flu
Update: outbreak of influenza A infection--Alaska and the Yukon Territory, July-August 1998.

[No authors listed]

On July 26, 1998, CDC and Health Canada, in cooperation with local public health authorities, began investigating reports of febrile respiratory illnesses and associated pneumonia among summer land and sea travelers to Alaska and the Yukon Territory (1). Epidemiologic and laboratory evidence has implicated influenza A virus as the etiologic agent of the outbreak. From June 11 through August 22, completed viral cultures of 101 (48%) of 209 nasopharyngeal specimens have yielded 26 influenza A isolates, four other respiratory viruses, and 71 negative results; results are pending for 108 additional specimens. Of the 26 influenza A isolates, five have been characterized at CDC; all have been identified as influenza A/Sydney/5/97 (H3N2)-like viruses, a strain included in the 1998-99 influenza vaccine. This report presents updated information about the outbreak and includes recommendations for influenza A prevention and control in this setting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9733414&dopt=Abstract flu, influenza



flu
In vitro characterization of A-315675, a highly potent inhibitor of A and B strain influenza virus neuraminidases and influenza virus replication.

Kati WM, Montgomery D, Carrick R, Gubareva L, Maring C, McDaniel K, Steffy K, Molla A, Hayden F, Kempf D, Kohlbrenner W.

Antiviral Drug Discovery Research, Abbott Laboratories, Abbott Park, Illinois 60064-6217, USA. warren.kati abbott.com

A-315675 is a novel, pyrrolidine-based compound that was evaluated in this study for its ability to inhibit A and B strain influenza virus neuraminidases in enzyme assays and influenza virus replication in cell culture. A-315675 effectively inhibited influenza A N1, N2, and N9 and B strain neuraminidases with inhibitor constant (K(i)) values between 0.024 and 0.31 nM. These values were comparable to or lower than the K(i) values measured for oseltamivir carboxylate (GS4071), zanamivir, and BCX-1812, except for the N1 enzymes that were found to be the most sensitive to BCX-1812. The time-dependent inhibition of neuraminidase catalytic activity observed with A-315675 is likely due to its very low rate of dissociation from the active site of neuraminidase. The half times for dissociation of A-315675 from B/Memphis/3/89 and A/Tokyo/3/67 (H3N2) influenza virus neuraminidases of 10 to 12 h are significantly slower than the half times measured for oseltamivir carboxylate (33 to 60 min). A-315675 inhibited the replication of several laboratory strains of influenza virus in cell culture with potencies that were comparable or superior to those for oseltamivir carboxylate and BCX-1812, except for the A/H1N1 viruses that were found to be two- to fourfold more susceptible to BCX-1812. A-315675 and oseltamivir carboxylate exhibited comparable potencies against a panel of A/H1N1 and A/H3N2 influenza virus clinical isolates, but A-315675 was found to be significantly more potent than oseltamivir carboxylate against the B strain isolates. The favorable in vitro results relative to other clinically effective agents provide strong support for the further investigation of A-315675 as a potential therapy for influenza virus infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11897583&dopt=Abstract flu, influenza



flu
The matrix 1 protein of influenza A virus inhibits the transcriptase activity of a model influenza reporter genome in vivo.

Perez DR, Donis RO.

Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, 68583-0905, USA.

The M1 protein of influenza virus inhibits the in vitro transcriptase activity of ribonucleoprotein cores from virions. This inhibitory activity is thought to be relevant in vivo because accumulation of M1 at the late stages of viral replication may be the cue to halt viral mRNA production. A model influenza reporter genome was used to explore the effect of M1 on the activity of the influenza virus transcriptase complex within cultured cells. Expression of M1 in cells bearing the model influenza virus reporter genome was accompanied by a reduction of CAT gene expression to 12% of control levels. Quantification of RNA by ribonuclease protection assay revealed that the influenza reporter genome mRNA levels in M1-expressing cells were reduced by approximately 74% compared with those of cells expressing a control protein. These findings are consistent with the proposed model in which M1 is responsible for limiting viral transcription during late stages of infection. By expressing truncated forms of M1, the inhibitory activity was found to reside within the amino-terminal half of the M1 protein. Two independent inhibitory domains were identified in this region: one between amino acid residues 1-90 and the other spanning residues 91-127. Copyright 1998 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9740776&dopt=Abstract flu, influenza



flu
[Different patterns of molecular evolution of influenza A viruses in avian and human population]

[Article in Russian]

Makarova KS, Wulf YuI, Tereza EP, Ratner VA.

Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia.

Patterns of molecular evolution of the influenza virus proteins and genes are discussed. The subsets of all viral genes corresponding to statistically significant clusters on dendrogram were shown to fall into two distinct groups. The first group was characterized by the presence of an exact linear relationship between the year of the strain isolation and the evolutionary distance. The subsets of human influenza virus genes belong to this group. A method for eliminating the "frozen" strains from the subsets and for calculating the evolutionary rates without construction of phylogenetic trees has been elaborated. The substitution rates calculated according to this technique agreed with the data obtained previously. A linear relationship was not observed in the second group. This group was predominantly composed of avian influenza virus genes. The lack of linear correlation pointed to the cocirculation of a large amount of different influenza virus genomic segments in the avian population. An approach for an examination of the role of intragenic recombination in the development of the antigenic subtypes of hemagglutinin is suggested. Our results suggest that recombination did not play a considerable role in this process, and that all modern subtypes of this protein were probably formed before the introduction of the influenza viruses into the human population. These findings are consistent with the hypothesis that influenza viruses penetrated into human population from their pools in avian populations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9749330&dopt=Abstract flu, influenza



flu
The role of interferon in influenza virus tissue tropism.

Garcia-Sastre A, Durbin RK, Zheng H, Palese P, Gertner R, Levy DE, Durbin JE.

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.

We have studied the pathogenesis of influenza virus infection in mice that are unable to respond to type I or II interferons due to a targeted disruption of the STAT1 gene. STAT1-/- animals are 100-fold more sensitive to lethal infection with influenza A/WSN/33 virus than are their wild-type (WT) counterparts. Virus replicated only in the lungs of WT animals following intranasal (i.n.) virus inoculation, while STAT1-/- mice developed a fulminant systemic influenza virus infection following either i.n. or intraperitoneal inoculation. We investigated the mechanism underlying this altered virus tropism by comparing levels of virus replication in fibroblast cell lines and murine embryonic fibroblasts derived from WT mice, STAT-/- mice, and mice lacking gamma interferon (IFNgamma-/- mice) or the IFN-alpha receptor (IFNalphaR-/- mice). Influenza A/WSN/33 virus replicates to high titers in STAT1-/- or IFNalphaR-/- fibroblasts, while cells derived from WT or IFNgamma-/- animals are resistant to influenza virus infection. Immunofluorescence studies using WT fibroblast cell lines demonstrated that only a small subpopulation of WT cells can be infected and that in the few infected WT cells, virus replication is aborted at an early, nuclear phase. In all organs examined except the lung, influenza A WSN/33 virus infection is apparently prevented by an intact type I interferon response. Our results demonstrate that type I interferon plays an important role in determining the pathogenicity and tissue restriction of influenza A/WSN/33 virus in vivo and in vitro.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9765393&dopt=Abstract flu, influenza



flu
Mortality associated with an influenza outbreak on a dementia care unit.

Brandeis GH, Berlowitz DR, Coughlin N.

Department of Veterans Affairs, Edith Nourse Rogers Veterans Administration Medical Center, Bedford, Massachusetts, USA.

The purpose of this study was to describe an episode of increased mortality, whose cause was initially unknown. This retrospective cohort investigation was conducted on a dementia special care unit of a Department of Veterans Affairs facility, with more than 75% of residents clinically diagnosed with dementia of the Alzheimer type. One hundred five residents residing in the facility during February 1995 were included as subjects. A cluster of deaths occurred, triggering the investigation. Ultimately, 21 deaths (three times greater than any previous month in the past 5 years) occurred during the 1-month period. Measures included the presence of clinical influenza-like illness based on signs, serology, and autopsy results. Of the 105 residents, 45 (42.8%) met the clinical definition for influenza-like illness. Eight autopsies were performed, and the causes of death consisting of bronchopneumonia in seven and aspiration pneumonia in one were compatible with influenza. There were no differences among those who died from those who lived with regards to age, race, gender, clinical influenza-like illness, vaccination status, diagnosis of Alzheimer disease, or duration of dementia (all p > or = 0.2). However, those who died were at a higher risk of dying due to a greater number of coexisting conditions (p < 0.01). Also, overall the groups differed in Mini-Mental State Examination and Bedford Alzheimer Nursing Scale scores with those who died being more impaired (p < 0.01). Thus, the presentation of influenza-like illness can be subtle in onset, underappreciated in this population, and not recognized until excess mortality, which affects the most frail, is noted. Care providers need to be vigilant during the winter months for the presence of influenza.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9772015&dopt=Abstract flu, influenza



