Safety and immunogenicity of a multivalent pneumococcal conjugate vaccine given with 13-valent pneumococcal conjugate vaccine in healthy infants: A phase 2 randomized trial.

Use of pneumococcal conjugate vaccines (PCVs) has led to substantial reductions in the global burden of pediatric pneumococcal disease. Expansion of serotype coverage has been achieved by increasing PCV valency, but this may carry the potential risk of antibody interference. A complementary 7-valent PCV (cPCV7) including polysaccharide conjugates from 7 non-13-valent (PCV13) serotypes was developed to potentially complement PCV13-mediated protection and expand serotype coverage. This study evaluated cPCV7 and PCV13 coadministered in separate limbs or separated in time in infants. This phase 2, multicenter, open-label study included 512 infants randomized 1:1:1 to receive cPCV7 coadministered with PCV13 at ages 2, 4, 6, and 12 months (cPCV7 Coadministered); cPCV7 given at ages 3, 5, 7, and 13 months, 3‒5 weeks after PCV13 (cPCV7 Separated); or PCV13 at ages 2, 4, 6, and 12 months followed by a single supplemental dose of cPCV7 at 13 months (PCV13 Control). Safety evaluations included local reactions, systemic events, and adverse events. Serotype-specific immunoglobulin G concentrations and opsonophagocytic activity titers were assessed. The safety profile of cPCV7 was similar to that of PCV13. cPCV7 was well-tolerated in infants when coadministered with or given separately from PCV13. Robust and functional immune responses for all cPCV7 serotypes were observed in both cPCV7 groups. No immunologic interference was observed for either the cPCV7 or PCV13 serotypes with coadministration. A single cPCV7 dose induced immune responses in toddlers. These findings support potential coadministration of a complementary PCV to supplement protection provided by existing PCVs.Trial registration: ClinicalTrials.gov, NCT03550313.

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine in Healthy Meningococcal-Naïve Children 2-9 Years of Age: A Phase III, Randomized Study.

BACKGROUND: Invasive meningococcal disease is a major cause of meningitis in children. An investigational meningococcal (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine (MenACYW-TT) could offer protection against invasive meningococcal disease in this population. This phase III study assessed the immunogenicity and safety of MenACYW-TT in children compared with a licensed quadrivalent meningococcal vaccine conjugated with diphtheria protein CRM197 (MenACWY-CRM). METHODS: Healthy children 2-9 years of age in the United States, including Puerto Rico, were randomized (1:1) to receive MenACYW-TT (n = 499) or MenACWY-CRM (n = 501) (NCT03077438). Meningococcal antibody titers to the 4 vaccine serogroups were measured using a serum bactericidal antibody assay with human complement (hSBA) before and at day 30 after vaccination. Noninferiority between the vaccine groups was assessed by comparing seroresponse rates (postvaccination titers ≥1:16 when prevaccination titers were <1:8, or ≥4-fold increase if prevaccination titers were ≥1:8) to the 4 serogroups at day 30. Safety was monitored. RESULTS: The proportion of participants achieving seroresponse at day 30 in the MenACYW-TT group was noninferior to the MenACWY-CRM group (A: 55.4% vs. 47.8%; C: 95.2% vs. 47.8%; W: 78.8% vs. 64.1%; Y: 91.5% vs. 79.3%, respectively). Geometric mean titers for serogroups C, W, and Y were higher with MenACYW-TT than for MenACWY-CRM. Both vaccines were well-tolerated and had similar safety profiles. CONCLUSIONS: MenACYW-TT was well-tolerated in children and achieved noninferior immune responses to MenACWY-CRM against each of the 4 vaccine serogroups.

Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a Phase III randomized study.

The quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) was assessed as a booster in this Phase III trial (NCT02752906). Quadrivalent meningococcal conjugate vaccine (MCV4)-primed individuals aged ≥15 y (n = 810) were randomized 1:1 to receive a single booster dose of MenACYW-TT (n = 403) or a licensed MCV4 (Menactra®; MCV4-DT [n = 407]). Serum bactericidal antibody assay with human complement (hSBA) was used to measure functional antibodies against serogroups A, C, W, and Y at baseline and Day 30 post-vaccination. Proportions of participants achieving seroresponse (post-vaccination titer ≥1:16 for those with baseline titer <1:8 or ≥4-fold increase in post-vaccination titer for those with baseline titer ≥1:8) were determined. Safety data were collected for 180 d post-vaccination. Non-inferiority of the immune response was demonstrated for MenACYW-TT compared with MCV4-DT based on the proportion of participants achieving hSBA vaccine seroresponse for each of the meningococcal serogroups at Day 30. Moreover, ≥99% of participants in both study groups had hSBA titers ≥1:8 for the four meningococcal serogroups at Day 30. Reactogenicity profiles were comparable between groups. These Phase III data in adolescents and adults show that MenACYW-TT boosts the immune response in those primed with MCV4 vaccines 4-10 y previously, irrespective of whether MCV4-DT or MCV4-CRM was used for priming.

Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine coadministered with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine and/or meningococcal conjugate vaccine to healthy girls 11 to 18 years of age: results from a randomized open trial.

