flu
[International cooperation on problems in acute respiratory viral infections]

[Article in Czech]

Tumova B.

Narodni referencni laborator pro chripku, Statni zdravotni ustav, Praha.

The annual occurrence of acute respiratory infections (ARI) of viral origin incl. influenza, the serious character of influenza epidemics and pandemics were the reason why a network of 110 national influenza centres and four international collaborating centres were created. This worldwide surveillance programme is coordinated by WHO. With advancing integration of Europe scientific groups were created which implement this programme in Europe. EUROSENTINEL analyzes the notified morbidity from influenza and ARI in eight participating countries, EUROGEIG concentrates on the programme of influenza prevention and the preparation of anti-pandemic provisions, EUROGROG associates 27 National influenza centres which in the course of the season exchange information on the incidence of influenza and other respiratory viruses. ESWI (European Scientific Working Group on Influenza) organizes clinical and epidemiological investigations on the influence of influenza infection and the impact of anti-flu vaccination; it tries to harmonize the surveillance programme and raise its standard and strives for joint research projects. The National reference laboratory in Prague participates in all these programmes and takes also active part in some projects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8665102&dopt=Abstract flu, influenza



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Factors associated with influenza vaccination coverage among the elderly: role of health care personnel.

Honkanen PO, Keistinen T, Kivela SL.

National Public Health Institute, Department in Oulu, Finland.

Factors associated with acceptance of influenza vaccination in an elderly population were investigated in order to find ways of improving vaccination coverage. Three administrative districts with different vaccination coverages were selected, and a random sample of 10 percent (N = 497) of the elderly population living outside institutions was taken from the official lists maintained by the Central Statistical Office. The data were collected by means of a postal questionnaire. The questionnaire inquired about influenza vaccination status during the autumn 1992 campaign, demographic factors, health status, previous experiences and beliefs about influenza vaccination and influenza as a disease, and source of information about the vaccination campaign. The highest positive associations were found between a high influenza vaccination acceptance rate and the perceived need for vaccination (Relative risk (RR) 4.6, 95% confidence interval (CI) 2.7-7.9), belief in its effectiveness (RR 3.6, 95% CI 2.1-6.1) and information received from health visitors (RR 2.2, 95% CI 1.8-2.6). Vaccination acceptance was negatively associated with a belief in its adverse effects, (RR 0.4, 95% CI 0.2-0.6). Information received from health visitors was associated with more frequent occurrence of positive beliefs about influenza vaccination and with higher acceptance of vaccination irrespective of positive or negative beliefs regarding it. In order to obtain high vaccination coverage health care personnel should be carefully informed about the importance of influenza vaccination and encouraged to inform the public.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8668762&dopt=Abstract flu, influenza



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Serum antibody response to influenza vaccine in pulmonary patients receiving corticosteroids.

Kubiet MA, Gonzalez-Rothi RJ, Cottey R, Bender BS.

Division of Pulmonary Medicine, University of Florida College of Medicine, USA.

OBJECTIVE: Despite the recommendation that patients with chronic lung diseases--many of whom receive corticosteroids--receive annual influenza vaccination, it is not known whether corticosteroids influence antibody response to influenza vaccine in this population. The purpose of this study was to assess whether patients with pulmonary conditions receiving long-term corticosteroid therapy develop an adequate antibody response. DESIGN: We prospectively studied 39 consecutive candidates for influenza vaccination, 25 of whom were receiving corticosteroids for underlying lung diseases. Patients with immunosuppression besides corticosteroids were excluded. Serum samples were obtained prior to and 1 month after vaccination with inactivated trivalent influenza vaccine and assayed for antibodies to the three strains using a hemagglutination inhibition assay. No patients had any intercurrent illness compatible with influenza during the study period and patients receiving corticosteroids continued treatment with them during this time. RESULTS: A fourfold rise in antibody titer at 1 month to at least one component was seen in 21 of 25 (84%) of corticosteroid-treated patients, which was similar to patients not receiving corticosteroids (11/14, 79%). There was no corticosteroid-antibody, dose-response relationship. CONCLUSIONS: Patients with pulmonary conditions receiving corticosteroids can generate an adequate antibody response to killed influenza virus vaccine. Long-term therapy with corticosteroids should not preclude influenza vaccination in patients with chronic pulmonary diseases who are deemed vaccine candidates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8697835&dopt=Abstract flu, influenza



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[An outbreak of influenza A (H3N2) in a nursing home]

[Article in Japanese]

Yamakoshi M, Suzuki K, Yamamoto T, Yamamoto T, Goto N, Nakakita T, Yamanaka K.

