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_|SELECTED RESEARCH ARTICLES ABSTRACTS, JULY 20, 2008|_

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  • _|SELECTED RESEARCH ARTICLES ABSTRACTS, JULY 20, 2008|_

    Research Articles Abstracts.

    Contents:
    (1.1) Increasing influenza vaccination rates: the need to vaccinate throughout the entire influenza season.

    (1.2) Lessons learned: role of influenza vaccine production, distribution, supply, and demand--what it means for the provider.

    (1.3) Introduction: Expanding the influenza vaccination season.

    (1.4) Cell-based influenza vaccines : progress to date.

    (1.5) Molecular characterization and epidemiology of the highly pathogenic avian influenza H5N1 in Nigeria.

    (1.6) Increased sensitivity for detecting avian influenza-specific antibodies by a modified hemagglutination inhibition assay using horse erythrocytes.

    (1.7) Co-morbidities associated with influenza-attributed mortality, 1994-2000, Canada.

    (1.8) Avian influenza virus isolated in wild waterfowl in Argentina: Evidence of a potentially unique phylogenetic lineage in South America.

    (1.9) Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide in 2004-2008.

    (1.10) A morpholino oligomer targeting highly conserved internal ribosome entry site sequence is able to inhibit multiple species of picornavirus.

    See original abstracts at the source site. EDITED.]
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    (1.1): Am J Med. 2008 Jul;121(7 Suppl 2):S3-10.

    Increasing influenza vaccination rates: the need to vaccinate throughout the entire influenza season.

    Poland GA, Johnson DR. - Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA. poland.gregory@mayo.edu

    The burden of influenza on affected individuals and the healthcare system, as well as on society, is substantial.
    Although the supply of an effective and safe influenza vaccine was limited in previous years, advances in manufacture and distribution have alleviated such shortages.
    In most seasons, millions of doses go unused, and large numbers of unvaccinated, at-risk persons are left vulnerable to infection and its complications.
    According to insurance claims data, high-risk patients are seen by their healthcare providers on average 2.2 times between the peaks in vaccination (November) and in disease activity (February), yet they remain unvaccinated.
    The current 2- to 3-month time frame over which patients are traditionally immunized is too short to fully implement immunization recommendations and inconsistent with the duration of influenza activity.
    Both healthcare providers and patients should reevaluate their approach to influenza vaccination and recognize the need to extend the immunization time period into January and beyond.
    To increase influenza immunization rates, the Centers for Disease Control and Prevention (CDC) and other professional societies recommend an expanded immunization season, with vaccination offered at every opportunity between October and May.
    PMID: 18589066 [PubMed - in process]
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    (1.2): Am J Med. 2008 Jul;121(7 Suppl 2):S22-7.

    Lessons learned: role of influenza vaccine production, distribution, supply, and demand--what it means for the provider.

    Orenstein WA, Schaffner W. - Emory Vaccine Center, Atlanta, Georgia 30322, USA. worenst@emory.edu

    The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) has been increasing the size of the population for whom influenza vaccine is recommended to reduce the substantial and persistent annual health burden of influenza.
    Realization of current and future public health influenza immunization goals requires assuring vaccine supply will be adequate to meet demand.
    This has posed distinct challenges for the many stakeholders in the influenza vaccine program--government agencies, federal, state, and local policymakers, vaccine manufacturers and distributors, and the medical community--each of whom must make critical decisions in a constantly shifting environment.
    Factors such as the yearly changes in influenza virus strains, the complicated vaccine production and distribution process, revisions in vaccination recommendations, and changing demographics can all affect the delicate balance between supply and demand.
    While vaccine shortages and delays have been well-publicized concerns in the recent past, there has been a marked increase in supply in the past several years, with substantial growth in supply expected in the future.
    The primary issue today is to strengthen the demand for the influenza vaccine, which would in turn help ensure the continued availability of the vaccine to reduce disease burden.
    A number of strategies are discussed, including increased efforts to publicize and fully implement current CDC recommendations and to offer influenza vaccine beyond the typical vaccination season of October and November, because in the great majority of years, vaccination into January and beyond will still provide health benefits.
    PMID: 18589064 [PubMed - in process]
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    (1.3): Am J Med. 2008 Jul;121(7 Suppl 2):S1-2.

    Introduction: Expanding the influenza vaccination season.

    Schaffner W.
    PMID: 18589062 [PubMed - in process]
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    (1.4): Drugs. 2008;68(11):1483-91.

