144 resultados para Tetanus antitoxin
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Based on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants against Bordetella pertussis according to their chronological age. However, as specific T-cell responses also are involved in the protection against B. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa; n = 24) or a whole-cell (Pw; n = 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-gamma) response to the B. pertussis antigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-gamma secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.
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Two different types of pertussis vaccines are currently available to protect children against whooping cough, the first-generation whole-cell (Pw) vaccines and the more recent acellular (Pa) vaccines. Both types provide good protection, yet induce different types of immune responses in 6-month-old infants, with a strong Th1 response induced by Pw vaccines compared to a mixed Th1/Th2 response and a delay in non-specific IFN-gamma secretions after the administration of Pa vaccines. We show here that at 13 months of age, most Pw- or Pa-vaccinated children display Bordetella pertussis-specific T-cell responses, in addition to significant antibody levels, although a higher Th2/Th1 cytokine ratio remained in Pa recipients compared to Pw recipients. In contrast, the proportion of children with tetanus toxin-specific T-cell responses was lower in Pa than in Pw vaccine recipients, although most children had protective anti-tetanus toxin IgG levels. In addition, the global Th2 bias observed in 6-month-old infants vaccinated with a Pa vaccine was normalized at 13 months.
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Few studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients, and at 4 month follow up in 17 patients. All patients who demonstrated a significant increase in IgC antibodies against PPD at 4 months follow up had a significant increase already at 6 weeks of follow up. In contrast, IgG antibodies against hsp increased significantly from 6 weeks to 4 months post- treatment. A significant increase in IgG antibodies against PPD, hsp65, P64, GroEL, and hsp70 at 4 months follow up was observed in 10/17, 8/17, 10/17, 4/17 and 8/17 patients. Native P64 protein elicited a higher antibody response than recombinant mycobacterial hsp65. No increase in antibody response was observed against Dnak from E. coli, against AG85 or tetanus toxoid after BCG therapy. An increase in IgG antibodies against P64 at 4 months follow up compared with pretreatment values was found to be a significant predictor of tumour recurrence (P < 0.01). Further studies with a larger number of patients are needed to confirm the value of the antibody response against P64 as a clinical independent prognostic factor.
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OBJECTIVES: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. METHODS: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. RESULTS: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy. CONCLUSIONS: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.
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The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
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Background: Fruit and vegetable (FV) intake, which is often low in older people, is associated with reduced chronic disease risk. Objective: We determined whether increased FV intake improves measures of immune function. Design: We conducted a randomized controlled trial (The Ageing and Dietary Intervention Trial) in 83 healthy volunteers aged 65-85 y with low FV intakes (=2 portions/d); 82 subjects completed the intervention. Participants were assigned to continue their normal diets or to consume =5 FV portions/d for 16 wk. At 12 wk, tetanus toxoid (0.5 mL intramuscular) and Pneumovax II vaccine (0.5 mL intramuscular; both vaccines from Sanofi Pasteur) were administered. FV intake was monitored by using diet histories, and biomarkers of nutritional status were assessed. The primary endpoint was the antibody response to vaccination. Specific antibodies binding to tetanus toxoid (total IgG) and pneumococcal capsular polysaccharide (total IgG and IgG2) were assessed at baseline and 16 wk. Participants were recruited between October 2006 and June 2008. Results: The change in FV consumption differed significantly between groups [mean change in number of portions (95% CI): in the 2-portion/d group, 0.4 portions/d (0.2, 0.7 portions/d); in the 5-portion/d group, 4.6 portions/d (4.1, 5.0 portions/d); P < 0.001)] and also in micronutrient status. Antibody binding to pneumococcal capsular polysaccharide (total IgG) increased more in the 5-portion/d group than in the 2-portion/d group [geometric mean (95% CI) of the week 16:baseline ratio: 3.1 (2.1, 4.4) and 1.7 (1.3, 2.1), respectively; P = 0.005)]. There was no significant difference in the increases in antibody binding to tetanus toxoid. Conclusion: Increased FV intake improves the Pneumovax II vaccination antibody response in older people, which links an achievable dietary goal with improved immune function. This trial was registered at clinicaltrials.gov as NCT00858728. © 2012 American Society for Nutrition.
