flu
Reactivity and vulnerability to stress-associated risk for upper respiratory illness.

Cohen S, Hamrick N, Rodriguez MS, Feldman PJ, Rabin BS, Manuck SB.

Department of Psychology, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213-3890, USA. scohen andrew.cmu.edu

OBJECTIVE: We tested the hypothesis that the greater a person's laboratory stress-elicited elevation in cortisol, the greater the life stress-related risk for upper respiratory infection (URI). We also tested the prediction that the greater the laboratory stress-elicited rise in natural killer cell (NK) cytotoxicity, the smaller the life stress-related URI risk. Finally, we explored whether sympathetic nervous system (SNS) and enumerative immune reactivities to laboratory stress moderate the relation between life stress and URI. METHODS: At baseline, 115 healthy subjects were administered a negative stressful life events checklist and were tested to assess their SNS (blood pressure, heart rate, and catecholamines), HPA (cortisol), and immune (NK cell cytotoxicity and lymphocyte subsets) reactivities to laboratory speech tasks administered 2 weeks apart. Responses were averaged across the two laboratory assessments to create reactivity scores. After these assessments were completed, participants were followed weekly for 12 consecutive weeks. At each follow-up they completed a measure of perceived stress experienced over the last week. They were also instructed to contact the study coordinator if they had a cold or flu at any time during follow-up. A health care worker verified reported illnesses. RESULTS: In a traditional prospective analysis, high cortisol reactors with high levels of life events had a greater incidence of verified URI than did high reactors with low levels of life events and low reactors irrespective of their life event scores. Using hierarchical linear modeling, CD8(+) number, Natural Killer (NK) cell number, and NK cell cytotoxicity, each interacted with weekly perceived stress levels in predicting concurrent occurrences of self-reported URIs. For these outcomes, low immune reactors were more likely to experience an URI during high stress than low stress weeks. High immune reactors did not exhibit differences in weekly URIs as a function of weekly stress level. The SNS reactivity markers did not moderate the association of stress and URI incidence in either analysis. CONCLUSIONS: Acute HPA and immune responses to laboratory stressors are markers of how vulnerable people are to the increased risk for URI associated with stressors in the natural environment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11914447&dopt=Abstract flu, flu medicine, tamiflu



flu
Infection with influenza a virus leads to flu antigen-induced cutaneous anaphylaxis in mice.

Grunewald SM, Hahn C, Wohlleben G, Teufel M, Major T, Moll H, Brocker EB, Erb KJ.

Klinik und Poliklinik fur Haut- und Geschlechtskrankheiten, Universitat Wurzburg, Wurzburg, Germany. grunewald-s.derma mail.uni-wuerzburg.de

It is well established, that viral infections may trigger urticaria or allergic asthma; however, as viral infections induce T helper 1 polarized responses, which lead to the inhibition of T helper 2 cell development, the opposite would be plausible. We wanted to investigate how viral infections may mediate allergic symptoms in a mouse model; therefore, we infected BALB/C mice with influenza A virus intranasally. Histologic analyses of lung sections and bronchoalveolar lavages were performed. In addition, cells from the mediastinal lymph nodes were restimulated in vitro to analyze which types of cytokines were induced by the flu infection. Furthermore, flu-specific antibody titers were determined and local anaphylaxis was measured after rechallenge with flu antigen. We found that airways inflammation consisted predominately of macrophages and lymphocytes, whereas only a few eosinophils were observed. interferon-gamma but no interleukin-4 and little interleukin-5 could be detected in the culture supernatants from in vitro restimulated T cells from the draining lymph nodes. The antibody response was characterized by high levels of virus-specific IgG2a, IgG2b, and IgG1 and, surprisingly, low levels of virus-specific IgE antibodies. Interestingly, flu-infected mice developed active and passive cutaneous anaphylaxis after rechallenge with flu-antigen. As the passive cutaneous anaphylaxis reaction persisted over 48 h and was significantly lower after passive transfer of the serum, which was IgE depleted, local anaphylaxis seemed to be mediated predominately by specific IgE antibodies. Taken together, our results demonstrate that mice infected with flu virus develop virus-specific mast cell degranulation in the skin. Our results may also have implications for the pathogenesis of urticaria or other atopic disorders in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11918711&dopt=Abstract flu, flu medicine, tamiflu



flu
Rapid and sensitive detection of respiratory virus infections for directed antiviral treatment using R-Mix cultures.

