After the H1N1 influenza pandemic of 2009 with a swine origin virus, the most recent research in "influenzology" is directed at improving knowledge of porcine influenza virus infection. This tendency is probably due to the fact that domestic pigs are closely related to humans and represent an excellent animal model to study various microbial infectious diseases. In spite of the role of the pig in influenza virus ecology, swine immune responses against influenza viruses are not fully understood. Considering these premises, the aim of this review is to focus on the in vitro studies performed with porcine cells and influenza virus and on the immune responses of pigs against human, avian and swine influenza viruses in vivo. The increased acceptance of pigs as suitable and valuable models in the scientific community may stimulate the development of new tools to assess porcine immune responses, paving the way for their consideration as the future "gold standard" large-animal model in immunology.

  3. Fatal Cases of Seasonal Influenza in Russia in 2015–2016

    PubMed Central

    Durymanov, A.; Susloparov, I.; Kolosova, N.; Goncharova, N.; Svyatchenko, S.; Petrova, O.; Bondar, A.; Mikheev, V.; Ryzhikov, A.

    2016-01-01

    The influenza epidemic in 2015–2016 in Russia is characterized by a sharp increase of influenza cases (beginning from the second week of 2016) with increased fatalities. Influenza was confirmed in 20 fatal cases registered among children (0–10 years), in 5 cases among pregnant women, and in 173 cases among elderly people (60 years and older). Two hundred and ninety nine people died from influenza were patients with some chronic problems. The overwhelming majority among the deceased (more than 98%) were not vaccinated against influenza. We isolated 109 influenza A(H1N1)pdm09 and one A(H3N2) virus strains from 501 autopsy material samples. The antigenic features of the strains were similar to the vaccine strains. A phylogenic analysis of hemagglutinin revealed that influenza A(H1N1)pdm09 virus strains belonged to 6B genetic group that had two main dominant subgroups during the 2015–2016 season. In Russia strains of the first group predominated. We registered an increased proportion of strains with D222G mutation in receptor-binding site. A herd immunity analysis carried out immediately prior to the epidemic showed that 34.4% blood sera samples collected in different regions of Russia were positive to A/California/07/09(H1N1)pdm09. We came to a conclusion that public awareness enhancement is necessary to reduce unreasonable refusals of vaccination. PMID:27776172

  4. Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets.

    PubMed

    Huang, Stephen S H; Banner, David; Fang, Yuan; Ng, Derek C K; Kanagasabai, Thirumagal; Kelvin, David J; Kelvin, Alyson A

    2011-01-01

    Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses). The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology) correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response). Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.

  5. Pandemic influenza planning, United States, 1978-2008.

    PubMed

    Iskander, John; Strikas, Raymond A; Gensheimer, Kathleen F; Cox, Nancy J; Redd, Stephen C

    2013-06-01

    During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community's response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.

  6. Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine.

    PubMed

    Davlin, Stacy L; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Smith, Sophie; Kramer, Natalie; Cohen, Jessica; Cummings, Charisse Nitura; Garg, Shikha; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Bresee, Joseph; Wallis, Teresa; Sessions, Wendy; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

    2016-01-01

    During the 2015-16 influenza season (October 4, 2015-May 21, 2016) in the United States, influenza activity* was lower and peaked later compared with the previous three seasons (2012-13, 2013-14, and 2014-15). Activity remained low from October 2015 until late December 2015 and peaked in mid-March 2016. During the most recent 18 influenza seasons (including this season), only two other seasons have peaked in March (2011-12 and 2005-06). Overall influenza activity was moderate this season, with a lower percentage of outpatient visits for influenza-like illness (ILI),(†) lower hospitalization rates, and a lower percentage of deaths attributed to pneumonia and influenza (P&I) compared with the preceding three seasons. Influenza A(H1N1)pdm09 viruses predominated overall, but influenza A(H3N2) viruses were more commonly identified from October to early December, and influenza B viruses were more commonly identified from mid-April through mid-May. The majority of viruses characterized this season were antigenically similar to the reference viruses representing the recommended components of the 2015-16 Northern Hemisphere influenza vaccine (1). This report summarizes influenza activity in the United States during the 2015-16 influenza season (October 4, 2015-May 21, 2016)(§) and reports the vaccine virus components recommended for the 2016-17 Northern Hemisphere influenza vaccines. PMID:27281364

  7. Epidemiological aspects of influenza A related to climatic conditions during and after a pandemic period in the city of Salvador, northeastern Brazil

