Genetic diversity of influenza A(H1N1)2009 virus circulating during the season 2010-2011 in Spain.

PubMed

Ledesma, Juan; Pozo, Francisco; Reina, Gabriel; Blasco, Miriam; Rodríguez, Guadalupe; Montes, Milagrosa; López-Miragaya, Isabel; Salvador, Carmen; Reina, Jordi; Ortíz de Lejarazu, Raúl; Egido, Pilar; López Barba, José; Delgado, Concepción; Cuevas, María Teresa; Casas, Inmaculada

2012-01-01

Genetic diversity of influenza A(H1N1)2009 viruses has been reported since the pandemic virus emerged in April 2009. Different genetic clades have been identified and defined based on amino acid substitutions found in the haemagglutinin (HA) protein sequences. In Spain, circulating influenza viruses are monitored each season by the regional laboratories enrolled in the Spanish Influenza Surveillance System (SISS). The analysis of the HA gene sequence helps to detect the genetic diversity and viral evolution. To perform an analysis of the genetic diversity of influenza A(H1N1)2009 viruses circulating in Spain during the season 2010-2011 based on analysis of the HA sequence gene. Phylogenetic analysis based on the HA1 subunit of the haemagglutinin gene was carried out on 220 influenza A(H1N1)2009 viruses circulating during the season 2010-2011. Six different genetic groups were identified among circulating A(H1N1)2009 viruses, five of them were previously reported during season 2010-2011. A new group, characterized by E172K and K308E changes and a proline at position 83, was observed in 12.27% of the Spanish viruses. Co-circulation of six different genetic groups of influenza A(H1N1)2009 viruses was identified in Spain during the season 2010-2011. Nevertheless, at this stage, none of the groups identified to date have resulted in significant antigenic changes according to data collected by World Health Organization Collaborating Centres for influenza surveillance. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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

2010-04-01

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

Influenza A(H6N1) Virus in Dogs, Taiwan

PubMed Central

Lin, Hui-Ting; Wang, Ching-Ho; Chueh, Ling-Ling; Su, Bi-Ling

2015-01-01

We determined the prevalence of influenza A virus in dogs in Taiwan and isolated A/canine/Taiwan/E01/2014. Molecular analysis indicated that this isolate was closely related to influenza A(H6N1) viruses circulating in Taiwan and harbored the E627K substitution in the polymerase basic 2 protein, which indicated its ability to replicate in mammalian species. PMID:26583707

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

PubMed Central

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

2015-01-01

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

Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.

PubMed

Petrie, Joshua G; Parkhouse, Kaela; Ohmit, Suzanne E; Malosh, Ryan E; Monto, Arnold S; Hensley, Scott E

2016-12-15

During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Influenza A(H1N1)pdm09 Virus among Healthy Show Pigs, United States

PubMed Central

Bender, Jeffrey B.; Bridges, Carolyn B.; Daly, Russell F.; Krueger, Whitney S.; Male, Michael J.; Heil, Gary L.; Friary, John A.; Derby, Robin B.; Cox, Nancy J.

2012-01-01

Within 5 months after the earliest detection of human influenza A(H1N1)pdm09 virus, we found molecular and culture evidence of the virus in healthy US show pigs. The mixing of humans and pigs at swine shows possibly could further the geographic and cross-species spread of influenza A viruses. PMID:22932697

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

PubMed

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

2016-04-01

In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection and isolation of 2009 pandemic influenza A/H1N1 virus in commercial piggery, Lagos Nigeria.

PubMed

Meseko, C A; Odaibo, G N; Olaleye, D O

2014-01-10

WHO declared pandemic of A/H1N1 influenza in 2009 following global spread of the newly emerged strain of the virus from swine. Presently there is a dearth of data on the ecology of pandemic influenza H1N1 required for planning of intervention measures in sub Saharan Africa. Herein we report isolation of 2009 pandemic influenza A/H1N1 in an intensive mega piggery farms operation in South West Nigeria. Sentinel surveillance was carried out in a cohort of intensively reared pigs over a period of two years. Nasal swab specimens were collected at monthly interval from observed clinical cases of influenza like illness in pigs and pig handlers. Samples were analyzed by real time RT-PCR and isolation in chicken embryonated eggs. A total of 227 clinical cases of influenza like illness were observed among pigs out of which 31 (13.7%) were positive for influenza A matrix gene by real time RT-PCR. Virus isolation yielded 29 (12%) isolates out of which 18 (18%) were identified as influenza A/H1N1 by Heamaglutination Inhibition test using H1 antisera. RT-PCR positive samples were subtyped as 2009 pandemic A/H1N1 with subtype specific primers and probes. This is the first report of detection and isolation of pandemic influenza H1N1 from pigs in Nigeria. Continuous circulation of this virus in pigs may cause reassortments with seasonal influenza or mutations and substitutions in the gene that may result in the emergence of novel or pandemic influenza virus of economic and public health importance. Nigeria is considered a geographical hotspot of zoonotic diseases, which necessitate active surveillance and monitoring of emerging pandemic threats. Copyright © 2013 Elsevier B.V. All rights reserved.

Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

PubMed

Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; Svraka, Sanela; van Boven, Michiel; Haverkate, Manon R; Timen, Aura; van Dissel, Jaap T; Koopmans, Marion Pg; Bestebroer, Theo M; Fouchier, Ron Am

2018-04-01

A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general practitioner participating in the routine sentinel surveillance of ILI in the Netherlands. The patient recovered fully. Further epidemiological and virological investigation did not reveal additional cases.

Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the United States.

PubMed

Flannery, Brendan; Smith, Catherine; Garten, Rebecca J; Levine, Min Z; Chung, Jessie R; Jackson, Michael L; Jackson, Lisa A; Monto, Arnold S; Martin, Emily T; Belongia, Edward A; McLean, Huong Q; Gaglani, Manjusha; Murthy, Kempapura; Zimmerman, Richard; Nowalk, Mary Patricia; Griffin, Marie R; Keipp Talbot, H; Treanor, John J; Wentworth, David E; Fry, Alicia M

2018-06-20

The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 × [1 - adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged ≥6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

Epidemiology of pandemic influenza A/H1N1 virus during 2009-2010 in Taiwan.

PubMed

Lan, Yu-Ching; Su, Mei-Chi; Chen, Chao-Hsien; Huang, Su-Hua; Chen, Wan-Li; Tien, Ni; Lin, Cheng-Wen

2013-10-01

Outbreak of swine-origin influenza A/H1N1 virus (pdmH1N1) occurred in 2009. Taiwanese authorities implemented nationwide vaccinations with pdmH1N1-specific inactivated vaccine as of November 2009. This study evaluates prevalence, HA phylogenetic relationship, and transmission dynamic of influenza A and B viruses in Taiwan in 2009-2010. Respiratory tract specimens were analyzed for influenza A and B viruses. The pdmH1N1 peaked in November 2009, was predominant from August 2009 to January 2010, then sharply dropped in February 2010. Significant prevalence peaks of influenza B in April-June of 2010 and H3N2 virus in July and August were observed. Highest percentage of pdmH1N1- and H3N2-positive cases appeared among 11-15-year-olds; influenza B-positive cases were dominant among those 6-10 years old. Maximum likelihood phylogenetic trees showed 11 unique clusters of pdmH1N1, seasonal H3N2 influenza A and B viruses, as well as transmission clusters and mixed infections of influenza strains in Taiwan. The 2009 pdmH1N1 virus was predominant in Taiwan from August 2009 to January 2010; seasonal H3N2 influenza A and B viruses exhibited small prevalence peaks after nationwide vaccinations. Phylogenetic evidence indicated transmission clusters and multiple independent clades of co-circulating influenza A and B strains in Taiwan. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future. PMID:26108286

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

PubMed

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

2014-12-01

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

Incidental late diagnosis of cystic fibrosis following AH1N1 influenza virus pneumonia: a case report.

PubMed

Iadevaia, Carlo; Iacotucci, Paola; Carnovale, Vincenzo; Calabrese, Cecilia; Rea, Gaetano; Ferrara, Nicola; Perrotta, Fabio; Mazzarella, Gennaro; Bianco, Andrea

2017-10-01

Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes. We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.

Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

PubMed Central

Guarnaccia, Teagan; Carolan, Louise A.; Maurer-Stroh, Sebastian; Lee, Raphael T. C.; Job, Emma; Reading, Patrick C.; Petrie, Stephen; McCaw, James M.; McVernon, Jodie; Hurt, Aeron C.; Kelso, Anne; Mosse, Jennifer; Barr, Ian G.; Laurie, Karen L.

2013-01-01

Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance

High doses of recombinant mannan-binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC-SIGN.

PubMed

Yu, Lei; Shang, Shiqiang; Tao, Ran; Wang, Caiyun; Zhang, Li; Peng, Hao; Chen, Yinghu

2017-07-01

The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human health. Low doses of mannan-binding lectin (MBL) (<1 μg/mL) were shown not to protect against influenza A(H1N1)pdm09 infection. However, the effect of high doses of MBL has not been investigated. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) has been proposed as an alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined the expression of DC-SIGN on DCs as well as on acute monocytic leukemia cell line, THP-1. High doses of recombinant or human MBL inhibited binding of influenza A(H1N1)pdm09 to both these cell types in the presence of complement derived from bovine serum. Further, anti-DC-SIGN monoclonal antibody inhibited binding of influenza A(H1N1)pdm09 to both DC-SIGN-expressing DCs and THP-1 cells. This study demonstrates that high doses of MBL can inhibit binding of influenza A(H1N1)pdm09 virus to DC-SIGN-expressing cells in the presence of complement. Our results suggest that DC-SIGN may be an alternative receptor for influenza A(H1N1)pdm09 virus. © 2017 APMIS. Published by John Wiley & Sons Ltd.

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

PubMed

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

2015-11-27

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

Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses.

PubMed

Chen, Haifen; Zhou, Xinrui; Zheng, Jie; Kwoh, Chee-Keong

2016-12-05

The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. We obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the "observed" mutations in different years. The sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites. Our study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.

Epidemiology of influenza in West Africa after the 2009 influenza A(H1N1) pandemic, 2010-2012.

PubMed

Talla Nzussouo, Ndahwouh; Duque, Jazmin; Adedeji, Adebayo Abel; Coulibaly, Daouda; Sow, Samba; Tarnagda, Zekiba; Maman, Issaka; Lagare, Adamou; Makaya, Sonia; Elkory, Mohamed Brahim; Kadjo Adje, Herve; Shilo, Paul Alhassan; Tamboura, Boubou; Cisse, Assana; Badziklou, Kossi; Maïnassara, Halima Boubacar; Bara, Ahmed Ould; Keita, Adama Mamby; Williams, Thelma; Moen, Ann; Widdowson, Marc-Alain; McMorrow, Meredith

2017-12-04

Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened. Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent. We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012. Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d'Ivoire, Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo. Countries used standard World Health Organization (WHO) case definitions for influenza-like illness (ILI) and severe acute respiratory illness (SARI) or slight variations thereof. There were 70 surveillance sites: 26 SARI and 44 ILI. Seven countries conducted SARI surveillance and collected 3114 specimens of which 209 (7%) were positive for influenza viruses. Among influenza-positive SARI patients, 132 (63%) were influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were influenza B. All eight countries conducted ILI surveillance and collected 20,375 specimens, of which 2278 (11%) were positive for influenza viruses. Among influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B. A majority of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59% ILI) were children aged 0-4 years, as were a majority of those enrolled in surveillance. The seasonality of influenza and the predominant influenza type or subtype varied by country and year. Influenza A(H1N1)pdm09 continued to circulate in West Africa along with influenza A(H3N2) and influenza B during 2010-2012. Although ILI surveillance systems produced a robust number of samples

Influenza A(H1N1)v in Germany: the first 10,000 cases.

PubMed

Gilsdorf, Andreas; Poggensee, Gabriele

2009-08-27

The analysis of the first 10,000 cases of influenza A(H1N1)v in Germany confirms findings from other sources that the virus is currently mainly causing mild diseases, affecting mostly adolescents and young adults. Overall hospitalisation rate for influenza A(H1N1)v was low (7%). Only 3% of the cases had underlying conditions and pneumonia was rare (0.4%). Both reporting and testing requirements have been adapted recently, taking into consideration the additional information available on influenza A(H1N1)v infections.

Whole-Genome Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil

PubMed Central

Born, Priscila Silva; Matos, Aline Rocha; Motta, Fernando Couto; Caetano, Braulia Costa; Debur, Maria do Carmo; Riediger, Irina Nastassja; Brown, David; Siqueira, Marilda M.

2017-01-01

We report the characterization of a novel reassortant influenza A(H1N2) virus not previously reported in humans. Recovered from a a pig farm worker in southeast Brazil who had influenza-like illness, this virus is a triple reassortant containing gene segments from subtypes H1N2 (hemagglutinin), H3N2 (neuraminidase), and pandemic H1N1 (remaining genes). PMID:27983507

Whole-Genome Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil.

PubMed

Resende, Paola Cristina; Born, Priscila Silva; Matos, Aline Rocha; Motta, Fernando Couto; Caetano, Braulia Costa; Debur, Maria do Carmo; Riediger, Irina Nastassja; Brown, David; Siqueira, Marilda M

2017-01-01

We report the characterization of a novel reassortant influenza A(H1N2) virus not previously reported in humans. Recovered from a a pig farm worker in southeast Brazil who had influenza-like illness, this virus is a triple reassortant containing gene segments from subtypes H1N2 (hemagglutinin), H3N2 (neuraminidase), and pandemic H1N1 (remaining genes).

