RESUMO
BACKGROUND: Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data. METHODS: Healthy 4-16 year olds (nâ =â 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction. RESULTS: Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6-66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8-88.4) against hospitalized VCD. Efficacy was 54.3% (41.9-64.1) against VCD and 77.1% (58.6-87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9-70.1) against VCD and 86.0% (78.4-91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5-54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6-83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified. CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.
Assuntos
Vacinas contra Dengue , Vírus da Dengue , Dengue , Anticorpos Antivirais , Humanos , Sorogrupo , Resultado do Tratamento , Vacinas Atenuadas/efeitos adversos , Vacinas CombinadasRESUMO
BACKGROUND: The identification of susceptible periods to Pb-induced decrements in childhood cognitive abilities remains elusive. OBJECTIVE: To draw inferences about windows of susceptibility using the pattern of associations between serial childhood blood lead (BPb) concentrations and children's cognitive abilities at 4 years of age among 1035 mother-child pairs enrolled in 4 prospective birth cohorts from Mexico City. METHODS: Multiple longitudinally collected BPb measurements were obtained from children (1, 2, 3, and 4 years) between 1994 and 2007. Child cognitive abilities were assessed at 4 years using the general cognitive index (GCI) of the McCarthy Scales of Children's Abilities. We used multivariable linear regression to estimate the change in cognitive abilities at 4 years of age with a 10 µg/dL increase in childhood BPb concentrations adjusting for maternal IQ, education, marital status, child sex, breastfeeding duration, and cohort. RESULTS: In separate models for each BPb measurement, 2 year BPb concentrations were most strongly associated with reduced GCI scores at 4 years after adjusting for confounders (ß: -3.8; 95% confidence interval CI: -6.3, -1.4). Mutual adjustment for other BPb concentrations in a single model resulted in larger, but less precise estimate between 2 year BPb concentrations and GCI scores at 4 years of age (ß: -7.1; 95% CI: -12, -2.0). The association between 2 year BPb and GCI was not heterogeneous (p=0.89), but some BPb and GCI associations varied in magnitude and direction across the cohorts. Additional adjustment for child hemoglobin, birth weight, gestational age, gestational BPb concentrations, or test examiner did not change the pattern of associations. CONCLUSIONS: Higher BPb concentrations at 2 years of age were most predictive of decreased cognitive abilities among these Mexico City children; however, the observed pattern may be due to exposure, outcome, or cohort related factors. These results may help developing countries more efficiently implement childhood Pb prevention strategies.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/epidemiologia , Deficiências do Desenvolvimento/induzido quimicamente , Suscetibilidade a Doenças , Intoxicação por Chumbo/complicações , Intoxicação por Chumbo/epidemiologia , Adulto , Pré-Escolar , Transtornos Cognitivos/sangue , Estudos de Coortes , Deficiências do Desenvolvimento/epidemiologia , Feminino , Humanos , Lactente , Chumbo/sangue , Modelos Lineares , Masculino , México/epidemiologia , Relações Mãe-Filho , Testes Neuropsicológicos , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
O sangramento gastrintestinal macico e uma complicacao incomum da febre tifoide, ocorrendo em 4 por cento dos pacientes com esta patologia. Neste artigo os autores revisam a literatura e relatam o caso de uma paciente jovem com sangramento importante devido a febre tifoide