Science.gov

Sample records for ah1n1 pandemic vaccine

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  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. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. [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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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...

  6. 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

  7. 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...

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

    Background A substantial recrudescent wave of pandemic influenza A/H1N1 that began in December 2011 is ongoing and has not yet peaked in Mexico, following a 2-year period of sporadic transmission. Mexico previously experienced three pandemic waves of A/H1N1 in 2009, associated with higher excess mortality rates than those reported in other countries, and prompting a large influenza vaccination campaign. Here we describe changes in the epidemiological patterns of the ongoing 4th pandemic wave in 2011-12, relative to the earlier waves in 2009. The analysis is intended to guide public health intervention strategies in near real time. Methods We analyzed demographic and geographic data on all hospitalizations with acute respiratory infection (ARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-April 2009 to 10-Feb 2012. We characterized the age and regional patterns of A/H1N1-positive hospitalizations and inpatient-deaths relative to the 2009 A/H1N1 influenza pandemic. 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 5,795 ARI hospitalizations and 186 inpatient-deaths (3.2%) were reported between 01-December 2011 and 10-February 2012 (685 A/H1N1-positive inpatients and 75 A/H1N1-positive deaths). The nationwide peak of daily ARI hospitalizations in early 2012 has already exceeded the peak of ARI hospitalizations observed during the major fall pandemic wave in 2009. The mean age was 34.3 y (SD=21.3) among A/H1N1 inpatients and 43.5 y (SD=21) among A/H1N1 deaths in 2011-12. The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among seniors >=60 years of age (Chi-square test P<0.001) and lower among younger age groups (Chi-square test, P<0.03) for the 2011-2012 pandemic wave, compared to the earlier waves in 2009. The

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. '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

  4. ‘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

  5. '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.

  6. 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

  7. 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.

  8. 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.

  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. [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. 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.

  12. 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

  13. 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

  14. 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

  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. 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…

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. "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.

  4. 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.).

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. [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.

  17. 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

  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. 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

  20. 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

  1. 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.

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

    PubMed Central

    2012-01-01

    Background The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S. Methods We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods. Results While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period. Conclusions There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. [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%.

  16. 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

  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. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  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. 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. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  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. 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

  16. 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

  17. 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

  18. [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.

  19. 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.

  20. 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.

  1. [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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. Multiple outbreaks for the same pandemic: Local transportation and social distancing explain the different "waves" of A-H1N1pdm cases observed in México during 2009.

    PubMed

    Herrera-Valdez, Marco Arieli; Cruz-Aponte, Maytee; Castillo-Chavez, Carlos

    2011-01-01

    Influenza outbreaks have been of relatively limited historical interest in Mexico. The 2009 influenza pandemic not only changed Mexico's health priorities but also brought to the forefront some of the strengths and weaknesses of Mexico's epidemiological surveillance and public health system. A year later, Mexico's data show an epidemic pattern characterized by three "waves''. The reasons this three-wave patterns are theoretically investigated via models that incorporate Mexico's general trends of land transportation, public health measures, and the regular opening and closing of schools during 2009. The role of vaccination is also studied taking into account delays in access and limitations in the total and daily numbers of vaccines available. The research in this article supports the view that the three epidemic "waves" are the result of the synergistic interactions of three factors: regional movement patterns of Mexicans, the impact and effectiveness of dramatic social distancing measures imposed during the first outbreak, and the summer release of school children followed by their subsequent return to classes in the fall. The three "waves" cannot be explained by the transportation patterns alone but only through the combination of transport patterns and changes in contact rates due to the use of explicit or scheduled social distancing measures. The research identifies possible vaccination schemes that account for the school calendar and whose effectiveness are enhanced by social distancing measures. The limited impact of the late arrival of the vaccine is also analyzed.

  15. Geographic Prioritization of Distributing Pandemic Influenza Vaccines

    PubMed Central

    Galvani, Alison; Meyers, Lauren A

    2014-01-01

    Pandemic influenza is an international public health concern. In light of the persistent threat of H5N1 avian influenza and the recent pandemic of A/H1N1swine influenza outbreak, public health agencies around the globe are continuously revising their preparedness plans. The A/H1N1 pandemic of 2009 demonstrated that influenza activity and severity might vary considerably among age groups and locations, and the distribution of an effective influenza vaccine may be significantly delayed and staggered. Thus, pandemic influenza vaccine distribution policies should be tailored to the demographic and spatial structures of communities. Here, we introduce a bi-criteria decision-making framework for vaccine distribution policies that is based on a geospatial and demographically-structured model of pandemic influenza transmission within and between counties of Arizona in the Unites States. Based on data from the 2009–2010 H1N1 pandemic, the policy predicted to reduce overall attack rate most effectively is prioritizing counties expected to experience the latest epidemic waves (a policy that may be politically untenable). However, when we consider reductions in both the attack rate and the waiting period for those seeking vaccines, the widely adopted pro rata policy (distributing according to population size) is also predicted to be an effective strategy. PMID:22618029

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Attitudes of the General Public and General Practitioners in Five Countries towards Pandemic and Seasonal Influenza Vaccines during Season 2009/2010

    PubMed Central

    Blank, Patricia R.; Bonnelye, Genevieve; Ducastel, Aurore; Szucs, Thomas D.

    2012-01-01

    Background Vaccination coverage rates for seasonal influenza are not meeting national and international targets. Here, we investigated whether the 2009/2010 A/H1N1 pandemic influenza affected the uptake of influenza vaccines. Methodology/Principal Findings In December 2009/January 2010 and April 2010, 500 randomly selected members of the general public in Germany, France, the United States, China, and Mexico were surveyed by telephone about vaccination for seasonal and A/H1N1 pandemic influenza. Also, in April 2010, 100 randomly selected general practitioners were surveyed. Adult vaccine coverage in December 2009/January 2010 for A/H1N1 pandemic and seasonal influenza were, respectively, 12% and 29% in France, 11% and 25% in Germany, 41% and 46% in the US, 13% and 30% in Mexico, and 12% and 10% in China. Adult uptake rates in April 2010 were higher in Mexico but similar or slightly lower in the other countries. Coverage rates in children were higher than in adults in the US, Mexico, and China but mostly lower in Germany and France. Germans and French viewed the threat of A/H1N1 pandemic influenza as low to moderate, whereas Mexicans, Americans, and Chinese viewed it as moderate to serious, opinions generally mirrored by general practitioners. The recommendation of a general practitioner was a common reason for receiving the pandemic vaccine, while not feeling at risk and concerns with vaccine safety and efficacy were common reasons for not being vaccinated. Inclusion of the A/H1N1 pandemic strain increased willingness to be vaccinated for seasonal influenza in the United States, Mexico, and China but not in Germany or France. Conclusions/Significance The 2009/2010 A/H1N1 influenza pandemic increased vaccine uptake rates for seasonal influenza in Mexico but had little effect in other countries. Accurate communication of health information, especially by general practitioners, is needed to improve vaccine coverage rates. PMID:23071519

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  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. 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

  9. Predicting AH1N1 2009 influenza epidemic in Southeast Europe

    PubMed Central

    Smoljanović, Mladen; Smoljanović, Ankica; Mlikotić, Marijana

    2011-01-01

    AH1N1 2009 mortality rates. In the 2010/2011 season, the forecast of 10% increase in total mortality in SEE countries and Europe compared with the 2009/2010 season was significantly exceeded, while the expected impact of type-specific vaccines against influenza AH1N1 2009 was not achieved. Consumption of epidemic potential has greater importance for the prognosis of the course and size of influenza epidemic than the degree of vaccine immunity. PMID:21495193

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  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. 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

  17. 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.

  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. 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

  20. 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

  1. 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

  2. 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.

  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. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. Developing vaccines against pandemic influenza.

    PubMed Central

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illustrated by the production of over 150 million doses of 'swine flu' vaccine in the USA within a 3 month period in 1976. However, there is cause for concern that the lead time to begin vaccine production is likely to be about 7-8 months. Attempts to reduce this time should receive urgent attention. Immunogenicity of vaccines in pandemic situations is compared over the period 1968-1998. A consistent feature of the vaccine trials is the demonstration that one conventional 15 microg haemagglutinin dose of vaccine is not sufficiently immunogenic in naive individuals. Much larger doses or two lower doses are needed to induce satisfactory immunity. There is some evidence that whole-virus vaccines are more immunogenic than split or subunit vaccines, but this needs substantiating by further studies. H5 vaccines appeared to be particularly poor immunogens and there is evidence that an adjuvant may be needed. Prospects for improving the development of pandemic vaccines are discussed. PMID:11779397

  1. 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...

  2. 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.

  3. [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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability

    PubMed Central

    2012-01-01

    Background The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins. Results Our data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability. Conclusion We conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages. PMID:23110350

  9. 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

  10. A pandemic influenza vaccine in India: from strain to sale within 12 months.

    PubMed

    Dhere, Rajeev; Yeolekar, Leena; Kulkarni, Prasad; Menon, Ravi; Vaidya, Vivek; Ganguly, Milan; Tyagi, Parikshit; Barde, Prajakt; Jadhav, Suresh

    2011-07-01

    In the event of a highly pathogenic influenza pandemic, the Indian subcontinent would need 1.2 billion doses of vaccine to immunize its entire population, double if two doses were required to assure immunity. Serum Institute of India Limited (SII) thus became one of six initial grantees of the World Health Organization (WHO) technology transfer initiative to create capacity in developing countries to manufacture H5N1 pandemic influenza vaccine. At the outbreak of the A(H1N1) 2009 influenza pandemic, experience gained from the H5N1 project was used to develop a live attenuated influenza vaccine (LAIV), since this was the only option for the level of surge capacity required for a large-scale immunization campaign in India. SII took <12 months to develop and market its LAIV intranasal vaccine from receipt of the seed strain from WHO. As of November 2010, over 2.5 million persons have been vaccinated with Nasovac(®) with no serious adverse reactions or vaccine failure after 3 months' post-marketing surveillance. The product has been submitted for prequalification by WHO for purchase by United Nations agencies. In parallel, SII also developed an inactivated influenza vaccine, and is currently looking to ensure the sustainability of its influenza vaccine manufacturing capacity.

  11. 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.

  12. 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 during and after the flight. Public health authorities should take into account patient delays in seeking medical advise and laboratory confirmation in relation to maximum time to provide postexposure prophylaxis when deciding to install contact tracing measures. International standardization of CT guidelines is recommended. PMID:22204494

  13. 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

  14. 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.

  15. [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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Pandemic vaccines: promises and pitfalls.

    PubMed

    Booy, Robert; Brown, Lorena E; Grohmann, Gary S; Macintyre, C Raina

    2006-11-20

    Prototype vaccines against influenza A/H5N1 may be poorly immunogenic, and two or more doses may be required to induce levels of neutralising antibody that are deemed to be protective. The actual levels of antibody required to protect against a highly pathogenic virus that potentially can spread beyond the large airways is unknown. The global capacity for vaccine manufacture in eggs or tissue culture is considerable, but the number of doses that can theoretically be produced in a pandemic context will only be sufficient for a small fraction of the world's population, even less if a high antigen content is required. The safety of new pandemic vaccines should be addressed in an internationally coordinated way. Steps are underway through the Therapeutic Goods Administration to evaluate mock-up vaccines now, so that the time to registration of a new product can be minimised. It will be 3-6 months into the pandemic before an effective vaccine becomes available, so other control measures will be important in the early stages of a pandemic. The primary goal of a pandemic influenza vaccine must be to prevent death, and not necessarily to prevent infection. PMID:17115955

  3. Epidemiological Characteristics and Underlying Risk Factors for Mortality during the Autumn 2009 Pandemic Wave in Mexico

    PubMed Central

    Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cécile; Simonsen, Lone; Miller, Mark A.; Fernández-Gárate, Irma; González-Bonilla, Cesar; Borja-Aburto, Víctor H.

    2012-01-01

    Background Elucidating the role of the underlying risk factors for severe outcomes of the 2009 A/H1N1 influenza pandemic could be crucial to define priority risk groups in resource-limited settings in future pandemics. Methods We use individual-level clinical data on a large series of ARI (acute respiratory infection) hospitalizations from a prospective surveillance system of the Mexican Social Security medical system to analyze clinical features at presentation, admission delays, selected comorbidities and receipt of seasonal vaccine on the risk of A/H1N1-related death. We considered ARI hospitalizations and inpatient-deaths, and recorded demographic, geographic, and medical information on individual patients during August-December, 2009. Results Seasonal influenza vaccination was associated with a reduced risk of death among A/H1N1 inpatients (OR = 0.43 (95% CI: 0.25, 0.74)) after adjustment for age, gender, geography, antiviral treatment, admission delays, comorbidities and medical conditions. However, this result should be interpreted with caution as it could have been affected by factors not directly measured in our study. Moreover, the effect of antiviral treatment against A/H1N1 inpatient death did not reach statistical significance (OR = 0.56 (95% CI: 0.29, 1.10)) probably because only 8.9% of A/H1N1 inpatients received antiviral treatment. Moreover, diabetes (OR = 1.6) and immune suppression (OR = 2.3) were statistically significant risk factors for death whereas asthmatic persons (OR = 0.3) or pregnant women (OR = 0.4) experienced a reduced fatality rate among A/H1N1 inpatients. We also observed an increased risk of death among A/H1N1 inpatients with admission delays >2 days after symptom onset (OR = 2.7). Similar associations were also observed for A/H1N1-negative inpatients. Conclusions Geographical variation in identified medical risk factors including prevalence of diabetes and immune suppression may in part explain between

  4. 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 population.

  5. 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 population. PMID:20129961

  6. 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

  7. Factors associated with vaccination for hepatitis B, pertussis, seasonal and pandemic influenza among French general practitioners: a 2010 survey.

    PubMed

    Pulcini, Céline; Massin, Sophie; Launay, Odile; Verger, Pierre

    2013-08-20

    Our objectives were to describe the vaccine coverage (VC(1)) for some occupational vaccines (hepatitis B, pertussis, seasonal and pandemic influenza) among French General Practitioners (GPs(2)) and to study the factors associated with being vaccinated for each of these four diseases. We surveyed a representative national sample of 1431 self-employed GPs in France. Self-reported VC was 76.9% for 2009/10 seasonal influenza, 73.0% for hepatitis B, 63.9% for pertussis and 60.8% for A/H1N1 pandemic influenza. The factors associated with reporting being vaccinated were quite different from one vaccine to another. For some or all four vaccines, we found a significant positive association (p<0.05) with the following factors in the multivariate analysis: GP's male gender, high volume of activity, no particular mode of exercise (e.g. homoeopathy), no use of Internet at the practice, Continuing Medical Education sessions, discussing the benefits and risks of vaccination with the patients and performing prevention investigations for oneself (lipid profile). Being vaccinated for one vaccine also increased the VC for some or all three other studied vaccines. All these findings argue for public health campaigns using messages adapted to each vaccine. PMID:23806242

  8. 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

  9. 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...

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

    PubMed

    Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

    2015-01-01

    As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. PMID:25444798

  17. Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

    PubMed

    Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

    2015-01-01

    As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. [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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Prioritization of delayed vaccination for pandemic influenza.

    PubMed

    Shim, Eunha

    2011-01-01

    Limited production capacity and delays in vaccine development are major obstacles to vaccination programs that are designed to mitigate a pandemic influenza. In order to evaluate and compare the impact of various vaccination strategies during a pandemic influenza, we developed an age/risk-structured model of influenza transmission, and parameterized it with epidemiological data from the 2009 H1N1 influenza A pandemic. Our model predicts that the impact of vaccination would be considerably diminished by delays in vaccination and staggered vaccine supply. Nonetheless, prioritizing limited H1N1 vaccine to individuals with a high risk of complications, followed by school-age children, and then preschool-age children, would minimize an overall attack rate as well as hospitalizations and deaths. This vaccination scheme would maximize the benefits of vaccination by protecting the high-risk people directly, and generating indirect protection by vaccinating children who are most likely to transmit the disease. PMID:21361402

  11. 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

  12. 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

  13. 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

  14. 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.

  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. 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

  17. 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

  18. 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

  19. [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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. The Effects of Influenza Vaccination during Pregnancy on Birth Outcomes: A Systematic Review and Meta-Analysis.

    PubMed

    Nunes, Marta C; Aqil, Anushka R; Omer, Saad B; Madhi, Shabir A

    2016-09-01

    Objective Numerous observational studies have evaluated the relationship between influenza vaccination during pregnancy and birth outcomes. The number of studies on this subject has increased, especially after the 2009 A/H1N1 pandemic (A/H1N1pdm09). This meta-analysis aims to determine the impact of maternal vaccination with either seasonal trivalent inactivated influenza vaccines (IIV) or A/H1N1pdm09 monovalent vaccines on the rates of preterm (PTB), small for gestational age (SGA), and low birth weight (LBW) births. Methods English language randomized controlled trials and observational studies assessing the proposed outcomes after administration of influenza vaccine during pregnancy were screened. Observational studies were included if they presented adjusted measures and if the total number of women evaluated reached predefined thresholds. Sensitivity analyses were performed, including all published observational studies irrespectively of the sample size. Results A total of 5 and 13 publications that assessed the impact of IIV and monovalent A/H1N1pdm09 vaccines, respectively, fulfilled the inclusion criteria for the main analyses. The rate of PTB and LBW was lower in women who received IIV during pregnancy compared with nonvaccinated women (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77, 0.98 for PTB and OR: 0.74; 95% CI: 0.61, 0.88 for LBW); and in women vaccinated with monovalent A/H1N1pdm09 versus nonvaccinated women (OR: 0.92; 95% CI: 0.85, 0.99 for PTB and OR: 0.88; 95% CI: 0.79, 0.98 for LBW). No significant impact of vaccination on SGA birth rates was detected in the main analyses independently of the vaccine group. Conclusion Receipt of influenza vaccine during pregnancy was associated with a decreased risk of PTB and LBW. PMID:27603545

  5. 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

  6. 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 pigs. Sensitivity analysis showed that final prevalence had the greatest impact on the conditional mean and variation of the marginal effects of infections. Batch transmission point was the next most influential factor. Lowering the final prevalence and preventing older fattening pigs from being infected will have the greatest benefit in saving feed cost and reducing delay in getting the pigs to the market. PMID:27065145

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Phase 2 Assessment of the Safety and Immunogenicity of Two Inactivated Pandemic Monovalent H1N1 Vaccines in Adults as a Component of the U.S. Pandemic Preparedness Plan in 2009

    PubMed Central

    Chen, Wilbur H.; Winokur, Patricia L.; Edwards, Kathryn M.; Jackson, Lisa A.; Wald, Anna; Walter, Emmanuel B.; Noah, Diana L.; Wolff, Mark; Kotloff, Karen L.