    Cell-based influenza vaccines : progress to date.

    Audsley JM, Tannock GA. - Department of Medicine, Monash University, Melbourne, Victoria, Australia.

    Human vaccines against influenza have been available for almost 60 years and, until recently, were prepared almost entirely from viruses grown in the allantoic cavity of 9- to 11-day-old embryonated chicken eggs.
    Manufacture involving eggs is not sufficiently flexible to allow vaccine supplies to be rapidly expanded, especially in the face of an impending pandemic.
    Other problems may arise from the infections of progenitor flocks that adversely affect egg supplies, and from the manufacturing process itself, where breakdowns in sterility can occur from the occasional contamination of large batches of viral allantoic fluid.
    In addition, egg-grown viruses exhibit differences in antigenicity from viruses isolated in mammalian cell lines from clinical specimens.
    These concerns and the probable need for greatly expanded manufacturing capability in the future have been brought into focus in recent years by the limited spread of H5N1 avian influenza infections to humans in several Asian countries.
    Alternative approaches involving the use of accredited anchorage-dependent and -independent preparations of the African Green monkey kidney (Vero), Madin-Darby canine kidney (MDCK) and other cell lines have been pursued by several manufacturers in recent years.
    Yields comparable with those obtained in embryonated eggs have been achieved.
    These improvements have occurred in parallel with newer technologies that allow the growth of cells in newer synthetic media that do not contain animal serum, in order to allay the concerns of regulators about the potential for spread of transmissible spongiform encephalopathies.
    PMID: 18627206 [PubMed - in process]
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    (1.5): Epidemiol Infect. 2008 Jul 17:1-8. [Epub ahead of print]

    Molecular characterization and epidemiology of the highly pathogenic avian influenza H5N1 in Nigeria.

    Fasina FO, Bisschop SP, Joannis TM, Lombin LH, Abolnik C. - National Veterinary Research Institute, Vom, Nigeria.

    SUMMARY
    Avian influenza caused infection and spread throughout Nigeria in 2006.
    Carcass samples (lung, liver, spleen, heart, trachea and intestine) from the different regions of Nigeria were processed for virus isolation.
    Infective allantoic fluids were tested for avian influenza viruses (AIV) and Newcastle disease virus using monospecific antisera.
    Thirty-five isolates were generated and characterized molecularly using the haemagglutinin gene.
    The molecular analysis indicated that different sublineages of the highly pathogenic avian influenza (HPAI) H5N1 viruses spread throughout Nigeria.
    We compared the Nigerian isolates with others from Africa and results indicated close similarities between isolates from West Africa and Sudan.
    Some of the analysed viruses showed genetic drift, and the implications of these for future epidemiology and ecology of avian influenza in Africa require further evaluation.
    The spread of primary outbreaks was strongly linked to trade (legal and illegal), live bird markets, inappropriate disposal, and poorly implemented control measures.
    No strong correlation existed between wild birds and HPAI H5N1 in Nigeria.
    PMID: 18631423 [PubMed - as supplied by publisher]
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    (1.6): J Virol Methods. 2008 Jul 14. [Epub ahead of print]

    Increased sensitivity for detecting avian influenza-specific antibodies by a modified hemagglutination inhibition assay using horse erythrocytes.

    Jia N, Wang SX, Liu YX, Zhang PH, Zuo SQ, Lin-Zhan , Dang RL, Ma YH, Zhang C, Zhang L, Lu S, Cao WC. - Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.

    The hemagglutination inhibition (HI) assay is a widely used serological method to measure the levels of protective antibody responses against influenza viruses.
    However, the traditional HI assay which uses chicken erythrocytes is not sufficiently sensitive for detecting HI antibodies specific to avian influenza viruses.
    Previously, it was demonstrated that employing an assay using horse erythrocytes was able to increase the sensitivity of HI assay.
    The current report describes further optimization of this modified HI assay.
    It was shown that this method was able to increase detection of HI activities in rabbit sera immunized with H5 HA antigens, and proved that this increased sensitivity is useful in dissecting the strain specificity of HI antibody responses.
    In addition, the modified HI assay using horse erythrocytes increased the sensitivity of detecting HI antibodies specific for three major serotypes of avian influenza viruses, H5, H7 and H9, in people who may have asymptomatic infection with avian influenza viruses.
    Based on these results, the optimized use of horse erythrocytes should be standard practice for detecting HI activities against avian influenza viruses.
    PMID: 18634828 [PubMed - as supplied by publisher]
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    (1.7): Vaccine. 2008 Jul 9. [Epub ahead of print]

    Co-morbidities associated with influenza-attributed mortality, 1994-2000, Canada.

