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[Use of sentinel reporting clinics for influenza surveillance in the winter of 1996-1997]

[Article in Hebrew]

Shohat T, Versano N, Kiro A, Golan G, Mendelson E, Weingarten M.

Influenza Surveillance Network, Israel Center for Disease Control, Israel.

In a joint effort of the Israel Center for Disease Control, the National Center for Influenza in the Central Virology Laboratory, together with a group of collaborating pediatricians and family physicians, a network for influenza surveillance was established in the winter of 1996-97. Nose and throat swabs were obtained from 571 patients with flu-like illness. 133 (23%) were positive for influenza virus. Both influenza A(H3N2) and B were isolated, predominantly influenza B during the beginning of the season. Both circulating strains were antigenically similar to those included in the vaccine for 1996-1997. Patients from whom influenza virus was isolated were significantly more likely to suffer from cough and myalgia in comparison with patients whose cultures were negative (p = 0.02 and 0.003, respectively). Results of the first year of surveillance indicate that sentinel reporting clinics are useful for timely detection and identification of the viral strains circulating in the community, thus allowing prompt intervention in preventing the spread of influenza. Conclusions from the first year of the study were drawn and applied in the winter of 1997-1998.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10914192&dopt=Abstract flu, influenza



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An outbreak of influenza A in a neonatal intensive care unit.

Cunney RJ, Bialachowski A, Thornley D, Smaill FM, Pennie RA.

Dept Microbiology, McMaster University Medical Centre, Hamilton, Ontario, Canada.

OBJECTIVES: Investigation of an outbreak of influenza A in a neonatal intensive care unit (NICU) with examination of risk factors for infection and outcomes. DESIGN: Retrospective cohort study of infants admitted to the unit during the outbreak period. Prospective survey of NICU staff and mothers of infants in the cohort study. SETTING: Level III nursery in a university-affiliated tertiary referral center. RESULTS: Nineteen infants in the NICU were infected with influenza A There were six symptomatic cases and one death who had evidence of virus-associated hemophagocytic syndrome at autopsy. Amantadine prophylaxis was offered to the NICU staff, and amantadine therapy was given to five of the six symptomatic infants. Mechanical ventilation, gestational age, birth weight, Clinical Risk Index for Babies score, and twin pregnancy were associated with acquisition of influenza A on univariate analysis. Mechanical ventilation (odds ratio [OR], 6.2; P=.02) and twin pregnancy (OR, 7.0; P=.04) remained as significant risk factors for infection on multiple logistic regression analysis. Only 15% of respondents to the NICU staff survey were vaccinated against influenza. There was no association between a history of an influenza-like illness during pregnancy and acquisition of influenza A by infants of mothers who responded to the maternal survey (OR, 0.91; P=1.0). CONCLUSIONS: Influenza A is an important pathogen in the neonatal population and is readily transmissible in the NICU setting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10926394&dopt=Abstract flu, influenza



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Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus.

Han SN, Wu D, Ha WK, Beharka A, Smith DE, Bender BS, Meydani SN.

Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

Compared with young mice, old mice infected with influenza virus have significantly higher pulmonary viral titres, although these can be reduced significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon-gamma (IFN-gamma), play an important role in defending against influenza infection. However, there is an age-associated loss of Th1 cytokine production. Prostaglandin E2 (PGE2) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of influenza severity in old mice, we studied the cytokine production by splenocytes, and PGE2 production by macrophages (Mphi), in young and old C57BL mice fed semipurified diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral titres than young mice; old mice fed the vitamin E-supplemented diet had significantly lower pulmonary viral titres than those fed the control diet (P = 0.02 and 0.001 for overall age and diet effect, respectively). Following influenza infection, interleukin (IL)-2 and IFN-gamma production was significantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL-2 and IFN-gamma in old mice; higher IFN-gamma production was associated with lower pulmonary viral titre. Old mice fed the control diet showed significantly higher lipopolysaccharide (LPS)-stimulated Mphi PGE2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no significant age difference in IL-6, IL-1beta, or tumour necrosis factor-alpha (TNF-alpha) production by splenocytes. Young mice fed the vitamin E-supplemented diet had significantly lower IL-1beta (day 7) and TNF-alpha production (day 5) compared with those fed the control diet. Old mice fed the vitamin E-supplemented diet had significantly lower TNF-alpha production (day 2) than those fed the control diet. Our results indicate that the vitamin E-induced decrease in influenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE2 production caused by vitamin E.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10929076&dopt=Abstract flu, influenza



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Utilization of alpha-1-acid glycoprotein levels in the serum as a parameter for in vivo assay of influenza virus inhibitors.