    2012-01-01

    Background The influenza A/H1N1 pandemic in 2009 created an urgent need to develop vaccines for mass immunization. To guide decisions regarding the optimal immunization dosage and schedule for adults, we evaluated two monovalent, inactivated, unadjuvanted H1N1 influenza vaccines in independent, but simultaneously conducted, multi-center Phase 2 trials of identical design. Methods Healthy adults, stratified by age (18 to 64 years and ≥65 years), were randomized (1:1 allocation), in a double-blind, parallel-group design, to receive two intramuscular doses (21 days apart) of vaccine containing approximately 15 μg or 30 μg of hemagglutinin (HA). Primary endpoints were safety (reactogenicity for 8 days after each vaccination and vaccine-associated serious adverse events during the 7 month study) and immunogenicity (proportion of subjects, stratified by age, achieving a serum hemagglutination inhibition [HI] antibody titer ≥1:40 or a ≥4-fold rise in titer after a single injection of either dosage). Results Both vaccines were well-tolerated. A single 15 μg dose induced HI titers ≥1:40 in 90% of younger adults (95% confidence interval [CI] 82%-95%) and 81% of elderly (95% CI 71%–88%) who received Sanofi-Pasteur vaccine (subsequently found to contain 24 μg HA in the standard potency assay), and in 80% of younger adults (95% CI 71%–88%) and 60% of elderly (95% CI 50%–70%) who received CSL vaccine. Both vaccines were significantly more immunogenic in younger compared with elderly adults by at least one endpoint measure. Increasing the dose to 30 μg raised the frequency of HI titers ≥1:40 in the elderly by approximately 10%. Higher dosage did not significantly enhance immunogenicity in younger adults and a second dose provided little additional benefit to either age group. Conclusion These trials provided evidence for policymakers that a single 15 μg dose of 2009 A/H1N1 vaccine would likely protect most U.S. adults and suggest a potential benefit of a 30

  12. Vaccination against influenza: role and limitations in pandemic intervention plans.

    PubMed

    Rebmann, Terri; Zelicoff, Alan

    2012-08-01

    Influenza pandemics occur periodically and the subtype of the next pandemic strain cannot be predicted. Vaccination remains a critical intervention during pandemics, but current production technology requires several months to develop sufficient vaccine to meet anticipated worldwide need. Candidate prepandemic vaccines for use in population priming or rapid deployment during an epidemic are in development but are subtype specific and logistical obstacles to timely distribution exist. Intensive research is underway to identify a universal vaccine, providing protection against all known influenza strains based on shared epitopes. Vaccine access is expected to be limited during early response to a pandemic, necessitating ethical vaccine distribution plans for within-country and global allocation. Mass vaccination plans must be in place prior to an event to ensure appropriate infrastructures are in place. Carefully crafted education campaigns regarding pandemic vaccine safety and efficacy should aid in maximizing pandemic vaccine uptake during a future event.

  13. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine. PMID:27228647

  14. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

  15. Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization.

    PubMed

    Domínguez, Angela; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martín, Vicente; Saez, Marc; Soldevila, Núria; Quintana, José María; Mayoral, José María; Astray, Jenaro; González-Candelas, Fernando; Cantón, Rafael; Tamames, Sonia; Castro, Ady; Baricot, Maretva; Alonso, Jordi; Pumarola, Tomás

    2012-08-17

    Vaccines are leading pharmacological measures for limiting the impact of pandemic influenza in the community. The objective of this study was to investigate the effectiveness of influenza (pandemic and seasonal) vaccines in preventing pandemic influenza-associated hospitalization. We conducted a multicenter matched case-control study in 36 Spanish hospitals. Patients hospitalized with confirmed pandemic influenza between November 2009 and February 2010 and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence, were selected. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the vaccine >14 days (seasonal influenza vaccine) or >7 days (pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms of the matched case (controls). For the pandemic influenza vaccine, vaccination effectiveness (VE) was estimated taking into account only patients recruited from November 23, 2009, seven days after the beginning of the pandemic influenza vaccination campaign. 638 cases and 1250 controls were included. The adjusted VE of the pandemic vaccine in the ≥18 years age group was 74.2% (95% CI, 29-90) and that of the influenza seasonal vaccine 15.0% (-34 to 43). The recommendation of influenza vaccination should be reinforced as a regular measure to reduce influenza-associated hospitalization during pandemics and seasonal epidemics.

  16. 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.

  17. 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

  18. Intensive care unit surveillance of influenza infection in France: the 2009/10 pandemic and the three subsequent seasons.

    PubMed

    Bonmarin, Isabelle; Belchior, Emmanuel; Bergounioux, Jean; Brun-Buisson, Christian; Mégarbane, Bruno; Chappert, Jean Loup; Hubert, Bruno; Le Strat, Yann; Lévy-Bruhl, Daniel

    2015-01-01

    During the 2009/10 pandemic, a national surveillance system for severe influenza cases was set up in France. We present results from the system's first four years. All severe influenza cases admitted to intensive care units (ICU) were reported to the Institut de Veille Sanitaire using a standardised form: data on demographics, immunisation and virological status, risk factors, severity (e.g. acute respiratory distress syndrome (ARDS) onset, mechanical ventilation, extracorporeal life support) and outcome. Multivariate analysis was performed to identify factors associated with ARDS and death. The number of confirmed influenza cases varied from 1,210 in 2009/10 to 321 in 2011/12. Most ICU patients were infected with A(H1N1)pdm09, except during the 2011/12 winter season when A(H3N2)-related infections predominated. Patients' characteristics varied according to the predominant strain. Based on multivariate analysis, risk factors associated with death were age ≥ 65 years, patients with any of the usual recommended indications for vaccination and clinical severity. ARDS occurred more frequently in patients who were middle-aged (36-55 years), pregnant, obese, or infected with A(H1N1)pdm09. Female sex and influenza vaccination were protective. These data confirm the persistent virulence of A(H1N1)pdm09 after the pandemic and the heterogeneity of influenza seasons, and reinforce the need for surveillance of severe influenza cases. PMID:26607262

  19. 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

  20. 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 immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome. PMID:23468921

  1. Modeling control strategies for concurrent epidemics of seasonal and pandemic H1N1 influenza.

    PubMed

    Prosper, Olivia; Saucedo, Omar; Thompson, Doria; Torres-Garcia, Griselle; Wang, Xiaohong; Castillo-Chavez, Carlos

    2011-01-01

    The lessons learned from the 2009-2010 H1N1 influenza pandemic, as it moves out of the limelight, should not be under-estimated, particularly since the probability of novel influenza epidemics in the near future is not negligible and the potential consequences might be huge. Hence, as the world, particularly the industrialized world, responded to the potentially devastating effects of this novel A-H1N1 strain with substantial resources, reminders of the recurrent loss of life from a well established foe, seasonal influenza, could not be ignored. The uncertainties associated with the reported and expected levels of morbidity and mortality with this novel A-H1N1 live in a backdrop of deaths, over 200,000 hospitalizations, and millions of infections (20% of the population) attributed to seasonal influenza in the USA alone, each year. So, as the Northern Hemisphere braced for the possibility of a potentially "lethal" second wave of the novel A-H1N1 without a vaccine ready to mitigate its impact, questions of who should be vaccinated first if a vaccine became available, came to the forefront of the discussion. Uncertainty grew as we learned that the vaccine, once available, would be unevenly distributed around the world. Nations capable of acquiring large vaccine supplies soon became aware that those who could pay would have to compete for a limited vaccine stockpile. The challenges faced by nations dealing jointly with seasonal and novel A-H1N1 co-circulating strains under limited resources, that is, those with no access to novel A-H1N1 vaccine supplies, limited access to the seasonal influenza vaccine, and limited access to antivirals (like Tamiflu) are explored in this study. One- and two-strain models are introduced to mimic the influenza dynamics of a single and co-circulating strains, in the context of a single epidemic outbreak. Optimal control theory is used to identify and evaluate the "best" control policies. The controls account for the cost associated with

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 75 FR 10268 - Pandemic Influenza Vaccines-Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ..., H2, H6, H7, H9 and 2009 H1N1 Vaccines'' and replace with ``for Vaccines Against Pandemic Influenza A..., first paragraph, delete ``the pandemic countermeasures influenza A H5N1, H2, H6, H7, H9, and 2009 H1N1... HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines--Amendment Authority: 42 U.S.C....

  9. 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

    ) pdm09 was substantially higher at r = 0.89 (95% CI: 0.49, 1.28), in fact highest among all the waves detected in this study. Moreover, when AH3 or A(H1N1)pdm09 exhibit high incidence, reported cases of subtype B decreases and vice versa. Further modeling analysis indicated that during the study period, Taiwan nearly experienced at least one wave of influenza epidemic of some strain every summer except in 2012. Discussion Estimates of R for seasonal influenza are consistent with that of temperate and tropical-subtropical regions, while estimate of R for A(H1N1)pdm09 is comparatively less than countries in Europe and North America, but similar to that of tropical-subtropical regions. This offers indication of regional differences in transmissibility of influenza virus that exists only for pandemic influenza. Despite obvious limitations in the data used, this study, designed to qualitatively compare the temporal patterns and transmissibility of the waves of different strains, illustrates how influenza subtyping data can be utilized to explore the mechanism for various influenza strains to compete or to circulate, to possibly provide predictors of future trends in the evolution of influenza viruses of various subtypes, and perhaps more importantly, to be of use to future annual seasonal influenza vaccine design. PMID:27139905

  10. 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

  11. 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

  12. Influenza update 2007-2008: vaccine advances, pandemic preparation.

    PubMed

    Mossad, Sherif B

    2007-12-01

    Influenza vaccination remains our best measure to prevent epidemic and pandemic influenza. We must continue to improve vaccination rates for targeted populations. Antiviral options are currently limited to the neuraminidase inhibitors. PMID:18183839

  13. [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.

  14. 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.

  15. 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.

  16. 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

  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. Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey

    PubMed Central

    2011-01-01

    Background China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks. Methods A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method. Results 30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23). Conclusions This A/H1N1 epidemic

  19. Phylogenetic analyses of influenza A (H1N1)pdm09 hemagglutinin gene during and after the pandemic event in Brazil.

    PubMed

    Resende, Paola Cristina; Motta, Fernando Couto; Born, Priscila Silva; Machado, Daniela; Caetano, Braulia Costa; Brown, David; Siqueira, Marilda Mendonça

    2015-12-01

    Pandemic influenza A H1N1 [A(H1N1)pdm09] was first detected in Brazil in May 2009, and spread extensively throughout the country causing a peak of infection during June to August 2009. Since then, it has continued to circulate with a seasonal pattern, causing high rates of morbidity and mortality. Over this period, the virus has continually evolved with the accumulation of new mutations. In this study we analyze the phylogenetic relationship in a collection of 220 A(H1N1)pdm09 hemagglutinin (HA) gene sequences collected during and after the pandemic period (2009 to 2014) in Brazil. In addition, we have looked for evidence of viral polymorphisms associated with severe disease and compared the range of viral variants with the vaccine strain (A/California/7/2009) used throughout this period. The phylogenetic analyses in this study revealed the circulation of at least eight genetic groups in Brazil. Two (G6-pdm and G7-pdm) co-circulated during the pandemic period, showing an early pattern of viral diversification with a low genetic distance from vaccine strain. Other phylogenetic groups, G5, G6 (including 6B, 6C and 6D subgroups), and G7 were found in the subsequent epidemic seasons from 2011 to 2014. These viruses exhibited more amino acid differences from the vaccine strain with several substitutions at the antigenic sites. This is associated with a theoretical decrease in the vaccine efficacy. Furthermore, we observed that the presence of any polymorphism at residue 222 of the HA gene was significantly associated with severe/fatal cases, reinforcing previous reports that described this residue as a potential virulence marker. This study provides new information about the circulation of some viral variants in Brazil, follows up potential genetic markers associated with virulence and allows infer if the efficacy of the current vaccine against more recent A(H1N1)pdm09 strains may be reduced.

  20. 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.

  1. Influenza Vaccination Guidelines and Vaccine Sales in Southeast Asia: 2008–2011

    PubMed Central

    Gupta, Vinay; Dawood, Fatimah S.; Muangchana, Charung; Lan, Phan Trong; Xeuatvongsa, Anonh; Sovann, Ly; Olveda, Remigio; Cutter, Jeffery; Oo, Khin Yi; Ratih, Theresia Sandra Diah; Kheong, Chong Chee; Kapella, Bryan K.; Kitsutani, Paul; Corwin, Andrew; Olsen, Sonja J.

    2012-01-01

    Background Southeast Asia is a region with great potential for the emergence of a pandemic influenza virus. Global efforts to improve influenza surveillance in this region have documented the burden and seasonality of influenza viruses and have informed influenza prevention strategies, but little information exists about influenza vaccination guidelines and vaccine sales. Methods To ascertain the existence of influenza vaccine guidelines and define the scope of vaccine sales, we sent a standard three-page questionnaire to the ten member nations of the Association of Southeast Asian Nations. We also surveyed three multinational manufacturers who supply influenza vaccines in the region. Results Vaccine sales in the private sector were <1000 per 100,000 population in the 10 countries. Five countries reported purchasing vaccine for use in the public sector. In 2011, Thailand had the highest combined reported rate of vaccine sales (10,333 per 100,000). In the 10 countries combined, the rate of private sector sales during 2010–2011 (after the A(H1N1)2009pdm pandemic) exceeded 2008 pre-pandemic levels. Five countries (Indonesia, Malaysia, Singapore, Thailand and Vietnam) had guidelines for influenza vaccination but only two were consistent with global guidelines. Four recommended vaccination for health care workers, four for elderly persons, three for young children, three for persons with underlying disease, and two for pregnant women. Conclusions The rate of vaccine sales in Southeast Asia remains low, but there was a positive impact in sales after the A(H1N1)2009pdm pandemic. Low adherence to global vaccine guidelines suggests that more work is needed in the policy arena. PMID:23285200

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

    PubMed

    Luke, Catherine J; Subbarao, Kanta

    2014-07-01

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

  3. 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

  4. 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

  5. Getting vaccinated or not getting vaccinated? Different reasons for getting vaccinated against seasonal or pandemic influenza

    PubMed Central

    2013-01-01

    Background A large number of studies have investigated the motivation behind health care workers (HCWs) taking the influenza vaccine. But with the appearance of pandemic influenza, it became important to better analyse the reasons why workers get vaccinated against seasonal and/or pandemic influenza. Methods Three main categories of reasons were identified with an Exploratory Factor Analysis. An analysis of variance (ANOVA) was used to verify the existence of differences between three categories of choices (taking of seasonal and pandemic vaccine, only the seasonal vaccine or none). In addition, a multinomial logistic regression analysis was performed to analyse the association between stated intentions and update of seasonal and pandemic vaccine. Questionnaires were returned from 168 HCWs (67.3% women). Results The results showed that age and being well-informed about vaccination topics are the most important variables in determining the choice to take the vaccine. Conclusions The results highlight the importance of enhancing education programs to improve awareness among HCWs concerning the benefits of taking the influenza vaccination, with particular attention paid to younger workers. PMID:24359091

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

    PubMed

    Grødeland, Gunnveig; Bogen, Bjarne

    2015-06-01

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

  7. "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.

  8. Determinants of adults' intention to vaccinate against pandemic swine flu

    PubMed Central

    2011-01-01

    Background Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306) or pen and paper (n = 56) questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results The extended Theory of Planned Behaviour predicted 60% of adults' intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity), intention to have a seasonal vaccine this year, one perceived barrier: "I cannot be bothered to get a swine flu vaccination" and two perceived benefits: "vaccination decreases my chance of getting swine flu or its complications" and "if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor," being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications. PMID:21211000

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

    PubMed

    Bijl, D

    2011-01-01

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

  10. Les formes graves de la grippe A(H1N1) 2009 chez la femme enceinte: expérience du centre hospitalier universitaire de Fès, Maroc et revue de la littérature

    PubMed Central

    Adnane Berdai, Mohamed; Labib, Smael; Harandou, Mustapha

    2012-01-01

    Introduction Le but de cette étude est de décrire les caractéristiques épidémiologiques, cliniques, paracliniques ainsi que l’évolution des femmes enceintes ou en post partum atteintes de formes graves de Grippe A(H1N1) 2009. Méthodes C’est une étude prospective observationnelle monocentrique, menée au sein de notre service de réanimation mère et enfant au centre hospitalier universitaire Hassan II à Fès, sur une période de 3 mois, allant de novembre 2009 à janvier 2010. Résultats L’âge moyen était de 28 ans, dans 85% des cas la grossesse se situaient au troisième trimestre, le syndrome grippal était constant, la SpO2 initiale était en moyenne de 86%. A la radiographie thoracique, un syndrome alvéolaire bilatéral était toujours présent. L’infection virale était confirmée dans tous les cas par la polymerase chain reaction. Chez 3 patientes la PaO2/FiO2 était inférieure à 300. L’Oseltamivir était l’antiviral utilisé chez toutes les parturientes. Un syndrome de détresse respiratoire aigu a été développé chez 28% des parturientes, elles ont été ventilées artificiellement avec des niveaux de pressions expiratoires positives à 14 +/- 1 cmH2O. L’évolution était favorable dans 71% des cas, cependant, 2 décès ont été déplorés. Conclusion Les résultats rejoignent les données de la littérature, à savoir, un risque accru pour la femme enceinte de développer une forme grave, une présentation clinique similaire au reste de la population, l’intérêt de la vaccination et d’un traitement antiviral précoce et le rôle de l’ECMO dans le traitement des hypoxémies réfractaires. PMID:22514770

  11. Pathogenic Responses among Young Adults during the 1918 Influenza Pandemic

    PubMed Central

    Brundage, John F.

    2012-01-01

    Of the unexplained characteristics of the 1918–19 influenza pandemic, the extreme mortality rate among young adults (W-shaped mortality curve) is the foremost. Lack of a coherent explanation of this and other epidemiologic and clinical manifestations of the pandemic contributes to uncertainty in preparing for future pandemics. Contemporaneous records suggest that immunopathologic responses were a critical determinant of the high mortality rate among young adults and other high-risk subgroups. Historical records and findings from laboratory animal studies suggest that persons who were exposed to influenza once before 1918 (e.g., A/H3Nx 1890 pandemic strain) were likely to have dysregulated, pathologic cellular immune responses to infections with the A/H1N1 1918 pandemic strain. The immunopathologic effects transiently increased susceptibility to ultimately lethal secondary bacterial pneumonia. The extreme mortality rate associated with the 1918–19 pandemic is unlikely to recur naturally. However, T-cell–mediated immunopathologic effects should be carefully monitored in developing and using universal influenza vaccines. PMID:22306191

  12. 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.

  13. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus.

    PubMed

    Saariaho, Anna-Helena; Vuorela, Arja; Freitag, Tobias L; Pizza, Fabio; Plazzi, Giuseppe; Partinen, Markku; Vaarala, Outi; Meri, Seppo

    2015-09-01

    Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination.

  14. Development of pandemic influenza vaccine production capacity in Viet Nam.

    PubMed

    Hoa, L K; Hiep, L V; Be, L V

    2011-07-01

    The Institute of Vaccines and Medical Biologicals (IVAC), a state-owned vaccine manufacturer, initiated research into avian influenza vaccines in the early 1990 s in response to the threat of a highly pathogenic avian influenza pandemic. Successful results from laboratory studies on A(H5N1) influenza virus attracted seed funds and led to participation in the WHO technology transfer project to enhance influenza vaccine production in developing countries. IVAC's goal is to produce 500,000 doses of inactivated monovalent whole-virion influenza vaccine per year by 2012, and progressively increase capacity to more than 1 million doses to protect essential populations in Viet Nam in the event of an influenza pandemic. The WHO seed grants, supplemented by other international partner support, enabled IVAC to build in a very short time an influenza vaccine manufacturing plant under Good Manufacturing Practice and relevant biosafety standards, a waste treatment system and a dedicated chicken farm for high-quality eggs. Much of the equipment and instrumentation required for vaccine production has been installed and tested for functional operation. Staff have been trained on site and at specialized courses which provided comprehensive manuals on egg-based manufacturing processes and biosafety. Following process validation, clinical trials will start in 2011 and the first domestic influenza vaccine doses are expected in 2012.