St George K, Patel NM, Hartwig RA, Scholl DR, Jollick JA Jr, Kauffmann LM, Evans MR, Rinaldo CR Jr.

Clinical Virology Laboratory, University of Pittsburgh Medical Center, A-912, Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA. stgeorgek msx.upmc.edu

BACKGROUND: The development of new anti-influenza drugs has led to concerns regarding the impact on healthcare costs if they are used indiscriminately. Restricting their use to proven influenza virus infections has the potential to overcome costly inappropriate therapy. However, conventional culture (CC) does not generate results quickly enough to facilitate the timely initiation of treatment, and rapid detection tests have suboptimal sensitivity. We therefore investigated a new rapid culture system (R-Mix) that contains a mixture of two cell lines and detects respiratory viruses within 24 h. OBJECTIVES: To compare the analytical sensitivity of R-Mix with CC and rapid detection methods, for the detection of influenza and other respiratory viruses. To compare the clinical sensitivity of R-Mix with CC and direct antigen detection for the detection of respiratory viruses in primary and acute care settings. STUDY DESIGN: Stock cultures of influenza virus were titrated and tested by R-Mix, ZstatFlu and FLU OIA. Stock cultures of adenovirus and parainfluenza virus type 3 were titrated and tested by R-Mix and CC. Specimens, which had previously tested positive for influenza viruses, were titrated and tested by R-Mix and CC. In symptomatic patients, the majority of whom were from primary care settings, 124 sequential specimens were tested for influenza viruses by immunofluorescent direct antigen detection and R-Mix. A separate set of 111 sequential specimens, from various symptomatic patient groups, were tested for influenza viruses by CC and R-Mix. Additionally, in acute care patients being surveillance tested during periods of immunosuppression, 155 specimens were tested for respiratory viruses (influenza A and B, parainfluenza 1-3, adenovirus and respiratory syncytial virus (RSV)) by CC and R-Mix. RESULTS: With titrated stock cultures, R-Mix showed an analytical limit of detection of ten infectious virus particles per vial for influenza A, compared with 100,000 particles per test for FLU OIA and 1,000,000 for ZstatFlu. R-Mix also showed a 100-fold greater sensitivity for the detection of influenza A and equivalent sensitivity for the detection of influenza B when compared with CC in titrated known positive specimens. Further, it showed equivalent sensitivity to CC for the detection of adenovirus and parainfluenza virus type 3 in titrated stock cultures. Among prospective specimens from symptomatic patients, the sensitivity of R-Mix, CC and direct antigen detection tests (DAT) for influenza virus detection, was 100, 67 and 66%, respectively, and the specificity was 100, 100 and 98%, respectively. In surveillance specimens from immunosuppressed patients, the sensitivities of R-Mix and CC for respiratory virus detection were equivalent. Moreover, R-Mix results were available within 24 h, and by altering the antibody staining reagents either influenza viruses, or all seven major respiratory viruses, could be detected and distinguished in a single test. CONCLUSIONS: R-Mix is a simple, rapid and sensitive system for the detection of influenza viruses that facilitates the restriction of antiviral drugs to patients with culture-confirmed infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11744435&dopt=Abstract flu, flu medicine, tamiflu



flu
Effects of the nature of adjuvant and site of parenteral immunization on the serum and mucosal immune responses induced by a nasal boost with a vaccine alone.

Guy B, Fourage S, Hessler C, Sanchez V, Millet MJ.

Research Department, Pasteur Merieux Connaught, 69280 Marcy l'Etoile, France. bguy fr.pmc-vacc.com

