Research from JAMA — Immunogenicity of 2 Doses of HPV Vaccine in Younger Adolescents vs 3 Doses in Young Women — A Randomized Clinical Trial

Background. Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock,

Infants born at 33 through 35 completed weeks of gestation (33-35GA) are at risk for severe respiratory syncytial virus (RSV) infection, and palivizumab prophylaxis lowers hospitalizations for RSV infection by as much as 80%. The 33-35GA cohort comprises 3-5% of annual births; thus expert panels recommend limiting prophylaxis to situations in which frequency or health care impact of RSV infection is high. This study sought to identify independent risk factors for hospitalization for RSV infection. This was a multicenter, prospective, observational cohort study of 33-35GA infants followed through their first RSV season (2001/2002 or 2002/2003). Baseline data were collected by interview with parents and review of medical records. Respiratory tract illnesses were identified by monthly phone calls, and medical records were reviewed for emergency room visits or hospitalizations. Risk factors were determined by stepwise logistic regression. Of 1860 enrolled subjects, 1832 (98.5%) were followed for at least 1 month, and 1760 (94.6%) completed all follow-ups. Of 140 (7.6%) subjects hospitalized for respiratory tract illnesses, 66 infants had proven RSV infection. Independent predictors for hospitalization for RSV infection were: day-care attendance (odds ratio, 12.32; 95% confidence interval, 2.56, 59.34); November through January birth (odds ratio, 4.89; 95% confidence interval, 2.57, 9.29); preschool age sibling(s) (odds ratio, 2.76; 95% confidence interval, 1.51, 5.03); birth weight 5 people, counting the subject (odds ratio, 1.79; 95% confidence interval, 1.02, 3.16). Family history of eczema (odds ratio, 0.42; 95% confidence interval, 0.18, 0.996) was protective. Specific host/environmental factors can be used to identify which 33-35GA infants are at greatest risk of hospitalization for RSV infection and likely to benefit from palivizumab prophylaxis.

Research from JAMA — Immunogenicity of a Tetravalent Meningococcal Glycoconjugate Vaccine in Infants — A Randomized Controlled Trial — Context Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. Objective To determine the immunogenicity of a novel tetravalent CRM197-conjugated meningococcal vaccine (MenACWY) in infants. Design, Setting, and ParticipantsRandomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006.Intervention UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months; at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Main Outcome MeasurePercentage of infants with a human complement serum bactericidal activity (hSBA) titer ≥1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed.Results According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers ≥1:4 after primary immunization were serogroup A, 93% (84%-98%); C, 96% (89%-99%); W-135, 97% (90%-100%); and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y; for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%); C, 98% (92%-100%); W-135, 99% (93%-100%); and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%); C, 98% (93%-99%); W-135, 99% (94%-100%); and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers ≥1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers ≥1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients; a temperature of 38°C or greater was observed in 4% and 2% in these groups, respectively. ConclusionMenACWY is well tolerated and immunogenic in infancy.Trial Registration clinicaltrials.gov Identifier: NCT00262002

Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011–2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%–73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%–73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. NCT01517191.