RESUMEN
This evidence-based clinical guideline provides consensus-recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non-infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG-replacement therapy. Summary and consensus-recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG-replacement therapy. Special aspects of concomitant impaired T-cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA-4-, and LRBA-deficiency).
Asunto(s)
Inmunoglobulinas/uso terapéutico , Enfermedades de Inmunodeficiencia Primaria/terapia , Austria , Autoinmunidad , Consenso , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Medicina Basada en la Evidencia , Alemania , Humanos , Comunicación Interdisciplinaria , Guías de Práctica Clínica como Asunto , Enfermedades de Inmunodeficiencia Primaria/inmunología , SuizaRESUMEN
This study compared intramuscular and subcutaneous administration of two doses of measles-mumps-rubella-varicella (MMRV) combination vaccine (Priorix-Tetra, GlaxoSmithKline Biologicals) in children. Healthy children (N = 328) were randomised to receive MMRV either intramuscularly or subcutaneously. Reactogenicity was similar between treatment groups for immediate vaccination pain, vaccination site pain, redness and incidence of fever and rashes. Slightly less vaccination site swelling occurred during days 0-3 of the post-vaccination period after intramuscular administration. Seroconversion rates for all components, 42-56 days post-dose 2, ranged from 99.3% to 100% in the intramuscular group and from 98.6% to 100% in the subcutaneous. Cell-mediated immunity data supported the humoral immunogenicity findings. In summary, the MMRV vaccine is well tolerated and highly immunogenic when administered either subcutaneously or intramuscularly to children in the second year of life.
Asunto(s)
Anticuerpos Antivirales/sangre , Vacuna contra la Varicela/administración & dosificación , Vacuna contra la Varicela/inmunología , Exantema/inducido químicamente , Fiebre/inducido químicamente , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Dolor/inducido químicamente , Formación de Anticuerpos/inmunología , Vacuna contra la Varicela/efectos adversos , Exantema/epidemiología , Femenino , Fiebre/epidemiología , Técnica del Anticuerpo Fluorescente , Humanos , Inmunidad Humoral/inmunología , Lactante , Inyecciones Intramusculares , Inyecciones Subcutáneas , Masculino , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Dolor/epidemiología , Vacunas CombinadasRESUMEN
Combined HibMenCY and HibMenC conjugate vaccines may facilitate inclusion of vaccination against MenC and MenY into routine vaccination schedules, without additional injections. Immunogenicity and reactogenicity of vaccination with three different formulations of a novel HibMenCY-conjugate vaccine, or a HibMenC-conjugate vaccine was assessed. Infants were randomized to receive either Hib(2.5 µg)-MenC(5 µg)-MenY(5 µg)-TT, Hib(5 µg)-MenC(10 µg)-MenY(10 µg)-TT, Hib(5 µg)-MenC(5 µg)-MenY(5 µg)-TT or Hib(5 µg)-MenC(5 µg)-TT vaccines co-administered with DTPa-HBV-IPV at 2-3-4 months of age. Controls received licensed conjugate MenC-CRM197 vaccine co-administered with DTPa-HBV-IPV/Hib. A fourth dose was administered to a subset of children at age 12-18 months. Anti-PRP concentrations and meningococcal bactericidal (rSBA-MenC/Y) titres were measured prior to and one month post third and fourth vaccination dose. Solicited local, general symptoms and unsolicited adverse events were recorded for 7 and 30 days after each vaccination, respectively. Post dose 3, all subjects had anti-PRP antibody levels ≥ 0.15 µg/ml and rSBA-MenC ≥ 1:8. 97.0%-98.6% of HibMenCY recipients had rSBA-MenY ≥ 1:8. Pre-dose-4, 95.6%-100% of HibMenCY and HibMenC recipients had anti-PRP ≥ 0.15 µg/ml and 90.7%-97.6% recipients had rSBA-MenC titres ≥ 1:8. In HibMenCY groups, 78.6%-86.7% had persisting rSBA-MenY ≥ 1:8. The post-dose-4 response was robust after all vaccines with all subjects having anti-PRP ≥ 1 µg/ml and 92.3%-100% rSBA-MenC ≥ 1:128. All HibMenCY recipients had rSBA-MenY ≥ 1:128. Vaccination with the novel Hib-meningococcal vaccines had a safety profile similar to control. HibMenCY and HibMenC conjugate vaccine formulations given at 2-3-4 months of age with a fourth dose in the second year of life were immunogenic and had a comparable safety profile to licensed vaccines. (study 792014 and 100381;www.clinicaltrial.govID:NCT00129116)
Asunto(s)
