Influenza ( Flu ) immunization and mortality among diabetic Medicare beneficiaries in West Virginia.

This study estimated the increased risk of death among Medicare beneficiaries with diabetes in West Virginia who do not receive influenza ( flu ) beneficiaries with diabetes. Medicare beneficiaries with diabetes who did not have claims for influenza ( flu ) vaccination had approximately a 1.7-fold risk of death during a subsequent influenza ( flu ) season, compared with those with a vaccination. This risk was observed in all age and sex subgroups, and was changed very little by adjustment for comorbidity. The adjusted odds ratio for death in the vaccinated group (compared with the unvaccinated group) during the 1996-97 influenza ( flu ) season was 0.639 (95% confidence interval 0.565-0.722); in 1997-98 it was 0.601 (95% confidence interval 0.527-0.687). West Virginia Medicare beneficiaries with diabetes are at a significantly increased risk of death during an influenza ( flu ) season if they do not have prior claims for influenza ( flu ) vaccination.

Diagnostic methods applied to analysis of an outbreak of equine influenza ( flu ) in a riding school in which vaccine failure occurred.

An outbreak of equine influenza ( flu ) H3N8 in a riding school is described retrospectively with emphasis on diagnosis and putative vaccine failure. In March 1995 an outbreak of equine influenza ( flu ) occurred among 11 horses in a riding school, where most horses had received basic primary immunizations and several booster vaccinations against influenza ( flu ). Six of the 11 diseased horses had received their last booster vaccination within 5 months of the outbreak. Nevertheless, the influenza ( flu ) infection spread rapidly and clinical manifestations were prominent with frequent, harsh, dry coughing often accompanied by high fever.Nasal swabs were taken from 11 diseased horses. Influenza ( Flu ) A virus of the equine H3N8 (equi-2) subtype was isolated from five nasal swab extracts. Stored nasal swab extracts were also retrospectively investigated in two different enzyme immunoassays designed to detect the type-specific conserved nucleoprotein of influenza ( flu ) A viruses, and in a single-tube reverse transcription-PCR (RT-PCR) using a set of primers based on highly conserved regions of the matrix gene of influenza ( flu ) A viruses. Five nasal swab extracts were found positive in a DAS-ELISA and seven in the Directigen((R)) Flu A (DFA) assay, respectively. Two nasal swab extracts from which virus was isolated did not give a positive result in the DAS-ELISA, and one of these also did not give a positive result in the DFA assay. Nine nasal swab extracts were found positive by RT-PCR. Moreover, all virus isolation and/or ELISA positive nasal swab extracts were confirmed by RT-PCR. Three nasal swab extracts were negative by virus isolation, PCR and ELISA. A significant rise in HI titre against influenza ( flu ) A/eq/Miami/63 (H3N8) virus was detected in seven of the nine paired sera available.In acute phase serum samples from 10 horses, SRH antibody levels varied widely. However, some horses with high, or at least putatively clinically protective SRH antibody levels, showed clinical signs and infection was confirmed. Antigenic analysis of two isolates showed that A/eq/Holland/1/95 (H3N8) and A/eq/Holland/2/95 (H3N8) cluster with the UK isolate Osgodsby/92, the Swedish isolate Borlange/91 and some other European isolates, with H/2/95 identical in reactivity to Borlange/91 and H/1/95 more similar in reactivity to Osgodsby/92 than H/2/95. Nucleotide and deduced amino-acid sequences showed large differences of both isolates as compared with Miami/63, Fontainebleau/79 and Kentucky/81, the influenza ( flu ) A H3N8 subtype strains incorporated in the vaccines used in this riding school. The role of antigenic drift in vaccine breakdown is discussed in the light of evidence for vaccine breakdown in the UK in 1989, Sweden in 1991 and in the USA since 1991.

Influenza ( Flu ) A virus infection inhibits the efficient recruitment of Th2 cells into the airways and the development of airway eosinophilia.

