Explore the vast range of titles available.

•Non-immunization was significantly associated with increased risk of SUDI.•The immunization schedule analyzed contained the combined hexavalent vaccine.•The immunization schedule analyzed contained the conjugated pneumococcal vaccine. In the context of vaccine scepticism, our study aimed to analyse the association between immunization status and the occurrence of sudden unexpected death in infancy (SUDI). Study design: A multi-centre case–control study was conducted between May 2015 and June 2017 with data from the French national SUDI registry (OMIN) for 35 French regional SUDI centres. Cases were infants under age 1 year who died from SUDI and who were registered in OMIN. Controls, matched to cases by age and sex at a 2:1 ratio, were infants admitted to Nantes University Hospital. All immunization data for diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), Haemophilus influenzae b (Hib), hepatitis B (HB) and 13-valent pneumococcal conjugate vaccine (PCV13) were collected by a physician. Cases and controls were considered immunized if at least one dose of vaccine was administered. A total of 91 cases and 182 controls were included. The median age was 131 days (interquartile range 98–200.0) and the sex ratio (M/F) was about 1.1. For all vaccines combined (D-T-aP-IPV-Hib and PCV13), 22 % of SUDI cases versus 12 % of controls were non-immunized, which was significantly associated with SUDI after adjustment for potential adjustment factors (adjusted odds ratio 2.01 [95 % confidence interval 1.01–3.98, p = 0,047]). Non-immunization for D-T-aP-IPV-Hib-HB and PCV13 was associated with increased risk of SUDI. This result can be used to inform the general public and health professionals about this risk of SUDI in case of vaccine hesitancy.

Combination vaccines simplify immunization schedules and improve compliance, making them a global priority in pediatric immunization strategies. The DTaP-IPV-Hib pentavalent vaccine has been widely adopted, and with the incorporation of the hepatitis B vaccine (HepB), the DTaP-IPV-Hib-HepB hexavalent vaccine was developed. However, whether the addition of antigens in the hexavalent formulation is linked to differences in the reporting of adverse events following immunization (AEFIs) remains a matter of ongoing debate. This study aims to compare the safety profiles and differences in AEFIs between the pentavalent vaccine and the hexavalent vaccine in infants aged 6 weeks to 2 years, based on real-world data from the U.S. Vaccine Adverse Event Reporting System (VAERS). The study also seeks to identify potential safety signals and evaluate correlates of death classification among reports. AEFIs reported to the VAERS from 2018 to 2024 were analyzed. Four disproportionality analysis methods-including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS)-were used to identify potential safety signals. A multivariable logistic regression model was employed to examine factors associated with reports classified as death. A total of 4,980 AEFI reports were included (3,259 for the pentavalent vaccine and 1,720 for the hexavalent vaccine). Reports following hexavalent vaccination more frequently involved serious AEFIs-particularly hospitalization and life-threatening events-than reports following pentavalent vaccination, especially among infants aged 6 weeks to 4 months, in whom apnea and cyanosis were more frequently reported. Disproportionality analysis showed that reports for the hexavalent vaccine generated stronger disproportionality signals in multiple systems, including nervous system disorders (ROR = 1.95; IC025 = 0.70), vascular disorders (ROR = 2.89; IC025 = 1.17), cardiac disorders (ROR = 1.92; IC025 = 0.45), and respiratory disorders (ROR = 1.33; IC025 = 0.19). In the multivariable model, increasing age and female sex were associated with lower odds of reports being classified as death. Co-administration with other vaccines was associated with higher odds of death classification in the pentavalent subset, with no clear association observed in the hexavalent subset. While reports for both vaccines were generally consistent with known safety profiles, those following hexavalent vaccination showed stronger disproportionality signals in younger infants. These findings are hypothesis-generating and highlight the importance of targeted post-vaccination monitoring; they do not establish causality.

Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12–23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥97.3% of ACWY-TT vaccinees had rSBA titres ≥1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.

With the increase in the number of routine vaccinations the development of pentavalent and hexavalent combination vaccines fitting the routine vaccination schedules became a necessity. In this respect, Europe has taken the lead in comparison with other world regions, and routine vaccination with pentavalent and hexavalent combinations including DTPa, Hib, HepB and IPV has been on European vaccination programs for >15years. Since the marketing authorization of Hexavac® and Infanrix Hexa® in 2000, immunization schedules in most European countries have included hexavalent vaccines. In the last years, two new hexavalent vaccines have been licensed and commercialized worldwide. This paper presents a review of the pharmaceutical profiles of the three hexavalent vaccines currently available. In addition, we aim to review safety, co-administration, tolerability and other practical concerns of their use.