Anticuerpos Antibacterianos/sangre , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Hepatitis B/administración & dosificación , Vacunas Meningococicas/administración & dosificación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Toxoide Tetánico/administración & dosificación , Vacunas Combinadas/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Vacunas contra Hepatitis B/inmunología , Humanos , Esquemas de Inmunización , Inmunización Secundaria , Lactante , Vacunas Meningococicas/efectos adversos , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo C/inmunología , Vacuna Antipolio de Virus Inactivados/inmunología , Toxoide Tetánico/efectos adversos , Toxoide Tetánico/inmunología , Resultado del Tratamiento , Vacunación , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunologíaRESUMEN
BACKGROUND: When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) compared with the subcutaneous route. METHODS: An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to 18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit. RESULTS: Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of >or= 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (Asunto(s)
Vacuna contra la Varicela/efectos adversos
, Vacuna contra la Varicela/inmunología
, Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos
, Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología
, Anticuerpos Antivirales/sangre
, Vacuna contra la Varicela/administración & dosificación
, Femenino
, Francia
, Alemania
, Humanos
, Lactante
, Inyecciones Intramusculares
, Inyecciones Subcutáneas
, Masculino
, Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación
RESUMEN
Booster vaccination with a reduced-antigen-content dTpa, pediatric DTPa or adult Td vaccine in DTPa-primed children aged 4-6 years was evaluated. Immunogenicity and CMI was assessed one month and 3.5 years after vaccination. Symptoms were solicited for 15 days post-vaccination. There were no differences between groups in diphtheria or tetanus seroprotection or pertussis vaccine-response rates. Anti-diphtheria and anti-PRN concentrations were higher after DTPa, but groups differences reduced over time. Non-significant trends toward reduced reactogenicity of dTpa were observed. Many factors influence vaccine choice at preschool age. The dTpa vaccine was as immunogenic and possibly better tolerated than DTPa at this age.
Asunto(s)
Inmunización Secundaria/métodos , Vacuna contra la Tos Ferina/efectos adversos , Vacuna contra la Tos Ferina/inmunología , Tos Ferina/inmunología , Tos Ferina/prevención & control , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/efectos adversos , Antígenos Bacterianos/inmunología , Niño , Preescolar , Difteria/inmunología , Difteria/prevención & control , Femenino , Alemania , Humanos , Masculino , Tétanos/inmunología , Tétanos/prevención & control , Vacunas Acelulares/efectos adversos , Vacunas Acelulares/inmunologíaRESUMEN
BACKGROUND: Mannose-binding lectin (MBL) is an important factor of the innate immune system, and MBL-initiated complement activation is an important early defense mechanism against various bacterial infections, including invasive meningococcal disease. METHODS: In a pediatric cohort (ages 2-215 months) with invasive meningococcal disease, we investigated the overall and age-stratified frequency of 3 MBL exon 1 variations (C154T, G161A, G170A), previously shown to result in markedly decreased MBL plasma concentrations, by allele specific fluorescent hybridization probe real-time PCR assays and direct sequencing. Healthy age-matched volunteers with the same ethnic background and no history of meningococcal disease served as a control group. RESULTS: The overall frequency of a MBL exon 1 variant genotype was significantly higher in patients than in controls (31.8% vs. 8.2%, P < 0.001). In the patient group with disease onset less than 24 months of age, the prevalence of MBL structural variant genotype was further increased (39.3%; P < 0.001) and most pronounced in children with disease onset less than 12 months of age (57.1%; P < 0.001) when compared with healthy controls. Analysis of clinical severity and outcome revealed no significant difference between patients with wild-type and mutant alleles. CONCLUSIONS: Our data suggest that MBL exon 1 structural variants are significantly associated with susceptibility to childhood meningococcal disease in an age-dependent manner.