Pathogenesis of Influenza A/H5N1 virus infection in ferrets differs between intranasal and intratracheal routes of inoculation.

PubMed

Bodewes, Rogier; Kreijtz, Joost H C M; van Amerongen, Geert; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F; Kuiken, Thijs

2011-07-01

Most patients infected with highly pathogenic avian influenza A/H5N1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. Intranasal inoculation of ferrets with influenza A/H5N1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). However, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are largely unknown. In the present study, we characterized lesions in the respiratory tract and central nervous system (CNS) of ferrets (n = 8) inoculated intranasally with influenza virus A/Indonesia/5/2005 (H5N1). By 7 days after inoculation, only 3 of 8 ferrets had a mild or moderate bronchointerstitial pneumonia. In contrast, all 8 ferrets had moderate or severe CNS lesions, characterized by meningoencephalitis, choroiditis, and ependymitis, and centered on tissues adjoining the cerebrospinal fluid. These findings indicate that influenza A/H5N1 virus spread directly from nasal cavity to brain, and that CNS lesions contributed more than pulmonary lesions to the pathogenicity of influenza A/H5N1 virus infection in ferrets. In comparison, intratracheal inoculation of ferrets with the same virus reproducibly caused severe bronchointerstitial pneumonia. The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2013-03-01

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

Molecular and epidemiological analysis of pandemic and post-pandemic influenza A(H1N1)pdm09 virus from central India.

PubMed

Sahu, Mahima; Singh, Neeru; Shukla, Mohan K; Potdar, Varhsa A; Sharma, Ravendra K; Sahare, Lalit Kumar; Ukey, Mahendra J; Barde, Pradip V

2018-03-01

Influenza A(H1N1)pdm09 virus pandemic struck India in 2009 and continues to cause outbreaks in its post-pandemic phase. Diminutive information is available about influenza A(H1N1)pdm09 from central India. This observational study presents epidemiological and molecular findings for the period of 6 years. Throat swab samples referred from districts of Madhya Pradesh were subjected to diagnosis of influenza A(H1N1)pdm09 following WHO guidelines. Clinical and epidemiological data were recorded and analyzed. Hemagglutinin (HA) gene sequencing and phylogenetic analysis were performed. The H275Y mutation responsible for antiviral resistance was tested using allelic real-time RT-PCR. Out of 7365 tested samples, 2406 (32.7%) were positive for influenza A(H1N1)pdm09, of which 363 (15.08%) succumbed to infection. Significant trends were observed in positivity (χ 2  = 50.8; P < 0.001) and mortality (χ 2  = 24.4; P < 0.001) with increasing age. Mutations having clinical and epidemiological importance were detected. Phylogenetic analysis of HA gene sequences revealed that clade 7, 6A, and 6B viruses were in circulation. Oseltamivir resistance was detected in three fatal cases. Influenza A(H1N1)pdm09 viruses having genetic diversity were detected from central India and continues to be a concern for public health. This study highlights the need of year-round monitoring by establishment of strong molecular and clinical surveillance program. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2016-09-01

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

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

PubMed

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

2015-10-01

This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants. Copyright © 2015 Elsevier GmbH. All rights reserved.

Optimization of trypsins for influenza A/H1N1 virus replication in MDCK SI-6 cells, a novel MDCK cell line.

PubMed

Iskandar, Viska I; Sasaki, Yutaka; Yoshino, Naoto; Abubakar, Raden Z R; Sato, Shigehiro; Muraki, Yasushi

2018-02-01

A cell-based vaccine production method for influenza virus may be an effective and more rapid alternative to egg-based systems. For high-yield virus production, the effect of bovine, porcine, fungal, and recombinant trypsins on influenza A/H1N1 virus replication in MDCK SI-6 cells (SI-6 cells), a novel MDCK cell line developed by our research group, was examined. SI-6 cells infected with influenza A/H1N1 virus were incubated in the presence of four trypsin types at various concentrations, and virus yields in the culture medium were evaluated by a hemagglutination (HA) assay. Virus growth was most efficient in the presence of bovine and porcine trypsins. An analysis of the optimized concentration and definitive HA titer of each trypsin by Gaussian distribution revealed that comparable high virus yields (166.1 and 164.2 HAU/50μl) were obtained at the optimized concentrations of bovine (0.4μg/ml) and porcine (2.1μg/ml) trypsins, respectively, the yields of which were significantly higher than that of fungal and recombinant trypsins. We conclude that bovine and porcine trypsins are suitable for influenza A/H1N1 virus replication in SI-6 cells. This result complements our previous study and suggests the possible application of SI-6 cells to the development of cell-based influenza vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

An outbreak of influenza A(H1N1)pdm09 virus in a primary school in Vietnam.

PubMed

Duong, Tran Nhu; Tho, Nguyen Thi Thi; Hien, Nguyen Tran; Olowokure, Babatunde

2015-10-15

Despite school pupils being at greatest risk during the 2009 influenza pandemic there are limited data on outbreaks of influenza A(H1N1)pdm09 in primary schools in South-East Asia. This prospective cohort study describes an outbreak of influenza A(H1N1)pdm09 in a primary school in rural Vietnam. In total 103 cases of influenza-like illness were found among the 407 pupils in the primary school. Ten of these were laboratory confirmed cases of influenza A(H1N1)pdm09 virus. The overall attack rate (AR) was 25% (103/407), and was highest (41%) in grade 4 pupils, where the outbreak started. All cases in the outbreak presented with a mild and self-limiting illness, acute respiratory symptoms and fever. Public health interventions to contain the outbreak could explain the lower attack rates in other grades. Ill pupils were asked to stay at home. Oseltamivir was not given to pupils and the school did not close during the outbreak. The last detected case occurred 12 days following identification of the first case. This is the first report of an outbreak of influenza A(H1N1)pdm09 among pupils in a primary school in Vietnam. High attack rates in Grade 4 pupils suggest shared activities contributed to transmission. The public health response using non-pharmaceutical measures may have played a role in ending the outbreak.

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

PubMed

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

2016-06-01

An influenza pandemic caused by a novel influenza virus A(H1N1)pdm09 spread worldwide in 2009 and is estimated to have caused between 151,700 and 575,400 deaths globally. While whole genome data on new virus enables a deeper insight in the pathogenesis, epidemiology, and drug sensitivities of the circulating viruses, there are relatively limited complete genetic sequences available for this virus from African countries. We describe herein the full genome analysis of influenza A(H1N1)pdm09 viruses isolated in Kenya between June 2009 and August 2010. A total of 40 influenza A(H1N1)pdm09 viruses isolated during the pandemic were selected. The segments from each isolate were amplified and directly sequenced. The resulting sequences of individual gene segments were concatenated and used for subsequent analysis. These were used to infer phylogenetic relationships and also to reconstruct the time of most recent ancestor, time of introduction into the country, rates of substitution and to estimate a time-resolved phylogeny. The Kenyan complete genome sequences clustered with globally distributed clade 2 and clade 7 sequences but local clade 2 viruses did not circulate beyond the introductory foci while clade 7 viruses disseminated country wide. The time of the most recent common ancestor was estimated between April and June 2009, and distinct clusters circulated during the pandemic. The complete genome had an estimated rate of nucleotide substitution of 4.9×10(-3) substitutions/site/year and greater diversity in surface expressed proteins was observed. We show that two clades of influenza A(H1N1)pdm09 virus were introduced into Kenya from the UK and the pandemic was sustained as a result of importations. Several closely related but distinct clusters co-circulated locally during the peak pandemic phase but only one cluster dominated in the late phase of the pandemic suggesting that it possessed greater adaptability. Copyright © 2016 Elsevier B.V. All rights reserved.

Pandemic influenza A(H1N1)pdm09: An unrecognized cause of mortality in children in Pakistan

PubMed Central

ALI, SYED ASAD; AZIZ, FATIMA; AKHTAR, NIDA; QURESHI, SHAHIDA; EDWARDS, KATHRYN; ZAIDI, ANITA

2016-01-01

The role of influenza virus as a cause of child mortality in South Asia is under-recognized. We aimed to determine the incidence and case fatality rate of influenza A(H1N1)pdm09 infections in hospitalized children in Karachi, Pakistan. Children less than 5 y old admitted with respiratory illnesses to the Aga Khan University Hospital, Karachi, from 17 August 2009 to 16 September 2011, were tested for influenza A(H1N1)pdm09 using a real-time reverse transcriptase polymerase chain reaction. Out of 2650 children less than 5 y old admitted with a respiratory illness during the study period, 812 (31%) were enrolled. Influenza A(H1N1)pdm09 virus was detected in 27 (3.3%) children. There were 4 deaths in children who tested positive for influenza A(H1N1)pdm09 (case fatality rate of 15%). Children with influenza A(H1N1)pdm09 were 5 times more likely to be admitted or transferred to the intensive care unit, 5.5 times more likely to be intubated, and 12.9 times more likely to die as compared to children testing negative for influenza A(H1N1)pdm09. PMID:23826795

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain.

PubMed

Gherasim, Alin; Martínez-Baz, Iván; Castilla, Jesús; Pozo, Francisco; Larrauri, Amparo

2017-01-01

Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus.

Influenza A(H1N1)pdm09 virus infection in Norwegian swine herds 2009/10: the risk of human to swine transmission.

PubMed

Grøntvedt, Carl Andreas; Er, Chiek; Gjerset, Britt; Hauge, Anna Germundsson; Brun, Edgar; Jørgensen, Anne; Lium, Bjørn; Framstad, Tore

2013-07-01

Influenza A viruses cause respiratory infection in humans and pigs, and some serotypes can be transmitted between these species. The emergence of influenza A(H1N1)pdm09 virus infections in the spring of 2009 quickly led to a worldwide pandemic in humans, with subsequent introduction of the virus to pig populations. Following a widespread infection in the human population in Norway, influenza A(H1N1)pdm09 virus was introduced to the influenza A naïve Norwegian pig population, and within a few months pigs in more than one third of Norwegian swine herds had antibodies against the virus. A cross-sectional study was performed on all swine nucleus and multiplier herds in Norway to analyze risk factors for introduction of infection, and the preventive effects of recommended biosecurity practices. A surveillance program provided information on infection status of the study herds, and a questionnaire was administered to all 118 nucleus and multiplier herds to collect information on herd variables. The surveillance program revealed that pigs in 42% of the herds had antibodies against influenza A(H1N1)pdm09 virus. The incidence of serologically positive pigs was similar in both multiplier herds (41%) and closed nucleus herds (43%). Multivariable logistic regression showed that presence of farm staff with influenza-like illness (ILI) (OR=4.15, CI 1.5-11.4, p=0.005) and herd size (OR=1.01, CI 1-1.02, p=0.009) were risk factors for infection. The rapid and widespread seroconversion for antibodies against influenza A(H1N1)pdm09 virus in the Norwegian pig population can be explained by the emergence of a novel virus that is readily transmitted between people and swine in a largely susceptible population of humans, and an entirely naïve population of pigs. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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

2010-01-01

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

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain

PubMed Central

Castilla, Jesús; Pozo, Francisco

2017-01-01

Background Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010–2011 season to the 2015–2016 season in Spain. Methods We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. Results We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Conclusion Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus. PMID:28614376

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

PubMed

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

2013-06-01

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

Liver Biochemistry During the Course of Influenza A/H1N1 Infection

PubMed Central

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

2013-01-01

Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus. PMID:27785237

Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013–2014 in the United States

PubMed Central

Gaglani, Manjusha; Pruszynski, Jessica; Murthy, Kempapura; Clipper, Lydia; Robertson, Anne; Reis, Michael; Chung, Jessie R.; Piedra, Pedro A.; Avadhanula, Vasanthi; Nowalk, Mary Patricia; Zimmerman, Richard K.; Jackson, Michael L.; Jackson, Lisa A.; Petrie, Joshua G.; Ohmit, Suzanne E.; Monto, Arnold S.; McLean, Huong Q.; Belongia, Edward A.; Fry, Alicia M.; Flannery, Brendan

2016-01-01

Background. The predominant strain during the 2013–2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009. Methods. The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2–17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed. Results. We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR–confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%–61%). Among fully vaccinated children aged 2–17 years, the effectiveness of LAIV4 was 17% (95% CI, −39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%–74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season. Conclusions. During 2013–2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States. PMID:26743842

Molecular epidemiology of influenza A(H1N1)PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season.

PubMed

Santos, Katia Corrêa de Oliveira; Silva, Daniela Bernardes Borges da; Sasaki, Norio Augusto; Benega, Margarete Aparecida; Garten, Rebecca; Paiva, Terezinha Maria de

2017-04-03

Compared to previous years, seasonal influenza activity commenced early in São Paulo State, Brazil, Southern hemisphere during the 2016 year. In order to investigate the genetic pattern of influenza A(H1N1)pdm09 in the State of Sao Paulo a total of 479 respiratory samples, collected in January by Sentinel Surveillance Units, were screened by real-time RT-PCR. A total of 6 Influenza viruses A(H1N1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. The present study identified the circulation of the new 6B.1 subgroup (A/Sao Paulo/10-118/2016 and A/Sao Paulo/3032/2016). In addition, influenza A(H1N1)pdm09 group 6B has also been identified during January in the State of Sao Paulo. Despite amino acid changes and changes in potential glycosylation motifs, 6B.1 viruses were well inhibited by the reference ferret antiserum against A/California/07/2009 virus, the A(H1N1)pdm09 component of the vaccine for the 2016 influenza season.

