Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

Science.gov (United States)

Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

2011-09-28

Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

Novel pandemic influenza A(H1N1 viruses are potently inhibited by DAS181, a sialidase fusion protein.

Directory of Open Access Journals (Sweden)

Gallen B Triana-Baltzer

2009-11-01

Full Text Available The recent emergence of a novel pandemic influenza A(H1N1 strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV. Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1. Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1 viruses.The activity of DAS181 against several pandemic influenza A(H1N1 virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1 strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1 strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus.The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1 viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y, DAS181 may be active against the antigenically novel pandemic influenza A(H1N1 virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for

Evidence of cross-reactive immunity to 2009 pandemic influenza A virus in workers seropositive to swine H1N1 influenza viruses circulating in Italy.

Directory of Open Access Journals (Sweden)

Maria A De Marco

Full Text Available BACKGROUND: Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm virus. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 123 swine workers (SWs and 379 control subjects (Cs, not exposed to pig herds, were tested by haemagglutination inhibition (HI assay against selected SIVs belonging to H1N1 (swH1N1, H1N2 (swH1N2 and H3N2 (swH3N2 subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes. Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs and after (n. 39 SWs; n. 145 Cs the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively. Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively. No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4% and swH3N2 (51.2 vs. 55.4% viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs. CONCLUSION/SIGNIFICANCE: A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p<0.001 whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed

Influenza Pandemic Infrastructure Response in Thailand

Centers for Disease Control (CDC) Podcasts

2009-03-05

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

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

NARCIS (Netherlands)

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

2011-01-01

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

Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection: Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza.

Science.gov (United States)

Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas

2009-08-24

On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.

The impact of the pandemic influenza A(H1N1) 2009 virus on seasonal influenza A viruses in the southern hemisphere, 2009.

Science.gov (United States)

Blyth, C C; Kelso, A; McPhie, K A; Ratnamohan, V M; Catton, M; Druce, J D; Smith, D W; Williams, S H; Huang, Q S; Lopez, L; Schoub, B D; Venter, M; Dwyer, D E

2010-08-05

Data collected over winter 2009 by five World Health Organisation National Influenza Centres in the southern hemisphere were used to examine the circulation of pandemic and seasonal influenza A strains during the first pandemic wave in the southern hemisphere.There is compelling evidence that the pandemic influenza A(H1N1) 2009 virus significantly displaced seasonal influenza A(H1N1) and, to a lesser extent, A(H3N2) viruses circulating in the southern hemisphere. Complete replacement of seasonal influenza A strains, however, was not observed during the first pandemic wave.

Adaptation of Pandemic H1N1 Influenza Viruses in Mice▿

Science.gov (United States)

Ilyushina, Natalia A.; Khalenkov, Alexey M.; Seiler, Jon P.; Forrest, Heather L.; Bovin, Nicolai V.; Marjuki, Henju; Barman, Subrata; Webster, Robert G.; Webby, Richard J.

2010-01-01

The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to α2,3 together with decreasing binding to α2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID:20592084

Prevention and control of infectious diseases with pandemic potential: The EU-project SARSControl

NARCIS (Netherlands)

R.A. Ahmad (Riris); R. Krumkamp (R.); J.H. Richardus (Jan Hendrik); R. Reintjes (R.)

2009-01-01

textabstractIntroduction: The influenza pandemics of the 20 th century, the SARS epidemic in 2002 / 03 and the growing number of human cases infected with the H5N1 avian infl uenza virus clearly demonstrate that the threat of new pandemics is very real. These events have intensifi ed pandemic

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

Science.gov (United States)

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. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

Emerging influenza viruses and the prospect of a universal influenza virus vaccine.

Science.gov (United States)

Krammer, Florian

2015-05-01

Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evolving RNA Virus Pandemics: HIV, HCV, Ebola, Dengue, Chikunguya, and now Zika!

Science.gov (United States)

Barreiro, Pablo

2016-01-01

The Zika virus (ZIKV), a flavivirus related to yellow fever, dengue, and West Nile, originated in the Zika forest in Uganda and was discovered in a rhesus monkey in 1947. The disease now has "explosive" pandemic potential, with outbreaks in Africa, Southeast Asia, the Pacific Islands, and the Americas. To date, the CDC has issued travel alerts for at least 30 countries and territories in Latin America, the Caribbean, Polynesia, and Cape Verde in Africa.

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

Directory of Open Access Journals (Sweden)

Nuriban Valero-Pacheco

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

The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus.

Science.gov (United States)

Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter; Matrosovich, Mikhail

2015-04-01

The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2

Transmission of Hemagglutinin D222G Mutant Strain of Pandemic (H1N1) 2009 Virus

Science.gov (United States)

Facchini, Marzia; Spagnolo, Domenico; De Marco, Maria A.; Calzoletti, Laura; Zanetti, Alessandro; Fumagalli, Roberto; Tanzi, Maria L.; Cassone, Antonio; Rezza, Giovanni; Donatelli, Isabella

2010-01-01

A pandemic (H1N1) 2009 virus strain carrying the D222G mutation was identified in a severely ill man and was transmitted to a household contact. Only mild illness developed in the contact, despite his obesity and diabetes. The isolated virus reacted fully with an antiserum against the pandemic vaccine strain. PMID:20409386

Considerable progress in European preparations for a potential influenza pandemic.

NARCIS (Netherlands)

Paget, J.

2005-01-01

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

Ecosystem Interactions Underlie the Spread of Avian Influenza A Viruses with Pandemic Potential.

Directory of Open Access Journals (Sweden)

Justin Bahl

2016-05-01

Full Text Available Despite evidence for avian influenza A virus (AIV transmission between wild and domestic ecosystems, the roles of bird migration and poultry trade in the spread of viruses remain enigmatic. In this study, we integrate ecosystem interactions into a phylogeographic model to assess the contribution of wild and domestic hosts to AIV distribution and persistence. Analysis of globally sampled AIV datasets shows frequent two-way transmission between wild and domestic ecosystems. In general, viral flow from domestic to wild bird populations was restricted to within a geographic region. In contrast, spillover from wild to domestic populations occurred both within and between regions. Wild birds mediated long-distance dispersal at intercontinental scales whereas viral spread among poultry populations was a major driver of regional spread. Viral spread between poultry flocks frequently originated from persistent lineages circulating in regions of intensive poultry production. Our analysis of long-term surveillance data demonstrates that meaningful insights can be inferred from integrating ecosystem into phylogeographic reconstructions that may be consequential for pandemic preparedness and livestock protection.

Ecosystem Interactions Underlie the Spread of Avian Influenza A Viruses with Pandemic Potential

Science.gov (United States)

Bahl, Justin; Pham, Truc T.; Hill, Nichola J.; Hussein, Islam T. M.; Ma, Eric J.; Easterday, Bernard C.; Halpin, Rebecca A.; Stockwell, Timothy B.; Wentworth, David E.; Kayali, Ghazi; Krauss, Scott; Schultz-Cherry, Stacey; Webster, Robert G.; Webby, Richard J.; Swartz, Michael D.; Smith, Gavin J. D.; Runstadler, Jonathan A.

2016-01-01

Despite evidence for avian influenza A virus (AIV) transmission between wild and domestic ecosystems, the roles of bird migration and poultry trade in the spread of viruses remain enigmatic. In this study, we integrate ecosystem interactions into a phylogeographic model to assess the contribution of wild and domestic hosts to AIV distribution and persistence. Analysis of globally sampled AIV datasets shows frequent two-way transmission between wild and domestic ecosystems. In general, viral flow from domestic to wild bird populations was restricted to within a geographic region. In contrast, spillover from wild to domestic populations occurred both within and between regions. Wild birds mediated long-distance dispersal at intercontinental scales whereas viral spread among poultry populations was a major driver of regional spread. Viral spread between poultry flocks frequently originated from persistent lineages circulating in regions of intensive poultry production. Our analysis of long-term surveillance data demonstrates that meaningful insights can be inferred from integrating ecosystem into phylogeographic reconstructions that may be consequential for pandemic preparedness and livestock protection. PMID:27166585

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

NARCIS (Netherlands)

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

2008-01-01

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

Evolution and adaptation of the pandemic A/H1N1 2009 influenza virus

Directory of Open Access Journals (Sweden)

Ducatez MF

2011-07-01

Full Text Available Mariette F Ducatez, Thomas P Fabrizio, Richard J WebbyDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USAAbstract: The emergence of the 2009 H1N1 pandemic influenza virus [A(H1N1pdm09] has provided the public health community with many challenges, but also the scientific community with an opportunity to monitor closely its evolution through the processes of drift and shift. To date, and despite having circulated in humans for nearly two years, little antigenic variation has been observed in the A(H1N1pdm09 viruses. However, as the A(H1N1pdm09 virus continues to circulate and the immunologic pressure within the human population increases, future antigenic change is almost a certainty. Several coinfections of A(H1N1pdm09 and seasonal A(H1N1 or A(H3N2 viruses have been observed, but no reassortant viruses have been described in humans, suggesting a lack of fitness of reassortant viruses or a lack of opportunities for interaction of different viral lineages. In contrast, multiple reassortment events have been detected in swine populations between A(H1N1 pdm09 and other endemic swine viruses. Somewhat surprisingly, many of the well characterized influenza virus virulence markers appear to have limited impact on the phenotype of the A(H1N1pdm09 viruses when they have been introduced into mutant viruses in laboratory settings. As such, it is unclear what the evolutionary path of the pandemic virus will be, but the monitoring of any changes in the circulating viruses will remain a global public and animal health priority.Keywords: influenza, pandemic, evolution, adaptation

Pandemic influenza: certain uncertainties

Science.gov (United States)

Morens, David M.; Taubenberger, Jeffery K.

2011-01-01

SUMMARY For at least five centuries, major epidemics and pandemics of influenza have occurred unexpectedly and at irregular intervals. Despite the modern notion that pandemic influenza is a distinct phenomenon obeying such constant (if incompletely understood) rules such as dramatic genetic change, cyclicity, “wave” patterning, virus replacement, and predictable epidemic behavior, much evidence suggests the opposite. Although there is much that we know about pandemic influenza, there appears to be much more that we do not know. Pandemics arise as a result of various genetic mechanisms, have no predictable patterns of mortality among different age groups, and vary greatly in how and when they arise and recur. Some are followed by new pandemics, whereas others fade gradually or abruptly into long-term endemicity. Human influenza pandemics have been caused by viruses that evolved singly or in co-circulation with other pandemic virus descendants and often have involved significant transmission between, or establishment of, viral reservoirs within other animal hosts. In recent decades, pandemic influenza has continued to produce numerous unanticipated events that expose fundamental gaps in scientific knowledge. Influenza pandemics appear to be not a single phenomenon but a heterogeneous collection of viral evolutionary events whose similarities are overshadowed by important differences, the determinants of which remain poorly understood. These uncertainties make it difficult to predict influenza pandemics and, therefore, to adequately plan to prevent them. PMID:21706672

Vaccines for pandemic influenza. The history of our current vaccines, their limitations and the requirements to deal with a pandemic threat.

Science.gov (United States)

Hampson, Alan W

2008-06-01

Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention on our current vaccines, their shortcomings, and concerns regarding global vaccine supply in a pandemic. The bulk of current vaccines are inactivated split virus vaccines produced from egg-grown virus and have only modest improvements compared with those first introduced over 60 years ago. Splitting, which was introduced some years ago to reduce reactogenicity, also reduces the immunogenicity of vaccines in immunologically naïve recipients. The A(H5N1) viruses have been found poorly immunogenic and present other challenges for vaccine producers which further exacerbate an already limited global production capacity. There have been some recent improvements in vaccine production methods and improvements to immunogenicity by the development of new adjuvants, however, these still fall short of providing timely supplies of vaccine for all in the face of a pandemic. New approaches to influenza vaccines which might fulfil the demands of a pandemic situation are under evaluation, however, these remain some distance from clinical reality and face significant regulatory hurdles.

The age distribution of mortality due to influenza: pandemic and peri-pandemic

Science.gov (United States)

2012-01-01

Background Pandemic influenza is said to 'shift mortality' to younger age groups; but also to spare a subpopulation of the elderly population. Does one of these effects dominate? Might this have important ramifications? Methods We estimated age-specific excess mortality rates for all-years for which data were available in the 20th century for Australia, Canada, France, Japan, the UK, and the USA for people older than 44 years of age. We modeled variation with age, and standardized estimates to allow direct comparison across age groups and countries. Attack rate data for four pandemics were assembled. Results For nearly all seasons, an exponential model characterized mortality data extremely well. For seasons of emergence and a variable number of seasons following, however, a subpopulation above a threshold age invariably enjoyed reduced mortality. 'Immune escape', a stepwise increase in mortality among the oldest elderly, was observed a number of seasons after both the A(H2N2) and A(H3N2) pandemics. The number of seasons from emergence to escape varied by country. For the latter pandemic, mortality rates in four countries increased for younger age groups but only in the season following that of emergence. Adaptation to both emergent viruses was apparent as a progressive decrease in mortality rates, which, with two exceptions, was seen only in younger age groups. Pandemic attack rate variation with age was estimated to be similar across four pandemics with very different mortality impact. Conclusions In all influenza pandemics of the 20th century, emergent viruses resembled those that had circulated previously within the lifespan of then-living people. Such individuals were relatively immune to the emergent strain, but this immunity waned with mutation of the emergent virus. An immune subpopulation complicates and may invalidate vaccine trials. Pandemic influenza does not 'shift' mortality to younger age groups; rather, the mortality level is reset by the virulence

Respiratory virus laboratory pandemic planning and surveillance in central Viet Nam, 2008-2010.

Science.gov (United States)

Tran, Thomas; Chien, Bui Trong; Papadakis, Georgina; Druce, Julian; Birch, Chris; Chibo, Doris; An, Truong Phuoc; Trang, Le Thi Kim; Trieu, Nguyen Bao; Thuy, Doan Thi Thanh; Catton, Mike; Mai, Trinh Xuan

2012-07-01

Laboratory capacity is needed in central Viet Nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health, for example the outbreak of influenza A(H1N1) pandemic in 2009. Polymerase chain reaction (PCR) procedures established as part of a capacity-building process were used to conduct prospective respiratory surveillance in a region where few previous studies have been undertaken. Between October 2008 and September 2010, nose and throat swabs from adults and children (approximately 20 per week) presenting with an acute respiratory illness to the Ninh Hoa General Hospital were collected. Same-day PCR testing and result reporting for 13 respiratory viruses were carried out by locally trained scientists. Of 2144 surveillance samples tested, 1235 (57.6%) were positive for at least one virus. The most common were influenza A strains (17.9%), with pandemic influenza A(H1N1) 2009 and seasonal H3N2 strain accounting for 52% and 43% of these, respectively. Other virus detections included: rhinovirus (12.4%), enterovirus (8.9%), influenza B (8.3%), adenovirus (5.3%), parainfluenza (4.7%), respiratory syncytial virus (RSV) (3.9%), human coronavirus (3.0%) and human metapneumovirus (0.3%). The detection rate was greatest in the 0-5 year age group. Viral co-infections were identified in 148 (6.9%) cases. The outbreak in 2009 of the influenza A(H1N1) pandemic strain provided a practical test of the laboratory's pandemic plan. This study shows that the availability of appropriate equipment and molecular-based testing can contribute to important individual and public health outcomes in geographical locations susceptible to emerging infections.

Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

Science.gov (United States)

Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

2017-08-01

Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

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

Directory of Open Access Journals (Sweden)

Nigel J Dimmock

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

Respiratory virus laboratory pandemic planning an surveillance in central Viet Nam, 2008-2010

Directory of Open Access Journals (Sweden)

Trinh Xuan Mai

2012-07-01

Full Text Available Introduction: Laboratory capacity is needed in central Viet Nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health, for example the outbreak of influenza A(H1N1 pandemic in 2009. Polymerase chain reaction (PCR procedures established as part of a capacity-building process were used to conduct prospective respiratory surveillance in a region where few previous studies have been undertaken.Methods: Between October 2008 and September 2010, nose and throat swabs from adults and children (approximately 20 per week presenting with an acute respiratory illness to the Ninh Hoa General Hospital were collected. Same-day PCR testing and result reporting for 13 respiratory viruses were carried out by locally trained scientists.Results: Of 2144 surveillance samples tested, 1235 (57.6% were positive for at least one virus. The most common were influenza A strains (17.9%, with pandemic influenza A(H1N1 2009 and seasonal H3N2 strain accounting for 52% and 43% of these, respectively. Other virus detections included: rhinovirus (12.4%, enterovirus (8.9%, influenza B (8.3%, adenovirus (5.3%, parainfluenza (4.7%, respiratory syncytial virus (RSV (3.9%, human coronavirus (3.0% and human metapneumovirus (0.3%. The detection rate was greatest in the 0–5 year age group. Viral co-infections were identified in 148 (6.9% cases.Discussion: The outbreak in 2009 of the influenza A(H1N1 pandemic strain provided a practical test of the laboratory’s pandemic plan. This study shows that the availability of appropriate equipment and molecular-based testing can contribute to important individual and public health outcomes in geographical locations susceptible to emerging infections.

Novel triple reassortant H1N2 influenza viruses bearing six internal genes of the pandemic 2009/H1N1 influenza virus were detected in pigs in China.

Science.gov (United States)

Qiao, Chuanling; Liu, Liping; Yang, Huanliang; Chen, Yan; Xu, Huiyang; Chen, Hualan

2014-12-01

The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. Transmissions of the pandemic 2009/H1N1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 H1N1 pandemic. Reassortant H1N1, H1N2, and H3N2 viruses containing genes of the pandemic 2009/H1N1 viruses appeared in pigs in some countries. In winter of 2012, a total of 2600 nasal swabs were collected from healthy pigs in slaughterhouses located throughout 10 provinces in China. The isolated viruses were subjected to genetic and antigenic analysis. Two novel triple-reassortant H1N2 influenza viruses were isolated from swine in China in 2012, with the HA gene derived from Eurasian avian-like swine H1N1, the NA gene from North American swine H1N2, and the six internal genes from the pandemic 2009/H1N1 viruses. The two viruses had similar antigenic features and some significant changes in antigenic characteristics emerged when compared to the previously identified isolates. We inferred that the novel reassortant viruses in China may have arisen from the accumulation of the three types of influenza viruses, which further indicates that swine herds serve as "mixing vessels" for influenza viruses. Influenza virus reassortment is an ongoing process, and our findings highlight the urgent need for continued influenza surveillance among swine herds. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Yu-Fen Tseng

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

Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

Science.gov (United States)

Sun, Yipeng; Bi, Yuhai; Pu, Juan; Hu, Yanxin; Wang, Jingjing; Gao, Huijie; Liu, Linqing; Xu, Qi; Tan, Yuanyuan; Liu, Mengda; Guo, Xin; Yang, Hanchun; Liu, Jinhua

2010-11-23

The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1) 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1) 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

Transmission dynamics of pandemic influenza A(H1N1)pdm09 virus in humans and swine in backyard farms in Tumbes, Peru.

Science.gov (United States)

Tinoco, Yeny O; Montgomery, Joel M; Kasper, Mathew R; Nelson, Martha I; Razuri, Hugo; Guezala, Maria C; Azziz-Baumgartner, Eduardo; Widdowson, Marc-Alain; Barnes, John; Gilman, Robert H; Bausch, Daniel G; Gonzalez, Armando E

2016-01-01

We aimed to determine the frequency of pH1N1 transmission between humans and swine on backyard farms in Tumbes, Peru. Two-year serial cross-sectional study comprising four sampling periods: March 2009 (pre-pandemic), October 2009 (peak of the pandemic in Peru), April 2010 (1st post-pandemic period), and October 2011 (2nd post-pandemic period). Backyard swine serum, tracheal swabs, and lung sample were collected during each sampling period. We assessed current and past pH1N1 infection in swine through serological testing, virus culture, and RT-PCR and compared the results with human incidence data from a population-based active surveillance cohort study in Peru. Among 1303 swine sampled, the antibody prevalence to pH1N1 was 0% pre-pandemic, 8% at the peak of the human pandemic (October 2009), and 24% in April 2010 and 1% in October 2011 (post-pandemic sampling periods). Trends in swine seropositivity paralleled those seen in humans in Tumbes. The pH1N1 virus was isolated from three pigs during the peak of the pandemic. Phylogenetic analysis revealed that these viruses likely represent two separate human-to-swine transmission events in backyard farm settings. Our findings suggest that human-to-swine pH1N1 transmission occurred during the pandemic among backyard farms in Peru, emphasizing the importance of interspecies transmission in backyard pig populations. Continued surveillance for influenza viruses in backyard farms is warranted. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Avian Influenza Pandemic May Expand the Military Role in Disaster Relief

National Research Council Canada - National Science Library

Sherod, II, Frank W

2006-01-01

.... The next national disaster facing the U.S. could be an influenza pandemic. The bird flu virus H5N1 currently threatening Asia and Europe can potentially mutate into a deadly human influenza pandemic with global consequences...

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

Directory of Open Access Journals (Sweden)

Béatrice Labrosse

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

Pandemic influenza A/H1N1 virus incursion into Africa: countries ...

African Journals Online (AJOL)

Pandemic influenza A/H1N1 virus incursion into Africa: countries, hosts and ... features are important for planning control measures between countries and to ... in humans, infections in pigs earlier reported in America, Europe and Asia were ...

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

Directory of Open Access Journals (Sweden)

Qin E-de

2010-06-01

Full Text Available Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009 influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.

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

Science.gov (United States)

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

2015-12-08

Large outbreaks of zoonotic influenza A virus (IAV) infections may presage an influenza pandemic. However, the likelihood that an airborne-transmissible variant evolves upon zoonotic infection or co-infection with zoonotic and seasonal IAVs remains poorly understood, as does the relative importance of accumulating mutations versus re-assortment in this process. Using discrete-time probabilistic models, we determined quantitative probability ranges that transmissible variants with 1-5 mutations and transmissible re-assortants evolve after a given number of zoonotic IAV infections. The systematic exploration of a large population of model parameter values was designed to account for uncertainty and variability in influenza virus infection, epidemiological and evolutionary processes. The models suggested that immunocompromised individuals are at high risk of generating IAV variants with pandemic potential by accumulation of mutations. Yet, both immunocompetent and immunocompromised individuals could generate high viral loads of single and double mutants, which may facilitate their onward transmission and the subsequent accumulation of additional 1-2 mutations in newly-infected individuals. This may result in the evolution of a full transmissible genotype along short chains of contact transmission. Although co-infection with zoonotic and seasonal IAVs was shown to be a rare event, it consistently resulted in high viral loads of re-assortants, which may facilitate their onward transmission among humans. The prevention or limitation of zoonotic IAV infection in immunocompromised and contact individuals, including health care workers, as well as vaccination against seasonal IAVs-limiting the risk of co-infection-should be considered fundamental tools to thwart the evolution of a novel pandemic IAV by accumulation of mutations and re-assortment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

Directory of Open Access Journals (Sweden)

Yipeng Sun

Full Text Available BACKGROUND: The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. CONCLUSIONS/SIGNIFICANCE: We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

Respiratory virus laboratory pandemic planning and surveillance in central Viet Nam, 2008–2010

Science.gov (United States)

Chien, Bui Trong; Papadakis, Georgina; Druce, Julian; Birch, Chris; Chibo, Doris; An, Truong Phuoc; Trang, Le Thi Kim; Trieu, Nguyen Bao; Thuy, Doan Thi Thanh; Catton, Mike; Mai, Trinh Xuan

2012-01-01

Introduction Laboratory capacity is needed in central Viet Nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health, for example the outbreak of influenza A(H1N1) pandemic in 2009. Polymerase chain reaction (PCR) procedures established as part of a capacity-building process were used to conduct prospective respiratory surveillance in a region where few previous studies have been undertaken. Methods Between October 2008 and September 2010, nose and throat swabs from adults and children (approximately 20 per week) presenting with an acute respiratory illness to the Ninh Hoa General Hospital were collected. Same-day PCR testing and result reporting for 13 respiratory viruses were carried out by locally trained scientists. Results Of 2144 surveillance samples tested, 1235 (57.6%) were positive for at least one virus. The most common were influenza A strains (17.9%), with pandemic influenza A(H1N1) 2009 and seasonal H3N2 strain accounting for 52% and 43% of these, respectively. Other virus detections included: rhinovirus (12.4%), enterovirus (8.9%), influenza B (8.3%), adenovirus (5.3%), parainfluenza (4.7%), respiratory syncytial virus (RSV) (3.9%), human coronavirus (3.0%) and human metapneumovirus (0.3%). The detection rate was greatest in the 0–5 year age group. Viral co-infections were identified in 148 (6.9%) cases. Discussion The outbreak in 2009 of the influenza A(H1N1) pandemic strain provided a practical test of the laboratory’s pandemic plan. This study shows that the availability of appropriate equipment and molecular-based testing can contribute to important individual and public health outcomes in geographical locations susceptible to emerging infections. PMID:23908924

Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

Directory of Open Access Journals (Sweden)

Farooqui Amber

2012-06-01

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

Contemporary Avian Influenza A Virus Subtype H1, H6, H7, H10, and H15 Hemagglutinin Genes Encode a Mammalian Virulence Factor Similar to the 1918 Pandemic Virus H1 Hemagglutinin

OpenAIRE

Qi, Li; Pujanauski, Lindsey M.; Davis, A. Sally; Schwartzman, Louis M.; Chertow, Daniel S.; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L.; Slemons, Richard D.; Walters, Kathie-Anne; Kash, John C.; Taubenberger, Jeffery K.

2014-01-01

ABSTRACT Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backb...

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

Science.gov (United States)

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Toward a method for tracking virus evolutionary trajectory applied to the pandemic H1N1 2009 influenza virus.

Science.gov (United States)

Squires, R Burke; Pickett, Brett E; Das, Sajal; Scheuermann, Richard H

2014-12-01

In 2009 a novel pandemic H1N1 influenza virus (H1N1pdm09) emerged as the first official influenza pandemic of the 21st century. Early genomic sequence analysis pointed to the swine origin of the virus. Here we report a novel computational approach to determine the evolutionary trajectory of viral sequences that uses data-driven estimations of nucleotide substitution rates to track the gradual accumulation of observed sequence alterations over time. Phylogenetic analysis and multiple sequence alignments show that sequences belonging to the resulting evolutionary trajectory of the H1N1pdm09 lineage exhibit a gradual accumulation of sequence variations and tight temporal correlations in the topological structure of the phylogenetic trees. These results suggest that our evolutionary trajectory analysis (ETA) can more effectively pinpoint the evolutionary history of viruses, including the host and geographical location traversed by each segment, when compared against either BLAST or traditional phylogenetic analysis alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

Science.gov (United States)

Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

2012-07-06

In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

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

NARCIS (Netherlands)

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

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

A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection

DEFF Research Database (Denmark)

Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif

2013-01-01

seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs...... intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA...... of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the risk for epidemics and pandemics to evolve....

Low adherence to influenza vaccination campaigns: is the H1N1 virus pandemic to be blamed?

Directory of Open Access Journals (Sweden)

Trivellin Valeria

2011-11-01

Full Text Available Abstract Background Over the last few months, debates about the handling of the influenza virus A (H1N1 pandemic took place, in particular regarding the change of the WHO pandemic definition, economic interests, the dramatic communication style of mass media. The activation of plans to reduce the virus diffusion resulted in an important investment of resources. Were those investments proportionate to the risk? Was the pandemic overrated? The workload of the Pediatric Emergency Room (P.E.R. at a teaching hospital in Varese (Northern Italy was investigated in order to evaluate the local diffusion and severity of the new H1N1 influenza epidemic. Discussion A 100% increase of the number of P.E.R. visits, particularly for influenza-like illness, was recorded during weeks 42-46 of 2009 (October, 17 to November, 2; the low rate of hospitalization and the mild presentation of the infection gave rise to the conclusion that the pandemic risk was overrated. Mass media communications concerning the new virus created a disproportionate fear in the population that significantly enhanced the burden of cares at the hospital. In the absence of generally implemented measures for etiological diagnosis, the actual incidence of the H1N1 infection could not be estimated. Virus identification, in fact, was limited to children showing severe symptoms after consultancy with an infectious disease specialist. The alarming nature of the communication campaign and the choice to limit etiologic diagnosis to severe cases created a climate of uncertainty which significantly contributed to the massive admissions to the P.E.R.. Summary The communication strategy adopted by the mass media was an important element during the pandemic: the absence of clarity contributed to the spread of a pandemic phobia that appeared to result more from the sensationalism of the campaign than from infection with the novel influenza A variant of human, avian, swine origin virus. One relevant effect

Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th‐century pandemics

Science.gov (United States)

Pasricha, Gunisha; Mishra, Akhilesh C.; Chakrabarti, Alok K.

2012-01-01

Please cite this paper as: Pasricha et al. (2012) Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the Influenza A virus subtypes responsible for the 20th‐century pandemics. Influenza and Other Respiratory Viruses 7(4), 497–505. Background  PB1F2 is the 11th protein of influenza A virus translated from +1 alternate reading frame of PB1 gene. Since the discovery, varying sizes and functions of the PB1F2 protein of influenza A viruses have been reported. Selection of PB1 gene segment in the pandemics, variable size and pleiotropic effect of PB1F2 intrigued us to analyze amino acid sequences of this protein in various influenza A viruses. Methods  Amino acid sequences for PB1F2 protein of influenza A H5N1, H1N1, H2N2, and H3N2 subtypes were obtained from Influenza Research Database. Multiple sequence alignments of the PB1F2 protein sequences of the aforementioned subtypes were used to determine the size, variable and conserved domains and to perform mutational analysis. Results  Analysis showed that 96·4% of the H5N1 influenza viruses harbored full‐length PB1F2 protein. Except for the 2009 pandemic H1N1 virus, all the subtypes of the 20th‐century pandemic influenza viruses contained full‐length PB1F2 protein. Through the years, PB1F2 protein of the H1N1 and H3N2 viruses has undergone much variation. PB1F2 protein sequences of H5N1 viruses showed both human‐ and avian host‐specific conserved domains. Global database of PB1F2 protein revealed that N66S mutation was present only in 3·8% of the H5N1 strains. We found a novel mutation, N84S in the PB1F2 protein of 9·35% of the highly pathogenic avian influenza H5N1 influenza viruses. Conclusions  Varying sizes and mutations of the PB1F2 protein in different influenza A virus subtypes with pandemic potential were obtained. There was genetic divergence of the protein in various hosts which highlighted the host‐specific evolution of the virus

X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus

International Nuclear Information System (INIS)

Ha Ya; Stevens, David J.; Skehel, John J.; Wiley, Don C.

2003-01-01

We have determined the structure of the HA of an avian influenza virus, A/duck/Ukraine/63, a member of the same antigenic subtype, H3, as the virus that caused the 1968 Hong Kong influenza pandemic, and a possible progenitor of the pandemic virus. We find that structurally significant differences between the avian and the human HAs are restricted to the receptor-binding site particularly the substitutions Q226L and G228S that cause the site to open and residues within it to rearrange, including the conserved residues Y98, W153, and H183. We have also analyzed complexes formed by the HA with sialopentasaccharides in which the terminal sialic acid is in either α2,3- or α2,6-linkage to galactose. Comparing the structures of complexes in which an α2,3-linked receptor analog is bound to the H3 avian HA or to an H5 avian HA leads to the suggestion that all avian influenza HAs bind to their preferred α2,3-linked receptors similarly, with the analog in a trans conformation about the glycosidic linkage. We find that α2,6-linked analogs are bound by both human and avian HAs in a cis conformation, and that the incompatibility of an α2,6-linked receptor with the α2,3-linkage-specific H3 avian HA-binding site is partially resolved by a small change in the position and orientation of the sialic acid. We discuss our results in relation to the mechanism of transfer of influenza viruses between species

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

OpenAIRE

Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

2010-01-01

Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same a...

Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

Science.gov (United States)

Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

2017-09-01

In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

Molecular characterization of a novel reassortant H1N2 influenza virus containing genes from the 2009 pandemic human H1N1 virus in swine from eastern China.

Science.gov (United States)

Peng, Xiuming; Wu, Haibo; Xu, Lihua; Peng, Xiaorong; Cheng, Linfang; Jin, Changzhong; Xie, Tiansheng; Lu, Xiangyun; Wu, Nanping

2016-06-01

Pandemic outbreaks of H1N1 swine influenza virus have been reported since 2009. Reassortant H1N2 viruses that contain genes from the pandemic H1N1 virus have been isolated in Italy and the United States. However, there is limited information regarding the molecular characteristics of reassortant H1N2 swine influenza viruses in eastern China. Active influenza surveillance programs in Zhejiang Province identified a novel H1N2 influenza virus isolated from pigs displaying clinical signs of influenza virus infection. Whole-genome sequencing was performed and this strain was compared with other influenza viruses available in GenBank. Phylogenetic analysis suggested that the novel strain contained genes from the 2009 pandemic human H1N1 and swine H3N2 viruses. BALB/c mice were infected with the isolated virus to assess its virulence in mice. While the novel H1N2 isolate replicated well in mice, it was found to be less virulent. These results provide additional evidence that swine serve as intermediate hosts or 'mixing vessels' for novel influenza viruses. They also emphasize the importance of surveillance in the swine population for use as an early warning system for influenza outbreaks in swine and human populations.

Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th-century pandemics.

Science.gov (United States)

Pasricha, Gunisha; Mishra, Akhilesh C; Chakrabarti, Alok K

2013-07-01

PB1F2 is the 11th protein of influenza A virus translated from +1 alternate reading frame of PB1 gene. Since the discovery, varying sizes and functions of the PB1F2 protein of influenza A viruses have been reported. Selection of PB1 gene segment in the pandemics, variable size and pleiotropic effect of PB1F2 intrigued us to analyze amino acid sequences of this protein in various influenza A viruses. Amino acid sequences for PB1F2 protein of influenza A H5N1, H1N1, H2N2, and H3N2 subtypes were obtained from Influenza Research Database. Multiple sequence alignments of the PB1F2 protein sequences of the aforementioned subtypes were used to determine the size, variable and conserved domains and to perform mutational analysis. Analysis showed that 96·4% of the H5N1 influenza viruses harbored full-length PB1F2 protein. Except for the 2009 pandemic H1N1 virus, all the subtypes of the 20th-century pandemic influenza viruses contained full-length PB1F2 protein. Through the years, PB1F2 protein of the H1N1 and H3N2 viruses has undergone much variation. PB1F2 protein sequences of H5N1 viruses showed both human- and avian host-specific conserved domains. Global database of PB1F2 protein revealed that N66S mutation was present only in 3·8% of the H5N1 strains. We found a novel mutation, N84S in the PB1F2 protein of 9·35% of the highly pathogenic avian influenza H5N1 influenza viruses. Varying sizes and mutations of the PB1F2 protein in different influenza A virus subtypes with pandemic potential were obtained. There was genetic divergence of the protein in various hosts which highlighted the host-specific evolution of the virus. However, studies are required to correlate this sequence variability with the virulence and pathogenicity. © 2012 John Wiley & Sons Ltd.

An Ecological Assessment of the Pandemic Threat of Zika Virus.

Science.gov (United States)

Carlson, Colin J; Dougherty, Eric R; Getz, Wayne

2016-08-01

The current outbreak of Zika virus poses a severe threat to human health. While the range of the virus has been cataloged growing slowly over the last 50 years, the recent explosive expansion in the Americas indicates that the full potential distribution of Zika remains uncertain. Moreover, many studies rely on its similarity to dengue fever, a phylogenetically closely related disease of unknown ecological comparability. Here we compile a comprehensive spatially-explicit occurrence dataset from Zika viral surveillance and serological surveys based in its native range, and construct ecological niche models to test basic hypotheses about its spread and potential establishment. The hypothesis that the outbreak of cases in Mexico and North America are anomalous and outside the native ecological niche of the disease, and may be linked to either genetic shifts between strains, or El Nino or similar climatic events, remains plausible at this time. Comparison of the Zika niche against the known distribution of dengue fever suggests that Zika is more constrained by the seasonality of precipitation and diurnal temperature fluctuations, likely confining autochthonous non-sexual transmission to the tropics without significant evolutionary change. Projecting the range of the diseases in conjunction with three major vector species (Aedes africanus, Ae. aegypti, and Ae. albopictus) that transmit the pathogens, under climate change, suggests that Zika has potential for northward expansion; but, based on current knowledge, our models indicate Zika is unlikely to fill the full range its vectors occupy, and public fear of a vector-borne Zika epidemic in the mainland United States is potentially informed by biased or limited scientific knowledge. With recent sexual transmission of the virus globally, we caution that our results only apply to the vector-borne transmission route of the pathogen, and while the threat of a mosquito-carried Zika pandemic may be overstated in the media

Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

Science.gov (United States)

Zhao, Xueli; Sun, Yipeng; Pu, Juan; Fan, Lihong; Shi, Weimin; Hu, Yanxin; Yang, Jun; Xu, Qi; Wang, Jingjing; Hou, Dongjun; Ma, Guangpeng; Liu, Jinhua

2011-01-01

Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1) with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus). Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

Directory of Open Access Journals (Sweden)

Xueli Zhao

Full Text Available Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1 with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus. Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

Potential of Complementary and Alternative Medicine in Preventive Management of Novel H1N1 Flu (Swine Flu Pandemic: Thwarting Potential Disasters in the Bud

Directory of Open Access Journals (Sweden)

Rajesh Arora

2011-01-01

Full Text Available The emergence of novel H1N1 has posed a situation that warrants urgent global attention. Though antiviral drugs are available in mainstream medicine for treating symptoms of swine flu, currently there is no preventive medicine available. Even when available, they would be in short supply and ineffective in a pandemic situation, for treating the masses worldwide. Besides the development of drug resistance, emergence of mutant strains of the virus, emergence of a more virulent strain, prohibitive costs of available drugs, time lag between vaccine developments, and mass casualties would pose difficult problems. In view of this, complementary and alternative medicine (CAM offers a plethora of interesting preventive possibilities in patients. Herbs exhibit a diverse array of biological activities and can be effectively harnessed for managing pandemic flu. Potentially active herbs can serve as effective anti influenza agents. The role of CAM for managing novel H1N1 flu and the mode of action of these botanicals is presented here in an evidence-based approach that can be followed to establish their potential use in the management of influenza pandemics. The complementary and alternative medicine approach deliberated in the paper should also be useful in treating the patients with serious influenza in non pandemic situations.

Influenza Pandemics: Past, Present and Future

Directory of Open Access Journals (Sweden)

Yu-Chia Hsieh

2006-01-01

Full Text Available Influenza A virus is well known for its capability for genetic changes either through antigen drift or antigen shift. Antigen shift is derived from reassortment of gene segments between viruses, and may result in an antigenically novel virus that is capable of causing a worldwide pandemic. As we trace backwards through the history of influenza pandemics, a repeating pattern can be observed, namely, a limited wave in the first year followed by global spread in the following year. In the 20th century alone, there were three overwhelming pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu, H2N2 (Asian flu and H3N2 (Hong Kong flu, respectively. In 1957 and 1968, excess mortality was noted in infants, the elderly and persons with chronic diseases, similar to what occurred during interpandemic periods. In 1918, there was one distinct peak of excess death in young adults aged between 20 and 40 years old; leukopenia and hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic pneumonia contributed to rapidly lethal outcome in young adults. Autopsies disclosed multiple-organ involvement, including pericarditis, myocarditis, hepatitis and splenomegaly. These findings are, in part, consistent with clinical manifestations of human infection with avian influenza A H5N1 virus, in which reactive hemophagocytic syndrome was a characteristic pathologic finding that accounted for pancytopenia, abnormal liver function and multiple organ failure. All the elements of an impending pandemic are in place. Unless effective measures are implemented, we will likely observe a pandemic in the coming seasons. Host immune response plays a crucial role in disease caused by newly emerged influenza virus, such as the 1918 pandemic strain and the recent avian H5N1 strain. Sustained activation of lymphocytes and macrophages after infection results in massive cytokine response, thus leading to severe systemic inflammation. Further investigations into how

Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies

DEFF Research Database (Denmark)

Dwyer, Dominic E; Nielsen, Henrik Ib

2011-01-01

The novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community...... and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection...

Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

International Nuclear Information System (INIS)

Wörmann, Xenia; Lesch, Markus; Welke, Robert-William; Okonechnikov, Konstantin; Abdurishid, Mirshat; Sieben, Christian; Geissner, Andreas; Brinkmann, Volker; Kastner, Markus; Karner, Andreas; Zhu, Rong; Hinterdorfer, Peter; Anish, Chakkumkal; Seeberger, Peter H.; Herrmann, Andreas

2016-01-01

The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA_1 D130E, HA_2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

2016-05-15

The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

Contemporary avian influenza A virus subtype H1, H6, H7, H10, and H15 hemagglutinin genes encode a mammalian virulence factor similar to the 1918 pandemic virus H1 hemagglutinin.

Science.gov (United States)

Qi, Li; Pujanauski, Lindsey M; Davis, A Sally; Schwartzman, Louis M; Chertow, Daniel S; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L; Slemons, Richard D; Walters, Kathie-Anne; Kash, John C; Taubenberger, Jeffery K

2014-11-18

Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals. Influenza viruses from birds can cause outbreaks in humans and may contribute to the development of pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its main surface protein, an H1 subtype hemagglutinin, was identified as a key mammalian virulence factor. In a previous study, a 1918 virus expressing an avian H1 gene was as virulent in mice as the reconstructed 1918 virus. Here, a set of avian influenza viruses was constructed, differing only by hemagglutinin subtype. Viruses with the avian H1, H6, H7, H10, and H15 subtypes caused severe disease in mice and damaged human lung cells. Consequently, infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals, and therefore surveillance for human infections

Public health intelligence and the detection of potential pandemics.

Science.gov (United States)

French, Martin; Mykhalovskiy, Eric

2013-02-01

This article considers contemporary developments in public health intelligence (PHI), especially their focus on health events of pandemic potential. It argues that the sociological study of PHI can yield important insights for the sociology of pandemics. PHI aims to detect health events as (or even before) they unfold. Whilst its apparatuses envelope traditional public health activities, such as epidemiological surveillance, they increasingly extend to non-traditional public health activities such as data-mining in electronically mediated social networks. With a focus on non-traditional PHI activities, the article first situates the study of PHI in relation to the sociology of public health. It then discusses the conceptualisation and actualisation of pandemics, reflecting on how public health professionals and organisations must equip themselves with diverse allies in order to realise the claims they make about pandemic phenomena. Finally, using the analytic tools of actor-network theory, sites for future empirical research that can contribute to the sociology of pandemics are suggested. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

Pandemic influenza--including a risk assessment of H5N1.

Science.gov (United States)

Taubenberger, J K; Morens, D M

2009-04-01

Influenza pandemics and epidemics have apparently occurred since at least the Middle Ages. When pandemics appear, 50% or more of an affected population can be infected in a single year, and the number of deaths caused by influenza can dramatically exceed what is normally expected. Since 1500, there appear to have been 13 or more influenza pandemics. In the past 120 years there were undoubted pandemics in 1889, 1918, 1957, 1968, and 1977. Although most experts believe we will face another influenza pandemic, it is impossible to predict when it will appear, where it will originate, or how severe it will be. Nor is there agreement about the subtype of influenza virus most likely to cause the next pandemic. The continuing spread of H5N1 highly pathogenic avian influenza viruses has heightened interest in pandemic prediction. Despite uncertainties in the historical record of the pre-virology era, study of previous pandemics may help guide future pandemic planning and lead to a better understanding of the complex ecobiology underlying the formation of pandemic strains of influenza A viruses.

Mathematical Assessment of Canada’s Pandemic Influenza Preparedness Plan

Directory of Open Access Journals (Sweden)

Abba B Gumel

2008-01-01

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

Pandemic H1N1 2009 virus in Norwegian pigs naïve to influenza A viruses

DEFF Research Database (Denmark)

Germundsson, A.; Gjerset, B.; Hjulsager, Charlotte Kristiane

In March-April 2009, a novel pandemic influenza A (H1N1) virus (pH1N1-09v) emerged in the human population. The first case of pH1N1v infection in pigs was reported from Canada in May 2009. In Norway, pH1N1v infection was recorded in a swine herd on the 10th of October of 2009. Here, we report...... isolated from a confirmed human case at the farm. The majority of the positive herds had a history of contact with humans that were diagnosed with pandemic influenza or with ILI. This suggests that infected humans are the most likely source for introduction of pH1N1-09v to the Norwegian pig herds...

Mutation analysis of 2009 pandemic influenza A(H1N1 viruses collected in Japan during the peak phase of the pandemic.

Directory of Open Access Journals (Sweden)

Jean-Étienne Morlighem

Full Text Available 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.

A definition for influenza pandemics based on historical records.

Science.gov (United States)

Potter, Chris W; Jennings, Roy

2011-10-01

To analyse the records of past influenza outbreaks to determine a definition for pandemics. Analysis of publications of large outbreaks of influenza which have occurred since 1889/90, and to match the results against the current definitions of an influenza pandemic. According to the general understanding of a pandemic, nine outbreaks of influenza since 1889/90 satisfy the definition; however, for two of these, occurring in 1900 and 1933, the data are limited. The special condition for an influenza pandemic requires, in one definition, that the virus strain responsible could not have arisen from the previous circulating strain by mutation; and in the second, that the new strain be a different subtype to the previously circulating strain. Both these restrictions deny pandemic status to two, and possibly three, influenza outbreaks which were pandemics according to the more general understanding of the term. These observations suggest that a re-evaluation of the criteria which define influenza pandemics should be carried out. The contradiction outlined above brings the previous definitions of an influenza pandemic into question; however, this can be resolved by defining an influenza pandemic by the following criteria. Thus, an influenza pandemic arises at a single, specific place and spreads rapidly to involve numerous countries. The haemagglutinin (HA) of the emergent virus does not cross-react serologically with the previously dominant virus strain(s), and there is a significant lack of immunity in the population against the emergent virus. These three criteria are interlinked and can be determined early to alert authorities who could respond appropriately. Other criteria associated with pandemics are necessarily retrospective, although important and valid. The implications of this definition are discussed. Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2010-04-01

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

Simplifying influenza vaccination during pandemics : sublingual priming and intramuscular boosting of immune responses with heterologous whole inactivated influenza vaccine

NARCIS (Netherlands)

Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

2014-01-01

The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been

Serological response to the 2009 pandemic influenza A (H1N1 virus for disease diagnosis and estimating the infection rate in Thai population.

Directory of Open Access Journals (Sweden)

Hatairat Lerdsamran

Full Text Available BACKGROUND: Individuals infected with the 2009 pandemic virus A(H1N1 developed serological response which can be measured by hemagglutination-inhibition (HI and microneutralization (microNT assays. METHODOLOGY/PRINCIPAL FINDINGS: MicroNT and HI assays for specific antibody to the 2009 pandemic virus were conducted in serum samples collected at the end of the first epidemic wave from various groups of Thai people: laboratory confirmed cases, blood donors and health care workers (HCW in Bangkok and neighboring province, general population in the North and the South, as well as archival sera collected at pre- and post-vaccination from vaccinees who received influenza vaccine of the 2006 season. This study demonstrated that goose erythrocytes yielded comparable HI antibody titer as compared to turkey erythrocytes. In contrast to the standard protocol, our investigation found out the necessity to eliminate nonspecific inhibitor present in the test sera by receptor destroying enzyme (RDE prior to performing microNT assay. The investigation in pre-pandemic serum samples showed that HI antibody was more specific to the 2009 pandemic virus than NT antibody. Based on data from pre-pandemic sera together with those from the laboratory confirmed cases, HI antibody titers ≥ 40 for adults and ≥ 20 for children could be used as the cut-off level to differentiate between the individuals with or without past infection by the 2009 pandemic virus. CONCLUSIONS/SIGNIFICANCE: Based on the cut-off criteria, the infection rates of 7 and 12.8% were estimated in blood donors and HCW, respectively after the first wave of the 2009 influenza pandemic. Among general population, the infection rate of 58.6% was found in children versus 3.1% in adults.

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

Science.gov (United States)

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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pandemic influenza – including a risk assessment of H5N1

Science.gov (United States)

Taubenberger, J.K.; Morens, D.M.

2009-01-01

Summary Influenza pandemics and epidemics have apparently occurred since at least the Middle Ages. When pandemics appear, 50% or more of an affected population can be infected in a single year, and the number of deaths caused by influenza can dramatically exceed what is normally expected. Since 1500, there appear to have been 13 or more influenza pandemics. In the past 120 years there were undoubted pandemics in 1889, 1918, 1957, 1968, and 1977. Although most experts believe we will face another influenza pandemic, it is impossible to predict when it will appear, where it will originate, or how severe it will be. Nor is there agreement about the subtype of influenza virus most likely to cause the next pandemic. The continuing spread of H5N1 highly pathogenic avian influenza viruses has heightened interest in pandemic prediction. Despite uncertainties in the historical record of the pre-virology era, study of previous pandemics may help guide future pandemic planning and lead to a better understanding of the complex ecobiology underlying the formation of pandemic strains of influenza A viruses. PMID:19618626

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

Science.gov (United States)

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

2013-09-01

To screen children with influenza like illness or with symptoms of acute respiratory tract infections for influenza A virus infection - post swine flu pandemic era - using rapid influenza diagnostic tests. During two years (2010 & 2011), 1 200 children with influenza like illness or acute respiratory tract infections (according to World Health Organization criteria) were recruited. Their ages ranged from 2-60 months. Nasopharyngeal aspirates specimens were collected from all children for rapid influenza A diagnostic test. Influenza A virus rapid test was positive in 47.5% of the children; the majority (89.6%) were presented with lower respiratory tract infections. Respiratory rate and temperature were significantly higher among positive rapid influenza test patients. Influenza A virus infection is still a major cause of respiratory tract infections in Egyptian children. It should be considered in all cases with cough and febrile episodes and influenza like symptoms even post swine flu pandemic. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Radiologic Review of an Outbreak of the Pandemic (H1N1) 2009 Virus Infection at a University Hospital in Seoul, Korea

International Nuclear Information System (INIS)

Choi, Seung Hee; Kang, Eun Young; Kim, Yoon Kyung; Woo, Ok Hee; Yong, Hwan Seok; Oh, Yu Whan; Kim, Jang Su

2011-01-01

To assess the frequency of radiologic abnormalities and investigate the radiologic findings of patients with a pandemic (H1N1) 2009 virus infection at a University hospital in Seoul, Korea. In November 2009, 9,427 patients were tested for pandemic (H1N1) 2009 virus and 3,849 (41%) were positive. Among them, only 338 (9%) underwent chest radiographs and 13 (0.3%) received chest CT. Two radiologists retrospectively reviewed all the radiologic images. Among the 338 patients, 287 (85%) were normal and 51 (15%) showed abnormalities. The frequency of abnormalities was significantly higher in children (41/212=19%) than in adults (10/126=8%) (p = 0.005). Of them, 42 (82%) patients had airspace pneumonia, whereas the remaining patients showed a bronchopneumonia pattern. Unilateral (82%) involvement was more common than bilateral (18%) involvement. Among patients who received chest CT, 12 (92%) showed abnormalities, with bilateral (67%) and random (75%) involvement being more common. Ground-glass opacity (67%) and centrilobular nodules (58%) were the more common CT findings. Only a small number of patients were critically ill enough to undergo further radiologic evaluation as a result of pandemic (H1N1) 2009 virus infection, and most patients had normal chest radiographs. Unilateral airspace pneumonia was the most common abnormality in patients infected with pandemic (H1N1) 2009 virus.

Memory immune responses against pandemic (H1N1 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.

Directory of Open Access Journals (Sweden)

Masahiko Arikata

Full Text Available We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009 H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02, were used to analyze peptide-specific CD8(+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1 than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1 in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8(+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses

Avian Influenza Virus (H5N1): a Threat to Human Health

OpenAIRE

Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

2007-01-01

Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, ...

Updated preparedness and response framework for influenza pandemics.

Science.gov (United States)

Holloway, Rachel; Rasmussen, Sonja A; Zaza, Stephanie; Cox, Nancy J; Jernigan, Daniel B

2014-09-26

The complexities of planning for and responding to the emergence of novel influenza viruses emphasize the need for systematic frameworks to describe the progression of the event; weigh the risk of emergence and potential public health impact; evaluate transmissibility, antiviral resistance, and severity; and make decisions about interventions. On the basis of experience from recent influenza responses, CDC has updated its framework to describe influenza pandemic progression using six intervals (two prepandemic and four pandemic intervals) and eight domains. This updated framework can be used for influenza pandemic planning and serves as recommendations for risk assessment, decision-making, and action in the United States. The updated framework replaces the U.S. federal government stages from the 2006 implementation plan for the National Strategy for Pandemic Influenza (US Homeland Security Council. National strategy for pandemic influenza: implementation plan. Washington, DC: US Homeland Security Council; 2006. Available at http://www.flu.gov/planning-preparedness/federal/pandemic-influenza-implementation.pdf). The six intervals of the updated framework are as follows: 1) investigation of cases of novel influenza, 2) recognition of increased potential for ongoing transmission, 3) initiation of a pandemic wave, 4) acceleration of a pandemic wave, 5) deceleration of a pandemic wave, and 6) preparation for future pandemic waves. The following eight domains are used to organize response efforts within each interval: incident management, surveillance and epidemiology, laboratory, community mitigation, medical care and countermeasures, vaccine, risk communications, and state/local coordination. Compared with the previous U.S. government stages, this updated framework provides greater detail and clarity regarding the potential timing of key decisions and actions aimed at slowing the spread and mitigating the impact of an emerging pandemic. Use of this updated framework is

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

Science.gov (United States)

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

1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

DEFF Research Database (Denmark)

Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

[Influenza A/H5N1 virus outbreaks and prepardness to avert flu pandemic].

Science.gov (United States)

Haque, A; Lucas, B; Hober, D

2007-01-01

This review emphasizes the need to improve the knowledge of the biology of H5N1 virus, a candidate for causing the next influenza pandemic. In-depth knowledge of mode of infection, mechanisms of pathogenesis and immune response will help in devising an efficient and practical control strategy against this flu virus. We have discussed limitations of currently available vaccines and proposed novel approaches for making better vaccines against H5N1 influenza virus. They include cell-culture system, reverse genetics, adjuvant development. Our review has also underscored the concept of therapeutic vaccine (anti-disease vaccine), which is aimed at diminishing 'cytokine storm' seen in acute respiratory distress syndrome and/or hemophagocytosis.

Early-warning signals for an outbreak of the influenza pandemic

Science.gov (United States)

Ren, Di; Gao, Jie

2011-12-01

Over the course of human history, influenza pandemics have been seen as major disasters, so studies on the influenza virus have become an important issue for many experts and scholars. Comprehensive research has been performed over the years on the biological properties, chemical characteristics, external environmental factors and other aspects of the virus, and some results have been achieved. Based on the chaos game representation walk model, this paper uses the time series analysis method to study the DNA sequences of the influenza virus from 1913 to 2010, and works out the early-warning signals indicator value for the outbreak of an influenza pandemic. The variances in the CGR walk sequences for the pandemic years (or + -1 to 2 years) are significantly higher than those for the adjacent years, while those in the non-pandemic years are usually smaller. In this way we can provide an influenza early-warning mechanism so that people can take precautions and be well prepared prior to a pandemic.

Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells.

Directory of Open Access Journals (Sweden)

Rachael L Gerlach

Full Text Available Replication, cell tropism and the magnitude of the host's antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host responses during infection of well-differentiated, primary human bronchial epithelial cells (wd-NHBE may differ between seasonal (H1N1 A/BN/59/07 and H1N1pdm isolates from a fatal (A/KY/180/10 and nonfatal (A/KY/136/09 case. For each virus, the level of infectious virus and host response to infection (gene expression and apical/basal cytokine/chemokine profiles were measured in wd-NHBE at 8, 24, 36, 48 and 72 hours post-infection (hpi. At 24 and 36 hpi, KY/180 showed a significant, ten-fold higher titer as compared to the other two isolates. Apical cytokine/chemokine levels of IL-6, IL-8 and GRO were similar in wd-NHBE cells infected by each of these viruses. At 24 and 36 hpi, NHBE cells had greater levels of pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, and CCL5, when infected by pandemic viruses as compared with seasonal. Polarization of IL-6 in wd-NHBE cells was greatest at 36 hpi for all isolates. Differential polarized secretion was suggested for CCL5 across isolates. Despite differences in viral titer across isolates, no significant differences were observed in KY/180 and KY/136 gene expression intensity profiles. Microarray profiles of wd-NHBE cells diverged at 36 hpi with 1647 genes commonly shared by wd-NHBE cells infected by pandemic, but not seasonal isolates. Significant differences were observed in cytokine signaling, apoptosis, and cytoskeletal arrangement pathways. Our studies revealed differences in temporal dynamics and basal levels of cytokine/chemokine responses of wd-NHBE cells infected with each isolate; however, wd-NHBE cell gene intensity profiles were not significantly

The global antigenic diversity of swine influenza A viruses

DEFF Research Database (Denmark)

Lewis, Nicola S; Russell, Colin A; Langat, Pinky

2016-01-01

Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential...

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

Directory of Open Access Journals (Sweden)

Steven Rockman

2017-05-01

Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

International Nuclear Information System (INIS)

Pan, Yang; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Inoue, Yuji; Yasugi, Mayo; Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha; Du, Anariwa; Boonsathorn, Naphatsawan; Ibrahim, Madiha S.

2014-01-01

Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses

Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

Energy Technology Data Exchange (ETDEWEB)

Pan, Yang [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Sasaki, Tadahiro [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Inoue, Yuji [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yasugi, Mayo [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Du, Anariwa [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Boonsathorn, Naphatsawan [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Ibrahim, Madiha S. [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour (Egypt); and others

2014-07-18

Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

Development of an influenza virus vaccine using the baculovirus-insect cell expression system : implications for pandemic preparedness

NARCIS (Netherlands)

Cox, M.M.J.

2009-01-01

Key word

Influenza, rHA, vaccine, baculovirus, insect cells, production, pandemic preparedness

Influenza (or flu) is a highly contagious, acute viral respiratory disease that occurs seasonally in most parts of the world and is caused by influenza viruses. Influenza

Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

Science.gov (United States)

Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

2010-01-01

The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.

Avian influenza virus transmission to mammals.

Science.gov (United States)

Herfst, S; Imai, M; Kawaoka, Y; Fouchier, R A M

2014-01-01

Influenza A viruses cause yearly epidemics and occasional pandemics. In addition, zoonotic influenza A viruses sporadically infect humans and may cause severe respiratory disease and fatalities. Fortunately, most of these viruses do not have the ability to be efficiently spread among humans via aerosols or respiratory droplets (airborne transmission) and to subsequently cause a pandemic. However, adaptation of these zoonotic viruses to humans by mutation or reassortment with human influenza A viruses may result in airborne transmissible viruses with pandemic potential. Although our knowledge of factors that affect mammalian adaptation and transmissibility of influenza viruses is still limited, we are beginning to understand some of the biological traits that drive airborne transmission of influenza viruses among mammals. Increased understanding of the determinants and mechanisms of airborne transmission may aid in assessing the risks posed by avian influenza viruses to human health, and preparedness for such risks. This chapter summarizes recent discoveries on the genetic and phenotypic traits required for avian influenza viruses to become airborne transmissible between mammals.

Immunocapture isotope dilution mass spectrometry in response to a pandemic influenza threat.

Science.gov (United States)

Pierce, Carrie L; Williams, Tracie L; Santana, Wanda I; Levine, Marnie; Chen, Li-Mei; Cooper, Hans C; Solano, Maria I; Woolfitt, Adrian R; Marasco, Wayne A; Fang, He; Donis, Ruben O; Barr, John R

2017-09-05

As a result of recent advances in mass spectrometry-based protein quantitation methods, these techniques are now poised to play a critical role in rapid formulation of pandemic influenza vaccines. Analytical techniques that have been developed and validated on seasonal influenza strains can be used to increase the quality and decrease the time required to deliver protective pandemic vaccines to the global population. The emergence of a potentially pandemic avian influenza A (H7N9) virus in March of 2013, prompted the US public health authorities and the vaccine industry to initiate production of a pre-pandemic vaccine for preparedness purposes. To this end, we evaluated the feasibility of using immunocapture isotope dilution mass spectrometry (IC-IDMS) to evaluate the suitability of the underlying monoclonal and polyclonal antibodies (mAbs and pAbs) for their capacity to isolate the H7 hemagglutinin (HA) in this new vaccine for quantification by IDMS. A broad range of H7 capture efficiencies was observed among mAbs tested by IC-IDMS with FR-545, 46/6, and G3 A533 exhibiting the highest cross-reactivity capabilities to H7 of A/Shanghai/2/2013. MAb FR-545 was selected for continued assessment, evaluated by IC-IDMS for mAb reactivity against H7 in the H7N9 candidate vaccine virus and compared with/to reactivity to the reference polyclonal antiserum in allantoic fluid, purified whole virus, lyophilized whole virus and final detergent-split monovalent vaccine preparations for vaccine development. IC-IDMS assessment of FR-545 alongside IC-IDMS using the reference polyclonal antiserum to A/Shanghai/2/2013 and with the regulatory SRID method showed strong correlation and mAb IC-IDMS could have played an important role in the event a potential surrogate potency test was required to be rapidly implemented. Published by Elsevier Ltd.

Pandemic H1N1 2009 virus in Danish pigs: Diagnosis and lack of surveillance

DEFF Research Database (Denmark)

Larsen, Lars Erik; Nielsen, L. P.; Breum, Solvej Østergaard

In March-April 2009, a novel pandemic H1N1 virus (H1N1v) of likely swine origin emerged in the human population globally. The first case in pigs was reported from Canada in May 2009 and presently almost all countries with pig production have reported cases. The emergence of a new influenza subtype...

Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

Science.gov (United States)

O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

2012-08-01

Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

Early-warning signals for an outbreak of the influenza pandemic

International Nuclear Information System (INIS)

Ren Di; Gao Jie

2011-01-01

Over the course of human history, influenza pandemics have been seen as major disasters, so studies on the influenza virus have become an important issue for many experts and scholars. Comprehensive research has been performed over the years on the biological properties, chemical characteristics, external environmental factors and other aspects of the virus, and some results have been achieved. Based on the chaos game representation walk model, this paper uses the time series analysis method to study the DNA sequences of the influenza virus from 1913 to 2010, and works out the early-warning signals indicator value for the outbreak of an influenza pandemic. The variances in the CGR walk sequences for the pandemic years (or + −1 to 2 years) are significantly higher than those for the adjacent years, while those in the non-pandemic years are usually smaller. In this way we can provide an influenza early-warning mechanism so that people can take precautions and be well prepared prior to a pandemic. (interdisciplinary physics and related areas of science and technology)

Pandemic (H1N1 2009 influenza community transmission was established in one Australian state when the virus was first identified in North America.