  15. 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.

  16. 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.

  17. 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.

  18. Refining the approach to vaccines against influenza A viruses with pandemic potential

    PubMed Central

    Czako, Rita; Subbarao, Kanta

    2015-01-01

    Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration. PMID:26587050

  19. 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

  20. Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1pdm infection in England.

    PubMed

    Birrell, Paul J; Zhang, Xu-Sheng; Pebody, Richard G; Gay, Nigel J; De Angelis, Daniela

    2016-01-01

    Understanding how the geographic distribution of and movements within a population influence the spatial spread of infections is crucial for the design of interventions to curb transmission. Existing knowledge is typically based on results from simulation studies whereas analyses of real data remain sparse. The main difficulty in quantifying the spatial pattern of disease spread is the paucity of available data together with the challenge of incorporating optimally the limited information into models of disease transmission. To address this challenge the role of routine migration on the spatial pattern of infection during the epidemic of 2009 pandemic influenza in England is investigated here through two modelling approaches: parallel-region models, where epidemics in different regions are assumed to occur in isolation with shared characteristics; and meta-region models where inter-region transmission is expressed as a function of the commuter flux between regions. Results highlight that the significantly less computationally demanding parallel-region approach is sufficiently flexible to capture the underlying dynamics. This suggests that inter-region movement is either inaccurately characterized by the available commuting data or insignificant once its initial impact on transmission has subsided. PMID:27404957

  1. Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1pdm infection in England

    NASA Astrophysics Data System (ADS)

    Birrell, Paul J.; Zhang, Xu-Sheng; Pebody, Richard G.; Gay, Nigel J.; de Angelis, Daniela

    2016-07-01

    Understanding how the geographic distribution of and movements within a population influence the spatial spread of infections is crucial for the design of interventions to curb transmission. Existing knowledge is typically based on results from simulation studies whereas analyses of real data remain sparse. The main difficulty in quantifying the spatial pattern of disease spread is the paucity of available data together with the challenge of incorporating optimally the limited information into models of disease transmission. To address this challenge the role of routine migration on the spatial pattern of infection during the epidemic of 2009 pandemic influenza in England is investigated here through two modelling approaches: parallel-region models, where epidemics in different regions are assumed to occur in isolation with shared characteristics; and meta-region models where inter-region transmission is expressed as a function of the commuter flux between regions. Results highlight that the significantly less computationally demanding parallel-region approach is sufficiently flexible to capture the underlying dynamics. This suggests that inter-region movement is either inaccurately characterized by the available commuting data or insignificant once its initial impact on transmission has subsided.

  2. Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1pdm infection in England

    PubMed Central

    Birrell, Paul J.; Zhang, Xu-Sheng; Pebody, Richard G.; Gay, Nigel J.; De Angelis, Daniela

    2016-01-01

    Understanding how the geographic distribution of and movements within a population influence the spatial spread of infections is crucial for the design of interventions to curb transmission. Existing knowledge is typically based on results from simulation studies whereas analyses of real data remain sparse. The main difficulty in quantifying the spatial pattern of disease spread is the paucity of available data together with the challenge of incorporating optimally the limited information into models of disease transmission. To address this challenge the role of routine migration on the spatial pattern of infection during the epidemic of 2009 pandemic influenza in England is investigated here through two modelling approaches: parallel-region models, where epidemics in different regions are assumed to occur in isolation with shared characteristics; and meta-region models where inter-region transmission is expressed as a function of the commuter flux between regions. Results highlight that the significantly less computationally demanding parallel-region approach is sufficiently flexible to capture the underlying dynamics. This suggests that inter-region movement is either inaccurately characterized by the available commuting data or insignificant once its initial impact on transmission has subsided. PMID:27404957

  3. Anticipating crisis: towards a pandemic flu vaccination strategy through alignment of public health and industrial policy.

    PubMed

    Daems, Rudi; Del Giudice, Giuseppe; Rappuoli, Rino

    2005-12-30

    Flu pandemics (worldwide epidemics) have occurred at irregular and unpredictable intervals, and have been associated with substantial morbidity, mortality and economic cost. In response to the emerging potential for a new pandemic to occur, national and international preparedness plans are being drawn up specifying the use of antivirals and vaccines. A number of challenges to pandemic vaccine development, large-scale production and the timing of distribution have also been highlighted. This article reviews the rationale and consequential policy for aligned public- and private sector planning in the present inter-pandemic period despite the prevalent risks and uncertainties. We propose a model for product development of pandemic flu vaccine based on public-private partnership, including push and pull incentive mechanisms for stimulating work in this therapeutic area. In addition, we argue that innovative vaccination strategies, together with special vaccine formulations which may offer cross-protection against multiple flu pandemic strains might avert the worse effects of an influenza infection.

  4. Vaccination coverage with seasonal and pandemic influenza vaccines in children in France, 2009-2010 season.

    PubMed

    Weil-Olivier, Catherine; Lina, Bruno

    2011-09-16

    For a number of years now, GEIG, the Groupement d'Expertise et d'Information sur la Grippe (Influenza Expertise and Information Group) has conducted surveys to monitor seasonal trivalent vaccine uptake in France in adults. During the H1N1 pandemic in 2009, this survey was conducted to determine vaccination uptake for both pandemic and seasonal vaccines. An additional specific questionnaire was used to collect data on vaccination in children under 15 years of age. This additional study was carried out because pandemic vaccination (PV) was offered to the French population and children were listed as a priority target group by the national health authorities, whereas seasonal trivalent inactivated vaccines (TIV) are not recommended in children in France. Overall, we collected 2443 questionnaires on children, including children with underlying conditions (9.2%) for whom TIV vaccination was recommended. Overall, 17.9% of children (438/2443) received at least one shot of PV, compared to 3.4% (83/2443) who received at least one shot of TIV. PV uptake was statistically different between non at-risk and at-risk children (366/2218 [16.5%] vs. 71/225 [31.8%], p<0.0001). This difference was even more significant in the subgroup of children with severe underlying diseases (42.7%, p<0.0001). This confirms that despite the low overall PV uptake in the French population (9%), the specific recommendation for PV for children increased vaccine uptake in this specific population, suggesting that the disease burden of influenza in children is recognised by both practitioners and parents. The next few years will tell us whether TIV uptake in children increases as a consequence of the specific recommendations made for children during the 2009 pandemic wave, or whether it will return to the very low level of 3.4% observed before the pandemic.

  5. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring.

    PubMed

    Vellozzi, Claudia; Burwen, Dale R; Dobardzic, Azra; Ball, Robert; Walton, Kimp; Haber, Penina

    2009-03-26

    In preparation for pandemic vaccine safety monitoring, we assessed adverse events reported to the Vaccine Adverse Event Reporting System following receipt of trivalent inactivated influenza vaccines among adults from 1990 through 2005. We calculated reporting rates for nonserious, serious, and neurological adverse events. We reviewed reports of recurrent events and deaths, as well as reports identified through advanced signal detection. The most frequently reported events were local reactions and systemic symptoms. Guillain-Barré syndrome was the most frequently reported serious event (0.70 reports per million vaccinations). Adverse event reporting rates have been reasonably constant over time. No new safety concerns emerged after our review of 15 years of post-licensure surveillance data. These findings provide useful information if pandemic vaccine is rapidly distributed and pre-licensure data are limited.

  6. 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

  7. Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis

    PubMed Central

    2013-01-01

    Background A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. Methods A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Results Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and

  8. Summary of knowledge gaps related to quality and efficacy of current influenza vaccines.

    PubMed

    Pfleiderer, Michael; Trouvin, Jean-Hugues; Brasseur, Daniel; Gränstrom, Marta; Shivji, Ragini; Mura, Manuela; Cavaleri, Marco

    2014-07-31

    Influenza viruses are a public health threat, as they are pathogenic, highly transmissible and prone to genetic changes. For decades vaccination strategies have been based on trivalent inactivated vaccines, which are regulated by specific guidelines. The progress in scientific knowledge and the lessons learned from the A(H1N1)2009 pandemic have highlighted further the need to improve current guidelines, including the immunogenicity criteria set by the CHMP in 1997, and to promote the discussion on the shortcomings encountered, e.g. the evaluation of vaccine efficacy in the paediatric and elderly populations, the measurement of the naivety of a population, the impact of prior immunity on subsequent vaccinations, and the technical issues with the serological assays for detection of immunity and immunogenicity. The authors attempted to summarise and tackle key gaps in the existing evidence concerning quality and efficacy of influenza vaccines, aiming at favouring a common understanding and a coordinated approach across stakeholders.

  9. Ending the Global HIV/AIDS Pandemic: The Critical Role of an HIV Vaccine

    PubMed Central

    Fauci, Anthony S.; Folkers, Gregory K.; Marston, Hilary D.

    2014-01-01

    While the human immunodeficiency virus (HIV)/AIDS pandemic continues, the incidence of HIV infections has fallen because of the deployment of antiretroviral drugs and multiple prevention modalities. To achieve a durable end to the pandemic, a vaccine remains essential. Recent advances in vaccinology offer new promise for an effective HIV vaccine. PMID:25151483

  10. A cell-based backup to speed up pandemic influenza vaccine production.

    PubMed

    Lee, Min-Shi; Hu, Alan Yung-Chih

    2012-03-01

    Influenza vaccines are currently produced through egg-based methods, with one drawback being that this system is slow to respond to the surging global demand during an influenza pandemic. Alternative influenza vaccine production strategies, such as using a cell-based strategy, should be considered in pandemic situations.

  11. Bench-to-bedside review: Vaccine protection strategies during pandemic flu outbreaks

    PubMed Central

    2010-01-01

    Vaccination is the most effective means for the prevention of influenza, including pandemic strains. An ideal pandemic influenza vaccine should provide effective protection with the fewest number of doses in the shortest amount of time, and among the greatest proportion of the population. The current manufacturing processes required for embryonated chicken-egg-based influenza vaccines are limited in their ability to respond to pandemic situations - these limitations include problems with surge capacity, the need for egg-adapted strains, the possibility of contamination, and the presence of trace egg protein. Several vaccine strategies to circumvent the deficiencies intrinsic to an egg-based influenza vaccine are in various phases of development. These include the use of cell-culture-based growth systems, concomitant use of adjuvants, whole virus vaccines, recombinant protein vaccines, plasmid DNA vaccines, virus-like particle vaccines, and universal flu vaccines. PMID:20497595

  12. Low-dose aspirin use does not diminish the immune response to monovalent H1N1 influenza vaccine in older adults.

    PubMed

    Jackson, M L; Bellamy, A; Wolff, M; Hill, H; Jackson, L A

    2016-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.

  13. 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.

  14. Vaccine Narratives and Public Health: Investigating Criticisms of H1N1 Pandemic Vaccination

    PubMed Central

    Abeysinghe, Sudeepa

    2015-01-01

    Vaccine hesitancy is often understood and explored on the level of individual decision-making. However, questions surrounding the risk and efficacy of vaccination are evident in wider public discourse; social narratives of vaccination inform and impact on the individual level. This paper takes a narrative analysis approach from the sociology of health to examine data drawn from a wider study on global public health responses to the H1N1 pandemic. The paper concentrates upon criticisms to mass vaccination as recounted within the Council of Europe’s debate of the handling of H1N1. It shows that three narratives were particularly dominant: problematizing the use of vaccination as a public health response; criticising the efficacy of the vaccines; and, questioning the safety of the strategy. This debate presents an important case study in understanding the way in which vaccines are problematized within the public discourse. PMID:25789204

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-20

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

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

    PubMed

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

    2015-08-20

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

  18. Pandemic planning in the shipping industry--lessons learnt from the 2009 Influenza Pandemic.

    PubMed

    Bunyan, Kate

    2011-01-01

    The events around the 2009 A/H1N1 Influenza Pandemic highlighted the need for better planning to ensure protection of those on vessels, protection for ports of call, and protection of business assets (business continuity). The variety of stakeholders involved in the management of a pandemic made it difficult to achieve a cohesive plan during the event itself. By considering the actions during the last pandemic, and the literature available for the shipping industry on pandemic planning, a pathway to better preparation is suggested.

  19. Pandemic planning in the shipping industry--lessons learnt from the 2009 Influenza Pandemic.

    PubMed

    Bunyan, Kate

    2011-01-01

    The events around the 2009 A/H1N1 Influenza Pandemic highlighted the need for better planning to ensure protection of those on vessels, protection for ports of call, and protection of business assets (business continuity). The variety of stakeholders involved in the management of a pandemic made it difficult to achieve a cohesive plan during the event itself. By considering the actions during the last pandemic, and the literature available for the shipping industry on pandemic planning, a pathway to better preparation is suggested. PMID:22258847

  20. The global swine flu pandemic 2: infection control measures and preparedness strategies.

    PubMed

    Pratt, Robert J

    This second in a two-part unit on swine flu looks at infection control measures for nurses. During late spring and early summer, increasing numbers of people became infected with novel swine origin influenza type A virus (influenza A(H1N1)v 2009) and a global pandemic started. Part 1 of this unit explored the biology of influenza viruses and the origins and characteristics of flu pandemics. This part reviews viral transmission, infection prevention and control and pandemic preparedness.

  1. Spatiotemporal characteristics of pandemic influenza

    PubMed Central

    2014-01-01

    Background Prediction of timing for the onset and peak of an influenza pandemic is of vital importance for preventive measures. In order to identify common spatiotemporal patterns and climate influences for pandemics in Sweden we have studied the propagation in space and time of A(H1N1)pdm09 (10,000 laboratory verified cases), the Asian Influenza 1957–1958 (275,000 cases of influenza-like illness (ILI), reported by local physicians) and the Russian Influenza 1889–1890 (32,600 ILI cases reported by physicians shortly after the end of the outbreak). Methods All cases were geocoded and analysed in space and time. Animated video sequences, showing weekly incidence per municipality and its geographically weighted mean (GWM), were created to depict and compare the spread of the pandemics. Daily data from 1957–1958 on temperature and precipitation from 39 weather stations were collected and analysed with the case data to examine possible climatological effects on the influenza dissemination. Results The epidemic period lasted 11 weeks for the Russian Influenza, 10 weeks for the Asian Influenza and 9 weeks for the A(H1N1)pdm09. The Russian Influenza arrived in Sweden during the winter and was immediately disseminated, while both the Asian Influenza and the A(H1N1)pdm09 arrived during the spring. They were seeded over the country during the summer, but did not peak until October-November. The weekly GWM of the incidence moved along a line from southwest to northeast for the Russian and Asian Influenza but northeast to southwest for the A(H1N1)pdm09. The local epidemic periods of the Asian Influenza were preceded by falling temperature in all but one of the locations analysed. Conclusions The power of spatiotemporal analysis and modeling for pandemic spread was clearly demonstrated. The epidemic period lasted approximately 10 weeks for all pandemics. None of the pandemics had its epidemic period before late autumn. The epidemic period of the Asian Influenza was

  2. 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

  3. 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.

  4. Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study

    PubMed Central

    Maro, Judith C.; Fryback, Dennis G.; Lieu, Tracy A.; Lee, Grace M.; Martin, David B.

    2014-01-01

    Background Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. Methods We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Results Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3∶1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. Conclusions The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior. PMID:25536228

  5. [Pandemic influenza vaccines. Concepts, European mock-up licenses, and acceptance criteria].

    PubMed

    Pfleiderer, M

    2010-12-01

    The concept of identifying appropriate scientific and regulatory principles to ensure rapid availability of pandemic influenza vaccines when needed were already developed starting in the year 2003. These principles allowed licensing of three so-called mock-up vaccines far ahead of any real presenting pandemic event. Those licenses (Marketing Authorizations) were immediately adapted to the novel H1N1 strain shortly after its identification in April 2009 ensuring that as early as September 2009 large parts of the German as well as of the EU population had access to licensed products which had undergone sufficient evaluation before first use in humans. In contrast, for pandemic vaccine concepts without a previously licensed mock-up version it generally took twice as much time to accumulate data supporting the granting of a Marketing Authorization. This article describes in detail the translation of concepts of producing, testing, and licensing of pandemic influenza vaccines into practice under real conditions. PMID:21161474

  6. Cross Sectional Survey of Influenza Antibodies before and during the 2009 Pandemic in Shenzhen, China

    PubMed Central

    Lv, Xing; Chen, Ying; Kung, Hsiang-fu; Zee, Benny; Cheng, Xiao-wen; He, Ming-Liang

    2013-01-01

    Much information is available for the 2009 H1N1 influenza immunity response, but little is known about the antibody change in seasonal influenza before and during the novel influenza A pandemic. In this study, we conducted a cross-sectional serological survey of 4 types of major seasonal influenza in March and September 2009 on a full range of age groups, to investigate seasonal influenza immunity response before and during the outbreak of the sH1N1 influenza in Shenzhen – the largest migration city in China. We found that the 0–5 age group had an increased antibody level for all types of seasonal influenza during the pandemic compared to the pre-outbreak level, in contrast with almost all other age groups, in which the antibody level decreased. Also, distinct from the antibodies of A/H3N2, B/Yamagata and B/Victoria that decreased significantly during the 2009 H1N1 pandemic, the antibody of A/H1N1 showed no statistical difference from the pre-outbreak level. The results suggest that the antibodies against the 2009 sH1N1 cross-reacted with seasonal H1N1. Moreover, the 0–5 age group was under attack by both seasonal and 2009 H1N1 influenza during the pandemic, hence vaccination merely against a new strain of flu might not be enough to protect the youngest group. PMID:23382854

  7. Effectiveness of seasonal influenza vaccine against pandemic (H1N1) 2009 virus, Australia, 2010.

    PubMed

    Fielding, James E; Grant, Kristina A; Garcia, Katherine; Kelly, Heath A

    2011-07-01

    To estimate effectiveness of seasonal trivalent and monovalent influenza vaccines against pandemic influenza A (H1N1) 2009 virus, we conducted a test-negative case-control study in Victoria, Australia, in 2010. Patients seen for influenza-like illness by general practitioners in a sentinel surveillance network during 2010 were tested for influenza; vaccination status was recorded. Case-patients had positive PCRs for pandemic (H1N1) 2009 virus, and controls had negative influenza test results. Of 319 eligible patients, test results for 139 (44%) were pandemic (H1N1) 2009 virus positive. Adjusted effectiveness of seasonal vaccine against pandemic (H1N1) 2009 virus was 79% (95% confidence interval 33%-93%); effectiveness of monovalent vaccine was 47% and not statistically significant. Vaccine effectiveness was higher among adults. Despite some limitations, this study indicates that the first seasonal trivalent influenza vaccine to include the pandemic (H1N1) 2009 virus strain provided significant protection against laboratory-confirmed pandemic (H1N1) 2009 infection. PMID:21762570

  8. 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.

