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Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP).

Harper SA, Fukuda K, Cox NJ, Bridges CB; Advisory Committee on Immunization Practices.

Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, USA.

This report summarizes recommendations by the Advisory Committee on Immunization Practices (ACIP) for using intranasally administered, trivalent, cold-adapted, live, attenuated influenza vaccine (LAIV), which was approved for use in the United States on June 17, 2003 (FluMist trade mark, produced by MedImmune, Inc., Gaithersburg, Maryland). LAIV is currently approved for use among healthy persons (i.e., those not at high risk for complications from influenza infection) aged 5-49 years. This report includes information regarding 1) vaccine composition and mechanisms of action; 2) comparison between LAIV and trivalent inactivated influenza vaccine; 3) effectiveness and safety of LAIV; 4) transmission and stability of LAIV viruses; 5) recommendations and contraindications for using LAIV; and 6) dosage and administration of LAIV. This report supplements the 2003 ACIP recommendations regarding prevention and control of influenza (CDC. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2003;52[No. RR-8]:1-36.)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14557799&dopt=Abstract flu, influenza



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Public health and aging: influenza vaccination coverage among adults aged > or =50 years and pneumococcal vaccination coverage among adults aged > or =65 years--United States, 2002.

Centers for Disease Control and Prevention (CDC).

Vaccination of persons at risk for complications from influenza and pneumococcal disease is a key public health strategy in preventing morbidity and mortality in the United States. During the 1990-1999 influenza seasons, approximately 36,000 deaths were attributed annually to influenza infection, with approximately 90% of deaths occurring among adults aged > or =65 years. In 1998, an estimated 3,400 adults aged > or =65 years died as a result of invasive pneumococcal disease. One of the national health objectives for 2010 is to achieve 90% coverage of noninstitutionalized adults aged > or =65 years for both influenza and pneumococcal vaccinations (objective no. 14.29). In 2000, the Advisory Committee on Immunization Practices (ACIP) broadened the universal recommendations for influenza vaccination to include adults aged 50-64 years in addition to adults aged > or =65 years. To assess progress toward achieving the 2010 national health objective and implementing the ACIP recommendations, CDC analyzed data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicate that influenza and pneumococcal vaccination levels among adults aged > or =65 years and influenza vaccination levels among adults aged 50-64 years varied widely among states/areas and racial/ethnic populations. Innovative approaches are needed to increase vaccination coverage, particularly among certain populations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14561957&dopt=Abstract flu, influenza



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A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia.

Mustafa AN, Gessner BD, Ismail R, Yusoff AF, Abdullah N, Ishak I, Abdullah N, Merican MI.

Institute for Medical Research, Kuala Lumpur, Malaysia.

OBJECTIVES: To determine influenza vaccine effectiveness against clinically defined influenza-like illness among Malaysian pilgrims attending the Haj in Saudi Arabia. METHODS: During February and March 2000, the authors conducted an unmatched case-control study. Case patients were identified at one of five hotel clinics, while controls were residents of these hotels who had not attended a clinic. Results: Among 820 case patients--84% of whom had received antibiotics--and 600 controls, the adjusted vaccine effectiveness against clinic visits for influenza-like illness was 77% (95% confidence interval: 69, 83), and that against receipt of antibiotics was 66% (95% confidence interval, 54, 75). The vaccine did not prevent clinic visits for non-influenza-like upper respiratory tract illness (adjusted vaccine effectiveness, 20%; 95% confidence interval: -24, 49). CONCLUSIONS: Influenza vaccine was effective in preventing clinic visits for influenza-like illness and antibiotic use. Pilgrims traveling to the Haj in Saudi Arabia should consider influenza vaccination use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14563225&dopt=Abstract flu, influenza



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Effects of the year 2000 influenza vaccine delay on elderly patients' attitudes and behaviors.

Santibanez TA, Nowalk MP, Zimmerman RK, Bruehlman RD.

Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

BACKGROUND: A substantial delay in distribution of influenza vaccine occurred in the 2000-2001 influenza season. Our objective was to quantify the impact of this delay on immunization rates, location of receipt of immunization, and patient attitudes and beliefs about the influenza vaccine. METHODS: Inner-city and suburban medical practices that received influenza vaccine supply on-time or late in the season (late-receipt) were selected. A random sample of elderly patients from each practice completed telephone interviews. RESULTS: Of 775 eligible patients, we interviewed 72%. The odds of receiving influenza vaccine in late-receipt practices compared to on-time practices did not significantly differ in either the suburban stratum (adjusted OR = 0.9, 95% CI 0.5-1.6) or the inner-city stratum (adjusted OR = 1.5, 95% CI 0.8-2.8). Very few respondents (4%-11%) reported changes in their beliefs about the vaccine, its safety or efficacy, from previous years. More patients in late-receipt practices reported receiving influenza vaccine at locations other than their regular doctor's offices in the shortage year compared with the previous year. CONCLUSIONS: The 2000-2001 influenza vaccine delay changed vaccination location, but did not change influenza vaccination rates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14572426&dopt=Abstract flu, influenza



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[The 2002/2003 influenza season in the Netherlands and the vaccine composition for the 2003/2004 season]

[Article in Dutch]

de Jong JC, Rimmelzwaan GF, Bartelds AI, Wilbrink B, Fouchier RA, Osterhaus AD.

Erasmus Medisch Centrum, afd. Virologie, Postbus 1738, 3000 DR Rotterdam. jc.de.jong wxs.nl

As in the 2000/2001 and 2001/2002 seasons, the influenza epidemic in the 2002/2003 season started late (week 7 of 2003) and was only moderate in size. Influenza A (H3N2) and B viruses were detected in equal numbers among patients of general practitioners and these two viruses were therefore equally responsible for the epidemic. However, H3N2 viruses dominated isolates taken from hospitals. In haemagglutination-inhibition (HI) assays most of the H3N2 viruses proved highly reactive with antiserum to the vaccine-reference strain A/Moscow/10/99. This was also true for a number of isolates, including those obtained from nursing home residents, closely related to the reference strain A/Finland/170/03. However, an estimated 4% of the H3N2 isolates belonged to the variant A/Fujian/411/02 from China, which constituted the majority of the H3N2 viruses isolated in Europe in the later phase of the season. This variant reacted poorly with antiserum to A/Moscow/10/99. In H1 tests all influenza A(H1N1)-virus isolates and all B-virus isolates were closelyrelated to the corresponding vaccine-reference strains. Taking this data into consideration, the World Health Organization has advised the same vaccine composition for the 2003/2004 season as for the 2002/2003 season, namely: A/Moscow/10/99 (H3N2), A/New Caledonia/20/99 (H1N1) and B/Hong Kong/330/01. There is the possibility of a mismatch occurring between the H3N2-vaccine strain and the circulating H3N2 viruses in the coming influenza season. In March and April 2003 there was an outbreak of influenza-A (H7N7) fowl plague in the Netherlands. A special monitoring survey revealed that 91 people who had handled infected poultry became infected with the H7N7 virus. One of these later died as a result of this. None of the avian and human H7N7-virus isolates examined contained human or porcine influenza-A virus genes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14574782&dopt=Abstract flu, influenza



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The quest of influenza A viruses for new hosts.

Liu M, Guan Y, Peiris M, He S, Webby RJ, Perez D, Webster RG.

St. Jude Children's Research Hospital, Division of Virology, Department of Infectious Diseases, 332 N. Lauderdale, Memphis, TN 38105, USA.

There is increasing evidence that stable lineages of influenza viruses are being established in chickens. H9N2 viruses are established in chickens in Eurasia, and there are increasing reports of H3N2, H6N1, and H6N2 influenza viruses in chickens both in Asia and North America. Surveillance in a live poultry market in Nanchang, South Central China, reveals that influenza viruses were isolated form 1% of fecal samples taken from healthy poultry over the course of 16 months. The highest isolation rates were from chickens (1.3%) and ducks (1.2%), followed by quail (0.8%), then pigeon (0.5%). H3N6, H9N2, H2N9, and H4N6 viruses were isolated from multiple samples, while single isolates of H1N1, H3N2, and H3N3 viruses were made. Representatives of each virus subtype were experimentally inoculated into both quail and chickens. All the viruses replicated in the trachea of quail, but efficient replication in chickens was confined to 25% of the tested isolates. In quail, these viruses were shed primarily by the aerosol route, raising the possibility that quail may be the "route modulator" that changes the route of transmission of influenza viruses from fecal-oral to aerosol transmission. Thus, quail may play an important role in the natural history of influenza viruses. The pros and cons of the use of inactivated and recombinant fowl pox-influenza vaccines to control the spread of avian influenza are also evaluated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14575076&dopt=Abstract flu, influenza



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Update on molecular epidemiology of H1, H5, and H7 influenza virus infections in poultry in North America.