Most infections with respiratory viruses induce Th1 responses characterized by the generation of Th1 and CD8(+) T cells secreting IFN-gamma, which in turn have been shown to inhibit the development of Th2 cells. Therefore, it could be expected that respiratory viral infections mediate protection against asthma. However, the opposite seems to be true, because viral infections are often associated with the exacerbation of asthma. For this reason, we investigated what effect an influenza ( flu ) A (flu) virus infection has on the development of asthma. We found that flu infection 1, 3, 6, or 9 wk before allergen airway challenge resulted in a strong suppression of allergen-induced airway eosinophilia. This effect was associated with strongly reduced numbers of Th2 cells in the airways and was not observed in IFN-gamma- or IL-12 p35-deficient mice. Mice infected with flu virus and immunized with OVA showed decreased IL-5 and increased IFN-gamma, eotaxin/CC chemokine ligand (CCL)11, RANTES/CCL5, and monocyte chemoattractant protein-1/CCL2 levels in the bronchoalveolar lavage fluid, and increased airway hyperreactivity compared with OVA-immunized mice. These results suggest that the flu virus infection reduced airway eosinophilia by inducing Th1 responses, which lead to the inefficient recruitment of Th2 cells into the airways. However, OVA-specific IgE and IgG1 serum levels, blood eosinophilia, and goblet cell metaplasia in the lung were not reduced by the flu infection. Flu virus infection also directly induced AHR and goblet cell metaplasia. Taken together, our results show that flu virus infections can induce, exacerbate, and suppress features of asthmatic disease in mice.

Effects of immunoglobulin upon murine myocarditis caused by influenza ( flu ) A virus: superiority of intact type to F(ab')2 type.

Influenza ( Flu ) viruses play the largest role in the worldwide epidemiology of infectious diseases. Management of some inflammatory disease (eg, Kawasaki disease) with immunoglobulin has been demonstrated to be effective. We examined the effects of intact type and F(ab')2 type of immunoglobulin preparations upon murine influenza ( flu ) A virus myocarditis in mice. In vitro study showed that intact type and F(ab')2 type of immunoglobulin preparations exhibit antiviral activities against many substrains of influenza ( flu ) virus and other cardiotropic viruses. Dose-dependent suppression of an influenza ( flu ) A virus (NWS) was demonstrated by management with both intact immunoglobulin and F(ab')2 fragments of immunoglobulin. The dose inhibiting 50% of plaques was the same between intact type and F(ab')2 type (both 0.0002 mg/dl). Intact immunoglobulin, but not F(ab')2 fragments of immunoglobulin, suppressed serum macrophage inflammatory protein-2 (MIP-2) productions in influenza ( flu ) A virus-infected macrophages in vitro, which is a murine counterpart of interleukin-8. This suppression of MIP-2 production by intact immunoglobulin treatment was blocked by a specific Fc receptor (Fc gamma III/II receptor) antibody pretreatment. Intact immunoglobulin or F(ab')2 fragments of immunoglobulin were administered to virus-inoculated A/J mice intraperitoneally daily, starting simultaneously with virus inoculation (Experiment I) and 2 days after the virus inoculation (Experiment II), until 10 days after virus inoculation. In Experiment I, survival was higher in treated than in control mice; intact type and F(ab')2 type immunoglobulins administration completely suppressed the development of myocarditis. In Experiment II, survival rate was significantly higher and myocarditis was less severe in intact immunoglobulin-treated mice, but not in F(ab')2 fragments-treated mice compared with untreated mice. Serum neutralizing antibody titers in treated mice were significantly higher compared with untreated mice in Experiments I and II. In addition, serum MIP-2 concentrations in intact immunoglobulin-treated mice, but not in F(ab')2 fragments-treated mice, were lower compared with untreated mice in Experiment II. Immunoglobulin therapy suppresses influenza ( flu ) A virus myocarditis by increasing neutralizing antibody titers and the suppression of myocardial virus activities. From the standpoint of suppression of MIP-2 concentrations, intact type is superior to F(ab')2 type. Thus, immunoglobulin treatment may be promising for prevention of influenza ( flu ) virus myocarditis.

Rapid diagnosis of influenza ( flu ) type A infection: comparison of shell-vial culture, directigen flu-A and enzyme-linked immunosorbent assay.

Two direct antigen detection methods (Directigen FLU A, Becton-Dickinson, Cokeysville, Md. and Influenza ( Flu ) A virus ELISA Antigen detection kit, Alpha Biotech, Milano) were compared with isolation by shell-vial cultures for rapid diagnosis of influenza ( flu ) type A virus infection. The three methods were performed using a reference viral suspension consisting of a clinical isolate of influenza ( flu ) type A virus as well as 41 nasopharyngeal aspirates collected from patients with influenza ( flu ) symptoms. Influenza ( Flu ) type A virus was recovered from 14 specimens by shell-vials. Ten specimens were positive by Directigen FLU A and 7 by ELISA antigen detection kit. When performed on clinical samples the sensitivity of Directigen FLU A and ELISA was 64.2% and 42.8%, respectively. The limit of sensitivity of the shell-vials, performed on a virus stock suspension titrated by haemagglutinin activity, was 0.06-0.03 HA units/ml at 24 hours or 72 hours after inoculation. Directigen FLU A and ELISA detected as positive a virus stock suspension containing 0.25 HA units/ml and 1 HA units/ml, respectively.