Asunto(s)
Envejecimiento/fisiología , Predisposición Genética a la Enfermedad/genética , Lectina de Unión a Manosa/genética , Infecciones Meningocócicas/genética , Mutación/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Infecciones Meningocócicas/metabolismo , PrevalenciaRESUMEN
Peripheral blood cells express the complete non-neuronal cholinergic system. For example synthesis of acetylcholine and nicotinic as well muscarinic receptors have been demonstrated in leucocytes isolated from human peripheral blood. In the present experiments mononuclear cells and granulocytes were isolated from the peripheral blood to investigate content and synthesis of acetylcholine as well as phenotypic functions like respiratory burst, phagocytosis and migration. Mononuclear cells (T-cells and monocytes) contained 0.36 pmol/10(6) cells acetylcholine, whereas acetylcholine content in granulocytes was 100-fold lower. Acetylcholine synthesis amounted to 23.2+/-4.7 nmol/mg protein/h and 2.90+/-0.84 in CD15+ (granulocytes) and CD3+ cells (T-lymphocytes), respectively. Neither atropine (blockade of muscarinic receptors) nor tubocurarine (blockade of nicotinic receptors) exerted an effect on the respiratory burst. Tubocurarine (30 muM), alone or in combination with atropine (1 microM), reduced phagocytosis in granulocytes by 13% and 19%, respectively (p<0.05). Spontaneous transwell migration of granulocytes was doubled by tubocurarine combined with atropine (p>0.05). Also alpha-bungarotoxin (10 microg/ml) enhanced spontaneous granulocyte migration, but hexamethonium (300 microM) was without effect. The present experiments demonstrate a cholinergic modulation of immune functions in peripheral leucocytes under in vitro conditions, i.e. in the absence of a neuronal innervation. Blockade of nicotine receptors (alpha1 muscular subtype) facilitates spontaneous migration of granulocytes.
Asunto(s)
Acetilcolina/metabolismo , Granulocitos/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Antagonistas Muscarínicos/farmacología , Antagonistas Nicotínicos/farmacología , Acetilcolina/farmacología , Atropina/farmacología , Bungarotoxinas/farmacología , Movimiento Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Granulocitos/citología , Granulocitos/metabolismo , Hexametonio/farmacología , Humanos , Leucocitos Mononucleares/citología , Neuronas/metabolismo , Fagocitosis/efectos de los fármacos , Estallido Respiratorio/efectos de los fármacos , Tubocurarina/farmacologíaRESUMEN
BACKGROUND: Combination vaccines against common childhood diseases are widely used, provide an improved coverage, are more convenient and are more cost-effective than multiple injections. We conducted a study to evaluate the safety and immunogenicity of a combined measles-mumps-rubella-varicella (MMRV) candidate vaccine in comparison with the separate administration of licensed measles-mumps-rubella (MMR; Priorix) and varicella (V; Varilrix) vaccines. METHODS: Healthy children 12-18 months of age received 2 doses of MMRV vaccine (3 lots) 6-8 weeks apart (MMRV group) or 1 dose of MMR vaccine administered concomitantly with 1 dose of varicella vaccine, followed by a second dose of MMR at 6-8 weeks later (MMR+V group). Local symptoms (redness, pain and swelling) were recorded for 4 days after vaccination, and fever (any, axillary temperature > or =37.5 degrees C or rectal temperature > or =38.0 degrees C; grade 3, axillary temperature >39.0 degrees C or rectal temperature >39.5 degrees C) was monitored daily for 15 days. Other adverse events were monitored for 6 weeks. RESULTS: A total of 494 children were vaccinated (371 in the MMRV group and 123 in the MMR+V group. Two doses of MMRV vaccine were at least as immunogenic as 2 doses of MMR and 1 dose of varicella vaccine. After the second dose, all children had seroconverted to measles, rubella and varicella in both vaccine groups, and 98% versus 99% had seroconverted to mumps in the MMRV versus the MMR+V group, respectively. The MMRV vaccine did not induce an increased local or general reactogenicity compared with the separate administration, although a higher incidence of low grade fever was seen after the first dose in the MMRV group (67.7% after MMRV versus 48.8% after MMR+V; P < 0.05), this was not observed for grade 3 fever (11.6% after MMRV versus 10.6% after MMR+V; P = 0.87). After the second dose, no differences in incidence of fever were found in either MMRV or MMR+V groups. CONCLUSION: Administration of 2 doses of the combined MMRV vaccine was as immunogenic and well-tolerated as separate injections of MMR and varicella vaccine.