    Schanzer DL, Langley JM, Tam TW. - Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Ontario, Canada.

    The elderly and persons with specific chronic conditions are known to face elevated morbidity and mortality risks resulting from an influenza infection, and hence are routinely recommended for annual influenza vaccination.
    However, risk-specific mortality rates have not been established.
    We estimated age-specific influenza-attributable mortality rates stratified by the presence of chronic conditions and type of residence based on deaths of persons who were admitted to hospital with a respiratory complication captured in our national database.
    The majority of patients had chronic heart or respiratory conditions (80%) and were admitted from the community (80%).
    Influenza-attributable mortality rates clearly increase with age for all risk groups.
    Our influenza-specific estimates identified higher risk ratios for chronic lung or heart disease than have been suggested by other methods.
    These estimates identify groups most in need of improved vaccines and for whom the use of additional strategies, such as immunization of household contacts or caregivers should be considered.
    PMID: 18620016 [PubMed - as supplied by publisher]
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    (1.8): Virology. 2008 Jul 14. [Epub ahead of print]

    Avian influenza virus isolated in wild waterfowl in Argentina: Evidence of a potentially unique phylogenetic lineage in South America.

    Pereda AJ, Uhart M, Perez AA, Zaccagnini ME, La Sala L, Decarre J, Goijman A, Solari L, Suarez R, Craig MI, Vagnozzi A, Rimondi A, K?nig G, Terrera MV, Kaloghlian A, Song H, Sorrell EM, Perez DR. - Instituto de Virolog?a, CICVyA, Instituto Nacional de Tecnolog?a Agropecuaria (INTA), C.C. 25, Castelar (1712), Buenos Aires, Argentina.

    Avian influenza (AI) viruses have been sporadically isolated in South America.
    The most recent reports are from an outbreak in commercial poultry in Chile in 2002 and its putative ancestor from a wild bird in Bolivia in 2001.
    Extensive surveillance in wild birds was carried out in Argentina during 2006-2007.
    Using RRT-PCR, 12 AI positive detections were made from cloacal swabs.
    One of those positive samples yielded an AI virus isolated from a wild kelp gull (Larus dominicanus) captured in the South Atlantic coastline of Argentina.
    Further characterization by nucleotide sequencing reveals that it belongs to the H13N9 subtype.
    Phylogenetic analysis of the 8 viral genes suggests that the 6 internal genes are related to the isolates from Chile and Bolivia.
    The analysis also indicates that a cluster of phylogenetically related AI viruses from South America may have evolved independently, with minimal gene exchange, from influenza viruses in other latitudes.
    The data produced from our investigations are valuable contributions to the study of AI viruses in South America.
    PMID: 18632129 [PubMed - as supplied by publisher]
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    (1.9): Antimicrob Agents Chemother. 2008 Jul 14. [Epub ahead of print]

    Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide in 2004-2008.

    Sheu TG, Deyde VM, Okomo-Adhiambo M, Garten R, Xu X, Bright R, Butler E, Wallis TR, Klimov AI, Gubareva LV. - Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, 30333, USA.

    Surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using a NA inhibition (NAI) assay.
    The IC50s of 4570 viruses collected globally from October 2004 to March 2008, were determined.
    Based on mean IC50s, A(H3N2) viruses (0.44nM) were more sensitive to oseltamivir compared to A(H1N1) viruses (0.91nM).
    The opposite trend was observed with zanamivir: 1.06nM for A(H1N1) and 2.54nM for A(H3N2).
    Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42nM) and zanamivir (3.87nM).
    To identify potentially resistant viruses (outliers), a threshold of IC50 > mean IC50 + 3SD was defined for type/subtype and drug.
    Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility.
    Molecular markers of oseltamivir-resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected from 2004-07.
    Some outliers contained previously reported mutations (e.g., I222T in B viruses), while others (e.g., R371K and H274Y in B; H274N in N2) were novel.
    The R371K B outlier exhibited high levels of resistance to both inhibitors (>100nM).
    A substantial variance at residue D151 was observed among A(H3N2) zanamivir-outliers.
    The clinical relevance of newly identified NA mutations is unknown.
    A rise in the incidence of oseltamivir-resistance in A(H1N1) viruses with the H274Y mutation was detected in the U.S. and other countries in the ongoing 2007-08 season.
    As of March 2008, the frequency of resistance in U.S. among A(H1N1) viruses was 8.6% (50/579).
    The recent increase in oseltamivir-resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors.
    PMID: 18625765 [PubMed - as supplied by publisher]
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    (1.10): Antimicrob Agents Chemother. 2008 Jun;52(6):1970-81. Epub 2008 Mar 17.