Nagoyashi-Koseiin Geriatric Hospital, Aichi, Japan.

In the nursing home belonging to our hospital, an outbreak of influenza A (H3N2) occurred in January 1995, and we studied 23 elderly residents with influenza A infection. Twenty three residents with influenza A (8 males and 15 females) ranged in age from 67 to 95 years (average 83.1 years), 91.3% of them were bedridden. And all had underlying medical conditions with neurologic, cardiac, orthopedic, being the most frequent. The most common complaints were fever (100%), followed by cough (95.7%), sputum (60.9%), but sore throat was significantly less frequent. Influenza A virus was isolated from throat swab specimens from 6 of 18 ill patients. Fourteen persons were hospitalized and 2 of them had pneumonia, but nobody died. The levels of CRP, WBC were significantly high in the influenza group, as compared to the non influenza group. So this result suggested that influenza A infection among elderly subjects was apt to cause bacterial infection such as bronchitis and pneumonia. This outbreak was caused by contact from the staff to residents, so we think the health care of the staffs and prevention of influenza should be a high priority in nursing homes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8699092&dopt=Abstract flu, influenza



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Effect of immobilization, cold and cold-restraint stress on liver monooxygenase activity and lipid peroxidation of influenza virus-infected mice.

Mileva M, Bakalova R, Tancheva L, Galabov S.

Department of Medical Physics and Biophysics, Medical University, 2 Zdrave Str., Sofia 1431, Bulgaria. mileva medfac.acad.bg

The present study provides a direct experimental evidence that the combination of influenza A/Aichi/2/68 (H3N2) infection with different models of "oxidative stress", such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the liver of mice, despite the absence of virus and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with a significant increase of lipid peroxidation products, a decrease of natural antioxidants (vitamin E, glutathione) and cytochrome P-450, an inhibition of cytochrome c reductase and liver monooxygenases (analgin- N-demethylase and amidopyrine- N-demethylase). Immobilization and cold stress, applied separately or in combination (cold-restraint), did not influence significantly any of the analysed parameters compared to those of the control group of non-infected mice. Preliminary exposure of mice to immobilization or cold stress and subsequent inoculation of influenza virus resulted in a significant increase of lipid peroxidation products and a significant decrease of vitamin E and reduced glutathione, compared with levels in control (non-infected) animals. Compared to influenza virus-infected and non-stressed animals, the changes in all these parameters were negligible. Immobilization or cold stress, applied in combination with influenza virus infection, partially prevented the suppressive effect of influenza virus on cytochrome P-450 and liver monooxygenases. A tendency towards normalization of these parameters to the control levels was observed. However, after application of cold-restraint plus influenza virus infection, the level of cytochrome P-450 and activity of cytochrome c reductase stayed markedly lower than in infected and non-stressed animals. The activities of liver monooxygenases were slightly increased compared with those of infected and non-stressed animals, but stayed relatively low compared to control (non-infected) mice. Combination of cold-restraint and influenza virus infection resulted in a greater synergistic increase of lipid peroxidation products and a greater synergistic decrease of vitamin E and reduced glutathione compared to controls, as well as to influenza virus-infected and non-stressed animals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11914779&dopt=Abstract flu, influenza



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Rescue of a synthetic chloramphenicol acetyltransferase RNA into influenza virus-like particles obtained from recombinant plasmids.

Mena I, Vivo A, Perez E, Portela A.

Centro Nacional de Biologia Celular y Retrovirus, Instituto de Salud Carlos III, Madrid, Spain.

