A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy.
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BACKGROUND: A phase 2 trial was conducted to assess in young infants the safety, tolerability, infectivity, and immunogenicity of multiple doses of an intranasal vaccine using bovine parainfluenza virus type 3 (bPIV3). METHODS: One hundred ninety-two healthy 2-month-old infants were randomized 1 : 1 : 1 to receive 1x10(5) median tissue culture infective dose (TCID(50)) bPIV3 vaccine, 1x10(6) TCID(50) bPIV3 vaccine, or placebo at 2, 4, 6, and 12-15 months of age. Safety information was collected by use of diary sheets and telephone interviews. Nasal wash and serum specimens were collected for assessment of infectivity and immunogenicity. RESULTS: The safety profiles of both dosages of bPIV3 were similar to that of placebo, with the exception of fever with temperature of >/=38.1 degrees C after dose 2 only, occurring in 34% of the 1x10(5) TCID(50) group, 35% of the 1x10(6) TCID(50) group, and 12% of the placebo group (P<.01). No vaccine-related serious adverse events were reported. The cumulative vaccine infectivity (isolation of bPIV3 and/or bPIV3 seroconversion) after dose 3 was similar in the 2 vaccine groups (87% in the 1x10(5) TCID(50) group and 77% in the 1x10(6) TCID(50) group) (P=.46). Seroconversion rates after dose 3, assessed by means of hemagglutination inhibition assay, after adjustment for decrease in maternal antibody titers, were 67% in the 1x10(5) TCID(50) group, 57% in the 1x10(6) TCID(50) group, and 12% in the placebo group (P<.01). Isolation of bPIV3 was common after dose 1, dose 2, or dose 3, but only 1 of 51 participants in the vaccine groups had bPIV3 isolated after dose 4. CONCLUSIONS: Multiple doses of bPIV3 vaccine were well tolerated and immunogenic in young infants. (+info)
Diagnostic system for rapid and sensitive differential detection of pathogens.
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Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples. (+info)
Evaluation of three immunoassay kits for rapid detection of influenza virus A and B.
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Influenza causes high morbidity and mortality in very young and elderly individuals, which can be controlled with antivirals and/or vaccines. The success of therapeutic measures is predicated on the rapid and precise diagnosis of the infection. We compared three rapid influenza immunoassay (RIIA) kits for the diagnosis of influenza virus A and B using 178 respiratory specimens submitted for routine testing. BD Directigen Flu A+B (Directigen), Directigen EZ Flu A+B (EZ), and NOW Flu A NOW Flu B (NOW; Binax) tests had comparable combined influenza virus A and B specificities, varying from 94 to 98%. In contrast, the sensitivity of EZ was significantly lower (39%) than that of NOW (76%) and marginally lower than that of Directigen (56%). The differences in sensitivity were most evident in patients who were >9 years old (Directigen, 53%; EZ, 32%; and NOW, 69%). Among specimens, bronchoalveolar lavage fluids yielded the most discrepant results, with sensitivities varying from 0 (EZ) to 100% (NOW), followed by nasopharyngeal swabs (sensitivities of 27 to 100%) and nasal washes (50 to 81%). The Directigen kit format allowed for faster completion but more cumbersome performance and more difficult interpretation compared with the other two kits. Overall, NOW provided the most accurate diagnoses and had user-friendly technical characteristics. However, the low overall sensitivity of the RIIAs indicates that these can be used as screening tools only. (+info)
Initial high-dose nasal allergen exposure prevents allergic sensitization to a neoantigen.
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Primary allergic sensitization--IgE formation after Ag exposure--is fundamental in the development of allergic respiratory disease. With the rising prevalence of asthma and allergic rhinitis, improved understanding of the determining factors for allergic sensitization is needed. Human epidemiologic studies suggest high-dose allergen exposure may paradoxically protect against sensitization. Prospective human studies of allergen dose effect on primary allergic sensitization are lacking. We prospectively examined the effect of respiratory Ag dose exposure on the rate of primary allergic sensitization to a neoantigen, keyhole limpet hemocyanin, using a unique model of human nasal allergic sensitization. Atopic human subjects were exposed to 0.1-, 10-, 1,000-, or 100,000-mug doses of intranasal keyhole limpet hemocyanin in conjunction with adjuvant intranasal diesel exhaust particles. Ag-specific IgE, IgG, and IgG4 were measured in nasal lavage samples at the conclusion of the sensitization protocol. Allergic sensitization rates for the 0.1-, 10-, 1,000-, and 100,000-mug dose groups were 0, 100, 57, and 11%, respectively. All subjects produced Ag-specific IgG with the highest levels observed in the high-dose group. These results provide direct evidence that primary allergic sensitization may be prevented by initial high levels of respiratory Ag exposure through induction of a modified, nonallergic immune response. This Ag dose effect was capable of overcoming the well-established allergic adjuvant effects of diesel exhaust particle exposure. Whether this immune response represents durable allergic tolerance is not yet known. Studies investigating the molecular mechanisms of this non-IgE response may be useful in developing therapy to prevent allergic sensitization. (+info)
Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects.
