RESUMEN
OBJECTIVES: The aim of this study was to evaluate the immunogenicity and safety of the influenza A H1N1/2009 vaccine in children under 9 years old with autoimmune rheumatic diseases (ARD). METHODS: Thirty-eight ARD patients and 11 healthy children received two doses of non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like vaccine. Subjects were evaluated before and 21 days after vaccination. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers (GMT) and factor increases (FI) in GMT were calculated. RESULTS: Mean ages were comparable between patients and controls. Pre-vaccination SP and GMT were similar in patients and controls (p > 0.05). Three weeks after immunization, SP (81.6% vs. 81.8%, p = 1.0), SC (81.6% vs. 90.9%, p = 0.66), GMT (151.5 vs. 282.1, p = 0.26) and the FI in GMT (16.7 vs. 36.3, p = 0.23) were similar in patients and controls, with both groups achieving an adequate response, according to the European Medicines Agency and Food and Drug Administration standards. Analysis of the possible factors influencing SC showed no difference in demographic data, leukocyte/lymphocyte counts or immunosuppressant use between seroconverted and non-seroconverted patients (p > 0.05). The vaccine demonstrated a satisfactory safety profile in this population. CONCLUSIONS: Two doses of influenza A H1N1/2009 vaccination induced an effective antibody response and caused adverse events in rare instances, suggesting this vaccine is appropriate and can be recommended for this age group.
Asunto(s)
Anticuerpos Antivirales/sangre , Enfermedades Autoinmunes/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Enfermedades Reumáticas/inmunología , Factores de Edad , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/tratamiento farmacológico , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Esquemas de Inmunización , Inmunosupresores/uso terapéutico , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/efectos adversos , Masculino , Selección de Paciente , Enfermedades Reumáticas/sangre , Enfermedades Reumáticas/tratamiento farmacológico , Factores de TiempoRESUMEN
BACKGROUND: Influenza may present a high morbidity and mortality in solid organ transplanted patients (SOTP). Annual influenza virus vaccine is recommended for SOTP. However, low levels of seroconversion in SOTP have been reported. The aim of this study was to evaluate the immunogenicity of 2009 pandemic influenza A (H1N1) - A(H1N1)pdm09--vaccine in kidney transplant patients and to analyze which features might affect seroconversion. METHODS: This study was conducted from March to August 2010 at the Renal Transplantation Unit of University of São Paulo, Brazil. A total of 85 renal transplant patients attending the outpatient unit received one 15-µg intramuscular dose of A(H1N1) pdm09 influenza vaccine (reassortant vaccine virus A/California/7/2009 [NYMC X-179A]). Blood samples were collected immediately before and 21 days after the vaccine was given. Antibody response was measured by the standard hemagglutination-inhibition (HI) assay. The primary immunogenicity endpoint for this study was seroconversion in previously seronegative patients (HI titers <1:40), and the secondary endpoint was the identification of features that could affect seroconversion in this population. RESULTS: Five (5.9%) patients presented HI titers prevaccination ≥ 1:40 and were excluded from further analysis. Seroconversion in previously negative patients occurred in 27 (34%) of 80 patients. Prevaccination HI titers geometrical mean was 5.8 and postvaccination 19.6 (ratio 3.4). Significant seroconversion rate factors were female gender, non-Caucasian ethnicity, and post-transplant time before vaccination. No impact was seen on seroconversion for age, donor type, tacrolimus and cyclosporine blood levels, renal function, or blood lymphocyte counts. Mycophenolate (MPA) showed a lower rate of seroconversion when compared with azathioprine. Tacrolimus and cyclosporine had similar seroconversion rates. Sirolimus use was associated with the highest rate of seroconversion, although these patient numbers were low. Immunosuppresssion containing MPA was considerably less effective in seroconversion than drug combinations with no MPA. Patients receiving sirolimus had more chance of seroconversion. HI titers geometric means pre/post vaccine were as follows: MPA (n = 56): 5.8/12.8; tacrolimus (n = 50): 5.9/16.2; cyclosporine (n = 18): 5.4/24.2; azathioprine (n = 19): 6.2/51.6; and sirolimus (n = 6): 8/80. By univariate analysis, being female and non-White were variables associated with 3.3 times more chance of seroconversion than being male and White. In the multivariate analysis, the variables remaining in the model showed similar hazard ratios. CONCLUSIONS: In this study, the monovalent A(H1N1)pdm09 influenza vaccine demonstrated low rates of seroconversion, particularly in patients on MPA, but with potentially higher response rates in patients on sirolimus.
Asunto(s)
Anticuerpos Antivirales/sangre , Inmunosupresores/sangre , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/inmunología , Trasplante de Riñón , Pandemias/prevención & control , Azatioprina/sangre , Azatioprina/uso terapéutico , Brasil/epidemiología , Ciclosporina/sangre , Ciclosporina/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/sangre , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Sirolimus/sangre , Sirolimus/uso terapéutico , Tacrolimus/sangre , Tacrolimus/uso terapéutico , Población BlancaAsunto(s)
Infecciones por VIH/complicaciones , Antígenos del Núcleo de la Hepatitis B/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Adulto , Brasil , Recuento de Linfocito CD4 , Coinfección , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/inmunología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Grazing incidence fast atom diffraction (GIFAD) is a sensitive tool for surface analysis, which strongly relies on the quantum coherence of the incident beam. In this article we study the spot-beam effect, due to contributions coming from different positions of the focus point of the incident particles, which affects the coherence of GIFAD spectra. We show that the influence of the spot-beam effect on GIFAD patterns depends on the width of the surface area that is coherently lighted by the atomic beam. While for extended illuminations the spot-beam contribution plays a minor role, when a narrow surface area is coherently lighted, the spot-beam effect allows projectiles to explore different zones of a single crystallographic channel, bringing to light intra-channel interference structures. In this last case the spot-beam effect gives also rise to a non-coherent background, which deteriorates the visibility of the interference structures. We found that by varying the impact energy, while keeping the same collimating setup, it is possible to switch gradually from quantum to classical projectile distributions. Present results are compared with available experimental data, making evident that the inclusion of focusing effects is necessary for the proper theoretical description of the experimental spectra.
RESUMEN
A decreased level of glucose-6-phosphate dehydrogenase might result from decreased rate of synthesis, synthesis of an enzyme of lower catalytic efficiency, increased lability, or a combined mechanism. To test the hypothesis of increased lability, the rate of decline of the enzyme in vivo was measured in three groups of individuals, controls, Gd(-),A-males, and Gd(-), Mediterranean males, by the slope of decline of activity in fractions containing erythrocytes of progressively increasing mean age. These fractions were obtained by ultracentrifugation on a discontinuous density gradient of erythrocyte suspensions free of contaminating platelets and leukocytes. The rate of in vivo decline of pyruvate kinase (another age-dependent enzyme) was also measured and found very similar in the three groups. The in vivo decline of glucose-6-phosphate dehydrogenase was found to follow an exponential rate, with a half-life of 62 days for controls and 13 days for Gd(-),A- erythrocytes. The activity in normal reticulocytes was estimated at 9.7 U and in Gd(-),A- reticulocytes at 8.8 U. These estimates were confirmed by direct measurements in reticulocytes isolated from patients with extreme reticulocytosis. In Gd(-),Mediterranean erythrocytes activity could be demonstrated only in reticulocytes, which were estimated to average 1.4 U. The rate of decline is so extreme that no activity could be detected in mature erythrocytes. These data suggest that the glucose-6-phosphate dehydrogenase deficiency of both the Gd(A-) and the GdMediterranean variant results from different degrees of in vivo instability of the abnormal enzyme.