  9. 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

  10. Vaccines against seasonal and pandemic influenza and the implications of changes in substrates for virus production.

    PubMed

    Minor, Philip D

    2010-02-15

    Influenza virus changes constantly, making vaccine production challenging. Changing the growth substrate from eggs to cell culture raises issues at all stages of the process, from surveillance to the assay of vaccines. The pandemic threat-first H5N1, then H1N1-encouraged a review of methods and brought issues into sharp relief. PMID:20085485

  11. Uptake of pandemic influenza (H1N1)-2009 vaccines in Brazil, 2010.

    PubMed

    Domingues, Carla Magda Allan S; de Oliveira, Wanderson Kleber

    2012-07-01

    In 2010, the Brazilian Ministry of Health organized a mass vaccination campaign of selected priority groups in response to the 2009 H1N1 influenza pandemic. The campaign was conducted in six phases from March to July, 2010. Priority groups included healthcare professionals, indigenous persons, pregnant women, young children, persons with chronic illnesses and otherwise healthy adults 20-39 years of age. Over 89 million doses of pandemic influenza vaccines were administered, surpassing immunization targets among several priority groups, including healthcare professionals. We reviewed strategies used in Brazil to promote vaccination against pandemic influenza as well as factors external to the campaign that may have contributed to vaccine uptake among priority groups. PMID:22609010

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

    PubMed

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

    2013-08-01

    Relatively little is known about the burden of influenza in tropical countries. The seroprevalence of pandemic influenza A (H1N1) 2009, seasonal H1N1 and H3N2 was determined in Kuala Lumpur, Malaysia. Pre- and post-pandemic residual laboratory sera were tested by hemagglutination-inhibition. The seroprevalence of A(H1N1)pdm09 increased from 3.7% pre-pandemic to 21.9% post-pandemic, giving an overall cumulative incidence of 18.1% (95% CI, 13.8-22.5%), mainly due to increases in those <5, 5-17, and 18-29 years old. In contrast with findings from USA, Europe, and Australia, pre-existing seroprevalence to A(H1N1)pdm09 was low at 5.6% in the elderly age group of >55 years. A(H1N1)pdm09 affected almost a third of those <30 years in Kuala Lumpur. Pre-pandemic seroprevalence was 14.7% for seasonal H1N1 and 21.0% for H3N2, and these rates did not change significantly after the pandemic. Seasonal and pandemic influenza cause a considerable burden in tropical Malaysia, particularly in children and young adults.

  13. Community awareness, use and preference for pandemic influenza vaccines in Pune, India

    PubMed Central

    Sundaram, Neisha; Purohit, Vidula; Schaetti, Christian; Kudale, Abhay; Joseph, Saju; Weiss, Mitchell G

    2015-01-01

    Vaccination is a cornerstone of influenza prevention, but limited vaccine uptake was a problem worldwide during the 2009–2010 pandemic. Community acceptance of a vaccine is a critical determinant of its effectiveness, but studies have been confined to high-income countries. We conducted a cross-sectional, mixed-method study in urban and rural Pune, India in 2012–2013. Semi-structured explanatory model interviews were administered to community residents (n = 436) to study awareness, experience and preference between available vaccines for pandemic influenza. Focus group discussions and in-depth interviews complemented the survey. Awareness of pandemic influenza vaccines was low (25%). Some respondents did not consider vaccines relevant for adults, but nearly all (94.7%), when asked, believed that a vaccine would prevent swine flu. Reported vaccine uptake however was 8.3%. Main themes identified as reasons for uptake were having heard of a death from swine flu, health care provider recommendation or affiliation with the health system, influence of peers and information from media. Reasons for non-use were low perceived personal risk, problems with access and cost, inadequate information and a perceived lack of a government mandate endorsing influenza vaccines. A majority indicated a preference for injectable over nasal vaccines, especially in remote rural areas. Hesitancy from a lack of confidence in pandemic influenza vaccines appears to have been less of an issue than access, complacency and other sociocultural considerations. Recent influenza outbreaks in 2015 highlight a need to reconsider policy for routine influenza vaccination while paying attention to sociocultural factors and community preferences for effective vaccine action. PMID:26110454

  14. Community awareness, use and preference for pandemic influenza vaccines in Pune, India.

    PubMed

    Sundaram, Neisha; Purohit, Vidula; Schaetti, Christian; Kudale, Abhay; Joseph, Saju; Weiss, Mitchell G

    2015-01-01

    Vaccination is a cornerstone of influenza prevention, but limited vaccine uptake was a problem worldwide during the 2009-2010 pandemic. Community acceptance of a vaccine is a critical determinant of its effectiveness, but studies have been confined to high-income countries. We conducted a cross-sectional, mixed-method study in urban and rural Pune, India in 2012-2013. Semi-structured explanatory model interviews were administered to community residents (n = 436) to study awareness, experience and preference between available vaccines for pandemic influenza. Focus group discussions and in-depth interviews complemented the survey. Awareness of pandemic influenza vaccines was low (25%). Some respondents did not consider vaccines relevant for adults, but nearly all (94.7%), when asked, believed that a vaccine would prevent swine flu. Reported vaccine uptake however was 8.3%. Main themes identified as reasons for uptake were having heard of a death from swine flu, health care provider recommendation or affiliation with the health system, influence of peers and information from media. Reasons for non-use were low perceived personal risk, problems with access and cost, inadequate information and a perceived lack of a government mandate endorsing influenza vaccines. A majority indicated a preference for injectable over nasal vaccines, especially in remote rural areas. Hesitancy from a lack of confidence in pandemic influenza vaccines appears to have been less of an issue than access, complacency and other sociocultural considerations. Recent influenza outbreaks in 2015 highlight a need to reconsider policy for routine influenza vaccination while paying attention to sociocultural factors and community preferences for effective vaccine action.

  15. Adverse events following vaccination in the French armed forces: An overview of surveillance conducted from 2002 to 2010.

    PubMed

    Mayet, A; Haus-Cheymol, R; Bouaiti, E A; Decam, C; Simon, F; Mérens, A; Spiegel, A; Meynard, J B; Deparis, X; Migliani, R

    2012-06-14

    French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to describe vaccine adverse events (VAE) reported from 2002 to 2010 in armed forces. VAE are routinely surveyed by the military Centre for epidemiology and public health. For each case, military practitioners fill a notification form, providing patient characteristics, clinical information and vaccines administered. For this study, VAE following influenza A(H1N1)pdm09 vaccination were excluded. Among the 473 cases retained, 442 (93%) corresponded to non-severe VAE,including local, regional and systemic events, while 31 corresponded to severe VAE, with two leading to significant disability. The global VAE reporting rate (RR) was 14.0 per 100,000 injections. While stationary from 2002 to 2008, the RR increased from 2009. The most important observations were a marked increase of VAE attributed to Bacillus Calmette-Guérin (BCG) vaccine from 2005 to 2008, a high RR observed with the inactivated diphtheria-tetanus (toxoids)-poliovirus vaccine combined with acellular pertussis vaccine (dTap-IPV) from 2008 and an increase in RR for seasonal influenza vaccine VAE in 2009. Our RR for severe VAE (1.1 VAEper 100,000) appears comparable with rates observed among United States civilians and military personnel. The increase observed from 2009 could be partly explained by the influenza A(H1N1)pdm09 pandemic which increased practitioner awareness towards VAE. In conclusion, the tolerance of the vaccines used in French armed forces appears acceptable.

  16. Synthetic generation of influenza vaccine viruses for rapid response to pandemics.

    PubMed

    Dormitzer, Philip R; Suphaphiphat, Pirada; Gibson, Daniel G; Wentworth, David E; Stockwell, Timothy B; Algire, Mikkel A; Alperovich, Nina; Barro, Mario; Brown, David M; Craig, Stewart; Dattilo, Brian M; Denisova, Evgeniya A; De Souza, Ivna; Eickmann, Markus; Dugan, Vivien G; Ferrari, Annette; Gomila, Raul C; Han, Liqun; Judge, Casey; Mane, Sarthak; Matrosovich, Mikhail; Merryman, Chuck; Palladino, Giuseppe; Palmer, Gene A; Spencer, Terika; Strecker, Thomas; Trusheim, Heidi; Uhlendorff, Jennifer; Wen, Yingxia; Yee, Anthony C; Zaveri, Jayshree; Zhou, Bin; Becker, Stephan; Donabedian, Armen; Mason, Peter W; Glass, John I; Rappuoli, Rino; Venter, J Craig

    2013-05-15

    During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production. PMID:23677594

  17. Synthetic generation of influenza vaccine viruses for rapid response to pandemics.

    PubMed

    Dormitzer, Philip R; Suphaphiphat, Pirada; Gibson, Daniel G; Wentworth, David E; Stockwell, Timothy B; Algire, Mikkel A; Alperovich, Nina; Barro, Mario; Brown, David M; Craig, Stewart; Dattilo, Brian M; Denisova, Evgeniya A; De Souza, Ivna; Eickmann, Markus; Dugan, Vivien G; Ferrari, Annette; Gomila, Raul C; Han, Liqun; Judge, Casey; Mane, Sarthak; Matrosovich, Mikhail; Merryman, Chuck; Palladino, Giuseppe; Palmer, Gene A; Spencer, Terika; Strecker, Thomas; Trusheim, Heidi; Uhlendorff, Jennifer; Wen, Yingxia; Yee, Anthony C; Zaveri, Jayshree; Zhou, Bin; Becker, Stephan; Donabedian, Armen; Mason, Peter W; Glass, John I; Rappuoli, Rino; Venter, J Craig

    2013-05-15

    During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.

  18. Modelling the strategies for age specific vaccination scheduling during influenza pandemic outbreaks.

    PubMed

    Knipl, Diána H; Röst, Gergely

    2011-01-01

    Finding optimal policies to reduce the morbidity and mortality of the ongoing pandemic is a top public health priority. Using a compartmental model with age structure and vaccination status, we examined the effect of age specific scheduling of vaccination during a pandemic influenza outbreak, when there is a race between the vaccination campaign and the dynamics of the pandemic. Our results agree with some recent studies on that age specificity is paramount to vaccination planning. However, little is known about the effectiveness of such control measures when they are applied during the outbreak. Comparing five possible strategies, we found that age specific scheduling can have a huge impact on the outcome of the epidemic. For the best scheme, the attack rates were up to 10% lower than for other strategies. We demonstrate the importance of early start of the vaccination campaign, since ten days delay may increase the attack rate by up to 6%. Taking into account the delay between developing immunity and vaccination is a key factor in evaluating the impact of vaccination campaigns. We provide a general framework which will be useful for the next pandemic waves as well. PMID:21361404

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

    PubMed

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

    2011-07-01

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

  20. Boosting Heterosubtypic Neutralization Antibodies in Recipients of 2009 Pandemic H1N1 Influenza Vaccine

    PubMed Central

    Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan

    2012-01-01

    Background. A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. Methods. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. Results. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Conclusions. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations. PMID:22052887

  1. [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

    . Predominance of B/Victoria lineage were observed during 2011-2012 season while the rest of the majority were B/Yamagata. The positivity rates of other respiratory viruses which were also analyzed in the scope of sentinel influenza surveillance were similar to influenza positivity for all seasons except 2010-2011. This fact has emphasized that, those viruses were also responsible for influenza-like illness especially during the early and late phases of the season. In conclusion, monitoring of the antigenic and genetic characteristics of influenza viruses by surveillance studies is essential for the early detection of potential pandemic variants as well as to ensure similarities among the circulating strains and the corresponding vaccine strains.

  2. [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

    . Predominance of B/Victoria lineage were observed during 2011-2012 season while the rest of the majority were B/Yamagata. The positivity rates of other respiratory viruses which were also analyzed in the scope of sentinel influenza surveillance were similar to influenza positivity for all seasons except 2010-2011. This fact has emphasized that, those viruses were also responsible for influenza-like illness especially during the early and late phases of the season. In conclusion, monitoring of the antigenic and genetic characteristics of influenza viruses by surveillance studies is essential for the early detection of potential pandemic variants as well as to ensure similarities among the circulating strains and the corresponding vaccine strains. PMID:27525396

  3. Assessing and responding in real time to online anti-vaccine sentiment during a flu pandemic.

    PubMed

    Seeman, Neil; Ing, Alton; Rizo, Carlos

    2010-01-01

    The perceived safety of vaccination is an important explanatory factor for vaccine uptake and, consequently, for rates of illness and death. The objectives of this study were (1) to evaluate Canadian attitudes around the safety of the H1N1 vaccine during the fall 2009 influenza pandemic and (2) to consider how public health communications can leverage the Internet to counteract, in real time, anti-vaccine sentiment. We surveyed a random sample of 175,257 Canadian web users from October 27 to November 19, 2009, about their perceptions of the safety of the HINI vaccine. In an independent analysis, we also assessed the popularity of online flu vaccine-related information using a tool developed for this purpose. A total of 27,382 unique online participants answered the survey (15.6% response rate). Of the respondents, 23.4% considered the vaccine safe, 41.4% thought it was unsafe and 35.2% reported ambivalence over its safety. Websites and blog posts with anti-vaccine sentiment remained popular during the course of the pandemic. Current public health communication and education strategies about the flu vaccine can be complemented by web analytics that identify, track and neutralize anti-vaccine sentiment on the Internet, thus increasing perceived vaccine safety. Counter-marketing strategies can be transparent and collaborative, engaging online "influencers" who spread misinformation.

  4. Mass vaccination for the 2009 H1N1 pandemic: approaches, challenges, and recommendations.

    PubMed

    Rambhia, Kunal J; Watson, Matthew; Sell, Tara Kirk; Waldhorn, Richard; Toner, Eric

    2010-12-01

    The 2009 H1N1 pandemic stimulated a nationwide response that included a mass vaccination effort coordinated at the federal, state, and local levels. This article examines a sampling of state and local efforts during the pandemic in order to better prepare for future public health emergencies involving mass distribution, dispensing, and administration of medical countermeasures. In this analysis, the authors interviewed national, state, and local leaders to gain a better understanding of the accomplishments and challenges of H1N1 vaccination programs during the 2009-10 influenza season. State and local health departments distributed and administered H1N1 vaccine using a combination of public and private efforts. Challenges encountered during the vaccination campaign included the supply of and demand for vaccine, prioritization strategies, and local logistics. To improve the response capabilities to deal with infectious disease emergencies, the authors recommend investing in technologies that will assure a more timely availability of the needed quantities of vaccine, developing local public health capacity and relationships with healthcare providers, and enhancing federal support of state and local activities. The authors support in principle the CDC recommendation to vaccinate annually all Americans over 6 months of age against seasonal influenza to establish a standard of practice on which to expand the ability to vaccinate during a pandemic. However, expanding seasonal influenza vaccination efforts will be an expensive and long-term investment that will need to be weighed against anticipated benefits and other public health needs. Such investments in public health infrastructure could be important for building capacity and practice for distributing, dispensing, and administering countermeasures in response to a future pandemic or biological weapons attack.

  5. "Wait and see" vaccinating behaviour during a pandemic: a game theoretic analysis.

    PubMed

    Bhattacharyya, Samit; Bauch, Chris T

    2011-07-26

    During the 2009 H1N1 pandemic, many individuals did not seek vaccination immediately but rather decided to "wait and see" until further information was available on vaccination costs. This behaviour implies two sources of strategic interaction: as more individuals become vaccinated, both the perceived vaccination cost and the probability that susceptible individuals become infected decline. Here we analyze the outcome of these two strategic interactions by combining game theory with a disease transmission model during an outbreak of a novel influenza strain. The model exhibits a "wait and see" Nash equilibrium strategy, with vaccine delayers relying on herd immunity and vaccine safety information generated by early vaccinators. This strategic behaviour causes the timing of the epidemic peak to be strongly conserved across a broad range of plausible transmission rates, in contrast to models without such adaptive behaviour. The model exhibits not only feedback mechanisms but also a feed-forward mechanism: a high initial perceived vaccination cost perpetuates high perceived vaccine costs (and lower vaccine coverage) throughout the remainder of the outbreak. This suggests that any effect of risk communication at the start of a pandemic outbreak will be amplified compared to the same amount of risk communication effort distributed throughout the outbreak.

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

    PubMed

    Matrajt, Laura; Britton, Tom; Halloran, M Elizabeth; Longini, Ira M

    2015-12-01

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

  7. Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives.

    PubMed

    Song, Joon Young; Noh, Ji Yun; Choi, Won Suk; Cheong, Hee Jin; Kim, Woo Joo

    2015-01-01

    Influenza is a major cause of substantial morbidity and mortality in humans every year. Vaccination is the main strategy to prevent influenza infection, but antiviral agents also play an important role in the control of both seasonal and pandemic influenza. During the influenza A/H1N1 pandemic in 2009, early prompt antiviral therapy may have reduced the severity of the influenza outcomes including pneumonia, hospitalization and mortality in the Republic of Korea. Since the 2009 H1N1 pandemic, there have been increasing usages of antiviral agents for the treatment of patients with seasonal influenza. Although currently rare, antiviral resistance among influenza viruses may emerge and increase with increased use of neuraminidase inhibitors. New agents with different modes of action are under investigation, including favipiravir, DAS181, nitazoxanide and broad-spectrum neutralizing monoclonal antibodies. Data are limited with respect to high-dose and combination antiviral therapies. So, clinical trials are warranted to evaluate diverse antiviral combinations that may be synergistic and less likely to induce breakthrough resistance.

  8. Influenza pandemic planning.

    PubMed

    Cox, Nancy J; Tamblyn, Susan E; Tam, Theresa

    2003-05-01

    Periodically, novel influenza viruses emerge and spread rapidly through susceptible populations, resulting in worldwide epidemics or pandemics. Three pandemics occurred in the 20th century. The first and most devastating of these, the "Spanish Flu" (A/H1N1) pandemic of 1918-1919, is estimated to have resulted in 20-50 million or more deaths worldwide, with unusually high mortality among young adults [C.W. Potter, Chronicle of influenza pandemics, in: K.G. Nicholson, R.G. Webster, A.J. Hay (Eds.), Textbook of Influenza, Blackwell Science, Oxford, 1998, p. 3]. Mortality associated with the 1957 "Asian Flu" (A/H2N2) and the 1968 "Hong Kong Flu" (A/H3N2) pandemics was less severe, with the highest excess mortality in the elderly and persons with chronic diseases [J. Infect. Dis. 178 (1998) 53]. However, considerable morbidity, social disruption and economic loss occurred during both of these pandemics [J. Infect. Dis. 176 (Suppl. 1) (1997) S4]. It is reasonable to assume that future influenza pandemics will occur, given historical evidence and current understanding of the biology, ecology, and epidemiology of influenza. Influenza viruses are impossible to eradicate, as there is a large reservoir of all subtypes of influenza A viruses in wild aquatic birds. In agricultural-based communities with high human population density such as are found in China, conditions exist for the emergence and spread of pandemic viruses. It is also impossible to predict when the next pandemic will occur. Moreover, the severity of illness is also unpredictable, so contingency plans must be put in place now during the inter-pandemic period. These plans must be flexible enough to respond to different levels of disease. PMID:12686098

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  10. Critical immune and vaccination thresholds for determining multiple influenza epidemic waves

    PubMed Central

    Matrajt, Laura; Longini, Ira M.