flu
Isolation and identification of influenza viruses from clinical materials in 1977-1993 at Veterans General Hospital-Taipei.

Liu WT, Wei HY, Hu ST, Tsai CH, Chern SR, Wang HC.

Department of Pathology, Veterans General Hospital-Taipei, Taiwan, R.O.C.

From 1977 to 1993, 15,189 throat swab samples were received for isolation and identification of influenza virus in the Clinical Virology Laboratory, Veterans General Hospital-Taipei. Most of the samples came from the Pediatric Department. There were 634 identified strains of the influenza virus; the successful isolation rate was 4.17% in average/year. Among these isolates, 56.3% (357/634) were influenza B; 12.1% (77/634) were influenza A/H1N1 and 28.1% (178/634) were influenza A/H3N2. About 3.5% (22/634) were classified as flu-like agents because of no reaction with available monoclonal antibodies. In recent years, reverse transcriptase polymerase chain reaction (RT-PCR) was established here to re-evaluate these virus stocks. This method can provide rapid diagnosis method to identify influenza A/H1N1, A/H3N2 and B. Further, the RT-PCR method and sequencing of amplified DNA could be used to see the variation of virus isolates which were recirculated or which reappeared in the Taipei area.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9774990&dopt=Abstract flu, influenza



flu
Cytokine production after influenza vaccination in a healthy elderly population.

Bernstein ED, Gardner EM, Abrutyn E, Gross P, Murasko DM.

Influenza vaccination is less efficacious in the elderly than in the young. To characterize this age-related decrease in immune response to influenza vaccination, antibody and cell-mediated responses to influenza vaccine were assessed before immunization and 4 weeks after vaccination of a population of 270 healthy elderly individuals (mean age: 80.2 years) living in eight local continuing care retirement communities (CCRCs) and 30 young individuals (mean age: 27.8 years). The antibody titres produced against all three influenza strains increased significantly after vaccination in both the young and elderly (p < 0.0005); however, the young demonstrated significantly higher titres to all three strains than did the elderly (p < 0.03). Peripheral blood mononuclear cells (PBMC) cultured with influenza vaccine demonstrated significantly increased proliferation (elderly: p < 0.00005; young: p < 0.001) after vaccination, with proliferative responses in the young significantly higher than the elderly both before (p < 0.04) and after (p < 0.0005) vaccination. Similarly, IFN gamma production in these PBMC cultures increased significantly pre- to postvaccination in both young and elderly (young: p < 0.006; elderly: p < 0.00005), but the young produced more than the elderly both pre- and postvaccination (p < 0.0001). Following vaccination, PBMC production of IL-10 was higher in the young than in the elderly (p < 0.0015), while IL-6 production was comparable in both young and elderly individuals. Greater than 13% of the elderly population did not produce detectable IL-6, IL-10, or IFN gamma either before or after vaccination. The data show that the decreased cell-mediated and humoral responses to influenza vaccination of this healthy elderly population are accompanied by the production of lower levels of cytokines. A unique finding in this population of 270 healthy elderly was the association between a TH0 cytokine profile and intact immune responses to influenza vaccine. A similar relationship was not seen in the young.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9778748&dopt=Abstract flu, influenza



flu
Regional perspectives on influenza surveillance in Africa.

Schoub BD, McAnerney JM, Besselaar TG.

