[Show abstract][Hide abstract] ABSTRACT: Background:
The quadrivalent meningococcal glycoconjugate vaccine MenACWY-CRM is licensed for children from two months of age as a 4-dose series. This study assessed the immunogenicity of a 3-dose MenACWY-CRM vaccination series in infants, compared to the 4-dose series, and evaluated the impact of MenACWY-CRM concomitant administration on immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13).
Overall, 751 healthy infants (55-89 days-old) were randomized to receive three or four doses of MenACWY-CRM (2/4/12 or 2/4/6/12 months of age) with PCV13+routine vaccinations (ACWY3 and ACWY4 groups, respectively) or PCV13+routine vaccinations only (Routine group). Immunological noninferiority of the 3-dose versus 4-dose MenACWY-CRM vaccination series was evaluated at 13 months of age for serogroups CWY; noninferiority of immune responses to PCV13 serotypes for concomitant administration of MenACWY-CRM and PCV13 was evaluated at 7 and 13 months of age.
At 13 months, 88-100% of subjects in Groups ACWY3 and ACWY4 achieved seroprotective bactericidal antibody titers against serogroups ACWY; non-inferiority criteria for the 3-dose versus 4-dose MenACWY-CRM vaccination series were met. At 7 months, noninferiority criteria were met for all PCV13 serotypes except for serotypes 3 and 5 (Group ACWY3) and 19A (Group ACWY4). At 13 months, noninferiority criteria were met for all PCV13 serotypes for both ACWY groups.
After completion of either MenACWY-CRM vaccination series, most subjects achieved seroprotective titers against serogroups ACWY, with the 3-dose series being noninferior to the 4-dose series for serogroups CWY, and no interference on immune responses against PCV13 serotypes was observed.(NCT01214837).
Full-text · Article · Oct 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and pre-cancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide.
Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 8 years since licensure, including more than 15 studies in more than one million pre-adolescents, adolescents, and adults from various countries. Most have been performed in the general population though there have been some in special populations (pregnant women, human immunodeficiency virus infected individuals, and those with Systemic Lupus Erythematosus).
We present a summary of the published, post-licensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the post-licensure setting. Serious adverse events such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism, and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates.
These results, along with the safety data from the pre-licensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical, and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.
Full-text · Article · Jun 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Background: In infants, concomitant administration of quadrivalent meningococcal conjugate MenACWYCRM
vaccine (Novartis Vaccines) with 13-valent pneumococcal conjugate PCV13 vaccine (Pfizer) could potentially cause immunologic interference, since both vaccines contain the CRM197 carrier protein.
Methods: Overall 751 infants were randomized to receive 3 or 4 doses of MenACWY-CRM (2, 6, 12 or 2, 4, 6, 12 months of age) with PCV13+routine vaccinations (ACWY3 and ACWY4 groups, respectively) or PCV13+routine vaccinations alone. Here we report on the immune responses to PCV13 antigens; immunological non-inferiority was evaluated at 7 and 13 months of age. At 7 months, prespecified noninferiority criteria were based on the percentage of subjects with anti-pneumococcal capsular IgG concentrations ≥0.35 μg/mL against each PCV13 serotype. At 13 months, prespecified noninferiority criteria were based on geometric mean concentrations of anti-pneumococcal capsular antibodies.
Results: At 7 months of age, noninferiority criteria were met for all PCV13 serotypes except for serotypes
3 and 5 in Group ACWY3 and 19A in Group ACWY4. At 13 months of age, noninferiority criteria were met for all PCV13 serotypes for both ACWY groups. MenACWY-CRM induced a robust immune response against serogroups ACWY (88-100%) at 13 months of age.
Conclusion: After completing the vaccination series, immune responses to all PCV13 antigens were noninferior in subjects receiving MenACWY+PCV13+routine vaccinations versus those receiving PCV13+routine vaccinations alone. Immunological noninferiority was not established for all PCV13 serotypes at 7 months, although no serotype consistently failed to meet the criteria. This likely reflects insufficient power to test noninferiority, rather than vaccine interference.