Directory of Open Access Journals (Sweden)

Heath A Kelly

Full Text Available BACKGROUND: In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1 2009 influenza in the world. We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA. METHODS: We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. RESULTS: Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. CONCLUSION: Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.

Novel framework for assessing epidemiologic effects of influenza epidemics and pandemics.

Science.gov (United States)

Reed, Carrie; Biggerstaff, Matthew; Finelli, Lyn; Koonin, Lisa M; Beauvais, Denise; Uzicanin, Amra; Plummer, Andrew; Bresee, Joe; Redd, Stephen C; Jernigan, Daniel B

2013-01-01

The effects of influenza on a population are attributable to the clinical severity of illness and the number of persons infected, which can vary greatly between seasons or pandemics. To create a systematic framework for assessing the public health effects of an emerging pandemic, we reviewed data from past influenza seasons and pandemics to characterize severity and transmissibility (based on ranges of these measures in the United States) and outlined a formal assessment of the potential effects of a novel virus. The assessment was divided into 2 periods. Because early in a pandemic, measurement of severity and transmissibility is uncertain, we used a broad dichotomous scale in the initial assessment to divide the range of historic values. In the refined assessment, as more data became available, we categorized those values more precisely. By organizing and prioritizing data collection, this approach may inform an evidence-based assessment of pandemic effects and guide decision making.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

Science.gov (United States)

Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

2011-03-23

The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal

Directory of Open Access Journals (Sweden)

Shrestha Sirjana

2011-03-01

Full Text Available Abstract Background The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Results Out of 609 collected samples, 302 (49.6% were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3% were positive for Pandemic influenza A/H1N1 and 130 (21.3% were Seasonal influenza A. Most of the pandemic cases (53% were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1v type. Conclusion The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1v type.

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

Directory of Open Access Journals (Sweden)

Yonghui Zhang

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

Deciphering the Swine-Flu Pandemics of 1918 and 2009

Science.gov (United States)

Goldstein, Richard; Dos Reis, Mario; Tamuri, Asif; Hay, Alan

The devastating "Spanish flu" of 1918 killed an estimated 50 million people worldwide, ranking it as the deadliest pandemic in recorded human history. It is generally believed that the virus transferred from birds directly to humans shortly before the start of the pandemic, subsequently jumping from humans to swine. By developing 'non-homogeneous' substitution models that consider that substitution patterns may be different in human, avian, and swine hosts, we can determine the timing of the host shift to mammals. We find it likely that the Spanish flu of 1918, like the current 2009 pandemic, was a 'swine-origin' influenza virus. Now that we are faced with a new pandemic, can we understand how influenza is able to change hosts? Again by modelling the evolutionary process, considering the different selective constraints for viruses in the different hosts, we can identify locations that seem to be under different selective constraints in humans and avian hosts. This allows us to identify changes that may have facilitated the establishment of the 2009 swine-origin flu in humans.

Differential host determinants contribute to the pathogenesis of 2009 pandemic H1N1 and human H5N1 influenza A viruses in experimental mouse models.

Science.gov (United States)

Otte, Anna; Sauter, Martina; Alleva, Lisa; Baumgarte, Sigrid; Klingel, Karin; Gabriel, Gülsah

2011-07-01

Influenza viruses are responsible for high morbidities in humans and may, eventually, cause pandemics. Herein, we compared the pathogenesis and host innate immune responses of a seasonal H1N1, two 2009 pandemic H1N1, and a human H5N1 influenza virus in experimental BALB/c and C57BL/6J mouse models. We found that both 2009 pandemic H1N1 isolates studied (A/Hamburg/05/09 and A/Hamburg/NY1580/09) were low pathogenic in BALB/c mice [log mouse lethal dose 50 (MLD(50)) >6 plaque-forming units (PFU)] but displayed remarkable differences in virulence in C57BL/6J mice. A/Hamburg/NY1580/09 was more virulent (logMLD(50) = 3.5 PFU) than A/Hamburg/05/09 (logMLD(50) = 5.2 PFU) in C57BL/6J mice. In contrast, the H5N1 influenza virus was more virulent in BALB/c mice (logMLD(50) = 0.3 PFU) than in C57BL/6J mice (logMLD(50) = 1.8 PFU). Seasonal H1N1 influenza revealed marginal pathogenicity in BALB/c or C57BL/6J mice (logMLD(50) >6 PFU). Enhanced susceptibility of C57BL/6J mice to pandemic H1N1 correlated with a depressed cytokine response. In contrast, enhanced H5N1 virulence in BALB/c mice correlated with an elevated proinflammatory cytokine response. These findings highlight that host determinants responsible for the pathogenesis of 2009 pandemic H1N1 influenza viruses are different from those contributing to H5N1 pathogenesis. Our results show, for the first time to our knowledge, that the C57BL/6J mouse strain is more appropriate for the evaluation and identification of intrinsic pathogenicity markers of 2009 pandemic H1N1 influenza viruses that are "masked" in BALB/c mice. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Initial Identification and Characterization of an Emerging Zoonotic Influenza Prior to Pandemic Spread

Science.gov (United States)

2010-11-01

equally closely strains of both H1N2 influenza A virus of swine origin and H3N2 influenza A virus of avian origin. The expected matches for each of...Naval Health Research Center Initial Identification and Characterization of an Emerging Zoonotic Influenza Virus Prior to Pandemic Spread...10.1128/JCM.01336-10 PMCID: PMC3020883 Initial Identification and Characterization of an Emerging Zoonotic Influenza Virus Prior to Pandemic

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

DEFF Research Database (Denmark)

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

2011-01-01

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13-23. Background Alternative influenza vaccines...... and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change...... in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were...

Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

Directory of Open Access Journals (Sweden)

Qiang Shao

Full Text Available The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50 and cytopathic effect (CPE inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731 and A/California/04/2009 H1N1 (CA04 replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8, A/WSN/1933 H1N1 (WSN, A/Swine/Beijing/26/2008 H1N1 (SW26, A/Chicken/Shandong/LY/2008 H9N2 (LY08, and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07 viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice

Science.gov (United States)

The HA protein of the 2009 pandemic H1N1viruses (14 H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through reassortment and incorporation of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains...

Mathematical assessment of Canada's pandemic influenza preparedness plan.

Science.gov (United States)

Gumel, Abba B; Nuño, Miriam; Chowell, Gerardo

2008-03-01

The presence of the highly pathogenic avian H5N1 virus in wild bird populations in several regions of the world, together with recurrent cases of H5N1 influenza arising primarily from direct contact with poultry, have highlighted the urgent need for prepared-ness and coordinated global strategies to effectively combat a potential influenza pandemic. The purpose of the present study was to evaluate the Canadian pandemic influenza preparedness plan. A mathematical model of the transmission dynamics of influenza was used to keep track of the population according to risk of infection (low or high) and infection status (susceptible, exposed or infectious). The model was parametrized using available Canadian demographic data. The model was then used to evaluate the key components outlined in the Canadian plan. The results indicated that the number of cases, mortalities and hospitalizations estimated in the Canadian plan may have been underestimated; the use of antivirals, administered therapeutically, prophylactically or both, is the most effective single intervention followed by the use of a vaccine and basic public health measures; and the combined use of pharmaceutical interventions (antivirals and vaccine) can dramatically minimize the burden of the pending influenza pandemic in Canada. Based on increasing concerns of Oseltamivir resistance (wide-scale implementation), coupled with the expected unavailability of a suitable vaccine during the early stages of a pandemic, the present study evaluated the potential impact of non-pharmaceutical interventions (NPIs) which were not emphasized in the current Canadian plan. To this end, the findings suggest that the use of NPIs can drastically reduce the burden of a pandemic in Canada. A deterministic model was designed and used to assess Canada's pandemic preparedness plan. The study showed that the estimates of pandemic influenza burden given in the Canada pandemic preparedness plan may be an underestimate, and that Canada

The public health impact of avian influenza viruses.

Science.gov (United States)

Katz, J M; Veguilla, V; Belser, J A; Maines, T R; Van Hoeven, N; Pappas, C; Hancock, K; Tumpey, T M

2009-04-01

Influenza viruses with novel hemagglutinin and 1 or more accompanying genes derived from avian influenza viruses sporadically emerge in humans and have the potential to result in a pandemic if the virus causes disease and spreads efficiently in a population that lacks immunity to the novel hemagglutinin. Since 1997, multiple avian influenza virus subtypes have been transmitted directly from domestic poultry to humans and have caused a spectrum of human disease, from asymptomatic to severe and fatal. To assess the pandemic risk that avian influenza viruses pose, we have used multiple strategies to better understand the capacity of avian viruses to infect, cause disease, and transmit among mammals, including humans. Seroepidemiologic studies that evaluate the frequency and risk of human infection with avian influenza viruses in populations with exposure to domestic or wild birds can provide a better understanding of the pandemic potential of avian influenza subtypes. Investigations conducted in Hong Kong following the first H5N1 outbreak in humans in 1997 determined that exposure to poultry in live bird markets was a key risk factor for human disease. Among poultry workers, butchering and exposure to sick poultry were risk factors for antibody to H5 virus, which provided evidence for infection. A second risk assessment tool, the ferret, can be used to evaluate the level of virulence and potential for host-to-host transmission of avian influenza viruses in this naturally susceptible host. Avian viruses isolated from humans exhibit a level of virulence and transmissibility in ferrets that generally reflects that seen in humans. The ferret model thus provides a means to monitor emerging avian influenza viruses for pandemic risk, as well as to evaluate laboratory-generated reassortants and mutants to better understand the molecular basis of influenza virus transmissibility. Taken together, such studies provide valuable information with which we can assess the public

Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

Science.gov (United States)

Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

2015-09-24

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs.

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

International Nuclear Information System (INIS)

Yun, Tae Jin; Kwon, Gu Jin; Oh, Mi Kyeong; Woo, Sung Koo; Park, Seung Hoon; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo; Yim, Jae Joon; Kim, Jong Sung; Park, Chang Min

2010-01-01

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

The early days of pandemic (H1N1 2009 virus infection in the central region of Portugal

Directory of Open Access Journals (Sweden)

V. Duque

2010-11-01

Full Text Available Background: The first case of pandemic (H1N1 2009 virus infection was diagnosed in the central region of Portugal on June 16, 2009, in a woman infected in Canada. Methods: The aim of our study was, first to characterize the clinical and epidemiologic aspects of all the patients with clinical manifestations included in the definition of a case for investigation with samples submitted to diagnosis of the pandemic (H1N1 2009 virus infection, in the central region of Portugal; second, to assess the precision of the case definition of case for investigation considered in the study according to the presence or the absence of fever at the moment of clinical observation. We reviewed the medical records of all the patients presenting with Influenza like-illness classified as a case for investigation and the first cases of patients infected with the new pandemic (H1N1 2009 virus, diagnosed in the central region of Portugal during the pandemic period between June and August, 2009, were analyzed. Real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR testing was used to confirm the pandemic (H1N1 2009 virus infection. Data collection was performed using a standardized paper format in agreement with the General Health Directorate. Results and discussion: Pandemic (H1N1 2009 virus infection was confirmed in 255 patients. Overall, median age was 23 years and 42.7% were included in the category of 20 to 29 years. Confirmed infection in patients with less than 2 years or greater than 50 years was a rare event. The first cases were imported from Europe, namely France, Spain and England. In a second phase, pandemic (H1N1 2009 virus infection was acquired in the south of Portugal (Algarve. The incidence rate for pandemic (H1N1 2009 virus infection was 10.7 per 100,000 persons and was different according to the district. It was higher in the district of Coimbra and Guarda where the main roads are connecting to Europe. The median calculated incubation

Cross talk between animal and human influenza viruses.

Science.gov (United States)

Ozawa, Makoto; Kawaoka, Yoshihiro

2013-01-01

Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the past decade, the first pandemic of the twenty-first century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses.

Mutations in polymerase genes enhanced the virulence of 2009 pandemic H1N1 influenza virus in mice.

Directory of Open Access Journals (Sweden)

Wenfei Zhu

Full Text Available Influenza A virus can infect a wide variety of animal species with illness ranging from mild to severe, and is a continual cause for concern. Genetic mutations that occur either naturally or during viral adaptation in a poorly susceptible host are key mechanisms underlying the evolution and virulence of influenza A virus. Here, the variants containing PA-A36T or PB2-H357N observed in the mouse-adapted descendants of 2009 pandemic H1N1 virus (pH1N1, A/Sichuan/1/2009 (SC, were characterized. Both mutations enhanced polymerase activity in mammalian cells. These effects were confirmed using recombinant SC virus containing polymerase genes with wild type (WT or mutant PA or PB2. The PA-A36T mutant showed enhanced growth property compared to the WT in both human A549 cells and porcine PK15 cells in vitro, without significant effect on viral propagation in murine LA-4 cells and pathogenicity in mice; however, it did enhance the lung virus titer. PB2-H357N variant demonstrated growth ability comparable to the WT in A549 cells, but replicated well in PK15, LA-4 cells and in mice with an enhanced pathogenic phenotype. Despite such mutations are rare in nature, they could be observed in avian H5 and H7 subtype viruses which were currently recognized to pose potential threat to human. Our findings indicated that pH1N1 may adapt well in mammals when acquiring these mutations. Therefore, future molecular epidemiological surveillance should include scrutiny of both markers because of their potential impact on pathogenesis.

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses.

Science.gov (United States)

Pascua, Philippe Noriel Q; Song, Min-Suk; Lee, Jun Han; Baek, Yun Hee; Kwon, Hyeok-il; Park, Su-Jin; Choi, Eun Hye; Lim, Gyo-Jin; Lee, Ok-Jun; Kim, Si-Wook; Kim, Chul-Joong; Sung, Moon Hee; Kim, Myung Hee; Yoon, Sun-Woo; Govorkova, Elena A; Webby, Richard J; Webster, Robert G; Choi, Young-Ki

2012-09-25

Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA(225G) and NA(315N) substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA(225G) and NA(315N) as potential virulence markers in mammals.

Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season

Directory of Open Access Journals (Sweden)

Timen Aura

2011-10-01

Full Text Available Abstract Background In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1 2009 virus infection was performed. Methods The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season. Results A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02, and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005. Conclusions The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward

Swine flu - A pandemic outbreak

Directory of Open Access Journals (Sweden)

Jini George

Full Text Available Hippocrates had described influenza like outbreak in 412 B.C. and since then repeated influenza like epidemics and pandemics have been recorded in recent times. One of the greatest killers of all time was the pandemic of swine flu (Spanish flu of 1918-1919, when 230 million people died. Annual influenza epidemics are estimated to affect 5–15% of the global population, resulting in severe illness in 3–5 million patients causing 250,000–500,000 deaths worldwide. Severe illness and deaths occur mainly in the high-risk populations of infants, the elderly and chronically ill patients. The 2009 outbreak of swine flu is thought to be a mutation more specifically a reassortment of four known strains of influenza A virus subtype H1N1; one endemic in humans, one endemic in birds, and two endemic in pigs. WHO officially declared the outbreak to be a pandemic on June 11, 2009, but stressed that the new designation was a result of the global "spread of the virus," not its severity. [Vet World 2009; 2(12.000: 472-474

The potential impact of the next influenza pandemic on a national primary care medical workforce

OpenAIRE

Wilson, Nick; Baker, Michael; Crampton, Peter; Mansoor, Osman

2005-01-01

Abstract Background Another influenza pandemic is all but inevitable. We estimated its potential impact on the primary care medical workforce in New Zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. Methods The model in the "FluAid" software (Centers for Disease Control and Prevention, CDC, Atlanta) was applied to the New Zealand primary care medical workforce (i.e., general practitioners). Results At its peak (week 4) the pandemic would lead to...

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

Science.gov (United States)

Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

2011-02-01

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

Science.gov (United States)

Mooney, Alaina J; Gabbard, Jon D; Li, Zhuo; Dlugolenski, Daniel A; Johnson, Scott K; Tripp, Ralph A; He, Biao; Tompkins, S Mark

2017-12-01

Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. IMPORTANCE Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing

New reassortant and enzootic European swine influenza 1 viruses transmits efficiently through direct contact in the ferret model

DEFF Research Database (Denmark)

Fobian, Kristina; P. Fabrizio, Thomas; Yoon, Sun-Woo

2015-01-01

The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs...... with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2 and two were new reassortants, one with avian-like H1...... and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titers in nasal wash- and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics...

A historical perspective of influenza A(H1N2) virus.

Science.gov (United States)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Cuiling Xu

2011-04-01

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

Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential.

Directory of Open Access Journals (Sweden)

Hongquan Wan

2008-08-01

Full Text Available H9N2 avian influenza A viruses are endemic in poultry of many Eurasian countries and have caused repeated human infections in Asia since 1998. To evaluate the potential threat of H9N2 viruses to humans, we investigated the replication and transmission efficiency of H9N2 viruses in the ferret model. Five wild-type (WT H9N2 viruses, isolated from different avian species from 1988 through 2003, were tested in vivo and found to replicate in ferrets. However these viruses achieved mild peak viral titers in nasal washes when compared to those observed with a human H3N2 virus. Two of these H9N2 viruses transmitted to direct contact ferrets, however no aerosol transmission was detected in the virus displaying the most efficient direct contact transmission. A leucine (Leu residue at amino acid position 226 in the hemagglutinin (HA receptor-binding site (RBS, responsible for human virus-like receptor specificity, was found to be important for the transmission of the H9N2 viruses in ferrets. In addition, an H9N2 avian-human reassortant virus, which contains the surface glycoprotein genes from an H9N2 virus and the six internal genes of a human H3N2 virus, showed enhanced replication and efficient transmission to direct contacts. Although no aerosol transmission was observed, the virus replicated in multiple respiratory tissues and induced clinical signs similar to those observed with the parental human H3N2 virus. Our results suggest that the establishment and prevalence of H9N2 viruses in poultry pose a significant threat for humans.

Evidence of infection with avian, human, and swine influenza viruses in pigs in Cairo, Egypt.

Science.gov (United States)

Gomaa, Mokhtar R; Kandeil, Ahmed; El-Shesheny, Rabeh; Shehata, Mahmoud M; McKenzie, Pamela P; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

2018-02-01

The majority of the Egyptian swine population was culled in the aftermath of the 2009 H1N1 pandemic, but small-scale growing remains. We sampled pigs from piggeries and an abattoir in Cairo. We found virological evidence of infection with avian H9N2 and H5N1 viruses as well as human pandemic H1N1 influenza virus. Serological evidence suggested previous exposure to avian H5N1 and H9N2, human pandemic H1N1, and swine avian-like and human-like viruses. This raises concern about potential reassortment of influenza viruses in pigs and highlights the need for better control and prevention of influenza virus infection in pigs.

Influenza: the next pandemic?: a review | Adungo, | East African ...

African Journals Online (AJOL)

Due to the diversity of susceptible reservoirs of influenza viruses and the interspecies transmission recently reported, a mutated strain of the virus to which people have no immunity could cause an influenza pandemic once the virus gains efficient and sustained human-to-human transmission. The fear that avian influenza ...

Broadly-reactive human monoclonal antibodies elicited following pandemic H1N1 influenza virus exposure protect mice from highly pathogenic H5N1 challenge.

Science.gov (United States)

Nachbagauer, Raffael; Shore, David; Yang, Hua; Johnson, Scott K; Gabbard, Jon D; Tompkins, S Mark; Wrammert, Jens; Wilson, Patrick C; Stevens, James; Ahmed, Rafi; Krammer, Florian; Ellebedy, Ali H

2018-06-13

Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the mAbs bound HAs from multiple strains of group 1 viruses, and one mAb, 05-2G02, bound to both group 1 and group 2 influenza A HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two mAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One mAb, 70-1F02, was co-crystallized with H5 HA and showed similar heavy chain only interactions as a the previously described anti-stalk antibody CR6261. Finally, we showed that antibodies that compete with these mAbs are prevalent in serum from an individual recently infected with A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections with zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans with emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually

Military and Military Medical Support in Highly Pathogenic Avian Influenza (HPAI/H5N1) Pandemic Scenario

International Nuclear Information System (INIS)

Taleski, V.

2007-01-01

Avian influenza (Bird flu) is a highly contagious viral disease affecting mainly chickens, turkeys, ducks, other birds and mammals. Reservoirs for HPAI /H5N1 virus are shore birds and waterfowl (asymptomatic, excrete virus in feces for a long periods of time), live bird markets and commercial swine facilities. Virus tends to cycle between pigs and birds. HPAI (H5N1) virus is on every 'top ten' list available for potential agricultural bio-weapon agents. The threat of a HPAI/H5N1 pandemic is a definitively global phenomenon and the response must be global. A number of National plans led to various measures of preventing and dealing with epidemics/pandemics. Lessons learned form the pandemic history indicated essential role of military and military medical support to civil authorities in a crisis situation. Based on International Military Medical Avian Influenza Pandemic workshop (Vienna 2006), an expected scenario would involve 30-50% outpatients, 20-30% hospital admission, 2-3% deaths, 10-20% complicated cases. Activities of civil hospital may be reduced by 50%. Benefits of military support could be in: Transportation of patients (primarily by air); Mass vaccination and provision of all other preventive measures (masks, Tamiflu); Restriction of movements; Infection control of health care facilities; Field hospitals for triage and quarantine, military barracks to treat milder cases and military hospitals for severe cases; Deal with corpses; Stockpiling (vaccines, antiviral, antibiotics, protective equipment, supplies); Training; Laboratories; Ensure public safety, etc. With the aim of minimizing the risk of a pandemic spread by means of rapid and uncomplicated cooperation, an early warning system has to be established to improve surveillance, improve international contacts (WHO, ECDC, CDC), establish Platform for sharing information, close contacts of national and international military and civilian surveillance networks and databases, cooperation between military

Influenza and Other Respiratory Viruses Involved in Severe Acute Respiratory Disease in Northern Italy during the Pandemic and Postpandemic Period (2009–2011

Directory of Open Access Journals (Sweden)

Elena Pariani

2014-01-01

Full Text Available Since 2009 pandemic, international health authorities recommended monitoring severe and complicated cases of respiratory disease, that is, severe acute respiratory infection (SARI and acute respiratory distress syndrome (ARDS. We evaluated the proportion of SARI/ARDS cases and deaths due to influenza A(H1N1pdm09 infection and the impact of other respiratory viruses during pandemic and postpandemic period (2009–2011 in northern Italy; additionally we searched for unknown viruses in those cases for which diagnosis remained negative. 206 respiratory samples were collected from SARI/ARDS cases and analyzed by real-time RT-PCR/PCR to investigate influenza viruses and other common respiratory pathogens; also, a virus discovery technique (VIDISCA-454 was applied on those samples tested negative to all pathogens. Influenza A(H1N1pdm09 virus was detected in 58.3% of specimens, with a case fatality rate of 11.3%. The impact of other respiratory viruses was 19.4%, and the most commonly detected viruses were human rhinovirus/enterovirus and influenza A(H3N2. VIDISCA-454 enabled the identification of one previously undiagnosed measles infection. Nearly 22% of SARI/ARDS cases did not obtain a definite diagnosis. In clinical practice, great efforts should be dedicated to improving the diagnosis of severe respiratory disease; the introduction of innovative molecular technologies, as VIDISCA-454, will certainly help in reducing such “diagnostic gap.”

Preparing ICUs for pandemics.

Science.gov (United States)

Gabriel, Lucinda E K; Webb, Steve A R

2013-10-01

Influenza pandemics occur intermittently and represent an existential global infectious diseases threat. The purpose of this review is to describe clinical and research preparedness for future pandemics. Pandemic influenza typically results in large numbers of individuals with life-threatening pneumonia requiring treatment in ICUs. Clinical preparedness of ICUs relates to planning to provide increased 'surge' capacity to meet increased demand and requires consideration of staffing, equipment and consumables, bed-space availability and management systems. Research preparedness is also necessary, as timely clinical research has the potential to change the trajectory of a pandemic. The clinical research response during the 2009 H1N1 influenza pandemic was suboptimal. Better planning is necessary to optimize both clinical and research responses to future pandemics.

Signal Immune Reactions of Macrophages Differentiated from THP-1 Monocytes to Infection with Pandemic H1N1PDM09 Virus and H5N2 and H9N2 Avian Influenza A Virus.

Science.gov (United States)

Sokolova, T M; Poloskov, V V; Shuvalov, A N; Rudneva, I A; Timofeeva, T A

2018-03-01

In culture of THP-1 cells differentiated into macrophages with PMA (THP-PMA macrophages) infected with influenza viruses of subtypes H1, H5 and H9, we measured the expression of TLR7 and RIG1 receptor genes, sensors of viral RNA and ribonucleoprotein, and the levels of production of inflammatory cytokines IL-1β, TNFα, IL-10, and IFNα. The sensitivity and inflammatory response of THP-PMA macrophages to pandemic influenza A virus H1N1pdm09 and avian influenza H5N2 and H9N2 viruses correlate with the intracellular level of their viral RNA and activation of the RIG1 gene. Abortive infection is accompanied by intensive macrophage secretion of TNFα, IL-1β, and toxic factors inducing cell death. Activity of endosomal TLR7 receptor gene changed insignificantly in 24 h after infection and significantly decreased in 48 and 72 h under the action of H5N2 and H9N2, which correlated with manifestation of the cytopathogenic effect of these viruses. H5N2 and H9N2 avian viruses in THP-PMA macrophages are strong activators of the expression of the gene of the cytoplasmic RIG1 receptor 24 and 48 h after infection, and the pandemic virus H1N1pdm09 is a weak stimulator of RIG1 gene. Avian influenza H5N2 and H9N2 viruses are released by rapid induction of the inflammatory response in macrophages. At the late stages of infection, we observed a minor increase in IL-10 secretion in macrophages and, probably, the polarization of a part of the population in type M2. The studied influenza A viruses are weak inductors of IFN in THP-PMA macrophages. In the culture medium of THP-PMA macrophages infected with H9N2 and H5N2 viruses, MTT test revealed high levels of toxic factors causing the death of Caco-2 cells. In contrast to avian viruses, pandemic virus H1N1pdm09 did not induce production of toxic factors.

Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

Science.gov (United States)

Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

2011-03-24

Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

Whole Genome Characterization, Phylogenetic and Genome Signature Analysis of Human Pandemic H1N1 Virus in Thailand, 2009–2012

Science.gov (United States)

Makkoch, Jarika; Suwannakarn, Kamol; Payungporn, Sunchai; Prachayangprecha, Slinporn; Cheiocharnsin, Thaweesak; Linsuwanon, Piyada; Theamboonlers, Apiradee; Poovorawan, Yong

2012-01-01

Background Three waves of human pandemic influenza occurred in Thailand in 2009–2012. The genome signature features and evolution of pH1N1 need to be characterized to elucidate the aspects responsible for the multiple waves of pandemic. Methodology/Findings Forty whole genome sequences and 584 partial sequences of pH1N1 circulating in Thailand, divided into 1st, 2nd and 3rd wave and post-pandemic were characterized and 77 genome signatures were analyzed. Phylogenetic trees of concatenated whole genome and HA gene sequences were constructed calculating substitution rate and dN/dS of each gene. Phylogenetic analysis showed a distinct pattern of pH1N1 circulation in Thailand, with the first two isolates from May, 2009 belonging to clade 5 while clades 5, 6 and 7 co-circulated during the first wave of pH1N1 pandemic in Thailand. Clade 8 predominated during the second wave and different proportions of the pH1N1 viruses circulating during the third wave and post pandemic period belonged to clades 8, 11.1 and 11.2. The mutation analysis of pH1N1 revealed many adaptive mutations which have become the signature of each clade and may be responsible for the multiple pandemic waves in Thailand, especially with regard to clades 11.1 and 11.2 as evidenced with V731I, G154D of PB1 gene, PA I330V, HA A214T S160G and S202T. The substitution rate of pH1N1 in Thailand ranged from 2.53×10−3±0.02 (M2 genes) to 5.27×10−3±0.03 per site per year (NA gene). Conclusions All results suggested that this virus is still adaptive, maybe to evade the host's immune response and tends to remain in the human host although the dN/dS were under purifying selection in all 8 genes. Due to the gradual evolution of pH1N1 in Thailand, continuous monitoring is essential for evaluation and surveillance to be prepared for and able to control future influenza activities. PMID:23251479

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-01-20

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

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

International Nuclear Information System (INIS)

Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing

2013-01-01

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

Adjuvant solution for pandemic influenza vaccine production.

Science.gov (United States)

Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G

2012-10-23

Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period

Directory of Open Access Journals (Sweden)

Ivan Sanz

2015-01-01

Full Text Available Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD. Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012, respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.

Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression.

Science.gov (United States)

Dlugolenski, Daniel; Jones, Les; Howerth, Elizabeth; Wentworth, David; Tompkins, S Mark; Tripp, Ralph A

2015-05-01

Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment

Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model▿

OpenAIRE

Yen, Hui-Ling; Lipatov, Aleksandr S.; Ilyushina, Natalia A.; Govorkova, Elena A.; Franks, John; Yilmaz, Neziha; Douglas, Alan; Hay, Alan; Krauss, Scott; Rehg, Jerold E.; Hoffmann, Erich; Webster, Robert G.

2007-01-01

The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synth...

Evolutionary ecology of virus emergence.

Science.gov (United States)

Dennehy, John J

2017-02-01

The cross-species transmission of viruses into new host populations, termed virus emergence, is a significant issue in public health, agriculture, wildlife management, and related fields. Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between-host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. A firm understanding of the ecology of viruses and how they evolve is required for understanding how and why viruses emerge. In this paper, I address the evolutionary mechanisms of virus emergence and how they relate to virus ecology. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between-host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead-end spillover infections. Despite the relative rarity of pandemic emerging viruses, the potential of viruses to search evolutionary space and find means to spread epidemically and the consequences of pandemic viruses that do emerge necessitate sustained attention to virus research, surveillance, prophylaxis, and treatment. © 2016 New York Academy of Sciences.

CROSSREACTIVE ANTIBODIES AND MEMORY T CELLS TO HUMAN AND ZOONOTIC INFLUENZA A VIRUSES IN VOLUNTEERS

Directory of Open Access Journals (Sweden)

I. V. Losev

2015-01-01

Full Text Available There exists a real hazard of transferring zoonotic influenza A viruses, either swine, or avian, into human population. In such case, severity of such pandemics depends on the pathogen-specific immunity in the population. Virtual absence of such immunity in humans was declared in the literature. In this work, we assessed systemic, local, and T-cell immunity to potentially pandemic H3N2sw, H5N1, H5N2, H7N3, H7N9 and H2N2 influenza A viruses in a group of healthy adults of different age. Our results indicate that these subjects develop the following immune reactions: (i local (i.e., nasal IgA and cellular (CD4+ and CD8v memory T cells heterosubtypic immunity, in absence of detectable virus-specific serum antibodies to avian influenza A viruses; (ii Local immune responses (as nasal IgA to human A (H2N2 virus which circulated in 1957-1968 were detected both in subjects who could be primed at that time, but also in subjects born after 1968; (iii full-scale systemic and local immunity to potentially pandemic А (H3N2sw swine virus was found in the group. Conclusion. In order of proper epidemiological forecasts and planning appropriate preventive measures for potentially pandemic Influenza A viruses, a regular monitoring of collective immunity should be performed using different adaptive markers. In this respect, any conclusion based on molecular analysis only could lead to considerable mistakes, and should be accomplished by the mentioned immunological studies.

Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico

Science.gov (United States)

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

Seroprevalence of Antibodies to Pandemic (H1N1 2009 Influenza Virus Among Hospital Staff in a Medical Center in Taiwan

Directory of Open Access Journals (Sweden)

Yu-Jiun Chan

2010-02-01

Conclusion: The SPR of antibodies against the pandemic (H1N1 2009 virus in the hospital staff was higher than that in the general population, reflecting a higher contact risk. Prevaccination surveillance of the immune status of different risk groups may help to prioritize which groups should be vaccinated first.

Influenza infection in the intensive care unit: Four years after the 2009 pandemic.

Science.gov (United States)

Pérez-Carrasco, Marcos; Lagunes, Leonel; Antón, Andrés; Gattarello, Simone; Laborda, César; Pumarola, Tomás; Rello, Jordi

2016-03-01

The role of influenza viruses in severe acute respiratory infection (SARI) in Intensive Care Units (ICU) remains unknown. The post-pandemic influenza A(H1N1)pdm09 period, in particular, has been poorly studied. To identify influenza SARI patients in ICU, to assess the usefulness of the symptoms of influenza-like illness (ILI), and to compare the features of pandemic vs. post-pandemic influenza A(H1N1) pdm09 infection. A prospective observational study with SARI patients admitted to ICU during the first three post-pandemic seasons. Patient demographics, characteristics and outcomes were recorded. An influenza epidemic period (IEP) was defined as >100 cases/100,000 inhabitants per week. One hundred sixty-three patients were diagnosed with SARI. ILI was present in 65 (39.9%) patients. Influenza infection was documented in 41 patients, 27 (41.5%) ILI patients, and 14 (14.3%) non-ILI patients, 27 of them during an IEP. Influenza A viruses were mainly responsible. Only five patients had influenza B virus infection, which were non-ILI during an IEP. SARI overall mortality was 22.1%, and 15% in influenza infection patients. Pandemic and post-pandemic influenza infection patients shared similar clinical features. During influenza epidemic periods, influenza infection screening should be considered in all SARI patients. Influenza SARI was mainly caused by subtype A(H1N1)pdm09 and A(H3N2) in post-pandemic seasons, and no differences were observed in ILI and mortality rate compared with a pandemic season. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

A Historical Perspective of Influenza A(H1N2) Virus

OpenAIRE

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

2014-01-01

The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase ...

Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia

OpenAIRE

Mangiri, Amalya; Iuliano, A. Danielle; Wahyuningrum, Yunita; Praptiningsih, Catharina Y.; Lafond, Kathryn E.; Storms, Aaron D.; Samaan, Gina; Ariawan, Iwan; Soeharno, Nugroho; Kreslake, Jennifer M.; Storey, J. Douglas; Uyeki, Timothy M.

2016-01-01

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 vir...

A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

Science.gov (United States)

This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

Susceptibility of turkeys to pandemic-H1N1 virus by reproductive tract insemination

Directory of Open Access Journals (Sweden)

Suarez David L

2010-02-01

Full Text Available Abstract The current pandemic influenza A H1N1 2009 (pH1N1 was first recognized in humans with acute respiratory diseases in April 2009 in Mexico, in swine in Canada in June, 2009 with respiratory disease, and in turkeys in Chile in June 2009 with a severe drop in egg production. Several experimental studies attempted to reproduce the disease in turkeys, but failed to produce respiratory infection in turkeys using standard inoculation routes. We demonstrated that pH1N1 virus can infect the reproductive tract of turkey hens after experimental intrauterine inoculation, causing decreased egg production. This route of exposure is realistic in modern turkey production because turkey hens are handled once a week for intrauterine insemination in order to produce fertile eggs. This understanding of virus exposure provides an improved understanding of the pathogenesis of the disease and can improve poultry husbandry to prevent disease outbreaks.

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

Science.gov (United States)

Smith, Maxwell J; Silva, Diego S

2015-01-01

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

Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

African Journals Online (AJOL)

Background: A novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in ...

Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

African Journals Online (AJOL)

... novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in Zhanjiang, China ...

New reassortant and enzootic European swine influenza viruses transmit efficiently through direct contact in the ferret model.

Science.gov (United States)

Fobian, Kristina; Fabrizio, Thomas P; Yoon, Sun-Woo; Hansen, Mette Sif; Webby, Richard J; Larsen, Lars E

2015-07-01

The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2, and two were new reassortants, one with avian-like H1 and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titres in nasal wash and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics using a differentiated human bronchial epithelial cell line showed that all four viruses were able to replicate to high titres. Further, the viruses revealed preferential binding to the 2,6-α-silalylated glycans and investigation of the antiviral susceptibility of the viruses revealed that all were sensitive to neuraminidase inhibitors. These findings suggested that these viruses have the potential to infect humans and further underline the need for continued surveillance as well as biological characterization of new influenza A viruses.

Genomic profiling of tumor necrosis factor alpha (TNF-alpha) receptor and interleukin-1 receptor knockout mice reveals a link between TNF-alpha signaling and increased severity of 1918 pandemic influenza virus infection

Science.gov (United States)

The influenza pandemic of 1918-1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated pro-inflammatory cytokine response. In the present study, we...

Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

Science.gov (United States)

Thacker, Eileen; Janke, Bruce

2008-02-15

Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.

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

NARCIS (Netherlands)

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

2013-01-01

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

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

NARCIS (Netherlands)

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Petra Mooij

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

Interspecies Interactions and Potential Influenza A Virus Risk in Small Swine Farms in Peru

Science.gov (United States)

2012-03-15

and swine influenza viruses : our current understanding of the zoonotic risk. Vet Res 2007, 38(2):243–260. 4. Wertheim JO: When pigs fly: the avian ...first authors. Abstract Background The recent avian influenza epidemic in Asia and the H1N1 pandemic demonstrated that influenza A viruses pose a...prime “mixing vessels” due to the dual receptivity of their trachea to human and avian strains. Additionally, avian and human influenza viruses

In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses

Science.gov (United States)

Schmier, Sonja; Mostafa, Ahmed; Haarmann, Thomas; Bannert, Norbert; Ziebuhr, John; Veljkovic, Veljko; Dietrich, Ursula; Pleschka, Stephan

2015-06-01

Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.

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

Directory of Open Access Journals (Sweden)

Nuriban Valero-Pacheco

2013-01-01

Full Text Available 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(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 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(H1N1pdm09 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(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

Reducing Biosecurity Threats from Infectious Diseases of Pandemic ...

International Development Research Centre (IDRC) Digital Library (Canada)

The emergence of the H7N9 avian influenza virus and the Middle East Respiratory ... develop and implement pandemic preparedness and response policies. ... available to support partnered teams of Canadian and African Ebola researchers.

Emergence of influenza viruses with zoonotic potential: open issues which need to be addressed. A review.

Science.gov (United States)

Capua, Ilaria; Munoz, Olga

2013-07-26

The real and perceived impact of influenza infections in animals has changed dramatically over the last 10 years, due mainly to the better understanding of the public health implications of avian and swine influenza viruses. On a number of occasions in the last decade avian-to-human transmissions of H5, H7 and H9 virus subtypes have occurred, and the first influenza pandemic of the new millennium occurred as a result of the emergence and spread of a virus from pigs. Although the mechanisms that allow influenza viruses to jump from one host species to another are not fully understood, several genetic signatures linked to the crossing of species barriers have been identified. This has led to a re-evaluation of the importance of understanding these viruses in the animal reservoir, to the extent that millions of euros have been invested in surveillance, research and capacity building worldwide. This has resulted in an enhanced collaboration with our medical counterparts, leading to many discoveries that will contribute to an understanding of the complex mechanisms that lead to the emergence of a pandemic virus. Copyright © 2013 Elsevier B.V. All rights reserved.

Adenovirus-Vectored Vaccine as a Rapid-Response Tool Against Avian Influenza Pandemic

International Nuclear Information System (INIS)

Van Kampen, K. R.; Tang, D. C.

2007-01-01

Influenza viruses in nature undergo genetic mutation and reassortment. Three pandemics of avian influenza in man were recorded in the twentieth century. Highly pathogenic avian influenza (HPAI) viruses currently in circulation pose a threat for another world-wide pandemic, if they become transmissible from man to man. Manufacturing protective vaccines using current egg-based technology is often difficult due to the virulence of the virus and its adverse effects on the embryonating egg substrate. New technologies allow the creation of safe and protective pandemic influenza vaccines without the need for egg based substrates. These technologies allow new vaccines to be created in less than one month. Manufacturing is in tissue culture, not eggs. Vaccine can be administered to man non-invasively, without adjuvants, eliciting a rapid and protective immune response. Protective immunity against avian influenza (AI) virus was elicited in chickens by single-dose in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad5)-derived vector encoding an H5N9 avian influenza virus hemagglutinin. Vaccinated chickens were protected against both H5N1 and H5N2 HPAI virus challenges. Mass-administration of this bird flu vaccine can be streamlined with available robotic in ovo injectors. Vaccination using this vaccine could protect the the largest host reservoir (chickens) and greatly reduce the exposure of man to avian influenza. In addition, Ad5-vectored vaccines can be produced rapidly and the safety margin of a non-replicating vector is superior to that of a replicating counterpart. Furthermore, this mode of vaccination is compatible with epidemiological surveys of natural AI virus infections. In addition to mass immunization of poultry, both animals and humans have been effectively immunized by intranasal administration of Ad5-vectored influenza vaccines without any appreciable side effects, even in mice and human volunteers with

The potential impact of the next influenza pandemic on a national primary care medical workforce.

Science.gov (United States)

Wilson, Nick; Baker, Michael; Crampton, Peter; Mansoor, Osman

2005-08-11

Another influenza pandemic is all but inevitable. We estimated its potential impact on the primary care medical workforce in New Zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. The model in the "FluAid" software (Centers for Disease Control and Prevention, CDC, Atlanta) was applied to the New Zealand primary care medical workforce (i.e., general practitioners). At its peak (week 4) the pandemic would lead to 1.2% to 2.7% loss of medical work time, using conservative baseline assumptions. Most workdays (88%) would be lost due to illness, followed by hospitalisation (8%), and then premature death (4%). Inputs for a "more severe" scenario included greater health effects and time spent caring for sick relatives. For this scenario, 9% of medical workdays would be lost in the peak week, and 3% over a more compressed six-week period of the first pandemic wave. As with the base case, most (64%) of lost workdays would be due to illness, followed by caring for others (31%), hospitalisation (4%), and then premature death (1%). Preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity.

Effectiveness of non-adjuvanted pandemic influenza A vaccines for preventing pandemic influenza acute respiratory illness visits in 4 U.S. communities.

Directory of Open Access Journals (Sweden)

Marie R Griffin

Full Text Available We estimated the effectiveness of four monovalent pandemic influenza A (H1N1 vaccines (three unadjuvanted inactivated, one live attenuated available in the U.S. during the pandemic. Patients with acute respiratory illness presenting to inpatient and outpatient facilities affiliated with four collaborating institutions were prospectively recruited, consented, and tested for influenza. Analyses were restricted to October 2009 through April 2010, when pandemic vaccine was available. Patients testing positive for pandemic influenza by real-time RT-PCR were cases; those testing negative were controls. Vaccine effectiveness was estimated in logistic regression models adjusted for study community, patient age, timing of illness, insurance status, enrollment site, and presence of high-risk medical conditions. Pandemic virus was detected in 1,011 (15% of 6,757 enrolled patients. Fifteen (1% of 1,011 influenza positive cases and 1,042 (18% of 5,746 test-negative controls had record-verified pandemic vaccination >14 days prior to illness onset. Adjusted effectiveness (95% confidence interval for pandemic vaccines combined was 56% (23%, 75%. Adjusted effectiveness for inactivated vaccines alone (79% of total was 62% (25%, 81% overall and 32% (-92%, 76%, 89% (15%, 99%, and -6% (-231%, 66% in those aged 0.5 to 9, 10 to 49, and 50+ years, respectively. Effectiveness for the live attenuated vaccine in those aged 2 to 49 years was only demonstrated if vaccination >7 rather than >14 days prior to illness onset was considered (61%∶ 12%, 82%. Inactivated non-adjuvanted pandemic vaccines offered significant protection against confirmed pandemic influenza-associated medical care visits in young adults.

[Incidence of avian flu worldwide and in the Russian Federation. Improvement of surveillance and control of influenza during preparation for potential pandemic].

Science.gov (United States)

Onishchenko, G G

2006-01-01

necessary to organize medical monitoring of sea ships, aircraft and train crews, arriving from the countries where influenza H5N1 cases were detected, in case of need to arrange raids to outlets and markets to detect poultry and poultry products brought from these countries. In Russia it is necessary to prepare a reserve of vaccine strains of viruses--potential causative agent of pandemic, including H5N1 and H7N7, that can start to vaccine reproduction immediately in case of pandemic.

Pandemic Influenza A (N1H1: what to learn from it?

Directory of Open Access Journals (Sweden)

Cristina Rolim Neumann

2009-09-01

Full Text Available Influenza pandemics are natural events that occur periodically. The pandemic’s current agent, Influenza virus A (H1N1 was first identified in Mexico in April 2009, spread rapidly and has caused deaths mainly among young adults. The objective of this manuscript is to present the biological aspects involved in the outbreak of this pandemic, as well as population-control strategies for pandemic influenza. In addition to the population mitigation measures, whose efficacy has been described by theoretical models, today we also have drugs with efficacy valued in some patient groups. These drugs reduce moderately the duration and severity of symptoms, as long as they are started early. This pandemic, with a large number of cases, but caused by a virus of low lethality, could be managed preferably in Units of Primary Health Care, that would treat the wild cases and forward the severe ones to the hospitals. However, what occurred in numerous cities was the burden on emergency care with triage situations, forcing managers to improvise field hospitals, tents and containers to house the extra work in services that were already at the limit of physical infrastructure and human resources. Pandemic Influenza exposed the fragility of our network of primary care and lack of ICU beds.

Aedes (Stegomyia albopictus (Skuse: a potential vector of Zika virus in Singapore.

Directory of Open Access Journals (Sweden)

Pei-Sze Jeslyn Wong

Full Text Available Zika virus (ZIKV is a little known arbovirus until it caused a major outbreak in the Pacific Island of Yap in 2007. Although the virus has a wide geographic distribution, most of the known vectors are sylvatic Aedes mosquitoes from Africa where the virus was first isolated. Presently, Ae. aegypti is the only known vector to transmit the virus outside the African continent, though Ae. albopictus has long been a suspected vector. Currently, Ae. albopictus has been shown capable of transmitting more than 20 arboviruses and its notoriety as an important vector came to light during the recent chikungunya pandemic. The vulnerability of Singapore to emerging infectious arboviruses has stimulated our interest to determine the competence of local Ae. albopictus to transmit ZIKV.To determine the competence of Ae. albopictus to ZIKV, we orally infected local mosquito strains to a Ugandan strain virus. Fully engorged mosquitoes were maintained in an environmental chamber set at 29°C and 80-85%RH. Twelve mosquitoes were then sampled daily from day one to seven and on day 10 and 14 post infection (pi. Zika virus titre in the midgut and salivary glands of each mosquito were determined using tissue culture infectious dose50 assay, while transmissibility of the virus was determined by detecting viral antigen in the mosquito saliva by qRT-PCR. High dissemination and transmission rate of ZIKV were observed. By day 7-pi, all mosquitoes have disseminated infection and 73% of these mosquitoes have ZIKV in their saliva. By day 10-pi, all mosquitoes were potentially infectious.The study highlighted the potential of Ae. albopictus to transmit ZIKV and the possibility that the virus could be established locally. Nonetheless, the threat of ZIKV can be mitigated by existing dengue and chikungunya control program being implemented in Singapore.

Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein.

Directory of Open Access Journals (Sweden)

Benjamin Mänz

2013-03-01

Full Text Available The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP of pandemic strains A/Brevig Mission/1/1918 (1918 and A/Hamburg/4/2009 (pH1N1 that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1/04 (H5N1 resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.

In vitro reassortment between endemic H1N2 and 2009 H1N1 pandemic swine influenza viruses generates attenuated viruses.

Directory of Open Access Journals (Sweden)

Ben M Hause

Full Text Available The pandemic H1N1 (pH1N1 influenza virus was first reported in humans in the spring of 2009 and soon thereafter was identified in numerous species, including swine. Reassortant viruses, presumably arising from the co-infection of pH1N1 and endemic swine influenza virus (SIV, were subsequently identified from diagnostic samples collected from swine. In this study, co-infection of swine testicle (ST cells with swine-derived endemic H1N2 (MN745 and pH1N1 (MN432 yielded two reassortant H1N2 viruses (R1 and R2, both possessing a matrix gene derived from pH1N1. In ST cells, the reassortant viruses had growth kinetics similar to the parental H1N2 virus and reached titers approximately 2 log(10 TCID(50/mL higher than the pH1N1 virus, while in A549 cells these viruses had similar growth kinetics. Intranasal challenge of pigs with H1N2, pH1N1, R1 or R2 found that all viruses were capable of infecting and transmitting between direct contact pigs as measured by real time reverse transcription PCR of nasal swabs. Lung samples were also PCR-positive for all challenge groups and influenza-associated microscopic lesions were detected by histology. Interestingly, infectious virus was detected in lung samples for pigs challenged with the parental H1N2 and pH1N1 at levels significantly higher than either reassortant virus despite similar levels of viral RNA. Results of our experiment suggested that the reassortant viruses generated through in vitro cell culture system were attenuated without gaining any selective growth advantage in pigs over the parental lineages. Thus, reassortant influenza viruses described in this study may provide a good system to study genetic basis of the attenuation and its mechanism.

Potent peptidic fusion inhibitors of influenza virus

Energy Technology Data Exchange (ETDEWEB)

Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

2017-09-28

Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

The potential impact of the next influenza pandemic on a national primary care medical workforce

Directory of Open Access Journals (Sweden)

Crampton Peter

2005-08-01

Full Text Available Abstract Background Another influenza pandemic is all but inevitable. We estimated its potential impact on the primary care medical workforce in New Zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. Methods The model in the "FluAid" software (Centers for Disease Control and Prevention, CDC, Atlanta was applied to the New Zealand primary care medical workforce (i.e., general practitioners. Results At its peak (week 4 the pandemic would lead to 1.2% to 2.7% loss of medical work time, using conservative baseline assumptions. Most workdays (88% would be lost due to illness, followed by hospitalisation (8%, and then premature death (4%. Inputs for a "more severe" scenario included greater health effects and time spent caring for sick relatives. For this scenario, 9% of medical workdays would be lost in the peak week, and 3% over a more compressed six-week period of the first pandemic wave. As with the base case, most (64% of lost workdays would be due to illness, followed by caring for others (31%, hospitalisation (4%, and then premature death (1%. Conclusion Preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity.

Mitigation approaches to combat the flu pandemic.

Science.gov (United States)

Chawla, Raman; Sharma, Rakesh Kumar; Madaan, Deepali; Dubey, Neha; Arora, Rajesh; Goel, Rajeev; Singh, Shefali; Kaushik, Vinod; Singh, Pankaj Kumar; Chabbra, Vivek; Bhardwaj, Janak Raj

2009-07-01

Management of flu pandemic is a perpetual challenge for the medical fraternity since time immemorial. Animal to human transmission has been observed thrice in the last century within an average range of 11-39 years of antigenic recycling. The recent outbreak of influenza A (H1N1, also termed as swine flu), first reported in Mexico on April 26, 2009, occurred in the forty first year since last reported flu pandemic (July 1968). Within less than 50 days, it has assumed pandemic proportions (phase VI) affecting over 76 countries with 163 deaths/35,928 cases (as on 15(th) June 2009). It indicated the re-emergence of genetically reassorted virus having strains endemic to humans, swine and avian (H5N1). The World Health Organisation (WHO) member states have already pulled up their socks and geared up to combat such criticalities. Earlier outbreaks of avian flu (H5N1) in different countries led WHO to develop pandemic preparedness strategies with national/regional plans on pandemic preparedness. Numerous factors related to climatic conditions, socio-economic strata, governance and sharing of information/logistics at all levels have been considered critical indicators in monitoring the dynamics of escalation towards a pandemic situation.The National Disaster Management Authority (NDMA), Government of India, with the active cooperation of UN agencies and other stakeholders/experts has formulated a concept paper on role of nonhealth service providers during pandemics in April 2008 and released national guidelines - management of biological disasters in July 2008. These guidelines enumerate that the success of medical management endeavors like pharmaceutical (anti-viral Oseltamivir and Zanamivir therapies), nonpharmaceutical interventions and vaccination development etc., largely depends on level of resistance offered by mutagenic viral strain and rationale use of pharmaco therapeutic interventions. This article describes the mitigation approach to combat flu pandemic with

Distribution of selected healthcare resources for influenza pandemic response in Cambodia.

Science.gov (United States)

Schwanke Khilji, Sara U; Rudge, James W; Drake, Tom; Chavez, Irwin; Borin, Khieu; Touch, Sok; Coker, Richard

2013-10-04

Human influenza infection poses a serious public health threat in Cambodia, a country at risk for the emergence and spread of novel influenza viruses with pandemic potential. Prior pandemics demonstrated the adverse impact of influenza on poor communities in developing countries. Investigation of healthcare resource distribution can inform decisions regarding resource mobilization and investment for pandemic mitigation. A health facility survey performed across Cambodia obtained data on availability of healthcare resources important for pandemic influenza response. Focusing on five key resources considered most necessary for treating severe influenza (inpatient beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were analyzed at the Operational District (OD) and Province levels, refining data analysis from earlier studies. Resources were stratified by respondent type (hospital vs. District Health Office [DHO]). A summary index of distribution inequality was calculated using the Gini coefficient. Indices for local spatial autocorrelation were measured at the OD level using geographical information system (GIS) analysis. Finally, a potential link between socioeconomic status and resource distribution was explored by mapping resource densities against poverty rates. Gini coefficient calculation revealed variable inequality in distribution of the five key resources at the Province and OD levels. A greater percentage of the population resides in areas of relative under-supply (28.5%) than over-supply (21.3%). Areas with more resources per capita showed significant clustering in central Cambodia while areas with fewer resources clustered in the northern and western provinces. Hospital-based inpatient beds, doctors, and nurses were most heavily concentrated in areas of the country with the lowest poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF) showed increasing concentrations at higher levels of poverty. There is

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

Science.gov (United States)

Pan, Po-Lin; Meng, Juan

2015-01-01

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

The 2009-2010 influenza pandemic: effects on pandemic and seasonal vaccine uptake and lessons learned for seasonal vaccination campaigns.

Science.gov (United States)

Poland, Gregory A

2010-09-07

Individual and national/cultural differences were apparent in response to the 2009-2010 influenza pandemic. Overall pandemic influenza immunization rates were low across all nations, including among healthcare workers. Among the reasons for the low coverage rates may have been a lack of concern about the individual risk of influenza, which may translate into a lack of willingness or urgency to be vaccinated, particularly if there is mistrust of information provided by public health or governmental authorities. Intuitively, a link between willingness to be vaccinated against seasonal influenza and against pandemic influenza exists, given the similarities in decision-making for this infection. As such, the public is likely to share common concerns regarding pandemic and seasonal influenza vaccination, particularly in the areas of vaccine safety and side effects, and personal risk. Given the public's perception of the low level of virulence of the recent pandemic influenza virus, there is concern that the perception of a lack of personal risk of infection and risk of vaccine side effects could adversely affect seasonal vaccine uptake. While governments are more often concerned about public anxiety and panic, as well as absenteeism of healthcare and other essential workers during a pandemic, convincing the public of the threat posed by pandemic or seasonal influenza is often the more difficult, and underappreciated task. Thus, appropriate, timely, and data-driven health information are very important issues in increasing influenza vaccine coverage, perhaps even more so in western societies where trust in government and public health reports may be lower than in other countries. This article explores what has been learned about cross-cultural responses to pandemic influenza, and seeks to apply those lessons to seasonal influenza immunization programs. 2010 Elsevier Ltd. All rights reserved.

Zika threatens to become a huge worldwide pandemic

Institute of Scientific and Technical Information of China (English)

Alcides Troncoso

2016-01-01

The Aedes aegypti mosquito which transmits Zika virus (as well as dengue, chikungunya and yellow fever) represents a high risk for global transmission. This virus comes from Africa, the Zika forest in Uganda, where it was discovered in 1947 in a rhesus monkey. In May 2015, the first local cases were recorded in Brazil, surpassing 1.5 million cases in December of the same year. By March 2016, local transmission of Zika was recognized in 34 countries. Its clinical condition is similar to dengue febrile illness, although milder. The final geographical distribution area is constantly expanding. Recently, it has been associated with cases of Guillain-Barr ´e syndrome in Brazil, Colombia, El Salvador, Venezuela and Suriname. Microcephaly was documented in Brazil. This article discusses some factors that contributed to the spread of Zika virus in South America. Climate change associated with the events of the phenomenon of“El Niño”is also analyzed. The biggest concern is how quickly Zika is spreading around the world and that it could be far more dangerous than previously thought. Zika virus infection, by its explosive potential, has every chance of becoming a global pandemic.

Zika threatens to become a huge worldwide pandemic

Institute of Scientific and Technical Information of China (English)

Alcides Troncoso

2016-01-01

The Aedes aegypti mosquito which transmits Zika virus(as well as dengue, chikungunya and yellow fever) represents a high risk for global transmission. This virus comes from Africa, the Zika forest in Uganda, where it was discovered in 1947 in a rhesus monkey. In May 2015, the first local cases were recorded in Brazil, surpassing 1.5 million cases in December of the same year. By March 2016, local transmission of Zika was recognized in 34 countries. Its clinical condition is similar to dengue febrile illness, although milder.The final geographical distribution area is constantly expanding. Recently, it has been associated with cases of Guillain-Barre′ syndrome in Brazil, Colombia, El Salvador,Venezuela and Suriname. Microcephaly was documented in Brazil. This article discusses some factors that contributed to the spread of Zika virus in South America. Climate change associated with the events of the phenomenon of "El Ni?o" is also analyzed. The biggest concern is how quickly Zika is spreading around the world and that it could be far more dangerous than previously thought. Zika virus infection, by its explosive potential,has every chance of becoming a global pandemic.

Zika threatens to become a huge worldwide pandemic

Directory of Open Access Journals (Sweden)

Alcides Troncoso

2016-06-01

Full Text Available The Aedes aegypti mosquito which transmits Zika virus (as well as dengue, chikungunya and yellow fever represents a high risk for global transmission. This virus comes from Africa, the Zika forest in Uganda, where it was discovered in 1947 in a rhesus monkey. In May 2015, the first local cases were recorded in Brazil, surpassing 1.5 million cases in December of the same year. By March 2016, local transmission of Zika was recognized in 34 countries. Its clinical condition is similar to dengue febrile illness, although milder. The final geographical distribution area is constantly expanding. Recently, it has been associated with cases of Guillain-Barré syndrome in Brazil, Colombia, El Salvador, Venezuela and Suriname. Microcephaly was documented in Brazil. This article discusses some factors that contributed to the spread of Zika virus in South America. Climate change associated with the events of the phenomenon of “El Niño” is also analyzed. The biggest concern is how quickly Zika is spreading around the world and that it could be far more dangerous than previously thought. Zika virus infection, by its explosive potential, has every chance of becoming a global pandemic.

Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

Directory of Open Access Journals (Sweden)

Bin Zhou

2014-10-01

Full Text Available Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV. Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1. This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2 showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

Science.gov (United States)

Zhou, Bin; Ma, Jingjiao; Liu, Qinfang; Bawa, Bhupinder; Wang, Wei; Shabman, Reed S; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B; Richt, Juergen A; Wentworth, David E; Ma, Wenjun

2014-10-01

Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

Influenza (Flu) Viruses

Science.gov (United States)

... Types Seasonal Avian Swine Variant Pandemic Other Influenza (Flu) Viruses Language: English (US) Español Recommend on Facebook ... influenza circulate and cause illness. More Information about Flu Viruses Types of Influenza Viruses Influenza A and ...

Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

Science.gov (United States)

Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

2016-11-28

H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

Replication of swine and human influenza viruses in juvenile and layer turkey hens.

Science.gov (United States)

Ali, Ahmed; Yassine, Hadi; Awe, Olusegun O; Ibrahim, Mahmoud; Saif, Yehia M; Lee, Chang-Won

2013-04-12

Since the first reported isolation of swine influenza viruses (SIVs) in turkeys in the 1980s, transmission of SIVs to turkeys was frequently documented. Recently, the 2009 pandemic H1N1 virus, that was thought to be of swine origin, was detected in turkeys with a severe drop in egg production. In this study, we assessed the infectivity of different mammalian influenza viruses including swine, pandemic H1N1 and seasonal human influenza viruses in both juvenile and layer turkeys. In addition, we investigated the potential influenza virus dissemination in the semen of experimentally infected turkey toms. Results showed that all mammalian origin influenza viruses tested can infect turkeys. SIVs were detected in respiratory and digestive tracts of both juvenile and layer turkeys. Variations in replication efficiencies among SIVs were observed especially in the reproductive tract of layer turkeys. Compared to SIVs, limited replication of seasonal human H1N1 and no detectable replication of recent human-like swine H1N2, pandemic H1N1 and seasonal human H3N2 viruses was noticed. All birds seroconverted to all tested viruses regardless of their replication level. In turkey toms, we were able to detect swine H3N2 virus in semen and reproductive tract of infected toms by real-time RT-PCR although virus isolation was not successful. These data suggest that turkey hens could be affected by diverse influenza strains especially SIVs. Moreover, the differences in the replication efficiency we demonstrated among SIVs and between SIV and human influenza viruses in layer turkeys suggest a possible use of turkeys as an animal model to study host tropism and pathogenesis of influenza viruses. Our results also indicate a potential risk of venereal transmission of influenza viruses in turkeys. Copyright © 2012 Elsevier B.V. All rights reserved.

Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection.

Science.gov (United States)

Ling, Man To; Tu, Wenwei; Han, Yan; Mao, Huawei; Chong, Wai Po; Guan, Jing; Liu, Ming; Lam, Kwok Tai; Law, Helen K W; Peiris, J S Malik; Takahashi, K; Lau, Yu Lung

2012-01-01

Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.

The nonadaptive nature of the H1N1 2009 Swine Flu pandemic contrasts with the adaptive facilitation of transmission to a new host

Directory of Open Access Journals (Sweden)

Abdussamad Juwaeriah

2011-01-01

Full Text Available Abstract Background The emergence of the 2009 H1N1 Influenza pandemic followed a multiple reassortment event from viruses originally circulating in swines and humans, but the adaptive nature of this emergence is poorly understood. Results Here we base our analysis on 1180 complete genomes of H1N1 viruses sampled in North America between 2000 and 2010 in swine and human hosts. We show that while transmission to a human host might require an adaptive phase in the HA and NA antigens, the emergence of the 2009 pandemic was essentially nonadaptive. A more detailed analysis of the NA protein shows that the 2009 pandemic sequence is characterized by novel epitopes and by a particular substitution in loop 150, which is responsible for a nonadaptive structural change tightly associated with the emergence of the pandemic. Conclusions Because this substitution was not present in the 1918 H1N1 pandemic virus, we posit that the emergence of pandemics is due to epistatic interactions between sites distributed over different segments. Altogether, our results are consistent with population dynamics models that highlight the epistatic and nonadaptive rise of novel epitopes in viral populations, followed by their demise when the resulting virus is too virulent.

Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice.

Science.gov (United States)

Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella

2014-05-01

To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. © 2013 The Authors Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine

Science.gov (United States)

Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

2013-01-01

H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571

Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

Directory of Open Access Journals (Sweden)

Misako Nakayama

Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

The 1918–1920 influenza pandemic in Peru

Science.gov (United States)

Chowell, G.; Viboud, C.; Simonsen, L.; Miller, M.A.; Hurtado, J.; Soto, G.; Vargas, R.; Guzman, M.A.; Ulloa, M.; Munayco, C.V.

2011-01-01

respiratory mortality during November 1918-February 1919 in Lima, Iquitos, Ica, followed by asynchronous recrudescent waves in 1920. Cumulative data from quantitative studies of the 1918 influenza pandemic in Latin American settings have confirmed the high mortality impact associated with this pandemic. Further historical studies in lesser-studied regions of Latin America, Africa, and Asia are warranted for a full understanding of the global impact of the 1918 pandemic virus. PMID:21757099

Potential of acylated peptides to target the influenza A virus

Directory of Open Access Journals (Sweden)

Daniel Lauster

2015-04-01

Full Text Available For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF, preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010, and the “Entry Blocker” (EB (Jones et al. 2006, with respect to their antiviral activity against infection by Influenza A Virus (IAV H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.

Pandemic influenza A (H1N1)

African Journals Online (AJOL)

... in Port Shepstone, South Africa. Introduction. Influenza A (H1N1) 2009 'swine flu' variant is currently a global pandemic.1 The infection associated with this virus is usually a mild, self-limiting illness. However, it may progress to severe pneumonia requiring intensive care unit (ICU) therapy in 31% of patients.2 This may.

The impact that the influenza A (H1N1) pandemic had on news reporting in the state of Paraná, Brazil.

Science.gov (United States)

Maciel-Lima, Sandra Mara; Rasia, José Miguel; Bagatelli, Rodrigo Cechelero; Gontarski, Giseli; Colares, Máximo José D

2015-01-01

This study aims to analyze how influenza A (H1N1) in 2009 was reported in the state of Paraná. A total of 189 articles were analyzed in two newspapers from Paraná. Pursuant to analysis, four themes were identified: the spread of the virus; the pandemic and fear; influenza in the health service; and influenza in public policies. By studying how influenza A was reported in the media, it was possible to see the social impact that the H1N1 pandemic represented for society, presenting challenges for public institutions and ordinary citizens, who sensed that they were in a high-risk group exposed to a potentially lethal virus. This disease radically changed the habits of a globalized community seeking to escape from vulnerability.

The impact that the influenza A (H1N1 pandemic had on news reporting in the state of Paraná, Brazil

Directory of Open Access Journals (Sweden)

Sandra Mara Maciel-Lima

2015-03-01

Full Text Available This study aims to analyze how influenza A (H1N1 in 2009 was reported in the state of Paraná. A total of 189 articles were analyzed in two newspapers from Paraná. Pursuant to analysis, four themes were identified: the spread of the virus; the pandemic and fear; influenza in the health service; and influenza in public policies. By studying how influenza A was reported in the media, it was possible to see the social impact that the H1N1 pandemic represented for society, presenting challenges for public institutions and ordinary citizens, who sensed that they were in a high-risk group exposed to a potentially lethal virus. This disease radically changed the habits of a globalized community seeking to escape from vulnerability.

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

Directory of Open Access Journals (Sweden)

Vittoria Colizza

2007-01-01

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

[History of pandemic influenza in Japan].

Science.gov (United States)

Matsumoto, Keizo

2010-09-01

In Japan, influenza like epidemics were described many times since Heian era. However, Spanish flu as the modern medicine invaded Japan in 1918, thus almost infected 390,000 patients died with associated pneumonia. After the discovery of influenza virus in 1933, Japan experienced pandemic influenza--Asian flu(H2N2) in 1957. After about 10 years, Hong Kong flu (H3N2) came to Japan at 1968. However, we had many reliable antibiotics but had not any antiviral drug at the early time. After year 2000, we fortunately obtained reliable three antiviral drugs such as amantadine, oseltamivir and zanamivir. Moreover, very useful rapid test kits for influenza A and B viruses were developed and used in Japan. 2009 H1N1 influenza epidemic occured in Japan after the great epidemic in Mexico and North America but elderly patient was few. With together, host conditions regarding with high risk are changing. Lessons from past several pandemic influenza are those that many issues for changing high risk conditions, viral genetic changes, developing antiviral agents, developing new useful vaccins and determinating bacterial secondary pathogens are important.

Recombinant HA1 produced in E. coli forms functional oligomers and generates strain-specific SRID potency antibodies for pandemic influenza vaccines.

Science.gov (United States)

Khurana, Surender; Larkin, Christopher; Verma, Swati; Joshi, Manju B; Fontana, Juan; Steven, Alasdair C; King, Lisa R; Manischewitz, Jody; McCormick, William; Gupta, Rajesh K; Golding, Hana

2011-08-05

Vaccine production and initiation of mass vaccination is a key factor in rapid response to new influenza pandemic. During the 2009-2010 H1N1 pandemic, several bottlenecks were identified, including the delayed availability of vaccine potency reagents. Currently, antisera for the single-radial immunodiffusion (SRID) potency assay are generated in sheep immunized repeatedly with HA released and purified after bromelain-treatment of influenza virus grown in eggs. This approach was a major bottleneck for pandemic H1N1 (H1N1pdm09) potency reagent development in 2009. Alternative approaches are needed to make HA immunogens for generation of SRID reagents in the shortest possible time. In this study, we found that properly folded recombinant HA1 globular domain (rHA1) from several type A viruses including H1N1pdm09 and two H5N1 viruses could be produced efficiently using a bacterial expression system and subsequent purification. The rHA1 proteins were shown to form functional oligomers of trimers, similar to virus derived HA, and elicited high titer of neutralizing antibodies in rabbits and sheep. Importantly, the immune sera formed precipitation rings with reference antigens in the SRID assay in a dose-dependent manner. The HA contents in multiple H1N1 vaccine products from different manufacturers (and in several lots) as determined with the rHA1-generated sheep sera were similar to the values obtained with a traditionally generated sheep serum from NIBSC. We conclude that bacterially expressed recombinant HA1 proteins can be produced rapidly and used to generate SRID potency reagents shortly after new influenza strains with pandemic potential are identified. Published by Elsevier Ltd.

Comparison of temporal and spatial dynamics of seasonal H3N2, pandemic H1N1 and highly pathogenic avian influenza H5N1 virus infections in ferrets.

Directory of Open Access Journals (Sweden)

Judith M A van den Brand

Full Text Available Humans may be infected by different influenza A viruses--seasonal, pandemic, and zoonotic--which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1, and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi, as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues--including the central nervous system--for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.

Pandemic H1N1 2009 ('swine flu'): diagnostic and other challenges.

Science.gov (United States)

Burkardt, Hans-Joachim

2011-01-01

Pandemic H1N1 2009 ('swine flu') virus was 'the virus of the year 2009' because it affected the lives of many people in this year. H1N1 was first described in California in April 2009 and spread very rapidly all over the globe. The fast global penetration of the swine flu caused the WHO in Geneva to call the infection with H1N1 a new pandemic with a rapid escalation of the different pandemic phases that ended on 11 June 2009, with the declaration of phase 6 (full-blown pandemic). This had far-reaching consequences for the local health authorities in the different affected countries and created awareness in the public and fear in the experts and even more so in many lay people. The consequences were: setting up reliable diagnostic tests as soon as possible; enhanced production, distribution and stock creation of the few drugs that were available to treat newly infected persons; and development, production, distribution and stock creation of new and appropriate anti-H1N1 swine flu vaccines. This all resulted in enormous costs in the local healthcare systems and also required smart and diligent logistics, because demand for all this was, in most cases, much higher than availability. Fortunately, the pandemic ended quite quickly (there was no 'second wave' as had been anticipated by some experts) and the death toll was moderate, compared with other influenza pandemic in the past and even to the regular annual appearance of the seasonal flu. This favorable outcome, however, provoked some harsh criticism that the WHO and healthcare systems in general had over-reacted and by doing so, a lot of money was thrown out of the window. This article describes the history of the H1N1 pandemic, the diagnostic challenges and resolutions, touches on treatment and vaccination very briefly and also comments on the criticism and arguments that came up immediately at the end and following the termination of the pandemic situation.

Measuring the potential of individual airports for pandemic spread over the world airline network.

Science.gov (United States)

Lawyer, Glenn

2016-02-09

Massive growth in human mobility has dramatically increased the risk and rate of pandemic spread. Macro-level descriptors of the topology of the World Airline Network (WAN) explains middle and late stage dynamics of pandemic spread mediated by this network, but necessarily regard early stage variation as stochastic. We propose that much of this early stage variation can be explained by appropriately characterizing the local network topology surrounding an outbreak's debut location. Based on a model of the WAN derived from public data, we measure for each airport the expected force of infection (AEF) which a pandemic originating at that airport would generate, assuming an epidemic process which transmits from airport to airport via scheduled commercial flights. We observe, for a subset of world airports, the minimum transmission rate at which a disease becomes pandemically competent at each airport. We also observe, for a larger subset, the time until a pandemically competent outbreak achieves pandemic status given its debut location. Observations are generated using a highly sophisticated metapopulation reaction-diffusion simulator under a disease model known to well replicate the 2009 influenza pandemic. The robustness of the AEF measure to model misspecification is examined by degrading the underlying model WAN. AEF powerfully explains pandemic risk, showing correlation of 0.90 to the transmission level needed to give a disease pandemic competence, and correlation of 0.85 to the delay until an outbreak becomes a pandemic. The AEF is robust to model misspecification. For 97 % of airports, removing 15 % of airports from the model changes their AEF metric by less than 1 %. Appropriately summarizing the size, shape, and diversity of an airport's local neighborhood in the WAN accurately explains much of the macro-level stochasticity in pandemic outcomes.

History of Swine influenza viruses in Asia.

Science.gov (United States)

Zhu, Huachen; Webby, Richard; Lam, Tommy T Y; Smith, David K; Peiris, Joseph S M; Guan, Yi

2013-01-01

The pig is one of the main hosts of influenza A viruses and plays important roles in shaping the current influenza ecology. The occurrence of the 2009 H1N1 pandemic influenza virus demonstrated that pigs could independently facilitate the genesis of a pandemic influenza strain. Genetic analyses revealed that this virus was derived by reassortment between at least two parent swine influenza viruses (SIV), from the northern American triple reassortant H1N2 (TR) and European avian-like H1N1 (EA) lineages. The movement of live pigs between different continents and subsequent virus establishment are preconditions for such a reassortment event to occur. Asia, especially China, has the largest human and pig populations in the world, and seems to be the only region frequently importing pigs from other continents. Virological surveillance revealed that not only classical swine H1N1 (CS), and human-origin H3N2 viruses circulated, but all of the EA, TR and their reassortant variants were introduced into and co-circulated in pigs in this region. Understanding the long-term evolution and history of SIV in Asia would provide insights into the emergence of influenza viruses with epidemic potential in swine and humans.

Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission

Science.gov (United States)

Saunders-Hastings, Patrick R.; Krewski, Daniel

2016-01-01

For centuries, novel strains of influenza have emerged to produce human pandemics, causing widespread illness, death, and disruption. There have been four influenza pandemics in the past hundred years. During this time, globalization processes, alongside advances in medicine and epidemiology, have altered the way these pandemics are experienced. Drawing on international case studies, this paper provides a review of the impact of past influenza pandemics, while examining the evolution of our understanding of, and response to, these viruses. This review argues that pandemic influenza is in part a consequence of human development, and highlights the importance of considering outbreaks within the context of shifting global landscapes. While progress in infectious disease prevention, control, and treatment has improved our ability to respond to such outbreaks, globalization processes relating to human behaviour, demographics, and mobility have increased the threat of pandemic emergence and accelerated global disease transmission. Preparedness planning must continue to evolve to keep pace with this heightened risk. Herein, we look to the past for insights on the pandemic experience, underlining both progress and persisting challenges. However, given the uncertain timing and severity of future pandemics, we emphasize the need for flexible policies capable of responding to change as such emergencies develop. PMID:27929449

Mitigation Approaches to Combat the Flu Pandemic

Science.gov (United States)

Chawla, Raman; Sharma, Rakesh Kumar; Madaan, Deepali; Dubey, Neha; Arora, Rajesh; Goel, Rajeev; Singh, Shefali; Kaushik, Vinod; Singh, Pankaj Kumar; Chabbra, Vivek; Bhardwaj, Janak Raj

2009-01-01

Management of flu pandemic is a perpetual challenge for the medical fraternity since time immemorial. Animal to human transmission has been observed thrice in the last century within an average range of 11-39 years of antigenic recycling. The recent outbreak of influenza A (H1N1, also termed as swine flu), first reported in Mexico on April 26, 2009, occurred in the forty first year since last reported flu pandemic (July 1968). Within less than 50 days, it has assumed pandemic proportions (phase VI) affecting over 76 countries with 163 deaths/35,928 cases (as on 15th June 2009). It indicated the re-emergence of genetically reassorted virus having strains endemic to humans, swine and avian (H5N1). The World Health Organisation (WHO) member states have already pulled up their socks and geared up to combat such criticalities. Earlier outbreaks of avian flu (H5N1) in different countries led WHO to develop pandemic preparedness strategies with national/regional plans on pandemic preparedness. Numerous factors related to climatic conditions, socio-economic strata, governance and sharing of information/logistics at all levels have been considered critical indicators in monitoring the dynamics of escalation towards a pandemic situation. The National Disaster Management Authority (NDMA), Government of India, with the active cooperation of UN agencies and other stakeholders/experts has formulated a concept paper on role of nonhealth service providers during pandemics in April 2008 and released national guidelines - management of biological disasters in July 2008. These guidelines enumerate that the success of medical management endeavors like pharmaceutical (anti-viral Oseltamivir and Zanamivir therapies), nonpharmaceutical interventions and vaccination development etc., largely depends on level of resistance offered by mutagenic viral strain and rationale use of pharmaco therapeutic interventions. This article describes the mitigation approach to combat flu pandemic with its

Transmission of Influenza A Viruses

Science.gov (United States)

Neumann, Gabriele; Kawaoka, Yoshihiro

2015-01-01

Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

Waves of El Nino-southern Oscillation and Influenza Pandemics

Directory of Open Access Journals (Sweden)

Olusegun Steven Ayodele Oluwole

2016-04-01

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

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

Science.gov (United States)

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

2015-03-02

Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba. Copyright © 2015 Elsevier B.V. All rights reserved.

Addressing ethical issues in pandemic influenza planning: equitable access to scare medical resources

NARCIS (Netherlands)

Verweij, M.F.

2007-01-01

It is generally expected that sooner or later a novel influenza A virus subtype, easily transmissible from person to person, will emerge and cause pandemic disease. Humans will have little or no immunity to this virus, which could spread at least as easily as common seasonal influenza and

Antiviral resistance and the control of pandemic influenza.

Directory of Open Access Journals (Sweden)

Marc Lipsitch

2007-01-01

Full Text Available The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir, combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness. Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans.We designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains.The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance

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

Science.gov (United States)

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. © 2011 APJPH.

Identification of cross-reacting T-cell epitopes in structural and non-structural proteins of swine and pandemic H1N1 influenza A virus strains in pigs

DEFF Research Database (Denmark)

Baratelli, Massimiliano; Pedersen, Lasse Eggers; Trebbien, Ramona

2017-01-01

Heterologous protection against swine influenza viruses (SwIVs) of different lineages is an important concern for the pig industry. Cross-protection between 'avian-like' H1N1 and 2009 pandemic H1N1 lineages has been observed previously, indicating the involvement of cross-reacting T-cells. Here...

Are we prepared to help low-resource communities cope with a severe influenza pandemic?

Science.gov (United States)

Starbuck, Eric S; von Bernuth, Rudolph; Bolles, Kathryn; Koepsell, Jeanne

2013-11-01

Recent research involving lab-modified H5N1 influenza viruses with increased transmissibility and the ongoing evolution of the virus in nature should remind us of the continuing importance of preparedness for a severe influenza pandemic. Current vaccine technology and antiviral supply remain inadequate, and in a severe pandemic, most low-resource communities will fail to receive adequate medical supplies. However, with suitable guidance, these communities can take appropriate actions without substantial outside resources to reduce influenza transmission and care for the ill. Such guidance should be completed, and support provided to developing countries to adapt it for their settings and prepare for implementation. © 2012 John Wiley & Sons Ltd.

Avian influenza viruses in humans.

Science.gov (United States)

Malik Peiris, J S

2009-04-01

Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.

Pandemic Flu

Science.gov (United States)

... Influenza Types Seasonal Avian Swine Variant Pandemic Other Pandemic Influenza Language: English (US) Español Recommend on Facebook ... Planning State and Local Government Planning More 1918 Pandemic Flu Commemoration 100 years later, read about the ...

Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1 viruses.

Directory of Open Access Journals (Sweden)

Marion Desdouits

Full Text Available 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.

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1 virus infection during pregnancy.

Directory of Open Access Journals (Sweden)

Miloje Savic

Full Text Available Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI responses in pandemic influenza A(H1N1pdm09 (pdm09 virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu. The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC. Infected cases (N = 75 were defined by having a serum hemagglutination inhibition (HI titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75 were randomly selected among non-infected pregnant women (HI titer <10. In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7- and naive (CD45RA+CCR7+ CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+ CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1) virus infection during pregnancy.

Science.gov (United States)

Savic, Miloje; Dembinski, Jennifer L; Laake, Ida; Hungnes, Olav; Cox, Rebecca; Oftung, Fredrik; Trogstad, Lill; Mjaaland, Siri

2017-01-01

Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI) responses in pandemic influenza A(H1N1)pdm09 (pdm09) virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu). The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC). Infected cases (N = 75) were defined by having a serum hemagglutination inhibition (HI) titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75) were randomly selected among non-infected pregnant women (HI titer <10). In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7-) and naive (CD45RA+CCR7+) CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI) symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+) CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.

The Benefits and Risks of Pandemic Influenza Vaccines

NARCIS (Netherlands)

E.G. Wijnans (Leonoor)

2015-01-01

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

Comparison of temporal and spatial dynamics of seasonal H3N2, pandemic H1N1 and highly pathogenic avian influenza H5N1 virus infections in ferrets

NARCIS (Netherlands)

J.M.A. van den Brand (Judith); K.J. Stittelaar (Koert); G. van Amerongen (Geert); L.A. Reperant (Leslie); L. de Waal (Leon); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

2012-01-01

textabstractHumans may be infected by different influenza A viruses-seasonal, pandemic, and zoonotic-which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-02-13

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

Acceptance of vaccinations in pandemic outbreaks: A discrete choice experiment

NARCIS (Netherlands)

D. Determann (Domino); I.J. Korfage (Ida); A.C. Lambooij (Antoinette); M.C.J. Bliemer (Michiel); J.H. Richardus (Jan Hendrik); E.W. Steyerberg (Ewout); E.W. de Bekker-Grob (Esther)

2014-01-01

textabstractBackground: Preventive measures are essential to limit the spread of new viruses; their uptake is key to their success. However, the vaccination uptake in pandemic outbreaks is often low. We aim to elicit how disease and vaccination characteristics determine preferences of the general

Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic

Energy Technology Data Exchange (ETDEWEB)

Xu, Rui; McBride, Ryan; Paulson, James C.; Basler, Christopher F.; Wilson, Ian A. (Sinai); (Scripps)

2010-03-04

The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 {angstrom} resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

A monoclonal antibody-based ELISA for differential diagnosis of 2009 pandemic H1N1

Science.gov (United States)

The swine-origin 2009 pandemic H1N1 virus (pdmH1N1) is genetically related to North American swine H1 influenza viruses and unrelated to human seasonal H1 viruses. Currently, specific diagnosis of pdmH1N1 relies on RT-PCR. In order to develop an assay that does not rely in amplification of the viral...

The antigenic property of the H5N1 avian influenza viruses isolated in central China

Directory of Open Access Journals (Sweden)

Zou Wei

2012-08-01

Full Text Available Abstract Background Three influenza pandemics outbroke in the last century accompanied the viral antigen shift and drift, resulting in the change of antigenic property and the low cross protective ability of the existed antibody to the newly emerged pandemic virus, and eventually the death of millions of people. The antigenic characterizations of the viruses isolated in central China in 2004 and 2006–2007 were investigated in the present study. Results Hemagglutinin inhibition assay and neutralization assay displayed differential antigenic characteristics of the viruses isolated in central China in two periods (2004 and 2006–2007. HA genes of the viruses mainly located in two branches in phylogeny analysis. 53 mutations of the deduced amino acids of the HA genes were divided into 4 patterns. Mutations in pattern 2 and 3 showed the main difference between viruses isolated in 2004 and 2006–2007. Meanwhile, most amino acids in pattern 2 and 3 located in the globular head of the HA protein, and some of the mutations evenly distributed at the epitope sites. Conclusions The study demonstrated that a major antigenic drift had occurred in the viruses isolated in central China. And monitoring the antigenic property should be the priority in preventing the potential pandemic of H5N1 avian influenza virus.

Swine Influenza Virus Antibodies in Humans, Western Europe, 2009

Science.gov (United States)

Gerloff, Nancy A.; Kremer, Jacques R.; Charpentier, Emilie; Sausy, Aurélie; Olinger, Christophe M.; Weicherding, Pierre; Schuh, John; Van Reeth, Kristien

2011-01-01

Serologic studies for swine influenza viruses (SIVs) in humans with occupational exposure to swine have been reported from the Americas but not from Europe. We compared levels of neutralizing antibodies against 3 influenza viruses—pandemic (H1N1) 2009, an avian-like enzootic subtype H1N1 SIV, and a 2007–08 seasonal subtype H1N1—in 211 persons with swine contact and 224 matched controls in Luxembourg. Persons whose profession involved contact with swine had more neutralizing antibodies against SIV and pandemic (H1N1) 2009 virus than did the controls. Controls also had antibodies against these viruses although exposure to them was unlikely. Antibodies against SIV and pandemic (H1N1) 2009 virus correlated with each other but not with seasonal subtype H1N1 virus. Sequential exposure to variants of seasonal influenza (H1N1) viruses may have increased chances for serologic cross-reactivity with antigenically distinct viruses. Further studies are needed to determine the extent to which serologic responses correlate with infection. PMID:21392430

Nonpharmaceutical Interventions for Military Populations During Pandemic Influenza

Directory of Open Access Journals (Sweden)

Selim Kilic

2007-08-01

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

Predicting Hotspots for Influenza Virus Reassortment

Science.gov (United States)

Gilbert, Marius; Martin, Vincent; Cappelle, Julien; Hosseini, Parviez; Njabo, Kevin Y.; Abdel Aziz, Soad; Xiao, Xiangming; Daszak, Peter; Smith, Thomas B.

2013-01-01

The 1957 and 1968 influenza pandemics, each of which killed ≈1 million persons, arose through reassortment events. Influenza virus in humans and domestic animals could reassort and cause another pandemic. To identify geographic areas where agricultural production systems are conducive to reassortment, we fitted multivariate regression models to surveillance data on influenza A virus subtype H5N1 among poultry in China and Egypt and subtype H3N2 among humans. We then applied the models across Asia and Egypt to predict where subtype H3N2 from humans and subtype H5N1 from birds overlap; this overlap serves as a proxy for co-infection and in vivo reassortment. For Asia, we refined the prioritization by identifying areas that also have high swine density. Potential geographic foci of reassortment include the northern plains of India, coastal and central provinces of China, the western Korean Peninsula and southwestern Japan in Asia, and the Nile Delta in Egypt. PMID:23628436

Phase 1 study of pandemic H1 DNA vaccine in healthy adults.

Directory of Open Access Journals (Sweden)

Michelle C Crank

Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.Clinicaltrials.gov NCT00973895.

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

Directory of Open Access Journals (Sweden)

Lee Albert

2010-11-01

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

The cost effectiveness of pandemic influenza interventions: a pandemic severity based analysis.

Directory of Open Access Journals (Sweden)

George J Milne

Full Text Available BACKGROUND: The impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning. METHODS: A cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ∼30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR, using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR. RESULTS: Intervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5% the cost is ∼$9 k per LYS; for a low severity pandemic (CFR of 0.1% this strategy costs ∼$58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03% the cost is ∼$155 per LYS. With high severity pandemics (CFR >0.75% the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death. CONCLUSIONS: The most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in

The Cost Effectiveness of Pandemic Influenza Interventions: A Pandemic Severity Based Analysis

Science.gov (United States)

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

2013-01-01

Background The impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning. Methods A cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ∼30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR), using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR. Results Intervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS) for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5%) the cost is ∼$9 k per LYS; for a low severity pandemic (CFR of 0.1%) this strategy costs ∼$58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03%) the cost is ∼$155 per LYS. With high severity pandemics (CFR >0.75%) the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death. Conclusions The most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in reducing the

A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

NARCIS (Netherlands)

Zhang, Heng; de Vries, Robert P; Tzarum, Netanel; Zhu, Xueyong; Yu, Wenli; McBride, Ryan; Paulson, James C; Wilson, Ian A

2015-01-01

Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8

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

Science.gov (United States)

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

2014-04-03

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

Productive confusions: learning from simulations of pandemic virus outbreaks in Second Life

Science.gov (United States)

Cárdenas, Micha; Greci, Laura S.; Hurst, Samantha; Garman, Karen; Hoffman, Helene; Huang, Ricky; Gates, Michael; Kho, Kristen; Mehrmand, Elle; Porteous, Todd; Calvitti, Alan; Higginbotham, Erin; Agha, Zia

2011-03-01

Users of immersive virtual reality environments have reported a wide variety of side and after effects including the confusion of characteristics of the real and virtual worlds. Perhaps this side effect of confusing the virtual and real can be turned around to explore the possibilities for immersion with minimal technological support in virtual world group training simulations. This paper will describe observations from my time working as an artist/researcher with the UCSD School of Medicine (SoM) and Veterans Administration San Diego Healthcare System (VASDHS) to develop trainings for nurses, doctors and Hospital Incident Command staff that simulate pandemic virus outbreaks. By examining moments of slippage between realities, both into and out of the virtual environment, moments of the confusion of boundaries between real and virtual, we can better understand methods for creating immersion. I will use the mixing of realities as a transversal line of inquiry, borrowing from virtual reality studies, game studies, and anthropological studies to better understand the mechanisms of immersion in virtual worlds. Focusing on drills conducted in Second Life, I will examine moments of training to learn the software interface, moments within the drill and interviews after the drill.

Transmisibilidad y gravedad de la pandemia de gripe A(H1N12009 en España Transmissibility and severity of the pandemic influenza A (H1N1 2009 virus in Spain

Directory of Open Access Journals (Sweden)

Lorena Simón Méndez

2011-08-01

veces el promedio anual ajustado de las temporadas interpandémicas de comparación (1.802. Conclusiones: Los valores estimados de R0 durante la fase de crecimiento de la onda pandémica se encuentran en el rango inferior de estimaciones de ese parámetro en pandemias anteriores. Los indicadores de mortalidad calculados en el periodo pandémico señalan un aumento de las defunciones, en comparación con temporadas interpándemicas previas, más acusado en edades jóvenes.Objectives: To estimate the value of the basic reproduction number for the pandemic wave of influenza A (H1N1 2009 in Spain and to assess its impact on morbidity and mortality in the Spanish population compared with those in the previous influenza season. Methods: Data on the incidence of influenza and viral detections were obtained from the Spanish Influenza Surveillance System. Deaths from pandemic influenza were obtained from the Coordinating Center for Health Alerts and Emergencies of the Spanish Ministry of Health and Social Policy, and deaths from seasonal influenza during the period 2003-2008 were obtained from the National Statistics Institute. The reproduction number was estimated by two methods: firstly, by using the growth rate of the cumulative incidence of influenza during the exponential growth phase of the pandemic wave, and secondly (maximum likelihood estimation, through analysis the dates of onset of symptoms observed in pairs of cases based on generation time distribution. We calculated the fatality rate and mortality from influenza by comparing potential years of life lost in the pandemic season with those in previous interpandemic seasons. Results: The start of the pandemic wave occurred in Spain earlier in week 40/2009 (from 4 to 10 October, with an absolute predominance of the new strain in the pattern of circulating viruses. The value of R0 in the growth phase of the wave was 1.29 (95% CI: 1.25-1.33, estimated with the first method, and was 1.01 (95% CI: 0.99-1.03 with the second

Rapid detection and subtyping of human influenza A viruses and reassortants by pyrosequencing.

Directory of Open Access Journals (Sweden)

Yi-Mo Deng

Full Text Available BACKGROUND: Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. METHODOLOGY/PRINCIPAL FINDINGS: A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. CONCLUSIONS/SIGNIFICANCE: In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches.

Rapid detection and subtyping of human influenza A viruses and reassortants by pyrosequencing.

Science.gov (United States)

Deng, Yi-Mo; Caldwell, Natalie; Barr, Ian G

2011-01-01

Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches.

Relevance of workplace social mixing during influenza pandemics: an experimental modelling study of workplace cultures.

Science.gov (United States)

Timpka, T; Eriksson, H; Holm, E; Strömgren, M; Ekberg, J; Spreco, A; Dahlström, Ö

2016-07-01

Workplaces are one of the most important regular meeting places in society. The aim of this study was to use simulation experiments to examine the impact of different workplace cultures on influenza dissemination during pandemics. The impact is investigated by experiments with defined social-mixing patterns at workplaces using semi-virtual models based on authentic sociodemographic and geographical data from a North European community (population 136 000). A simulated pandemic outbreak was found to affect 33% of the total population in the community with the reference academic-creative workplace culture; virus transmission at the workplace accounted for 10·6% of the cases. A model with a prevailing industrial-administrative workplace culture generated 11% lower incidence than the reference model, while the model with a self-employed workplace culture (also corresponding to a hypothetical scenario with all workplaces closed) produced 20% fewer cases. The model representing an academic-creative workplace culture with restricted workplace interaction generated 12% lower cumulative incidence compared to the reference model. The results display important theoretical associations between workplace social-mixing cultures and community-level incidence rates during influenza pandemics. Social interaction patterns at workplaces should be taken into consideration when analysing virus transmission patterns during influenza pandemics.

A Literature Review of Zika Virus.

Science.gov (United States)

Plourde, Anna R; Bloch, Evan M

2016-07-01

Zika virus is a mosquitoborne flavivirus that is the focus of an ongoing pandemic and public health emergency. Previously limited to sporadic cases in Africa and Asia, the emergence of Zika virus in Brazil in 2015 heralded rapid spread throughout the Americas. Although most Zika virus infections are characterized by subclinical or mild influenza-like illness, severe manifestations have been described, including Guillain-Barre syndrome in adults and microcephaly in babies born to infected mothers. Neither an effective treatment nor a vaccine is available for Zika virus; therefore, the public health response primarily focuses on preventing infection, particularly in pregnant women. Despite growing knowledge about this virus, questions remain regarding the virus's vectors and reservoirs, pathogenesis, genetic diversity, and potential synergistic effects of co-infection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health intervention in the current Zika virus epidemic.