Suarez DL, Spackman E, Senne DA.

Southeast Poultry Research Laboratory, Agriculture Research Service, U.S. Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA.

Avian influenza is endemic in wild birds in North America, and the virus routinely has been transmitted from this reservoir to poultry. Influenza, once introduced into poultry, can become endemic within the poultry population. It may be successfully eradicated by human intervention, or the virus may fail to successfully spread on its own. In the last 5 yr, influenza virus has been isolated from poultry in the United States on numerous occasions, and, with the use of molecular epidemiology, the relationships of these different viruses can be determined. There are 15 different hemagglutinin subtypes of avian influenza viruses, but infections with virus of H5 and H7 subtypes are of the most concern because of the potential for these viruses to mutate to the highly pathogenic form of the virus. Most of the influenza isolations in the United States have been associated with the live-bird markets (LBMs) in the Northeast. This has included primarily H7N2 influenza viruses, but also H7N3, H5N2, and other subtypes. Most of the H7N2 viruses were part of a single lineage that was first observed in 1994, but new introductions of H7N2 and H7N3 were also observed. The predominant H7N2 LBM lineage of virus spread to large commercial poultry operations on at least three occasions since 1997, with the largest outbreak occurring in Virginia in 2002. The H5N2 viruses in the LBMs included viruses from domestic ducks, gamebirds, and environmental samples. Some H5N2 viruses isolated in different years and in different locations had a high degree of sequence relatedness, although the reservoir source, if it is endemic, has not been identified. Finally, an H1N2 virus, associated with a drop in egg production, was isolated from turkeys in Missouri in 1999. This virus was a complex reassortant with swine, human, and avian influenza genes that was similar to recent swine isolates from the Midwest. Additional serologic evidence suggests that flocks in other states were infected with a H1N2 virus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14575082&dopt=Abstract flu, influenza



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Development of real-time RT-PCR for the detection of avian influenza virus.

Spackman E, Senne DA, Bulaga LL, Myers TJ, Perdue ML, Garber LP, Lohman K, Daum LT, Suarez DL.

Southeast Poultry Research Laboratory, USDA-ARS, 934 College Station Road, Athens, GA 30605, USA.

A real-time reverse transcriptase/polymerase chain reaction (RRT-PCR) assay was developed using hydrolysis probes for the detection of avian influenza virus (AIV) and the H5 and H7 subtypes. The AIV specific primers and probes were directed to regions of the AIV matrix gene that are conserved among most type A influenza viruses. The H5 and H7 primers and probes are directed to H5 and H7 hemagglutinin gene regions that are conserved among North American avian influenza viruses. The sensitivity and specificity of this RRT-PCR assay was compared to virus isolation (VI) in chicken embryos with 1550 clinical swab samples from 109 live-bird markets (LBMs) in New York and New Jersey. RRT-PCR detected influenza in samples from 61 of 65 (93.8%) of the LBMs that were the sources of VI positive samples. Of the 58 markets that were positive for H7 influenza by hemagglutination inhibition assay, RRT-PCR detected H7 influenza in 56 markets (96.5%). Too few H5 positive samples were obtained to validate the H5 RRT-PCR assay in this study. Although RRT-PCR was less sensitive than VI on an individual sample basis, this study demonstrated that the AIV and H7 RRT-PCR assays are good tools for the rapid screening of flocks and LBMs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14575115&dopt=Abstract flu, influenza



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Effects of influenza vaccination on mortality among frail, community-living elderly patients: an observational study.

Landi F, Onder G, Cesari M, Gravina EM, Lattanzio F, Russo A, Bernabei R; SILVERNET-HC Study Group.