Asunto(s)
Vacuna contra la Varicela/efectos adversos , Vacuna contra la Varicela/inmunología , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunología , Anticuerpos Antivirales/sangre , Vacuna contra la Varicela/administración & dosificación , Femenino , Fiebre , Herpesvirus Humano 3/inmunología , Humanos , Hiperemia , Inmunoglobulina G/sangre , Lactante , Masculino , Virus del Sarampión/inmunología , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Virus de la Parotiditis/inmunología , Dolor , Vacunas Combinadas/administración & dosificaciónRESUMEN
Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp(299)Gly and Thr(399)Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.
Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones Meningocócicas/genética , Infecciones Meningocócicas/inmunología , Mutación Missense , Receptor Toll-Like 4/genética , Factores de Edad , Alelos , Sustitución de Aminoácidos , Niño , Preescolar , ADN/química , ADN/genética , Europa (Continente) , Femenino , Frecuencia de los Genes , Humanos , Lactante , Masculino , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
PURPOSE: The objective of this study was to assess the local and systemic tolerability of two batches of the Biken acellular pertussis (Pa) vaccine following administration of a single vaccine dose to adults with or without a history of prior pertussis immunization. The results from this study were compared to data from published literature. PATIENTS AND METHODS: In a controlled, open-labeled double-blind trial, 518 healthy male and female adults with or without primary pertussis immunization were enrolled at three centers. All study participants had received one single dose (0.5 ml) of the Biken two-component (23.4 mg PT; 23.4 mg FHA) Pa vaccine deeply intramuscularly. Local and systemic adverse events were solicited for 4 days using diary cards. On two occasions, between day 4-7 and between day 12-16 postvaccination, vaccinees were reexamined. At the end of the observation period (day 28) vaccinees had to send a preprinted letter to the study center indicating their state of health. RESULTS: One serious adverse event (acute appendicitis) occurred and was considered not to be related to the study vaccine. At the injection site, redness > 20 mm was observed in one subject (0.2%), and swelling > 20 mm was seen in ten subjects (1.98%). Edematous swelling occurred in three subjects (0.59%). In 27 subjects (5.34%) a "late-onset muscle mass swelling" could be palpated, usually occurring on day 6-12 postvaccination. 429 subjects (84.78%) experienced none or only slight tenderness on pressure during the. rst 4 days postvaccination, moderate tenderness on pressure was reported by 60 subjects (11.86%) and severe tenderness by 16 vaccinees (3.16%). Systemic side effects were rare: no fever > 38.5 degrees C was observed, and only seven subjects (1.39%) took antipyretics. Five patients (0.99%) experienced exhaustion or nausea. The vast majority of the participants (97.43%) would opt for the vaccination again. CONCLUSION: The study vaccine was safe and induced only infrequently and mostly mild, local or general symptoms that all resolved spontaneously. It was well tolerated and accepted in adults.
Asunto(s)
Vacuna contra la Tos Ferina/administración & dosificación , Adulto , Factores de Edad , Anciano , Interpretación Estadística de Datos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Vacuna contra la Tos Ferina/efectos adversos , Factores de TiempoRESUMEN
A new combination vaccine against measles, mumps, rubella and varicella (MMRV) from GlaxoSmithKline Biologicals has recently been approved in Europe. It combines the components from two well-established, live, attenuated vaccines against measles, mumps and rubella. This review presents a summary of the development of this MMRV vaccine from published clinical studies. Seroconversion rates and antibody titers after the first and second dose are similar to those observed after concomitant administration of the MMR and varicella vaccines. Furthermore, the clinical profile of this combination vaccine, in terms of injection- site and general tolerability, is similar to that of the component vaccines. A higher incidence of low-grade fever has been noted following the first dose of MMRV vaccine, although it is no different from component vaccines following the second dose. MMRV vaccines were recommended in Germany in 2006 for administration in two doses to children aged 11-14 months and 15-23 months. They offer a convenient way to implement varicella vaccination and to achieve high vaccine coverage rates mirroring those of MMR vaccines. For other countries considering introducing these vaccines, the advantages for children, parents and healthcare providers of protecting against four diseases in a single vaccine should be noted.