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

Science.gov (United States)

Schanzer, Dena L; Zheng, Hui; Gilmore, Jason

2011-04-12

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

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

Science.gov (United States)

2011-01-01

Background As many respiratory viruses are responsible for influenza like symptoms, accurate measures of the disease burden are not available and estimates are generally based on statistical methods. The objective of this study was to estimate absenteeism rates and hours lost due to seasonal influenza and compare these estimates with estimates of absenteeism attributable to the two H1N1 pandemic waves that occurred in 2009. Methods Key absenteeism variables were extracted from Statistics Canada's monthly labour force survey (LFS). Absenteeism and the proportion of hours lost due to own illness or disability were modelled as a function of trend, seasonality and proxy variables for influenza activity from 1998 to 2009. Results Hours lost due to the H1N1/09 pandemic strain were elevated compared to seasonal influenza, accounting for a loss of 0.2% of potential hours worked annually. In comparison, an estimated 0.08% of hours worked annually were lost due to seasonal influenza illnesses. Absenteeism rates due to influenza were estimated at 12% per year for seasonal influenza over the 1997/98 to 2008/09 seasons, and 13% for the two H1N1/09 pandemic waves. Employees who took time off due to a seasonal influenza infection took an average of 14 hours off. For the pandemic strain, the average absence was 25 hours. Conclusions This study confirms that absenteeism due to seasonal influenza has typically ranged from 5% to 20%, with higher rates associated with multiple circulating strains. Absenteeism rates for the 2009 pandemic were similar to those occurring for seasonal influenza. Employees took more time off due to the pandemic strain than was typical for seasonal influenza. PMID:21486453

Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014

NARCIS (Netherlands)

Ampofo, W.K.; Azziz-Baumgartner, E.; Bashir, U.; Cox, N.J.; Fasce, R.; Giovanni, M.; Grohmann, G.; Huang, S.; Katz, J.; Mironenko, A.; Mokhtari-Azad, T.; Sasono, P.M.; Rahman, M.; Sawanpanyalert, P.; Siqueira, M.; Waddell, A.L.; Waiboci, L.; Wood, J.; Zhang, W.; Ziegler, T.; Paget, W.J.; et al.,

2015-01-01

Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and

Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic Characteristics.

Science.gov (United States)

Peacock, Thomas P; Benton, Donald J; James, Joe; Sadeyen, Jean-Remy; Chang, Pengxiang; Sealy, Joshua E; Bryant, Juliet E; Martin, Stephen R; Shelton, Holly; Barclay, Wendy S; Iqbal, Munir

2017-07-15

H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa, where they pose a threat to human health as both zoonotic agents and potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions; however, vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza virus antigen hemagglutinin (HA). Using selection with HA-specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBSs). Here we analyzed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that mutant viruses with RBS deletions are able to escape polyclonal antiserum binding and are able to infect and be transmitted between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells; however, the mutant HAs also displayed reduced pH and thermal stability. In summary, we infer that variant influenza viruses with deletions in the 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude that these viruses are unlikely to be transmitted from human to human by the airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence. IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden; however, influenza viruses are able to

Avian Influenza A Viruses: Evolution and Zoonotic Infection.

Science.gov (United States)

Kim, Se Mi; Kim, Young-Il; Pascua, Philippe Noriel Q; Choi, Young Ki

2016-08-01

Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Characterization of Avian H9N2 Influenza Viruses from United Arab Emirates 2000 to 2003

Science.gov (United States)

Aamir, U. B.; Wernery, Ulrich; Ilyushina, N.; Webster, R. G.

2009-01-01

Our aim was to establish the phylogenetic relation of H9N2 avian viruses in the Middle East to other Asian H9N2 lineages by characterization of 7 viruses isolated from United Arab Emirates (2000-2003). All these viruses had an additional basic amino acid at the hemagglutinin-connecting peptide; 6 contained a mutation associated with increased affinity toward human-like sialic acid substrates. The viruses' surface glycoproteins and most internal genes were >90% similar to those of A/Quail/Hong Kong/G1/97 (H9N2) lineage. The hemadsorbing site of neuraminidase had up to 4 amino acid substitutions, as do human pandemic viruses. M2 sequence analysis revealed amino acid changes at 2 positions, with increasing resistance to amantadine in cell culture. They replicated efficiently in inoculated chickens and were successfully transmitted to contacts. They continue to maintain H5N1-like genes and may augment the spread of H5N1 viruses through regional co-circulation and inapparent infection. These viruses may present as potential pandemic candidates themselves. PMID:17157891

Investing in Immunity: Prepandemic Immunization to Combat Future Influenza Pandemics.

Science.gov (United States)

Goodman, Jesse L

2016-02-15

We are unlikely, with current technologies, to have sufficient pandemic influenza vaccine ready in time to impact the first wave of the next pandemic. Emerging data show that prior immunization with an immunologically distinct hemagglutinin of the same subtype offers the potential to "prime" recipients for rapid protection with a booster dose, years later, of a vaccine then manufactured to match the pandemic strain. This article proposes making prepandemic priming vaccine(s) available for voluntary use, particularly to those at high risk of early occupational exposure, such as first responders and healthcare workers, and to others maintaining critical infrastructure. In addition to providing faster protection and potentially reducing social disruption, being able, early in a pandemic, to immunize those who had received prepandemic vaccine with one dose of the pandemic vaccine, rather than the 2 doses typically required, would reduce the total doses of pandemic vaccine then needed, extending vaccine supplies. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Is sunspot activity a factor in influenza pandemics?

Science.gov (United States)

Qu, Jiangwen

2016-09-01

The 2009 AH1N1 pandemic became a global health concern, although fortunately, its worst anticipated effects were not realised. While the origins of such outbreaks remain poorly understood, it is very important to identify the precipitating factors in their emergence so that future pandemics can be detected as quickly as possible. Methords: Descriptive epidemiology was used to analyse the association between influenza pandemics and possible pandemics and relative number of sunspots. Non-conditional logistic regression was performed to analyse the statistical association between sunspot extremes and influenza pandemics to within plus or minus 1 year. Almost all recorded influenza/possible pandemics have occurred in time frames corresponding to sunspot extremes, or +/- 1 year within such extremes. These periods were identified as important risk factors in both possible and confirmed influenza pandemics (odds ratio: 3.87; 95% confidence interval: 1.08 to 13.85). Extremes of sunspot activity to within plus or minus 1 year may precipitate influenza pandemics. Mechanisms of epidemic initiation and early spread are discussed including primary causation by externally derived viral variants (from space via cometary dust). Efforts to construct a comprehensive early warning system for potential influenza and other viral pandemics that include analysis of sunspot activity and stratospheric sampling for viral variants should be supported. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

Directory of Open Access Journals (Sweden)

Wong Emily HM

2010-08-01

Full Text Available Abstract Background The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease. Results Relative Synonymous Codon Usage (RSCU values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA. The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus. Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes. Conclusions Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.

Full genomic analysis of an influenza A (H1N2) virus identified during 2009 pandemic in Eastern India: evidence of reassortment event between co-circulating A(H1N1)pdm09 and A/Brisbane/10/2007-like H3N2 strains.

Science.gov (United States)

Mukherjee, Tapasi Roy; Agrawal, Anurodh S; Chakrabarti, Sekhar; Chawla-Sarkar, Mamta

2012-10-11

During the pandemic [Influenza A(H1N1)pdm09] period in 2009-2010, an influenza A (Inf-A) virus with H1N2 subtype (designated as A/Eastern India/N-1289/2009) was detected from a 25 years old male from Mizoram (North-eastern India). To characterize full genome of the H1N2 influenza virus. For initial detection of Influenza viruses, amplification of matrix protein (M) gene of Inf-A and B viruses was carried out by real time RT-PCR. Influenza A positive viruses are then further subtyped with HA and NA gene specific primers. Sequencing and the phylogenetic analysis was performed for the H1N2 strain to understand its origin. The outcome of this full genome study revealed a unique reassortment event where the N-1289 virus acquired it's HA gene from a 2009 pandemic H1N1 virus with swine origin and the other genes from H3N2-like viruses of human origin. This study provides information on possibility of occurrence of reassortment events during influenza season when infectivity is high and two different subtypes of Inf-A viruses co-circulate in same geographical location.

Adaptive policymaking under deep uncertainty : Optimal preparedness for the next pandemic

NARCIS (Netherlands)

Hamarat, C.; Kwakkel, J.H.; Pruyt, E.

2012-01-01

The recent flu pandemic in 2009 caused a panic about the possible consequences due to deep uncertainty about an unknown virus. Overstock of vaccines or unnecessary social measures to be taken were all due to uncertainty. However, what should be the necessary actions to take in such deeply uncertain

H9N2 influenza A virus isolated from a Greater White-fronted wild goose (Anser albifrons) in Alaska has a mutation in the PB2 gene, which is associated with pathogenicity in human pandemic 2009 H1N1

Science.gov (United States)

Reeves, Andrew; Ip, Hon S.

2016-01-01

We report here the genomic sequence of an H9N2 influenza A virus [A/greater white-fronted goose/Alaska/81081/2008 (H9N2)]. This virus shares ≥99.8% identity with a previously reported virus. Both strains contain a G590S mutation in the polymerase basic 2 (PB2) gene, which is a pathogenicity marker in the pandemic 2009 H1N1 virus when combined with R591.

Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

Directory of Open Access Journals (Sweden)

Cristian Cillóniz

2009-10-01

Full Text Available The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.

A neighborhood susceptibility index for planning of local physical interventions in response to pandemic influenza outbreaks

Science.gov (United States)

Timpka, Toomas; Eriksson, Henrik; Strömgren, Magnus; Eriksson, Olle; Ekberg, Joakim; Grimvall, Anders; Nyce, James; Gursky, Elin; Holm, Einar

2010-01-01

The global spread of a novel A (H1N1) influenza virus in 2009 has highlighted the possibility of a devastating pandemic similar to the ‘Spanish flu’ of 1917–1918. Responding to such pandemics requires careful planning for the early phases where there is no availability of pandemic vaccine. We set out to compute a Neighborhood Influenza Susceptibility Index (NISI) describing the vulnerability of local communities of different geo-socio-physical structure to a pandemic influenza outbreak. We used a spatially explicit geo-physical model of Linköping municipality (pop. 136,240) in Sweden, and employed an ontology-modeling tool to define simulation models and transmission settings. We found considerable differences in NISI between neighborhoods corresponding to primary care areas with regard to early progress of the outbreak, as well as in terms of the total accumulated share of infected residents counted after the outbreak. The NISI can be used in local preparations of physical response measures during pandemics. PMID:21347087

Factors associated with post-seasonal serological titer and risk factors for infection with the pandemic A/H1N1 virus in the French general population.

Directory of Open Access Journals (Sweden)

Nathanael Lapidus

Full Text Available The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households. The GMT for the general population was 47.1 (95% confidence interval (CI: 45.1, 49.2. According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.

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

Directory of Open Access Journals (Sweden)

Zheng Hui

2011-04-01

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

Influenza pandemics and avian flu

OpenAIRE

Fleming, Douglas

2005-01-01

Douglas Fleming is general practitioner in a large suburban practice in Birmingham. In this article he seeks to clarify clinical issues relating to potential pandemics of influenza, including avian influenza

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

Directory of Open Access Journals (Sweden)

Miller Joel C

2010-07-01

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

A new class of synthetic anti-lipopolysaccharide peptides inhibits influenza A virus replication by blocking cellular attachment.

Science.gov (United States)

Hoffmann, Julia; Schneider, Carola; Heinbockel, Lena; Brandenburg, Klaus; Reimer, Rudolph; Gabriel, Gülsah

2014-04-01

Influenza A viruses are a continuous threat to human health as illustrated by the 2009 H1N1 pandemic. Since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. Here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; SALPs) for their potential to inhibit influenza virus replication in vitro and in vivo. We found that particularly SALP PEP 19-2.5 shows high binding affinities for the influenza virus receptor molecule, N-Acetylneuraminic acid, leading to impaired viral attachment and cellular entry. As a result, replication of several influenza virus subtypes (H7N7, H3N2 and 2009 pandemic H1N1) was strongly reduced. Furthermore, mice co-treated with PEP 19-2.5 were protected against an otherwise 100% lethal H7N7 influenza virus infection. These findings show that SALPs exhibit antiviral activity against influenza viruses by blocking virus attachment and entry into host cells. Thus, SALPs present a new class of broad-spectrum antiviral peptides for further development for influenza virus therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Stability and infectivity of novel pandemic influenza A (H1N1) virus in blood-derived matrices under different storage conditions.

Science.gov (United States)

Wang, Xue; Zoueva, Olga; Zhao, Jiangqin; Ye, Zhiping; Hewlett, Indira

2011-12-22

Influenza A virus has been detected in the blood of some infected individuals, and may pose a safety concern for collection, handling and transport of specimens for epidemiological and public health investigations if infectious virus is present in samples. Furthermore the effect of storage on virus stability and infectivity has not been well studied. We examined the stability of novel pandemic influenza A (H1N1) virus RNA when the virus was stored in phosphate buffered saline (PBS), plasma, or buffy coated blood at either room temperature or 4°C using a sensitive Taqman RT-PCR assay. We also investigated virus infectivity using the EID(50) assay when virus was stored in PBS, plasma, or buffy coats isolated from blood at 4°C. Viral RNA stability was affected by the matrix used for storage. The recovery of viral RNA was highest when virus was stored in PBS with lower amounts being recovered from plasma and buffy coats at either room temperature or 4°C. Incubation time did not appear to be a major factor for viral RNA stability, although there was gradual decline after longer periods post-incubation. Both sample matrix and incubation time affected virus infectivity. The decay in virus infectivity was greatest in PBS followed by buffy coats and plasma. Virus infectivity was abolished in buffy coats at day 20 post-incubation when virus concentrations were low. These data indicate that encapsidated viral RNA was stable overall in all three liquid matrices at room temperature or 4°C although it was most stable in PBS; virus infectivity in buffy coats at 4°C decayed in a time dependent manner while it remained unchanged in plasma. These findings have implications for storage, handling and transport of blood derived samples from influenza patients for epidemiological and laboratory investigations. It should be noted that there is little known about influenza viremia, and whether influenza viruses can be transmitted by blood or blood derived samples.

Stability and infectivity of novel pandemic influenza A (H1N1 virus in blood-derived matrices under different storage conditions

Directory of Open Access Journals (Sweden)

Wang Xue

2011-12-01

Full Text Available Abstract Background Influenza A virus has been detected in the blood of some infected individuals, and may pose a safety concern for collection, handling and transport of specimens for epidemiological and public health investigations if infectious virus is present in samples. Furthermore the effect of storage on virus stability and infectivity has not been well studied. Methods We examined the stability of novel pandemic influenza A (H1N1 virus RNA when the virus was stored in phosphate buffered saline (PBS, plasma, or buffy coated blood at either room temperature or 4°C using a sensitive Taqman RT-PCR assay. We also investigated virus infectivity using the EID50 assay when virus was stored in PBS, plasma, or buffy coats isolated from blood at 4°C. Results Viral RNA stability was affected by the matrix used for storage. The recovery of viral RNA was highest when virus was stored in PBS with lower amounts being recovered from plasma and buffy coats at either room temperature or 4°C. Incubation time did not appear to be a major factor for viral RNA stability, although there was gradual decline after longer periods post-incubation. Both sample matrix and incubation time affected virus infectivity. The decay in virus infectivity was greatest in PBS followed by buffy coats and plasma. Virus infectivity was abolished in buffy coats at day 20 post-incubation when virus concentrations were low. Conclusion These data indicate that encapsidated viral RNA was stable overall in all three liquid matrices at room temperature or 4°C although it was most stable in PBS; virus infectivity in buffy coats at 4°C decayed in a time dependent manner while it remained unchanged in plasma. These findings have implications for storage, handling and transport of blood derived samples from influenza patients for epidemiological and laboratory investigations. It should be noted that there is little known about influenza viremia, and whether influenza viruses can be

A Literature Review of Zika Virus

Science.gov (United States)

Bloch, Evan M.

2016-01-01

Zika virus is a mosquitoborne flavivirus that is the focus of an ongoing pandemic and public health emergency. Previously limited to sporadic cases in Africa and Asia, the emergence of Zika virus in Brazil in 2015 heralded rapid spread throughout the Americas. Although most Zika virus infections are characterized by subclinical or mild influenza-like illness, severe manifestations have been described, including Guillain-Barre syndrome in adults and microcephaly in babies born to infected mothers. Neither an effective treatment nor a vaccine is available for Zika virus; therefore, the public health response primarily focuses on preventing infection, particularly in pregnant women. Despite growing knowledge about this virus, questions remain regarding the virus’s vectors and reservoirs, pathogenesis, genetic diversity, and potential synergistic effects of co-infection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health intervention in the current Zika virus epidemic. PMID:27070380

Oseltamivir (Tamiflu® in the environment, resistance development in influenza A viruses of dabbling ducks and the risk of transmission of an oseltamivir-resistant virus to humans – a review

Directory of Open Access Journals (Sweden)

Josef D. Järhult

2012-06-01

Full Text Available The antiviral drug oseltamivir (Tamiflu® is a cornerstone in influenza pandemic preparedness plans worldwide. However, resistance to the drug is a growing concern. The active metabolite oseltamivir carboxylate (OC is not degraded in surface water or sewage treatment plants and has been detected in river water during seasonal influenza outbreaks. The natural influenza reservoir, dabbling ducks, can thus be exposed to OC in aquatic environments. Environmental-like levels of OC induce resistance development in influenza A/H1N1 virus in mallards. There is a risk of resistance accumulation in influenza viruses circulating among wild birds when oseltamivir is used extensively. By reassortment or direct transmission, oseltamivir resistance can be transmitted to humans potentially causing a resistant pandemic or human-adapted highly-pathogenic avian influenza virus. There is a need for more research on resistance development in the natural influenza reservoir and for a prudent use of antivirals.

Pandemic planning

National Research Council Canada - National Science Library

Dietz, J. Eric; Black, David R

2012-01-01

... that may arise throughout the process. The book details the threat of pandemic illness and the need and actions required for efficient and effective preparation, prevention, response, and recovery to a pandemic threat at all levels...

Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus in ferrets

Science.gov (United States)

The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...

The transmissibility and control of pandemic influenza A (H1N1) virus.

Science.gov (United States)

Yang, Yang; Sugimoto, Jonathan D; Halloran, M Elizabeth; Basta, Nicole E; Chao, Dennis L; Matrajt, Laura; Potter, Gail; Kenah, Eben; Longini, Ira M

2009-10-30

Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R0, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.

Controlling pandemic flu: the value of international air travel restrictions.

OpenAIRE

Joshua M Epstein; D Michael Goedecke; Feng Yu; Robert J Morris; Diane K Wagener; Georgiy V Bobashev

2007-01-01

Background Planning for a possible influenza pandemic is an extremely high priority, as social and economic effects of an unmitigated pandemic would be devastating. Mathematical models can be used to explore different scenarios and provide insight into potential costs, benefits, and effectiveness of prevention and control strategies under consideration. Methods and Findings A stochastic, equation-based epidemic model is used to study global transmission of pandemic flu, including the effects ...

Full genomic analysis of an influenza A (H1N2 virus identified during 2009 pandemic in Eastern India: evidence of reassortment event between co-circulating A(H1N1pdm09 and A/Brisbane/10/2007-like H3N2 strains

Directory of Open Access Journals (Sweden)

Mukherjee Tapasi Roy

2012-10-01

Full Text Available Abstract Background During the pandemic [Influenza A(H1N1pdm09] period in 2009-2010, an influenza A (Inf-A virus with H1N2 subtype (designated as A/Eastern India/N-1289/2009 was detected from a 25 years old male from Mizoram (North-eastern India. Objective To characterize full genome of the H1N2 influenza virus. Methods For initial detection of Influenza viruses, amplification of matrix protein (M gene of Inf-A and B viruses was carried out by real time RT-PCR. Influenza A positive viruses are then further subtyped with HA and NA gene specific primers. Sequencing and the phylogenetic analysis was performed for the H1N2 strain to understand its origin. Results The outcome of this full genome study revealed a unique reassortment event where the N-1289 virus acquired it’s HA gene from a 2009 pandemic H1N1 virus with swine origin and the other genes from H3N2-like viruses of human origin. Conclusions This study provides information on possibility of occurrence of reassortment events during influenza season when infectivity is high and two different subtypes of Inf-A viruses co-circulate in same geographical location.

Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus.

Science.gov (United States)

O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

2014-05-01

The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

Determinants of individuals' risks to 2009 pandemic influenza virus infection at household level amongst Djibouti city residents--a CoPanFlu cross-sectional study.

Science.gov (United States)

Andayi, Fred; Crepey, Pascal; Kieffer, Alexia; Salez, Nicolas; Abdo, Ammar A; Carrat, Fabrice; Flahault, Antoine; de Lamballerie, Xavier

2014-01-27

Following the 2009 swine flu pandemic, a cohort for pandemic influenza (CoPanFlu) study was established in Djibouti, the Horn of Africa, to investigate its case prevalence and risk predictors' at household level. From the four city administrative districts, 1,045 subjects from 324 households were included during a face-to-face encounter between 11th November 2010 and 15th February 2011. Socio-demographic details were collected and blood samples were analysed in haemagglutination inhibition (HI) assays. Risk assessments were performed in a generalised estimating equation model. In this study, the indicator of positive infection status was set at an HI titre of ≥ 80, which was a relevant surrogate to the seroconversion criterion. All positive cases were considered to be either recent infections or past contact with an antigenically closely related virus in humans older than 65 years. An overall sero-prevalence of 29.1% and a geometrical mean titre (GMT) of 39.5% among the residents was observed. Youths, ≤ 25 years and the elderly, ≥65 years had the highest titres, with values of 35.9% and 29.5%, respectively. Significantly, risk was high amongst youths ≤ 25 years, (OR 1.5-2.2), residents of District 4(OR 2.9), students (OR 1.4) and individuals living near to river banks (OR 2.5). Belonging to a large household (OR 0.6), being employed (OR 0.5) and working in open space-outdoor (OR 0.4) were significantly protective. Only 1.4% of the cohort had vaccination against the pandemic virus and none were immunised against seasonal influenza. Despite the limited number of incident cases detected by the surveillance system, A(H1N1)pdm09 virus circulated broadly in Djibouti in 2010 and 2011. Age-group distribution of cases was similar to what has been reported elsewhere, with youths at the greatest risk of infection. Future respiratory infection control should therefore be tailored to reach specific and vulnerable individuals such as students and those working

Determinants of individuals’ risks to 2009 pandemic influenza virus infection at household level amongst Djibouti city residents - A CoPanFlu cross-sectional study

Science.gov (United States)

2014-01-01

Background Following the 2009 swine flu pandemic, a cohort for pandemic influenza (CoPanFlu) study was established in Djibouti, the Horn of Africa, to investigate its case prevalence and risk predictors’ at household level. Methods From the four city administrative districts, 1,045 subjects from 324 households were included during a face-to-face encounter between 11th November 2010 and 15th February 2011. Socio-demographic details were collected and blood samples were analysed in haemagglutination inhibition (HI) assays. Risk assessments were performed in a generalised estimating equation model. Results In this study, the indicator of positive infection status was set at an HI titre of ≥ 80, which was a relevant surrogate to the seroconversion criterion. All positive cases were considered to be either recent infections or past contact with an antigenically closely related virus in humans older than 65 years. An overall sero-prevalence of 29.1% and a geometrical mean titre (GMT) of 39.5% among the residents was observed. Youths, ≤ 25 years and the elderly, ≥65 years had the highest titres, with values of 35.9% and 29.5%, respectively. Significantly, risk was high amongst youths ≤ 25 years, (OR 1.5-2.2), residents of District 4(OR 2.9), students (OR 1.4) and individuals living near to river banks (OR 2.5). Belonging to a large household (OR 0.6), being employed (OR 0.5) and working in open space-outdoor (OR 0.4) were significantly protective. Only 1.4% of the cohort had vaccination against the pandemic virus and none were immunised against seasonal influenza. Conclusion Despite the limited number of incident cases detected by the surveillance system, A(H1N1)pdm09 virus circulated broadly in Djibouti in 2010 and 2011. Age-group distribution of cases was similar to what has been reported elsewhere, with youths at the greatest risk of infection. Future respiratory infection control should therefore be tailored to reach specific and vulnerable

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

Directory of Open Access Journals (Sweden)

Gerardo Chowell

2011-05-01

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

Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

Science.gov (United States)

Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

2017-10-01

Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adaptive pathways of zoonotic influenza viruses: from exposure to establishment in humans.

Science.gov (United States)

Reperant, Leslie A; Kuiken, Thijs; Osterhaus, Albert D M E

2012-06-22

Human influenza viruses have their ultimate origin in avian reservoirs and may adapt, either directly or after passage through another mammalian species, to circulate independently in the human population. Three sets of barriers must be crossed by a zoonotic influenza virus before it can become a human virus: animal-to-human transmission barriers; virus-cell interaction barriers; and human-to-human transmission barriers. Adaptive changes allowing zoonotic influenza viruses to cross these barriers have been studied extensively, generating key knowledge for improved pandemic preparedness. Most of these adaptive changes link acquired genetic alterations of the virus to specific adaptation mechanisms that can be screened for, both genetically and phenotypically, as part of zoonotic influenza virus surveillance programs. Human-to-human transmission barriers are only sporadically crossed by zoonotic influenza viruses, eventually triggering a worldwide influenza outbreak or pandemic. This is the most devastating consequence of influenza virus cross-species transmission. Progress has been made in identifying some of the determinants of influenza virus transmissibility. However, interdisciplinary research is needed to further characterize these ultimate barriers to the development of influenza pandemics, at both the level of the individual host and that of the population. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

Mcmahon, Benjamin [Los Alamos National Laboratory

2009-01-01

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

In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein.

Science.gov (United States)

Deeg, Christoph M; Hassan, Ebrahim; Mutz, Pascal; Rheinemann, Lara; Götz, Veronika; Magar, Linda; Schilling, Mirjam; Kallfass, Carsten; Nürnberger, Cindy; Soubies, Sébastien; Kochs, Georg; Haller, Otto; Schwemmle, Martin; Staeheli, Peter

2017-05-01

Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population. © 2017 Deeg et al.

The Pandemic and its Impacts

Directory of Open Access Journals (Sweden)

W. Qiu

2017-12-01

Full Text Available The Pandemic has a long history, but the term of “pandemic” is still not been defined by many medical texts. There have been many significant pandemics recorded in human history, and the pandemic related crises have caused enormous negative impacts on health, economies, and even national security in the world. This article will explore the literature for the concept and history of pandemics; summarises the key features of a pandemics, and discusses the negative impacts on health, economy, social and global security of pandemics and disease outbreaks.

Serosurveillance for pandemic influenza A (H1N1 2009 virus infection in domestic elephants, Thailand.

Directory of Open Access Journals (Sweden)

Weena Paungpin

Full Text Available The present study conducted serosurveillance for the presence of antibody to pandemic influenza A (H1N1 2009 virus (H1N1pdm virus in archival serum samples collected between 2009 and 2013 from 317 domestic elephants living in 19 provinces situated in various parts of Thailand. To obtain the most accurate data, hemagglutination-inhibition (HI assay was employed as the screening test; and sera with HI antibody titers ≥20 were further confirmed by other methods, including cytopathic effect/hemagglutination based-microneutralization (microNT and Western blot (WB assays using H1N1pdm matrix 1 (M1 or hemagglutinin (HA recombinant protein as the test antigen. Conclusively, the appropriate assays using HI in conjunction with WB assays for HA antibody revealed an overall seropositive rate of 8.5% (27 of 317. The prevalence of antibody to H1N1pdm virus was 2% (4/172 in 2009, 32% (17/53 in 2010, 9% (2/22 in 2011, 12% (1/8 in 2012, and 5% (3/62 in 2013. Notably, these positive serum samples were collected from elephants living in 7 tourist provinces of Thailand. The highest seropositive rate was obtained from elephants in Phuket, a popular tourist beach city. Young elephants had higher seropositive rate than older elephants. The source of H1N1pdm viral infection in these elephants was not explored, but most likely came from close contact with the infected mahouts or from the infected tourists who engaged in activities such as elephant riding and feeding. Nevertheless, it could not be excluded that elephant-to-elephant transmission did occur.

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

Directory of Open Access Journals (Sweden)

Itziar Casado

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

Immune protection induced on day 10 following administration of the 2009 A/H1N1 pandemic influenza vaccine.

Directory of Open Access Journals (Sweden)

Yizhuo Sun

Full Text Available BACKGROUND: The 2009 swine-origin influenza virus (S-OIV H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. METHODOLOGY/PRINCIPAL FINDINGS: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose. The sera were collected before Day 0 (pre-vaccination and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%. This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21. However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1 more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2. The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21 than that in Group 2 (geometric mean titer: 70 on Day 21. CONCLUSIONS/SIGNIFICANCE: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a

[Swine influenza virus: evolution mechanism and epidemic characterization--a review].

Science.gov (United States)

Qi, Xian; Lu, Chengping

2009-09-01

. Worldwide, more than 50 cases of SIV infection in human have been documented since the 1970s, which indicate that SIV is also an important zoonosis, and the potential of SIV as human pandemic virus or genes donator. In view of SIV in the importance of ecology, as well as a potential threat to human public health, it is recommended to start as soon as possible regular surveillance, paying close attention to its prevalence and molecular evolution. At the same time, we should establish the surveillance network of the whole influenza virus (including human and animal influenza virus) in China, ecologically mastering the prevalence and evolution of influenza viruses, which is of great significance for the protection of animal health and the prevention of human pandemic.

Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

Directory of Open Access Journals (Sweden)

Erhard van der Vries

Full Text Available Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15% cases with prolonged 2009 pandemic virus replication (longer than 14 days, despite antiviral therapy. In 5 out of these 11 (45% cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.

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

Science.gov (United States)

2013-01-01

Background The threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza A(H5N1) is very real, and is reinforced by recent results showing that genetically modified A(H5N1) may be readily transmitted between ferrets. Public health authorities are hesitant in introducing social distancing interventions due to societal disruption and productivity losses. This study estimates the effectiveness and total cost (from a societal perspective, with a lifespan time horizon) of a comprehensive range of social distancing and antiviral drug strategies, under a range of pandemic severity categories. Methods An economic analysis was conducted using a simulation model of a community of ~30,000 in Australia. Data from the 2009 pandemic was used to derive relationships between the Case Fatality Rate (CFR) and hospitalization rates for each of five pandemic severity categories, with CFR ranging from 0.1% to 2.5%. Results For a pandemic with basic reproduction number R0 = 1.8, adopting no interventions resulted in total costs ranging from $441 per person for a pandemic at category 1 (CFR 0.1%) to $8,550 per person at category 5 (CFR 2.5%). For severe pandemics of category 3 (CFR 0.75%) and greater, a strategy combining antiviral treatment and prophylaxis, extended school closure and community contact reduction resulted in the lowest total cost of any strategy, costing $1,584 per person at category 5. This strategy was highly effective, reducing the attack rate to 5%. With low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, whereas higher severity pandemic costs are dominated by healthcare costs and costs arising from productivity losses due to death. Conclusions For pandemics in high severity categories the strategies with the lowest total cost to society involve rigorous, sustained social distancing, which are considered unacceptable for low severity pandemics due to societal

Experiences after Twenty Months with Pandemic Influenza A (H1N1) 2009 Infection in the Naïve Norwegian Pig Population

Science.gov (United States)

Gjerset, B.; Er, C.; Løtvedt, S.; Jørgensen, A.; Hungnes, O.; Lium, B.; Germundsson, A.