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

PubMed

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

2014-06-01

In 2013, three reassortant swine influenza viruses (SIVs)-two H1N2 and one H3N2-were isolated from symptomatic pigs in Japan; each contained genes from the pandemic A(H1N1) 2009 virus and endemic SIVs. Phylogenetic analysis revealed that the two H1N2 viruses, A/swine/Gunma/1/2013 and A/swine/Ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) H1 and nucleoprotein (NP) genes derived from a classical swine H1 HA lineage uniquely circulating among Japanese SIVs; (ii) neuraminidase (NA) genes from human-like H1N2 swine viruses; and (iii) other genes from pandemic A(H1N1) 2009 viruses. The H3N2 virus, A/swine/Miyazaki/2/2013, comprised genes from two sources: (i) hemagglutinin (HA) and NA genes derived from human and human-like H3N2 swine viruses and (ii) other genes from pandemic A(H1N1) 2009 viruses. Phylogenetic analysis also indicated that each of the reassortants may have arisen independently in Japanese pigs. A/swine/Miyazaki/2/2013 were found to have strong antigenic reactivities with antisera generated for some seasonal human-lineage viruses isolated during or before 2003, whereas A/swine/Miyazaki/2/2013 reactivities with antisera against viruses isolated after 2004 were clearly weaker. In addition, antisera against some strains of seasonal human-lineage H1 viruses did not react with either A/swine/Gunma/1/2013 or A/swine/Ibaraki/1/2013. These findings indicate that emergence and spread of these reassortant SIVs is a potential public health risk. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

Characterization of influenza A(H1N1)pdm09 viruses isolated from Nepalese and Indian outbreak patients in early 2015.

PubMed

Nakamura, Kazuya; Shirakura, Masayuki; Fujisaki, Seiichiro; Kishida, Noriko; Burke, David F; Smith, Derek J; Kuwahara, Tomoko; Takashita, Emi; Takayama, Ikuyo; Nakauchi, Mina; Chadha, Mandeep; Potdar, Varsha; Bhushan, Arvind; Upadhyay, Bishnu Prasad; Shakya, Geeta; Odagiri, Takato; Kageyama, Tsutomu; Watanabe, Shinji

2017-09-01

We characterized influenza A(H1N1)pdm09 isolates from large-scale outbreaks that occurred in Nepal and India in early 2015. Although no specific viral features, which may have caused the outbreaks, were identified, an S84N substitution in hemagglutinin was frequently observed. Chronological phylogenetic analysis revealed that these Nepalese and Indian viruses possessing the S84N substitution constitute potential ancestors of the novel genetic subclade 6B.1 virus that spread globally in the following (2015/16) influenza season. Thus, active surveillance of circulating influenza viruses in the Southern Asia region, including Nepal and India, would be beneficial for detecting novel variant viruses prior to their worldwide spread. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

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

PubMed Central

Grant, Kristina; Franklin, Lucinda; Kaczmarek, Marlena; Hurt, Aeron; Kostecki, Renata; Kelly, Heath

2011-01-01

The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1) 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95%) were influenza A infections – 1001 (55%) pandemic A(H1N1) 2009, 4 (< 1%) A(H3N2) and 807 (45%) not subtyped; 88 (5%) were influenza B; and 14 (< 1%) were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1) 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9%) were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene. PMID:23908889

Lack of evidence for pre‐symptomatic transmission of pandemic influenza virus A(H1N1) 2009 in an outbreak among teenagers; Germany, 2009

PubMed Central

Hermes, Julia; Bernard, Helen; Buchholz, Udo; Spackova, Michaela; Löw, Johann; Loytved, Gunther; Suess, Thorsten; Hautmann, Wolfgang; Werber, Dirk

2011-01-01

Please cite this paper as: Hermes et al. (2011) Lack of evidence for pre‐symptomatic transmission of pandemic influenza virus A(H1N1) 2009 in an outbreak among teenagers; Germany, 2009. Influenza and Other Respiratory Viruses 5(6), e499–e503. Background  Observations on the role of pre‐symptomatic transmission in the spread of influenza virus are scanty. In June 2009, an outbreak of pandemic A(H1N1) 2009 infection occurred at a teenager’s party in Germany. The objective of this study was to identify risk factors for pandemic A(H1N1) 2009 infection. Methods  We performed a retrospective cohort study among party guests. A case was defined as pandemic A(H1N1) 2009 infection confirmed by rRT‐PCR who developed influenza‐like illness between 1 and 5 June 2009. Contact patterns among party guests were evaluated. Results  In eight (36%) of 27 party guests, the outcome was ascertained. A travel returnee from a country with endemic pandemic A(H1N1) 2009 who fell ill toward the end of the party was identified as the source case. Party guests with pandemic A(H1N1) 2009 infection had talked significantly longer to the source case than non‐infected persons (P‐value: 0·001). Importantly, none (0/9) of those who had left the party prior to the source case’s symptom onset became infected compared to 7 (41%) of 17 who stayed overnight (P = 0·06), and these persons all had transmission‐prone contacts to the source case. Conclusions  In this outbreak with one index case, there was no evidence to support pre‐symptomatic transmission of pandemic A(H1N1) 2009. Further evidence is required, ideally from larger studies with multiple index cases, to more accurately characterize the potential for pre‐symptomatic transmission of influenza virus. PMID:21668675

Differential Immune Profiles in Two Pandemic Influenza A(H1N1)pdm09 Virus Waves at Pandemic Epicenter.

PubMed

Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Rodríguez-Abrego, Gabriela; Mancilla-Herrera, Ismael; Domínguez-Cerezo, Esteban; Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; Lozano-Patiño, Fernando; Laredo-Sánchez, Fernando; Malagón-Rangel, José; Nellen-Hummel, Haiko; González-Bonilla, César; Arteaga-Troncoso, Gabriel; Cérbulo-Vázquez, Arturo; Pastelin-Palacios, Rodolfo; Klenerman, Paul; Isibasi, Armando; López-Macías, Constantino

2015-11-01

Severe influenza A(H1N1)pdm2009 virus infection cases are characterized by sustained immune activation during influenza pandemics. Seasonal flu data suggest that immune mediators could be modified by wave-related changes. Our aim was to determine the behavior of soluble and cell-related mediators in two waves at the epicenter of the 2009 influenza pandemic. Leukocyte surface activation markers were studied in serum from peripheral blood samples, collected from the 1(st) (April-May, 2009) and 2(nd) (October 2009-February 2010) pandemic waves. Patients with confirmed influenza A(H1N1)pdm2009 virus infection (H1N1), influenza-like illness (ILI) or healthy donors (H) were analyzed. Serum IL-6, IL-4 and IL-10 levels were elevated in H1N1 patients from the 2(nd) pandemic wave. Additionally, the frequency of helper and cytotoxic T cells was reduced during the 1(st) wave, whereas CD69 expression in helper T cells was increased in the 2(nd) wave for both H1N1 and ILI patients. In contrast, CD62L expression in granulocytes from the ILI group was increased in both waves but in monocytes only in the 2(nd) wave. Triggering Receptor Expressed on Myeloid cells (TREM)-1 expression was elevated only in H1N1 patients at the 1(st) wave. Our results show that during the 2009 influenza pandemic a T cell activation phenotype is observed in a wave-dependent fashion, with an expanded activation in the 2(nd) wave, compared to the 1(st) wave. Conversely, granulocyte and monocyte activation is infection-dependent. This evidence collected at the pandemic epicenter in 2009 could help us understand the differences in the underlying cellular mechanisms that drive the wave-related immune profile behaviors that occur against influenza viruses during pandemics. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Genetic and phylogenetic analysis of multi-continent human influenza A(H1N2) reassortant viruses isolated in 2001 through 2003.

PubMed

Chen, M-J; La, T; Zhao, P; Tam, J S; Rappaport, R; Cheng, S-M

2006-12-01

Genetic analyses were performed on 228 influenza A(H1) viruses derived from clinical subjects participating in an experimental vaccine trial conducted in 20 countries on four continents between 2001 and 2003. HA1 phylogenetic analysis of these viruses showed multiple clades circulated around the world with regional prevalence patterns. Sixty-five of the A(H1) viruses were identified as A(H1N2), 40 of which were isolated from South Africa. The A(H1) sequences of these viruses cluster with published H1N2 viruses phylogenetically and share with them diagnostic signature V169A and A193T changes. The results also showed for the first time that H1N2 viruses were prominent in South Africa during the 2001-2002 influenza season, accounting for over 90% of the A(H1) cases in our study, and infecting both children (29/31) and the elderly (11/13). Phylogenetic analysis of the 65 H1N2 viruses we identified, in conjunction with the 56 recent H1N2 viruses currently available in the database, provided a comprehensive view of the circulation and evolution of distinct clades of H1N2 viruses in a temporal manner between early 2001 and mid-2003, shortly after the appearance of these recent reassortant viruses in or near year 2000.

Molecular epidemiology of influenza A(H1N1)PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season

PubMed Central

Santos, Katia Corrêa de Oliveira; da Silva, Daniela Bernardes Borges; Sasaki, Norio Augusto; Benega, Margarete Aparecida; Garten, Rebecca; de Paiva, Terezinha Maria

2017-01-01

ABSTRACT Compared to previous years, seasonal influenza activity commenced early in São Paulo State, Brazil, Southern hemisphere during the 2016 year. In order to investigate the genetic pattern of influenza A(H1N1)pdm09 in the State of Sao Paulo a total of 479 respiratory samples, collected in January by Sentinel Surveillance Units, were screened by real-time RT-PCR. A total of 6 Influenza viruses A(H1N1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. The present study identified the circulation of the new 6B.1 subgroup (A/Sao Paulo/10-118/2016 and A/Sao Paulo/3032/2016). In addition, influenza A(H1N1)pdm09 group 6B has also been identified during January in the State of Sao Paulo. Despite amino acid changes and changes in potential glycosylation motifs, 6B.1 viruses were well inhibited by the reference ferret antiserum against A/California/07/2009 virus, the A(H1N1)pdm09 component of the vaccine for the 2016 influenza season. PMID:28380120

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

PubMed

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

2014-01-01

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

Temporal distribution and genetic variants in influenza A(H1N1)pdm09 virus circulating in Mexico, seasons 2012 and 2013.

PubMed

Canche-Pech, Jose Reyes; Conde-Ferraez, Laura; Puerto-Solis, Marylin; Gonzalez-Losa, Refugio; Granja-Pérez, Pilar; Villanueva-Jorge, Salha; Chan-Gasca, Maria; Gómez-Carballo, Jesus; López-Ochoa, Luisa; Jiménez-Delgadillo, Bertha; Rodríguez-Sánchez, Iram; Ramírez-Prado, Jorge; Ayora-Talavera, Guadalupe

2017-01-01

The 2012 and 2013 annual influenza epidemics in Mexico were characterized by presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a high incidence of influenza infections after a two-year period of low circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09 virus throughout the year. We have characterized the molecular composition of the Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from both epidemic seasons, emphasizing the genetic characteristics of viruses isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from the 2012 revealed that all viruses from Mexico were predominantly grouped in clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed that viruses circulating in Yucatan were genetically different to viruses from other regions of Mexico. In fact, we identified the occurrence of two genetic variants containing relevant mutations at both the HA and NA surface antigens. There was a difference on the temporal circulation of each genetic variant, viruses containing the mutations HA-A141T / NA-N341S were detected in May, June and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated in August and September. We discuss the significance of these novel genetic changes.

Temporal distribution and genetic variants in influenza A(H1N1)pdm09 virus circulating in Mexico, seasons 2012 and 2013

PubMed Central

Canche-Pech, Jose Reyes; Conde-Ferraez, Laura; Puerto-Solis, Marylin; Gonzalez-Losa, Refugio; Granja-Pérez, Pilar; Villanueva-Jorge, Salha; Chan-Gasca, Maria; Gómez-Carballo, Jesus; López-Ochoa, Luisa; Jiménez-Delgadillo, Bertha; Rodríguez-Sánchez, Iram; Ramírez-Prado, Jorge

2017-01-01

The 2012 and 2013 annual influenza epidemics in Mexico were characterized by presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a high incidence of influenza infections after a two-year period of low circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09 virus throughout the year. We have characterized the molecular composition of the Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from both epidemic seasons, emphasizing the genetic characteristics of viruses isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from the 2012 revealed that all viruses from Mexico were predominantly grouped in clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed that viruses circulating in Yucatan were genetically different to viruses from other regions of Mexico. In fact, we identified the occurrence of two genetic variants containing relevant mutations at both the HA and NA surface antigens. There was a difference on the temporal circulation of each genetic variant, viruses containing the mutations HA-A141T / NA-N341S were detected in May, June and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated in August and September. We discuss the significance of these novel genetic changes. PMID:29220381

Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India

PubMed Central

Mukherjee, Anupam; Nayak, Mukti Kant; Dutta, Shanta; Panda, Samiran; Satpathi, Biswa Ranjan; Chawla-Sarkar, Mamta

2016-01-01

In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014–2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains. PMID:27997573

Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India.

PubMed

Mukherjee, Anupam; Nayak, Mukti Kant; Dutta, Shanta; Panda, Samiran; Satpathi, Biswa Ranjan; Chawla-Sarkar, Mamta

2016-01-01

In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014-2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains.

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

PubMed Central

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

2016-01-01

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

Influenza A(H1N1)pdm09 during air travel

PubMed Central

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

2015-01-01

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

Predominance of influenza A(H3N2) viruses during the 2016/2017 season in Bulgaria.