Sidwell RW, Wong MH, Bailey KW, Barnard DL, Jackson MK, Smee DF.

Institute for Antiviral Research, Utah State University, Logan, USA. rsidwell cc.usu.edu

Alpha-1-acid glycoprotein (AGP), an acute phase protein in serum assayed by single radial immunodiffusion using a commercially available kit, was found to significantly increase in mice infected with influenza A and B viruses. Experiments were run to determine the rate of increase of serum AGP and its relation to other influenza disease parameters, including lung consolidation, development of lung virus titres, decline in arterial oxygen saturation (SaO2), histopathological changes in the lung, and death of the animal. Maximal AGP levels occurred by day 3 in the animals, at about the same time lung virus titres reached their peak and inflammatory effects were evident in the lung. Serum levels of AGP were then compared with other disease parameters in the evaluation of the anti-influenza A and B virus efficacy of oseltamivir and ribavirin in mice. Treatment was by oral gavage twice daily for 5 days, beginning 4 h before virus exposure using doses of 100, 10, and 1 mg/kg per day of oseltamivir and 75 mg/kg per day of ribavirin. Against the influenza A infection, significant inhibition of death, SaO2 decline, and lung consolidation was seen at all doses of each compound; day-6 AGP levels were reduced in a dose-responsive manner. Lung virus titres were lessened at this time, but to a significant degree only at the high dose of oseltamivir and by ribavirin. The influenza B virus infection, which appeared more severe than the influenza A infection, was also significantly inhibited by both compounds, but to a lesser extent. The serum AGP levels were again lessened by therapy with both compounds. The influence of challenge dose of influenza A virus on AGP level and on the antiviral activity of 20 mg/kg per day of oseltamivir, administered by oral gavage, was determined in mice. The AGP level was in proportion to the viral challenge dose; oseltamivir significantly inhibited AGP levels and all other disease parameters regardless of size of viral inoculum. These data indicate murine AGP levels to be markedly stimulated by infection with influenza A and B viruses, and the level of the protein to be an additional measure of antiviral efficacy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12018681&dopt=Abstract flu, influenza



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Monitoring of influenza in the EISS European network member countries from October 2000 to April 2001.

Manuguerra JC, Mosnier A, Paget WJ; EISS (European Influenza Surveillance Scheme).

WHO Collaborating Centre for the reference and research on influenza virus and other respiratory viruses, National Influenza Centre for Northern France, Institut Pasteur, Paris, France.

In countries covered by the European Influenza Surveillance Scheme (EISS), the 2000-2001 winter was marked mainly by the spread of influenza A(H1N1) viruses. Influenza B, which globally represented a minority of cases, was common later in the season and predominant in Great Britain, Ireland, and Portugal. Influenza activity was at its maximum during the period of January and February/March 2001 with little time lag between countries (maximum four weeks). Overall, the morbidity rates reported were much lower than for the previous season, illustrating a moderate level of influenza activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11891380&dopt=Abstract flu, influenza



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Critical influenza virus infection.

Kappagoda C, Isaacs D, Mellis C, Peat J, De Silva L, O'Connell A.

Department of Immunology and Infectious Diseases, Royal Alexandra Hospital for Children, Westmead and The University of Sydney, New South Wales, Australia.

OBJECTIVE: To determine the risk of death from influenza infection in children with chronic underlying disease. METHODOLOGY: An 18-year retrospective study of children with 'critical' influenza A or B virus infection, defined as requiring admission to intensive care or resulting in death, but excluding laryngotracheobronchitis (LTB). Influenza infection was diagnosed by viral culture and/or immunofluorescence of respiratory secretions. Patients with LTB were analysed separately. RESULTS: There were 27 cases of critical influenza virus infection over the study period, comprising 26 admissions to the intensive care unit (excluding LTB) and one death on the general wards. Thirteen (48%) of the 27 children had chronic underlying disease. In addition, 12 children with LTB were admitted to the intensive care unit. The LTB children were older and less likely to have chronic underlying disease. Nosocomial infection caused seven (26%) of the 27 critical infections. Nine (33%) of the 27 children with critical influenza died. Six (46%) of 13 children with chronic underlying disease and influenza admitted to intensive care died, compared with three of 14 (21%) without any underlying disease (odds ratio = 3.1, 95% confidence interval 0.6-14.0). CONCLUSIONS: Critical life-threatening influenza virus infection was uncommon, but the mortality was high (33%), particularly in children with chronic underlying disease. Nosocomial infection with influenza was an important cause of admission to intensive care.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10940162&dopt=Abstract flu, influenza



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Influence of type 2 T cell responses on the severity of encephalitis associated with influenza virus infection.