2011-01-01

Pandemic (H1N1) 2009 influenza A virus was detected in Norwegian pigs in October 2009. Until then, Norway was regarded free of swine influenza. Intensified screening revealed 91 positive herds within three months. The virus was rapidly transmitted to the susceptible population, including closed breeding herds with high biosecurity. Humans were important for the introduction as well as spread of the virus to pigs. Mild or no clinical signs were observed in infected pigs. Surveillance of SIV in 2010 revealed that 41% of all the Norwegian pig herds had antibodies to pandemic (H1N1) 2009 virus. Furthermore, this surveillance indicated that pigs born in positive herds after the active phase did not seroconvert, suggesting no ongoing infection in the herds. However, results from surveillance in 2011 show a continuing spread of the infection in many herds, either caused by new introduction or by virus circulation since 2009. PMID:23074654

Promotion of Preventive Measures in Public Nursery Schools: Lessons From the H1N1 Pandemic.

Science.gov (United States)

Michail, Koralia A; Ioannidou, Christina; Galanis, Petros; Tsoumakas, Kostantinos; Pavlopoulou, Ioanna D

2017-09-01

Nursery schools serve as reservoirs of transmission of infectious diseases, and teachers should be able to implement and monitor hygiene measures to prevent them. The aim of the present study was to assess the compliance of nursery school teachers on promoting preventive interventions and to identify associated factors, during the novel H1N1 influenza pandemic. A secondary objective was to evaluate their knowledge and vaccination status regarding the novel virus. A cross-sectional study was performed, with the use of a predesigned anonymous, questionnaire, and distributed to all public nursery teachers of Athens, Greece. General etiquette practices were highly acceptable to over 92% of teachers. Those with longer teaching experience promoted simple preventive measures, such as hand washing and use of hand sanitizer, more often while older children were more likely to familiarize with them. However, teachers presented inadequate knowledge concerning the novel virus and their vaccination rates with the pandemic vaccine were unacceptably low (1.1%). Our study showed that promotion of simple preventive measures is feasible and may contribute to the prevention of outbreaks in nursery schools, although knowledge gaps and fear concerning the pandemic vaccine highlight communication issues.

Public views of the uk media and government reaction to the 2009 swine flu pandemic

Directory of Open Access Journals (Sweden)

Smith Emily

2010-11-01

Full Text Available Abstract Background The first cases of influenza A/H1N1 (swine flu were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. Methods Purposive sampling was used to recruit seventy three people (61 women and 12 men to take part in 14 focus group discussions around the time of the second wave in swine flu cases. Results These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. Conclusions This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.

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

Science.gov (United States)

Simonsen, Lone; Spreeuwenberg, Peter; Lustig, Roger; Taylor, Robert J; Fleming, Douglas M; Kroneman, Madelon; Van Kerkhove, Maria D; Mounts, Anthony W; Paget, W John

2013-11-01

Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012). We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.

Estimation of the burden of pandemic(H1N12009 in developing countries: experience from a tertiary care center in South India.

Directory of Open Access Journals (Sweden)

Mahesh Moorthy

Full Text Available The burden of the pandemic (H1N1 2009 influenza might be underestimated if detection of the virus is mandated to diagnose infection. Using an alternate approach, we propose that a much higher pandemic burden was experienced in our institution.Consecutive patients (n = 2588 presenting to our hospital with influenza like illness (ILI or severe acute respiratory infection (SARI during a 1-year period (May 2009-April 2010 were prospectively recruited and tested for influenza A by real-time RT-PCR. Analysis of weekly trends showed an 11-fold increase in patients presenting with ILI/SARI during the peak pandemic period when compared with the pre-pandemic period and a significant (P<0.001 increase in SARI admissions during the pandemic period (30 ± 15.9 admissions/week when compared with pre-pandemic (7 ± 2.5 and post-pandemic periods (5 ± 3.8. However, Influenza A was detected in less than one-third of patients with ILI/SARI [699 (27.0%]; a majority of these (557/699, 79.7% were Pandemic (H1N12009 virus [A/H1N1/09]. An A/H1N1/09 positive test was correlated with shorter symptom duration prior to presentation (p = 0.03. More ILI cases tested positive for A/H1N1/09 when compared with SARI (27.4% vs. 14.6%, P = 0.037. When the entire study population was considered, A/H1N1/09 positivity was associated with lower risk of hospitalization (p<0.0001 and ICU admission (p = 0.013 suggesting mild self-limiting illness in a majority.Analysis of weekly trends of ILI/SARI suggest a higher burden of the pandemic attributable to A/H1N1/09 than estimates assessed by a positive PCR test alone. The study highlights methodological consideration in the estimation of burden of pandemic influenza in developing countries using hospital-based data that may help assess the impact of future outbreaks of respiratory illnesses.

Genetic characterization of the influenza A pandemic (H1N1 2009 virus isolates from India.

Directory of Open Access Journals (Sweden)

Varsha A Potdar

Full Text Available BACKGROUND: The Influenza A pandemic H1N1 2009 (H1N1pdm virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus. METHODS: H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers. RESULTS: The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases. CONCLUSIONS: The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity.

Divergent H7 immunogens offer protection from H7N9 virus challenge.

Science.gov (United States)

Krammer, Florian; Albrecht, Randy A; Tan, Gene S; Margine, Irina; Hai, Rong; Schmolke, Mirco; Runstadler, Jonathan; Andrews, Sarah F; Wilson, Patrick C; Cox, Rebecca J; Treanor, John J; García-Sastre, Adolfo; Palese, Peter

2014-04-01

The emergence of avian H7N9 viruses in humans in China has renewed concerns about influenza pandemics emerging from Asia. Vaccines are still the best countermeasure against emerging influenza virus infections, but the process from the identification of vaccine seed strains to the distribution of the final product can take several months. In the case of the 2009 H1N1 pandemic, a vaccine was not available before the first pandemic wave hit and therefore came too late to reduce influenza morbidity. H7 vaccines based on divergent isolates of the Eurasian and North American lineages have been tested in clinical trials, and seed strains and reagents are already available and can potentially be used initially to curtail influenza-induced disease until a more appropriately matched H7N9 vaccine is ready. In a challenge experiment in the mouse model, we assessed the efficacy of both inactivated virus and recombinant hemagglutinin vaccines made from seed strains that are divergent from H7N9 from each of the two major H7 lineages. Furthermore, we analyzed the cross-reactive responses of sera from human subjects vaccinated with heterologous North American and Eurasian lineage H7 vaccines to H7N9. Vaccinations with inactivated virus and recombinant hemagglutinin protein preparations from both lineages raised hemagglutination-inhibiting antibodies against H7N9 viruses and protected mice from stringent viral challenges. Similar cross-reactivity was observed in sera of human subjects from a clinical trial with a divergent H7 vaccine. Existing H7 vaccine candidates based on divergent strains could be used as a first line of defense against an H7N9 pandemic. In addition, this also suggests that H7N9 vaccines that are currently under development might be stockpiled and used for divergent avian H7 strains that emerge in the future. Sporadic human infections with H7N9 viruses started being reported in China in the early spring of 2013. Despite a significant drop in the number of

Exploring national surveillance for health-related workplace absenteeism: lessons learned from the 2009 influenza A pandemic.

Science.gov (United States)

Groenewold, Matthew R; Konicki, Doris L; Luckhaupt, Sara E; Gomaa, Ahmed; Koonin, Lisa M

2013-04-01

During the 2009 influenza A (H1N1) virus pandemic, the Centers for Disease Control and Prevention did a pilot study to test the feasibility of using national surveillance of workplace absenteeism to assess the pandemic's impact on the workplace to plan for preparedness and continuity of operations and to contribute to health awareness during the emergency response. Population-based and sentinel worksite approaches were used. Monthly measures of the 1-week prevalence of health-related absenteeism among full-time workers were estimated using nationally representative data from the Current Population Survey. Enhanced passive surveillance of absenteeism was conducted using weekly data from a convenience sample of sentinel worksites. Nationally, the pandemic's impact on workplace absenteeism was small. Estimates of 1-week absenteeism prevalence did not exceed 3.7%. However, peak workplace absenteeism was correlated with the highest occurrence of both influenza-like illness and influenza-positive laboratory tests. Systems for monitoring workplace absenteeism should be included in pandemic preparedness planning.

Biochemical fingerprinting of Vibrio parahaemolyticus by the PhenePlate system: comparison between pandemic and non-pandemic serotypes.

Science.gov (United States)

Rahman, Mokhlasur; Bhuiyan, N A; Kuhn, I; Ramamurthy, T; Rahman, M; Mollby, R; Nair, G Balakrish

2006-10-01

During recent years a pandemic clone of Vibrio parahaemolyticus has emerged. Isolates of this clone are distributed among several serotypes, but are genotypically related. In the present study, a phenotyping method (biochemical fingerprinting) was used to characterize pandemic and non-pandemic isolates belonging to V. parahaemolyticus. It was found that the pandemic isolates showed a high level of phenotypic homogeneity and a majority of the pandemic isolates belonged to the same biochemical phenotype, whereas non-pandemic V. parahemolyticus isolates were more heterogeneous. In conclusion, biochemical fingerprinting of V. parahaemolyticus can be used as a first screening method to differentiate between pandemic and non-pandemic isolates of V. parahaemolyticus.

Spatial and temporal characteristics of the 2009 A/H1N1 influenza pandemic in Peru.

Science.gov (United States)

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

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. 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. 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. 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-age children, the age group most affected

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

Science.gov (United States)

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

Influenza A (H3N2) Variant Virus

Science.gov (United States)

... Swine Variant Pandemic Other Influenza A (H3N2) Variant Virus Language: English (US) Español Recommend on Facebook Tweet Share Compartir Influenza viruses that normally circulate in pigs are called “variant” ...

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

Science.gov (United States)

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

2013-02-01

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

What happened after the initial global spread of pandemic human influenza virus A (H1N1? A population genetics approach

Directory of Open Access Journals (Sweden)

Martinez-Hernandez Fernando

2010-08-01

Full Text Available Abstract Viral population evolution dynamics of influenza A is crucial for surveillance and control. In this paper we analyzed viral genetic features during the recent pandemic caused by the new influenza human virus A H1N1, using a conventional population genetics approach based on 4689 hemagglutinin (HA and neuraminidase (NA sequences available in GenBank submitted between March and December of 2009. This analysis showed several relevant aspects: a a scarce initial genetic variability within the viral isolates from some countries that increased along 2009 when influenza was dispersed around the world; b a worldwide virus polarized behavior identified when comparing paired countries, low differentiation and high gene flow were found in some pairs and high differentiation and moderate or scarce gene flow in others, independently of their geographical closeness, c lack of positive selection in HA and NA due to increase of the population size of virus variants, d HA and NA variants spread in a few months all over the world being identified in the same countries in different months along 2009, and e containment of viral variants in Mexico at the beginning of the outbreak, probably due to the control measures applied by the government.

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

DEFF Research Database (Denmark)

Bøtner, Anette; Capua, Ilaria; Gatherer, Derek

Following the emergence in 2009 of the new pandemic H1N1 influenza virus, which contained gene segments from pig, bird and human influenza viruses, it was apparent that a better scientific understanding is required of influenza viruses to protect public and animal health. The latest scientific da...

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Science.gov (United States)

Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

2010-01-01

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

The limitations of point of care testing for pandemic influenza: what clinicians and public health professionals need to know.

Science.gov (United States)

Hatchette, Todd F; Bastien, Nathalie; Berry, Jody; Booth, Tim F; Chernesky, Max; Couillard, Michel; Drews, Steven; Ebsworth, Anthony; Fearon, Margaret; Fonseca, Kevin; Fox, Julie; Gagnon, Jean-Nicolas; Guercio, Steven; Horsman, Greg; Jorowski, Cathy; Kuschak, Theodore; Li, Yan; Majury, Anna; Petric, Martin; Ratnam, Sam; Smieja, Marek; Van Caeseele, Paul

2009-01-01

As the world prepares for the next influenza pandemic, governments have made significant funding commitments to vaccine development and antiviral stockpiling. While these are essential components to pandemic response, rapid and accurate diagnostic testing remains an often neglected cornerstone of pandemic influenza preparedness. Clinicians and Public Health Practitioners need to understand the benefits and drawbacks of different influenza tests in both seasonal and pandemic settings. Culture has been the traditional gold standard for influenza diagnosis but requires from 1-10 days to generate a positive result, compared to nucleic acid detection methods such as real time reverse transcriptase polymerase chain reaction (RT-PCR). Although the currently available rapid antigen detection kits can generate results in less than 30 minutes, their sensitivity is suboptimal and they are not recommended for the detection of novel influenza viruses. Until point-of-care (POC) tests are improved, PILPN recommends that the best option for pandemic influenza preparation is the enhancement of nucleic acid-based testing capabilities across Canada.

Estimation of the reproductive number and the serial interval in early phase of the 2009 influenza A/H1N1 pandemic in the USA

NARCIS (Netherlands)

White, Laura Forsberg; Wallinga, Jacco; Finelli, Lyn; Reed, Carrie; Riley, Steven; Lipsitch, Marc; Pagano, Marcello

2009-01-01

Background The United States was the second country to have a major outbreak of novel influenza A/H1N1 in what has become a new pandemic. Appropriate public health responses to this pandemic depend in part on early estimates of key epidemiological parameters of the virus in defined populations.

H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

Directory of Open Access Journals (Sweden)

Marion Russier

2017-03-01

Full Text Available A pandemic-capable influenza virus requires a hemagglutinin (HA surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5 and human and ferret (pH ≤5.5 species. Using an early 2009 pandemic H1N1 (pH1N1 virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5, HA1-Y17H (pH 6.0, and HA2-R106K (pH 5.3. All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0 acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

A Predictable Unpredictability. The 2009 H1N1 pandemic and the concept of “strategic uncertainty” within global public health

Directory of Open Access Journals (Sweden)

Theresa MacPhail

2010-12-01

Full Text Available This essay will examine the seemingly new paradigm shift within global public health from the use of a scientific “certainty” to a biological and situational “uncertainty” as one of the foundations of response to infectious disease outbreaks. During the recent 2009 H1N1 influenza outbreak, national and international public health officials often referred directly to the “uncertainty” surrounding both the virus itself and of the course, duration and severity of the pandemic. The vague and flexible concept of “uncertainty” – especially as it was employed by top virologists and epidemiologists in relationship to questions about the predictability of the influenza virus – provided the scientific foundation for much of the rationale behind both national and international health responses to the global pandemic. Public health officials, epidemiologists, and scientists often deployed a type of “strategic uncertainty” as an effective tool for gaining or retaining trust and scientific authority during the H1N1 pandemic.

H1N1 pandemic preparedness and business continuity plan

Energy Technology Data Exchange (ETDEWEB)

NONE

2009-10-15

SaskPower's H1N1 pandemic preparedness and business continuity plan was designed to prepare SaskPower employees for elevated levels of absenteeism during a potential pandemic. Emergency management and business continuity will be facilitated if critical duties and essential services are maintained without interruption. A layered approach was used to develop a range of response measures designed to meet a range of possible pandemic threats. The plan identified essential activities, tasks and functions and outlined methods of mitigating supply disruptions and possible shortages. Methods of minimizing illness in employees were discussed, as well as methods of maintaining a safe and secure work environment. The measures were developed in accordance with the World Health Organization (WHO) 6 phases of pandemic alert. The plan was also designed to be read by SaskPower's key suppliers in order to ensure their pandemic readiness. 5 tabs.

Global Mortality Estimates for the 2009 Influenza Pandemic from the GLaMOR Project: A Modeling Study

Science.gov (United States)

Simonsen, Lone; Spreeuwenberg, Peter; Lustig, Roger; Taylor, Robert J.; Fleming, Douglas M.; Kroneman, Madelon; Van Kerkhove, Maria D.; Mounts, Anthony W.; Paget, W. John

2013-01-01

Background Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. Methods and Findings We obtained weekly virology and underlying cause-of-death mortality time series for 2005–2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%–85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000–249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary PMID:24302890

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

Directory of Open Access Journals (Sweden)

Morales-García Guadalupe

2012-11-01

Full Text Available Abstract 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

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

Science.gov (United States)

Morales-García, Guadalupe; Falfán-Valencia, Ramcés; García-Ramírez, Román Alejandro; Camarena, Ángel; Ramirez-Venegas, Alejandra; Castillejos-López, Manuel; Pérez-Rodríguez, Martha; González-Bonilla, César; Grajales-Muñíz, Concepción; Borja-Aburto, Víctor; Mejía-Aranguré, Juan Manuel

2012-11-13

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. 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. 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 with an elevated number of

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

Science.gov (United States)

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

Evolutionary trends of A(H1N1 influenza virus hemagglutinin since 1918.

Directory of Open Access Journals (Sweden)

Jun Shen

2009-11-01

Full Text Available The Pandemic (H1N1 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA is the major agent for host-driven antigenic drift in A(H3N2 virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1. Here, by analyzing hundreds of A(H1N1 HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1 HAs. Among a subgroup of human A(H1N1 HAs between 1918 approximately 2008, we found strong diversifying (positive selection at HA(1 156 and 190. We also analyzed the evolutionary trends at HA(1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1 HA. Different A(H1N1 viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1 HAs favor HA(1 190 while the 1918 pandemic and swine HAs favor HA(1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1 influenza viruses.

A small community model for the transmission of infectious diseases: comparison of school closure as an intervention in individual-based models of an influenza pandemic.

Directory of Open Access Journals (Sweden)

George J Milne

Full Text Available BACKGROUND: In the absence of other evidence, modelling has been used extensively to help policy makers plan for a potential future influenza pandemic. METHOD: We have constructed an individual based model of a small community in the developed world with detail down to exact household structure obtained from census collection datasets and precise simulation of household demographics, movement within the community and individual contact patterns. We modelled the spread of pandemic influenza in this community and the effect on daily and final attack rates of four social distancing measures: school closure, increased case isolation, workplace non-attendance and community contact reduction. We compared the modelled results of final attack rates in the absence of any interventions and the effect of school closure as a single intervention with other published individual based models of pandemic influenza in the developed world. RESULTS: We showed that published individual based models estimate similar final attack rates over a range of values for R(0 in a pandemic where no interventions have been implemented; that multiple social distancing measures applied early and continuously can be very effective in interrupting transmission of the pandemic virus for R(0 values up to 2.5; and that different conclusions reached on the simulated benefit of school closure in published models appear to result from differences in assumptions about the timing and duration of school closure and flow-on effects on other social contacts resulting from school closure. CONCLUSION: Models of the spread and control of pandemic influenza have the potential to assist policy makers with decisions about which control strategies to adopt. However, attention needs to be given by policy makers to the assumptions underpinning both the models and the control strategies examined.

Searching PubMed during a pandemic.

Directory of Open Access Journals (Sweden)

Ole Norgaard

Full Text Available BACKGROUND: The 2009 influenza A(H1N1 pandemic has generated thousands of articles and news items. However, finding relevant scientific articles in such rapidly developing health crises is a major challenge which, in turn, can affect decision-makers' ability to utilise up-to-date findings and ultimately shape public health interventions. This study set out to show the impact that the inconsistent naming of the pandemic can have on retrieving relevant scientific articles in PubMed/MEDLINE. METHODOLOGY: We first formulated a PubMed search algorithm covering different names of the influenza pandemic and simulated the results that it would have retrieved from weekly searches for relevant new records during the first 10 weeks of the pandemic. To assess the impact of failing to include every term in this search, we then conducted the same searches but omitted in turn "h1n1," "swine," "influenza" and "flu" from the search string, and compared the results to those for the full string. PRINCIPAL FINDINGS: On average, our core search string identified 44.3 potentially relevant new records at the end of each week. Of these, we determined that an average of 27.8 records were relevant. When we excluded one term from the string, the percentage of records missed out of the total number of relevant records averaged 18.7% for omitting "h1n1," 13.6% for "swine," 17.5% for "influenza," and 20.6% for "flu." CONCLUSIONS: Due to inconsistent naming, while searching for scientific material about rapidly evolving situations such as the influenza A(H1N1 pandemic, there is a risk that one will miss relevant articles. To address this problem, the international scientific community should agree on nomenclature and the specific name to be used earlier, and the National Library of Medicine in the US could index potentially relevant materials faster and allow publishers to add alert tags to such materials.

Does Glycosylation as a modifier of Original Antigenic Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza?

Directory of Open Access Journals (Sweden)

Nishiura Hiroshi

2010-01-01

Full Text Available Abstract Background A pandemic novel H1N1 swine-origin influenza virus has emerged. Most recently the World Health Organization has announced that in a country-dependent fashion, up to 15% of cases may require hospitalization, often including respiratory support. It is now clear that healthy children and young adults are disproportionately affected, most unusually among those with severe respiratory disease without underlying conditions. One possible explanation for this case age distribution is the doctrine of Original Antigenic Sin, i.e., novel H1N1 may be antigenically similar to H1N1 viruses that circulated at an earlier time. Persons whose first exposure to influenza viruses was to such similar viruses would be relatively immune. However, this principle is not sufficient to explain the graded susceptibility between ages 20 and 60, the reduced susceptibility in children below age 10, and the unusual toxicity observed. Methods We collected case data from 11 countries, about 60% of all cases reported through mid-July 2009. We compared sequence data for the hemagglutinin of novel H1N1 with sequences of H1N1 viruses from 1918 to the present. We searched for sequence differences that imply loss of antigenicity either directly through amino acid substitution or by the appearance of sites for potential glycosylation proximal to sites known to be antigenic in humans. We also considered T-cell epitopes. Results In our composite, over 75% of confirmed cases of novel H1N1 occurred in persons ≤ 30 years old, with peak incidence in the age range 10-19 years. Less than 3% of cases occurred in persons over 65, with a gradation in incidence between ages 20 and 60 years. The sequence data indicates that novel H1N1 is most similar to H1N1 viruses that circulated before 1943. Novel H1N1 lacks glycosylation sites on the globular head of hemagglutinin (HA1 near antigenic regions, a pattern shared with the 1918 pandemic strain and H1N1 viruses that circulated

Determinants of glycan receptor specificity of H2N2 influenza A virus hemagglutinin.

Science.gov (United States)

Viswanathan, Karthik; Koh, Xiaoying; Chandrasekaran, Aarthi; Pappas, Claudia; Raman, Rahul; Srinivasan, Aravind; Shriver, Zachary; Tumpey, Terrence M; Sasisekharan, Ram

2010-10-29

The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA). The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004) that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant) comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58) HA.

Determinants of glycan receptor specificity of H2N2 influenza A virus hemagglutinin.

Directory of Open Access Journals (Sweden)

Karthik Viswanathan

Full Text Available The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA. The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004 that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58 HA.

Swine Influenza/Variant Influenza Viruses

Science.gov (United States)

... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español Recommend ...

Emerging highly pathogenic H5 avian influenza viruses in France during winter 2015/16: phylogenetic analyses and markers for zoonotic potential.

Science.gov (United States)

Briand, François-Xavier; Schmitz, Audrey; Ogor, Katell; Le Prioux, Aurélie; Guillou-Cloarec, Cécile; Guillemoto, Carole; Allée, Chantal; Le Bras, Marie-Odile; Hirchaud, Edouard; Quenault, Hélène; Touzain, Fabrice; Cherbonnel-Pansart, Martine; Lemaitre, Evelyne; Courtillon, Céline; Gares, Hélène; Daniel, Patrick; Fediaevsky, Alexandre; Massin, Pascale; Blanchard, Yannick; Eterradossi, Nicolas; van der Werf, Sylvie; Jestin, Véronique; Niqueux, Eric

2017-03-02

Several new highly pathogenic (HP) H5 avian influenza virus (AIV) have been detected in poultry farms from south-western France since November 2015, among which an HP H5N1. The zoonotic potential and origin of these AIVs immediately became matters of concern. One virus of each subtype H5N1 (150169a), H5N2 (150233) and H5N9 (150236) was characterised. All proved highly pathogenic for poultry as demonstrated molecularly by the presence of a polybasic cleavage site in their HA protein - with a sequence (HQRRKR/GLF) previously unknown among avian H5 HPAI viruses - or experimentally by the in vivo demonstration of an intravenous pathogenicity index of 2.9 for the H5N1 HP isolate. Phylogenetic analyses based on the full genomes obtained by NGS confirmed that the eight viral segments of the three isolates were all part of avian Eurasian phylogenetic lineage but differed from the Gs/Gd/1/96-like lineage. The study of the genetic characteristics at specific amino acid positions relevant for modulating the adaptation to and the virulence for mammals showed that presently, these viruses possess most molecular features characteristic of AIV and lack some major characteristics required for efficient respiratory transmission to or between humans. The three isolates are therefore predicted to have no significant pandemic potential. This article is copyright of The Authors, 2017.

Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation.

Science.gov (United States)

Khan, Kamran; Eckhardt, Rose; Brownstein, John S; Naqvi, Raza; Hu, Wei; Kossowsky, David; Scales, David; Arino, Julien; MacDonald, Michael; Wang, Jun; Sears, Jennifer; Cetron, Martin S

2013-05-01

To evaluate the screening measures that would have been required to assess all travellers at risk of transporting A(H1N1)pdm09 out of Mexico by air at the start of the 2009 pandemic. Data from flight itineraries for travellers who flew from Mexico were used to estimate the number of international airports where health screening measures would have been needed, and the number of travellers who would have had to be screened, to assess all air travellers who could have transported the H1N1 influenza virus out of Mexico during the initial stages of the 2009 A(H1N1) pandemic. Exit screening at 36 airports in Mexico, or entry screening of travellers arriving on direct flights from Mexico at 82 airports in 26 other countries, would have resulted in the assessment of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico at the start of the pandemic. Entry screening of 116 travellers arriving from Mexico by direct or connecting flights would have been necessary for every one traveller at risk of transporting A(H1N1)pdm09. Screening at just eight airports would have resulted in the assessment of 90% of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico in the early stages of the pandemic. During the earliest stages of the A(H1N1) pandemic, most public health benefits potentially attainable through the screening of air travellers could have been achieved by screening travellers at only eight airports.

Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

Science.gov (United States)

Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

2011-02-01

As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

Acceptance of vaccinations in pandemic outbreaks: a discrete choice experiment.

Science.gov (United States)

Determann, Domino; Korfage, Ida J; Lambooij, Mattijs S; Bliemer, Michiel; Richardus, Jan Hendrik; Steyerberg, Ewout W; de Bekker-Grob, Esther W

2014-01-01

Preventive measures are essential to limit the spread of new viruses; their uptake is key to their success. However, the vaccination uptake in pandemic outbreaks is often low. We aim to elicit how disease and vaccination characteristics determine preferences of the general public for new pandemic vaccinations. In an internet-based discrete choice experiment (DCE) a representative sample of 536 participants (49% participation rate) from the Dutch population was asked for their preference for vaccination programs in hypothetical communicable disease outbreaks. We used scenarios based on two disease characteristics (susceptibility to and severity of the disease) and five vaccination program characteristics (effectiveness, safety, advice regarding vaccination, media attention, and out-of-pocket costs). The DCE design was based on a literature review, expert interviews and focus group discussions. A panel latent class logit model was used to estimate which trade-offs individuals were willing to make. All above mentioned characteristics proved to influence respondents' preferences for vaccination. Preference heterogeneity was substantial. Females who stated that they were never in favor of vaccination made different trade-offs than males who stated that they were (possibly) willing to get vaccinated. As expected, respondents preferred and were willing to pay more for more effective vaccines, especially if the outbreak was more serious (€6-€39 for a 10% more effective vaccine). Changes in effectiveness, out-of-pocket costs and in the body that advises the vaccine all substantially influenced the predicted uptake. We conclude that various disease and vaccination program characteristics influence respondents' preferences for pandemic vaccination programs. Agencies responsible for preventive measures during pandemics can use the knowledge that out-of-pocket costs and the way advice is given affect vaccination uptake to improve their plans for future pandemic outbreaks

The role of animal reservoirs in social-environmental landscapes: remarks on the control of avian influenza and preparedness for pandemics.

Science.gov (United States)

Ortiz-Rodríguez, M P; Ramírez-Nieto, G C; Villamil-Jiménez, L C

2016-12-01

Influenza viruses are well known for their ability to infect and cause disease in a broad range of hosts. Modern advances in reverse genetics have enabled scientists to probe the mutations that allow influenza viruses to perform host switching. Despite this detailed understanding of the molecular modifications that allow host switching and adaptation, there is a gap in knowledge regarding the factors external to the virus and their interactions that act as triggers leading to a pandemic. Studies on the ecology of zoonotic pathogens should be the new paradigm for understanding not only influenza viruses but any other infectious disease that can be a threat to animal and human health. The literature regarding influenza pandemics and influenza virus reservoirs was reviewed to analyse how social and economic changes can influence the appearance of new outbreaks of influenza. In addition, the importance of new research in a dynamic environment driven by the expansion of human territories and animal production systems is highlighted. A new paradigm is proposed for novel research approaches to infectious diseases such as influenza. © OIE (World Organisation for Animal Health), 2016.

Protection from the 2009 H1N1 pandemic influenza by an antibody from combinatorial survivor-based libraries.

Directory of Open Access Journals (Sweden)

Arun K Kashyap

2010-07-01

Full Text Available Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06 against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 "Swine" H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population.

Antigenically Diverse Swine Origin H1N1 Variant Influenza Viruses Exhibit Differential Ferret Pathogenesis and Transmission Phenotypes.

Science.gov (United States)

Pulit-Penaloza, Joanna A; Jones, Joyce; Sun, Xiangjie; Jang, Yunho; Thor, Sharmi; Belser, Jessica A; Zanders, Natosha; Creager, Hannah M; Ridenour, Callie; Wang, Li; Stark, Thomas J; Garten, Rebecca; Chen, Li-Mei; Barnes, John; Tumpey, Terrence M; Wentworth, David E; Maines, Taronna R; Davis, C Todd

2018-06-01

understand the genetic and virologic characteristics of a virus (A/Ohio/09/2015) associated with a fatal infection and a virus associated with a nonfatal infection (A/Iowa/39/2015), we performed genome sequence analysis, antigenic testing, and pathogenicity and transmission studies in a ferret model. Reverse genetics was employed to identify a single antigenic site substitution (HA G155E) responsible for antigenic variation of A/Ohio/09/2015 compared to related classical swine influenza A(H1N1) viruses. Ferrets with preexisting immunity to the pandemic A(H1N1) virus were challenged with A/Ohio/09/2015, demonstrating decreased protection. These data illustrate the potential for currently circulating swine influenza viruses to infect and cause illness in humans with preexisting immunity to H1N1 pandemic 2009 viruses and a need for ongoing risk assessment and development of candidate vaccine viruses for improved pandemic preparedness. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

Science.gov (United States)

Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling; Chen, Hualan

2017-11-01

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by

A metagenomic analysis of pandemic influenza A (2009 H1N1 infection in patients from North America.

