Human peripheral blood mononuclear cells produce IgA anti-influenza ( flu ) virus antibody in a secondary in vitro antibody response.

The function and immunoregulation of human IgA memory B cells producing anti-influenza ( flu ) virus antibody was analyzed in vitro in antigen-stimulated cultures. Peripheral blood mononuclear cells (PBMC) from seven of eight normal adult volunteers naturally immunized to influenza ( flu ) virus produced IgA anti-influenza ( flu ) virus antibody when stimulated in vitro with inactivated A/Aichi/68 [H3N2] influenza ( flu ) virus. This IgA antibody response was approximately one-eighth the IgG antibody response. PBMC from each of five patients with selective IgA deficiency failed to produce any measurable IgA antibody. When tonsillar mononuclear cells (TMC) were studied in a similar manner, a relatively higher IgA antibody response was obtained (one-third the IgG antibody) than with PBMC. Additional studies were undertaken to investigate the immunoregulation of this IgA antibody production and the relatively lower amount produced by PBMC than by TMC. Co-cultures of peripheral blood B cells with irradiated peripheral blood T cells (to possibly inactivate a radiosensitive IgA suppressor cell) did not result in a relative increase in IgA antibody production. Also, co-cultures of B cells with increasing numbers of T cells produced parallel increases of IgG and IgA antibody when plotted on a log scale with slopes of approximately 1, suggesting that a single helper T cell was limiting for both isotypes. Finally, pokeweed mitogen-stimulated co-cultures of peripheral blood and tonsillar B and T cells revealed that the B cell population, but not the T cell population, determined the amount of IgA anti-influenza ( flu ) virus antibody produced. Precursor frequency analyses of tonsillar and peripheral blood B cells in antigen-stimulated cultures confirmed that tonsils contained a higher precursor frequency of B cells for IgA anti-influenza ( flu ) virus antibody production (3.95/10(6) B cells) than did peripheral blood B cells (0.65/10(6) B cells). Thus, IgA memory cells are preferentially found in tonsillar tissue as compared with the peripheral blood, consistent with the role of the tonsils as a mucosal immune organ.

A pharmacoeconomic model for the treatment of influenza ( flu ).

OBJECTIVE: The aim of this study was to develop a generic treatment algorithm for influenza ( flu ) and influenza ( flu )-like illness (ILI) that could be used to estimate the costs and outcomes of current and new treatments for influenza ( flu ) in different countries for different patient subgroups. METHODS: A series of possible treatment pathways was identified and the probabilities of different patient subgroups following each pathway were estimated by using the published literature. The health outcomes and health service use and unit costs for each pathway were estimated from trial data and standard data sources. An interactive computer model was created, the base-case input parameter values were assigned, and estimates of the current costs of influenza ( flu ) and ILI in different population subgroups estimated. Sensitivity analyses were performed by changing input parameter values. RESULTS: The average healthcare cost of influenza ( flu ) and ILI per person in the US was $US72 for the general population and $US330 for a high risk population (1997 values). The average total cost per patient (healthcare cost plus productivity losses) was $US320 for the general population and $US546 for a high risk population. These costs are sensitive to changes in the proportion of patients visiting a physician and to the proportion of patients hospitalised with complications of the disease. Days to alleviate major symptoms and other health outcome measures are sensitive to the percentage of patients who receive antiviral therapy as well as to the efficacy of this therapy. CONCLUSIONS: The costs and health outcomes of influenza ( flu ) and ILI depend on the extent to which patients visit a physician, the use of antiviral drugs, and the incidence of complications requiring hospital care. The computer model will allow decision-makers to assess the cost effectiveness and the potential budget impact of new antivirals for treating influenza ( flu ).

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.

Influenza ( Flu ) (H1N1)-ISCOMs enhance immune responses and protection in aged mice.

Aging is associated with a decline in immune function and the elderly are therefore more susceptible to infectious disease and less responsive to vaccination. Influenza ( Flu ) antigens complexed as immunostimulatory complexes (ISCOMs) generate more potent protective immune responses compared with non-adjuvanted flu antigens in young adult mice. We report on the protective efficacy of flu-ISCOMs compared with the current split flu vaccine in an aged mouse model. DBA/2 mice aged 2 or 18 months were immunized with flu vaccine, ISCOMs or live virus, prior to challenge with the homologous virus. In aged mice, flu-ISCOMs induced significantly higher serum hemagglutination inhibition (HAI) titers compared to vaccine, similar to the levels obtained in young adult mice that received the split vaccine. Flu-ISCOMs but not vaccine induced cytotoxic T lymphocyte (CTL) responses in young and to a lesser degree in aged mice. In aged mice flu-ISCOMs significantly reduced illness and enhanced recovery from viral infection compared with vaccine. Our data suggests that flu-ISCOMs may offer an improved vaccine strategy for protection of elderly humans against the complications of influenza ( flu ) infection.