Asunto(s)
Vacuna contra la Varicela , Varicela/prevención & control , Vacuna contra el Sarampión-Parotiditis-Rubéola , Sarampión/prevención & control , Paperas/prevención & control , Rubéola (Sarampión Alemán)/prevención & control , Vacuna contra la Varicela/administración & dosificación , Vacuna contra la Varicela/efectos adversos , Vacuna contra la Varicela/inmunología , Niño , Preescolar , Humanos , Esquemas de Inmunización , Lactante , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Vacunación , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunologíaRESUMEN
We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM(197) plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (> or = 1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (> or = 0.15 microg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae/inmunología , Memoria Inmunológica , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo C/inmunología , Anticuerpos Antibacterianos/metabolismo , Reacciones Antígeno-Anticuerpo , Antígenos Bacterianos/metabolismo , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Haemophilus/metabolismo , Humanos , Lactante , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/metabolismo , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/metabolismoRESUMEN
Three hundred and nineteen adolescents aged 10-12 years who had been previously vaccinated with five doses of acellular pertussis-containing vaccines received single doses of Tdap (reduced-antigen-content tetanus, diphtheria, acellular pertussis) and hepatitis A vaccines in a double-blind crossover trial. Long-term antibody persistence following vaccination with Tdap at pre-school age was similar to that following vaccination with DTaP (diphtheria-tetanus-acellular pertussis). After the sixth dose booster, Tdap induced a vigorous immune response, consistent with protection against diphtheria, tetanus and pertussis diseases.
Asunto(s)
Antígenos Bacterianos/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Inmunización Secundaria/métodos , Anticuerpos Antibacterianos/sangre , Niño , Difteria/prevención & control , Método Doble Ciego , Femenino , Vacunas contra la Hepatitis A/administración & dosificación , Vacunas contra la Hepatitis A/inmunología , Humanos , Masculino , Tétanos/prevención & control , Factores de Tiempo , Tos Ferina/prevención & controlRESUMEN
OBJECTIVE: The safety of a booster dose of a reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap) vaccine was evaluated in adolescents previously vaccinated with five doses of acellular pertussis-containing vaccine. STUDY DESIGN: Adolescents (n = 319) previously vaccinated with either 5 doses of diphtheria-tetanus-acellular pertussis (DTaP) (n = 193) or 4 doses of DTaP plus another acellular pertussis-containing vaccine received one dose each of Tdap and hepatitis A vaccine in a double-blinded, randomized, crossover trial. Rates of adverse events (AEs) after vaccination with Tdap versus hepatitis A and rates of local AEs among adolescents vaccinated with Tdap (sixth acellular pertussis-containing vaccine dose) versus rates in these same individuals after vaccination with their fifth DTaP dose were assessed. RESULTS: After Tdap, pain (63.6%), redness (51.7%), and swelling (41.4%) were the most frequently reported AEs. Large injection site swelling (swelling > 100 mm, arm circumference increase > 50 mm or diffuse swelling interfering with daily activities) occurred in three adolescents and resolved without sequelae. After the sixth dose of acellular pertussis-containing vaccine, adolescents reported more pain and less redness and swelling compared with incidences of these AEs reported when these same individuals received their fifth DTaP dose. CONCLUSIONS: These results suggest that Tdap is well tolerated as a sixth consecutive dose of acellular pertussis-containing vaccine.