    A morpholino oligomer targeting highly conserved internal ribosome entry site sequence is able to inhibit multiple species of picornavirus.

    Stone JK, Rijnbrand R, Stein DA, Ma Y, Yang Y, Iversen PL, Andino R. - Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA.

    Members of the genera Enterovirus and Rhinovirus (family Picornaviridae) cause a wide range of human diseases.
    An established vaccine is available only for poliovirus, and no effective therapy is available for the treatment of infections caused by any pathogenic picornavirus.
    Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded DNA-like antisense agents that readily enter cells.
    A panel of PPMO was tested for their antiviral activities against various picornaviruses.
    PPMO targeting conserved internal ribosome entry site (IRES) sequence were highly active against human rhinovirus type 14, coxsackievirus type B2, and poliovirus type 1 (PV1), reducing PV1 titers by up to 6 log(10) in cell cultures.
    Comparative sequence analysis led us to design a PPMO (EnteroX) targeting 22 nucleotides of IRES sequence that are perfectly conserved across greater than 99% of all human enteroviruses and rhinoviruses.
    EnteroX reduced PV1 replication in cell culture to an extent similar to that of other IRES-specific PPMO.
    Resistant PV1 arose in cell cultures after 12 passages in the presence of EnteroX and were found to have two mutations within the EnteroX target sequence.
    Nevertheless, cPVR transgenic mice treated once daily by intraperitoneal (i.p.) injection with EnteroX before and/or after i.p. infection with 3 x 10(8) PFU (three times the 50% lethal dose) of PV1 had an approximately 80% higher rate of survival than the controls.
    The viral titer in tissues taken at day 5 postinfection showed that animals in the EnteroX-treated group averaged over 3, 4, and 5 log(10) less virus in the small intestine, spinal cord, and brain, respectively, than the amount in the control animals.
    These results suggest that EnteroX may have broad therapeutic potential against entero- and rhinoviruses.
    PMID: 18347107 [PubMed - indexed for MEDLINE]
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  • #2
    Re: _|SELECTED RESEARCH ARTICLES ABSTRACTS, JULY 20, 2008|_

    pandemic NPIs in nursing homes could be practical:

    The greatest danger in a pandemic flu outbreak is that it could spread quickly and devastate a broad swath of people across the United States before there is much of a chance to react. Now, researchers have taken a major step in determining what nonpharmaceutical interventions will work by developing mathematical models and testing scenarios that show which NPIs are appropriate for which levels of pandemic flu.


    (I'm searching for the paper....)


    ------edit1--------
    here it is:


    (PNAS loads slowly today for me)

    edit2-----



    Abstract
    It is widely believed that protecting health care facilities against outbreaks of pandemic influenza requires pharmaceutical resources such as antivirals and vaccines. However, early in a pandemic, vaccines will not likely be available and antivirals will probably be of limited supply. The containment of pandemic influenza within acute-care hospitals anywhere is problematic because of open connections with communities. However, other health care institutions, especially those providing care for the disabled, can potentially control community access. We modeled a residential care facility by using a stochastic compartmental model to address the question of whether conditions exist under which nonpharmaceutical interventions (NPIs) alone might prevent the introduction of a pandemic virus. The model projected that with currently recommended staff–visitor interactions and social distancing practices, virus introductions are inevitable in all pandemics, accompanied by rapid internal propagation. The model identified staff reentry as the critical pathway of contagion, and provided estimates of the reduction in risk required to minimize the probability of a virus introduction. By using information on latency for historical and candidate pandemic viruses, we developed NPIs that simulated notions of protective isolation for staff away from the facility that reduced the probability of bringing the pandemic infection back to the facility to levels providing protection over a large range of projected pandemic severities. The proposed form of protective isolation was evaluated for social plausibility by collaborators who operate residential facilities. It appears unavoidable that NPI combinations effective against pandemics more severe than mild imply social disruption that increases with severity.

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    ahh, it's an old hattip to pixie:

    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

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