Treatment of an influenza ( flu ) A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control.

The safety and efficacy of current ACIP guidelines for the prevention and control of influenza ( flu ) in nursing home populations are uncertain. An outbreak of influenza ( flu ) A/Sichuan (H3N2) in a teaching nursing home during 1988 gave us the opportunity to evaluate the effectiveness of an influenza ( flu ) vaccination and amantadine prophylaxis protocol. Over 13 days, 12 of 60 residents developed influenza ( flu ). Prior influenza ( flu ) vaccination had been given to 94% of the residents. Protection from infection occurred in those tested who had antibody levels greater than or equal to 1:16 to the A/Leningrad (H3N2) antigen contained in the standard 1987-88 trivalent vaccine. However, five of 17 vaccinated residents who were tested had antibody levels less than or equal to 1:16 at the start of the outbreak. Amantadine (less than or equal to 100 mg/day) was given to all but one resident starting on the third day of the outbreak, and to employees starting on the sixth day of the outbreaks. Seven residents developed illness after the start of amantadine, although amantadine appeared to ameliorate their symptoms. Although amantadine was generally well tolerated by residents, employees receiving amantadine identified a high incidence of side effects and only 44% of employees took at least 70% of the prescribed amantadine. In our opinion, early detection and protocol-directed intervention probably abated a more severe influenza ( flu ) outbreak. Therefore we support existing recommendations that formal nursing home policies be established to ensure that residents and employees receive annual influenza ( flu ) vaccine and that chemoprophylaxis be used when outbreaks of influenza ( flu ) A are suspected.

Monovalent influenza ( flu ) A(H1N1) vaccine, 1986-1987. Recommendations of the Immunization Practices Advisory Committee. Centers for Disease Control, Department of Health and Human Services.

These supplemental recommendations provide guidelines for a monovalent influenza ( flu ) A(H1N1) vaccine for protection against a newly emerged variant of influenza ( flu ) that has recently caused outbreaks among children and young adults in Asia. Guidance is provided for the use of this monovalent vaccine, which contains 15 micrograms of A/Taiwan/1/86(H1N1) antigen, as a supplement to the standard trivalent influenza ( flu ) vaccine. Recommendations for the use of the standard trivalent influenza ( flu ) vaccine for the 1986-1987 season and the use of antivirals for the prevention and treatment of influenza ( flu ) remain in effect and should be referred to in conjunction with this supplemental recommendation. The trivalent vaccine is intended to protect against currently circulating strains of influenza ( flu ) A(H3N2) and influenza ( flu ) B viruses and may provide partial protection against the new influenza ( flu ) A(H1N1) variant.

Efficacy of subunit trivalent influenza ( flu ) vaccine in previously vaccinated children suffering from hemophilia.

OBJECTIVE: To assess humoral immune response to subunit trivalent influenza ( flu ) vaccine in children suffering from hemophilia who had been immunized for the first time in 1993-94 and then in 1996-97. METHODS: In autumn 1996-97, 38 previously vaccinated hemophiliac patients were subcutaneously immunized with a single 0.5-mL dose of subunit influenza ( flu ) vaccine containing the following three virus strains: A/Singapore/6/86 (H1N1), A/Wuhan/359/95 (H3N2) and B/Beijing/184/93 (HB). Antibody response to influenza ( flu ) vaccine was measured before vaccination, 3 weeks after vaccination and 6 months after vaccination, by use of hemagglutinin- and neuraminidase-inhibition tests. To present the level of seroconversion, geometric mean titers of anti-influenza ( flu ) antibodies, mean fold increase, protection rate and conversion rate were determined. All results were compared with the control group of 23 healthy persons who had never been vaccinated against influenza ( flu ) and for whom the same serologic tests were carried out as for the vaccinated group. RESULTS: Three weeks after immunization, antihemagglutinin antibody levels were 3.9-10.9 times higher than before vaccination, but the highest mean fold increase values were recorded 6 months after vaccination, ranging from 8.4 to 28.6. In the case of neuraminidase, mean fold increases of antibodies reached values of 3.6-12.3 three weeks after vaccination and 7.1-29.1 six months after vaccination. The highest proportion of subjects protected was observed 6 months after immunization and ranged from 76.3% to 97.4%, compared to 52.6-60.5% 3 weeks after vaccination. Similar values were obtained for conversion rate: 71.1-86.8% 6 months after vaccination, in comparison with 39.5-42.1% 3 weeks after immunization. CONCLUSIONS: All data obtained in the present study indicate a significant immune response to subunit trivalent influenza ( flu ) vaccine in patients suffering from hemophilia; this is additionally confirmed by the fact that none of the vaccinated children were infected with the influenza ( flu ) virus and no serious adverse reactions were observed after administration of the vaccine.

