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Promoting influenza vaccination of elderly patients in primary care.

Humair JP, Buchs CR, Stalder H.

Department of Community Medicine, Geneva University Hospital, 24 Rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. Jean-Paul.Humair hcuge.ch

BACKGROUND: Though influenza is a serious health problem for elderly people, their influenza vaccination rate remains low in Switzerland. OBJECTIVE: Our aim was to assess the impact of an intervention combining multiple strategies to promote influenza vaccination of elderly patients in primary care. METHODS: We conducted a pre-/post-intervention study in a university-based primary care clinic in Geneva, Switzerland, where an annual community-wide campaign promotes influenza vaccination of people at high risk. We included 318 and 346 patients aged over 64 years attending the clinic during the last trimesters of 1995 and 1996, respectively. The intervention included: patient information by leaflets and posters, a walk-in vaccination clinic, a training workshop for physicians, record reminders and peer comparison feedback on vaccination performance. Using the computerized database, medical records and the vaccination register, we measured influenza immunization rates and relative benefits (RBs) of the intervention. RESULTS: Influenza vaccine uptake globally increased from 21.7% before the intervention to 51.7% thereafter. Among 144 patients attending in both phases, the immunization rate rose from 29.2 to 69.4% [matched RB estimate (<RB>) = 2.4; 95% confidence interval (CI) 1.9-3.0]; vaccine uptake increased particularly among all chronic patients (<RB> = 3.2; 95% CI 2.2-4.6), cardiac patients (<RB> = 3.4; 95% CI 2.1-5.4) and diabetics (<RB> = 3.3; 95% CI 1.9-5.9). For 376 patients attending in a single phase, the vaccination rate rose from 15.5 to 39.1% (adjusted RB = 2.8; 95% CI 1.8-4.4), particularly among the elderly aged 65-75 years (adjusted RB = 5.7; 95% CI 2.7-12.4). CONCLUSION: An intervention combining strategies targeting patients, physicians and care delivery significantly increased influenza vaccine uptake of elderly patients in primary care, particularly those at high risk.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110560&dopt=Abstract flu, influenza



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Restored humoral immune response to influenza vaccination in HIV-infected adults treated with highly active antiretroviral therapy.

Kroon FP, Rimmelzwaan GF, Roos MT, Osterhaus AD, Hamann D, Miedema F, van Dissel JT.

Department of Infectious Diseases, Leiden University Medical Center, The Netherlands.

BACKGROUND: Highly active antiretroviral therapy (HAART) effectively suppresses replication of HIV and is accompanied by an increase in CD4+ T lymphocytes. Whether the increase in CD4+ T lymphocytes in the blood is a reflection of a reconstitution of the immune functions is unknown. We investigated the recovery of the humoral immune response during HAART after immunization with T-cell-dependent influenza vaccine. METHODS: Forty-one men and three women infected with HIV and treated with HAART, and 15 healthy hospital staff members were immunized with trivalent influenza subunit vaccine. Antibody titres were determined by haemagglutination inhibiting assay in sera obtained before and 30 days after immunization. Lymphocyte subsets were determined in blood samples taken at the time of vaccination. RESULTS: In all HIV-infected individuals, treatment with HAART caused a median reduction of 2.3 log10 in HIV-1 load. The median increase of CD4+ T lymphocytes after initiation of HAART was 170 x 10(6)/l. The antibody response to influenza antigens was proportional to the number of memory CD4+ T lymphocytes in the blood at the time of vaccination. When a group of patients and healthy controls with approximately similar CD4+ T-lymphocyte counts were considered, the antibody titres after vaccination for influenza strain H1N1 and influenza B did not differ between patients and controls (P=0.12). Vaccination of patients with a CD4+ T-lymphocyte count of < 200 x 10(6)/l (mean 85 x 10(6)/l) before the start of HAART and with a mean of 282 x 10(6)/l CD4+ T lymphocytes at the time of vaccination as a result of HAART, demonstrated a substantial antibody response whereas patients with a CD4+ T lymphocyte count of < 200 x 10(6)/l (mean 56 x 10(6)/l) not treated with HAART (historical controls), and vaccinated with a similar influenza vaccine, failed to induce an antibody response. CONCLUSION: The present findings demonstrate a recovery of the humoral immune response to influenza antigens in HIV-infected individuals treated with HAART. This indicates that functional improvement of antigen specific CD4+ T helper cell reponses occurs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9863863&dopt=Abstract flu, influenza



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Comparison of influenza immunization rates for Oklahoma Medicare patients: 1995, 1996 and 1997.

Millar JS, Scheffler SA, Murray CK, Bratzler DW.