Kaji M, Kobayashi M, Pollard RB, Suzuki F.

Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555-0835, USA.

The role of type 2 T cell responses on the severity of post-infectious encephalitis was investigated in a mouse model of influenza virus infection. When mice were infected intracerebrally with 3.0 LD(50) of A/NWS33 strain of influenza virus, they all showed clinical signs of encephalitis, and 90% of them died within 10 days of the infection. However, the post-infectious encephalitis was not demonstrated in mice exposed to 0.5 LD50 of the same virus. The mortality rates of mice infected with 0.5 LD(50) of the virus were increased to levels observed in mice exposed to 3.0 LD(50) of influenza virus infection, after the administration of a mixture of interleukin (IL)-4 and IL-10 (2 ng/mouse each; immediately, 1 and 2 days after the infection). In contrast, mortality rates of mice exposed to 3.0 LD(50) of influenza virus were substantially decreased when these mice were treated with a mixture of monoclonal antibodies directed against IL-4 and IL-10. A predominance of type 2 T cell responses was demonstrated in splenic T cells of mice infected with 3.0 LD(50) of influenza virus, although these responses were minimal in mice infected with 0.5 LD(50) of the virus. After the treatment with the mixture of type 2 cytokines, an increase in the type 2 T cell responses in mice exposed to 0.5 LD(50) of the virus was shown. These results indicate that type 2 T cell responses associated with the viral infection play an important role in the severity of post-infectious encephalitis induced in mice by the intracerebral infection of influenza A virus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10947061&dopt=Abstract flu, influenza



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[Inhibitory activity of blood group antigens M and N in inhibition of virus hemagglutination reactions of influenza viruses]

[Article in Croatian]

Vojvodic S.

Zavod za transfuziju krvi, Novi Sad. vukuna EUnet.yu

INTRODUCTION: M and N blood group antigens demonstrate inhibitory activity in inhibition reaction of viral hemagglutination with some influenza virus strains, with help of N-acetylneuraminic acid (sialic acid) which occurs in glycophorins on the red blood cells surface, and represent specific hemagglutunation receptors and substrate for action of influenza virus neuraminidase. MATERIAL AND METHODS: Reactivity of human O red blood cells with MM and NN phenotypes is established in inhibition reaction of viral hemagglutination by influenza virus A2 Singapore, with intention to fortify possibility of using human red blood cells in viral hemagglutination, to determine their reactivity in titration, retitration of hemagglutinins and inhibition reaction of hemagglutination. The aim of investigation was to describe destinations between different red blood cells in view of speed of reaction and receptor capacity. Material included 69 samples of sera from persons infected with influenza virus, among them 32 samples were positive with titres 1/80 and more. RESULTS: Reactivity of erythrocytes with MM and NN phenotypes in titration of hemagglutinins of influenza virus A2 Singapore in which base is viral hemagglutination is identical, because there are no statistically significant differences of average geomaterical levels of antibody titers. Enzymatically derived red cells by papain, which do not contain M and N blood group antigens, not cause viral hemagglutination phenomenon, because they sediment in all dilutions. Reactivity of red blood cells with MM and NN phenotypes in retitration of haemagglutinins and inhibition reaction of hemagglutination is identical, because there are no statistically significant differences in results with two kinds red blood cells. DISCUSSION: Results of investigation revealed that the reactivity of O human red blood cells different in MN phenotype is identical in regard to speed of reaction and receptor capacity in titration, retitration and inhibition reaction of viral hemagglutinatination and also showed that they demonstrate viral hemagglutination phenomenon in contrast with papainised red blood cells which do not contain M and N blood group antigens, which indirectly means that M and N blood group antigens contain receptors for influenza virus. CONCLUSIONS: Human red cells with MM and NN phenotypes cause viral hemagglutination phenomenon with influenza virus A2 Singapore, and could be used in routine virusological diagnostic procedures. O blood group red cells (MM and NN) in reaction of viral hemagglutination result identically in view of speed of reaction and receptor capacity, and have the same impact on result of this reaction. Enzymatically derived red cells by papain do not cause viral hemagglutination phenomenon, because they do not contain receptors for viral hemagglutinin on red cell membrane surface, which are hydrolazed by papain. Receptors for influenza virus on red cell membrane surface are a component part of M and N blood group antigens which are destroyed by papain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10953546&dopt=Abstract flu, influenza



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Influenza virus assembly: effect of influenza virus glycoproteins on the membrane association of M1 protein.

Ali A, Avalos RT, Ponimaskin E, Nayak DP.

