It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one-or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n ؍ 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10-g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of >8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of >8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.In November 1999, the United Kingdom introduced universal meningococcal C conjugate (MCC) vaccination at 2, 3, and 4 months of age, on the basis of safety and immunogenicity studies (15). A prelicensure study in 83 infants in the United Kingdom (18) who were given one of the three candidate MCC vaccines, a tetanus toxoid conjugate (MCC-TT) (14), at 2, 3, and 4 months of age demonstrated that the vaccine was highly immunogenic after a single dose at 2 months of age, with all infants achieving a putative protective antibody titer of Ն8 (bactericidal antibody levels in serum were measured with baby rabbit complement [rSBA]) (1a, 3). There was a further significant increase in antibody levels after a second dose of MCC-TT vaccine but no further increase after the third dose at 4 months of age. Antibody levels fell by 14 months of age, but booster antibody responses to meningococcal C polysaccharide and MCC vaccines provided evidence of successful priming for immunologic memory after the full course of three doses (18).The excellent response to this MCC-TT vaccine among infants at 2 months of age and the modest response to the third dose of vaccine raise the possibility that a one-or two-dose schedule in infants may be sufficient to provide protection from meningococcal C disease. Demonstration of priming for immune memory by the one-or two-dose schedules suggests that these regims could also provide long-term protection. This could be assessed by examining antibody responses to meningococcal C polysaccharide vaccination in the second year of life since children do not normally respond to polysaccharide ...
Objective: We sought to describe characteristics and operative outcomes of children who underwent repair of truncus arteriosus and identify risk factors for the occurrence of major adverse cardiac events (MACE) in the immediate postoperative period in a contemporary multicenter cohort.Methods: We conducted a retrospective review of children who underwent repair of truncus arteriosus between 2009 and 2016 at 15 centers within the United States. Patients with associated interrupted or obstructed aortic arch were excluded. MACE was defined as the need for postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or operative mortality. Risk factors for MACE were identified using multivariable logistic regression analysis and reported as odds ratios (ORs) with 95% confidence intervals (CIs).Results: We reviewed 216 patients. MACE occurred in 44 patients (20%) and did not vary significantly over time. Twenty-two patients (10%) received postoperative extracorporeal membrane oxygenation, 26 (12%) received cardiopulmonary resuscitation, and 15 (7%) suffered operative mortality. With multivariable logistic regression analysis (which included adjustment for center effect), factors independently associated with MACE were failure to diagnose truncus arteriosus before discharge from the nursery (OR, 3.1; 95% CI, 1.3-7.4), cardiopulmonary bypass duration>150 minutes (OR, 3.5; 95% CI, 1.5-8.5), and right ventricle-topulmonary artery conduit diameter >50 mm/m 2 (OR, 4.7; 95% CI, 2.0-11.1).
Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n ؍ 130) to immunization with the MCC vaccine was investigated. Asplenic individuals had a significantly lower geometric mean titer (GMT) (157.8; 95% confidence interval [CI], 94.5 to 263.3) of bactericidal antibody in serum (SBA) than an age-matched control group (n ؍ 48) (1448.2; 95% CI, 751.1 to 2792.0). However, 80% of asplenic individuals achieved the proposed protective SBA titer of >8. No differences were observed between the two groups in the serogroup C-specific immunoglobulin G geometric mean concentration. A significant reduction in SBA GMT or the number of responders achieving an SBA titer of >8 was observed if the reason for splenectomy was a medical cause or if MCC vaccination occurred <10 years after splenectomy. Individuals (n ؍ 29) who did not achieve an SBA titer of >16 were offered a second dose of MCC vaccine. Analysis of the SBA response revealed that 61% (14 of 23) of the individuals who received a second dose achieved a protective titer. In total, 93% of asplenic individuals achieved a titer of >8 following MCC vaccination (one or two doses combined). We recommend that, following vaccination of asplenics, either the level of functional antibody should be determined, with a second dose of MCC vaccine offered to nonresponders, or two doses of MCC vaccine should be routinely offered.Asplenic individuals are at an increased risk of infection from encapsulated bacteria, including Neisseria meningitidis (9, 15). Overwhelming postsplenectomy infection has a high mortality rate, between 40% and 70% (7). Immunization with the 23-valent pneumococcal plain polysaccharide and Haemophilus influenzae type b (Hib) conjugate (29) vaccines is recommended for individuals with functional or anatomic asplenia. In 2001, the United Kingdom Department of Health extended this recommendation to include vaccination with meningococcal serogroup C conjugate (MCC) vaccine, although no data on immune responses are available to date for MCC vaccines in this group (6).Various studies have provided conflicting evidence on the immune response to polysaccharide antigens in asplenic individuals (12, 21), and the limitations of plain polysaccharide vaccines are well documented (13,17,18,29). Meningococcal serogroup C plain polysaccharide vaccines are not immunogenic in those under the age of 2 years (13, 17), and repeated doses can lead to hyporesponsiveness (2,13,18,29). MCC vaccines that have been shown to be highly immunogenic and to generate immune memory in all age groups from infants to adults are now available (10, 25-29). MCC vaccines have been shown to be efficacious in all the age groups targeted during the vaccination campaign initiated in 1999 in the Uni...
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