Keywords: Neisseria meningitidis; infants; conjugate vaccine; immunogenicity; meningococcal disease
[Show abstract][Hide abstract] ABSTRACT: Background:
A meningococcal vaccine protective against all major disease-associated serogroups (A, B, C, W and Y) is an unmet public health need. In this phase 2 observer-blinded, randomized, controlled study, two investigational meningococcal ABCWY vaccine formulations were evaluated to assess their immunological noninferiority to a licensed quadrivalent meningococcal ACWY glycoconjugate vaccine (MenACWY-CRM) for serogroups ACWY and immunogenicity against serogroup B test strains, as well as for formulation selection based on a desirability index (DI). Each investigational MenABCWY formulation contained recombinant protein and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine (4CMenB) combined with components of MenACWY-CRM.
A total of 484 healthy 10-25 year-old participants were randomized to receive two doses, two months apart, of an investigational MenABCWY formulation that contained either a full or one-quarter dose of OMV, 4CMenB alone, or a Placebo followed by MenACWY-CRM. Immunogenicity against each of serogroups ACWY and four serogroup B test strains was assessed by serum bactericidal assay with human complement (hSBA). MenABCWY formulations were compared by a DI based on key immunogenicity and reactogenicity parameters.
Seroresponse rates for serogroups ACWY were significantly higher after two doses of either MenABCWY formulation than after one dose of MenACWY-CRM: respectively, A: 90-92% vs. 73%; C: 93-95% vs. 63%; W: 80-84% vs. 65%; and Y: 90-92% vs. 75%. Prespecified noninferiority criteria were met. Both MenABCWY formulations induced substantial immune responses against serogroup B test strains, although 4CMenB responses were higher. Overall DIs for both MenABCWY formulations were similar. Reactogenicity profiles of the MenABCWY formulations were similar to each other and to that of 4CMenB. No vaccine-related serious adverse events were reported.
Both investigational MenABCWY formulations elicited robust immune responses against serogroups ACWY and serogroup B test strains, and had acceptable reactogenicity profiles, with no safety concerns identified.
[Show abstract][Hide abstract] ABSTRACT: Managing pediatric patients with atypical rashes and seemingly simple diagnostic illnesses will continue to challenge pediatricians. Considering the presence of an alternative diagnosis or more than one concomitant diagnosis or pathogen in the evaluation, although we try to avoid it, may often lead to better outcomes. Complex pediatric patients who vex and perplex each of us are to be expected in any outpatient general pediatric practice. [Pediatr Ann. 2014;43(12):470-474.].
Copyright 2014, SLACK Incorporated.
[Show abstract][Hide abstract] ABSTRACT: "Nailing" the management of the severely ingrown great toenail, commonly encountered in the adolescent population, is an important tool in the pediatrician's armamentarium. I have found great toenail removal to be worthwhile, with straightforward indications; and quite rewarding for my patients in terms of time, convenience, and costs. The key to the procedure is to keep it simple. Four basic vital steps are involved: (1) operative permit and explanation; (2) performing a careful complete digital nerve block; (3) removing the entire toenail; and, importantly, (4) performing a partial chemical matricectomy-with readily available silver nitrate sticks-to prevent frequent recurrences. [Pediatr Ann. 2014;43(11):434-439.].
[Show abstract][Hide abstract] ABSTRACT: Background A quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM) is immunogenic in 4-dose infant or 2-dose toddler schedules. We report on persistence of bactericidal antibodies in each group at 60 months of age, and responses 1 month after a booster.
Methods In this phase IIIb, multi-center, open-label, controlled study (clinicaltrials.gov NCT01148017), subjects vaccinated as infants or toddlers were re-evaluated at 60 months of age, with age-matched vaccine-naïve controls. Bactericidal antibodies with human complement (hSBA) measured before and 1 month after booster were expressed as geometric mean titers (GMT) and proportions with seroprotective titers (≥ 8).