PubMed

Korsun, Neli; Angelova, Svetla; Trifonova, Ivelina; Tzotcheva, Iren; Mileva, Sirma; Voleva, Silvia; Georgieva, Irina; Perenovska, Penka

2018-02-01

Influenza viruses are characterised by high variability, which makes them able to cause annual epidemics. The aim of this study is to determine the antigenic and genetic characteristics of influenza viruses circulating in Bulgaria during the 2016/2017 season. The detection and typing/subtyping of influenza viruses were performed using real time RT-PCR. Results of antigenic characterisation, phylogenetic and amino acid sequence analyses of representative influenza strains are presented herein. The 2016/2017 season was characterised by an early start, an exclusive dominance of A(H3N2) viruses accounting for 93 % of total influenza virus detections, and a low circulation of A(H1N1)pdm09 (4.2 %) and type B (2.5 %) viruses. The analysed A(H3N2) viruses belonged to subclades 3C.2a (52 %) and 3C.2a1 (48 %); all studied A(H1N1)pdm09 and B/Victoria-lineage viruses belonged to subclades 6B.1 and 1A, respectively. The amino acid sequence analysis of 56 A(H3N2) isolates revealed the presence of substitutions in 18 positions in haemagglutinin (HA) as compared to the A/Hong Kong/4801/2014 vaccine virus, seven of which occurred in four antigenic sites, together with changes in 23 positions in neuraminidase (NA), and a number of substitutions in internal proteins PB2, PB1, PB1-F2, PA, NP and NS1. Despite the many amino acid substitutions, A(H3N2) viruses remained antigenically similar to the vaccine strain. Substitutions in HA and NA sequences of A(H1N1)pdm09 and B/Victoria-lineage strains were also identified, including in antigenic sites. The results of this study confirm the genetic variability of circulating influenza viruses, particularly A(H3N2), and the need for continued antigenic and molecular surveillance.

Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

PubMed

Adlhoch, C; Gossner, C; Koch, G; Brown, I; Bouwstra, R; Verdonck, F; Penttinen, P; Harder, T

2014-12-18

Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

[Investigation on a seasonal influenza accompanying with the first locale novel A/H1N1 influenza outbreak in China].

PubMed

Yuan, Jun; Li, Mei-xia; Liu, Yu-fei; Di, Biao; Xiao, Xiao-ling; Mao, Xin-wu; Wu, Ye-jian; Xie, Hua-ping; Xie, Zhao-jun; Zhang, Hao; Liu, Jian-ping; Li, Hai-lin; Shen, Ji-chuan; Yang, Zhi-cong; Wang, Ming

2009-10-01

To timely summarize past experience and to provide more pertinent reference for control and prevention in A/H1N1 cases in influenza season. During May 25 to 31, 2009, 2 secondary community cases caused by a influenza A/H1N1 imported case. In the close contacts of 3 A/H1N1 cases, 14 had some aspirator symptoms onset, such as fever (> or = 37.5 degrees C), cough, sore throat and etc. Laboratory tests excluded the infection of A/H1N1 influenza. For throat swab test for the 14 cases, 7 were tested for seasonal influenza virus. A face-to-face or telephone interview was conducted by CDC staff to collect information of 62 close contacts. Of 14 fever cases, there was no significant by differences by age[15-age group: 19.2% (5/26), over 25-age group: 25.0% (9/36); chi(2) = 0.287, P = 0.592]; by sex group [24.0% (6/25) for male and 21.6% (8/37) for female; chi(2) = 0.048, P = 0.826], by working units [dressing and design, photograph, saleroom and others, consumer group: 42.1% (8/19), 27.3% (3/11), 12.5% (2/16) and 6.3% (1/16); chi(2) = 7.653, P = 0.054], by dormitory style [dormitory style = 33.3% (4/12), non-dormitory style = 29.4% (10/34); chi(2) = 0.699, P = 0.403]. All the cases had fever (37.5 - 37.9 degrees C), no case had diarrhea. One in 3 A/H1N1 cases had diarrhea. All the 14 cases were negative result for A/H1N1 RNA. Six from 7 cases were positive for seasonal influenza test. This was a seasonal influenza outbreak happened in the close contacts of first confirmed A/H1N1 cases in community in mainland China. It showed that we should exclude the seasonal influenza in the investigation of A/H1N1 cases in the seasonal influenza period in some time. It is necessary to take effective measure to strengthen the control and prevention of seasonal influenza.

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

PubMed

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

2013-01-01

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

Protection by Face Masks against Influenza A(H1N1)pdm09 Virus on Trans-Pacific Passenger Aircraft, 2009

PubMed Central

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

2013-01-01

In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0–0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect. PMID:23968983

Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort.

PubMed

Fragaszy, Ellen; Ishola, David A; Brown, Ian H; Enstone, Joanne; Nguyen-Van-Tam, Jonathan S; Simons, Robin; Tucker, Alexander W; Wieland, Barbara; Williamson, Susanna M; Hayward, Andrew C; Wood, James L N

2016-07-01

Pigs are mixing vessels for influenza viral reassortment, but the extent of influenza transmission between swine and humans is not well understood. To assess whether occupational exposure to pigs is a risk factor for human infection with human and swine-adapted influenza viruses. UK pig industry workers were frequency-matched on age, region, sampling month, and gender with a community-based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres ≥ 40 considered seropositive and indicative of infection). Virus-specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity. Forty-two percent of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CIs), adjusted odds ratio after accounting for possible cross-reactivity with other swine A(H1) viruses (aOR) 25·3, 95% CI (1·4-536·3), P = 0·028. The results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunisation of pig industry workers may reduce transmission and the potential for virus reassortment. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Pandemic A/H1N1 influenza: transmission of the first cases in Spain.

PubMed

Català, Laura; Rius, Cristina; García de Olalla, Patricia; Nelson, Jeanne L; Alvarez, Josep; Minguell, Sofía; Camps, Neus; Sala, María Rosa; Arias, Carlos; Barrabeig, Irene; Carol, Mónica; Torra, Roser; Cardeñosa, Neus; Pumarola, Tomas; Caylà, Joan A

2012-02-01

Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe. Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases. On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1-16.1) and their contacts (13.2%; CI: 4.4-22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel. The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests.

PubMed

Balish, Amanda; Garten, Rebecca; Klimov, Alexander; Villanueva, Julie

2013-07-01

The performance of rapid influenza diagnostic tests (RIDTs) that detect influenza viral nucleoprotein (NP) antigen has been reported to be variable. Recent human infections with variant influenza A viruses that are circulating in pigs prompted the investigation of the analytical reactivity of RIDTs with these variant viruses. To determine analytical reactivity of seven FDA-cleared RIDTs with influenza A variant viruses in comparison with the reactivity with recently circulating seasonal influenza A viruses. Tenfold serial dilutions of cell culture-grown seasonal and variant influenza A viruses were prepared and tested in duplicate with seven RIDTs. All RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus, although detection limits varied among assays. All but one examined RIDT identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced sensitivity of RIDTs to variant influenza viruses may be due to amino acid differences between the NP proteins of seasonal viruses and the NP proteins from viruses circulating in pigs. Clinicians should be aware of the limitations of RIDTs to detect influenza A variant viruses. Specimens from patients with influenza-like illness in whom H3N2v is suspected should be sent to public health laboratories for additional diagnostic testing. Published 2012. This article is a US Government work and is in the public domain in the USA.

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

PubMed Central

2013-01-01

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

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies

PubMed Central

Feldstein, Leora R.; Matrajt, Laura; Halloran, M. Elizabeth; Keitel, Wendy A.; Longini, Ira M.

2016-01-01

Influenza A virus subtype H5N1 has been a public health concern for almost 20 years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: 1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and 2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48–0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32–0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15 mcg had the highest estimated theoretical vaccine efficacy: Dose 1) 45% (95%CI: 36–57%), 53% (95%CI: 42–63%) and 55% (95%CI: 44–64%), respectively and Dose 2) 93% (95%CI: 89–96%), 97% (95%CI: 95–98%) and 97% (95%CI: 96–100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect

Genetic characterization and diversity of circulating influenza A/H1N1pdm09 viruses isolated in Jeddah, Saudi Arabia between 2014 and 2015.

PubMed

Hashem, Anwar M; Azhar, Esam I; Shalhoub, Sarah; Abujamel, Turki S; Othman, Norah A; Al Zahrani, Abdulwahab B; Abdullah, Hanan M; Al-Alawi, Maha M; Sindi, Anees A

2018-05-01

The emerged influenza A/H1N1pdm09 viruses have replaced the previously circulating seasonal H1N1 viruses. The close antigenic properties of these viruses to the 1918 H1N1 pandemic viruses and their post-pandemic evolution pattern could further enhance their adaptation and pathogenicity in humans representing a major public health threat. Given that data on the dynamics and evolution of these viruses in Saudi Arabia is sparse we investigated the genetic diversity of circulating influenza A/H1N1pdm09 viruses from Jeddah, Saudi Arabia, by analyzing 39 full genomes from isolates obtained between 2014-2015, from patients with varying symptoms. Phylogenetic analysis of all gene segments and concatenated genomes showed similar topologies and co-circulation of clades 6b, 6b.1 and 6b.2, with clade 6b.1 being the most predominate since 2015. Most viruses were more closely related to the vaccine strain (Michigan/45/2015) recommended for the 2017/2018 season, than to the California/07/2009 strain. Low sequence variability was observed in the haemagglutinin protein compared to the neuraminidase protein. Resistance to neuraminidase inhibitors was limited as only one isolate had the H275Y substitution. Interestingly, two isolates had short PA-X proteins of 206 amino acids compared to the 232 amino acid protein found in most influenza A/H1N1pdm09 viruses. Together, the co-circulation of several clades and the predominance of clade 6b.1, despite its low circulation in Asia in 2015, suggests multiple introductions most probably during the mass gathering events of Hajj and Umrah. Jeddah represents the main port of entry to the holy cities of Makkah and Al-Madinah, emphasizing the need for vigilant surveillance in the kingdom.

Effectiveness of monovalent 2009 pandemic influenza A virus subtype H1N1 and 2010-2011 trivalent inactivated influenza vaccines in Wisconsin during the 2010-2011 influenza season.

PubMed

Bateman, Allen C; Kieke, Burney A; Irving, Stephanie A; Meece, Jennifer K; Shay, David K; Belongia, Edward A

2013-04-15

The 2009 influenza A virus subtype H1N1 (A[H1N1]pdm09) did not exhibit antigenic drift during the 2010-2011 influenza season, providing an opportunity to investigate the duration of protection after vaccination. We estimated the independent effects of 2010-2011 seasonal trivalent inactivated influenza vaccine (TIV) and A(H1N1)pdm09 vaccine for preventing medically attended influenza A virus infection during the 2010-2011 season. Individuals were tested for influenza A virus by real-time reverse transcription polymerase chain reaction (rRT-PCR) after a clinical encounter for acute respiratory illness. Case-control analyses compared participants with rRT-PCR-confirmed influenza A virus infection and test-negative controls. Vaccine effectiveness was estimated separately for monovalent pandemic vaccine and TIV and was calculated as 100 × [1 - adjusted odds ratio], where the odds ratio was adjusted for potential confounders. The effectiveness of TIV against influenza A virus infection was 63% (95% confidence interval [CI], 37%-78%). The effectiveness of TIV against A(H1N1)pdm09 infection was 77% (95% CI, 44%-90%). Monovalent vaccine administered between October 2009 and April 2010 was not protective during the 2010-2011 season, with an effectiveness of -1% (95% CI, -146% to 59%) against A(H1N1)pdm09 infection.  Monovalent vaccine provided no sustained protection against A(H1N1)pdm09 infection during the 2010-2011 season. This waning effectiveness supports the need for annual revaccination, even in the absence of antigenic drift in A(H1N1)pdm09.

Lack of evidence for pre-symptomatic transmission of pandemic influenza virus A(H1N1) 2009 in an outbreak among teenagers; Germany, 2009.

PubMed

Hermes, Julia; Bernard, Helen; Buchholz, Udo; Spackova, Michaela; Löw, Johann; Loytved, Gunther; Suess, Thorsten; Hautmann, Wolfgang; Werber, Dirk

2011-11-01

Observations on the role of pre-symptomatic transmission in the spread of influenza virus are scanty. In June 2009, an outbreak of pandemic A(H1N1) 2009 infection occurred at a teenager's party in Germany. The objective of this study was to identify risk factors for pandemic A(H1N1) 2009 infection. We performed a retrospective cohort study among party guests. A case was defined as pandemic A(H1N1) 2009 infection confirmed by rRT-PCR who developed influenza-like illness between 1 and 5 June 2009. Contact patterns among party guests were evaluated. In eight (36%) of 27 party guests, the outcome was ascertained. A travel returnee from a country with endemic pandemic A(H1N1) 2009 who fell ill toward the end of the party was identified as the source case. Party guests with pandemic A(H1N1) 2009 infection had talked significantly longer to the source case than non-infected persons (P-value: 0·001). Importantly, none (0/9) of those who had left the party prior to the source case's symptom onset became infected compared to 7 (41%) of 17 who stayed overnight (P = 0·06), and these persons all had transmission-prone contacts to the source case. In this outbreak with one index case, there was no evidence to support pre-symptomatic transmission of pandemic A(H1N1) 2009. Further evidence is required, ideally from larger studies with multiple index cases, to more accurately characterize the potential for pre-symptomatic transmission of influenza virus. © 2011 Blackwell Publishing Ltd.