Department of Gerontology, Geriatric and Physiatric Medicine, Catholic University of the Sacred Heart, Roma, Italy. francesco_landi rm.unicatt.it

BACKGROUND AND AIMS: The annual winter outbreak of influenza is one of the major causes of morbidity and mortality among frail elderly people. The aims of the present study were to describe the prevalence of vaccination against influenza in a population of older people living in the community, and to examine the relationship between influenza vaccination and mortality. METHODS: This was an observational cohort study. We analyzed data from the Italian Silver Network Home Care project, which collected data on patients admitted to home care programs. A total of twelve Home Health Agencies participated in this project, evaluating the implementation of the Minimum Data Set for Home Care (MDS-HC) instrument. A total of 2082 patients were enrolled in the present study. The main outcome measures were prevalence of vaccination against influenza and 1-year survival according to vaccination status. RESULTS: Nearly half the subjects in our Italian sample did not receive influenza vaccination. During a mean follow-up period of 10 months from initial MDS-HC assessment, 167 vaccinated subjects (15%) died compared with 192 non-vaccinated subjects (19%) (p = 0.01). After adjusting for age, gender, and all variables significantly different between vaccinated and non-vaccinated subjects at baseline (functional and cognitive impairment, number of diseases, number of medications, depression, pressure ulcers), vaccinated subjects were less likely to die than non-vaccinated ones (RR 0.73; 95% CI 0.56-0.94). CONCLUSIONS: Vaccination against influenza has important prognostic implications for frail geriatric patients living in the community, independent of age, gender, and other clinical and functional variables. Despite extensive scientific evidence, recommendations for annual vaccination against influenza among subjects at higher risk have never been adequately implemented.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14582688&dopt=Abstract flu, influenza



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[The use of bromelain in obtaining the subviral particles of influenza A and B viruses]

[Article in Russian]

Ivanova VT, Kordiukova LV, Manykin AA, Burtseva EI, Zagorskaia IuV, Oskerko TA, Slepushkin AN.

Subviral particles of modern strains of influenza A viruses, i.e. A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), reassortant X-31 (subtype H3N2) and B/Sichuan/379/99, were obtained by using two preparations of bromeline ("Sigma Co., Catalogues' Nos. B2252 and B5144). A selective ability of bromeline B5144 was detected to the proteolytic splitting of hemagglutinin of influenza A and B viruses. An influence of enzyme B5144 produced on influenza B viruses brought about an appearance of subviral particles. As for influenza A(H1N1) virus, the above enzyme did not have any impact on it under the similar experimental conditions. An incomplete effect was noted for the influenza A(H3N2) virus with particles (with intact external coatings) being found in the reaction mixture. Enzyme B2252 was found to be effective in respect to all viruses selected for testing, however, the highest effect was noted for influenza A(H1N1) and B viruses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14598475&dopt=Abstract flu, influenza



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Analysis of the frequencies and of the memory T cell phenotypes of human CD8+ T cells specific for influenza A viruses.

He XS, Mahmood K, Maecker HT, Holmes TH, Kemble GW, Arvin AM, Greenberg HB.

Stanford University School of Medicine, Stanford, California, USA. xiaosong stanford.edu

We characterized the human CD8+ T cell response against influenza A viruses by a flow cytometry-based assay. Peripheral blood mononuclear cells (PBMCs) were incubated with inactivated influenza virus preparation, for 17 h, and were stained for intracellular interferon-gamma. Major histocompatibility complex class I-restricted memory CD8+ T cells specific for influenza antigens were detected in PBMCs from all 19 adult donors, at an average frequency of 0.39%. On average, 83% of influenza virus-specific CD8+ T cells expressed the differentiation-associated marker CD27, a percentage that is significantly higher than that of CD8+ T cells specific for pp65 of human cytomegalovirus (53%). These observations indicate that class I-restricted immunity against influenza A viruses is characterized by the persistence, after clearance of infection, of circulating antigen-specific CD8+ T cells. The different patterns of CD27 expression in influenza virus- and cytomegalovirus-specific CD8+ T cells suggest that influenza virus-specific memory and effector CD8+ T cells can be differentiated by phenotypic analysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12660922&dopt=Abstract flu, influenza