Clinical effectiveness of conventional influenza ( flu ) vaccination in asthmatic children.

Influenza ( Flu ) immunization rates among young asthmatics remain unsatisfactory due to persistent concern about the impact of influenza ( flu ) and the benefits of the vaccine. We assessed the effectiveness of the conventional inactivated trivalent sub-unit influenza ( flu ) vaccine in reducing acute respiratory disease in asthmatic children. We conducted a two-season retrospective cohort study covering the 1995-6 and 1996-7 influenza ( flu ) outbreaks in 22 computerized primary care practices in The Netherlands. In total, 349 patients aged between 0 and 12 years meeting clinical asthma-criteria were included; 14 children were lost to follow-up in the second season. The occurrence of physician-diagnosed acute respiratory disease episodes including influenza ( flu )-like illness, pneumonia. bronchitis, bronchiolitis, asthma exacerbation and acute otitis media in vaccinated and unvaccinated children were compared after adjustments for age, prior health care and medication use. The occurrence of acute respiratory disease in unvaccinated children was 28% and 24% in the 1995-6 and 1996-7 season, respectively, and was highest in children under 6 years of age (43%). The overall pooled clinical vaccine effectiveness was 27% (95% confidence interval -7 to 51%, P = 0.11) after adjustments. A statistically higher vaccine protectiveness of 55% (95% CI 20-75%, P = 0.01) was observed among asthmatics under 6 years of age compared with -5% in older children (95% CI -81 to 39%). The occurrence of acute respiratory disease among asthmatic children during influenza ( flu ) epidemics is very high, notably in the youngest. Influenza ( Flu ) vaccination may reduce morbidity in asthmatic infants and pre-school children. However, larger, preferably experimental, studies are needed to establish the benefits of vaccination, notably in older asthmatic children.

Thujaplicin-copper chelates inhibit replication of human influenza ( flu ) viruses.

The effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza ( flu ) virus-induced apoptosis in Madin-Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza ( flu ) A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 microM. These results indicate that the copper chelates inhibit influenza ( flu ) virus-induced apoptosis and that the inhibitory effects may be independent of influenza ( flu ) virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2 4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza ( flu ) virus-induced apoptosis. In this study, we demonstrated that thujaplicin-copper chelates inhibit influenza ( flu ) virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.

A review of influenza ( flu ) immunisation in Lothian.

OBJECTIVES. To assess the influence of the Chief Medical Officer's annual guidelines on influenza ( flu ) immunisation and to estimate vaccine uptake particularly of those resident in long-stay residential facilities and of other recommended at-risk groups. DESIGN. Postal questionnaires. SETTING. Lothian, Scotland (population 750,000). SUBJECTS. All consultants caring for patients in long stay National Health Service facilities; a random sample of all general practitioners (GP's) in Lothian; managers/charge nurses of all local authority, private and voluntary long stay facilities in Lothian and continuing care facilities in the National Health Service including adults and children. MAIN OUTCOME MEASURES. Number (%) of general practitioners offering influenza ( flu ) vaccine to at-risk groups as defined in the Chief Medical Officer's guidelines; number (%) of hospital consultants caring for long-stay patients in hospital in Lothian who offer influenza ( flu ) vaccine to the same at-risk groups; percentage of long-stay residents/patients who received influenza ( flu ) vaccine in 1992-3. RESULTS. Seventy nine (75%) GPs said they offered influenza ( flu ) vaccine to all at-risk groups; 15 (14%) GPs said they did not care for patients in long-stay facilities but offered vaccine to the other at-risk groups; 12 (11%) GPs who did have long-stay residents on their list, offered vaccine to some of them only and to all other at-risk groups; 14 (56%) hospital consultants did not offer influenza ( flu ) vaccine to long-stay patients; 10 (40%) immunised only those at risk from chronic medical conditions if their quality of life was good; 1 (4%) consultant offered vaccine to all long-stay patients. In the winter of 1992-3, the mean proportion of residents immunised in private nursing homes was 65%, in residential homes 68.5%, and in long-stay National Health Service wards 4.5%. GPs commented that annual publicity was confusing for the public, vaccine was not available at the right time and there was uncertainty on the efficacy of the vaccine. Hospital consultants were reluctant to immunise patients with a poor quality of life or who were demented and unable to give consent. CONCLUSIONS. A large majority of GPs followed official advice and offered influenza ( flu ) vaccine to long-stay patients and other at risk groups. Hospital consultants offered influenza ( flu ) vaccine only to a small proportion of their long-stay patients, primarily those with a good quality of life.