Directory of Open Access Journals (Sweden)

Alexander L Greninger

2010-10-01

Full Text Available Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17, the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%, with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.

Zika Virus and Transgenic Mosquitoes: Potentials of a Public Health Tool

Directory of Open Access Journals (Sweden)

Ike Val Iyioke

2017-01-01

Full Text Available With transgenic mosquitoes now being deployed as a major solution to the pandemic Zika virus disease, more curious questions have arisen about this public health technology. This essay reviews the philosophical considerations that presaged the development, by WHO, of the genetically modified mosquitoes. It focuses more specifically on the inter-disciplinary approach in formulating the clinical trials process. While it is still early to determine the full merits of this health intervention tool, it is nonetheless timely to examine the rich vein of form that constitutes the clinical trial protocol. I argue that the steps it suggests should be a gold standard for all clinical trial procedures including those that use human subjects and those with both direct and indirect environmental implications. Also, the early signs portend that its application could indeed be widespread. For instance, malaria and dengue fever were the original targets, but now the development of transgenic mosquito technology is deemed a potent option in the fight against Zika virus disease. In addition, this clinical trial protocol has remarkably gone beyond the four pillars of principlism to recognize the possibility that a new technology (such as GMM, can have the potential to simultaneously impact human individuals, the community and the ecosystem in tandem. In “Guidance framework for testing of genetically modified mosquito,” the WHO has set an example that calls for emulation. With the right awareness, biomedical researchers, scholars, policy makers, and students stand to benefit immensely from this reformulated approach.

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

Directory of Open Access Journals (Sweden)

Lone Simonsen

2013-11-01

Full Text Available Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09 is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries.We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85% were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012.We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A

Influenza type A virus: an outstandingly protean pathogen and a potent modular weapon.

Science.gov (United States)

Shoham, Dany

2013-05-01

A remarkable debate recently arose on a global scale, about bioethics, biohazard, bioweaponry and bioterrorism issues related to scientific research concerning the induced transition of the highly lethal H5N1 avian flu virus from a non-pandemic to a tentatively pandemic strain, which might fall into malevolent hands. Appreciable ecogenetic complexity marks the main attributes of influenza type A viruses, namely infectivity, virulence, antigenicity, transmissibility, host range, endemicity, and epidemicity. They all shape, conjunctively, the outstanding protean nature of this pathogen, hence the modularity of the latter as a potent weapon. The present analysis inquires into those attributes, so as to profile and gauge threat, usability, impact and coping, particularly that the dimension of genetic engineering of this virus largely amplifies its potential. Within that context, various human interventions and misuses, including human experimental infections, undesirable vaccinations, as well as unauthorized and unskillful operations, led to bad corollaries and are also discussed in the present study. Altogether, a variety of interrelated properties underlying the complicatedness of and menaces posed by influenza A virus as a grave medical challenge, a dually explorable pathogen, and a modular biological warfare agent, are thereby illuminated, alongside with their scientific, strategic and practical implications.

The possible macroeconomic impact on the UK of an influenza pandemic.

Science.gov (United States)

Keogh-Brown, Marcus R; Wren-Lewis, Simon; Edmunds, W John; Beutels, Philippe; Smith, Richard D

2010-11-01

Little is known about the possible impact of an influenza pandemic on a nation's economy. We applied the UK macroeconomic model 'COMPACT' to epidemiological data on previous UK influenza pandemics, and extrapolated a sensitivity analysis to cover more extreme disease scenarios. Analysis suggests that the economic impact of a repeat of the 1957 or 1968 pandemics, allowing for school closures, would be short-lived, constituting a loss of 3.35 and 0.58% of GDP in the first pandemic quarter and year, respectively. A more severe scenario (with more than 1% of the population dying) could yield impacts of 21 and 4.5%, respectively. The economic shockwave would be gravest when absenteeism (through school closures) increases beyond a few weeks, creating policy repercussions for influenza pandemic planning as the most severe economic impact is due to policies to contain the pandemic rather than the pandemic itself.Accounting for changes in consumption patterns made in an attempt to avoid infection worsens the potential impact. Our mild disease scenario then shows first quarter/first year reductions in GDP of 9.5/2.5%, compared with our severe scenario reductions of 29.5/6%. These results clearly indicate the significance of behavioural change over disease parameters. Copyright © 2009 John Wiley & Sons, Ltd.

Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

LENUS (Irish Health Repository)

Li, Wenfu

2011-04-21

Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

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

Directory of Open Access Journals (Sweden)

MacIntyre C Raina

2010-03-01

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

Burden of hospitalizations for pandemic influenza in Slovenia

Science.gov (United States)

Sočan, Maja

2011-01-01

Aim To analyze the 2009/2010 epidemiological data of patients hospitalized for confirmed pandemic influenza in Slovenia. Methods We conducted a retrospective analysis of health statistical data collected in an electronic data set Diagnosis-related Group system. Data on age, sex, primary and secondary diagnoses, duration of hospital stay, admission to the intensive care unit, disease outcome, and the week of the admission to the hospital were extracted for patients diagnosed with confirmed influenza virus infection. Results A total of 748 (hospitalization rate 37.4/100,000) patients diagnosed with confirmed influenza virus infection were admitted to 19 public hospitals and 7 private acute care providers during the period from September 28, 2009 to April 11, 2010. The highest admission rate was recorded for mid-November 2009. Out of 748 hospitalized patients, 411 (55%) were children younger than 15 years. Influenza was coded as the primary diagnosis in 536 patients. In 35% of the patients, influenza caused viral pneumonia. Fewer than one third of patients (28%) had a pre-existing chronic disease and/or condition predisposing them to complicated or adverse outcomes of influenza, most frequently chronic lung diseases, mainly asthma. A median hospital stay was 2 days for children and 5 days for adult patients. Longer hospitalization was required in patients who had a secondary diagnosis of influenza. Older male individuals suffering from pneumonia and chronic diseases were overrepresented among cases admitted to the intensive care units. Conclusions The epidemiological data extracted from the Diagnosis-related Group system in Slovenia were comparable with the data on pandemic patients published elsewhere. PMID:21495197

Design and performance of the CDC real-time reverse transcriptase PCR swine flu panel for detection of 2009 A (H1N1) pandemic influenza virus.

Science.gov (United States)

Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

2011-07-01

Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10(-1.3 - -0.7) 50% infectious doses (ID(50)) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.

Epidemiological aspects of influenza A related to climatic conditions during and after a pandemic period in the city of Salvador, northeastern Brazil

Directory of Open Access Journals (Sweden)

Rosangela de Castro Silva

2014-04-01

Full Text Available During the influenza pandemic of 2009, the A(H1N1pdm09, A/H3N2 seasonal and influenza B viruses were observed to be co-circulating with other respiratory viruses. To observe the epidemiological pattern of the influenza virus between May 2009-August 2011, 467 nasopharyngeal aspirates were collected from children less than five years of age in the city of Salvador. In addition, data on weather conditions were obtained. Indirect immunofluorescence, real-time transcription reverse polymerase chain reaction (RT-PCR, and sequencing assays were performed for influenza virus detection. Of all 467 samples, 34 (7% specimens were positive for influenza A and of these, viral characterisation identified Flu A/H3N2 in 25/34 (74% and A(H1N1pdm09 in 9/34 (26%. Influenza B accounted for a small proportion (0.8% and the other respiratory viruses for 27.2% (127/467. No deaths were registered and no pattern of seasonality or expected climatic conditions could be established. These observations are important for predicting the evolution of epidemics and in implementing future anti-pandemic measures.

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

International Nuclear Information System (INIS)

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

2016-01-01

The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and "3H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain why

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

Energy Technology Data Exchange (ETDEWEB)

Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Zhou, Hui [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States); Ethen, Cheryl M. [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States)

2016-04-29

The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and {sup 3}H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain

Assessing the ecotoxicologic hazards of a pandemic influenza medical response.

Science.gov (United States)

Singer, Andrew C; Colizza, Vittoria; Schmitt, Heike; Andrews, Johanna; Balcan, Duygu; Huang, Wei E; Keller, Virginie D J; Vespignani, Alessandro; Williams, Richard J

2011-08-01

The global public health community has closely monitored the unfolding of the 2009 H1N1 influenza pandemic to best mitigate its impact on society. However, little attention has been given to the impact of this response on the environment. Antivirals and antibiotics prescribed to treat influenza are excreted into wastewater in a biologically active form, which presents a new and potentially significant ecotoxicologic challenge to microorganisms responsible for wastewater nutrient removal in wastewater treatment plants (WWTPs) and receiving rivers. We assessed the ecotoxicologic risks of a pandemic influenza medical response. To evaluate this risk, we coupled a global spatially structured epidemic model that simulates the quantities of antivirals and antibiotics used during an influenza pandemic of varying severity and a water quality model applied to the Thames catchment to determine predicted environmental concentrations. An additional model was then used to assess the effects of antibiotics on microorganisms in WWTPs and rivers. Consistent with expectations, our model projected a mild pandemic to exhibit a negligible ecotoxicologic hazard. In a moderate and severe pandemic, we projected WWTP toxicity to vary between 0-14% and 5-32% potentially affected fraction (PAF), respectively, and river toxicity to vary between 0-14% and 0-30% PAF, respectively, where PAF is the fraction of microbial species predicted to be growth inhibited (lower and upper 95% reference range). The current medical response to pandemic influenza might result in the discharge of insufficiently treated wastewater into receiving rivers, thereby increasing the risk of eutrophication and contamination of drinking water abstraction points. Widespread drugs in the environment could hasten the generation of drug resistance. Our results highlight the need for empirical data on the effects of antibiotics and antiviral medications on WWTPs and freshwater ecotoxicity.

Pandemic ventilator rationing and appeals processes.

Science.gov (United States)

Patrone, Daniel; Resnik, David

2011-06-01

In a severe influenza pandemic, hospitals will likely experience serious and widespread shortages of patient pulmonary ventilators and of staff qualified to operate them. Deciding who will receive access to mechanical ventilation will often determine who lives and who dies. This prospect raises an important question whether pandemic preparedness plans should include some process by which individuals affected by ventilator rationing would have the opportunity to appeal adverse decisions. However, the issue of appeals processes to ventilator rationing decisions has been largely neglected in state pandemic planning efforts. If we are to devise just and effective plans for coping with a severe influenza pandemic, more attention to the issue of appeals processes for pandemic ventilator rationing decisions is needed. Arguments for and against appeals processes are considered, and some suggestions are offered to help efforts at devising more rational pandemic preparedness plans.

2009 Pandemic Influenza A Virus Subtype H1N1 in Morocco, 2009–2010: Epidemiology, Transmissibility, and Factors Associated With Fatal Cases

Science.gov (United States)

Barakat, Amal; Ihazmad, Hassan; El Falaki, Fatima; Tempia, Stefano; Cherkaoui, Imad; El Aouad, Rajae

2012-01-01

Background. Following the emergence of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) in the United States and Mexico in April 2009, A(H1N1)pdm09 spread rapidly all over the world. There is a dearth of information about the epidemiology of A(H1N1)pdm09 in Africa, including Morocco. We describe the epidemiologic characteristics of the A(H1N1)pdm09 epidemic in Morocco during 2009–2010, including transmissibility and risk factors associated with fatal disease. Methods. We implemented influenza surveillance for patients presenting with influenza-like illness (ILI) at 136 private and public clinics for patients with severe acute respiratory illness (SARI) at 16 regional public hospitals from June 2009 through February 2010. Respiratory samples and structured questionnaires were collected from all enrolled patients, and samples were tested by real-time reverse-transcription polymerase chain reaction for influenza viruses. We estimated the risk factors associated with fatal disease as well as the basic reproduction number (R0) and the serial interval of the pandemic virus. Results. From June 2009 through February 2010, we obtained 3937 specimens, of which 1452 tested positive for influenza virus. Of these, 1398 (96%) were A(H1N1)pdm09. Forty percent of specimens from ILI cases (1056 of 2646) and 27% from SARI cases (342 of 1291) were positive for A(H1N1)pdm09. Sixty-four deaths occurred among laboratory-confirmed A(H1N1)pdm09 SARI cases. Among these cases, those who had hypertension (age-adjusted odd ratio [aOR], 28.2; 95% confidence interval [CI], 2.0–398.7), had neurological disorders (aOR, 7.5; 95% CI, 1.5–36.4), or were obese (aOR, 7.1; 95% CI, 1.6–31.1), as well as women of gestational age who were pregnant (aOR, 2.5; 95% CI, 1.1–5.6), were at increased risk of death. Across the country, elevated numbers of locally acquired infections were detected 4 months after the detection of the first laboratory-confirmed case and coincided with the

Social justice in pandemic preparedness.

Science.gov (United States)

DeBruin, Debra; Liaschenko, Joan; Marshall, Mary Faith

2012-04-01

Pandemic influenza planning in the United States violates the demands of social justice in 2 fundamental respects: it embraces the neutrality of procedural justice at the expense of more substantive concern with health disparities, thus perpetuating a predictable and preventable social injustice, and it fails to move beyond lament to practical planning for alleviating barriers to accessing care. A pragmatic social justice approach, addressing both health disparities and access barriers, should inform pandemic preparedness. Achieving social justice goals in pandemic response is challenging, but strategies are available to overcome the obstacles. The public engagement process of one state's pandemic ethics project influenced the development of these strategies.

Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season

DEFF Research Database (Denmark)

Gil Cuesta, Julita; Aavitsland, Preben; Englund, Hélène

2016-01-01

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...... 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...

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.

Science.gov (United States)

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

2016-04-02

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.

Macroepidemiology of the HIVs-AIDS (HAIDS) pandemic. Insufficiently considered zoological and geopolitical aspects.

Science.gov (United States)

Torres-Anjel, M J

1992-06-16

The human immunodeficiency viruses (HIVs)-acquired immunodeficiency syndrome (AIDS) or HAIDS pandemic originated from lentiviruses of nonhuman primates (thus qualifying as a zoonosis) that moved into humans in Africa. The HAIDS patients eventually die of opportunistic infections, all potentially zoonotic. The HAIDS infection remained parochial, first endemically and then epidemically, until the African urbanization that occurred in each of the countries postindependence. The latter included wars and the massive movement of soldiers (virologically naive) from the American continent to Africa and back. The HAIDS viral ecology coincided with African swine fever (ASF) in the Americas. Haiti became the focal point for both infections. Some infected Haitians also became, together with some infected drug addicts in the United States, a source of contaminated human blood for transfusions and production of plasma derivatives.

Acceptance of vaccinations in pandemic outbreaks: a discrete choice experiment.

Directory of Open Access Journals (Sweden)

Domino Determann

Full Text Available Preventive measures are essential to limit the spread of new viruses; their uptake is key to their success. However, the vaccination uptake in pandemic outbreaks is often low. We aim to elicit how disease and vaccination characteristics determine preferences of the general public for new pandemic vaccinations.In an internet-based discrete choice experiment (DCE a representative sample of 536 participants (49% participation rate from the Dutch population was asked for their preference for vaccination programs in hypothetical communicable disease outbreaks. We used scenarios based on two disease characteristics (susceptibility to and severity of the disease and five vaccination program characteristics (effectiveness, safety, advice regarding vaccination, media attention, and out-of-pocket costs. The DCE design was based on a literature review, expert interviews and focus group discussions. A panel latent class logit model was used to estimate which trade-offs individuals were willing to make.All above mentioned characteristics proved to influence respondents' preferences for vaccination. Preference heterogeneity was substantial. Females who stated that they were never in favor of vaccination made different trade-offs than males who stated that they were (possibly willing to get vaccinated. As expected, respondents preferred and were willing to pay more for more effective vaccines, especially if the outbreak was more serious (€6-€39 for a 10% more effective vaccine. Changes in effectiveness, out-of-pocket costs and in the body that advises the vaccine all substantially influenced the predicted uptake.We conclude that various disease and vaccination program characteristics influence respondents' preferences for pandemic vaccination programs. Agencies responsible for preventive measures during pandemics can use the knowledge that out-of-pocket costs and the way advice is given affect vaccination uptake to improve their plans for future pandemic

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

Science.gov (United States)

Wever, Peter C; van Bergen, Leo

2014-09-01

The Meuse-Argonne offensive, a decisive battle during the First World War, is the largest frontline commitment in American military history involving 1.2 million U.S. troops. With over 26,000 deaths among American soldiers, the offensive is considered "America's deadliest battle". The Meuse-Argonne offensive coincided with the highly fatal second wave of the influenza pandemic in 1918. In Europe and in U.S. Army training camps, 1918 pandemic influenza killed around 45,000 American soldiers making it questionable which battle should be regarded "America's deadliest". The origin of the influenza pandemic has been inextricably linked with the men who occupied the military camps and trenches during the First World War. The disease had a profound impact, both for the military apparatus and for the individual soldier. It struck all the armies and might have claimed toward 100 000 fatalities among soldiers overall during the conflict while rendering millions ineffective. Yet, it remains unclear whether 1918 pandemic influenza had an impact on the course of the First World War. Still, even until this day, virological and bacteriological analysis of preserved archived remains of soldiers that succumbed to 1918 pandemic influenza has important implications for preparedness for future pandemics. These aspects are reviewed here in a context of citations, images, and documents illustrating the tragic events of 1918. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Avian influenza virus (H5N1): a threat to human health

NARCIS (Netherlands)

Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

2007-01-01

Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes.

Major incidents in rural areas: managing a pandemic A/H1N1/2009 cluster.

Science.gov (United States)

Stark, Cameron; Garman, Elaine; McMenamin, Jim; McCormick, Duncan; Oates, Ken

2010-01-01

Pandemic Influenza (A/H1N1/2009) caused worldwide concern because of its potential to spread rapidly in human populations. In Scotland, Government policy had been to seek to contain the spread of the virus for as long as possible in order to allow time for service preparations, and for vaccine development and supply. The first major Scottish outbreak of pandemic A/H1N1/2009 was in the rural area of Cowal and Bute. After two initial cases were identified, contact tracing found a cluster of cases associated with a football supporters' bus. Within 3 weeks, 130 cases had been identified in the area. Rapid provision of treatment doses of anti-viral medication to cases and prophylactic treatment of asymptomatic close contacts, advice on self-isolation and, where required, interruption of transmission by temporary school closure, were successful in containing the outbreak. Pre-existing Major Incident and Pandemic Flu plans were used and adapted to the particular circumstances of the outbreak and the area. Supporting operational decision-making as close to the cases as possible allowed for speed and flexibility of response. Contact tracing and tracking of cases and results was performed by specialist public health staff who were geographically removed from the cases. This was possible because of effective use of existing telephone conferencing facilities, clarity of roles, and frequent communication among staff working on all areas of the response. Basing the work on established plans, staff experience of rural areas and rural service provision was successful.

Proteotyping for the rapid identification of influenza virus and other biopathogens.

Science.gov (United States)

Downard, Kevin M

2013-11-21

The influenza virus is one of the most deadly infectious agents known to man and has been responsible for the deaths of some hundred million lives throughout human history. The need to rapidly and reliably survey circulating virus strains down to the molecular level is ever present. This tutorial describes the development and application of a new proteotyping approach that harnesses the power of high resolution of mass spectrometry to characterise the influenza virus, and by extension other bacterial and viral pathogens. The approach is shown to be able to type, subtype, and determine the lineage of human influenza virus strains through the detection of one or more signature peptide ions in the mass spectrum of whole virus digests. Pandemic strains can be similarly distinguished from seasonal ones, and new computer algorithms have been written to allow reassorted strains that pose the greatest pandemic risk to be rapidly identified from such datasets. The broader application of the approach is further demonstrated here for the parainfluenza virus, a virus which can be life threatening to children and presents similar clinical symptoms to influenza.

Pandemic influenza communication: views from a deliberative forum.

Science.gov (United States)

Rogers, Wendy A; Street, Jackie M; Braunack-Mayer, Annette J; Hiller, Janet E

2009-09-01

To use a deliberative forum to elicit community perspectives on communication about pandemic influenza planning, and to compare these findings with the current Australian national communication strategy. Deliberative forum of 12 persons randomly selected from urban South Australia. Forum members were briefed by experts in infection control, virology, ethics and public policy before deliberating on four key questions: what, how and when should the community be told about pandemic influenza and by whom? The forum recommended provision of detailed and comprehensive information by credible experts, rather than politicians, using a variety of media including television and internet. Recommendations included cumulative communication to build expertise in the community, and specific strategies to include groups such as young people, people with physical or mental disabilities, and rural and remote communities. Information provided should be practical, accurate, and timely, with no 'holding back' about the seriousness of a pandemic. The forum expressed confidence in the expert witnesses, despite the acknowledged uncertainty of many of the predictions. The deliberative forum's recommendations were largely consistent with the Australian national pandemic influenza communication strategy and the relevant literature. However, the forum recommended: release of more detailed information than currently proposed in the national strategy; use of non-political spokespersons; and use of novel communication methods. Their acceptance of uncertainty suggests that policy makers should be open about the limits of knowledge in potentially threatening situations. Our findings show that deliberative forums can provide community perspectives on topics such as communication about pandemic influenza.

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

Science.gov (United States)

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

2014-03-01

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

The ENSO-pandemic influenza connection: coincident or causal?

Science.gov (United States)

Shaman, J. L.; Lipsitch, M.

2011-12-01

The El Niño-Southern Oscillation (ENSO) is a coupled ocean-atmosphere system in the tropical Pacific, which affects weather conditions, including temperatures, precipitation, winds and storm activity, across the planet. ENSO has two extreme phases marked by either warmer (El Niño) or cooler (La Niña) than average sea surface temperatures in the central equatorial Pacific. We find that the 4 most recent human influenza pandemics (1918, 1957, 1968, 2009), all of which were first identified in boreal spring or summer, were preceded by La Niña conditions in the equatorial Pacific. Changes in ENSO have been shown to alter the migration, stopover time, fitness and interspecies mixing of migratory birds, and consequently likely affect their mixing with domestic animals. We hypothesize that La Niña conditions bring divergent influenza subtypes together in some parts of the world and favor the reassortment of influenza through simultaneous multiple infection of individual hosts and the generation of novel pandemic strains. We propose approaches to test this hypothesis using influenza population genetics, virus prevalence in various host species, and avian migration patterns.

Macroeconomic impact of pandemic influenza and associated policies in Thailand, South Africa and Uganda.

Science.gov (United States)

Smith, Richard D; Keogh-Brown, Marcus R

2013-09-01

Research has shown the value of conducting a macroeconomic analysis of the impact of influenza pandemics. However, previous modelling applications focus on high-income countries, and there is a lack of evidence concerning the potential impact of an influenza pandemic on lower- and middle-income countries. To estimate the macroeconomic impact of pandemic influenza in Thailand, South Africa and Uganda with particular reference to pandemic (H1N1) 2009. A single-country whole-economy Computable General Equilibrium (CGE) model was set up for each of the three countries in question and used to estimate the economic impact of declines in labour attributable to morbidity, mortality and school closure. Overall GDP impacts were less than 1% of GDP for all countries and scenarios. Uganda's losses were proportionally larger than those of Thailand and South Africa. Labour-intensive sectors suffer the largest losses. The economic cost of unavoidable absence in the event of an influenza pandemic could be proportionally larger for low-income countries. The cost of mild pandemics, such as pandemic (H1N1) 2009, appears to be small, but could increase for more severe pandemics and/or pandemics with greater behavioural change and avoidable absence. © 2013 Blackwell Publishing Ltd.

Preparing for a Pandemic Flu Outbreak

Science.gov (United States)

Dittbenner, Richard

2009-01-01

This article discusses the things college leaders should know and do in case of a pandemic influenza outbreak. The author talks about four principles that will guide college leaders in developing a pandemic influenza plan and presents the 10 elements of an effective college pandemic planning process.

Novel genetic reassortants in H9N2 influenza A viruses and their diverse pathogenicity to mice

Directory of Open Access Journals (Sweden)

Bi Yuhai

2011-11-01

Full Text Available Abstract Background H9N2 influenza A viruses have undergone extensive reassortments in different host species, and could lead to the epidemics or pandemics with the potential emergence of novel viruses. Methods To understand the genetic and pathogenic features of early and current circulating H9N2 viruses, 15 representative H9N2 viruses isolated from diseased chickens in northern China between 1998 and 2010 were characterized and compared with all Chinese H9N2 viruses available in the NCBI database. Then, the representative viruses of different genotypes were selected to study the pathogenicity in mice with the aim to investigate the adaptation and the potential pathogenicity of the novel H9N2 reassortants to mammals. Results Our results demonstrated that most of the 15 isolates were reassortants and generated four novel genotypes (B62-B65, which incorporated the gene segments from Eurasian H9N2 lineage, North American H9N2 branch, and H5N1 viruses. It was noteworthy that the newly identified genotype B65 has been prevalent in China since 2007, and more importantly, different H9N2 influenza viruses displayed a diverse pathogenicity to mice. The isolates of the 2008-2010 epidemic (genotypes B55 and B65 were lowly infectious, while two representative viruses of genotypes B0 and G2 isolated from the late 1990s were highly pathogenic to mice. In addition, Ck/SD/LY-1/08 (genotype 63, containing H5N1-like NP and PA genes was able to replicate well in mouse lungs with high virus titers but caused mild clinical signs. Conclusion Several lines of evidence indicated that the H9N2 influenza viruses constantly change their genetics and pathogenicity. Thus, the genetic evolution of H9N2 viruses and their pathogenicity to mammals should be closely monitored to prevent the emergence of novel pandemic viruses.

Memory T Cells Generated by Prior Exposure to Influenza Cross React with the Novel H7N9 Influenza Virus and Confer Protective Heterosubtypic Immunity

Science.gov (United States)

McMaster, Sean R.; Gabbard, Jon D.; Koutsonanos, Dimitris G.; Compans, Richard W.; Tripp, Ralph A.; Tompkins, S. Mark; Kohlmeier, Jacob E.

2015-01-01

Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic. PMID:25671696

Memory T cells generated by prior exposure to influenza cross react with the novel H7N9 influenza virus and confer protective heterosubtypic immunity.

Directory of Open Access Journals (Sweden)

Sean R McMaster

Full Text Available Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.

Continuity of Accelerator Operations during an Extended Pandemic

International Nuclear Information System (INIS)

Noel Okay

2010-01-01

The Operations group for the Continuous Electron Accelerator Facility in Newport News Virginia has developed a Continuity of Operations plan for pandemic conditions when high absenteeism may impact accelerator control room operations. Protocols to address both the potential spread of illnesses in the control room environment as well as maintaining minimum staffing requirements for contiguous accelerator operation will be presented. During acute pandemic conditions local government restrictions may prevent continued operations but during extended periods of high absenteeism accelerator operations can continue when some added precautionary measures and staffing adjustments are made in the way business is done.

Emerging influenza virus: A global threat

Indian Academy of Sciences (India)

PRAKASH KUMAR

Emerging influenza virus: A global threat. 475. J. Biosci. ... pathogens and are of major global health concern. Recently, ..... cases among persons in 14 countries in Asia, the Middle ... of influenza, investment in pandemic vaccine research and.

A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

Science.gov (United States)

Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

2014-01-23

During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens.

A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

International Nuclear Information System (INIS)

Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

2008-01-01

The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

Large Scale Genome Analysis Shows that the Epitopes for Broadly Cross-Reactive Antibodies Are Predominant in the Pandemic 2009 Influenza Virus A H1N1 Strain

Directory of Open Access Journals (Sweden)

Edgar E. Lara-Ramírez

2013-11-01

Full Text Available The past pandemic strain H1N1 (A (H1N1pdm09 has now become a common component of current seasonal influenza viruses. It has changed the pre-existing immunity of the human population to succeeding infections. In the present study, a total of 14,210 distinct sequences downloaded from National Center for Biotechnology Information (NCBI database were used for the analysis. The epitope compositions in A (H1N1pdm09, classic seasonal strains, swine strains as well as highly virulent avian strain H5N1, identified with the aid of the Immune Epitope DataBase (IEDB, were compared at genomic level. The result showed that A (H1N1 pdm09 contains the 90% of B-cell epitopes for broadly cross-reactive antibodies (EBCA, which is in consonance with the recent reports on the experimental identification of new epitopes or antibodies for this virus and the binding tests with influenza virus protein HA of different subtypes. Our analysis supports that high proportional EBCA depends on the epitope pattern of A (H1N1pdm09 virus. This study may be helpful for better understanding of A (H1N1pdm09 and the production of new influenza vaccines.

Conserved synthetic peptides from the hemagglutinin of influenza viruses induce broad humoral and T-cell responses in a pig model.

Directory of Open Access Journals (Sweden)

Júlia Vergara-Alert

Full Text Available Outbreaks involving either H5N1 or H1N1 influenza viruses (IV have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines à la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM. This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1 from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses than conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1, two swine influenza field isolates (SwH1N1 and SwH3N2 and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations.

Prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice.

Directory of Open Access Journals (Sweden)

Huan H Nguyen

Full Text Available BACKGROUND: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1. METHODS AND FINDINGS: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection. CONCLUSIONS: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus

[Survey about responsiveness of third-level hospitals to a medical disaster: after the pandemic influenza in Mexico].

Science.gov (United States)

Serna-Ojeda, Juan Carlos; Castañón-González, Jorge Alberto; Macías, Alejandro E; Mansilla-Olivares, Armando; Domínguez-Cherit, Guillermo; Polanco-González, Carlos

2012-01-01

The recent pandemic influenza AH1N1 virus made it clear that planning for medical disaster response is critical. To know the responsiveness of a sample of highly specialized hospitals in Mexico to a medical disaster, with the previous pandemic influenza AH1N1 as reference. A survey was conducted among the Medical Directors of a sample of highly specialized hospitals, covering: previous experience with the pandemic influenza, space considerations, material resources, staff, logistics, and current general perspectives. Descriptive statistics were used for analysis. A 95% response was obtained from the institutions (19 hospitals). Of these, 47.4% considered that the medical institution was not ready to respond to pandemic influenza. The median surge capacity for the Intensive Care Unit beds was 30% (range 0 to 32 beds). The least reserve in medication was found in the antivirals (26.3%). Only 47.4% considered having enough intensive care nurses and 57.9% enough respiratory technicians; 42.1% would not have an easy access to resources in an emergency. Prevention is key in responsiveness to medical disasters, and therefore the basic steps for planning strategies must be considered.

The H1N1 influenza pandemic: need for solutions to ethical problems.

Science.gov (United States)

Bhatia, Prateek

2013-01-01

The rapid spread of the novel influenza virus of H1N1 swine origin led to widespread fear, panic and unrest among the public and healthcare personnel. The pandemic not only tested the world's health preparedness, but also brought up new ethical issues which need to be addressed as soon as possible. This article highlights these issues and suggests ethical answers to the same. The main areas that require attention are the distribution of scarce resources, prioritisation of antiviral drugs and vaccines, obligations of healthcare workers, and adequate dissemination and proper communication of information related to the pandemic. It is of great importance to plan in advance how to confront these issues in an ethical manner. This is possible only if a comprehensive contingency plan is prepared with the involvement of and in consultation with all the stakeholders concerned.