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Rotavirus nonstructural protein 4 (NSP4) is a protein with pleiotropic properties. It functions in rotavirus morphogenesis, pathogenesis, and is the first described viral enterotoxin. Since many bacterial toxins function as potent mucosal adjuvants, we evaluated whether baculovirus-expressed recombinant simian rotavirus SA11 NSP4 possesses adjuvant activity by co-administering NSP4 with keyhole limpet hemocyanin (KLH), tetanus toxoid (TT) or ovalbumin (OVA) as model antigens in mice. Following intranasal immunization, NSP4 significantly enhanced both systemic and mucosal immune responses to model immunogens, as compared to the control group, in an antigen-specific manner. Both full-length and a cleavage product of SA11 NSP4 had adjuvant activity, localizing this activity to the C-terminus of the protein. NSP4 forms from virulent and avirulent porcine rotavirus OSU strain, and SA11 NSP4 localized within a 2/6-virus-like particle (VLP) also exhibited adjuvant effects. These studies suggest that the rotavirus enterotoxin NSP4 can function as an adjuvant to enhance immune responses for a co-administered antigen.
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Based on models with calibrated parameters for infection, case fatality rates, and vaccine efficacy, basic childhood vaccinations have been estimated to be highly cost effective. We estimate the association of vaccination with mortality directly from survey data. Using 149 cross-sectional Demographic and Health Surveys, we determine the relationship between vaccination coverage and under five mortality at the survey cluster level. Our data include approximately one million children in 68,490 clusters in 62 countries. We consider the childhood measles, Bacille Calmette-Guérin (BCG), Diphtheria-Pertussis-Tetanus (DPT), Polio, and maternal tetanus vaccinations. Using modified Poisson regression to estimate the relative risk of child mortality in each cluster, we also adjust for selection bias caused by the vaccination status of dead children not being reported. Childhood vaccination, and in particular measles and tetanus vaccination, is associated with substantial reductions in childhood mortality. We estimate that children in clusters with complete vaccination coverage have relative risk of mortality 0.73 (95% Confidence Interval: 0.68, 0.77) that of children in a cluster with no vaccination. While widely used, basic vaccines still have coverage rates well below 100% in many countries, and our results emphasize the effectiveness of increasing their coverage rates in order to reduce child mortality.
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O presente relatório surge na sequência da realização do estágio curricular na coo-perativa Fomento Extremeño Ovino Sociedad Agraria de Transformación no âmbito do Mestrado Integrado em Medicina Veterinária na Universidade de Évora. Este relatório apresenta-se dividido em duas partes. Na primeira são descritas as atividades desenvolvi-das no controlo reprodutivo, profilaxia médica e clínica médica. A segunda parte é cons-tituída por uma revisão bibliográfica sobre o tétano em ovinos, patologia que tem especial importância nesta espécie devido aos procedimentos realizados no maneio ainda muito tradicionais, e no final são apresentados dois casos clínicos e a sua respetiva discussão à luz do estado de arte; Ruminants clinics Abstract: This report follows up on the completion of the internship at the Fomento Extre-meño Ovino Sociedad Agraria de Transformación as part of the Master Degree in Vete-rinary Medicine at the University of Évora. Thereby the present repor is divided into two parts. The first part describes the activities performed in reproductive control, medical prophylaxis and medical clinic. The second part is composed by a bibliographical review about tetanus in sheeps, a pathology that has special importance in this species due to animal management procedures performed wich are still very tradicional. Lastly, this re-port presents two clínical cases and its respective discussion according to presente knowledge.
