BACKGROUND: Despite the importance of vaccinating children younger than 5 years, few studies evaluating vaccine prevention of influenza have been reported in this age group. We evaluated efficacy of an inactivated quadrivalent influenza vaccine (IIV4) in children aged 6-35 months. METHODS: In this phase 3, observer-blinded, multinational trial, healthy children from 13 countries in Europe, Central America, and Asia were recruited in five independent cohorts, each in a different influenza season. Participants were randomly assigned (1:1) to either IIV4 (15 μg haemagglutinin antigen per strain per 0·5 mL dose; a single dose on day 0 for vaccine-primed children, and two doses, on days 0 and 28, for vaccine-unprimed children) or to one or two doses of a non-influenza control vaccine. Primary endpoints were moderate-to-severe influenza or all influenza (irrespective of disease severity) confirmed by RT-PCR on nasal swabs. Cultured isolates were further characterised as antigenically matched or mismatched to vaccine strains. Efficacy was assessed in the per-protocol cohort and total vaccinated cohort (time-to-event analysis), and safety was assessed in the total vaccinated cohort. FINDINGS: Between Oct 1, 2011, and Dec 31, 2014, 12 018 children were recruited into the total vaccinated cohort (6006 children in the IIV4 group and 6012 children in the control group). 356 (6%) children in the IIV4 group and 693 (12%) children in the control group had at least one case of RT-PCR-confirmed influenza. Of these 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, 539 (64%) of 848 antigenically characterised isolates were vaccine-mismatched (16 [15%] of 105 for A/H1N1; 368 [97%] of 378 for A/H3N2; 54 [86%] of 63 for B/Victoria; 101 [33%] of 302 for B/Yamagata). Vaccine efficacy was 63% (97·5% CI 52-72) against moderate-to-severe influenza and 50% (42-57) against all influenza in the per-protocol cohort, and 64% (53-73) against moderate-to-severe influenza and 50% (42-57) against all influenza in the total vaccinated cohort. There were no clinically meaningful safety differences between IIV4 and control. INTERPRETATION: IIV4 prevented influenza A and B in children aged 6-35 months despite high levels of vaccine mismatch. Vaccine efficacy was highest against moderate-to-severe disease, which is the most clinically important endpoint associated with greatest burden. FUNDING: GlaxoSmithKline Biologicals SA.

• MeSH
• chřipka lidská epidemiologie   prevence a kontrola   MeSH
• internacionalita MeSH
• jednoduchá slepá metoda MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• roční období MeSH
• vakcíny proti chřipce * MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• vakcíny proti chřipce * MeSH

BACKGROUND: A serogroup B meningococcal vaccine (4CMenB) is licensed for infant use in countries including Canada, Australia and those of the European Union. Data on serum bactericidal antibody (hSBA) waning and the ideal timing of a "toddler" booster dose are essential to optimize vaccine utilization. METHODS: An open-labeled, multicenter phase-2b follow-on European study conducted from 2009 to 2012. Participants previously receiving 4CMenB with routine vaccines at 2, 4 and 6 or 2, 3 and 4 months (246Con and 234Con) or at 2, 4 and 6 months intercalated with routine vaccines (246Int) received a booster dose at 12, 18 or 24 months. 4CMenB-naïve "Control" participants aged 12, 18 or 24 months received 2 doses of 4CMenB 2 months apart. RESULTS: One thousand five hundred eighty-eight participants were recruited. At 12 months, before any booster doses, the proportions with hSBA titers ≥1:5 for strain 44/76-SL (testing vaccine component fHBP) were 73% (120/165) for the "246Con" group, 85% (125/147) for "246Int," 57% (51/90) for "234Con" and 13% (26/199) for Controls. For strain 5/99 (NadA) proportions were ≥96% (all 4CMenB-recipients) and 1% (Controls). For strain NZ98/254 (PorA), these were 18-35% (4CMenB-recipients) and 1% (Controls). By 24 months, 4CMenB-recipient proportions were 13-22% (44/76-SL), 82-94% (5/99) and 7-13% (NZ98/254) and in controls ≤4%. After a 12-month booster-dose, ≥95% of previously immunized participants had titers ≥1:5 (all strains). CONCLUSIONS: A 4CMenB booster-dose can overcome waning hSBA titers after early-infant immunization. Administration at 12 months could help to maintain immunity during an age of high risk, and the persistence of this response requires further study.

• MeSH
• hodnocení výsledků zdravotní péče MeSH
• kojenec MeSH
• lidé MeSH
• meningokoková meningitida prevence a kontrola   MeSH
• meningokokové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• Neisseria meningitidis séroskupiny B imunologie   MeSH
• očkovací schéma MeSH
• předškolní dítě MeSH
• protilátky bakteriální krev   imunologie   MeSH
• sekundární imunizace * MeSH
• vakcinace MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• meningokokové vakcíny MeSH
• protilátky bakteriální MeSH

• Publikační typ
• tisková chyba MeSH

• Publikační typ
• tisková chyba MeSH

BACKGROUND: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. AIMS: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. RESULTS: Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. CONCLUSIONS: Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

• MeSH
• argininjantarová acidurie diagnóza   MeSH
• chronické selhání ledvin komplikace   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• glutaryl-CoA-dehydrogenasa nedostatek   MeSH
• játra metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické nemoci mozku diagnóza   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc z nedostatku ornithinkarbamoyltransferázy diagnóza   MeSH
• novorozenec MeSH
• novorozenecký screening MeSH
• předškolní dítě MeSH
• propionová acidemie diagnóza   MeSH
• registrace MeSH
• senioři MeSH
• vrozené poruchy cyklu močoviny diagnóza   MeSH
• vrozené poruchy metabolismu aminokyselin diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• glutaryl-CoA-dehydrogenasa MeSH

BACKGROUND: The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific. AIMS/METHODS: To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry. RESULTS: We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients (69 %) were symptomatic. The majority of them (n = 463) presented with acute metabolic crisis during (n = 220) or after the newborn period (n = 243) frequently demonstrating impaired consciousness, vomiting and/or muscular hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency, unexpectedly low in male OTC deficiency, and least frequently in GA1 and female OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency (male and female), hyperammonemia was more severe in metabolic crises during than after the newborn period, whereas metabolic acidosis tended to be more severe in MMA and PA patients with late onset of symptoms. Symptomatic patients without metabolic crises (n = 94) often presented with a movement disorder, mental retardation, epilepsy and psychiatric disorders (the latter in UCD only). CONCLUSIONS: The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis.

• MeSH
• dítě MeSH
• dospělí MeSH
• glutaryl-CoA-dehydrogenasa nedostatek   MeSH
• hyperamonemie diagnóza   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mentální retardace MeSH
• metabolické nemoci mozku diagnóza   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc z nedostatku ornithinkarbamoyltransferázy diagnóza   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• registrace MeSH
• senioři MeSH
• vrozené poruchy cyklu močoviny diagnóza   MeSH
• vrozené poruchy metabolismu aminokyselin diagnóza   MeSH
• zvracení MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• glutaryl-CoA-dehydrogenasa MeSH