HA222 polymorphism in Influenza A(H1N1) 2009 isolates from Intensive Care Units and ambulatory patients during three influenza seasons.

PubMed

Corcioli, F; Arvia, R; Pierucci, F; Clausi, V; Bonizzoli, M; Peris, A; Azzi, A

2014-02-13

Amino acid substitutions which can affect the receptor binding specificity of the influenza virus, like the substitution of aspartic acid with glycine in position 222 of the haemagglutinin (HA) of influenza virus A(H1N1) 2009, have been associated with increased viral pathogenicity and increased tropism for the lower respiratory tract. In this paper, the polymorphic site 222 and the site 223 of the HA1 polypeptide of H1N1 2009 viruses were analyzed in order to better clarify the role of these substitutions in H1N1 2009 virus virulence. Viral strains included in this study were collected in Tuscany during 3 different influenza seasons from patients with severe as well as with mild forms of influenza caused by A(H1N1) 2009 virus. In addition, the oseltamivir resistance of the H1N1 2009 strains circulating during the same seasons was monitored with the aim to evaluate whether these changes in the HA and in neuraminidase (NA) tend to be linked and to influence each other. Altogether, the results indicate that in severe forms of influenza viral population is more variable than in mild influenza, as regards the site 222. The frequency of such substitutions varied among the three seasons, it was highest in the season 2010-2011 and very low in the season 2012-2013. However these differences were not significant. Copyright © 2013 Elsevier B.V. All rights reserved.

Pathogenicity and Transmissibility of Novel Reassortant H3N2 Influenza Viruses with 2009 Pandemic H1N1 Genes in Pigs

PubMed Central

Ma, Jingjiao; Shen, Huigang; Liu, Qinfang; Bawa, Bhupinder; Qi, Wenbao; Duff, Michael; Lang, Yuekun; Lee, Jinhwa; Yu, Hai; Bai, Jianfa; Tong, Guangzhi; Hesse, Richard A.; Richt, Jürgen A.

2014-01-01

ABSTRACT At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses. IMPORTANCE Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza

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

PubMed

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

2015-06-01

Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of efficacy and safety of pandemic A/H1N1/2009 influenza vaccine in a group of health care workers.

PubMed

Mascagni, P; Vicenzi, Elisa; Kajaste-Rudnitski, Anna; Pellicciotta, G; Monti, A; Cervi, Carla; Vitalucci, Roberta; Toffoletto, F

2012-01-01

The development in an extremely short time of an efficacious and safe vaccine against the pandemi A/H1N1 virus was a challenge that involved the entire scientific community. To assess the immunological and clinical efficacy of the new H1N1v monovalent influenza vaccine (Focetria Novartis Vaccines, Siena, Italy) in a group of health care workers (HCWs). A total of 148 volunteer HCWs were enrolled between Mid-Novembre 2009 and December 2009. After measuring antibody titers, a single intramuscular dose of 7.5 microg of Focetria monovalent vaccine against A/H1N1/2009 influenza virus with MF59C.1 adjuvant was administered. Antibody titers (median value) before and after a single dose of vaccine, measured by means of standard beam-agglutination inhibition test (HAI), increased from 32 to 256 (p < 0.001). After vaccination, 79.7% of the subjects showed antibody seroconversion, and in 97.3% seroprotection was achieved. The ratio between the geometric means of antibody titers (GMTR) was 6.69. For the 3 subjects who reported symptoms of ILI (Influenza-like illness), a regular nasal-pharyngeal swab sample was taken to identify the virus type by RT-PCR, the laboratory results of tests performed on these samples were negative for pandemic A/H1N1/2009 virus. During the entire follow-up period of 6 months no severe adverse events occurred. The vaccine against pandemic A/H1N1/2009 virus provided protection against the virus and not only contributed to a significant immunization (according to EMEA criteria), but kept all 148 subjects under study free from A/H1N1/2009 influenza illness.

Thromboembolic events in patients with severe pandemic influenza A/H1N1.

PubMed

Avnon, Lone Sølling; Munteanu, Daniela; Smoliakov, Alexander; Jotkowitz, Alan; Barski, Leonid

2015-10-01

The 2009 pandemic influenza A/H1N1 developed as a novel swine influenza which caused more diseases among younger age groups than in the elderly. Severe hypoxemic respiratory failure from A/H1N1 pneumonia resulted in an increased need for ICU beds. Several risk groups were identified that were at a higher risk for adverse outcomes. Pregnant women were a particularly vulnerable group of patients The CDC reported on the first ten patients with severe illness and acute hypoxemic respiratory failure associated with A/H1N1 infection, none of whom were pregnant, but they noticed that half of the patients had a pulmonary embolism. During a four-month period from September to December 2009, 252 patients were admitted to our hospital with confirmed pandemic influenza H1N1 by real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR). We cared for twenty patients (7.9%) admitted to MICU with severe A/H1N1. Results on Thrombotic events were identified in five (25%) of our critically ill patients. We recommend that patients with severe influenza A/H1N1 pneumonitis and respiratory failure be administered DVT prophylaxis in particular if there are additional risk factors for TVE. Further prospective studies on the relationship of influenza A/H1N1 and VTE are needed. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Avian Influenza A(H5N1) Virus in Egypt.

PubMed

Kayali, Ghazi; Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S; Maatouq, Asmaa M; Cai, Zhipeng; McKenzie, Pamela P; Webby, Richard J; El Refaey, Samir; Kandeel, Amr; Ali, Mohamed A

2016-03-01

In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt.

Avian Influenza A(H5N1) Virus in Egypt

PubMed Central

Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S.; Maatouq, Asmaa M.; Cai, Zhipeng; McKenzie, Pamela P.; Webby, Richard J.; El Refaey, Samir; Kandeel, Amr; Ali, Mohamed A.

2016-01-01

In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt. PMID:26886164

Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections.

PubMed

Horm, Srey Viseth; Tarantola, Arnaud; Rith, Sareth; Ly, Sowath; Gambaretti, Juliette; Duong, Veasna; Y, Phalla; Sorn, San; Holl, Davun; Allal, Lotfi; Kalpravidh, Wantanee; Dussart, Philippe; Horwood, Paul F; Buchy, Philippe

2016-07-20

Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.

Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus.

PubMed

Martínez-Baz, Iván; Casado, Itziar; Navascués, Ana; Díaz-González, Jorge; Aguinaga, Aitziber; Barrado, Laura; Delfrade, Josu; Ezpeleta, Carmen; Castilla, Jesús

2017-03-15

The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Full-Genome Analysis of Avian Influenza A(H5N1) Virus from a Human, North America, 2013

PubMed Central

Pabbaraju, Kanti; Tellier, Raymond; Wong, Sallene; Li, Yan; Bastien, Nathalie; Tang, Julian W.; Drews, Steven J.; Jang, Yunho; Davis, C. Todd; Tipples, Graham A.

2014-01-01

Full-genome analysis was conducted on the first isolate of a highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found. PMID:24755439

Correlations between A/H1N1 influenza and acute cellular rejection in liver transplantation patients.

PubMed

Stucchi, R S B; Boin, I F S F; Angerami, R Nogueira; Sinckoc, V; Sa, F Cesar; Seva-Pereira, T; Escanhoela, C A Fazzio

2010-12-01

Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes. Copyright © 2010 Elsevier Inc. All rights reserved.

Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

PubMed

Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

2013-04-01

The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009–2010

PubMed Central

Van Effelterre, Thierry; Dos Santos, Gaël; Shinde, Vivek

2016-01-01

Background Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model. Methods A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated. Results The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10–20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10–20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups. Conclusion This analysis

Spatiotemporal dynamics of influenza A(H1N1)pdm09 in Brazil during the pandemic and post-pandemic periods.

PubMed

Manito, Alessandra C B; Gräf, Tiago; Lunge, Vagner R; Ikuta, Nilo

2017-06-15

Influenza A(H1N1)pdm09 was responsible for the first global flu pandemic in 21st century affecting all the world. In Brazil, A(H1N1)pdm09 is still circulating as a seasonal virus, causing deaths every year. Nevertheless, the viral diffusion process that yearly seeds new influenza strains in the country was not investigated yet. The aim of the current study was to describe the phylodynamics and phylogeography of influenza A(H1N1)pdm09 in Brazil between 2009 and 2014. Neuraminidase sequences from Brazil and other regions of the World were retrieved and analyzed. Bayesian phylogeographic and phylodynamic model approaches were used to reconstruct the spatiotemporal and demographic history of influenza A(H1N1)pdm09 in Brazil (divided in subtropical and tropical regions) and related countries. Our analyses reveal that new influenza A(H1N1)pdm09 lineages are seeded in Brazil in almost each year and the main sources of viral diversity are North America, Europe and East Asia. The phylogeographic asymmetric model also revealed that Brazil, mainly the subtropical region, seeds viral lineages into other countries. Coalescent analysis of the compiled dataset reconstructed the peak of viral transmissions in the winter months of Southern hemisphere. The results presented in this study can be informative to public health, guide intervention strategies and in the understanding of flu virus migration, which helps to predict antigenic drift and consequently the developing of new vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Seroprevalence and Transmission of Human Influenza A(H5N1) Virus before and after Virus Reassortment, Cambodia, 2006-2014.

PubMed

Ly, Sowath; Horwood, Paul; Chan, Malen; Rith, Sareth; Sorn, Sopheak; Oeung, Kunthea; Nguon, Kunthy; Chan, Siam; Y, Phalla; Parry, Amy; Tsuyuoka, Reiko; Ly, Sovann; Richner, Beat; Laurent, Denis; Vong, Sirenda; Dussart, Philippe; Buchy, Philippe; Tarantola, Arnaud

2017-02-01

Thirty-five human influenza A(H5N1) cases were reported in Cambodia during 2013-2014 after emergence of a clade 1.1.2 reassortant virus. We tested 881 villagers and found 2 cases of pauci- or asymptomatic infection. Seroprevalence after emergence of the reassortant strain (0.2%) was lower than the aggregate seroprevalence of 1.3% reported in earlier studies.

Characterization of a Large Cluster of Influenza A(H1N1)pdm09 Viruses Cross-Resistant to Oseltamivir and Peramivir during the 2013-2014 Influenza Season in Japan

PubMed Central

Takashita, Emi; Kiso, Maki; Fujisaki, Seiichiro; Yokoyama, Masaru; Nakamura, Kazuya; Shirakura, Masayuki; Sato, Hironori; Odagiri, Takato; Kawaoka, Yoshihiro

2015-01-01

Between September 2013 and July 2014, 2,482 influenza 2009 pandemic A(H1N1) [A(H1N1)pdm09] viruses were screened in Japan for the H275Y substitution in their neuraminidase (NA) protein, which confers cross-resistance to oseltamivir and peramivir. We found that a large cluster of the H275Y mutant virus was present prior to the main influenza season in Sapporo/Hokkaido, with the detection rate for this mutant virus reaching 29% in this area. Phylogenetic analysis suggested the clonal expansion of a single mutant virus in Sapporo/Hokkaido. To understand the reason for this large cluster, we examined the in vitro and in vivo properties of the mutant virus. We found that it grew well in cell culture, with growth comparable to that of the wild-type virus. The cluster virus also replicated well in the upper respiratory tract of ferrets and was transmitted efficiently between ferrets by way of respiratory droplets. Almost all recently circulating A(H1N1)pdm09 viruses, including the cluster virus, possessed two substitutions in NA, V241I and N369K, which are known to increase replication and transmission fitness. A structural analysis of NA predicted that a third substitution (N386K) in the NA of the cluster virus destabilized the mutant NA structure in the presence of the V241I and N369K substitutions. Our results suggest that the cluster virus retained viral fitness to spread among humans and, accordingly, caused the large cluster in Sapporo/Hokkaido. However, the mutant NA structure was less stable than that of the wild-type virus. Therefore, once the wild-type virus began to circulate in the community, the mutant virus could not compete and faded out. PMID:25691635

Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia

PubMed Central

Song, Joon Y.; Cheong, Hee J.; Heo, Jung Y.; Noh, Ji Y.; Yong, Hwan S.; Kim, Yoon K.; Kang, Eun Y.; Choi, Won S.; Jo, Yu M.; Kim, Woo J.

2011-01-01

Please cite this paper as: Song et al. (2011). Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia. Influenza and Other Respiratory Viruses 5(6), e535–e543. Background  Although influenza virus usually involves the upper respiratory tract, pneumonia was seen more frequently with the 2009 pandemic influenza A/H1N1 than with seasonal influenza. Methods  From September 1, 2009, to January 31, 2010, a specialized clinic for patients (aged ≥15 years) with ILI was operated in Korea University Guro Hospital. RT‐PCR assay was performed to diagnose 2009 pandemic influenza A/H1N1. A retrospective case–case–control study was performed to determine the predictive factors for influenza pneumonia and to discriminate concomitant/secondary bacterial pneumonia from primary influenza pneumonia during the 2009–2010 pandemic. Results  During the study period, the proportions of fatal cases and pneumonia development were 0·12% and 1·59%, respectively. Patients with pneumonic influenza were less likely to have nasal symptoms and extra‐pulmonary symptoms (myalgia, headache, and diarrhea) compared to patients with non‐pneumonic influenza. Crackle was audible in just about half of the patients with pneumonic influenza (38·5% of patients with primary influenza pneumonia and 53·3% of patients with concomitant/secondary bacterial pneumonia). Procalcitonin, C‐reactive protein (CRP), and lactate dehydrogenase were markedly increased in patients with influenza pneumonia. Furthermore, procalcitonin (cutoff value 0·35 ng/ml, sensitivity 81·8%, and specificity 66·7%) and CRP (cutoff value 86·5 mg/IU, sensitivity 81·8%, and specificity 59·3%) were discriminative between patients with concomitant/secondary bacterial pneumonia and patients with primary influenza pneumonia. Conclusions  Considering the subtle manifestations of 2009 pandemic

Influenza A(H9N2) Virus, Myanmar, 2014-2015.

