Influenza A virus potentiates basophil histamine release caused by endotoxin-induced complement activation

Histamine release from human basophil leukocytes was triggered by complement activation by means of endotoxins isolated from E. coli and Salmonella bacteria. Influenza A virus was found to enhance the mediator release, and the effect was caused by synergism, since virus itself did not release histamine. The potentiating effect was similar in cells from normal individuals and from patients with intrinsic asthma. The involvement of viral neuraminidase was examined by a potent neuraminidase inhibitor and this inhibitor completely abolished the potentiating effect by virus. A purified neuraminidase preparation obtained from Vibrio cholerae caused a similar potentiating effect in mediator release and the effect was abolished by the neuraminidase inhibitor. These findings indicate that viral neuraminidase is responsible for the potentiating effect of virus on the histamine release. This effect might play a role in septic conditions and possibly contribute to asthmatic attacks by infections.     

Neuraminidase immunotherapy: Serum potentiation of lymphocyte cytotoxicity related to immunoglobulin levels

Seven patients completed courses of immunotherapy using neuraminidase-altered autochthonous cells. Their response to therapy was monitored by a cytotoxicity assay using ³ H-proline-tagged tumor cells from the patient's own cultured tumor in a strictly autologous system. Serum effects were measured by exposing the tumor target cells to serum to see whether this impeded (blocked) or augmented (potentiated) lymphocyte cytotoxicity. Three of the seven patients developed increasing degrees of serum blocking effect and all died within six months of completing therapy. Four of the seven showed rapidly decreasing blocking and three eventual potentiation. Three patients are living, improved, and free of evidence of tumor. There was an increase in average serum immunoglobulins in patients developing potentiation, and a decrease in those showing blocking. In any immunotherapy program attention must be given to in vitro monitoring studies, and such studies should include attention to the serum factors influencing host response.     

Influenza A virus enhances allergic histamine release

Histamine release was examined in leukocyte suspensions from patients allergic to house dust mite, grass pollen, birch pollen or cat dander. Influenza A virus was found to enhance the antigen-induced mediator release, but did not cause release of histamine from the cells per se. Also histamine release induced by anti-IgE in cell suspensions from normal individuals was enhanced by virus. The potentiating effect of influenza A virus might be due to neuraminidase on the surface of virus, since a similar effect was caused by a purified neuraminidase obtained from Vibrio cholerae, and the effect of virus as well as the neuraminidase was completely abolished by a potent neuraminidase inhibitor. The synergistic enhancement in IgE-mediated histamine release by virus could be of significance for the conversion from latent to manifest asthma.     

Regeneration of membrane sialic acid after neuraminidase treatment of leukemic granulocytes

Granulocytes from patients with chronic myelogenous leukemia (CML) were studied for their ability to regenerate surface sialic acid following treatment with Vibrio cholera neuraminidase (VCN) in vitro. Immediately after neuraminidase treatment, CML and normal granulocytes showed similar incorporation of radioactivity after surface labelling with sodium periodate/potassium-H3-borohydride (PI/BH3(4)). CML granulocytes treated with neuraminidase then incubated for 18 h in nutrient medium showed strikingly increased PI/BH3(4) labelling, usually greater than initial pretreatment values, consistent with a rapid reappearance of sialic acid in the cell membrane. This pattern was not seen in normal granulocytes. The aberrant regeneration of sialic acid in CML granulocytes in vitro could be inhibited by addition of 3 X 10(-6) M retinoic acid, suggesting either a direct effect on membrane glycoconjugate synthesis or an association with granulocyte differentiation.     

Detection of Anti-Red Blood Cell Antibodies by Treatment of the Cells with Neuraminidase

Neuraminidase treated RBC were used to detect incomplete unbound anti RBC antibodies in the plasma of patients with immune diseases. 80% (48 out of 60) of the examined patients gave positive results with this method while all the 50 normal normal controls were negative. The indirect antiglobulin test was negative in all the patients. In the direct antiglobulin test only two RBC samples, whether treated with neuraminidase or not, gave positive results. The present study indicates that the assay of plasma on neuraminidase treated RBC may serve as a sensitive method for the detection of the presence of anti RBC antibodies in various immunological diseases.     

Pediatric hospitalizations with influenza A infection during the 2009–2010 pandemic in five hospitals in Japan

Background: The aim of this study was to identify the clinical characteristics of hospitalized children with the 2009 pandemic influenza virus infection in Japan. Methods: We retrospectively reviewed cases of hospitalized children younger than 16 years with laboratory‐confirmed influenza A virus infection during the 2009–2010 pandemic season in five hospitals in Japan. Results: A total of 515 cases were included in the analysis. The median age was 6.3 years (range 0–15), and 216 subjects (41.9%) had one or more underlying medical conditions. There were no fatalities, but 16 patients (3.1%) required intensive care. More than 93% of the subjects received neuraminidase inhibitors, and more than 87% received these medications within 48 h of the onset of symptoms. Approximately 80% of all subjects were admitted to hospital within 48 h of the onset of symptoms. Conclusions: There were no fatalities, and the proportion of patients with serious illness was substantially lower than previously reported from other countries. Good access to medical services and proactive treatment may have contributed to the lower disease burden of the 2009 influenza pandemic on Japanese children.     

Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season

Please cite this paper as: Coleman et al. (2011) Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season. Influenza and Other Respiratory Viruses 5(6), 404–408. Background Data regarding both rates of acute respiratory illness in health care workers and experience with long‐term antiviral prophylaxis are sparse. Objective To determine the efficacy and tolerability of oseltamivir prophylaxis versus seasonal influenza vaccine for the prevention of influenza among health care workers. Methods We conducted a pilot, randomized control study during the 2007/2008 influenza season in a tertiary care setting. Adult health care workers 18–69 years of age were recruited and randomly assigned in a 4:1 ratio to receive either oseltamivir (Tamiflu^®; Roche) 75 mg once daily prophylaxis or seasonal influenza (Fluviral^®) vaccine. Results Of 56 adults enrolled, 12 received vaccine and 44 received prophylaxis. Incidence of symptomatic laboratory‐confirmed influenza was similar for participants in the vaccine and prophylaxis arms (17% and 24%, respectively; P = 0·71). Participants who developed an acute respiratory illness during the study period reported working 85% of scheduled work days, and 29% stated that they worked despite feeling miserable because they were too busy to stay home. Of 42 participants who initiated oseltamivir prophylaxis, four discontinued it owing to side effects. Median duration of oseltamivir prophylaxis was 121 days, with 34 (81%) continuing ≥12 weeks. Conclusions During an extended season of suboptimal vaccine match, 22% of health care workers receiving antiviral prophylaxis or seasonal influenza vaccine developed symptomatic laboratory‐confirmed influenza. Long‐term antiviral prophylaxis against influenza was generally well tolerated with good compliance.