National Institute for Virology, Private Bag X4, Sandringham, South Africa. schoub niv.ac.za

Africa possesses little capacity for influenza surveillance-Senegal and South Africa being the only countries in the WHO African region who regularly pursue active surveillance and characterize influenza isolates. South Africa has three sites-in Cape Town, Durban and the largest in Johannesburg at the National Institute for Virology (NIV). The NIV antigenically and molecularly characterizes influenza viruses isolated from specimens provided by a sentinel network of approximately 50 clinical sites. This information, together with the isolates themselves are supplied to WHO International Influenza Centres in London and Melbourne. In addition, proxy markers of influenza severity such as school absenteeism and doctor/clinic visits are monitored to assess the severity of epidemics. Although, influenza exacts a heavier toll of the illness burden in developing countries already beset with underlying chronic medical conditions and also has a more severe impact on economies largely dependent on single income earners and subsistence farmers, influenza surveillance and vaccination awareness is woefully lacking on the African continent, and this urgently needs to be remedied.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110256&dopt=Abstract flu, influenza



flu
Regional perspectives on influenza surveillance in South America.

Savy V.

Instituto Nacional de Enfermedades Infecciosas-ANLIS C.G. Malbran, 563 Avenida Velez Sarsfield, Buenos Aires, Argentina. vrmalbra datamarkets.com.ar

The implementation of influenza vaccination programs emphasize the necessity of an extended influenza surveillance in the countries of the region. As it is based on the activity of National Influenza Centers we intend to make a description of their work, their historical background and further development.Technical capacities in influenza South America laboratories, and networks in Argentina, Brazil and Chile are shown. Examples of different viral circulation in a unique country or in countries with common borders illustrate the importance of the information obtained by means of the virological surveillance. Specific characteristics of the region as long distances and the lack of modern information systems require a suitable fitting of the systems that are working in Northern Hemisphere countries. The contribution of motivated physicians and public health workers must not to be disregarded. The following actions are proposed: optimizing technical capacities of National Influenza Centers in order to improve the quality of data available; improving the communication of the information obtained by surveillance activities to all the participants; increasing the cooperation among the countries; motivate health authorities to become aware of influenza impact in public health.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110257&dopt=Abstract flu, influenza



flu
Demonstration of the feasibility of emergency department immunization against influenza and pneumococcus.

Slobodkin D, Zielske PG, Kitlas JL, McDermott MF, Miller S, Rydman R.

Department of Emergency Medicine, and the Division of Emergency Nursing, Cook County Hospital, School of Public Health, University of Chicago, Chicago, IL 60612, USA. davids uic.edu

STUDY OBJECTIVE: To demonstrate the feasibility of systematic immunization against influenza and pneumococcus in a public emergency department. METHODS: This was a demonstration project conducted from October 21, 1996, through December 2, 1996, at Cook County Hospital, an inner-city hospital with a 1996 adult ED census of 120,449. Seventy-eight percent of patients are uninsured; 92% are people of color; 73% deny having a primary physician. Only 15% have emergency complaints. Nurses received standing orders that all nonemergency adult patients meeting Centers for Disease Control and Prevention criteria for high risk should be offered immunization against influenza and pneumococcus at triage. Cash prizes were offered to nurses appropriately immunizing the most patients. The date of immunization was entered into the computerized patient registration system, available to all providers within the county system. From November 4 through November 18, an extra nurse was assigned to triage to test for improvement in immunization rates. A time-motion study determined the time required per immunization on the basis of a convenience sample of 8 nurses drawn from all 3 shifts. RESULTS: Only 3% of identified high-risk patients reported previous pneumococcal immunization. Despite extreme variation in nurse performance, 2,631 patients (24% of patients triaged) were screened, and 716 high-risk patients were identified (27% of patients screened). A total of 1234 patients were immunized against influenza, and 241 patients were appropriately immunized against pneumococcus. Sixty-one percent of high-risk patients with no contraindication to influenza immunization were immunized against influenza. Thirty-five percent of high-risk patients not previously immunized against pneumococcus were immunized against pneumococcus. Immunizations per shift per triage nurse varied from 0 to 24. Median time for all activities related to immunization was 4 minutes (range, 2 to 10 minutes). There was no increase in immunization rates with the addition of an extra nurse at triage (95% confidence interval for odds ratio, .929 to 1.153). CONCLUSION: Systematic immunization against influenza and pneumococcus is both needed and feasible in a public ED. "Buy-in" by nurses is variable. Increased staffing alone does not improve immunization rates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9795315&dopt=Abstract flu, influenza