PubMed

Lin, Thant Nyi; Nonthabenjawan, Nutthawan; Chaiyawong, Supassama; Bunpapong, Napawan; Boonyapisitsopa, Supanat; Janetanakit, Taveesak; Mon, Pont Pont; Mon, Hla Hla; Oo, Kyaw Naing; Oo, Sandi Myint; Mar Win, Mar; Amonsin, Alongkorn

2017-06-01

Routine surveillance of influenza A virus was conducted in Myanmar during 2014-2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole-genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2 virus of clade 4.2.5 from China.

Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011.

PubMed

Westgeest, Kim B; Russell, Colin A; Lin, Xudong; Spronken, Monique I J; Bestebroer, Theo M; Bahl, Justin; van Beek, Ruud; Skepner, Eugene; Halpin, Rebecca A; de Jong, Jan C; Rimmelzwaan, Guus F; Osterhaus, Albert D M E; Smith, Derek J; Wentworth, David E; Fouchier, Ron A M; de Graaf, Miranda

2014-03-01

Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses. Each winter, influenza virus infects approximately 5 to 15% of the world's population, resulting in significant morbidity and mortality. Influenza A(H3N2) viruses evolve continuously by reassortment and genomic evolution. This leads to changes in antigenic recognition (antigenic drift) which make it necessary to update vaccines against influenza A(H3N2) viruses frequently. In this study, the relationship of genetic evolution

Genesis of Influenza A(H5N8) Viruses

PubMed Central

El-Shesheny, Rabeh; Barman, Subrata; Feeroz, Mohammed M.; Hasan, M. Kamrul; Jones-Engel, Lisa; Franks, John; Turner, Jasmine; Seiler, Patrick; Walker, David; Friedman, Kimberly; Kercher, Lisa; Begum, Sajeda; Akhtar, Sharmin; Datta, Ashis Kumar; Krauss, Scott; Kayali, Ghazi; McKenzie, Pamela; Webby, Richard J.

2017-01-01

Highly pathogenic avian influenza A(H5N8) clade 2.3.4.4 virus emerged in 2016 and spread to Russia, Europe, and Africa. Our analysis of viruses from domestic ducks at Tanguar haor, Bangladesh, showed genetic similarities with other viruses from wild birds in central Asia, suggesting their potential role in the genesis of A(H5N8). PMID:28609260

Genesis of Influenza A(H5N8) Viruses.

PubMed

El-Shesheny, Rabeh; Barman, Subrata; Feeroz, Mohammed M; Hasan, M Kamrul; Jones-Engel, Lisa; Franks, John; Turner, Jasmine; Seiler, Patrick; Walker, David; Friedman, Kimberly; Kercher, Lisa; Begum, Sajeda; Akhtar, Sharmin; Datta, Ashis Kumar; Krauss, Scott; Kayali, Ghazi; McKenzie, Pamela; Webby, Richard J; Webster, Robert G

2017-08-01

Highly pathogenic avian influenza A(H5N8) clade 2.3.4.4 virus emerged in 2016 and spread to Russia, Europe, and Africa. Our analysis of viruses from domestic ducks at Tanguar haor, Bangladesh, showed genetic similarities with other viruses from wild birds in central Asia, suggesting their potential role in the genesis of A(H5N8).

Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014–2015

PubMed Central

Flannery, Brendan; Zimmerman, Richard K.; Gubareva, Larisa V.; Garten, Rebecca J.; Chung, Jessie R.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Monto, Arnold S.; Ohmit, Suzanne E.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Piedra, Pedro A.; Mishin, Vasiliy P.; Chesnokov, Anton P.; Spencer, Sarah; Thaker, Swathi N.; Barnes, John R.; Foust, Angie; Sessions, Wendy; Xu, Xiyan; Katz, Jacqueline; Fry, Alicia M.

2018-01-01

Background During the 2014–15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). Methods A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. Results Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014–15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], −14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. Conclusion Effectiveness of 2014–15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. PMID:27190176

Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

PubMed Central

Suess, Thorsten; Remschmidt, Cornelius; Schink, Susanne B.; Schweiger, Brunhilde; Heider, Alla; Milde, Jeanette; Nitsche, Andreas; Schroeder, Kati; Doellinger, Joerg; Braun, Christian; Haas, Walter; Krause, Gérard; Buchholz, Udo

2012-01-01

Background Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany. Methods Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily. Results We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03). Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics. On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status. Conclusion Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was

Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B).

PubMed

Song, Daesub; Kim, Hyekwon; Na, Woonsung; Hong, Minki; Park, Seong-Jun; Moon, Hyoungjoon; Kang, Bokyu; Lyoo, Kwang-Soo; Yeom, Minjoo; Jeong, Dae Gwin; An, Dong-Jun; Kim, Jeong-Ki

2015-02-01

We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses. © 2015 The Authors.

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

PubMed

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.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

PubMed Central

Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao

2016-01-01

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529

Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies.

PubMed

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

2014-01-01

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

Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

PubMed Central

He, Xiao-Song; Sasaki, Sanae; Baer, Jane; Khurana, Surender; Golding, Hana; Treanor, John J.; Topham, David J.; Sangster, Mark Y.; Jin, Hong; Dekker, Cornelia L.; Subbarao, Kanta; Greenberg, Harry B.

2013-01-01

Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults. Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1)pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens. Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain. Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. PMID:23107783

Binding affinity of the L-742,001 inhibitor to the endonuclease domain of A/H1N1/PA influenza virus variants: Molecular simulation approaches

NASA Astrophysics Data System (ADS)

Nguyen, Hung; Nguyen, Hoang Linh; Linh, Huynh Quang; Nguyen, Minh Tho

2018-01-01

The steered molecular dynamics (SMD), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and free energy perturbation (FEP) methods were used to determine the binding affinity of the L-742,001 inhibitor to the endonuclease domain of the A/H1N1/PA influenza viruses (including wild type (WT) and three mutations I79L, E119D and F105S for both pH1N1 PA and PR8 PA viruses). Calculated results showed that the L-742,001 inhibitor not only binds to the PR8 PAs (1934 A influenza virus) better than to the pH1N1 PAs (2009 A influenza virus) but also more strongly interacts with the WT endonuclease domain than with three mutant variants for both pH1N1 PA and PR8 PA viruses. The binding affinities obtained by the SMD, MM-PBSA and FEP methods attain high correlation with available experimental data. Here the FEP method appears to provide a more accurate determination of the binding affinity than the SMD and MM-PBSA counterparts.

The influence of social-cognitive factors on personal hygiene practices to protect against influenzas: using modelling to compare avian A/H5N1 and 2009 pandemic A/H1N1 influenzas in Hong Kong.

PubMed

Liao, Qiuyan; Cowling, Benjamin J; Lam, Wendy Wing Tak; Fielding, Richard

2011-06-01

Understanding population responses to influenza helps optimize public health interventions. Relevant theoretical frameworks remain nascent. To model associations between trust in information, perceived hygiene effectiveness, knowledge about the causes of influenza, perceived susceptibility and worry, and personal hygiene practices (PHPs) associated with influenza. Cross-sectional household telephone surveys on avian influenza A/H5N1 (2006) and pandemic influenza A/H1N1 (2009) gathered comparable data on trust in formal and informal sources of influenza information, influenza-related knowledge, perceived hygiene effectiveness, worry, perceived susceptibility, and PHPs. Exploratory factor analysis confirmed domain content while confirmatory factor analysis was used to evaluate the extracted factors. The hypothesized model, compiled from different theoretical frameworks, was optimized with structural equation modelling using the A/H5N1 data. The optimized model was then tested against the A/H1N1 dataset. The model was robust across datasets though corresponding path weights differed. Trust in formal information was positively associated with perceived hygiene effectiveness which was positively associated with PHPs in both datasets. Trust in formal information was positively associated with influenza worry in A/H5N1 data, and with knowledge of influenza cause in A/H1N1 data, both variables being positively associated with PHPs. Trust in informal information was positively associated with influenza worry in both datasets. Independent of information trust, perceived influenza susceptibility associated with influenza worry. Worry associated with PHPs in A/H5N1 data only. Knowledge of influenza cause and perceived PHP effectiveness were associated with PHPs. Improving trust in formal information should increase PHPs. Worry was significantly associated with PHPs in A/H5N1.

Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus

USDA-ARS?s Scientific Manuscript database

The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine delta-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, six-week-old, crossbred pigs were rand...

The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies.

PubMed

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

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

Environmental Levels of the Antiviral Oseltamivir Induce Development of Resistance Mutation H274Y in Influenza A/H1N1 Virus in Mallards

PubMed Central

Järhult, Josef D.; Söderström, Hanna; Orozovic, Goran; Gunnarsson, Gunnar; Bröjer, Caroline; Latorre-Margalef, Neus; Fick, Jerker; Grabic, Roman; Lennerstrand, Johan; Waldenström, Jonas; Lundkvist, Åke; Olsen, Björn

2011-01-01

Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008–2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC50 for OC was increased from 2–4 nM in wild-type viruses to 400–700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58–293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals. PMID:21931841

Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

PubMed Central

Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Cherry, Joshua L.; Lipman, David J.

2013-01-01

Individuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. PMID:23115287

Influenza Risk Management: Lessons Learned from an A(H1N1) pdm09 Outbreak Investigation in an Operational Military Setting

DTIC Science & Technology

2013-07-10

of the virus in Spain was detected during an outbreak investigation of influenza -like illness (ILI) in soldiers from an engineering military academy...SwInfA primer and probe set) and specific A(H1N1) pdm09 influenza A viruses using SwH1 primer and probe set developed by CDC, Atlanta (WHO...CY062374, CY062375 and CY062376. Viral culture Influenza viruses were isolated from clinical samples by infecting Madin Darby Canine Kidney (MDCK

Absence of influenza A(H1N1) during seasonal and pandemic seasons in a sentinel nursing home surveillance network in the Netherlands.

PubMed

Enserink, Remko; Meijer, Adam; Dijkstra, Frederika; van Benthem, Birgit; van der Steen, Jenny T; Haenen, Anja; van Delden, Hans; Cools, Herman; van der Sande, Marianne; Veldman-Ariesen, Marie-Jose

2011-12-01

To describe the epidemiological, virological, and institutional characteristics of influenza-like illness (ILI) in nursing homes (NHs). Continuous clinical surveillance of ILI and virological surveillance of ILI and other acute respiratory infections (ARIs) during four influenza seasons. National sentinel NH surveillance network. National sentinel residents. Weekly registration of ILI cases (influenza seasons 2008/09-2009/10), influenza virus detection (influenza seasons 2006/07-2009/10), and collection of institutional characteristics of NHs at start of participation. During the 2008/09 influenza season, ILI incidence started to rise in Week 49 of 2008, peaked in Week 3 of 2009 (158 cases per 10,000 resident weeks), and flattened out by Week 16 of 2009 (mean ILI incidence during epidemic: 73 cases per 10,000 resident weeks). During the 2009/10 influenza pandemic, there was no epidemic peak. Influenza virus type and subtype varied throughout virological surveillance but was limited to influenza A(H3N2) and B viruses. Higher staff vaccination coverage (>15%) was associated with lower ILI-incidence in the 2008/09 influenza season in a univariate negative binomial regression analysis (incidence rate ratio = 0.3, 95% confidence interval = 0.1-0.8)). Neither seasonal nor pandemic influenza A(H1N1) viruses were detected in the network, despite widespread community transmission of seasonal and influenza A(H1N1) virus. ILI incidence trends corresponded to virological trends. Sentinel surveillance of ILI combining clinical and virological data in NHs increases understanding of transmission risks in this specific vulnerable population. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

Seroevidence for a High Prevalence of Subclinical Infection With Avian Influenza A(H5N1) Virus Among Workers in a Live-Poultry Market in Indonesia

PubMed Central

Shimizu, Kazufumi; Wulandari, Laksmi; Poetranto, Emmanuel D.; Setyoningrum, Retno A.; Yudhawati, Resti; Sholikhah, Amelia; Nastri, Aldise M.; Poetranto, Anna L.; Candra, Adithya Y. R.; Puruhito, Edith F.; Takahara, Yusuke; Yamagishi, Yoshiaki; Yamaoka, Masaoki; Hotta, Hak; Ustumi, Takako; Lusida, Maria I.; Soetjipto; Shimizu, Yohko K.; Soegiarto, Gatot; Mori, Yasuko

2016-01-01

Background. In Indonesia, highly pathogenic avian influenza A(H5N1) virus has become endemic in poultry and has caused sporadic deadly infections in human. Since 2012, we have conducted fixed-point surveillance of avian influenza viruses at a live-poultry market in East Java, Indonesia. In this study, we examined the seroprevalence of avian influenza A(H5N1) virus infection among market workers. Methods. Sera were collected from 101 workers in early 2014 and examined for antibody activity against avian A(H5N1) Eurasian lineage virus by a hemagglutination-inhibition (HI) assay. Results. By the HI assay, 84% of the sera tested positive for antibody activity against the avian virus. Further analysis revealed that the average HI titer in 2014 was 2.9-fold higher than in 2012 and that seroconversion occurred in 44% of paired sera (11 of 25) between 2012 and 2014. A medical history survey was performed in 2016; responses to questionnaires indicated that none of workers had had severe acute respiratory illness during 2013. Conclusions. This study provides evidence of a high prevalence of avian A(H5N1) virus infection in 2013 among workers at a live-poultry market. However, because no instances of hospitalizations were reported, we can conclude the virus did not manifest any clinical symptoms in workers. PMID:27923953

Seroprevalence and Transmission of Human Influenza A(H5N1) Virus before and after Virus Reassortment, Cambodia, 2006–2014

PubMed Central

Ly, Sowath; Horwood, Paul; Chan, Malen; Rith, Sareth; Sorn, Sopheak; Oeung, Kunthea; Nguon, Kunthy; Chan, Siam; Y, Phalla; Parry, Amy; Tsuyuoka, Reiko; Ly, Sovann; Richner, Beat; Laurent, Denis; Vong, Sirenda; Dussart, Philippe; Buchy, Philippe

2017-01-01

Thirty-five human influenza A(H5N1) cases were reported in Cambodia during 2013–2014 after emergence of a clade 1.1.2 reassortant virus. We tested 881 villagers and found 2 cases of pauci- or asymptomatic infection. Seroprevalence after emergence of the reassortant strain (0.2%) was lower than the aggregate seroprevalence of 1.3% reported in earlier studies. PMID:28098551

Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

PubMed

Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

2015-01-01

The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

Novel influenza A(H1N1) outbreak among French armed forces in 2009: results of Military Influenza Surveillance System.