Outbred OF1 mice were immunized subcutaneously with flu vaccine, either in the neck or in the lumbar region (back), in combination with adjuvants inducing either a Th1- or a Th2-type response, referred to as adjuvants A1 and A2, respectively. After two parenteral immunizations, the mice were boosted intranasally with nonadjuvanted vaccine. The serum response was analyzed after each immunization by measuring specific immunoglobulin A (IgA), IgG1, and IgG2a antibody levels, while the local response (same isotypes) was measured in the salivary glands after the mucosal boost by ELISPOTs. We observed that systemic priming at any of the two sites with a Th2 rather than a Th1 adjuvant dramatically enhanced the mucosal IgG1 and IgA responses following a mucosal boost with unadjuvanted vaccine. In addition, as judged by the IgG2a/IgG1 ratios and serum IgA levels, immunization of mice in the back induced a rise in Th2 response compared to neck immunization with adjuvant A1. In contrast, such back immunization with adjuvant A2 reversed the Th1-Th2 balance in favor of the Th1 response compared to neck immunization. Similar differences were observed in mucosal antibody levels according to the site of priming with one given adjuvant; priming in the back with adjuvant A1 increased the mucosal IgA and IgG1 responses compared to neck priming, while the local IgG2a levels were decreased. The reverse was true for adjuvant A2. Back versus neck priming with this latter adjuvant decreased the mucosal IgG1 response, while local IgG2a levels were increased. The different lymphatic drainages of the two sites of parenteral immunization may explain these differences, due to the targeting of particular lymphoid inductive sites. Some of these sites may represent crossroads between systemic and mucosal immunity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9729544&dopt=Abstract flu, flu medicine, tamiflu



flu
Surveillance of influenza-like illness in France. The example of the 1995/1996 epidemic.

Carrat F, Flahault A, Boussard E, Farran N, Dangoumau L, Valleron AJ.

Epidemiologie et Sciences de l'Information, INSERM U444, Institut Saint-Antoine de Recherche sur la Sante, Paris, France.

STUDY OBJECTIVES: To discover if continuous computerised collection of morbidity data through a medical practice based sentinel network can be used to monitor influenza-like illness (ILI) epidemics. To obtain rough estimates of influenza vaccine effectiveness. DESIGN: Continuous passive surveillance of ILI through a computerised network of voluntary sentinel general practitioners (SGPs) in France (Sentinelle system). SETTING: Five hundred SGPs practices. PARTICIPANTS: Since 1984, SGPs updated a database with information on eight communicable diseases including ILI, via videotext terminals. Each ILI case is defined by the association of a sudden fever of 39 degrees C or above, respiratory symptoms, and myalgias. An ILI epidemic is detected when the national weekly incidence rate exceeds a seasonal threshold for two successive weeks. MAIN RESULTS: An ILI epidemic was reported from November 1995 to January 1996. In total, 13,951 individual cases were reported by SGPs during the epidemic period. The size of the epidemic (number of patients consulting a GP) was estimated to be 2,370,000 subjects. Maps of the epidemic showed that all regions have reported a high level ILI activity. The attack rate was the highest in school age children (13.5/100) and decreased as the age rose. Nearly 6% of the reported ILI cases among adults and elderly were vaccinated. The flu vaccine effectiveness against ILI was estimated to be 66% (95% CI 73%, 92%), ranging between 83% (95% CI 73%, 92%) among the subjects aged 15 to 24 years old to 16% (95% CI -12%, 44%) among the subjects aged 75 years or older. CONCLUSIONS: The Sentinelle system demonstrated adequate sensitivity and timeliness regarding ILI epidemic. Moreover, results of the monitoring were made available on the internet to increase the dissemination of information. Also, estimates of influenza vaccine effectiveness have been easily obtained. Altogether, they represent key points for the control of crisis situation such as ILI epidemics or pandemics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9764269&dopt=Abstract flu, flu medicine, tamiflu



flu
[Evaluation of a rapid enzyme immunoassay membrane test for diagnosis of influenza A virus infection]

[Article in Japanese]

Shimizu H, Watanabe S, Kawakami C, Hirai Y, Kimura K, Sugaya N, Imai M.

Kawasaki City Institute of Public Health.

A rapid enzyme immunoassay membrane test, Directigen Flu A (Becton Dickinson, USA), was evaluated by using virus isolates and clinical specimens. The reference laboratory diagnosis was based on the results of virus isolation. Directigen Flu A was reactive for all subtypes of human influenza A viruses, including reference strains of H1N1, H2N2 and H3N2. Moreover, H5N1 (Hongkong/156/97) was also detected by this kit. No cross reactivity was detected with other respiratory viruses. Directigen Flu A showed positive reaction with the solution containing influenza A virus of 2.4 x 10(3) pfu/assay. The rapid test demonstrated 77.9% sensitivity and 98.4% specificity for testing of throat swabs from children with respiratory symptoms. It showed higher sensitivity and specificity (92.1% and 100%) for testing of nasopharyngeal aspirates. Directigen Flu A should be useful for the rapid diagnosis of influenza A virus infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9780586&dopt=Abstract flu, flu medicine, tamiflu