Asunto(s)
Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Adolescente , Niño , Estudios Cruzados , Difteria/prevención & control , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Esquemas de Inmunización , Incidencia , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Tétanos/prevención & control , Resultado del Tratamiento , Vacunación/efectos adversos , Tos Ferina/prevención & controlRESUMEN
As an important component of the innate immune system, complement provides the initial response to prevent infections by pathogenic microorganisms. Patients with dysfunction of C5 display a propensity for severe recurrent infections. In this study, we present a patient with C5 deficiency demonstrated by immunochemical and functional analyses. Direct sequencing of all C5 exons displayed no mutation of obvious functional significance, except for an A to G transition in exon 10 predicting an exchange from lysine to arginine. This sequence alteration was present in only one allele of family members with a reduced serum C5 concentration and in both alleles of the patient with almost complete C5 deficiency, suggesting that this alteration may be producing the phenotype. Recent findings indicate that distinct nucleotide sequences, termed exonic splicing enhancers (ESEs), influence the splicing process. cDNA from all family members harboring the mutated allele showed skipping of exon 10, which resulted in a premature STOP codon, explaining the lack of C5 in the propositus. Sequence analysis of the mutated region revealed the substitution to be located within an ESE, as predicted by the RESCUE-ESE program. The altered ESE sequence is located close to the 5' splicing site and also lowers the predicted strength of the splice site itself. This apparently inconsequential sequence alteration represents a noncanonical splicing mutation altering an ESE. Our finding sheds a new light on the role of putative silent/conservative mutations in disease-associated genes.
Asunto(s)
Empalme Alternativo , Complemento C5/deficiencia , Exones , Mutación , Preescolar , Complemento C5/genética , Análisis Mutacional de ADN , Salud de la Familia , Humanos , Masculino , Fenotipo , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: It has been suggested that tungsten coils (TCs) may corrode 30 months after transcatheter embolisation (TCE). The aim of this study was to follow up children after TCE of aorto-pulmonary collaterals (APCs) with TCs. MATERIALS AND METHODS: Successful TCE of 99 APCs was performed in children using 152 TCs. Chest radiographs were obtained on the day after the procedure, after 3-6 months and 9-12 months, and yearly thereafter. RESULTS: Mean follow-up was 39.3 months. After 9-12 months, radiographs revealed a decrease in radio-opacity and reduction of coil width in 29 (37.6%) of 77 APCs. After a mean of 25 months (range 13-51 months), there was loss of visibility in 44 (57.2%) of 77 TCs and a reduction in 29 (37.6%) of 77. After a mean of 39.3 months, all TCs showed decrease or loss of radio-opacity. Exponential function predicts complete biodegradation of 95% of TCs within 10 years after TCE (r2= 0.923). After a mean of 28.4 months, repeat catheterisation was performed in 24 APCs with TCs with decreased or lost radio-opacity. Recanalisation had occurred in 58.3%. CONCLUSIONS: Dissolution occurred in 57.2% of TCs within a mean of 25 months, and within 39.3 months all TCs showed decrease or loss of radio-opacity. Recanalisation of closed APCs occurred in 58.3%.
Asunto(s)
Embolización Terapéutica/instrumentación , Compuestos de Tungsteno/química , Biodegradación Ambiental , Niño , Preescolar , Circulación Colateral , Falla de Equipo , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Radiografía Torácica , Análisis de RegresiónRESUMEN
UNLABELLED: Children undergoing cardiopulmonary bypass (CPB) operations have an increased risk of developing severe infections. Impairment of the immune system may contribute to the development of sequelae such as capillary leaks, pulmonary dysfunction and auto-immune reactions. The objective of this study was to investigate the impact of cardiac surgery with CPB on the immune system of infants and young children. We conducted a prospective study to investigate the changes in circulating lymphocyte subpopulations in a sample of 21 consecutive infants and young children undergoing cardiac surgery for congenital heart disease. The following statistically significant ( P<0.05) results were obtained: leucocyte counts rose 6 h after surgery due to the increase in neutrophils. Absolute T-cell number and absolute T-helper cell number decreased within 24 h after CPB. The proportion of T-cells expressing the T-cell receptor gammadelta as well as natural killer cells increased during CPB. In contrast, the proportion of T-cells expressing activation markers (CD25, CD45R0) decreased within 24 h after CPB, as did the number of cells expressing adhesion molecules (CD11b and ICAM). CONCLUSION: during cardiac surgery with cardiopulmonary bypass, absolute natural killer cell counts increase while T-cells decrease, presumably due to an extravasation or adhesion of activated T-cells. The relevance of this finding regarding the risk of infection is discussed.