    2013-01-01

    Previous influenza pandemics (1918, 1957, and 1968) have all had multiple waves. The 2009 pandemic influenza A(H1N1) (pandemic H1N1) started in April 2009 and was followed, in the United States (US) and temperate Northern Hemisphere, by a second wave during the fall of 2009. The ratio of susceptible and immune individuals in a population at the end of a wave determines the potential and magnitude of a subsequent wave. As influenza vaccines are not completely protective, there was a combined immunity in the population at the beginning of 2010 (due to vaccination and due to previous natural infection), and it was uncertain if this mixture of herd immunity was enough to prevent a third wave of pandemic influenza during the winter of 2010. Motivated by this problem, we developed a mathematical deterministic two-group epidemic model with vaccination and calibrated it for the 2009 pandemic H1N1. Then, applying methods from mathematical epidemiology we developed a scheme that allowed us to determine critical thresholds for vaccine-induced and natural immunity that would prevent the spread of influenza. Finally, we estimated the level of combined immunity in the US during winter 2010. Our results suggest that a third wave was unlikely if the basic reproduction number R0 were below 1.6, plausible if the original R0 was 1.6, and likely if the original R0 was 1.8 or higher. Given that the estimates for the basic reproduction number for pandemic influenza place it in the range between 1.4 and 1.6 [1, 2, 3, 4, 5, 6, 7], our approach accurately predicted the absence of a third wave of influenza in the US during the winter of 2010. We also used this scheme to accurately predict the second wave of pandemic influenza in London and the West Midlands, UK during the fall of 2009. PMID:22325011

  11. 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

  12. A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

    PubMed

    Feltelius, N; Persson, I; Ahlqvist-Rastad, J; Andersson, M; Arnheim-Dahlström, L; Bergman, P; Granath, F; Adori, C; Hökfelt, T; Kühlmann-Berenzon, S; Liljeström, P; Maeurer, M; Olsson, T; Örtqvist, Å; Partinen, M; Salmonson, T; Zethelius, B

    2015-10-01

    In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar

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

    PubMed

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)-forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

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

    PubMed Central

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

  15. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Development of vaccines to control the worldwide tuberculosis pandemic.

    PubMed

    Hoft, Daniel F

    2014-01-01

    Mycobacterium tuberculosis (Mtb) infection and tuberculosis (TB) disease are major public health problems. Available BCG vaccines are partially effective against severe disease, but have not reduced the overall prevalence of TB infection and disease. A third of the world's population is latently infected with Mtb, and therefore more effective prophylactic and therapeutic vaccines are urgently needed. The Hoft laboratory and the Saint Louis University Center for Vaccine Development (SLUCVD) are actively pursuing these important goals.

  19. Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

    PubMed

    Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

    2015-06-01

    Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

  20. Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

    PubMed

    Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

    2015-06-01

    Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

  1. The human potential of a recombinant pandemic influenza vaccine produced in tobacco plants.

    PubMed

    Jul-Larsen, Åsne; Madhun, Abdullah S; Brokstad, Karl A; Montomoli, Emanuele; Yusibov, Vidadi; Cox, Rebecca J

    2012-05-01

    Rapid production of influenza vaccine antigen is an important challenge when a new pandemic occurs. Production of recombinant antigens in plants is a quick, cost effective and up scalable new strategy for influenza vaccine production. In this study, we have characterized a recombinant influenza haemagglutinin antigen (HAC1) that was derived from the 2009 pandemic H1N1 (pdmH1N1) virus and expressed in tobacco plants. Volunteers vaccinated with the 2009 pdmH1N1 oil-in-water adjuvanted vaccine provided serum and lymphocyte samples that were used to study the immunogenic properties of the HAC1 antigen in vitro. By 7 d post vaccination, the vaccine fulfilled the licensing criteria for antibody responses to the HA detected by haemagglutination inhibition and single radial hemolysis. By ELISA and ELISPOT analysis we showed that HAC1 was recognized by specific serum antibodies and antibody secreting cells, respectively. We conducted a kinetic analysis and found a peak of serum HAC1 specific antibody response between day 14 and 21 post vaccination by ELISA. We also detected elevated production of IL-2 and IFNγ and low frequencies of CD4(+) T cells producing single or multiple Th1 cytokines after stimulating PBMCs (peripheral blood mononuclear cells) with the HAC1 antigen in vitro. This indicates that the antigen can interact with T cells, although confirming an effective adjuvant would be required to improve the T-cell stimulation of plant based vaccines. We conclude that the tobacco derived recombinant HAC1 antigen is a promising vaccine candidate recognized by both B- and T cells. PMID:22634440

  2. Pandemic preparedness with live attenuated influenza vaccines based on A/Leningrad/134/17/57 master donor virus.

    PubMed

    Rudenko, Larisa; Isakova-Sivak, Irina

    2015-03-01

    Continuously evolving avian influenza viruses pose a constant threat to the human public health. In response to this threat, a number of pandemic vaccine candidates have been prepared and evaluated in animal models and clinical trials. This review summarizes the data from the development and preclinical and clinical evaluation of pandemic live attenuated influenza vaccines (LAIV) based on Russian master donor virus A/Leningrad/134/17/57. LAIV candidates of H5N1, H5N2, H7N3, H1N1 and H2N2 subtypes were safe, immunogenic and protected animals from challenge with homologous and heterologous viruses. Clinical trials of the pandemic LAIVs demonstrated their safety and immunogenicity for healthy adult volunteers. The vaccine viruses were infectious, genetically stable and did not transmit to unvaccinated contacts. In addition, here we discuss criteria for the assessment of pandemic LAIV immunogenicity and efficacy necessary for their licensure.

  3. The ethics of sharing preliminary research findings during public health emergencies: a case study from the 2009 influenza pandemic.

    PubMed

    Crowcroft, N S; Rosella, L C; Pakes, B N

    2014-01-01

    During the 2009 A(H1N1) influenza pandemic, a suite of studies conducted in Canada showed an unexpected finding, that patients with medically attended laboratory-confirmed pandemic influenza were more likely to have received seasonal influenza vaccination than test-negative control patients. Different bodies, including scientific journals and government scientific advisory committees, reviewed the evidence simultaneously to determine its scientific validity and implications. Decision-making was complicated when the findings made their way into the media. The normal trajectory of non-urgent research includes peer-review publication after which decision-makers can process the information taking into account other evidence and logistic considerations. In the situation that arose, however, the congruence of an unexpected finding and the simultaneous review of the evidence both within and outside the traditional peer-review sphere raised several interesting issues about how to deal with emerging evidence during a public health emergency. These events are used in this article to aid discussion of the complex interrelationship between researchers, public health decision-makers and scientific journals, the trade-offs between sharing information early and maintaining the peer-review quality assurance process, and to emphasise the need for critical reflection on the practical and ethical norms that govern the way in which research is evaluated, published and communicated in public health emergencies. PMID:24970372

  4. The ethics of sharing preliminary research findings during public health emergencies: a case study from the 2009 influenza pandemic.

    PubMed

    Crowcroft, N S; Rosella, L C; Pakes, B N

    2014-06-19

    During the 2009 A(H1N1) influenza pandemic, a suite of studies conducted in Canada showed an unexpected finding, that patients with medically attended laboratory-confirmed pandemic influenza were more likely to have received seasonal influenza vaccination than test-negative control patients. Different bodies, including scientific journals and government scientific advisory committees, reviewed the evidence simultaneously to determine its scientific validity and implications. Decision-making was complicated when the findings made their way into the media. The normal trajectory of non-urgent research includes peer-review publication after which decision-makers can process the information taking into account other evidence and logistic considerations. In the situation that arose, however, the congruence of an unexpected finding and the simultaneous review of the evidence both within and outside the traditional peer-review sphere raised several interesting issues about how to deal with emerging evidence during a public health emergency. These events are used in this article to aid discussion of the complex interrelationship between researchers, public health decision-makers and scientific journals, the trade-offs between sharing information early and maintaining the peer-review quality assurance process, and to emphasise the need for critical reflection on the practical and ethical norms that govern the way in which research is evaluated, published and communicated in public health emergencies.

  5. Public health and economic benefits of new pediatric influenza vaccination programs in Argentina

    PubMed Central

    Giglio, Norberto; Gentile, Angela; Lees, Lydia; Micone, Paula; Armoni, Judith; Reygrobellet, Camille; Crepey, Pascal

    2012-01-01

    Background: Argentina’s population was heavily affected by the 2009 influenza pandemic, particularly children, in whom incidence of seasonal influenza is consistently high. Following the pandemic, Argentinean national recommendations for pediatric vaccination against A/H1N1 influenza were defined for all children aged up to five years, in line with programs implemented by national authorities elsewhere. Economic evaluations have found that vaccination programs for this population against seasonal influenza are cost-effective, if not cost-saving in many countries. Recently, Argentina decided to routinely vaccinate against influenza children aged 6–23 mo-old. But, the economic value of such strategies for the country has never been assessed.   Methods: A model was developed to assess the value of four different vaccination strategies: (1) no pediatric vaccination; (2) vaccination of 6–23 mo-old children; (3) vaccination of 6–36 mo-old children; (4) vaccination of 6 mo−5 y-old children. We first estimated community health benefits of vaccination then we evaluated the economic and quality-of-life impact of these strategies on the population. Data used in the model come from surveillance networks, published literature, national databases and retrospective hospital-based data. Results: Pediatric influenza vaccination benefited not only children but also the overall community, due to decreased disease transmission. Our results showed that the recent decision by Argentina to vaccinate 6–23 mo-old children is cost-effective as would be the incremental vaccination of broader age groups. Conclusions: Results from this study are consistent with previous analyses in other countries confirming that implementing influenza pediatric vaccination programs can be highly cost-effective through individual- and community protection against the disease. PMID:22330959

  6. An avian live attenuated master backbone for potential use in epidemic and pandemic influenza vaccines.

    PubMed

    Hickman, Danielle; Hossain, Md Jaber; Song, Haichen; Araya, Yonas; Solórzano, Alicia; Perez, Daniel R

    2008-11-01

    The unprecedented emergence in Asia of multiple avian influenza virus (AIV) subtypes with a broad host range poses a major challenge in the design of vaccination strategies that are both effective and available in a timely manner. The present study focused on the protective effects of a genetically modified AIV as a source for the preparation of vaccines for epidemic and pandemic influenza. It has previously been demonstrated that a live attenuated AIV based on the internal backbone of influenza A/Guinea fowl/Hong Kong/WF10/99 (H9N2), called WF10att, is effective at protecting poultry species against low- and high-pathogenicity influenza strains. More importantly, this live attenuated virus provided effective protection when administered in ovo. In order to characterize the WF10att backbone further for use in epidemic and pandemic influenza vaccines, this study evaluated its protective effects in mice. Intranasal inoculation of modified attenuated viruses in mice provided adequate protective immunity against homologous lethal challenges with both the wild-type influenza A/WSN/33 (H1N1) and A/Vietnam/1203/04 (H5N1) viruses. Adequate heterotypic immunity was also observed in mice vaccinated with modified attenuated viruses carrying H7N2 surface proteins. The results presented in this report suggest that the internal genes of a genetically modified AIV confer similar protection in a mouse model and thus could be used as a master donor strain for the generation of live attenuated vaccines for epidemic and pandemic influenza.

  7. HEALTH AND ECONOMIC BENEFITS OF EARLY VACCINATION FOR A HUMAN INFLUENZA A (H7N9) PANDEMIC

    PubMed Central

    Khazeni, Nayer; Hutton, David W; Collins, Ine; Garber, Alan M; Owens, Douglas K

    2014-01-01

    Background 2009 pandemic vaccination occurred late, limiting its benefits. Influenza A (H7N9) is causing high morbidity and mortality in China, and researchers have modified A (H5N1) to transmit via aerosol, again heightening concerns about pandemic influenza preparedness. Objective We sought to determine how much more quickly a vaccination program should be implemented to reduce infections, deaths, and healthcare costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1). Design We used a dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city. Data Sources Literature and expert opinion. Target Population Residents of a U.S. metropolitan city with characteristics similar to New York City. Perspective Societal. Time Horizon Lifetime. Interventions Vaccination of 30% of the population at 4 or 6 months. Outcome Measures Infections and deaths averted, cost-effectiveness. Results of Base Case Analysis 48,254 would die in 12 months; vaccinating at 9 months would avert 2,365 of these deaths. Vaccinating at 6 months would save 5,775 additional lives and $51 million at a city level. Further accelerating delivery to 4 months would save an additional 5,633 lives and $50 million. Results of Sensitivity Analysis In the event of a vaccine delay to 9 months, increasing reductions in contacts via non-pharmaceutical interventions by 8% would yield a similar reduction in infections and deaths as vaccination at 4 months. Limitations The model is not designed to evaluate programs targeting specific populations such as children or individuals with comorbidities. Conclusions Vaccination in an influenza A (H7N9) pandemic would need to be performed far more rapidly than in 2009 to substantially reduce morbidity, mortality, and healthcare costs. Maximizing non-pharmacological interventions can substantially mitigate the pandemic until matched vaccine becomes available. PMID:24842415

  8. Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis.

    PubMed

    Yin, J Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert

    2011-09-01

    The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection.

  9. Factors Affecting Medical Students' Uptake of the 2009 Pandemic Influenza A (H1N1) Vaccine.

    PubMed

    Lee, Siang I; Aung, Ei M; Chin, Ik S; Hing, Jeremy W; Mummadi, Sanghamitra; Palaniandy, Ghunavadee D; Jordan, Rachel

    2012-01-01

    Background. Pandemic influenza vaccination rate amongst healthcare workers in England 2009/2010 was suboptimal (40.3%). Targeting medical students before they enter the healthcare workforce is an attractive future option. This study assessed the H1N1 vaccine uptake rate amongst medical students and factors that influenced this. Methods. Anonymised, self-administered questionnaire at a medical school. Results. The uptake rate amongst 126 medical students offered the vaccine was 49.2% and intended uptake amongst 77 students was 63.6%. Amongst those offered the vaccine, the strongest barriers to acceptance were fear of side effects (67.9%), lack of vaccine information (50.9%), lack of perceived risk (45.3%), and inconvenience (35.8%). Having a chronic illness (OR 3.4 (95% CI 1.2-10.2)), 4th/5th year of study (OR 3.0 (95% CI 1.3-7.1)), and correct H1N1 knowledge (OR 2.6 (95% CI 1.1-6.0)) were positively associated with uptake. Non-white ethnicity was an independent negative predictor of uptake (OR 0.4 (95% CI 0.2-0.8)). Students who accepted the H1N1 vaccine were three times more likely (OR 3.1 (95% CI 1.2-7.7)) to accept future seasonal influenza vaccination. Conclusion. Efforts to increase uptake should focus on routine introduction of influenza vaccine and creating a culture of uptake during medical school years, evidence-based education on vaccination, and improving vaccine delivery. PMID:23251794

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

    PubMed

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

    2013-03-15

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

  11. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development. PMID:24551202

  12. Trends in influenza vaccination coverage in Portugal from 1998 to 2010: effect of major pandemic threats

    PubMed Central

    2013-01-01

    Background Vaccination is the key measure available for prevention of the public health burden of annual influenza epidemics. This article describes national trends in seasonal influenza vaccine (IV) coverage in Portugal from 1998/99 to 2010/11, analyzes progress towards meeting WHO 2010 coverage goals, and addresses the effect of major public health threats of the last 12 years (SARS in 2003/04, influenza A (H5N1) in 2005/06, and the influenza A (H1N1)2009 pandemic) on vaccination trends. Methods The National Institute of Health surveyed (12 times) a random sample of Portuguese families. IV coverage was estimated and was adjusted for age distribution and country region. Independence of age and sex coverage distribution was tested using a modified F-statistic with a 5% significance level. The effect of SARS, A (H5N1), and the A (H1N1)2009 pandemic was tested using a meta-regression model. The model was adjusted for IV coverage in the general population and in the age groups. Results Between 1998/99 and 2010/11 IV, coverage in the general population varied between 14.2% (CI 95%: 11.6%–16.8%) and 17.5% (CI 95%: 17.6%–21.6%). There was no trend in coverage (p = 0.097). In the younger age group (<15 years) a declining trend was identified until 2008/09 (p = 0.005). This trend reversed in 2009/10. There was also a gradual and significant increase in seasonal IV coverage in the elderly (p for trend < 0.001). After 2006/07, IV coverage remained near 50%. Adjusting for baseline trends, there was significantly higher coverage in the general population in 2003/04 (p = 0.032) and 2005/06 (p = 0.018). The high coverage observed in the <15-year age group in season 2009/10 was also significant (p = 0.015). Conclusions IV coverage in the elderly population displayed an increasing trend, but the 75% WHO 2010 target was not met. This result indicates that influenza vaccination strategy should be improved to meet the ambitious WHO coverage goals. The

  13. 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.

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

    PubMed

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

    2013-03-15

    With the current enzootic circulation of highly pathogenic avian influenza viruses, the ability to increase global pandemic influenza vaccine production capacity is of paramount importance. This has been highlighted by, and is one of the main pillars of, the WHO Global Action Plan for Influenza Vaccines (GAP). Such capacity expansion is especially relevant in developing countries. The Vaccine Formulation Laboratory at University of Lausanne is engaged in the technology transfer of an antigen-sparing oil-in-water adjuvant in order to empower developing countries vaccine manufacturers to increase pandemic influenza vaccine capacity. In a one-year project funded by United States Department of Health and Human Services, the Vaccine Formulation Laboratory transferred the process know-how and associated equipment for the pilot-scale manufacturing of an oil-in-water adjuvant to Bio Farma, Indonesia's state-owned vaccine manufacturer, for subsequent formulation with H5N1 pandemic influenza vaccines. This paper describes the experience acquired and lessons learnt from this technology transfer project. PMID:22884665

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

    PubMed

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

    2013-03-15

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

  16. 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.

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

    PubMed

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

    2010-12-09

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

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

    PubMed

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

    2010-12-01

    In a pandemic setting, surveillance is essential to monitor the spread of the disease and assess its impact. Appropriate mitigation and healthcare preparedness strategies depend on fast and accurate epidemic surveillance data. During the 2009 influenza A(H1N1) pandemic, rapid improvements in influenza surveillance were made in Iceland. Here, we describe the improvements made in influenza surveillance during the pandemic , which could also be of great value in outbreaks caused by other pathogens. Following the raised level of pandemic influenza alert in April 2009, influenza surveillance was intensified. A comprehensive automatic surveillance system for influenza-like illness was developed, surveillance of influenza-related deaths was established and laboratory surveillance for influenza was strengthened. School absenteeism reports were also collected and compared with results from the automatic surveillance system. The first case of 2009 pandemic influenza A(H1N1) was diagnosed in Iceland in May 2009, but sustained community transmission was not confirmed until mid-August. The pandemic virus circulated during the summer and early autumn before an abrupt increase in the number of cases was observed in October. There were large outbreaks in elementary schools for children aged 6–15 years throughout the country that peaked in late October. School absenteeism reports from all elementary schools in Iceland gave a similar epidemiological curve as that from data from the healthcare system. Estimates of the proportion of the population infected with the pandemic virus ranged from 10% to 22%. This study shows how the sudden need for improved surveillance in the pandemic led to rapid improvements in data collection in Iceland. This reporting system will be improved upon and expanded to include other notifiable diseases, to ensure accurate and timely collection of epidemiological data. PMID:21163181

  19. Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 - a rapid epidemiological and virological assessment.

    PubMed

    Emborg, Hanne Dorthe; Krause, Tyra Grove; Nielsen, Lene; Thomsen, Marianne Kragh; Christiansen, Claus Bohn; Skov, Marianne Nielsine; Nielsen, Xiaohui Chen; Weinreich, Lenette Sandborg; Fischer, Thea Kølsen; Rønn, Jesper; Trebbien, Ramona

    2016-01-01

    In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case-control design. The adjusted VE against influenza A(H1N1)pdm09 was 35.0% (95% confidence interval (CI): 11.1-52.4) and against influenza B 4.1% (95% CI: -22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1.