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The pathogenesis of Duchenne muscular dystrophy (DMD), characterised by lack of the cytoskeletal protein dystrophin, is not completely understood. An early event in the degenerative process of DMD muscle could be a rise in cytosolic calcium concentration. In order to investigate whether this leads to alterations of contractile behaviour, we studied the excitability and contractile properties of cultured myotubes from control (C57BL/10) and mdx mice, an animal model for DMD. The myotubes were stimulated electrically and their motion was recorded photometrically. No significant differences were found between control and mdx myotubes with respect to the following parameters: chronaxy and rheobase (0.33 +/- 0.03 ms and 23 +/- 4 V vs. 0.39 +/- 0.07 ms and 22 +/- 2 V for C57 and mdx myotubes, respectively), tetanisation frequency (a similar distribution pattern was found between 5 and 30 Hz), fatigue during tetanus (found in 35% of both types of myotubes) and post-tetanic contracture. In contrast, contraction and relaxation times were longer (P < 0.005) in mdx (36 +/- 2 and 142 +/- 13 ms, respectively) than in control myotubes (26 +/- 1 and 85 +/- 9 ms, respectively). Together with our earlier findings, these results suggest a decreased capacity for calcium removal in mdx cells leading, in particular, to alterations of muscle relaxation.
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RESUME Nous n'avons pas de connaissance précise des facteurs à l'origine de l'hétérogénéité phénotypique des cellules T CD4 mémoires. Une troisième population phénotypique des cellules T CD4 mémoires, caractérisée par les marqueurs CD45RA+CCR7- a été identifiée dans cette étude. Cette population présente un état de différentiation avancée, comme en témoigne son histoire de réplication, ainsi que sa capacité de prolifération homéostatique. Les réponses des cellules T CD4 mémoires à différentes conditions de persistance et charge antigénique ont trois patterns phénotypiques différents, caractérisés par les marqueurs CD45RA et CCR7. La réponse CD4 mono -phénotypique CD45RA-CCR7+ ou CD45RA- CCR7- est associée à des conditions d'élimination de l'antigène (telle la réponse CD4 tétanos spécifique) ou à des conditions de persistance antigénique et de virémie élevée (telle la réponse HIV chronique ou la primo-infection CMV) respectivement. D'autre part, les réponses T CD4 multi -phénotypiques CD45RA-CCR7+ sont associées à des conditions d'exposition antigénique prolongée et de faible virémie (telles les infections CMV, EBV et HSV ou les infections HIV chez les long term non progressons). La réponse mono -phénotypique CD45RA- CCR7+ est propre aux cellules T CD4 secrétant de IL2, définies également comme centrales mémoires, la réponse CD45RA- CCR7- aux cellules T CD4 secrétant de l'IFNγ et finalement la réponse mufti-phénotypique aux cellules T CD4 secrétant à la fois de l'IL2 et de l' IFNγ. En conclusion, ces résultats témoignent d'une régulation de l'hétérogénéité phénotypique par l'exposition et la charge antigénique. ABSTRACT The factors responsible for the phenotypic heterogeneity of memory CD4 T cells are unclear. In the present study, we have identified a third population of memory CD4 T cells characterized as CD45RA+CCRT that, based on its replication history and the homeostatic proliferative capacity, was at an advanced stage of differentiation. Three different phenotypic patterns of memory CD4 T cell responses were delineated under different conditions of antigen (Ag) persistence and load using CD45RA and CCR7 as markers of memory T cells. Mono-phenotypic CD45RA'CCR7+ or CD45RA'CCR7' CD4 T cell responses were associated with conditions of Ag clearance (tetanus toxoid-specific CD4 T cell response) or Ag persistence and high load (chronic HIV-1 and primary CMV infections), respectively. Multi-phenotypic CD45RA CCR7+, CD45RA'CCRT and CD45RA+CCRT CD4 T cell responses were associated with protracted Ag exposure and low load (chronic CMV, EBV and HSV infections and HIV-1 infection in long-term nonprogressors). The mono-phenotypic CD45RA'CCR7+ response was typical of central memory (TCM) IL-2-secreting CD4 T cells, the mono-phenotypic CD45RA CCRT response of effector memory (TEM) IFN-γ -secreting CD4 T cells and the multi-phenotypic response of both IL-2- and IFN-γ -secreting cells. The present results indicate that the heterogeneity of different Ag-specific CD4 T cell responses is regulated by Ag exposure and Ag load.
