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Influenza Pandemic

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https://www.readbyqxmd.com/read/28222682/a-statistical-method-utilizing-information-of-imported-cases-to-estimate-the-transmissibility-for-an-influenza-pandemic
#1
Ka Chun Chong, Benny Chung Ying Zee, Maggie Haitian Wang
BACKGROUND: In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections connecting the originating country with other regions. It can be a complete and timely source for estimating the basic reproduction number (R 0 ), a key indicator of disease transmissibility. METHOD: In this study, we developed a likelihood-based method using arrival times of infected cases in different countries to estimate R 0 for influenza pandemics...
February 21, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28222368/direct-and-label-free-influenza-virus-detection-based-on-multisite-binding-to-sialic-acid-receptors
#2
Yukichi Horiguchi, Tatsuro Goda, Akira Matsumoto, Hiroaki Takeuchi, Shoji Yamaoka, Yuji Miyahara
A system to discriminate human or avian influenza A remains a highly sought-after tool for prevention of influenza pandemics in humans. Selective binding of the influenza A viral hemagglutinin (HA) to specific sialic acid (SA) receptors (Neu5Acα(2-6)Gal in humans, Neu5Acα(2-3)Gal in birds) is determined by the genotype of the HA and neuraminidase (NA) segments, making it one of the key characteristics that distinguishes human or avian influenza A virus. Here we demonstrate the direct detection of whole H1N1 influenza A virus using 6'-sialyllactose (Neu5Acα(2-6)Galβ(1-4)Glc, 6SL)-immobilized gold electrodes as biosensing surfaces...
February 16, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28222123/deriving-effective-vaccine-allocation-strategies-for-pandemic-influenza-comparison-of-an-agent-based-simulation-and-a-compartmental-model
#3
Özden O Dalgıç, Osman Y Özaltın, William A Ciccotelli, Fatih S Erenay
Individuals are prioritized based on their risk profiles when allocating limited vaccine stocks during an influenza pandemic. Computationally expensive but realistic agent-based simulations and fast but stylized compartmental models are typically used to derive effective vaccine allocation strategies. A detailed comparison of these two approaches, however, is often omitted. We derive age-specific vaccine allocation strategies to mitigate a pandemic influenza outbreak in Seattle by applying derivative-free optimization to an agent-based simulation and also to a compartmental model...
2017: PloS One
https://www.readbyqxmd.com/read/28219461/evaluating-the-impact-of-pharmacies-on-pandemic-influenza-vaccine-administration
#4
Joy Schwerzmann, Samuel B Graitcer, Barbara Jester, David Krahl, Daniel Jernigan, Carolyn B Bridges, Joseph Miller
OBJECTIVES: The objective of this study was to quantify the potential retail pharmacy vaccine administration capacity and its possible impact on pandemic influenza vaccine uptake. METHODS: We developed a discrete event simulation model by use of ExtendSim software (Imagine That Inc, San Jose, CA) to forecast the potential effect of retail pharmacy vaccine administration on total weekly vaccine administration and the time needed to reach 80% vaccination coverage with a single dose of vaccine per person...
February 21, 2017: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/28216380/a-population-based-analysis-of-predictors-of-influenza-vaccination-uptake-in-pregnant-women-the-effect-of-gestational-and-calendar-time
#5
Luz Maria Vilca, Aman Verma, David Buckeridge, Magda Campins
Pregnant women are vaccinated against influenza less frequently than other high-risk groups. To design effective vaccination strategies, we must understand how decisions regarding vaccination may vary by trimester and over vaccination campaigns. We used a Cox model indexed by calendar time to estimate the effect of gestational trimester and other factors on vaccination uptake in a large cohort of pregnant women in Catalonia (Spain) during 2008-09 to 2012-13 influenza vaccination campaigns. We analyzed 247,316 pregnancies...