Department of Microbiology, Immunology and Molecular Genetics, Molecular Biology Institute, Johnsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095-1747, USA.

Influenza virus matrix protein (M1), a critical protein required for virus assembly and budding, is presumed to interact with viral glycoproteins on the outer side and viral ribonucleoprotein on the inner side. However, because of the inherent membrane-binding ability of M1 protein, it has been difficult to demonstrate the specific interaction of M1 protein with hemagglutinin (HA) or neuraminidase (NA), the influenza virus envelope glycoproteins. Using Triton X-100 (TX-100) detergent treatment of membrane fractions and floatation in sucrose gradients, we observed that the membrane-bound M1 protein expressed alone or coexpressed with heterologous Sendai virus F was totally TX-100 soluble but the membrane-bound M1 protein expressed in the presence of HA and NA was predominantly detergent resistant and floated to the top of the density gradient. Furthermore, both the cytoplasmic tail and the transmembrane domain of HA facilitated binding of M1 to detergent-resistant membranes. Analysis of the membrane association of M1 in the early and late phases of the influenza virus infectious cycle revealed that the interaction of M1 with mature glycoproteins which associated with the detergent-resistant lipid rafts was responsible for the detergent resistance of membrane-bound M1. Immunofluorescence analysis by confocal microscopy also demonstrated that, in influenza virus-infected cells, a fraction of M1 protein colocalized with HA and associated with the HA in transit to the plasma membrane via the exocytic pathway. Similar results for colocalization were obtained when M1 and HA were coexpressed and HA transport was blocked by monensin treatment. These studies indicate that both HA and NA interact with influenza virus M1 and that HA associates with M1 via its cytoplasmic tail and transmembrane domain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10954572&dopt=Abstract flu, influenza



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Cost of treating influenza in emergency department and hospital settings.

Cox FM, Cobb MM, Chua WQ, McLaughlin TP, Okamoto LJ.

USMA Health Outcomes Research, Glaxo Wellcome Research and Development, Research Triangle Park, NC, USA.

OBJECTIVES: To provide an estimate of the costs of treating influenza in emergency department and hospital settings. STUDY DESIGN: Retrospective, descriptive study using patient-level data from the Perspective Comparative Database. PATIENTS AND METHODS: We analyzed clinical and cost data obtained from 75 of the 169 hospitals in the database. These hospitals were located throughout the United States. Patients were included in the study if they visited the emergency department between January 1, 1997, and June 30, 1998, and had a primary diagnosis of influenza. RESULTS: A total of 1362 patients with influenza visited the emergency department during the study period. Of these, 333 (24.4%) required hospitalization. The mean cost of treatment for patients discharged directly from the emergency department was $141.89; the mean cost of treatment for hospitalized patients was $3251.04. The mean length of stay for hospitalized patients was 4.3 days. Compared with younger patients, elderly patients were more likely to be hospitalized and incur higher costs. Thirty-eight percent of hospitalized patients for whom drug data were available received either amantadine or rimantadine during their stay. CONCLUSIONS: Few data are available documenting resource utilization and associated costs for patients with influenza treated in the emergency department or hospital. Our results represent a significant addition to the identification of the costs associated with the treatment of influenza. This suggests early intervention care aimed at minimizing the impact of influenza, especially in the elderly, could result in decreased hospitalizations and substantial cost savings to managed care.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10977420&dopt=Abstract flu, influenza



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Surveillance of influenza viruses isolated from travellers at Nagoya International Airport.

Sato K, Morishita T, Nobusawa E, Suzuki Y, Miyazaki Y, Fukui Y, Suzuki S, Nakajima K.

Department of Microbiology, Aichi Prefectural Institute of Public Health, Nagoya, Japan.

In order to conduct a survey of influenza viruses entering Japan via travellers arriving by airplanes, gargle solutions were collected from passengers who reported to the quarantine station of Nagoya International Airport complaining of respiratory symptoms. From 504 samples collected between August 1996 and March 1999, 30 influenza virus strains were isolated. Twenty-eight of the isolates were influenza A (H3N2) viruses and two were influenza B viruses. No H1N1 virus was isolated. Among 28 isolates of H3N2 virus, 3 strains were obtained outside the influenza season. Nucleotide sequences of the haemagglutinin (HA) genes of these isolates along with those from domestic patients were analysed in order to determine the influence of imported influenza viruses by travellers on epidemics in Japan. From the phylogenetic and chronological aspects, the possibility was suggested in one case in 1997/8 and two in the 1998/9 season that imported virus by travellers may have influenced the domestic influenza epidemics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10982075&dopt=Abstract flu, influenza