PubMed

Mayet, A; Duron, S; Nivoix, P; Haus-Cheymol, R; Ligier, C; Gache, K; Dia, A; Manet, G; Verret, C; Pommier de Santi, V; Bigaillon, C; Martinaud, C; Piarroux, M; Faure, N; Hupin, C; Decam, C; Chaudet, H; Meynard, J B; Nicand, E; Deparis, X; Migliani, R

2011-08-01

An outbreak of novel A(H1N1) virus influenza, detected in Mexico in April 2009, spread worldwide in 9 weeks. The aim of this paper is to present the monitoring results of this influenza outbreak among French armed forces. The period of monitoring by the Military Influenza Surveillance System (MISS) was 9 months, from May 2009 to April 2010. The main monitored events were acute respiratory infection (ARI), defined by oral temperature ≥38.5 °C and cough, and laboratory-confirmed influenza. Weekly incidence rates were calculated by relating cases to the number of servicepersons monitored. In continental France, the incidence of ARI increased from September 2009, with a weekly maxima of 401 cases per 100,000 in early December 2009 according to MISS. Estimations of the incidence of consultations which could be related to novel A(H1N1) influenza ranged from 48 to 57 cases per 100,000. The trends observed by MISS are compatible with French national estimations. The incidence of consultations which could be related to A(H1N1) influenza at the peak of the epidemic (194 cases per 100,000) was much lower than the national estimate (1321 cases per 100,000). This may be due to servicepersons who consulted in civilian facilities and were not monitored. Other explanations are the healthy worker effect and the younger age of the military population. Copyright © 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

PubMed

Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Jiménez-Jorge, Silvia; Horváth, Judit K; Donnell, Joan M O; Pitigoi, Daniela; Machado, Ausenda; Pozo, Francisco

2015-06-04

In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses. Copyright © 2015 The Authors

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease

PubMed Central

Kim, Jin Hyang; Reber, Adrian J.; Kumar, Amrita; Ramos, Patricia; Sica, Gabriel; Music, Nedzad; Guo, Zhu; Mishina, Margarita; Stevens, James; York, Ian A.; Jacob, Joshy; Sambhara, Suryaprakash

2016-01-01

The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses. PMID:27849030

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease.

PubMed

Kim, Jin Hyang; Reber, Adrian J; Kumar, Amrita; Ramos, Patricia; Sica, Gabriel; Music, Nedzad; Guo, Zhu; Mishina, Margarita; Stevens, James; York, Ian A; Jacob, Joshy; Sambhara, Suryaprakash

2016-11-16

The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.

Travel-related influenza A/H1N1 infection at a rock festival in Hungary: one virus may hide another one.

PubMed

Botelho-Nevers, Elizabeth; Gautret, Philippe; Benarous, Lucas; Charrel, Rémi; Felkai, Peter; Parola, Philippe

2010-01-01

Mass gathering is well known to concentrate and amplify the transmission of infectious respiratory diseases. Here we report a possible case of coinfection with influenza A/H1N1 and varicella in a young French traveler returning from a rock festival in Hungary. We report a cluster of influenza A/H1N1 cases at this festival.

Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China.

PubMed

Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan

2013-01-01

The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China. Copyright © 2012 Elsevier B.V. All rights reserved.

Heterologous Humoral Response against H5N1, H7N3, and H9N2 Avian Influenza Viruses after Seasonal Vaccination in a European Elderly Population

PubMed Central

Sanz, Ivan; Rojo, Silvia; Tamames, Sonia; Eiros, José María; Ortiz de Lejarazu, Raúl

2017-01-01

Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad

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

PubMed Central

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

2011-01-01

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

Characteristics of a Widespread Community Cluster of H275Y Oseltamivir-Resistant A(H1N1)pdm09 Influenza in Australia

PubMed Central

Hurt, A. C.; Hardie, K.; Wilson, N. J.; Deng, Y. M.; Osbourn, M.; Leang, S. K.; Lee, R. T. C.; Iannello, P.; Gehrig, N.; Shaw, R.; Wark, P.; Caldwell, N.; Givney, R. C.; Xue, L.; Maurer-Stroh, S.; Dwyer, D. E.; Wang, B.; Smith, D. W.; Levy, A.; Booy, R.; Dixit, R.; Merritt, T.; Kelso, A.; Dalton, C.; Durrheim, D.; Barr, I. G.

2012-01-01

Background. Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. Methods. Influenza specimens from the Asia–Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. Results. Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. Conclusions This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely. PMID:22561367

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

PubMed

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.

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

PubMed Central

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

2009-01-01

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

Seasonal influenza A/H3N2 virus infection and IL-1Β, IL-10, IL-17, and IL-28 polymorphisms in Iranian population.

PubMed

Rogo, Lawal Dahiru; Rezaei, Farhad; Marashi, Seyed Mahdi; Yekaninejad, Mir Saeed; Naseri, Maryam; Ghavami, Nastaran; Mokhtari-Azad, Talat

2016-12-01

Increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A/H3N2 virus infection. The study was aimed to investigate the polymorphisms of IL-1β, IL-10, IL-17, and IL-28 genes to find the possibility of their association with the clinical outcome of influenza A/H3N2 virus infection among the infected patients in Iran. This is a Case-Control study in which influenza A/H3N2 virus positive confirmed with real-time PCR were the cases. DNA samples from groups were genotyped for polymorphisms in rs16944 (IL-1β), rs1800872 (IL-10), rs2275913 (IL-17), and rs8099917 (IL-28). Confidence interval (95%CI) and Odds ratio (OR) were calculated. IL-17 rs2275913 (GG and AG) were associated with risk of infection with that were statistically significant (P < 0.05, OR = 2.08-2.94). IL-1β (rs16944) (GG) was associated with reduced risk of infection (P < 0.01, OR = 0.46). Genotype GG and GT of IL-10 (rs1800872) were associated with increased risk of infection with influenza A/H3N2 virus (P < 0.05, OR = 2.04-2.58). In addition, IL-28 (rs8099917) genotypes GG (P < 0.05, OR = 0.49) and TG (P < 0.05, OR = 0.59) were associated with reduced risk of ILI symptom while genotype TT (P < 0.01, OR = 4.31) was associated with increased risk of ILI symptom. The results of this study demonstrated that polymorphisms of genes involved in the inflammatory and anti-inflammatory process affect the outcome of disease caused by influenza A/H3N2 virus. Thorough insight on host immune response at the time of influenza A virus infection is required to ensure adequate patient care in the case of feature outbreaks. J. Med. Virol. 88:2078-2084, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed Central

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

2014-01-01

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

Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012

PubMed Central

Grgić, Helena; Costa, Marcio; Friendship, Robert M.; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

2015-01-01

The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614

Testing of human specimens for the presence of highly pathogenic zoonotic avian influenza virus A(H5N1) in Poland in 2006-2008 - justified or unnecessary steps?

PubMed

Romanowska, Magdalena; Nowak, Iwona; Brydak, Lidia; Wojtyla, Andrzej

2009-01-01

Since 1997, human infections with highly pathogenic zoonotic avian influenza viruses have shown that the risk of influenza pandemic is significant. In Europe, infections caused by the highly pathogenic avian influenza A(H7N7) virus were confirmed in the human population in 2003 in the Netherlands. Moreover, outbreaks of A(H5N1) infections were observed in wild and farm birds in different European regions, including Poland in 2006-2008. This study presents 16 patients in Poland from whom clinical specimens were collected and tested for A(H5N1) highly pathogenic avian influenza. This article shows the results of laboratory tests and discusses the legitimacy of the collection and testing of the specimens. All patients were negative for A(H5N1) infection. Nevertheless, only two patients met clinical and epidemiological criteria from the avian influenza case definition. The conclusion is that there is still a strong necessity for increasing the awareness of medical and laboratory staff, as well as the awareness of some occupational groups about human infections with avian influenza viruses, including the importance of seasonal influenza vaccination. It should also be emphasized that in the case of patients suspected of being infected with avian influenza, the information about clinical symptoms is insufficient and must be accompanied by a wide epidemiological investigation.

Seroevidence for a High Prevalence of Subclinical Infection With Avian Influenza A(H5N1) Virus Among Workers in a Live-Poultry Market in Indonesia.

PubMed

Shimizu, Kazufumi; Wulandari, Laksmi; Poetranto, Emmanuel D; Setyoningrum, Retno A; Yudhawati, Resti; Sholikhah, Amelia; Nastri, Aldise M; Poetranto, Anna L; Candra, Adithya Y R; Puruhito, Edith F; Takahara, Yusuke; Yamagishi, Yoshiaki; Yamaoka, Masaoki; Hotta, Hak; Ustumi, Takako; Lusida, Maria I; Soetjipto; Shimizu, Yohko K; Soegiarto, Gatot; Mori, Yasuko

2016-12-15

 In Indonesia, highly pathogenic avian influenza A(H5N1) virus has become endemic in poultry and has caused sporadic deadly infections in human. Since 2012, we have conducted fixed-point surveillance of avian influenza viruses at a live-poultry market in East Java, Indonesia. In this study, we examined the seroprevalence of avian influenza A(H5N1) virus infection among market workers.  Sera were collected from 101 workers in early 2014 and examined for antibody activity against avian A(H5N1) Eurasian lineage virus by a hemagglutination-inhibition (HI) assay.  By the HI assay, 84% of the sera tested positive for antibody activity against the avian virus. Further analysis revealed that the average HI titer in 2014 was 2.9-fold higher than in 2012 and that seroconversion occurred in 44% of paired sera (11 of 25) between 2012 and 2014. A medical history survey was performed in 2016; responses to questionnaires indicated that none of workers had had severe acute respiratory illness during 2013.  This study provides evidence of a high prevalence of avian A(H5N1) virus infection in 2013 among workers at a live-poultry market. However, because no instances of hospitalizations were reported, we can conclude the virus did not manifest any clinical symptoms in workers. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

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

PubMed

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

2015-12-01

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

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

PubMed

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

2017-05-01

This report describes a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004 to 2005, N2 from influenza A virus already established in swine, and the internal gene cassette from A(H1N1)pdm09 has spread in Danish pig herds. The virus has been detected in several Danish pig herds during the last 2-3 years and may possess a challenge for human as well as animal health. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011.

PubMed

Dung, Tham Chi; Dinh, Pham Ngoc; Nam, Vu Sinh; Tan, Luong Minh; Hang, Nguyen Le Khanh; Thanh, Le Thi; Mai, Le Quynh

2014-01-01

Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces. We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004. The overall seroprevalence was 6.1% (95% confidence interval: 4.6-8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry. The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian-human transmission of influenza A(H5N1) in Viet Nam.

Swine-to-Human Transmission of Influenza A(H3N2) Virus at Agricultural Fairs, Ohio, USA, 2012

PubMed Central

Nelson, Sarah W.; Page, Shannon L.; Nolting, Jacqueline M.; Killian, Mary L.; Sreevatsan, Srinand; Slemons, Richard D.

2014-01-01

Agricultural fairs provide an opportunity for bidirectional transmission of influenza A viruses. We sought to determine influenza A virus activity among swine at fairs in the United States. As part of an ongoing active influenza A virus surveillance project, nasal swab samples were collected from exhibition swine at 40 selected Ohio agricultural fairs during 2012. Influenza A(H3N2) virus was isolated from swine at 10 of the fairs. According to a concurrent public health investigation, 7 of the 10 fairs were epidemiologically linked to confirmed human infections with influenza A(H3N2) variant virus. Comparison of genome sequences of the subtype H3N2 isolates recovered from humans and swine from each fair revealed nucleotide identities of >99.7%, confirming zoonotic transmission between swine and humans. All influenza A(H3N2) viruses isolated in this study, regardless of host species or fair, were >99.5% identical, indicating that 1 virus strain was widely circulating among exhibition swine in Ohio during 2012. PMID:25148572

Characterization of neuraminidase inhibitor-resistant influenza A(H1N1)pdm09 viruses isolated in four seasons during pandemic and post-pandemic periods in Japan.