Influenza ( Flu ) surveillance: experiences from establishing a sentinel surveillance system in Germany.

OBJECTIVES--Before and during peak influenza ( flu ) periods there is increased morbidity from other respiratory tract disorders. Sentinel networks of primary care physicians can be very effective in the early detection of influenza ( flu ) epidemics and the German network, the Arbeitsgemeinschaft Influenza ( Flu ) (AGI), began its work in this area in 1992. METHODS--Data are transmitted weekly from the doctor's computer via Btx to a central computer. The numerator is the weekly number of acute respiratory infections (ARI) in five age groups and the denominator is the weekly number of patient consultations. Data on hospitalisation, mortality, and days of sick leave from work or school are also collected. Swabs for influenza ( flu ) specimens are collected in 30 physicians' offices each Monday and sent to three reference centres. FINDINGS--During the last recording period, from week 46 1993 to week 15 1994, 411 physicians' offices participated in the network. For 16 to 22 weeks, more than 60% of the participants transmitted data. During both the 1992-93 and 1993-94 influenza ( flu ) seasons, peaks were observed in the rate of ARI. There was a corresponding increase in sick leave from work and school. Rates for hospitalisation and deaths due to influenza ( flu ) showed no peaks during either season. CONCLUSIONS--Although the German sentinel network for influenza ( flu ) experienced some technical problems in the first year, it was possible to solve these. Reporting rates were very satisfactory in the second year. The network will now be expanded to include 750 physicians in order to receive 600 weekly reports and obtain a solid baseline for an early warning system.

Effect of mytilane, a bioglycan from the mussel Crenomytilus grayanus, on the course and outcome of experimental flu infection

Materials characterizing the antiviral activity of Mytilane, manifested by the protection of 50-60% of mice infected with the lethal dose of influenza ( flu ) virus and by a decrease in the severity of pathological changes in the lungs of mice, are presented. The inhibiting activity of Mytilane with respect to the reproduction of influenza ( flu ) virus in vivo and in vitro under experimental conditions is demonstrated.

Fusion-mediated microinjection of liposome-enclosed DNA into cultured cells with the aid of influenza ( flu ) virus glycoproteins.

Influenza ( Flu ) viruses were able to mediate fusion of DNA-loaded liposomes with living cultured cells such as monkey COS-7 cells. This was inferred from the appearance of CAT activity in recipient cells incubated with the combination of influenza ( flu ) viruses and liposomes loaded with the plasmid pSV2CAT. Influenza ( Flu ) virions were found to be as efficient as intact Sendai virions in mediating microinjection of foreign DNA into living cells. Also, reconstituted envelopes bearing either influenza ( flu ) glycoproteins or the combination of Sendai and influenza ( flu ) glycoproteins were highly efficient in promoting fusion of loaded liposomes with recipient cells. Introduction of DNA into cultured cells required the presence of an active influenza ( flu ) fusion protein; namely, an active HA glycoprotein. Very little or no CAT activity was observed in cells incubated with loaded liposomes and unfusogenic influenza ( flu ) viruses. The virus-induced fusion event probably occurs within intracellular organelles such as endosomes following receptor-mediated endocytosis of virus-liposome complexes. This is due to the fact that the viral fusion glycoprotein is activated only at acidic pH values such as those which characterize the intraendosomal environment. Results of the present work demonstrate for the first time microinjection of foreign DNA via fusion with membranes of intracellular organelles. The potential of the present system to serve as a biological carrier for in vivo use is discussed.