  20. Evaluation of Haemagglutinin Content by RP-HPLC to Generate Pandemic Influenza Vaccine

    PubMed Central

    Kang, Hyunkyung; Roh, Hang Sik; Song, Hyemin; Lee, Kwangmoon; Chung, Seung-Tae; Ban, Sang-ja; Mo, In Pil; An, Beum-Soo; Ahn, Chi-Young

    2016-01-01

    The potency of influenza vaccine is determined based on its hemagglutinin (HA) content. In general, single radial immunodiffusion (SRID) assay has been utilized as the standard method to measure HA content. However, preparation of reagents for SRID such as antigen and antibody takes approximately 2~3 months, which causes delays in the development of influenza vaccine. Therefore, quantification of HA content by other alternative methods is required. In this study, we measured HA contents of H1N1 antigen and H1N1 influenza vaccine by reverse phase-high performance liquid chromatography (RP-HPLC) methods. The presence of HA1 and HA2 was investigated by silver staining and Western blot assay. In addition, accuracy and repeatability of HA measurement by RP-HPLC were evaluated. Comparison of HA concentration by SRID and RP-HPLC revealed a precise correlation between the two methods. Our results suggest that RP-HPLC assay can replace SRID in the event of a pandemic flu outbreak for rapid vaccine development.

  1. 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

  2. Safety of AS03-adjuvanted split-virion H1N1 (2009) pandemic influenza vaccine: a prospective cohort study

    PubMed Central

    Nazareth, Irwin; Tavares, Fernanda; Rosillon, Dominique; Haguinet, François; Bauchau, Vincent

    2013-01-01

    Objectives To assess the safety of an AS03-adjuvanted split virion H1N1 (2009) vaccine (Pandemrix) in persons vaccinated during the national pandemic influenza vaccination campaign in the UK. Design Prospective, cohort, observational, postauthorisation safety study. Setting 87 general practices forming part of the Medical Research Council General Practice Research Framework and widely distributed throughout England. Participants A cohort of 9143 individuals aged 7 months to 97 years who received at least one dose of the AS03-adjuvanted H1N1 pandemic vaccine during the national pandemic influenza vaccination campaign in the UK was enrolled. 94% completed the 6-month follow-up. Exclusion criteria were previous vaccination with other H1N1 pandemic vaccine and any child in care. Primary and secondary outcome measures Medically attended adverse events (MAEs) occurring within 31 days after any dose, serious adverse events (SAEs) and adverse events of special interest (AESIs) following vaccination were collected for all participants. Solicited adverse events (AEs) were assessed in a subset of participants. Results MAEs were reported in 1219 participants and SAEs in 113 participants during the 31-day postvaccination period. The most frequently reported MAEs and SAEs were consistent with events expected to be reported during the winter season in this population: lower respiratory tract infections, asthma and pneumonia. The most commonly reported solicited AEs were irritability in young children aged <5 years (61.8%), muscle aches in children aged 5–17 years (61.9%) and adults (46.9%). 18 AESIs, experienced by 14 patients, met the criteria to be considered for the observed-to-expected analyses. AESIs above the expected number were neuritis (1 case within 31 days) and convulsions (8 cases within 181 days). There were 41 deaths during the 181-day period after vaccination, fewer than expected. Conclusions Results indicate that the AS03-adjuvanted H1N1 pandemic

  3. DNA Vaccination Elicits Protective Immune Responses against Pandemic and Classic Swine Influenza Viruses in Pigs ▿ †

    PubMed Central

    Gorres, J. Patrick; Lager, Kelly M.; Kong, Wing-Pui; Royals, Michael; Todd, John-Paul; Vincent, Amy L.; Wei, Chih-Jen; Loving, Crystal L.; Zanella, Eraldo L.; Janke, Bruce; Kehrli, Marcus E.; Nabel, Gary J.; Rao, Srinivas S.

    2011-01-01

    Swine influenza is a highly contagious viral infection in pigs that significantly impacts the pork industry due to weight loss and secondary infections. There is also the potential of a significant threat to public health, as was seen in 2009 when the pandemic H1N1 influenza virus strain emerged from reassortment events among avian, swine, and human influenza viruses within pigs. As classic and pandemic H1N1 strains now circulate in swine, an effective vaccine may be the best strategy to protect the pork industry and public health. Current inactivated-virus vaccines available for swine influenza protect only against viral strains closely related to the vaccine strain, and egg-based production of these vaccines is insufficient to respond to large outbreaks. DNA vaccines are a promising alternative since they can potentially induce broad-based protection with more efficient production methods. In this study we evaluated the potentials of monovalent and trivalent DNA vaccine constructs to (i) elicit both humoral and gamma interferon (IFN-γ) responses and (ii) protect pigs against viral shedding and lung disease after challenge with pandemic H1N1 or classic swine H1N1 influenza virus. We also compared the efficiency of a needle-free vaccine delivery method to that of a conventional needle/syringe injection. We report that DNA vaccination elicits robust serum antibody and cellular responses after three immunizations and confers significant protection against influenza virus challenge. Needle-free delivery elicited improved antibody responses with the same efficiency as conventional injection and should be considered for development as a practical alternative for vaccine administration. PMID:21918118

  4. [Attitudes and side effects related to pandemic influenza A (H1N1) vaccination in healthcare personnel].

    PubMed

    Ormen, Bahar; Türker, Nesrin; Vardar, Ilknur; Kaptan, Figen; El, Sibel; Ural, Serap; Kaya, Fatih; Coşkun, Nejat Ali

    2012-01-01

    The aims of this study were to evaluate the attitudes towards H1N1 vaccination and to determine the safety and side effects following 2009 pandemic influenza A (H1N1) vaccination. Pandemic influenza vaccine had been administered to the healthcare personnel in our research and training hospital in December 2009. The rate being vaccinated was established as 40% (800/2000). Four months following vaccination, the opinions about vaccination were asked to the healthcare workers, and also side effects were questioned to the vaccinated group. Two different questionnaires (for vaccinated and unvaccinated subjects) were delivered to the volunteers who agreed to participate in the study. Demographic features, reasons related to being vaccinated or not, were questioned. The vaccinated group was also questioned for the presence of chronic diseases, previous vaccinations (pandemic/seasonal influenza), local or systemic reactions that develop after vaccination. A total of 332 volunteers participated in the questionnaire. Of them 247 (74.4%) were vaccinated and 85 (25.6%) were unvaccinated. Male/female ratio of the participants was 1.2, and 55.7% of them were older than 30-year-old. Most of the participants (82.8%) were highly educated (high school and faculty-graduated). Vaccination rates were found statistically significant in advanced age group compared to young adults (p= 0.042); in male gender compared to females (p= 0.001) and in parents compared to subjects who didn't have children (p= 0.021). Vaccination rates were observed to be higher (57.5%) in non-medical staff (cleaning employers, administrative personnel, etc.) than the physicians (29.1%) and nurses (13.4%), and the rate was also high (54.7%) in personnel who worked in intensive care units, emergency department and administrative units than the personnel who worked in the clinics of internal medicine (22.3%) and surgery (23.1%) (p= 0.001). The most important causes of rejecting vaccination were being afraid of the

  5. 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.

  6. 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

  7. A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations

    PubMed Central

    2010-01-01

    Background Influenza is one of the most common vaccine-preventable diseases in travellers. By performing two cross-sectional questionnaire surveys during winter 2009 and winter 2010 among European travellers to resource-limited destinations, we aimed to investigate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination. Methods Questionnaires were distributed in the waiting room to the visitors of the University of Zurich Centre for Travel' Health (CTH) in January and February 2009 and January 2010 prior to travel health counselling (CTH09 and CTH10). Questions included demographic data, travel-related characteristics and KAP regarding influenza vaccination. Data were analysed by using SPSS® version 14.0 for Windows. Differences in proportions were compared using the Chi-square test and the significance level was set at p ≤ 0.05. Predictors for seasonal and pandemic influenza vaccination were determined by multiple logistic regression analyses. Results With a response rate of 96.6%, 906 individuals were enrolled and 868 (92.5%) provided complete data. Seasonal influenza vaccination coverage was 13.7% (n = 119). Only 43 (14.2%) participants were vaccinated against pandemic influenza A/H1N1, mostly having received both vaccines simultaneously, the seasonal and pandemic one. Job-related purposes (44, 37%), age > 64 yrs (25, 21%) and recommendations of the family physician (27, 22.7%) were the most often reported reasons for being vaccinated. In the multiple logistic regression analyses of the pooled data increasing age (OR = 1.03, 95% CI 1.01 - 1.04), a business trip (OR = 0.39, 95% CI 0.17 - 0.92) and seasonal influenza vaccination in the previous winter seasons (OR = 12.91, 95% CI 8.09 - 20.58) were independent predictors for seasonal influenza vaccination in 2009 or 2010. Influenza vaccination recommended by the family doctor (327, 37.7%), travel to regions with known high risk of influenza (305, 35.1%), and influenza vaccination

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

    PubMed

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

    2015-01-01

    This updated systematic review and meta-analyses aims to systematically evaluate the cross-protection of seasonal influenza vaccines against the 2009 pandemic A (H1N1) influenza infection, and investigate the potential effect of the influenza strains circulating previous to the pandemic on the association between vaccine receipt and pandemic infection. In addition, subgroup analysis was performed based on the study locations and previous circulating influenza viruses. Relevant articles in English and Chinese from 2009 to October 2013 were systematically searched, and 21 eligible studies were included. For case-control studies, an insignificant 20% reduced risk for pandemic influenza infection based on combined national data (OR = 0.80; 95%CI: 0.60, 1.05) was calculated for people receiving seasonal influenza vaccination. However, for RCTs, an insignificant increase in the risk of seasonal influenza vaccines was observed (RR = 1.27; 95% CI: 0.46, 3.53). For the subgroup analysis, a significant 35% cross-protection was observed in the subgroup where influenza A outbreaks were detected before the 2009 pandemic. Moreover, the results indicated that seasonal influenza vaccination may reduce the risk of influenza-like illnesses (ILIs) (RR = 0.91; 95% CI: 0.84, 0.99). Our findings partially support the hypothesis that seasonal vaccines may offer moderate cross-protection for adults against laboratory-confirmed pandemic influenza A (H1N1) infection and ILIs. Further immunological studies are needed to understand the mechanism underlying these findings. PMID:25692308

  9. 75 FR 55776 - Request for Comments on Vaccine Production and Additional Planning for Future Possible Pandemic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... INFORMATION: Written comments are sought in light of the announced end of the H1N1 influenza pandemic (see... Possible Pandemic Influenza AGENCY: International Trade Administration, Department of Commerce. ACTION... possible pandemic influenza. DATES: Written comments must be submitted on or before October 1,...

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

    PubMed

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

    2014-06-17

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

  11. Attitudes toward and Uptake of H1N1 Vaccine among Health Care Workers during the 2009 H1N1 Pandemic

    PubMed Central

    Henriksen Hellyer, Joan M.; DeVries, Aaron S.; Jenkins, Sarah M.; Lackore, Kandace A.; James, Katherine M.; Ziegenfuss, Jeanette Y.; Poland, Gregory A.; Tilburt, Jon C.

    2011-01-01

    Background Though recommended by many and mandated by some, influenza vaccination rates among health care workers, even in pandemics, remain below optimal levels. The objective of this study was to assess vaccination uptake, attitudes, and distinguishing characteristics (including doctor-nurse differences) of health care workers who did and did not receive the pandemic H1N1 influenza vaccine in late 2009. Methodology/Principal Findings In early 2010 we mailed a self-administered survey to 800 physicians and 800 nurses currently licensed and practicing in Minnesota. 1,073 individuals responded (cooperation rate: 69%). 85% and 62% of Minnesota physicians and nurses, respectively, reported being vaccinated. Accurately estimating the risk of vaccine side effects (OR 2.0; 95% CI 1.5–2.7), agreeing with a professional obligation to be vaccinated (OR 10.1; 95% CI 7.1–14.2), an ethical obligation to follow public health authorities' recommendations (OR 9.9; 95% CI 6.6–14.9), and laws mandating pandemic vaccination (OR 3.1; 95% CI 2.3–4.1) were all independently associated with receiving the H1N1 influenza vaccine. Conclusions/Significance While a majority of health care workers in one midwestern state reported receiving the pandemic H1N1 vaccine, physicians and nurses differed significantly in vaccination uptake. Several key attitudes and perceptions may influence health care workers' decisions regarding vaccination. These data inform how states might optimally enlist health care workers' support in achieving vaccination goals during a pandemic. PMID:22216290

  12. A monoclonal antibody-based immunoassay for measuring the potency of 2009 pandemic influenza H1N1 vaccines

    PubMed Central

    Schmeisser, Falko; Vasudevan, Anupama; Soto, Jackeline; Kumar, Arunima; Williams, Ollie; Weir, Jerry P

    2014-01-01

    Background The potency of inactivated influenza vaccines is determined using a single radial immunodiffusion (SRID) assay. This assay is relatively easy to standardize, it is not technically demanding, and it is capable of measuring the potency of several vaccine strain subtypes in a multivalent vaccine. Nevertheless, alternative methods that retain the major advantages of the SRID, but with a greater dynamic range of measurement and with reduced reagent requirements, are needed. Objectives The feasibility of an ELISA-based assay format was explored as an alternative potency assay for inactivated influenza vaccines. Methods Several murine monoclonal antibodies (mAbs), specific for the 2009 pandemic H1N1 influenza virus hemagglutinin (HA), were evaluated for their potential to capture and quantify HA antigen. Vaccine samples, obtained from four licensed influenza vaccine manufacturers, included monovalent bulk vaccine, monovalent vaccine, and trivalent vaccine. Traditional SRID potency assays were run in parallel with the mAb–ELISA potency assay using the reference antigen standard appropriate for the vaccine samples being tested. Results The results indicated that the ELISA potency assay can quantify HA over a wide range of concentrations, including vaccine at subpotent doses, and the ELISA and SRID potency values correlated well for most vaccine samples. Importantly, the assay was capable of quantifying A/California HA in a trivalent formulation. Conclusions This study demonstrates the general feasibility of the mAb approach and strongly suggests that such ELISAs have potential for continued development as an alternative method to assay the potency of inactivated influenza vaccines. PMID:25087462

  13. Pandemic influenza A (H1N1) in non-vaccinated, pregnant women in Spain (2009-2010).

    PubMed

    Morales-Suárez-Varela, María; González-Candelas, Fernando; Astray, Jenaro; Alonso, Jordi; Castro, Ady; Cantón, Rafael; Galán, Juan Carlos; Garin, Olatz; Soldevila, Núria; Baricot, Maretva; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martín, Vicente; Mayoral, José María; Pumarola, Tomás; Quintana, José Maria; Tamames, Sonia; Llopis-González, Agustín; Domínguez, Angela

    2014-08-01

    The aim of this study was to investigate the main characteristics of non-vaccinated pregnant women who were hospitalised for influenza A (H1N1) pdm09 pandemic versus pregnant women hospitalised for non-influenza-related reasons in Spain, and to characterise the clinical presentation of the disease in this population to facilitate early diagnosis and future action programmes. Understanding influenza infection during pregnancy is important as pregnant women are a high-risk population for increased morbidity from influenza infection. We investigated the socio-demographic and clinical features of 51 non-vaccinated, pregnant women infected with the pandemic influenza A (H1N1) virus in Spain (cases) and compared them to 114 controls (non-vaccinated and non-infected pregnant women) aged 15-44 years. Substantial and significant odd ratios (ORs) for pandemic influenza A (H1N1) were found for the pregnant women who were obese compared with controls (body mass index > 30) (OR 3.03; 95% confidence intervals 1.13-8.11). The more prevalent symptoms observed in pandemic influenza-infected pregnant women were high temperature, cough (82.4%), malaise (80.5%), myalgia (56.1%), and headaches (54.9%). Our results suggest that the initial symptoms and risk factors for infection of pregnant women with the influenza A (H1N1) pdm09 virus are similar to the symptoms and risk factors for seasonal influenza, which make early diagnosis difficult, and reinforces the need to identify and protect high-risk groups.

  14. [Pandemic influenza A (H1N1)v vaccination status and factors affecting vaccination: Ankara and Diyarbakır 2009 data from Turkey].

    PubMed

    Ertek, Mustafa; Sevencan, Funda; Kalaycıoğlu, Handan; Gözalan, Ayşegül; Simşek, Ciğdem; Culha, Gönül; Dorman, Vedat; Ozlü, Ahmet; Arıkan, Füsun; Aktaş, Dilber; Akın, Levent; Korukluoğlu, Gülay; Sevindi, Demet Furkan

    2011-10-01

    In this study, it was aimed to determine the frequency of the symptoms of influenza-like illness during influenza A (H1N1)v pandemic in two provinces where sentinel influenza surveillance was conducted and also to obtain opinions about H1N1 influenza and vaccination, H1N1 vaccination status and factors affecting vaccination. This cross-sectional study was conducted in the provinces of Ankara (capital city, located at Central Anatolia) and Diyarbakır (located at southeastern Anatolia). It was planned to include 455 houses in Ankara and 276 houses in Diyarbakır. The household participation rate in the study was 78.9% and 53.6% for Ankara and Diyarbakır, respectively. Our study was carried out between January-February 2010, with 1164 participants from Ankara and 804 from Diyarbakır, including every household subjects except for infants younger than 11 months and patients with primary/secondary immunodeficiency diseases. Data was collected by site teams consisting of a physician and a healthcare staff with informed consent. Of the participants 45.5% from Ankara and 35.3% from Diyarbakır stated that they had gone through an influenza-like illness. The most frequently indicated clinical symptoms were fatigue/weakness, rhinitis, sore throat and cough. The rates of admission to a physician with influenza like illness complaints were 50.6% and 58.7%; rates of hospitalization due to influenza-like illness were 1% and 1.5%, and rates of antiviral drug use were 3.8% and 1.9%, in Ankara ve Diyarbakır participants, respectively. The rate of personal precautions taken by the subjects for prevention from pandemic influenza were 59% and 53.3%, in Ankara and Diyarbakır, respectively. These precautions most frequently were "hand washing" and "avoiding crowded public areas". H1N1 influenza vaccine was applied in 9.3% of the participants in Ankara and in 3.7% of the participants in Diyarbakır. Vaccination rate was higher in both of the provinces in adults over 25 years old than

  15. Review of strategies to enhance the uptake of seasonal influenza vaccination by Australian healthcare workers.

    PubMed

    Stuart, Michael J

    2012-09-01

    Annual vaccination of healthcare workers (HCWs) against seasonal influenza is recommended by The Australian Immunisation Handbook to prevent personal morbidity and transmission to patients. There are limited data available concerning the uptake of this vaccination by Australian healthcare workers, and few studies have investigated the determinants of this uptake. This report therefore aims to review the seasonal influenza immunisation uptake rates of Australian HCWs, the determinants of these rates, and strategies to improve them. The Cumulative Index to Nursing and Allied Health Literature, PubMed and the Cochrane Library were searched for literature published online between January 2000 and May 2011. A manual search of the grey literature was also undertaken. Studies of influenza pandemic A(H1N1) 2009 immunisation were excluded. Eleven relevant studies were identified. The published data suggests that annual seasonal influenza immunisation rates among Australian HCWs are below recommended levels (range 22%-70%). Factors contributing to the decision to be immunised demonstrate only minor variations from those identified in international samples. There is little high quality evidence to support specific strategies and interventions to increase uptake of immunisation in HCWs. Further high quality research is needed to demonstrate the efficacy of strategies and interventions on HCW immunisation uptake, particularly in Australian samples, and if conventional interventions continue to prove ineffective, policy change to mandatory seasonal influenza immunisation should be considered. PMID:23186238

  16. Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11).

