Immunogenicity and reactogenicity of a 13-valent-pneumococcal conjugate vaccine administered at 2, 4, and 12 months of age: a double-blind randomized active-controlled trial.

BACKGROUND: A 2-, 4-, and 12-month schedule of a novel 13-valent-pneumococcal conjugate vaccine (PCV13), containing serotype 1, 3, 4, 5, 6A, 6B 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharides individually conjugated to CRM197 was evaluated in a randomized, double-blind, controlled infant study. METHODS: Two hundred eighty-six healthy infants received PCV13 or the 7-valent-pneumococcal conjugate vaccine (PCV7) at 2, 4, and 12 months of age, alongside a serogroup C meningococcal (MenC) vaccine (2 and 4 months of age), DTaP-IPV-Hib (2, 3, and 4 months), and a Hib-MenC vaccine (12 months). Specific antibody responses were assessed at age 5, 12, and 13 months. RESULTS: At 13 months of age, >97% of PCV13 recipients had pneumococcal serotype-specific serum IgG concentrations ≥0.35 µg/mL for each vaccine serotype except serotype 3 (88.2%), and at least 93% of PCV13 recipients had OPA titers ≥1:8 for each serotype. At 5 months, 110/114 (96.5%) of PCV13 recipients and 100/102 (98.0%) of PCV7 recipients had serum anti-PRP (Hib) IgG concentration ≥0.15 µg/mL (difference, 1.5%; CI, -7.1%­3.7%), while 119/120 (99.2%) and 117/118 (99.2%), respectively, had MenC serum bactericidal assay titers of ≥1:8. All PCV13 recipients and 110/113 (97.3%) of PCV7 recipients had IgG concentrations against fimbrial agglutinogens of ≥2.2 EU/mL; IgG concentrations for the remaining pertussis antigens were ≥5 EU/mL for all participants. Local reactions and systemic events were similar in the PCV13 and PCV7 groups. CONCLUSIONS: A 2-, 4-, and 12-month course of PCV13 was immunogenic for all 13 vaccine serotypes and was well tolerated.

Diagnostic utility of two case definitions for anaphylaxis: a comparison using a retrospective case notes analysis in the UK.

Anaphylaxis is a clinical diagnosis with no gold-standard test. Recent case definitions have attempted to provide objective criteria for diagnosis. The aim of this study was to compare the diagnostic concordance of the Brighton Collaboration case definition (the 'Brighton' case definition) to the consensus case definition from the Second Symposium on the Definition and Management of Anaphylaxis (the 'Symposium' definition). The study setting was a hospital-based emergency department in the UK. We identified cases of anaphylaxis by physicians' discharge diagnoses over a 2-year period from 2005 to 2006, and used randomly selected cases of allergic reaction, asthma and urticaria as a control group. Data was extracted by clinicians (who were unaware of the content of either case definition), and the two case definitions were applied by Boolean operators in a Microsoft Excel spreadsheet. Concordance between the case definitions was measured using Cohen's kappa (kappa) statistic. We reviewed 128 sets of notes, with 47 cases of anaphylaxis. Brighton and Symposium definitions had sensitivities of 0.681 and 0.671, respectively, and specificities of 0.790 and 0.704, respectively. A discordant result was found in 36/128 cases (28.1%; kappa = 0.414 [95% CI 0.253, 0.574]), which represents a moderate level of agreement between case definitions. The Brighton case definition has a similar diagnostic concordance to the Symposium case definition. It does not seem to over- or underestimate cases and is sufficiently unique that the identification of an allergic trigger does not have to form part of the case definition. This will be important in the recognition of anaphylaxis resulting from the administration of drug and vaccines, where causality should be examined separately from case ascertainment.