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Dans le cortex visuel des mammifères, une cellule à panier (BC) qui représente un sous-type majoritaire d’interneurones GABAergiques, innerve une centaine de neurones par une multitude de synapses localisées sur le soma et sur les dendrites proximales de chacune de ses cibles. De plus, ces cellules sont importantes pour la génération des rythmes gammas, qui régulent de nombreuses fonctions cognitives, et pour la régulation de la plasticité corticale. Bien que la fonction des BC au sein des réseaux corticaux est à l'étude, les mécanismes qui contrôlent le développement de leur arborisation complexe ainsi que de leurs nombreux contacts synaptiques n’ont pas été entièrement déterminés. En utilisant les récepteurs allatostatines couplés aux protéines G de la drosophile (AlstR), nous démontrons in vitro que la réduction de l'excitation ainsi que la réduction de la libération des neurotransmetteurs par les BCs corticales individuelles des souris, diminuent le nombre de cellules innervées sans modifier le patron d'innervation périsomatique, durant et après la phase de prolifération des synapses périsomatiques. Inversement, lors de la suppression complète de la libération des neurotransmetteurs par les BCs individuelles avec l’utilisation de la chaîne légère de la toxine tétanus, nous observons des effets contraires selon le stade de développement. Les BCs exprimant TeNT-Lc pendant la phase de prolifération sont caractérisées par des arborisations axonales plus denses et un nombre accru de petits boutons homogènes autour des somas innervés. Toutefois, les cellules transfectées avec TeNT-Lc après la phase de la prolifération forment une innervation périsomatique avec moins de branchements terminaux d’axones et un nombre réduit de boutons avec une taille irrégulière autour des somas innervés. Nos résultats révèlent le rôle spécifique des niveaux de l’activité neuronale et de la neurotransmission dans l'établissement du territoire synaptique des cellules GABAergiques corticaux. Le facteur neurotrophique dérivé du cerveau (BDNF) est un modulateur puissant de la maturation activité-dépendante des synapses GABAergiques. Grâce à l'activation et à la signalisation de son récepteur tyrosine kinase B (TrkB), la liaison de mBDNF module fortement la prolifération des synapses périsomatiques GABAergiques formés par les BCs. Par contre, le rôle du récepteur neurotrophique de faible affinité, p75NTR, dans le développement du territoire synaptique des cellules reste encore inconnu. Dans ce projet, nous démontrons que la suppression de p75NTR au niveau des BCs individuelles in vitro provenant de souris p75NTRlox induit la formation d'une innervation périsomatique exubérante. BDNF est synthétisé sous une forme précurseur, proBDNF, qui est par la suite clivée par des enzymes, y compris la plasmine activée par tPA, pour produire une forme mature de BDNF (m)BDNF. mBDNF et proBDNF se lient avec une forte affinité à TrkB et p75NTR, respectivement. Nos résultats démontrent qu’un traitement des cultures organotypiques avec la forme résistante au clivage de proBDNF (mut-proBDNF) réduit fortement le territoire synaptique des BCs. Les cultures traitées avec le peptide PPACK, qui inactive tPA, ou avec tPA altèrent et favorisent respectivement la maturation de l’innervation synaptique des BCs. Nous démontrons aussi que l’innervation exubérante formée par les BCs p75NTR-/- n’est pas affectée par un traitement avec mut-proBDNF. L’ensemble de ces résultats suggère que l'activation de p75NTR via proBDNF régule négativement le territoire synaptique des BCs corticaux. Nous avons ensuite examiné si mut-proBDNF affecte l’innervation périsomatique formée par les BCs in vivo, chez la souris adulte. Nous avons constaté que les boutons GABAergiques périsomatiques sont significativement diminués dans le cortex infusé avec mut-proBDNF par rapport à l’hémisphère non-infusé ou traité avec de la saline. En outre, la plasticité de la dominance oculaire (OD) est rétablie par ce traitement chez la souris adulte. Enfin, en utilisant des souris qui ne possèdent pas le récepteur p75NTR dans leurs BCs spécifiquement, nous avons démontré que l'activation de p75NTR via proBDNF est nécessaire pour induire la plasticité de la OD chez les souris adultes. L’ensemble de ces résultats démontre un rôle critique de l'activation de p75NTR dans la régulation et le maintien de la connectivité des circuits GABAergiques, qui commencent lors du développement postnatal précoce jusqu’à l'âge adulte. De plus, nous suggérons que l'activation contrôlée de p75NTR pourrait être un outil utile pour restaurer la plasticité dans le cortex adulte.