BACKGROUND: A combined immunization strategy for administration of human papillomavirus (HPV) vaccine with other routine vaccines may lead to better compliance. Reactions and immunologic interference with concomitantly administered vaccines are unpredictable, necessitating clinical evaluation. METHODS: This was a randomized, open study conducted at 48 centers in the United States (NCT00369824). Healthy girls 11 to 18 years of age were randomized equally to 1 of 6 groups to receive 3 doses of HPV-16/18 AS04-adjuvanted vaccine administered at 0, 1, and 6 or 1, 2, and 7 months, with or without 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) and/or 1 dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MCV4) in different coadministration regimens (1283 girls vaccinated). Coadministered vaccines were injected at separate sites. Antibodies were measured for all vaccine components. Reactogenicity and safety were monitored. RESULTS: The prespecified criteria for noninferiority were met for all primary and secondary immunogenicity end points, demonstrating similar immunogenicity of Tdap and MCV4 when given alone or coadministered with the HPV vaccine. Immunogenicity of the HPV vaccine (in terms of seroconversion rates and geometric mean antibody titers to HPV antigens) was similar, regardless of whether it was given alone or coadministered with Tdap and/or MCV4. No differences were observed in the reactogenicity profile of the HPV vaccine administered alone or coadministered with either Tdap and/or MCV4 in different regimens. CONCLUSIONS: Concomitant administration of HPV-16/18 AS04-adjuvanted vaccine with Tdap and/or MCV4 in different regimens did not interfere with the immune response to any of the vaccines and had an acceptable safety profile.

Changes in newborn bathing practices may increase the risk for omphalitis.

Aseptic cord care, in conjunction with antibacterial skin care, has reduced the incidence of omphalitis specifically caused by Staphylococcus aureus. However, this practice has resulted in the emergence of resistant organisms that may pose a greater risk for newborn infections. Subsequently, many institutions have changed to dry cord care and nonantiseptic whole-body baths, a practice that has not been adequately studied to determine potential infectious risks. Three cases of omphalitis occurring after an institutional change to nonantiseptic whole-body baths are presented. Clinical diagnosis and treatment of omphalitis are reviewed. Recommendations for surveillance of omphalitis are offered.

Cutaneous larva migrans.

Cutaneous larva migrans is occasionally seen in pediatric emergency outpatient care settings. It results from infestation of hookworm larvae into the epidermis. The infestation is self-limited but may produce severe discomfort. The diagnosis relies entirely on clinical findings. Laboratory findings only support the clinical diagnosis but do not confirm it. Treatment is typically with topical thiabendazole, but oral thiabendazole may be indicated in severe cases.

Occurrence of Epstein-Barr virus illness in children diagnosed with group A streptococcal pharyngitis.

Epstein-Barr virus mononucleosis and group A streptococcal pharyngitis are acute infectious processes similar in both their clinical manifestations. Coinfections may occur and be a direct result of a synergistic effect on inflamed pharyngeal and tonsillar tissue. It was our observation that a population of children diagnosed with group A streptococcal pharyngitis and not responding to appropriate antimicrobial therapy had Epstein-Barr virus illness.

Congenital absence of the 5th digital ray and its proximal segmental structures.

Limb reduction anomalies involving digits or parts of limbs are not uncommon. Most cases take the form of terminal transverse absence defects involving hypoplasia or aplasia of all structures distal to a particular level on a limb with relative preservation of the more proximal tissues. Longitudinal absence defects are a more rare form of limb reduction anomalies. Structures within one or more digital rays are typically involved. More proximal segmental tissues may also be affected with the most serious cases resulting in absence of the radius or ulna. We report a case of isolated, longitudinal absence of the 5th finger and its corresponding proximal segmental structures in a newborn infant. The embryology of limb development and possible etiologies for skeletal absence defects are summarized.

Pharmacokinetics and safety of valaciclovir in children with Epstein-Barr virus illness.

OBJECTIVE: Valaciclovir has in vitro activity against Epstein-Barr virus (EBV) and, because of improved absorption with higher achievable serum concentrations, may be more effective than aciclovir in the treatment of EBV. No studies to date have evaluated the efficacy, safety or proper dosing of valaciclovir in children for the treatment of EBV infection. The objectives of this study were to determine the pharmacokinetics and safety of valaciclovir tablets and suspension in children with EBV illness. METHODS: 24 children with EBV illness were randomised to receive valaciclovir suspension 10 mg/kg or 20 mg/kg; eight children subsequently were crossed over and also received valaciclovir 500 mg tablets. Doses of either suspension or tablets were administered every 8 hours for four doses, and pharmacokinetic studies were performed to determine aciclovir serum concentrations. Samples for drug assay were obtained at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours. Samples were assayed by high performance liquid chromatography (HPLC) methods and aciclovir pharmacokinetics determined using non-compartmental analysis. RESULTS: Valaciclovir pharmacokinetic parameters (mean +/- SD) in children who received tablets and suspension (normalised to 500 mg dose) were: maximum serum concentration (C(max)) 3.16 +/- 1.30 and 2.42 +/- 0.74 mg/L, time to maximum serum concentration (t(max)) 1.88 +/- 0.99 and 1.31 +/- 0.53 hours, half-life (t 1/2) 1.72 +/- 0.41 and 1.94 +/- 0.60 hours, apparent total systemic clearance (CL/F) 20.01 +/- 6.61 and 15.58 +/- 3.34 ml/min/kg, volume of distribution/bioavailability (Vd/F) 3.04 +/- 1.26 and 2.58 +/- 0.81 L/kg, and area under the concentration-time curve (AUC) 10.13 +/- 3.47 and 8.59 +/- 2.52 mg x h/L, respectively. There were no statistically significant differences in the pharmacokinetics of valaciclovir tablets versus suspension. The relative bioavailability of the valaciclovir tablets compared with the suspension was 115 +/- 32%. Valaciclovir was well tolerated, with gastrointestinal disturbances and headache being the most common adverse effects in a small number of subjects. CONCLUSIONS: Valaciclovir is absorbed and achieves concentrations in children that appear to be effective for the treatment of herpes lesions. The pharmacokinetics of valaciclovir suspension and tablets are similar, and the pharmacokinetics of aciclovir after administration of valaciclovir to children are similar to historical observations of aciclovir pharmacokinetics in adults. Valaciclovir has a good safety profile and was well tolerated after oral administration in this group of children.