We have shown previously that COS-1 cells infected with a vaccinia virus recombinant (vTF7-3) which expresses the T7 RNA polymerase gene and then transfected with four pGEM-derived plasmids encoding the influenza A virus core proteins (nucleoprotein, PB1, PB2, and PA polypeptides) can express a synthetic influenza virus-like chloramphenicol [correction of chloramphenical] acetyltransferase (CAT) RNA (I. Mena, S. de la Luna, C. Albo, J. Martin, A. Nieto, J. Ortin, and A. Portela, J. Gen. Virol. 75:2109-2114, 1994). Here we demonstrate that by supplying the vTF7-3-infected cells with plasmids containing cDNAs of all 10 influenza virus-encoded proteins, the transfected CAT RNA can be expressed and rescued into particles that are budded into the supernatant fluids. The released particles can transfer the enclosed CAT RNA to MDCK cultures and resemble true influenza virions in that they require trypsin treatment to deliver the RNA to fresh cells and are neutralized by a monoclonal antibody specific for the influenza A virus hemagglutinin. Moreover, analysis by electron microscopy showed that the culture medium harvested from the transfected cells contained vesicles that could be labeled with an anti-HA monoclonal antibody and that were similar in size and morphology to authentic influenza virus particles. It is also shown that detection of recombinant particles capable of transmitting the CAT RNA does not require expression of the influenza virus nonstructural protein NS1. All of these data indicate that influenza virus-like particles enclosing a synthetic virus-like RNA can be assembled in cells expressing all viral structural components from recombinant plasmids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8764008&dopt=Abstract flu, influenza



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African green monkey kidney (Vero) cells provide an alternative host cell system for influenza A and B viruses.

Govorkova EA, Murti G, Meignier B, de Taisne C, Webster RG.

Department of Virology & Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

The preparation of live, attenuated human influenza virus vaccines and of large quantities of inactivated vaccines after the emergence or reemergence of a pandemic influenza virus will require an alternative host cell system, because embryonated chicken eggs will likely be insufficient and suboptimal. Preliminary studies indicated that an African green monkey kidney cell line (Vero) is a suitable system for the primary isolation and cultivation of influenza A viruses (E. A. Govorkova, N. V. Kaverin, L. V. Gubareva, B. Meignier, and R. G. Webster, J. Infect. Dis. 172:250-253, 1995). We now demonstrate for the first time that Vero cells are suitable for isolation and productive replication of influenza B viruses and determine the biological and genetic properties of both influenza A and B viruses in Vero cells; additionally, we characterize the receptors on Vero cells compared with those on Madin-Darby canine kidney (MDCK) cells. Sequence analysis indicated that the hemagglutinin of Vero cell-derived influenza B viruses was identical to that of MDCK-grown counterparts but differed from that of egg-grown viruses at amino acid positions 196 to 198. Fluorescence-activated cell sorting analysis showed that although Vero cells possess predominantly alpha2,3 galactose-linked sialic acid, they are fully susceptible to infection with either human influenza A or B viruses. Moreover, all virus-specific polypeptides were synthesized in the same proportions in Vero cells as in MDCK cells. Electron microscopic and immunofluorescence studies confirmed that infected Vero cells undergo the same morphological changes as do other polarized epithelia] cells. Taken together, these results indicate that Vero cell lines could serve as an alternative host system for the cultivation of influenza A and B viruses, providing adequate quantities of either virus to meet the vaccine requirements imposed by an emerging pandemic.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8764064&dopt=Abstract flu, influenza



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Synthesis and antiviral activity evaluation of some new aminoadamantane derivatives. 2.

Kolocouris N, Kolocouris A, Foscolos GB, Fytas G, Neyts J, Padalko E, Balzarini J, Snoeck R, Andrei G, De Clercq E.

Department of Pharmacy, University of Athens, Panepistimioupoli-Zografou, Greece.

The synthesis of some new aminoadamantane derivatives is described. The new compounds were evaluated against a wide range of viruses [influenza A H1N1, influenza A H2N2, influenza A H3N2, influenza B, parainfluenza 3, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), thymidine kinase-deficient (TK-) HSV-1, vaccinia, vesicular stomatitis, polio 1, Coxsackie B4, Sindbis, Semliki forest, Reo 1, varicella-zoster virus (VZV), TK- VZV, human cytomegalovirus (HCMV), and human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)]. Some of them proved markedly active against the influenza A H2N2 (compounds 4a,b, 5a, 6a, and 7a), H3N2 (compounds 5a, 6a, and 7a), and H1N1 (compounds 4b,c and 6d). Since compounds 5a, 6a, and 7a, amantadine, and rimantadine showed the same comparative pattern of potency against influenza strains H2N2, H3N2, and B, it may postulated that they act according to a similar mechanism, with regard to their "amine" effect, on the M2 ion channel of influenza A (H1N1, H2N2, or H3N2). In general, no significant activity was noted with any of the new compounds against any of the other viruses tested, making their activity against influenza virus more specific and striking. Borderline activity was noted with some of the compounds (4b,c, 5a-c, and 8a) against HIV-1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8765514&dopt=Abstract flu, influenza



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Lipid vesicle-entrapped influenza A antigen modulates the influenza A-specific human antibody response in immune reconstituted SCID-human mice.