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La incidencia de la tosferina ha mostrado un incremento en los últimos años; afectando predominantemente a los niños menores de 1 año, adolescentes y adultos. En el 2005 el Comité Asesor de Prácticas en Inmunización (ACIP) recomendó administrar una dosis de refuerzo de la vacuna acelular antipertussis a los adolescentes. Esta estrategia ha sido adoptada por distintos países. Sin embargo hasta el momento no existe una revisión sistemática que evalúe la efectividad de esta medida de prevención primaria. Métodos: Revisión sistemática de la literatura de artículos acerca de la efectividad de la vacuna acelular antipertussis como dosis de refuerzo en adolescentes. Resultados: La búsqueda inicial arrojó un total de 121 resultados, de los cuales solo 4 cumplieron los criterios de selección. Se evaluó en éstos, la inmunogenicidad generada contra tétanos y difteria por la vacuna Tdap vs Td con resultados significativos y similares. Además se documentó la respuesta inmunológica protectora generada por la Tdap contra tosferina. En cuanto a la reactogenicidad, en general fue baja. Discusión: La vacuna Tdap genera inmunogenicidad similar a la Td contra tétanos y difteria. Además proporciona adecuada protección contra la tosferina como dosis de refuerzo en los adolescentes. Conclusión: La evidencia disponible sugiere que se puede recomendar la vacuna Tdap como dosis de refuerzo en adolescentes entre los 10 y los 18 años de edad por su baja reactogenicidad y adecuada inmunogenicidad contra tétanos, difteria y B. Pertussis.
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INTRODUCCION. En Colombia y a nivel mundial la vacunación es una estrategia que ha reducido la mortalidad infantil, sin embargo existen bajas coberturas en algunas zonas del país, dentro de las causas de la no vacunación se encuentra el bajo peso al nacer, tema de gran importancia y poco estudiado, encontrándose como una causa controlable y que permitiría a la población acceder a la protección frente a enfermedades inmunoprevenibles. MATERIALES Y METODOS. Se realizó un estudio de tipo observacional de corte trasversal, la muestra fue tomada de la ENDS realizada por Profamilia en el año 2010, se tomó el número total de los encuestados que cumplían con los criterios de inclusión, en total fueron 9694 registros a los que se les realizo; análisis descriptivo, bivariado y multivariado. RESULTADOS. Los niños con bajo peso al nacer tienen menor probabilidad de estar vacunados con el esquema completo con respecto a los niños con peso normal, OR 0762 (IC 95% 0,650; 0,895), se observó que las vacunas en forma individual tienen un comportamiento similar al esquema completo, específicamente en la aplicación en el tiempo indicado para su aplicación, exceptuando triple viral donde no se encontró asociación. CONCLUSION. El bajo peso es un factor determinante en la vacunación a tiempo de los menores y del cumplimiento posterior del esquema, se encontraron variables asociadas al no cumplimiento como el lugar del parto, el índice de pobreza y pertenecer a la etnia afrodescendiente.
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We estimated the sensitivity, i.e., the proportion of all cases of adverse events following immunization (AEFIs) reported to the Brazilian passive surveillance for adverse events following immunization (PSAEFI) with the diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b (DTwP/Hib) vaccine, as well as investigating factors associated with AEFIs reporting. During 2003-2004, 8303 AEFIs associated with DTwP-Hib were reported; hypotonic-hyporesponsive episodes (HHEs), fever and convulsions being the most common. Cure without sequel was achieved in 98.4% of the cases. The mean sensitivity of the PSAEFI was 22.3% and 31.6%, respectively, for HHE and convulsions, varying widely among states. Reporting rates correlated positively with the Human Development Index and coverage of adequate prenatal care, correlating negatively with infant mortality rates. Quality of life indicators and the degree of organization of health services are associated with greater PSAEFI sensitivity. In addition to consistently describing the principal AEFIs, PSAEFI showed the DTwP/Hib vaccine to be safe and allayed public fears related to its use. (C) 2010 Elsevier Ltd. All rights reserved.