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BACKGROUND: Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. OBJECTIVE: The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. METHODS: Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600 mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. RESULTS: The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2-3 doubling concentration steps, no significant difference between treatments. Leukotriene E(4) in urine increased significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05 vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two-fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects (P<0.05 and P<0.001, respectively compared to placebo). CONCLUSIONS: Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB(4) release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects. (+info)
Protection of plasminogen activator inhibitor-1-deficient mice from nasal allergy.
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This study was performed to clarify the relationship between fibrinolytic components and the pathology of allergy, particularly that during the development of nasal allergy and nasal tissue changes. Intranasal OVA challenge after sensitization by i.p. administration of OVA induced a higher level of excess subepithelial collagen deposition in wild-type (WT) C57BL/6J mice than in plasminogen activator inhibitor (PAI)-1-deficient (PAI-1(-/-)) mice. The excess PAI-1 induction in the nasal mucosa and higher level of active PAI-1 in the nasal lavage fluid of WT-OVA mice compared with those in WT-control mice suggested that the decrease of proteolytic activity inhibits the removal of subepithelial collagen. The frequency of sneezing, nasal rubbing, nasal hyperresponsiveness, production of specific IgG1 and IgE in the serum, and production of IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-1(-/-) mice, these reactions were absent, and specific IgG2a in serum and IFN-gamma in splenocyte culture medium increased significantly. Histopathologically, there were marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-1(-/-) mice was down-regulated, and the immune response shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in immune response. (+info)
Changes in levels of nerve growth factor in nasal secretions after capsaicin inhalation in patients with airway symptoms from scents and chemicals.
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Patients complaining of upper and lower airway symptoms caused by scents and chemicals have previously been shown to have increased cough sensitivity to inhaled capsaicin, but the precise mechanisms behind this reaction are unknown. Hypothesizing that a neurochemical alteration related to sensory hyperreactivity (SHR) of the airway mucosa occurs, we measured levels of nerve growth factor (NGF) in nasal lavage fluid (NAL) before and after capsaicin inhalation provocations and related the capsaicin cough sensitivity to the NGF levels. Thirteen patients with SHR and 14 control subjects were provoked with capsaicin inhalation at three different doses. We measured NGF in NAL before and after provocation and recorded cough and capsaicin-induced symptoms. All subjects demonstrated a dose-dependent cough response to capsaicin inhalation, with a more pronounced effect in patients than in controls. Basal levels of NGF were significantly lower in the patient group than in the control subjects (p < 0.01). After capsaicin provocation, the patients showed a significant increase in NGF (p < 0.01), which was related to capsaicin cough sensitivity. The findings demonstrate that, in patients with airway symptoms induced by scents and chemicals, SHR is real and measurable, demonstrating a pathophysiology in the airways of these patients compared to healthy subjects. (+info)
An evaluation of Echinacea angustifolia in experimental rhinovirus infections.
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BACKGROUND: Echinacea has been widely used as an herbal remedy for the common cold, but efficacy studies have produced conflicting results, and there are a variety of echinacea products on the market with different phytochemical compositions. We evaluated the effect of chemically defined extracts from Echinacea angustifolia roots on rhinovirus infection. METHODS: Three preparations of echinacea, with distinct phytochemical profiles, were produced by extraction from E. angustifolia roots with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol. A total of 437 volunteers were randomly assigned to receive either prophylaxis (beginning seven days before the virus challenge) or treatment (beginning at the time of the challenge) either with one of these preparations or with placebo. The results for 399 volunteers who were challenged with rhinovirus type 39 and observed in a sequestered setting for five days were included in the data analysis. RESULTS: There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer. CONCLUSIONS: The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it. (+info)