Oklahoma Foundation for Medical Quality, Oklahoma City, Okla. 73118-7472, USA. okpro.jmillar sdps.org

The Health Care Financing Administration has reported influenza immunization rates since 1994. The Department of Health and Human Services has set a minimum national target rate for the annual immunization of the elderly population at 60 percent, as published in Healthy People 2000. The Oklahoma Foundation for Medical Quality analyzed the Medicare claims data for Oklahoma for the 1995, 1996, and 1997 influenza seasons. Additionally, we reviewed the Behavioral Risk Factor Surveillance System influenza immunization data for 1995. Claims data for the 1997 influenza season show the immunization rate for the Medicare population of Oklahoma is 41.4 percent. The immunization rate for the African-American Medicare population was 22.3 percent for 1997, compared with 42.2 percent for the Caucasian population. The ten most populous counties in the state had a 9-percent higher rate of immunization than the other 67 counties. The Medicare population in Oklahoma is not receiving the influenza vaccination at the target rate. Especially underserved are the African-American and non-urban populations. There appear to be opportunities for improvement in the provision of the influenza vaccination for the Medicare population of Oklahoma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9864958&dopt=Abstract flu, influenza



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Characterization of avian H5N1 influenza viruses from poultry in Hong Kong.

Shortridge KF, Zhou NN, Guan Y, Gao P, Ito T, Kawaoka Y, Kodihalli S, Krauss S, Markwell D, Murti KG, Norwood M, Senne D, Sims L, Takada A, Webster RG.

Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR.

The transmission of avian H5N1 influenza viruses to 18 humans in Hong Kong in 1997 with six deaths established that avian influenza viruses can transmit to and cause lethal infection in humans. This report characterizes the antigenic and biological properties of the H5N1 influenza viruses isolated from chickens, ducks, and geese from farms and poultry markets in Hong Kong during 1997 and compares them with those of virus isolated from the index human case. Each of the H5N1 viruses from Hong Kong poultry markets that were tested were lethal in chickens, possessed polybasic amino acids at the carboxy-terminus of HA1, and by definition were highly pathogenic in poultry. The available nonpathogenic H5 influenza viruses and the pathogenic H5N1 virus from Hong Kong were analyzed with monoclonal antibodies prepared to A/chicken/Pennsylvania/1370/83 (H5N2). The analysis revealed limited antigenic drift in 15 years and established that monoclonal antibodies are useful reagents for identification and antigenic analysis of avian strains that may transmit to humans in the future. One of the monoclonal antibodies permitted separation of the H5N1 influenza viruses from poultry into two groups that correlated with the presence or absence of a carbohydrate at residue 158 adjacent to the receptor binding site on HA. The H5N1 viruses examined replicated in geese, pigs, rats, and mice, but to only a very limited extent in ducks. It is noteworthy that all infected geese shed virus and that the H5N1 viruses caused disease signs and death in a portion (3 of 16) of the geese, with evidence of systemic spread to the brain. The tropism for geese is unusual and may provide insight into the origin of these viruses. In mice, the H5N1 virus caused lethal pneumonia and spread systemically to the brain. Mice would thus provide an ideal model system for studying immune responses and pathogenesis. Transmission experiments in chickens revealed that the H5N1 viruses are spread by fecal-oral transmission rather than by aerosol, and that the viruses are inactivated by drying of feces at ambient temperature. However, infectivity is maintained for at least 4 days in wet feces at 25 degreesC. There were differences in the morphology of the H5N1 viruses isolated from birds and humans. The perpetuation of H5N1 influenza viruses in the poultry markets in Hong Kong and the transmission of these viruses to humans emphasize the importance of these markets in the epidemiology of influenza. The poultry markets are of critical importance in the perpetuation and transmission of influenza viruses to other avian species and to mammals, including humans. Copyright 1998 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9878612&dopt=Abstract flu, influenza



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Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus.

Van Der Sluijs KF, Van Elden LJ, Arens R, Nijhuis M, Schuurman R, Florquin S, Kwakkel J, Akira S, Jansen HM, Lutter R, Van Der Polls T.

Laboratory of Experimental Internal Medicine, University of Amsterdam, Amsterdam, the Netherlands.

T helper 1 driven immune responses facilitate host defence during viral infections. Because interleukin-18 (IL-18) mediates T helper 1 driven immune responses, and since mature IL-18 is up-regulated in human macrophages after influenza virus infection in vitro, it has been suggested that IL-18 plays an important role in the immune response to influenza. To determine the role of IL-18 in respiratory tract infection with influenza, IL-18 gene-deficient (IL-18(-/-)) and normal wildtype mice were intranasally inoculated with influenza A virus. Influenza resulted in an increase in constitutively expressed IL-18 in the lungs of wildtype mice. The clearance of influenza A was inhibited by IL-18, as indicated by reduced viral loads on day 8 and day 12 after infection in IL-18(-/-) mice. This enhanced viral clearance correlated with increased CD4(+) T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-gamma (IFN-gamma) levels were similar in the lungs of IL-18(-/-) mice and wildtype mice. Intracellular IFN-gamma staining revealed similar expression levels in lung-derived natural killer cells, CD4(+) and CD8(+) T cells, indicating that IFN-gamma production is IL-18-independent during influenza virus infection. Tumour necrosis factor-alpha production by CD4(+) T cells was significantly lower in IL-18(-/-) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15606801&dopt=Abstract flu, influenza



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Influenza and pneumococcal vaccine distribution and use in primary care and hospital settings in Scotland: coverage, practice and policies.