Walker W, Brewer JM, Alexander J.

Department of Immunology, University of Strathclyde, Glasgow, Scotland.

This study was designed to investigate the capacity of purified influenza antigen in the presence and absence of adjuvant to induce human antibody responses in human-PBL-SCID mice. Non-ionic surfactant vesicles (NISV) were used as adjuvant as they have been shown to promote the development of Th1 responses in mouse studies. Human peripheral blood lymphocyte-SCID mice were inoculated with either purified influenza antigen (A/Texas, H3N2) or influenza antigen entrapped in NISV. Both vaccinated groups produced significantly higher plasma levels of influenza-specific human IgG when individually compared with non-vaccinated controls. However, similar comparisons revealed that specific IgM levels were significantly higher only in the group challenged with purified antigen. Further analysis of IgG subclasses also demonstrated an adjuvant-dependent dichotomy in the responses of the vaccine groups when compared with non-vaccinated controls. Thus, only influenza-specific IgG1 antibodies (associated with Th1 responses in humans) were significantly increased above control levels using antigen with adjuvant, while both this subclass and antigen-specific IgG4 (Th2 associated) were significantly increased with antigen alone. These results illustrate the suitability of this model for use in human vaccination studies and demonstrates that influenza antigen applied with NISV selectively promotes only Th1 responses, unlike free antigen which also promotes Th2 responses in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8766578&dopt=Abstract flu, influenza



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Outbreaks of influenza A among elderly hospital inpatients.

Everts RJ, Hanger HC, Jennings LC, Hawkins A, Sainsbury R.

Princess Margaret Hospital, Christchurch.

AIMS. To describe two outbreaks of influenza A that occurred in wards catering for assessment, treatment and rehabilitation of elderly patients at the Princess Margaret Hospital in Christchurch. METHODS. Infected patients and staff were identified clinically, and influenza subsequently confirmed or supported in some patients by viral antigen detection, culture of throat and nasopharyngeal swabs or serology. RESULTS. Overall, the attack rate of clinical influenza in the two wards affected was 13 of 27 patients (48%) and 15 of 26 patients (58%) respectively. Of all those with influenza, 13 patients (46%) developed lower respiratory tract infection and there were two deaths (7%) at least in part attributed to influenza. Patients in single rooms were not protected from infection. The vaccination rate among all patients was 18%. Immunised patients had a lower attack rate (21%) than those who had not received influenza vaccine that season (40%). The attack rate amongst staff in each ward was 69% and 36% respectively, and the overall staff vaccination rate was 12%. CONCLUSION. These outbreaks illustrate the severe consequences of influenza in an institutional setting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8769048&dopt=Abstract flu, influenza



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Sickness absence following a campaign of vaccination against influenza in the workplace.

Leighton L, Williams M, Aubery D, Parker SH.

Medical Centre FOR Limited, Basildon, Essex.

This study was designed as a retrospective cohort study of those employees vaccinated against influenza vs. unvaccinated employees in a service company. The objective was to investigate whether vaccinating employees against influenza in an occupational setting was of any benefit. There were 2,557 persons entered in the study who were in continuous employment between 1 October 1990 and 31 March 1992 of which 23.5% (601) were vaccinated. The study was carried out at First Data Resources Limited in Basildon, Essex UK. The main outcome measure was self-reported influenza sickness lasting four or more days and reduction in sickness absence due to vaccination against influenza. The results were surprising. In the vaccinated members of staff, influenza illness was halved, Relative Risk = 0.46, 95% confidence limits (0.27 < RR < 0.76). The conclusions were that the study showed a significant decrease in sickness absence due to influenza illness, as a result of an active vaccination campaign carried out amongst otherwise healthy individuals in the occupational health environment. This is the first study of this nature in the UK to show statistically significant evidence of benefit from vaccinating healthy employees. It lends support to immunization against influenza in the workplace.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8776252&dopt=Abstract flu, influenza