flu
Circumvention of defective CD4 T helper cell function in HIV-infected individuals by stimulation with HLA alloantigens.

Clerici M, Stocks NI, Zajac RA, Boswell RN, Via CS, Shearer GM.

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

PBL from approximately 50% of asymptomatic individuals infected with HIV have been previously demonstrated to exhibit defective in vitro Th function that is selective for influenza A virus (FLU), but not for HLA alloantigens (ALLO). In this report, we have further studied HIV+ individuals with this selective Th defect, and demonstrate that defective in vitro CTL responses to FLU can be restored by costimulation with FLU + ALLO. In contrast, HIV+ patients who have lost Th responses to ALLO were unable to correct CTL responses to FLU by this costimulation procedure. These findings indicate that intact Th responses to ALLO can be used in vitro to provide Th signals necessary to activate the T effector cell response to a potential pathogenic virus. Our results raise the possibility that a program of in vivo coimmunization with ALLO plus antigens of potential pathogens (including HIV) can be useful in HIV+ patients exhibiting selective defects in Th function. Furthermore, this approach could be incorporated in vaccine trials aimed at enhancing immunity to HIV in patients who have been infected previously with this virus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1970348&dopt=Abstract flu, flu medicine, tamiflu



flu
Frequency of adverse reactions after influenza vaccination.

Margolis KL, Poland GA, Nichol KL, MacPherson DS, Meyer JD, Korn JE, Lofgren RP.

Department of Medicine, University of Minnesota, Minneapolis.

PURPOSE: Although concern about side effects constitutes a major deterrent to patient compliance with recommendations for influenza vaccination, there is a paucity of data about the frequency of adverse reactions to newer trivalent vaccines. Our aim was to determine the frequency of adverse reactions to influenza vaccine in older, chronically ill persons, many of whom are at high risk for influenza-related morbidity. PATIENTS AND METHODS: We conducted a telephone survey of 40% of the patients who were vaccinated at a walk-in flu shot clinic. The subjects were randomly assigned to two groups. To determine postvaccine symptom rates, Group I was interviewed seven days after vaccination. Group II was interviewed 21 days after vaccination in order to control for baseline symptom rates. Both groups were queried about fever, disability, and flu-like illness in the week preceding the interview. RESULTS: Of 816 patients selected, 650 (79.6%) completed the interview. The mean age of the subjects was 63, and more than two thirds were at risk for influenza-related morbidity. The frequencies of self-reported fever (5.3% versus 5.1%, p = 0.91) and disability (10.4% versus 9.3%, p = 0.65) were similar in the two groups. However, a significantly higher proportion of Group I subjects reported a flu-like illness compared to the Group II subjects (14.2% versus 8.7%, p = 0.03). Although Group I subjects were more likely to report flu-like illness within two days of vaccination compared to a similar time interval for Group II subjects, there was no corresponding clustering of disability after vaccination. CONCLUSION: We conclude that the overall frequency of symptoms in both groups was low; however, the absolute risk of a flu-like illness was 5.5% higher during the first week following influenza vaccination when compared with the third week after the injection. These symptoms did not result in a decreased ability to perform usual daily activities.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2294762&dopt=Abstract flu, flu medicine, tamiflu



flu
Improving influenza vaccination performance in an HMO setting: the use of computer-generated reminders and peer comparison feedback.

Barton MB, Schoenbaum SC.

Harvard Community Health Plan, Brookline, MA 02146.

We evaluated a program for improving influenza immunization performance in a health maintenance organization (HMO). The HMO implemented several interventions successively from 1984-87: a postcard reminder to members at high risk for complications of influenza, a computer-generated reminder to the physician at the time of any primary care visit by high-risk patients, performance feedback to chiefs of service, and, finally, retrospective feedback to each physician comparing his/her performance with that of the other physicians. We examined immunization rates for a group of members older than age 65, a high-risk group under age 65, and a group of diabetic members who had not been subject to the reminders (vs a group who had been covered by the program). Vaccination rates were increased in those diabetic members who received reminders. Nevertheless, among members younger and older than age 65 whose experience was observed over three flu seasons, a significant increase in vaccination rates was not achieved until physician feedback was added to the program. We conclude that each element of the reminder and feedback program has contributed to the overall increase in vaccination rates at the HMO and that effective ongoing influenza immunization programs can be implemented in practice settings with appropriate systems support.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2327527&dopt=Abstract flu, flu medicine, tamiflu



flu
Achieving the national health objective for influenza immunization: success of an institution-wide vaccination program.

Nichol KL, Korn JE, Margolis KL, Poland GA, Petzel RA, Lofgren RP.

Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417.

PURPOSE: To enhance influenza vaccination rates for high-risk outpatients at the Department of Veterans Affairs Medical Center (VAMC) in Minneapolis, Minnesota, an institution-wide immunization program was implemented during 1987. PATIENTS AND METHODS: The program consisted of: (1) a hospital policy allowing nurses to vaccinate without a signed physician's order; (2) stamped reminders on all clinic progress notes; (3) a 2-week walk-in flu shot clinic; (4) influenza vaccination "stations" in the busiest clinic areas; and (5) a mailing to all outpatients. Risk characteristics and vaccination rates for patients were estimated from a validated self-administered postcard questionnaire mailed to 500 randomly selected outpatients. For comparison, 500 patients were surveyed from each of three other Midwestern VAMCs without similar programs. RESULTS: Overall, 70.6% of Minneapolis patients were high-risk and 58.3% of them were vaccinated. In contrast, 69.9% of patients at the comparison medical centers were high-risk, but only 29.9% of them were vaccinated. CONCLUSION: The Minneapolis VAMC influenza vaccination program was highly successful and may serve as a useful model for achieving the national health objective for influenza immunization.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2382664&dopt=Abstract flu, flu medicine, tamiflu



flu
Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging.

Clerici M, Stocks NI, Zajac RA, Boswell RN, Lucey DR, Via CS, Shearer GM.

Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.

We have tested the T helper cell (TH) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV- control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above. The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2574188&dopt=Abstract flu, flu medicine, tamiflu



flu
Interferon-alpha: an effective adjuvant for peptide-based cytotoxic T-cell vaccines.

Takasu H.

Department of Immunology, Kurume University School of Medicine, Kurume 830-0011, Japan.

An important issue for developing a vaccine therapy for human malignancy is identifying adjuvants that can elicit T-cell responses to peptides. The present study evaluates interferon-alpha (IFN-alpha) as a vaccine adjuvant. C57BL/6 mice were immunized subcutaneously with peptide derived from influenza virus (Flu) either with or without IFN-alpha using different vaccine formulations. IFN-alpha significantly enhanced cytotoxic T lymphocytes (CTL) induction in mice immunized with Flu peptide in incomplete Freund's adjuvant (IFA). Flu peptide administered continuously for 3 days by osmotic pump with IFN-alpha could elicit CTL induction, whereas either Flu peptide or IFN-alpha alone was non immunogenic. Furthermore, injection of the liquid formation of Flu peptide with IFN-alpha in phosphate-buffered saline (PBS) did not elicit CTL induction. These results suggest that the continuous administration of peptide and local delivery of IFN-alpha are important for efficient CTL induction, and that IFN-alpha is an effective adjuvant for peptide-based vaccines.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11501499&dopt=Abstract flu, flu medicine, tamiflu