Quadrivalent meningococcal tetanus toxoid-conjugate booster vaccination in adolescents and adults: phase III randomized study.

BACKGROUND: The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier. METHODS: This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study. RESULTS: The persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported. CONCLUSIONS: MenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile. IMPACT: A booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents.

Cardiac testing and outcomes in infants after an apparent life-threatening event.

OBJECTIVES: We sought to determine the yield of cardiac testing and to identify predictors of cardiac disease in infants with an apparent life-threatening event (ALTE). DESIGN: Retrospective longitudinal cohort study. SETTING: Paediatric hospital providing primary and tertiary care that is part of an integrated healthcare system. PATIENTS: Infants hospitalised for an ALTE from 1999 to 2003. MAIN EXPOSURES: Cardiac testing used at time of ALTE and results, and clinical risk factors for cardiac disease. OUTCOME MEASURES: Short-term (during hospitalisation) and long-term (through November 2009) follow-up for any diagnosis of significant cardiac anatomic or rhythm abnormality. RESULTS: Study criteria were met by 485 infants (mean age 1.9, SD±2.2 months; 49% boys). Cardiac testing was performed on 219 (45%) patients during ALTE hospitalisation, identifying two patients with significant cardiac disease (cardiomyopathy, ventricular pre-excitation). During 7.7 years of follow-up, three additional significant cardiac diagnoses (ventricular pre-excitation, frequent ventricular ectopy, moderate aortic stenosis) were identified. All cardiac tests had low positive predictive value (PPV). Significant cardiac disease was associated with prematurity (22% vs 80%, p=0.002), but not age, gender, prior ALTE or rescue breaths. CONCLUSIONS: This longitudinal study of an ALTE cohort revealed significant cardiac disease in <1% of patients. Prematurity was the only clinical predictor identified. ECG was sensitive for identifying significant cardiac disease, but routine testing warrants further investigation because of the low PPV.