    PubMed

    Mereckiene, J; Cotter, S; Nicoll, A; Lopalco, P; Noori, T; Weber, Jt; D'Ancona, F; Levy-Bruhl, D; Dematte, L; Giambi, C; Valentiner-Branth, P; Stankiewicz, I; Appelgren, E; O Flanagan, D

    2014-04-24

    Since 2008, annual surveys of influenza vaccination policies, practices and coverage have been undertaken in 29 European Union (EU)/ European Economic Area (EEA) countries. After 2009, this monitored the impact of European Council recommendation to increase vaccination coverage to 75% among risk groups. This paper summarises the results of three seasonal influenza seasons: 2008/09, 2009/10 and 2010/11. In 2008/09, 27/29 countries completed the survey; in 2009/10 and 2010/11, 28/29 completed it. All or almost all countries recommended vaccination of older people (defined as those aged ≥50, ≥55, ≥59, ≥60 or ≥65 years), and people aged ≥6 months with clinical risk and healthcare workers. A total of 23 countries provided vaccination coverage data for older people, but only 7 and 10 had data for the clinical risk groups and healthcare workers, respectively. The number of countries recommending vaccination for some or all pregnant women increased from 10 in 2008/09 to 22 in 2010/11. Only three countries could report coverage among pregnant women. Seasonal influenza vaccination coverage during and after the pandemic season in older people and clinical groups remained unchanged in countries with higher coverage. However, small decreases were seen in most countries during this period. The results of the surveys indicate that most EU/EEA countries recommend influenza vaccination for the main target groups; however, only a few countries have achieved the target of 75% coverage among risk groups. Coverage among healthcare workers remained low.

  17. Efficacy of Influenza A H1N1/2009 Vaccine in Hemodialysis and Kidney Transplant Patients

    PubMed Central

    Collado, Silvia; Mir, Marisa; Cao, Higini; Barbosa, Francesc; Serra, Consol; Hidalgo, Carlota; Faura, Anna; Montero, Milagros; García de Lomas, Juan; Horcajada, Juan P.; Puig, Josep M.; Pascual, Julio

    2011-01-01

    Summary Background and objectives Data are needed to assess safety and efficacy of the 2009 pandemic influenza A H1N1 vaccine in renal patients. Design, setting, participants, & measurements We prospectively evaluated seroconversion, predictors of response, and vaccine safety in renal patients. Hemagglutination inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus were performed in 79 transplant patients, 48 hemodialysis patients, and 15 healthy workers before and 1 month after vaccination. Healthy controls and 88 of 127 renal patients were vaccinated. Seroconversion was defined as at least 2 dilutions increase in titer. Results We excluded 19 individuals seroprotected (≥1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96 vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27 nonvaccinated patients, P = 0.007). For vaccinated subgroups, efficacy was 41.8% in transplant patients (P = 0.039 versus nonvaccinated), 33.3% in hemodialysis patients (P = 0.450), and 81.8% in controls. Healthy controls showed better response to vaccine than transplant (P = 0.021) and dialysis (P = 0.012) patients. For the transplant subgroup, longer time after transplantation (P = 0.028) was associated with seroconversion, but no influence was found for age, gender, renal function, or immunosuppression. In the hemodialysis subgroup, younger age was associated with response (55.7 ± 20.8 versus 71.6 ± 10.1 years, P = 0.042), but other specific variables, including Kt/V or time on dialysis, were not. No serious adverse events were reported, and kidney function was stable. Conclusion The novel influenza A 2009 H1N1 vaccine was safe in renal patients, although administration of a single dose of adjuvanted vaccine induced a poor response in these patients. PMID:21852661

  18. Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1) 2009 vaccine

    PubMed Central

    2010-01-01

    Background On the 30th September 2009, the pandemic (H1N1) 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1) 2009 influenza vaccine. Methods We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1) 2009 vaccine and issues relating to uptake and perceived safety. Results Of the 627 respondents, the majority felt that they had a "very low to low" (332/627, 52.9%) risk of acquiring H1N1. 24.5% (154/627) of respondents believed that the disease would "very seriously or extremely" affect their health. Nearly half (305/627, 48.6%) reported that in response to the "swine flu" outbreak they had undertaken one or more of the investigated behavioural changes. Overall, the self-reported likelihood of accepting vaccination against novel H1N1 was 54.7% (343/627). Conclusions While, most participants did not believe they were at high risk of acquiring pandemic H1N1 2009, over half of the sample indicated that they would accept the vaccine. Participants who were vaccinated against the seasonal influenza were more likely to receive the H1N1 vaccine. Concerns about safety, the possibility of side effects and the vaccine development process need to be addressed. PMID:20403201

  19. Public Willingness to Take a Vaccine or Drug Under Emergency Use Authorization during the 2009 H1N1 Pandemic

    PubMed Central

    Kumar, Supriya; Freimuth, Vicki S.; Kidwell, Kelley; Musa, Donald

    2009-01-01

    On April 26, 2009, the United States declared a public health emergency in response to a growing but uncertain threat from H1N1 influenza, or swine flu. In June, the World Health Organization declared a pandemic. In the U.S., hospitalizations due to swine flu numbered 6,506 on August 6, 2009, with 436 deaths; all 50 states have reported cases. The declaration of a public health emergency, followed by the approval of multiple Emergency Use Authorizations (EUAs) by the Food and Drug Administration, allowed the distribution of unapproved drugs or the off-label use of approved drugs to the public. Thus far, there are 2 antiviral medications available to the public as EUA drugs. It is possible that an H1N1 vaccine will be initially released as an EUA in the fall in the first large-scale use of the EUA mechanism. This study explores the public's willingness to use a drug or vaccine under the conditions stipulated in the FDA's nonbinding guidance regarding EUAs. Using Knowledge Networks' panel, we conducted an internet survey with 1,543 adults from a representative sample of the U.S. population with 2 oversamples of African Americans and Spanish-speaking Hispanics. Our completion rate was 62%. We examined willingness to accept an EUA drug or an H1N1 vaccine, the extent of worry associated with taking either, the conditions under which respondents would accept an EUA drug or vaccine, and the impact of language from the EUA fact sheets on people's willingness to accept a drug for themselves or their children. We also examined the association among these variables and race/ethnicity, education level, trust in government, previous vaccine acceptance, and perceived personal consequences from H1N1 influenza. These results provide critical insights into the challenges of communicating about EUA drugs and vaccine in our current pandemic. PMID:19775200

  20. Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers in the major teaching hospital of Sicily (Italy).

    PubMed

    Amodio, Emanuele; Anastasi, Giovanna; Marsala, Maria Grazia Laura; Torregrossa, Maria Valeria; Romano, Nino; Firenze, Alberto

    2011-02-01

    The aim of the study was to investigate factors involved in vaccination acceptance among healthcare workers (HCWs) and adverse reactions rates associated with pandemic influenza vaccination. The study was carried out in the major teaching hospital of Sicily from November 2009 to February 2010 on 2267 HCWs. A total of 407 (18%) HCWs were vaccinated against the 2009 pandemic influenza A (H1N1). A logistic regression analysis indicates an increased risk of non-vaccination against pandemic influenza in females (OR=1.6; 95% CI=1.3-2.1) compared to males, in nurses/technicians/administrative workers (OR=1.7; 95% CI=1.3-2.2) compared to doctors/biologists, and in HCWs who were non-vaccinated against seasonal influenza in 2008-2009 (OR=4.9; 95% CI=3.7-6.5) compared to vaccinated HCWs. Overall, 302 (74.2%) out of 407 questionnaires distributed to vaccinated HCWs were returned within the observation period. One hundred fifty-two workers (50.3%) experienced at least one adverse reaction (30.1%, local reactions; 6.6% systemic reactions and 13.6% both of them). The most frequent side effect of vaccination was pain at the injection site (43.4%). Twelve (3.9%) out of 302 HCWs stated they experienced influenza-like illness episodes during the follow-up period. The use of an adjuvanted vaccine against pandemic influenza A (H1N1) appears to be an effective and safe preventive strategy, showing a prevalence of both local and systemic adverse reactions not very different from that seen after vaccination with non-adjuvanted seasonal influenza vaccine. Despite this finding, vaccination coverage among HCWs remains very low, suggesting the need to implement educational campaigns directed to groups with lower coverage rates.

  1. Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study

    PubMed Central

    Liao, Qiuyan; Cowling, Benjamin; Lam, Wing Tak; Ng, Man Wai; Fielding, Richard

    2010-01-01

    Background Whether information sources influence health protective behaviours during influenza pandemics or other emerging infectious disease epidemics is uncertain. Methodology Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. Principal Findings Trust in formal (government/media) information about influenza was associated with greater reported understanding of A/H1N1 cause (β = 0.36) and A/H1N1 prevention self-efficacy (β = 0.25), which in turn were associated with more hand hygiene (β = 0.19 and β = 0.23, respectively). Trust in informal (interpersonal) information was negatively associated with perceived personal A/H1N1 susceptibility (β = −0.21), which was negatively associated with perceived self-efficacy (β = −0.42) but positively associated with influenza worry (β = 0.44). Trust in informal information was positively associated with influenza worry (β = 0.16) which was in turn associated with greater social distancing (β = 0.36). Multigroup comparisons showed gender differences regarding paths from trust in formal information to understanding of A/H1N1 cause, trust in informal information to understanding of A/H1N1 cause, and understanding of A/H1N1 cause to perceived self-efficacy. Conclusions/Significance Trust in government/media information was more strongly associated with greater self-efficacy and handwashing, whereas trust in informal information was strongly associated with perceived health threat and avoidance behaviour. Risk communication should consider the effect of gender differences. PMID:20967280

  2. Expanding practitioner scopes of practice during public health emergencies: experiences from the 2009 H1N1 pandemic vaccination efforts.

    PubMed

    Courtney, Brooke; Morhard, Ryan; Bouri, Nidhi; Cicero, Anita

    2010-09-01

    In a public health emergency involving significant surges in patients and shortages of medical staff, supplies, and space, temporarily expanding scopes of practice of certain healthcare practitioners may help to address heightened population health needs. Scopes of practice, which are defined by state practice acts, set forth the range of services that licensed practitioners are authorized to perform. The U.S. has had limited experience with temporarily expanding scopes of practice during emergencies. However, during the 2009 H1N1 pandemic response, many states took some form of action to expand the practice scopes of certain categories of practitioners in order to authorize them to administer the pandemic vaccine. No standard legal approach for expanding scopes of practice during emergencies exists across states, and scope of practice expansions during routine, nonemergency times have been the subject of professional society debate and legal action. These issues raise the question of how states could effectively implement expansions for health services beyond administering vaccine and ensure consistency in expansions across states during catastrophic events that require a shift to crisis standards of care. This article provides an overview of scopes of practice, a summary of the range of legal and regulatory approaches used in the U.S. to expand practice scopes for vaccination during the 2009 H1N1 response, and recommendations for future research.

  3. A proposed non-consequentialist policy for the ethical distribution of scarce vaccination in the face of an influenza pandemic.

    PubMed

    McLachlan, Hugh V

    2012-05-01

    The current UK policy for the distribution of scarce vaccination in an influenza pandemic is ethically dubious. It is based on the planned outcome of the maximum health benefit in terms of the saving of lives and the reduction of illness. To that end, the population is classified in terms of particular priority groups. An alternative policy with a non-consequentialist rationale is proposed in the present work. The state should give the vaccination, in the first instance, to those who are at risk of catching the pandemic flu in the line of their duties of public employment. Thereafter, if there is not sufficient vaccine to give all citizens equally an effective dose, the state should give all citizens an equal chance of receiving an effective dose. This would be the just thing to do because the state has a duty to treat each and all of its citizens impartially and they have a corresponding right to such impartial treatment. Although this article specifically refers to the UK, it is considered that the suggested alternative policy would be applicable generally. The duty to act justly is not merely a local one.

  4. Pandemic influenza and health system resource gaps in Bali: an analysis through a resource transmission dynamics model.

    PubMed

    Adisasmito, Wiku; Hunter, Benjamin M; Krumkamp, Ralf; Latief, Kamal; Rudge, James W; Hanvoravongchai, Piya; Coker, Richard J

    2015-03-01

    The failure to contain pandemic influenza A(H1N1) 2009 in Mexico has shifted global attention from containment to mitigation. Limited surveillance and reporting have, however, prevented detailed assessment of mitigation during the pandemic, particularly in low- and middle-income countries. To assess pandemic influenza case management capabilities in a resource-limited setting, the authors used a health system questionnaire and density-dependent, deterministic transmission model for Bali, Indonesia, determining resource gaps. The majority of health resources were focused in and around the provincial capital, Denpasar; however, gaps are found in every district for nursing staff, surgical masks, and N95 masks. A relatively low pathogenicity pandemic influenza virus would see an overall surplus for physicians, antivirals, and antimicrobials; however, a more pathogenic virus would lead to gaps in every resource except antimicrobials. Resources could be allocated more evenly across Bali. These, however, are in short supply universally and therefore redistribution would not fill resource gaps.

  5. Guillain-Barré syndrome and H1N1 (2009) pandemic influenza vaccination using an AS03 adjuvanted vaccine in the United Kingdom: self-controlled case series.

    PubMed

    Andrews, Nick; Stowe, Julia; Al-Shahi Salman, Rustam; Miller, Elizabeth

    2011-10-19

    In 1976 a swine influenza vaccine was associated with an increased risk of Guillain-Barré syndrome (GBS). Although subsequent studies did not find an increased risk of GBS following seasonal influenza vaccine, there was concern that the monovalent H1N1 vaccines developed against the swine influenza pandemic of 2009 might increase the risk of GBS. In the UK a split-virion AS03 oil-in-water adjuvanted vaccine (Pandemrix™) was predominantly used. To determine whether the risk of GBS increased after Pandemrix administration, we sought GBS cases during the period of vaccine use from neurologists and a patient support group, and following the vaccination period from hospital episode statistics (HES) in England. We obtained cases' vaccination histories and illness onset dates from general practitioners. We determined the relative incidence of GBS in the 6 weeks after vaccination using the self-controlled case series method on the cases identified in HES. We included 327 GBS cases, of whom 37 received pandemic vaccine in the study period, nine of whom developed GBS within 6 weeks of vaccination (relative incidence 1.05 [95% confidence interval (CI) 0.37 to 2.24]). We found no evidence of an increased risk of GBS in the 6 weeks following pandemic influenza vaccination.

  6. [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.

  7. 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

  8. Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results.

    PubMed

    Pebody, Richard; Warburton, Fiona; Ellis, Joanna; Andrews, Nick; Potts, Alison; Cottrell, Simon; Johnston, Jillian; Reynolds, Arlene; Gunson, Rory; Thompson, Catherine; Galiano, Monica; Robertson, Chris; Byford, Rachel; Gallagher, Naomh; Sinnathamby, Mary; Yonova, Ivelina; Pathirannehelage, Sameera; Donati, Matthew; Moore, Catherine; de Lusignan, Simon; McMenamin, Jim; Zambon, Maria

    2016-09-22

    The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17. PMID:27684603

  9. Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results.

    PubMed

    Pebody, Richard; Warburton, Fiona; Ellis, Joanna; Andrews, Nick; Potts, Alison; Cottrell, Simon; Johnston, Jillian; Reynolds, Arlene; Gunson, Rory; Thompson, Catherine; Galiano, Monica; Robertson, Chris; Byford, Rachel; Gallagher, Naomh; Sinnathamby, Mary; Yonova, Ivelina; Pathirannehelage, Sameera; Donati, Matthew; Moore, Catherine; de Lusignan, Simon; McMenamin, Jim; Zambon, Maria

    2016-09-22

    The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

  10. Live attenuated pandemic influenza vaccine: clinical studies on A/17/California/2009/38 (H1N1) and licensing of the Russian-developed technology to WHO for pandemic influenza preparedness in developing countries.

    PubMed

    Rudenko, Larisa; van den Bosch, Han; Kiseleva, Irina; Mironov, Alexander; Naikhin, Anatoly; Larionova, Natalie; Bushmenkov, Dimitry

    2011-07-01

    In February 2009, Nobilon granted the World Health Organization (WHO) a non-exclusive licence to develop, register, manufacture, use and sell seasonal a pandemic live attenuated influenza vaccine (LAIV) produced on embryonated chicken eggs. WHO was permitted to grant sub-licences to vaccine manufacturers in developing countries within the framework of its influenza vaccine technology transfer initiative. In parallel, the Institute of Experimental Medicine (IEM), Russia, concluded an agreement with WHO for the supply of Russian LAIV reassortants for use by these manufacturers. Also in 2009, IEM carried out a study on a novel A/17/California/2009/38 (H1N1) pandemic LAIV candidate derived from the pandemic-related A/California/07/2009 (H1N1) influenza virus and the attenuated A/Leningrad/134/17/57 (H2N2) master donor virus, using routine reassortant technique in embryonated chicken eggs. Following successful preclinical studies in eggs and in ferrets, a double-blind, controlled, randomized clinical trial was carried out in immunologically naïve study participants between 12-18 and 18-60 years old. Collectively, the immunogenicity data (haemagglutinin inhibition test, ELISA and cytokine tests for the detection of memory T cells) support the use of a single dose of the pandemic H1N1 LAIV in 12-60 year olds. The outcome of the studies showed no significant adverse reactions attributable to the vaccine, and suggests that the vaccine is as safe and immunogenic as seasonal influenza vaccines. Importantly, it was clearly demonstrated that reliance on the HAI assay alone is not recommended for testing LAIV. To date, via the licence agreement with WHO, the H1N1 LAIV has been transferred to the Government Pharmaceutical Organization in Thailand, the Serum Institute of India, and the Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd. in China.

  11. Differences in Antibody Responses of Individuals with Natural Infection and Those Vaccinated against Pandemic H1N1 2009 Influenza▿

    PubMed Central

    Chan, Kwok-Hung; To, Kelvin K. W.; Hung, Ivan F. N.; Zhang, Anna J. X.; Chan, Jasper F. W.; Cheng, Vincent C. C.; Tse, Herman; Che, Xiao-Yan; Chen, Honglin; Yuen, Kwok-Yung

    2011-01-01

    The differential antibody response measured by the commonly used hemagglutination inhibition (HI) and microneutralization (MN) assays in patients with natural infection and vaccination has not been fully assessed. HI and conventional MN (CMN) assays were performed on sera from 651 patients with natural infection by pandemic H1N1 2009 influenza virus and on sera from 567 recipients of the corresponding vaccine. Surprisingly, the overall seroprotection rates determined by CMN and HI assays in vaccine recipients were only 44.8 and 35.1%, respectively. Antibody titers measured by the CMN assay was significantly higher than that obtained by HI assay in vaccine recipients aged ≥50 years, but these titers were not significantly different among younger vaccine recipients. In contrast, the HI titer was greater than the CMN titer for the age group from 16 to 29 years but was not significantly different in other age groups for natural infection. Lower antibody levels were found in both naturally infected patients and immunized recipients in the older than in the younger age groups, but naturally infected patients exhibited higher HI and CMN titers than did the corresponding vaccine recipients. In addition, we developed a rapid fluorescent focus microneutralization (FFMN) assay to test sera from naturally infected patients. The FFMN assay has a better correlation with CMN than with HI (ρ = 0.810 versus 0.684), which is expected of neutralizing antibody mainly targeted toward the inhibition of viral entry into cells. The higher antibody level elicited by natural infection than by vaccination may be related to differences between antigen presentation by the intramuscular route of vaccination and mucosal viral replication in mucosal cells of the respiratory tract. PMID:21411604

  12. Pandemic Flu

    MedlinePlus

    ... address the pandemic. Characteristics and Challenges of a Flu Pandemic Rapid Worldwide Spread When a pandemic flu ... exposure could result in significant employee absenteeism. Seasonal Flu versus Pandemic Flu Pandemic Flu Seasonal Flu Rarely ...