PubMed

Takashita, Emi; Fujisaki, Seiichiro; Kishida, Noriko; Xu, Hong; Imai, Masaki; Tashiro, Masato; Odagiri, Takato

2013-11-01

Japan has the highest frequency of neuraminidase (NA) inhibitor use against influenza in the world. Therefore, Japan could be at high risk of the emergence and spread of NA inhibitor-resistant viruses. The aim of this study was to monitor the emergence of NA inhibitor-resistant viruses and the possibility of human-to-human transmission during four influenza seasons in Japan. To monitor antiviral-resistant A(H1N1)pdm09 viruses, we examined viruses isolated in four seasons from the 2008-2009 season through the 2011-2012 season in Japan by allelic discrimination, NA gene sequencing, and NA inhibitor susceptibility. We found that 157 (1·3%) of 12 026 A(H1N1)pdm09 isolates possessed an H275Y substitution in the NA protein that confers about 400- and 140-fold decreased susceptibility to oseltamivir and peramivir, respectively, compared with 275H wild-type viruses. The detection rate of resistant viruses increased from 1·0% during the pandemic period to 2·0% during the post-pandemic period. The highest detection rate of the resistant viruses was found in patients who were 0-9 years old. Furthermore, among the cases with resistant viruses, the percentage of no known exposure to antiviral drugs increased from 16% during the pandemic period to 44% during the post-pandemic period, implying that suspected human-to-human transmission of the resistant viruses gradually increased in the post-pandemic period. A(H1N1)pdm09 viruses resistant to oseltamivir and peramivir were sporadically detected in Japan, but they did not spread throughout the community. No viruses resistant to zanamivir and laninamivir were detected. © 2013 John Wiley & Sons Ltd.

Accumulation of Human-Adapting Mutations during Circulation of A(H1N1)pdm09 Influenza Virus in Humans in the United Kingdom

PubMed Central

Elderfield, Ruth A.; Watson, Simon J.; Godlee, Alexandra; Adamson, Walt E.; Thompson, Catherine I.; Dunning, Jake; Fernandez-Alonso, Mirian; Blumenkrantz, Deena; Hussell, Tracy; Zambon, Maria; Openshaw, Peter; Kellam, Paul

2014-01-01

ABSTRACT The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. IMPORTANCE Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes

Accumulation of human-adapting mutations during circulation of A(H1N1)pdm09 influenza virus in humans in the United Kingdom.

PubMed

Elderfield, Ruth A; Watson, Simon J; Godlee, Alexandra; Adamson, Walt E; Thompson, Catherine I; Dunning, Jake; Fernandez-Alonso, Mirian; Blumenkrantz, Deena; Hussell, Tracy; Zambon, Maria; Openshaw, Peter; Kellam, Paul; Barclay, Wendy S

2014-11-01

The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes of this variation

Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh.

PubMed

Haider, N; Sturm-Ramirez, K; Khan, S U; Rahman, M Z; Sarkar, S; Poh, M K; Shivaprasad, H L; Kalam, M A; Paul, S K; Karmakar, P C; Balish, A; Chakraborty, A; Mamun, A A; Mikolon, A B; Davis, C T; Rahman, M; Donis, R O; Heffelfinger, J D; Luby, S P; Zeidner, N

2017-02-01

Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June-July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide appropriate

Timing of Influenza A(H5N1) in Poultry and Humans and Seasonal Influenza Activity Worldwide, 2004–2013

PubMed Central

Durand, Lizette O.; Glew, Patrick; Gross, Diane; Kasper, Matthew; Trock, Susan; Kim, Inkyu K.; Bresee, Joseph S.; Donis, Ruben; Uyeki, Timothy M.; Widdowson, Marc-Alain

2015-01-01

Co-circulation of influenza A(H5N1) and seasonal influenza viruses among humans and animals could lead to co-infections, reassortment, and emergence of novel viruses with pandemic potential. We assessed the timing of subtype H5N1 outbreaks among poultry, human H5N1 cases, and human seasonal influenza in 8 countries that reported 97% of all human H5N1 cases and 90% of all poultry H5N1 outbreaks. In these countries, most outbreaks among poultry (7,001/11,331, 62%) and half of human cases (313/625, 50%) occurred during January–March. Human H5N1 cases occurred in 167 (45%) of 372 months during which outbreaks among poultry occurred, compared with 59 (10%) of 574 months that had no outbreaks among poultry. Human H5N1 cases also occurred in 59 (22%) of 267 months during seasonal influenza periods. To reduce risk for co-infection, surveillance and control of H5N1 should be enhanced during January–March, when H5N1 outbreaks typically occur and overlap with seasonal influenza virus circulation. PMID:25625302

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

PubMed

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

2012-02-24

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

Swine Influenza Virus (H1N2) Characterization and Transmission in Ferrets, Chile.

PubMed

Bravo-Vasquez, Nicolás; Karlsson, Erik A; Jimenez-Bluhm, Pedro; Meliopoulos, Victoria; Kaplan, Bryan; Marvin, Shauna; Cortez, Valerie; Freiden, Pamela; Beck, Melinda A; Hamilton-West, Christopher; Schultz-Cherry, Stacey

2017-02-01

Phylogenetic analysis of the influenza hemagglutinin gene (HA) has suggested that commercial pigs in Chile harbor unique human seasonal H1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. We isolated influenza virus (H1N2) from a swine in a backyard production farm in Central Chile and demonstrated that the HA gene was identical to that in a previous report. Its HA and neuraminidase genes were most similar to human H1 and N2 viruses from the early 1990s and internal segments were similar to influenza A(H1N1)pdm09 virus. The virus replicated efficiently in vitro and in vivo and transmitted in ferrets by respiratory droplet. Antigenically, it was distinct from other swine viruses. Hemagglutination inhibition analysis suggested that antibody titers to the swine Chilean H1N2 virus were decreased in persons born after 1990. Further studies are needed to characterize the potential risk to humans, as well as the ecology of influenza in swine in South America.

Swine Influenza Virus (H1N2) Characterization and Transmission in Ferrets, Chile

PubMed Central

Bravo-Vasquez, Nicolás; Karlsson, Erik A.; Jimenez-Bluhm, Pedro; Meliopoulos, Victoria; Kaplan, Bryan; Marvin, Shauna; Cortez, Valerie; Freiden, Pamela; Beck, Melinda A.

2017-01-01

Phylogenetic analysis of the influenza hemagglutinin gene (HA) has suggested that commercial pigs in Chile harbor unique human seasonal H1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. We isolated influenza virus (H1N2) from a swine in a backyard production farm in Central Chile and demonstrated that the HA gene was identical to that in a previous report. Its HA and neuraminidase genes were most similar to human H1 and N2 viruses from the early 1990s and internal segments were similar to influenza A(H1N1)pdm09 virus. The virus replicated efficiently in vitro and in vivo and transmitted in ferrets by respiratory droplet. Antigenically, it was distinct from other swine viruses. Hemagglutination inhibition analysis suggested that antibody titers to the swine Chilean H1N2 virus were decreased in persons born after 1990. Further studies are needed to characterize the potential risk to humans, as well as the ecology of influenza in swine in South America. PMID:28098524

Microevolution of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Humans, Egypt, 2007–2011

PubMed Central

Younan, Mary; Poh, Mee Kian; Elassal, Emad; Davis, Todd; Rivailler, Pierre; Balish, Amanda L.; Simpson, Natosha; Jones, Joyce; Deyde, Varough; Loughlin, Rosette; Perry, Ije; Gubareva, Larisa; ElBadry, Maha A.; Truelove, Shaun; Gaynor, Anne M.; Mohareb, Emad; Amin, Magdy; Cornelius, Claire; Pimentel, Guillermo; Earhart, Kenneth; Naguib, Amel; Abdelghani, Ahmed S.; Refaey, Samir; Klimov, Alexander I.; Kandeel, Amr

2013-01-01

We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007–2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift. PMID:23260983

Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh

PubMed Central

Haider, N.; Sturm-Ramirez, K.; Khan, S. U.; Rahman, M. Z.; Sarkar, S.; Poh, M. K.; Shivaprasad, H. L.; Kalam, M. A.; Paul, S. K.; Karmakar, P. C.; Balish, A.; Chakraborty, A.; Mamun, A. A.; Mikolon, A. B.; Davis, C. T.; Rahman, M.; Donis, R. O.; Heffelfinger, J. D.; Luby, S. P.; Zeidner, N.

2015-01-01

Summary Mortality in ducks and geese caused by highly pathogenic avian influenza A (H5N1) infection had not been previously identified in Bangladesh. In June–July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide

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.

PubMed

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.

Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010

PubMed Central

Baggett, Henry C.; Chittaganpitch, Malinee; Thamthitiwat, Somsak; Prapasiri, Prabda; Naorat, Sathapana; Sawatwong, Pongpun; Ditsungnoen, Darunee; Olsen, Sonja J.; Simmerman, James M.; Srisaengchai, Prasong; Chantra, Somrak; Peruski, Leonard F.; Sawanpanyalert, Pathom; Maloney, Susan A.; Akarasewi, Pasakorn

2012-01-01

Background Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010. Methods We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. Results Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). Conclusions Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children. PMID:23139802

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011

PubMed Central

Dung, Tham Chi; Dinh, Pham Ngoc; Nam, Vu Sinh; Tan, Luong Minh; Hang, Nguyen Le Khanh; Thanh, Le Thi

2014-01-01

Objective Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces. Methods We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004. Results The overall seroprevalence was 6.1% (95% confidence interval: 4.6–8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry. Discussion The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian–human transmission of influenza A(H5N1) in Viet Nam. PMID:25685601

Influenza A(H7N9) Virus Antibody Responses in Survivors 1 Year after Infection, China, 2017

PubMed Central

Ma, Mai-Juan; Liu, Cheng; Wu, Meng-Na; Zhao, Teng; Wang, Guo-Lin; Yang, Yang; Gu, Hong-Jing; Cui, Peng-Wei; Pang, Yuan-Yuan; Tan, Ya-Yun; Hang, Hui; Lin, Bao; Qin, Jiang-Chun; Cheng, Li-Ling

2018-01-01

Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016–February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for <40% of the survivors. Measured in vitro in infected mice, hemagglutination inhibition titer predicted serum protective ability. Our findings provide a helpful serologic guideline for identifying subclinical infections and for developing effective vaccines and therapeutics to counter H7N9 virus infections. PMID:29432091

Influenza A(H7N9) Virus Antibody Responses in Survivors 1 Year after Infection, China, 2017.

PubMed

Ma, Mai-Juan; Liu, Cheng; Wu, Meng-Na; Zhao, Teng; Wang, Guo-Lin; Yang, Yang; Gu, Hong-Jing; Cui, Peng-Wei; Pang, Yuan-Yuan; Tan, Ya-Yun; Hang, Hui; Lin, Bao; Qin, Jiang-Chun; Fang, Li-Qun; Cao, Wu-Chun; Cheng, Li-Ling

2018-04-01

Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016-February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for <40% of the survivors. Measured in vitro in infected mice, hemagglutination inhibition titer predicted serum protective ability. Our findings provide a helpful serologic guideline for identifying subclinical infections and for developing effective vaccines and therapeutics to counter H7N9 virus infections.

Frequent global transmission of H1N1pdm09 influenza viruses from humans to swine, 2009-2011

USDA-ARS?s Scientific Manuscript database

Using a large-scale phylogenetic approach we identify at least 52 human-to-swine transmission events of pandemic A/H1N1/09 influenza virus. These results highlight the global frequency of swine exposure to human influenza viruses and the permeability of the human-swine species barrier, even followin...

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

PubMed Central

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

2011-01-01

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

Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China.

PubMed

Qi, W; Zhou, X; Shi, W; Huang, L; Xia, W; Liu, D; Li, H; Chen, S; Lei, F; Cao, L; Wu, J; He, F; Song, W; Li, Q; Li, H; Liao, M; Liu, M

2014-06-26

Human infection with a novel influenza A(H10N8) virus was first described in China in December 2013. However, the origin and genetic diversity of this virus is still poorly understood. We performed a phylogenetic analysis and coalescent analysis of two viruses from the first case of influenza A(H10N8) (A/Jiangxi-Donghu/346-1/2013 and A/Jiangxi-Donghu/346-2/2013 and a novel A(H10N8) virus (A/chicken/Jiangxi/102/2013) isolated from a live poultry market that the patient had visited. The haemagglutinin (HA), neuraminidase (NA), PA subunit of the virus polymerase complex, nucleoprotein (NP), M and nonstructural protein (NS) genes of the three virus strains shared the same genetic origins. The origins of their HA and NA genes were similar: originally from wild birds to ducks, and then to chickens. The PA, NP, M, and NS genes were similar to those of chicken influenza A(H9N2) viruses. Coalescent analyses showed that the reassortment of these genes from A(H9N2) to A(H10N8) might have occurred at least twice. However, the PB1 and PB2 genes of the chicken A(H10N8) virus most likely originated from H7-like viruses of ducks, while those of the viruses from the case most likely stemmed from A(H9N2) viruses circulating in chickens. The oseltamivir-resistance mutation, R292K (R291K in A(H10N8) numbering) in the NA protein, occurred after four days of oseltamivir treatment. It seems that A(H10N8) viruses might have become established among poultry and their genetic diversity might be much higher than what we have observed.

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

PubMed

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

2014-04-01

We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

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