flu
Multiple defects of T helper cell function in newly diagnosed patients with Hodgkin's disease.

Clerici M, Ferrario E, Trabattoni D, Viviani S, Bonfanti V, Venzon DJ, Clerici E, Shearer GM, Villa ML.

Cattedra di Immunologia, Universita di Milano, Italy.

T helper cell (TH) function, as assessed by interleukin-2 (IL-2) production and [3H]thymidine incorporation, was studied in 47 newly diagnosed untreated patients with Hodgkin's disease (HD) and 34 healthy controls. Three different stimuli were used to stimulate in vitro peripheral blood mononuclear cells (PBMC): influenza A vaccine (FLU), HLA alloantigens (ALLO) and phytohaemagglutinin (PHA). Four different patterns of TH function were observed in HD patients: (1) IL-2 production in response to all of the stimuli (40%); (2) IL-2 production in response to ALLO and PHA but not to FLU (26%); (3) IL-2 production in response to PHA alone (19%); and (4) failure to respond by IL-2 production to any of the three of the stimuli (15%). Thus, defective in vitro TH function was detected in the majority of these patients (60%). Defective TH function was observed in none of the 34 controls. Severely compromised TH function (patterns 3 and 4) tended to be associated with more advanced clinical presentation and more compromised haematological parameters (P < 0.05). The IL-2 production assay was more sensitive than the proliferative assay as only 30% of the HD patients failed to proliferate in response to FLU, and none failed to proliferate in response to either ALLO or PHA; this assay can detect subtle, multiple patterns of immune dysregulation in untreated HD patients. Our results suggest that HD is associated with a fundamental dysregulation in TH function, illustrate the complexity of such dysregulation, and raise the possibility that HD progression will be associated with a type-1-type-2 switch in immunoregulatory cytokine production.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7833103&dopt=Abstract flu, flu medicine, tamiflu



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T helper cell dysfunction in systemic lupus erythematosus (SLE): relation to disease activity.

Bermas BL, Petri M, Goldman D, Mittleman B, Miller MW, Stocks NI, Via CS, Shearer GM.

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

Patients with systemic lupus erythematosus (SLE) are known to have defects in both humoral and cellular immunity. The significance of defective T cell-mediated immunity and its relationship to disease activity have not been clearly established. We studied in vitro T helper cell (Th) function in 150 SLE outpatients and correlated Th function with validated measures of disease activity. Interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC) was measured after stimulation with the recall antigens influenza A virus (FLU) and tetanus toxoid (TET), irradiated allogeneic peripheral blood mononuclear cells (ALLO), and phytohemagglutinin (PHA). We observed three patterns of Th response: (1) 76 of 150 (50%) of patients responded to the recall antigens FLU and/or TET, ALLO, and PHA; (2) 62 of 150 (42%) of patients did not respond to recall antigens but responded to ALLO and PHA; and (3) 12 of 150 (8%) of patients did not respond to either recall antigens or ALLO antigens. This diminished T cell function was correlated with higher disease activity as measured by four scales of clinical activity, such that individuals who exhibited more in vitro immune dysfunction presented with significant increases in their clinical activity indices. The alterations in T cell function could not be accounted for by medication doses alone. Thus, SLE patients have multiple distinct defects at the level of the Th cell which are associated with clinical measures of disease activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7929693&dopt=Abstract flu, flu medicine, tamiflu



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Adult bacterial nasopharyngitis: a clinical entity?

Heald A, Auckenthaler R, Borst F, Delaspre O, Germann D, Matter L, Kaiser L, Stalder H.

Policlinique de medecine, Hopital Cantonal Universitaire, Geneva, Switzerland.

OBJECTIVE: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. DESIGN: Prospective case series. SETTING: Walk-in medical clinic of a university hospital. PATIENTS: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. MEASUREMENTS AND MAIN RESULTS: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 334 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes. Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6-14.2), Moraxella catarrhalis (odds ratio 12.9, 95% confidence interval 3.1-79.5), and Hemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2-7.4) were all associated with the presence of leukocytes. In contrast, nasopharyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were "pathogenic" bacteria found. CONCLUSIONS: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8120682&dopt=Abstract flu, flu medicine, tamiflu



flu
Split-virus influenza vaccines: do they provide adequate immunity in the elderly?

McElhaney JE, Meneilly GS, Lechelt KE, Bleackley RC.