Kyaw MH, Wayne B, Chalmers J, Jones IG, Campbell H.

University of Edinburgh, Department of Public Health Services.

A survey of the coverage, distribution and the factors associated with use of influenza and pneumococcal vaccines among general practitioners (GPs) in primary care and in hospital settings was carried out in 53 general practices in Scotland taking part in the 'Continuous Morbidity Recording' (CMR) programme. The annual vaccine distribution increased substantially among 53 general practices from 1993 to 1999 and in Scotland as a whole from 1984 to 1999. From the questionnaire, overall coverage was 43% (95% CI 38-48) for influenza vaccine in the 2000-1 season and 13% (95% CI 9-16) for pneumococcal vaccine in the last 5 year period, in high-risk patients recommended for these vaccines by the Department of Health (DoH). Influenza vaccine coverage was highest in the elderly (65 years of age and above) at 62% (95% CI 59-74). Although pneumococcal vaccination is not currently recommended for all elderly, coverage of this vaccine was also higher in this group (22%, 95% CI 16-29). In the majority of patients (influenza vaccine, 98% and pneumococcal vaccine, 94%), vaccination was carried out in general practice. Only 2% of patients had received pneumococcal vaccination in a hospital setting. The level of influenza and pneumococcal vaccination varied with the level of deprivation. Most GPs considered that the responsibility for influenza and pneumococcal vaccination lay with them. Forty-five percent of GPs reported having a written policy with set target for influenza vaccination and 11% for pneumococcal vaccination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12113489&dopt=Abstract flu, influenza



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Experiences with obtaining influenza vaccination among persons in priority groups during a vaccine shortage--United States, October-November, 2004.

Centers for Disease Control and Prevention (CDC).

After the announcement that the supply of inactivated influenza vaccine available to the U.S. public for the 2004-05 influenza season would be reduced by approximately one half, the Advisory Committee on Immunization Practices (ACIP) recommended that the remaining vaccine supply should be reserved for 1) certain groups of persons at high risk for serious health problems from influenza, 2) health-care workers involved in direct patient care, and 3) close contacts of children aged <6 months. To determine what proportion of persons at increased risk for influenza complications had been vaccinated as of the day of the survey, what proportion sought vaccination but did not receive it because of the shortage, and what factors might be dissuading persons at high risk from seeking influenza vaccination, Harvard School of Public Health (HSPH), in collaboration with International Communications Research, conducted a national survey. This report summarizes the results of that survey, which indicated that approximately 63% of persons aged > or =65 years and 46% of chronically ill adults who tried to get the influenza vaccine were able to do so. More than half of adults at high risk did not try to get the influenza vaccine. Because available supplies of inactivated influenza vaccine are targeted to high-risk groups, persons in these groups should continue to pursue vaccination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15614228&dopt=Abstract flu, influenza



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Experiences with influenza-like illness and attitudes regarding influenza prevention--United States, 2003-04 influenza season.

Centers for Disease Control and Prevention (CDC).

Despite advances in medical treatment, influenza results in approximately 36,000 deaths each year in the United States. Vaccination has been a mainstay of influenza prevention, with annual vaccination recommended for adults and children at high risk; efforts to interrupt person-to-person transmission are also important. In October 2003, CDC recommended that health-care facilities implement a Universal Respiratory Hygiene Strategy, including providing masks or facial tissues in waiting rooms to persons with respiratory symptoms. To gather information on influenza-like illness (ILI) and attitudes regarding prevention of ILI (including use of vaccine and respiratory hygiene), CDC and 11 Emerging Infections Programs (EIPs) conducted a random-digit-dialed telephone survey of noninstitutionalized U.S. civilian adults in February 2004. This report summarizes the results of that survey, which determined that 43% of adults and 69% of children aged 6 months-17 years with ILI visited a health-care provider for the illness. Eight percent of adults with ILI reported having been asked by a health-care provider to wear a mask; 82% said they would wear a mask if requested. With the limited availability of influenza vaccine this season, the use of masks by persons with cough illnesses in health-care settings, a component of the Universal Respiratory Hygiene Strategy, might be a helpful and acceptable method for decreasing influenza transmission.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15614229&dopt=Abstract flu, influenza



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Updated interim influenza vaccination recommendations--2004-05 influenza season.