    PubMed Central

    Silva, Rosangela de Castro; Siqueira, Marilda Agudo Mendonça; Netto, Eduardo Martins; Bastos, Jacione Silva; Nascimento-Carvalho, Cristiana Maria; Vilas-Boas, Ana Luisa; Bouzas, Maiara Lana; Motta, Fernando do Couto; Brites, Carlos

    2014-01-01

    During the influenza pandemic of 2009, the A(H1N1)pdm09, 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(H1N1)pdm09 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. PMID:24714967

  8. Behavioural responses to influenza pandemics

    PubMed Central

    Balinska, Marta; Rizzo, Caterina

    2009-01-01

    The emergence of the novel A/H1N1 virus has made pandemic preparedness a crucial issue for public health worldwide. Although the epidemiological aspects of the three 20th century influenza pandemics have been widely investigated, little is known about population behaviour in a pandemic situation. Such knowledge is however critical, notably for predicting population compliance with non pharmaceutical interventions. This paper reviews the relevant scientific literature for the 1918-1920, 1957-1958, 1969-1969 influenza epidemics and the 2003 SARS outbreak. Although the evidence base of most non pharmaceutical interventions (NPIs) and personal protection measures is debated, it appears on the basis of past experience that NPIs implemented the most systematically, the earliest, and for the longest time could reduce overall mortality rates and spread out epidemic peaks. Adequate, transparent, and targeted communication on the part of public health authorities would be also of crucial importance in the event of a serious influenza pandemic. PMID:20025201

  9. Novel vaccines against influenza viruses

    PubMed Central

    Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

    2011-01-01

    Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccination. PMID:21968298

  10. Emergence of influenza A viruses.

    PubMed Central

    Webby, R J; Webster, R G

    2001-01-01

    Pandemic influenza in humans is a zoonotic disease caused by the transfer of influenza A viruses or virus gene segments from animal reservoirs. Influenza A viruses have been isolated from avian and mammalian hosts, although the primary reservoirs are the aquatic bird populations of the world. In the aquatic birds, influenza is asymptomatic, and the viruses are in evolutionary stasis. The aquatic bird viruses do not replicate well in humans, and these viruses need to reassort or adapt in an intermediate host before they emerge in human populations. Pigs can serve as a host for avian and human viruses and are logical candidates for the role of intermediate host. The transmission of avian H5N1 and H9N2 viruses directly to humans during the late 1990s showed that land-based poultry also can serve between aquatic birds and humans as intermediate hosts of influenza viruses. That these transmission events took place in Hong Kong and China adds further support to the hypothesis that Asia is an epicentre for influenza and stresses the importance of surveillance of pigs and live-bird markets in this area. PMID:11779380

  11. Variant (Swine Origin) Influenza Viruses in Humans

    MedlinePlus

    ... What's this? Submit Button Past Newsletters Variant Influenza Viruses: Background and CDC Risk Assessment and Reporting Language: ... Background CDC Assessment Reporting Background On Variant Influenza Viruses Swine flu viruses do not normally infect humans. ...

  12. New aspects of influenza viruses.

    PubMed Central

    Shaw, M W; Arden, N H; Maassab, H F

    1992-01-01

    Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands. PMID:1310439

  13. [Guillain-Barré syndrome after exposure to influenza].

    PubMed

    Hartung, H-P; Keller-Stanislawski, B; Hughes, R A; Lehmann, H C

    2012-06-01

    Guillain-Barré Syndrome (GBS) is an acquired, monophasic inflammatory polyradiculoneuritis of autoimmune origin, which occurs after infection and occasionally also after vaccination. Seasonal and pandemic influenza vaccines have in particular been implicated as triggers for GBS. However, a number of recent studies indicate that infection with influenza virus may also cause GBS. This review summarizes the epidemiological and experimental data of the association of GBS with exposure to influenza antigens by immunization (including vaccines against A/H1N1/2009) and infection. Vaccination against influenza is associated with a very low risk for the occurrence of GBS. In contrast infection with influenza may play a more important role as a triggering factor for GBS than previously assumed.

  14. Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China.

    PubMed

    Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan

    2013-01-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.

  15. Avian influenza virus RNA extraction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficient extraction and purification of viral RNA is critical for down-stream molecular applications whether it is the sensitive and specific detection of virus in clinical samples, virus gene cloning and expression, or quantification of avian influenza (AI) virus by mole