Department of Medicine, University of Alberta, Edmonton.

BACKGROUND. Senescence of T-cell function increases susceptibility to influenza with aging. In healthy elderly, we have found that inactivated whole-virus vaccine (WVV) effectively boosts helper T-cell (Th)-mediated immunity. Recently, however, the use of WVV has been superseded by split-virus vaccine (SVV) to questionably reduce adverse effects of vaccination. METHODS. Healthy young adults were compared to healthy elderly adults for their response to SVV. Peripheral blood mononuclear cells (PBMC) obtained pre-vaccination and 6 and 12 weeks post-vaccination, were cultured with live influenza virus, and supernatant IL2 activity was measured. RESULTS. Both groups showed an increase in in vitro IL2 activity by 6 weeks post-vaccination but IL2 decreased to pre-vaccination levels by 12 weeks. Young and elderly adults who had received WVV one year prior did not respond to SVV in this study. CONCLUSIONS. SVV does not provide Th-mediated immunity for the duration of the flu season and may actually suppress Th-mediated immunity in previous recipients of WVV.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8126350&dopt=Abstract flu, flu medicine, tamiflu



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Disassembly of influenza C viruses, distinct from that of influenza A and B viruses requires neutral-alkaline pH.

Zhirnov OP, Grigoriev VB.

D. I. Ivanovsky Virology Institute, Moscow, Russia.

Influenza C (Flu C) viruses comprise an internal ribonucleoprotein (RNP) and an outer lipoprotein envelope with surface spike glycoproteins and the M1 protein matrix. The lipoprotein envelope and spike glycoproteins are solubilized by nonionic detergent in a pH-independent manner. In contrast, disassembly of the M1 protein matrix appears to depend on pH. Treatment of Flu C viruses with nonionic detergent in neutral or alkaline medium (pH 9.0-7.4) results in disintegration of the virion M1 matrix and leads to a significant release of RNP free of the M1 protein. In acidic medium (pH 6.0-5.0), the M1 matrix is not removed and the viral core-like complex of RNP along with the M1 matrix cover is released. Since Flu A and B viruses were characterized by acid-dependent disassembly of the virion M1 matrix, Flu C viruses seem to resemble the paramyxoviruses, which also show a neutral-alkaline pH dependence on matrix disintegration. These observations suggest that uncoating mechanisms of influenza C viruses and paramyxoviruses in target cells may be similar.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8128628&dopt=Abstract flu, flu medicine, tamiflu



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[Vaccinations in adults: the coverage of the users of a health center]

[Article in Spanish]

Alonso Gordo JM, Hernandez Perlines MV, Sanz Fernandez E, Lopez Carabano A.

Unidad Docente de Medicina Familiar y Comunitaria, Centro de Salud Guadalajara-Sur Guadalajara.

OBJECTIVE. To find the cover and records of recommended adult vaccinations and to identify possible causes of deficient cover. DESIGN. A descriptive crossover study using analysis of histories and a questionnaire. SETTING. General Medical and Nursing stations at the urban Guadalajara-Sur Health Centre. PATIENTS. Those people over 15 and with a prior appointment who were treated at the stations. A random selection of 352 patients. Final size: 275 patients (78.1%). MEASUREMENTS AND MAIN RESULTS. 20.5% +/- 4.9 of the population surveyed had been correctly vaccinated against tetanus. There was better cover of males (p < 0.05) and under-45s (p < 0.001; Confidence level--95%). 41.8% +/- 13.6 of indicated patients stated that they had been vaccinated against German measles, while 79.5% +/- 7.0 had received an anti-flu vaccination in the last campaign. Between 5 and 21%, according to age groups, possessed a vaccination card, with the levels noted in the medical records oscillating between 5.7% and 38.6%, respectively, for German measles and flu vaccination. Causes cited for non-vaccination were: ignorance in the cases of anti-tetanus (87.3%) and German measles (97%), carelessness (40%) or rejection (26.7%) for the anti-flu. CONCLUSIONS. Only anti-flu vaccination reaches acceptable coverage and understanding among our Centre's adult users, lack of knowledge being the main problem cited. We consider the recording level insufficient, both in clinical notes and on the vaccination cards. An intensive information campaign by health workers is needed, along with widespread vaccination to correct these deficiencies and reach the optimum coverage.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8155795&dopt=Abstract flu, flu medicine, tamiflu