February 16, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28216325/universal-influenza-virus-vaccines-and-therapeutic-antibodies
#6
REVIEW
Raffael Nachbagauer, Florian Krammer
BACKGROUND: Current influenza virus vaccines are effective when well matched to the circulating strains. Unfortunately, antigenic drift and the high diversity of potential emerging zoonotic and pandemic viruses make it difficult to select the right strains for vaccine production. This problem causes vaccine mismatches which lead to sharp drops in vaccine effectiveness and long response times in case of novel pandemic viruses. AIMS: To provide an overview of universal influenza virus vaccines and therapeutic antibodies in pre-clinical and clinical development...
February 12, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28215994/safe-recombinant-outer-membrane-vesicles-that-display-m2e-elicit-heterologous-influenza-protection
#7
Hannah C Watkins, C Garrett Rappazzo, Jaclyn S Higgins, Xiangjie Sun, Nicole Brock, Annie Chau, Aditya Misra, Joseph P B Cannizzo, Michael R King, Taronna R Maines, Cynthia A Leifer, Gary R Whittaker, Matthew P DeLisa, David Putnam
Recombinant, Escherichia coli-derived outer membrane vesicles (rOMVs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. One drawback to rOMVs is their lipopolysaccharide (LPS) content, limiting their translatability to the clinic due to potential adverse effects. Here, we explore a unique rOMV construct with structurally remodeled lipids containing only the lipid IVa portion of LPS, which does not stimulate human TLR4. The rOMVs are derived from a genetically engineered B strain of E...
February 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28212428/a-novel-hemagglutinin-protein-produced-in-bacteria-protects-chickens-against-h5n1-highly-pathogenic-avian-influenza-viruses-by-inducing-h5-subtype-specific-neutralizing-antibodies
#8
Violetta Sączyńska, Agnieszka Romanik, Katarzyna Florys, Violetta Cecuda-Adamczewska, Małgorzata Kęsik-Brodacka, Krzysztof Śmietanka, Monika Olszewska, Katarzyna Domańska-Blicharz, Zenon Minta, Bogusław Szewczyk, Grażyna Płucienniczak, Andrzej Płucienniczak
The highly pathogenic (HP) H5N1 avian influenza viruses (AIVs) cause a mortality rate of up to 100% in infected chickens and pose a permanent pandemic threat. Attempts to obtain effective vaccines against H5N1 HPAIVs have focused on hemagglutinin (HA), an immunodominant viral antigen capable of eliciting neutralizing antibodies. The vast majority of vaccine projects have been performed using eukaryotic expression systems. In contrast, we used a bacterial expression system to produce vaccine HA protein (bacterial HA) according to our own design...
2017: PloS One
https://www.readbyqxmd.com/read/28210631/immunogenicity-and-cross-protection-in-mice-afforded-by-pandemic-h1n1-live-attenuated-influenza-vaccine-containing-wild-type-nucleoprotein
#9
Andrey Rekstin, Irina Isakova-Sivak, Galina Petukhova, Daniil Korenkov, Igor Losev, Tatiana Smolonogina, Tatiana Tretiak, Svetlana Donina, Svetlana Shcherbik, Tatiana Bousse, Larisa Rudenko
Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28207989/predictors-of-influenza-a-molecular-viral-shedding-in-hutterites-communities
#10
Biao Wang, Margaret L Russell, Kevin Fonseca, David J D Earn, Gregory Horsman, Paul Van Caeseele, Khami Chokani, Mark Vooght, Lorne Babiuk, Stephen D Walter, Mark Loeb
BACKGROUND: Patterns of influenza molecular viral shedding following influenza infection have been well established; predictors of viral shedding however remain uncertain. OBJECTIVES: We sought to determine factors associated with peak molecular viral load, duration of shedding, and viral area under curve (AUC) in children and adult Hutterite colony members with laboratory confirmed influenza. METHODS: A cohort study was conducted in Hutterite colonies in Alberta, Canada...