Results We enrolled 131 infant- and 54 toddler-vaccinated subjects, and 50 controls. At 60 months, titers had waned, but GMTs were higher in toddler-vaccinated than in infant-vaccinated subjects, and both were higher than controls. Immune responses to a booster dose of MenACWY-CRM were higher in both pre-vaccinated groups, who displayed anamnestic responses. Post-booster, GMTs for serogroups A, C, W, and Y were 177, 206, 1706 and 1135 in infant-vaccinated, 356, 723, 1960 and 1187 in toddler-vaccinated, and 47, 44, 37 and 18 in controls, respectively; 96–100% developed titers ≥ 8 compared with 73–89% of controls.
MenACWY-CRM vaccination at 60 months caused mainly mild or moderate solicited reactions in 62% of infant, 64% of toddler and 76% of control groups. No SAEs were reported.
Conclusion Modest antibody persistence after infant or toddler vaccination with MenACWY-CRM was observed at 60 months of age, with a robust booster effect and high seroprotection rates post-vaccination.
[Show abstract][Hide abstract] ABSTRACT: Background: MenACWY-CRM vaccine was immunogenic in 2–10 year-old children in 1- and 2-dose schedules. As only limited data is available on antibody persistence we assessed bactericidal antibodies 5 years after primary vaccination and response to a booster dose, compared with age-matched vaccine-naïve controls (clinicaltrials.gov NCT01823536).
Methods: We enrolled two groups of 7–10 year-olds after 1 (n = 101) or 2 (n = 73) doses of MenACWY-CRM as 2–5 year-olds, and a group of 11–15 year-olds after 1 dose (n = 66) as 6–10 year-olds, with age-matched naïve-controls (n = 120 and 101). We measured serum bactericidal activity with human complement (hSBA) at baseline and 30 days after a booster or first MenACWY-CRM vaccination. Local and systemic reactions and any adverse events were recorded.
Results: Five years postvaccination levels of antibodies were still higher than controls in the three vaccinated groups, who displayed anamnestic responses to a booster dose, with 99–100% having hSBA titers ≥ 8 against all four serogroups.
Reactogenicity was similar across groups, 50–67% and 27–36% of children had mild to moderate solicited local and systemic reactions. No vaccine-related SAEs were reported.
Conclusion: 5 years after 1- and 2-dose MenACWY-CRM vaccination in 2–10 year-olds, half or more of the children still had persistent antibodies against serogroups C, W and Y with robust responses to a booster dose.
[Show abstract][Hide abstract] ABSTRACT: Background: Novartis has licensed meningococcal vaccines against serogroups A, C, W and Y (MenACWY-CRM) and serogroup B (4CMenB). We evaluated 2 investigational formulations of MenABCWY vaccines, with primary objectives to assess their noninferiority compared with the licensed vaccine for ACWY serogroups and formulation selection based on a desirability index (DI) (Clinicaltrials.gov NCT01272180).
Methods: 480 healthy subjects, aged 10–25 years, were randomized to four groups and received either: one of two MenABCWY formulations with full or quarter doses of outer membrane vesicles (OMV), 4CMenB, or Placebo/MenACWY-CRM. Each was given as a 2-dose series at 0 and 2 months. A serum bactericidal assay with human complement (hSBA) was used to measure antibodies against serogroups A, C, W, Y and serogroup B test strains at baseline and 30 days after dose 2; seroresponses and hSBA GMTs were assessed. For MenABCWY vaccines we also compared a DI based on immunogenicity (post-vaccine hSBA GMT ratios) and reactogenicity parameters (percentages of doses associated with severe local and severe systemic reactions).
Results: Percentages of subjects with seroresponses to A, C, W and Y were significantly higher after 2 doses of either MenABCWY formulation (with full and quarter OMV) than after a single dose of MenACWY; respectively 90/92% vs 73% for A; 95/93% vs 63% for C; 80/84% vs 65% for W; and 92/90% vs 75% for Y. Prespecified noninferiority criteria were met. Both MenABCWY vaccines induced robust immune responses against serogroup B test strains, comparable with 4CMenB. Among the three serogroup B-containing formulations, DI analyses were comparable, although the full dose OMV vaccine induced higher GMTs than the quarter dose vaccine against most of the serogroup B test strains. Reactogenicity profiles of the MenABCWY vaccines were similar to each other and to that of 4CMenB. No vaccine-related serious adverse events were reported.