  13. The Matrix Gene Segment Destabilizes the Acid and Thermal Stability of the Hemagglutinin of Pandemic Live Attenuated Influenza Virus Vaccines

    PubMed Central

    O'Donnell, Christopher D.; Vogel, Leatrice; Matsuoka, Yumiko; Jin, Hong

    2014-01-01

    ABSTRACT The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated seven reassortant pandemic live attenuated influenza vaccines (pLAIVs) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the six internal protein gene segments of the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60 ca) of the licensed seasonal LAIV. The pLAIV viruses were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and, although they shared the same backbone, the pLAIV viruses had a lower shutoff temperature than seasonal LAIV viruses, suggesting that the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low-pathogenicity avian influenza viruses, as reported by others. However, pLAIV viruses had a consistently higher pH of HA activation and reduced HA thermostability compared to the corresponding wild-type parental viruses. From studies with single-gene reassortant viruses bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60 M gene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIV viruses we observed in seronegative adults. IMPORTANCE There is increasing evidence that the HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We

  14. Vaccination for 2009 pandemic H1N1 influenza A did not induce conserved epitope-specific memory CD8 T cell responses in HIV+ northern Thai children.

    PubMed

    Chawansuntati, Kriangkrai; Aurpibul, Linda; Wipasa, Jiraprapa

    2015-09-11

    The influenza virus causes severe illness in susceptible populations, including children and people living with human immunodeficiency virus (HIV). Here, we investigated cell-mediated immune responses (CMI) against influenza CD8 T cell conserved epitopes in HIV-infected (HIV+) northern Thai children following the 2009 pandemic H1N1 influenza A vaccination. Sixty HIV+ children were vaccinated with two doses of the 2009 pandemic influenza vaccine and their CD8T cell responses were assessed. We found no significant differences in the increase of cytokines-producing and CD107a-expressing CD8+ T cells or CD8+ memory T cells in response to pooled conserved epitopes stimulation in vitro between children with different serologic responses to the vaccine at all time points of the study. Our results suggest that the 2009 pandemic H1N1 vaccine did not induce the conserved epitope-specific immune responses in HIV+ children. Vaccine design and vaccination strategy against influenza in these populations warrant further studies.

  15. Assessment of viral replication in eggs and HA protein yield of pre-pandemic H5N1 candidate vaccine viruses.

    PubMed

    Jing, Xianghong; Soto, Jackeline; Gao, Yamei; Phy, Kathryn; Ye, Zhiping

    2013-08-28

    H5N1 infection and the potential for spread from human to human continue to pose a severe public health concern. Since vaccination remains the most effective way to prevent a potential H5N1 pandemic, the World Health Organization (WHO) Collaborating Centers (CCs) and Essential Regulatory Laboratories (ERLs) engineered and developed a panel of H5N1 pre-pandemic vaccine viruses for pandemic vaccine preparedness as well as production of antigen potency testing reagents (reference antigen and reference anti-serum) for vaccine standardization. To develop a strategy utilizing a number of biochemical methods for the characterization of the viral growth properties and protein yield in eggs, we have selected eight H5N1 pre-pandemic viruses and determined the viral Egg Infectious Dose 50 (EID50), total protein yield, hemagglutinin (HA) to nucleoprotein (NP) ratios (HA:NP), and HA1 content of each virus. Our results showed that all the tested H5N1 vaccine viruses grew to high titers in eggs. The total viral protein yield varies within a narrow range, whereas there were greater differences in the HA:NP protein ratios among the eight viruses. The RP-HPLC based HA1 content analysis demonstrated that the viruses A/Anhui/1/2010, A/Hubei/1/2005, and A/goose/Guiyang/337/2006 contained higher HA contents than other five viruses including A/Vietnam/1203/2003. Our approach for analyzing virus growth and protein yield will allow us identify optimal vaccine virus in a timely manner. In addition, we successfully purified the HA proteins of H5N1 vaccine viruses by optimizing bromelain cleavage conditions. Our studies on the HA protein purification may improve the quality control of the production of influenza vaccine test reagent.

  16. Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals Pandemic Vaccine Candidates.

    PubMed

    Anderson, Christopher S; DeDiego, Marta L; Thakar, Juilee; Topham, David J

    2016-01-01

    Recently, an avian influenza virus, H5NX subclade 2.3.4.4, emerged and spread to North America. This subclade has frequently reassorted, leading to multiple novel viruses capable of human infection. Four cases of human infections, three leading to death, have already occurred. Existing vaccine strains do not protect against these new viruses, raising a need to identify new vaccine candidate strains. We have developed a novel sequence-based mapping (SBM) tool capable of visualizing complex protein sequence data sets using a single intuitive map. We applied SBM on the complete set of avian H5 viruses in order to better understand hemagglutinin protein variance amongst H5 viruses and identify any patterns associated with this variation. The analysis successfully identified the original reassortments that lead to the emergence of this new subclade of H5 viruses, as well as their known unusual ability to re-assort among neuraminidase subtypes. In addition, our analysis revealed distinct clusters of 2.3.4.4 variants that would not be covered by existing strains in the H5 vaccine stockpile. The results suggest that our method may be useful for pandemic candidate vaccine virus selection. PMID:27494186

  17. Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals Pandemic Vaccine Candidates

    PubMed Central

    Anderson, Christopher S.; DeDiego, Marta L.; Thakar, Juilee; Topham, David J.

    2016-01-01

    Recently, an avian influenza virus, H5NX subclade 2.3.4.4, emerged and spread to North America. This subclade has frequently reassorted, leading to multiple novel viruses capable of human infection. Four cases of human infections, three leading to death, have already occurred. Existing vaccine strains do not protect against these new viruses, raising a need to identify new vaccine candidate strains. We have developed a novel sequence-based mapping (SBM) tool capable of visualizing complex protein sequence data sets using a single intuitive map. We applied SBM on the complete set of avian H5 viruses in order to better understand hemagglutinin protein variance amongst H5 viruses and identify any patterns associated with this variation. The analysis successfully identified the original reassortments that lead to the emergence of this new subclade of H5 viruses, as well as their known unusual ability to re-assort among neuraminidase subtypes. In addition, our analysis revealed distinct clusters of 2.3.4.4 variants that would not be covered by existing strains in the H5 vaccine stockpile. The results suggest that our method may be useful for pandemic candidate vaccine virus selection. PMID:27494186

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

    PubMed

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

    2013-03-01

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

  19. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    PubMed

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-01

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  20. Anti-ganglioside antibodies were not detected in human subjects infected with or vaccinated against 2009 pandemic influenza A (H1N1) virus.

    PubMed

    Lei, Ting; Siu, Kam-Leung; Kok, Kin-Hang; Chan, Kwok-Hung; Chan, Eric Y T; Hung, Ivan F N; To, Kelvin K W; Li, Patrick C K; Zhou, Jie; Zheng, Bo-Jian; Yuen, Kwok-Yung; Wang, Ming; Jin, Dong-Yan

    2012-03-30

    Recipients of influenza A (H1N1) vaccine in 1976 had an increased risk for the neurologic disorder Guillain-Barré syndrome (GBS). Anti-ganglioside antibodies, which might be associated with the development of GBS, were previously reported to be induced in mice immunized with an H1N1 vaccine of 1976 or another influenza vaccine. In this study we analyzed anti-ganglioside antibodies in human subjects infected with or vaccinated against 2009 pandemic H1N1, including eight patients diagnosed to have post-vaccination GBS. Antibodies against GM1 or another ganglioside were not detected in any subject or in vaccinated mice. Our results did not support the induction of anti-ganglioside antibodies by influenza viruses or vaccines.

  1. Predictors of influenza vaccine uptake during the 2009/10 influenza A H1N1v (‘swine flu’) pandemic: Results from five national surveys in the United Kingdom

    PubMed Central

    Han, You Kyung Julia; Michie, Susan; Potts, Henry W.W.; Rubin, G. James

    2016-01-01

    Objectives To investigate reasons underlying the low uptake of the influenza A H1N1v vaccination in the UK during the 2009/10 pandemic. Methods We analysed data from five national telephone surveys conducted in the UK during the latter stages of the pandemic to identify predictors of uptake amongst members of the public offered the vaccine by their primary care physician (n = 1320). In addition to demographic variables, participants reported: reasons for declining the vaccination, levels of worry about the risk of catching swine flu, whether too much fuss was being made about the pandemic, whether they or a close friend or relative had had swine flu, how effective they felt the vaccine was, whether they had previously had a seasonal flu vaccination, how well prepared they felt the government was for a pandemic and how satisfied they were with information available about the pandemic. Most participants (n = 734, 55.6%) reported being vaccinated against swine flu, compared to 396 who had not been vaccinated and were unlikely to be vaccinated in the future. Results The main reasons given for declining vaccination were concerns over the vaccine's safety, and being generally healthy. Controlling for demographic variables, risk factors for not being vaccinated were: being female, not having a long-standing infirmity or illness, not having been vaccinated against seasonal flu in previous years, feeling that too much fuss had been made about the pandemic and believing that the vaccine was ineffective. Conclusions Interventions that target these factors may be effective in improving uptake in a future pandemic. PMID:26757401

  2. Randomized Clinical Trial Of Immunogenicity And Safety Of A Recombinant H1N1/2009 Pandemic Influenza Vaccine Containing Advax™ Polysaccharide Adjuvant

    PubMed Central

    Gordon, David L.; Sajkov, Dimitar; Woodman, Richard J.; Honda-Okubo, Yoshikazu; Cox, Manon M.J.; Heinzel, Susanne; Petrovsky, Nikolai

    2012-01-01

    Background Timely vaccine supply is critical during influenza pandemics. A recombinant hemagglutinin (rHA)-based vaccine could overcome production hurdles of egg-based vaccines but has never previously been tested in a real-life pandemic setting. The primary aim was to determine the efficacy of a recombinant pandemic vaccine and whether its immunogenicity could be enhanced by a novel polysaccharide adjuvant (Advax™). Methods 281 adults aged 18–70 years were recruited in a randomized, subject and observer blinded, parallel-group study of rHA H1N1/2009 vaccine with or without adjuvant. Immunizations were at 0 and 3 weeks with rHA 3, 11 or 45 ug. Serology and safety was followed for 6 months. Results At baseline, only 9.1% of subjects (95% CI = 6.0 – 13.2) had seroprotective H1N1/2009 titers. Seroconversion rates varied by rHA dose, presence of adjuvant, subject age and number of immunizations. Eighty percent (95% CI = 52 – 96) of 18 – 49 year olds who received rHA 45ug with adjuvant were seroprotected at week 3, representing a 11.1-fold increase in antibody titers from baseline. Advax™ adjuvant increased seroprotection rates by 1.9 times after the first, and 2.5 times after the second, immunization when compared to rHA alone. Seroprotection was sustained at 26 weeks and the vaccine was well tolerated with no safety issues. Conclusions The study confirmed the ability to design, manufacture, and release a recombinant vaccine within a short time from the start of an actual influenza pandemic. Advax™ adjuvant significantly enhanced rHA immunogenicity. PMID:22717330

  3. DNA vaccination elicits protective immune responses against pandemic and classic swine influenza viruses in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Swine influenza is a highly contagious viral infection in pigs that significantly impacts the pork industry due to weight loss and secondary infections. There is also the potential of a significant public health threat, highlighted by the possibility that the 2009 H1N1 pandemic strain emerged from r...

  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. A post-marketing surveillance study of a human live-virus pandemic influenza A (H1N1) vaccine (Nasovac (®) ) in India.

    PubMed

    Kulkarni, Prasad S; Raut, Sidram K; Dhere, Rajeev M

    2013-01-01

    A live attenuated pandemic H1N1 influenza vaccine was developed in India. A post marketing surveillance was conducted retrospectively in healthy individuals (³ 3 years) who were vaccinated intranasally around one year before. After consent, the subjects recorded adverse events developing within 42 days. Among 7565 individuals (3 - 85 years), a total of 81 solicited adverse reactions (1%) were reported in 49 subjects (0.65%). The reactions included mild to moderate respiratory symptoms. No H1N1 case was encountered during one year postvaccination. The data show the safety of the live attenuated influenza vaccine platform developed in India.

  6. Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus vaccine against the two pandemic strains in swine.

    PubMed

    Zheng, Haixue; Lian, Kaiqi; Yang, Fan; Jin, Ye; Zhu, Zixiang; Guo, Jianhong; Cao, Weijun; Liu, Huanan; He, Jijun; Zhang, Keshan; Li, Dan; Liu, Xiangtao

    2015-10-26

    Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that affects domestic and wild cloven-hoofed animals worldwide. Recently, a series of outbreaks of type A FMDV occurred in Southeast Asian countries, China, the Russia Federation, Mongolia, Kazakhstan and South Korea. The FMD virus (A/GDMM/CHA/2013) from China's Guangdong province (2013) is representative of those responsible for the latest epidemic, and has low amino acid identity (93.9%) in VP1 protein with the epidemic strain A/WH/CHA/09 from Wuhan, China in 2009. Both of isolates belong to the Sea-97 genotype of ASIA topotype. Therefore, the application of a new vaccine strain with cross-protective efficacy is of fundamental importance to control the spread of the two described pandemic strains. A chimeric strain rA/P1-FMDV constructed by our lab previously through replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09, has been demonstrated to exhibit good growth characteristics in culture, and the rA/P1-FMDV inactivated vaccine can provide protection against epidemic strain A/WH/CHA/09 in cattle. However, it is still unclear whether the vaccine produces efficient protection against the new pandemic strain (A/GDMM/CHA/2013). Here, vaccine matching and pig 50% protective dose (PD50) tests were performed to assess the vaccine potency. The vaccine matching test showed cross-reactivity of sera from full dose vaccine vaccinated pigs with A/WH/CHA/09 and A/GDMM/CHA/2013 isolates, with average r1 values of 0.94±0.12 and 0.68±0.06 (r1≥0.3), which indicates that the rA/P1-FMDV vaccine is likely to confer good cross-protection against the two isolates. When challenged with two pandemic isolates A/WH/CHA/09 and A/GDMM/CHA/2013 strain, the vaccine achieved 12.51 PD50 and 10.05 PD50 per dose (2.8μg), respectively. The results indicated that the rA/P1-FMDV inactivated vaccine could protect pigs against both A/WH/CHA/09 and A/GDMM/CHA/2013 pandemic isolates.

  7. Description of a large urban school-located 2009 pandemic H1N1 vaccination campaign, New York City 2009-2010.

    PubMed

    Narciso, Heather E; Pathela, Preeti; Morgenthau, Beth Maldin; Kansagra, Susan M; May, Linda; Scaccia, Allison; Zucker, Jane R

    2012-04-01

    In the spring of 2009, New York City (NYC) experienced the emergence and rapid spread of pandemic influenza A H1N1 virus (pH1N1), which had a high attack rate in children and caused many school closures. During the 2009 fall wave of pH1N1, a school-located vaccination campaign for elementary schoolchildren was conducted in order to reduce infection and transmission in the school setting, thereby reducing the impact of pH1N1 that was observed earlier in the year. In this paper, we describe the planning and outcomes of the NYC school-located vaccination campaign. We compared consent and vaccination data for three vaccination models (school nurse alone, school nurse plus contract nurse, team). Overall, >1,200 of almost 1,600 eligible schools participated, achieving 26.8% consent and 21.5% first-dose vaccination rates, which did not vary significantly by vaccination model. A total of 189,902 doses were administered during two vaccination rounds to 115,668 students at 998 schools included in the analysis; vaccination rates varied by borough, school type, and poverty level. The team model achieved vaccination of more children per day and required fewer vaccination days per school. NYC's campaign is the largest described school-located influenza vaccination campaign to date. Despite substantial challenges, school-located vaccination is feasible in large, urban settings, and during a public health emergency. PMID:22318374

  8. A qualitative study of vaccine acceptability and decision making among pregnant women in Morocco during the A (H1N1) pdm09 pandemic.

    PubMed

    Lohiniva, Anna-Leena; Barakat, Amal; Dueger, Erica; Restrepo, Suzanne; El Aouad, Rajae

    2014-01-01

    Vaccination uptake of pregnant women in Morocco during the A (H1N1) pdm09 pandemic was lower than expected. A qualitative study using open-ended questions was developed to explore the main determinants of acceptance and non-acceptance of the monovalent A (H1N1) pdm09 vaccine among pregnant women in Morocco and to identify information sources that influenced their decision-making process. The study sample included 123 vaccinated and unvaccinated pregnant women who were in their second or third trimester between December 2009 and March 2010. They took part in 14 focus group discussions and eight in-depth interviews in the districts of Casablanca and Kenitra. Thematic qualitative analysis identified reasons for vaccine non-acceptance: (1) fear of the monovalent A (H1N1) pdm09 vaccine, (2) belief in an A (H1N1) pdm09 pandemic conspiracy, (3) belief in the inapplicability of the monovalent A (H1N1) pdm09 vaccine to Moroccans, (4) lack of knowledge of the monovalent A (H1N1) pdm09 vaccine, and (5) challenges of vaccination services/logistics. Reasons for vaccine acceptance included: (1) perceived benefits and (2) modeling. Decision-making was strongly influenced by family, community, mass media, religious leaders and health providers suggesting that broad communication efforts should also be used to advocate for vaccination. Meaningful communication for future vaccine campaigns must consider these context-specific findings. As cultural and religious values are shared across many Arab countries, these findings may also provide valuable insights for seasonal influenza vaccine planning in the Middle East and North Africa region at large. PMID:25313555

  9. A Qualitative Study of Vaccine Acceptability and Decision Making among Pregnant Women in Morocco during the A (H1N1) pdm09 Pandemic

    PubMed Central

    Lohiniva, Anna-Leena; Barakat, Amal; Dueger, Erica; Restrepo, Suzanne; El Aouad, Rajae

    2014-01-01

    Vaccination uptake of pregnant women in Morocco during the A (H1N1) pdm09 pandemic was lower than expected. A qualitative study using open-ended questions was developed to explore the main determinants of acceptance and non-acceptance of the monovalent A (H1N1) pdm09 vaccine among pregnant women in Morocco and to identify information sources that influenced their decision-making process. The study sample included 123 vaccinated and unvaccinated pregnant women who were in their second or third trimester between December 2009 and March 2010. They took part in 14 focus group discussions and eight in-depth interviews in the districts of Casablanca and Kenitra. Thematic qualitative analysis identified reasons for vaccine non-acceptance: (1) fear of the monovalent A (H1N1) pdm09 vaccine, (2) belief in an A (H1N1) pdm09 pandemic conspiracy, (3) belief in the inapplicability of the monovalent A (H1N1) pdm09 vaccine to Moroccans, (4) lack of knowledge of the monovalent A (H1N1) pdm09 vaccine, and (5) challenges of vaccination services/logistics. Reasons for vaccine acceptance included: (1) perceived benefits and (2) modeling. Decision-making was strongly influenced by family, community, mass media, religious leaders and health providers suggesting that broad communication efforts should also be used to advocate for vaccination. Meaningful communication for future vaccine campaigns must consider these context-specific findings. As cultural and religious values are shared across many Arab countries, these findings may also provide valuable insights for seasonal influenza vaccine planning in the Middle East and North Africa region at large. PMID:25313555