February 16, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28207898/distinct-susceptibility-and-applicability-of-mdck-derivatives-for-influenza-virus-research
#11
Shih-Chao Lin, Matthew A Kappes, Mei-Chun Chen, Chi-Chen Lin, Tony T Wang
Madin-Darby Canine Kidney (MDCK) cells are widely utilized as a substrate for influenza virus isolation and propagation due to the high yields of virus. Here we compared the conventional MDCK cell line, MDCK-SIAT1 and MDCK-London for viral production, cell survival, and suitability in testing antivirals using six influenza strains including two H1N1 (pandemic and epidemic strains), three H3N2 and one influenza B strain. Overall our results suggest that MDCK-London cell line is superior for virus culturing and quantification, and hence an ideal platform to evaluate antiviral drug efficacy against multiple strains of influenza...
2017: PloS One
https://www.readbyqxmd.com/read/28206909/a-highly-pathogenic-avian-derived-influenza-virus-h5n1-with-2009-pandemic-h1n1-internal-genes-demonstrates-increased-replication-and-transmission-in-pigs
#12
Eugenio J Abente, Pravina Kitikoon, Kelly M Lager, Phillip C Gauger, Tavis K Anderson, Amy L Vincent
This study investigated the pathogenicity and transmissibility of a reverse-genetics-derived highly pathogenic avian influenza (HPAI) H5N1 lineage influenza A virus that was isolated from a human, A/Iraq/755/06. We also examined surface gene reassortant viruses composed of the haemagglutinin and neuraminidase from A/Iraq/755/06 and the internal genes of a 2009 pandemic H1N1 virus, A/New York/18/2009 (2Iraq/06 : 6NY/09 H5N1), and haemagglutinin and neuraminidase from A/New York/18/2009 with the internal genes of A/Iraq/755/06 (2NY/09 : 6Iraq/06 H1N1)...
January 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28204554/safety-and-effectiveness-of-neuraminidase-inhibitors-in-situations-of-pandemic-and-or-novel-variant-influenza-a-systematic-review-of-the-literature-2009-15
#13
C Boikos, C Caya, M K Doll, H Kraicer-Melamed, M Dolph, G Delisle, N Winters, G Gore, C Quach
No abstract text is available yet for this article.
February 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28202753/mutation-of-the-2-nd-sialic-acid-binding-site-resulting-in-reduced-neuraminidase-activity-preceded-emergence-of-h7n9-influenza-a-virus
#14
Meiling Dai, Ryan McBride, Jos C F M Dortmans, Wenjie Peng, Mark J G Bakkers, Raoul J de Groot, Frank J M van Kuppeveld, James C Paulson, Erik de Vries, Cornelis A M de Haan
The emergence of novel influenza A virus (IAV) H7N9 since 2013 has caused concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of the H7 protein of a human isolate revealed modestly increased binding to α2,6 sialosides and reduced, but still dominant, binding to α2,3-linked sialic acids (SIAs) compared to a closely related avian H7N9 virus from 2008. Here we show that the corresponding N9 neuraminidases display equal enzymatic activity on a soluble monovalent substrate and similar substrate specificity on a glycan array...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28198028/proinflammatory-chemokines-are-major-mediators-of-exuberant-immune-response-associated-with-influenza-a-h1n1-pdm09-virus-infection
#15
Maria Thomas, Reeta Subramaniam Mani, Mariamma Philip, Ranjeeta Adhikary, Sangeeta Joshi, Srigiri S Revadi, Shashidhar Buggi, Anita Desai, Ravi Vasanthapuram
In India, the case fatality ratio of the pandemic A (H1N1) pdm09 influenza was relatively higher when compared to seasonal influenza A infection. Hypercytokinemia or "cytokine storm" has been previously implicated in the pathogenesis of other influenza viruses. The present study was undertaken to compare the cytokine profiles of A (H1N1) pdm09 influenza and seasonal H3 infection in Indian population and to correlate the findings with disease severity. Plasma levels of 18 cytokines/chemokines were measured by flow-cytometry using a bead based assay in patients infected with A (H1N1) pdm09 virus (n = 96) and Influenza A seasonal H3 virus (n = 30) categorised into mild, moderate and severe groups along with healthy controls (n = 36)...