The physician's office: can it influence adult immunization rates

OBJECTIVE: To determine which office and patient factors affect adult influenza ( flu ) and pneumococcal vaccination rates. STUDY DESIGN: Patient interviews and self-administered surveys of office managers. PATIENTS AND METHODS: In a 2-stage random cluster sample, 22 practices in 4 strata (Veterans' Affairs, rural, urban/suburban, and inner city) and 15 patients per physician in each practice (n = 946) were selected. Office managers completed a questionnaire regarding office practices and logistics affecting immunizations. Data were examined using chi2 and regression analyses without and with patient factors in the models. RESULTS: Practice factors significantly related to influenza ( flu ) vaccination status were stratum (VA OR = 2.04; 95% CI = 1.18, 3.53; P < .05 vs inner-city), time allotted for acute care visits (16-20 min vs 10-15 min OR = 2.49; 95% CI = 1.68, 3.09; P < .001), the practice not having a source of free vaccines (OR = .43; 95% CI = .3, .62; P < .001), and the interaction between being an urban/suburban practice and having a source of free flu vaccines (OR = 4.0; 95% CI = 2.63, 6.09; P < .001). Practice factors related to pneumococcal vaccination status were the number of immunization promotion activities (> or = 3 vs 0-2 OR = 1.97; 95% CI = 1.33, 2.94; P = .002) and the time allotted for acute care visits (16-20 min vs 10-15 min OR = 1.94; 95% CI = 1.18, 3.19; P = .011). When practice and patient factors were combined in the analyses, patient factors were more important. CONCLUSION: Although patient factors are more important than practice factors, practices that allot more time for acute care visits and use more immunization promotion activities have higher vaccination rates.

Molecular evolution of H6 influenza ( flu ) viruses from poultry in Southeastern China: prevalence of H6N1 influenza ( flu ) viruses possessing seven A/Hong Kong/156/97 (H5N1)-like genes in poultry.

The A/teal/Hong Kong/W312/97 (H6N1) influenza ( flu ) virus and the human H5N1 and H9N2 influenza ( flu ) viruses possess similar genes encoding internal proteins, suggesting that H6N1 viruses could become novel human pathogens. The molecular epidemiology and evolution of H6 influenza ( flu ) viruses were characterized by antigenic and genetic analyses of 29 H6 influenza ( flu ) viruses isolated from 1975 to 1981 and 1997 to 2000. Two distinct groups were identified on the basis of their antigenic characteristics. Phylogenetic analysis revealed that all H6N1 viruses isolated from terrestrial poultry in 1999 and 2000 are closely related to A/teal/Hong Kong/W312/97 (H6N1), and the nucleotide sequences of these viruses and of A/Hong Kong/156/97 (H5N1) were more than 96% homologous. The hemagglutinin (HA) of the 1999 and 2000 terrestrial viruses does not have multiple basic amino acids at the site of cleavage of HA1 to HA2; however, a unique insertion of aspartic acid in HA1 between positions 144 and 145 (H3 numbering) was found. The neuraminidase of these terrestrial H6N1 viruses has a deletion of 19 amino acids characteristic of A/Hong Kong/156/97 (H5N1). Evolutionary analysis suggested that these H6N1 viruses coevolved with A/quail/Hong Kong/G1/97-like H9N2 viruses and became more adapted to terrestrial poultry. These terrestrial 1999 and 2000 A/teal/Hong Kong/W312/97 (H6N1)-like viruses, along with the H9N2 viruses, could have been involved in the genesis of the pathogenic H5N1 influenza ( flu ) viruses of 1997. The presence of H6N1 viruses in poultry markets in Hong Kong that possess seven of the eight genes of the A/Hong Kong/156/97 (H5N1) virus raises the following fundamental questions relevant to influenza ( flu ) pandemic preparedness: could the pathogenic H5N1 virus reemerge and could the H6N1 viruses directly cross the species barrier to mammals?