Centers for Disease Control and Prevention (CDC).

On October 5, 2004, CDC was notified by Chiron Corporation that none of its inactivated influenza vaccine (Fluvirin) would be available for distribution in the United States for the 2004-05 influenza season. At that time, CDC, in coordination with the Advisory Committee on Immunization Practices (ACIP), issued interim recommendations to direct available inactivated influenza vaccine to persons in certain priority groups. CDC has been working with Aventis Pasteur, Inc., to distribute the remaining supply of its inactivated influenza vaccine Fluzone so that it reaches persons in the priority groups established on October 5. In addition, on December 7, the U.S. Department of Health and Human Services announced that up to 4 million doses of the GlaxoSmithKline influenza vaccine Fluarix, authorized for use by the Food and Drug Administration under an Investigational New Drug (IND) application, would be available to help alleviate the influenza vaccine shortage this season.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15614237&dopt=Abstract flu, influenza



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[Comparison of three rapid diagnostic kits using immunochromatography for detection of influenza A virsuses]

[Article in Japanese]

Hara M, Takao S, Fukuda S, Shimazu Y, Miyazaki K.

Hara Pediatric Clinic.

In 2004, 3 new rapid influenza diagnostic kits using immunochromatography that allow type differentiation became commercially available. They are the ESPLINE Influenza A & B-N (Fujirebio Corp., Japan: ESPLINE-N hereafter), QuickVue Rapid SP influ (Quidel Corp., USA: QuickVue), and POCTEM INFLUENZA A/B (INTERNATIONAL REAGENTS Corp., Japan: POCTEM). The authors performed a prospective study that compared the usefulness among the 3 kits in 151 children with suspected influenza, who were examined within 3 days after onset, between January and March, 2004. Nasopharyngeal aspirates were collected, and viruses were isolated. The residual samples were diluted and centrifuged, and the supernatant was used for the rapid diagnosis tests. Influenza virus AH3 was isolated in 95 children and influenza B virus in 3. In the 95 children with influenza virus AH3, the sensitivity and specificity of ESPLINE-N were 100% and 100%, respectively, those of QuickVue were 99% and 91%, and those of POCTEM were 91% and 100%. The sensitivity of POCTEM was significantly lower than that of the other 2 kits (p < 0.01), and the specificity of QuickVue was significantly lower than that of the other 2 kits (p < 0.05). Examination was performed within 1 day after onset in 55 of the 95 children, including 30 who underwent examination within 6 hours after the development of fever. The body temperature was less than 38.0 degrees C in 14 of the 95 children. In all children including these children, virus detection was possible by ESPLINE-N. ESPLINE-N allowed very accurate diagnosis of influenza A using samples prepared by diluting and centrifuging nasopharyngeal aspirates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15628525&dopt=Abstract flu, influenza



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Vaccination with an acidic polymerase epitope of influenza virus elicits a potent antiviral T cell response but delayed clearance of an influenza virus challenge.

Crowe SR, Miller SC, Shenyo RM, Woodland DL.

Trudeau Institute, Saranac Lake, NY 12983, USA.

The mechanisms underlying epitope selection and the potential impact of immunodominance hierarchies on peptide-based vaccines are not well understood. Recently, we have shown that two immunodominant MHC class I-restricted epitopes, NP(366-374)/D(b) (nucleoprotein (NP)) and PA(224-233)/D(b) (acidic polymerase (PA)), which drive the CD8(+) T cell response to influenza virus infection in C57BL/6 mice, are differentially expressed on infected cells. Whereas NP appears to be strongly expressed on all infected cells, PA appears to be strongly expressed on dendritic cells but only weakly expressed on nondendritic cells. Thus, the immune response to influenza virus may involve T cells specific for epitopes, such as PA, that are poorly expressed at the site of infection. To examine the consequences of differential Ag presentation on peptide vaccination, we compared the kinetics of the T cell response and influenza virus clearance in mice vaccinated with the NP or PA peptide. Vaccination with either the NP or PA peptide resulted in accelerated and enhanced Ag-specific T cell responses at the site of infection following influenza virus challenge. These T cells were fully functional in terms of their ability to produce IFN-gamma and TNF-alpha and to mediate cytolytic activity. Despite this enhancement of the Ag-specific T cell response, PA vaccination had a detrimental effect on the clearance of influenza virus compared with unvaccinated or NP-vaccinated mice. These data suggest that differential Ag presentation impacts the efficacy of T cell responses to specific epitopes and that this needs to be considered for the development of peptide-based vaccination strategies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15634888&dopt=Abstract flu, influenza