February 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28197323/novel-2-substituted-7-azaindole-and-7-azaindazole-analogues-as-potential-antiviral-agents-for-the-treatment-of-influenza
#16
Upul K Bandarage, Michael P Clark, Emanuele Perola, Huai Gao, Marc D Jacobs, Alice Tsai, Jeffery Gillespie, Joseph M Kennedy, François Maltais, Mark W Ledeboer, Ioana Davies, Wenxin Gu, Randal A Byrn, Kwame Nti Addae, Hamilton Bennett, Joshua R Leeman, Steven M Jones, Colleen O'Brien, Christine Memmott, Youssef Bennani, Paul S Charifson
JNJ-63623872 (2) is a first-in-class, orally bioavailable compound that offers significant potential for the treatment of pandemic and seasonal influenza. Early lead optimization efforts in our 7-azaindole series focused on 1,3-diaminocyclohexyl amide and urea substitutions on the pyrimidine-7-azaindole motif. In this work, we explored two strategies to eliminate observed aldehyde oxidase (AO)-mediated metabolism at the 2-position of these 7-azaindole analogues. Substitution at the 2-position of the azaindole ring generated somewhat less potent analogues, but reduced AO-mediated metabolism...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28197322/discovery-of-novel-orally-bioavailable-%C3%AE-amino-acid-azaindole-inhibitors-of-influenza-pb2
#17
Luc J Farmer, Michael P Clark, Michael J Boyd, Emanuele Perola, Steven M Jones, Alice Tsai, Marc D Jacobs, Upul K Bandarage, Mark W Ledeboer, Tiansheng Wang, Hongbo Deng, Brian Ledford, Wenxin Gu, John P Duffy, Randy S Bethiel, Dean Shannon, Randal A Byrn, Joshua R Leeman, Rene Rijnbrand, Hamilton B Bennett, Colleen O'Brien, Christine Memmott, Kwame Nti-Addae, Youssef L Bennani, Paul S Charifson
In our efforts to develop novel small-molecule inhibitors for the treatment of influenza, we utilized molecular modeling and the X-ray crystal structure of the PB2 subunit of the influenza polymerase to optimize a series of acyclic β-amino acid inhibitors, highlighted by compound 4. Compound 4 showed good oral exposure in both rat and mouse. More importantly, it showed strong potency versus multiple influenza-A strains, including pandemic 2009 H1N1 and avian H5N1 strains and showed a strong efficacy profile in a mouse influenza model even when treatment was initiated 48 h after infection...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28193481/epigenetic-and-transcriptomic-regulation-of-lung-repair-during-recovery-from-influenza-infection
#18
Derek A Pociask, Keven M Robinson, Kong Chen, Kevin J McHugh, Michelle E Clay, Grace T Huang, Panayiotis V Benos, Yvonne M W Janssen-Heininger, Jay K Kolls, Vikas Anathy, John F Alcorn
Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection...
February 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28192418/defining-the-antibody-cross-reactome-directed-against-the-influenza-virus-surface-glycoproteins
#19
Raffael Nachbagauer, Angela Choi, Ariana Hirsh, Irina Margine, Sayaka Iida, Aldo Barrera, Marcela Ferres, Randy A Albrecht, Adolfo García-Sastre, Nicole M Bouvier, Kimihito Ito, Rafael A Medina, Peter Palese, Florian Krammer
Infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. To assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent H1N1 or H3N2 subtypes of influenza virus. We measured antibody responses by ELISA of an extensive panel of recombinant glycoproteins representing the viral diversity in nature. Guinea pigs developed high titers of broadly cross-reactive antibodies; mice and ferrets exhibited narrower humoral responses...
February 13, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28188897/unmasking-survival-biases-in-observational-treatment-studies-of-influenza-patients
#20
Martin Wolkewitz, Martin Schumacher
BACKGROUND: Several observational studies reported that Oseltamivir (Tamiflu) reduced mortality in infected and hospitalized patients. Due to the restriction of observation to hospital stay and time-dependent treatment assignment, such findings were prone to common types of survival bias (length, time-dependent and competing risk bias). METHODS: British hospital data from the FLU-CIN study group were used which included 1391 patients with confirmed pandemic influenza A/H1N1 2009 infection...
February 7, 2017: Journal of Clinical Epidemiology
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