Conclusion: The MenABCWY vaccines had comparable immunogenicity for serogroups ACWY and for serogroup B, although GMT responses against B test strains appeared to be higher for the full OMV formulation. Reactogenicity was comparable between the investigational and the 4CMenB vaccine.
[Show abstract][Hide abstract] ABSTRACT: Background:
We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine.
Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6. At month 30, the placebo group (n = 482) received HPV4 vaccine following the same regimen and both cohorts were followed through month 96. Subjects ≥ 16 years were eligible for effectiveness evaluations. The primary objective was to evaluate the long-term anti-HPV6/11/16/18 serological levels. The secondary objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease.
For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6/11/16/18-related disease or persistent infection of ≥ 12 months' duration. Acquisition of new sexual partners (among those ≥ 16 years) was ∼1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to ≥ 1 of the 4 HPV types to those vaccinated at day 1 (mean age 12 years; 1.9% [9 of 474] vs 1.7% [20 of 1157]); however, 4 of the 9 subjects vaccinated at the later age were seropositive to 3 vaccine types, indicating previous HPV exposure. No new significant serious adverse events were observed for 8 years postvaccination in both genders.
When administered to adolescents, the HPV4 vaccine demonstrated durability in clinically effective protection and sustained antibody titers over 8 years.
[Show abstract][Hide abstract] ABSTRACT: Petechiae and purpura are among the most alarming findings a pediatrician will commonly observe in the office. Severity of illness can range from a temper tantrum, to common viral infections, to the most deadly infections and diseases. To avoid many of the pitfalls in diagnosis, practitioners will need to be thorough in history taking, assessing fever and immunization status, and physical examination. In addition, a few simple laboratory tests will usually be needed and possibly a manual differential. [Pediatr Ann. 2014;43(8):297-303.].
[Show abstract][Hide abstract] ABSTRACT: Retro-auricular cellulitis associated with otitis externa is now the great mimicker of mastoiditis. It may be the most common cause of this specific cellulitis/auricular protrusion when it is associated with otitis externa. This column presents six cases of children who presented with peri-auricular redness, four of whom had protuberant ear and retro-auricular cellulitis. [Pediatr Ann. 2014;43(9):342-347.].
[Show abstract][Hide abstract] ABSTRACT: Background:
To ensure adequate protection from seasonal influenza in the US, the Advisory Committee on Immunization Practices recommends vaccination of all persons aged 6 months or older, with rare exceptions. It also advises starting vaccination as soon as available and continuing throughout the influenza season. This study examined US seasonal vaccination trends during five consecutive influenza seasons in privately-insured children and adults.
This retrospective, observational cohort study examined trends in influenza vaccination during the 2007-2008 through 2011-2012 influenza seasons using administrative claims data from a large national insurer.
The size of analysis population ranged from 1144,098 to 1245,487 (children, ≥6 months-17 years of age) and from 3931,622 to 4158,223 (adults, 18-64 years of age). Vaccination frequency increased through 2010-2011, was most frequent in young children, and decreased with age. Vaccination rates were highest in the Northeast and lowest in the West and were higher in individuals with frequent outpatient office visits than in those with no or rare visits, with larger differences seen in children. Between 2007 and 2011, the use of preservative-free inactivated vaccine increased, the use of multidose vaccines containing preservatives decreased, and the use of live attenuated influenza vaccines increased among children 2-17 years of age. From 2007-2008 through 2009-2010, the timing of vaccination each year began earlier than the previous one; it remained stable from 2009-2010 through 2011-2012.
Annual influenza vaccination claims for privately-insured children and adults increased and shifted earlier from 2007 through 2009-2011. During the 2011-2012 influenza season, 25.4% of children aged 6 months-17 years and 12.3% of adults aged 18-64 years were vaccinated. Increasing influenza vaccination should remain a priority, and alternative venues for seasonal influenza vaccination should be considered in order to meet the Healthy People 2020 goal of 80% to 90% coverage among children.