Background This study aimed to estimate the economic impact of replacing the current Peruvian primary immunization scheme for infants under 1 year old with an alternative scheme with similar efficacy, based on a hexavalent vaccine. Methods A cost-minimization analysis compared the costs associated with vaccine administration, adverse reactions medical treatment, logistical activities, and indirect social costs associated with time spent by parents in both schemes. A budgetary impact analysis assessed the financial impact of the alternative scheme on healthcare budget. Results Incorporating the hexavalent vaccine would result in a 15.5% net increase in healthcare budget expenditure ($48,281,706 vs $55,744,653). Vaccination costs would increase by 54.1%, whereas logistical and adverse reaction costs would be reduced by 59.8% and 33.1%, respectively. When including indirect social costs in the analysis, the budgetary impact was reduced to 8.7%. Furthermore, the alternative scheme would enable the liberation of 17.5% of national vaccines storage capacity. Conclusions Despite of the significant reduction of logistical and adverse reaction costs, including the hexavalent vaccine into the National Immunization Program of Peru in place of the current vaccination scheme for infants under 1 year of age would increase the public financial budget of the government as it would represent larger vaccine acquisition costs. Incorporating the indirect costs would reduce the budgetary impact demonstrating the social value of the alternative scheme. This merits consideration by government bodies, and future studies investigating such benefits would be informative.

•ProQuad® and hexavalent vaccine immunogenicity is similar if given together or alone.•ProQuad® and hexavalent vaccine have consistent safety when given together or alone.•These data support concomitant use of ProQuad® with a hexavalent vaccine. Concomitant administration of vaccines can facilitate vaccination uptake, provided that no clinically significant effect on either vaccine is identified. We investigated the concomitant administration, during the second year of life, of one dose of the combined measles, mumps, rubella and varicella vaccine (ProQuad®) with a booster dose of a hexavalent vaccine. In this multicentre, open-label study, participants were randomized to 3 groups: Group 1, concomitant administration of one dose of ProQuad® and a booster of hexavalent vaccine; Group 2, one dose of ProQuad® alone; Group 3, a booster dose of hexavalent vaccine alone. Two serum samples were collected, within 7 days prior to vaccination and Days 42–56 post-vaccination for antibody testing. Antibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b following concomitant administration of ProQuad® and hexavalent vaccine were non-inferior compared with those following the individual vaccines. Antibody response rates to these antigens were all >95% in all groups. Antibody titres for the pertussis antigens following concomitant administration were also non-inferior to those following the individual vaccines. Antibody titres for the other valences were numerically comparable between groups with the exception of hepatitis B, Haemophilus influenzae type b, tetanus and poliomyelitis, which were higher in the concomitant than in the non-concomitant groups. The safety profiles of each vaccination regimen were comparable, with the exception of solicited ProQuad®-related injection-site reactions (Days 0–4), which occurred more frequently in the concomitant than in the non-concomitant groups. These immunogenicity data support the concomitant administration of ProQuad® with a hexavalent vaccine. The safety profile of concomitant ProQuad® and hexavalent vaccination was also in line with that of the individual Summaries of Product Characteristics.

A prospective, observational, survey of pediatricians and general practitioners (GPs) was conducted to assess pediatric vaccination knowledge and practices. The survey was distributed by email to 1069 pediatricians and 1700 GPs and completed by 151 pediatricians (14.1%) and 201 GPs (11.8%). Knowledge of the vaccination calendar was very good (99% overall). Of the respondents, 98% were confident in vaccine efficacy. Eight-one percent of pediatricians and 62% of GPs agreed that recommended vaccinations should become obligatory; all prescribed hexavalent vaccines often or always. More pediatricians (88%) than GPs (75%) used anti-pyretics; the use of anesthetic cream/patches was similar in each group (79% and 75%, respectively). The ambience at vaccination was considered to be important by both groups, and was disturbed in 37% of cases. Seventy percent of pediatricians and 57% of GPs agreed that vaccine reconstitution (e.g., Hib pellet) is a complicating factor: overall, 28% reported occasionally omitting to reconstitute a pentavalent or hexavalent vaccine in error, and 60% reported having not fully reconstituted the vaccine. Almost all (93%) considered non-reconstitution as an important error.Conclusion: Overall, adherence to good vaccination practices was good, although errors in reconstitution were reported by physicians. These problems would be minimized by wider use of fully liquid vaccines.What is Known:• Pediatric vaccination schedules are crowded.• Good vaccination practices and the use of multivalent vaccines are essential to maintain good compliance to pediatric vaccination recommendations.What is New:• Overall good compliance to good vaccination practices by both pediatricians and GPs in France.• Omission of pentavalent or hexavalent vaccine reconstitution of Hib pellet and incomplete reconstitution reported by pediatricians/GPs. Awareness of pediatricians/GPs that omission and incomplete reconstitution are important errors.

•Data show no reason to delay DTPa-HBV-IPV/Hib vaccination in preterm/(V)LBW infants.•The vaccine is immunogenic and well-tolerated in preterm/VLBW infants, although HepB/Hib response appeared lower.•Benefit/risk resembles in healthy preterm/term infants and routine vaccines can be co-administered.•13–30% of medically stable preterm infants developed apnea after DTPa-HBV-IPV/Hib.•Data for very preterm/VLBW infants are still limited, and more studies are necessary. Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed. Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK’s hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials. At least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13–30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens. GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK’s hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age. [Display omitted]

•42.4% preterms in Italy receive delayed hexavalent vaccine due to parents’ concerns.•Parents of preterms vaccinated with Hexyon reported systemic adverse effects as rarer.•We aimed at filling hexavalents safety knowledge gaps in pediatric clinical practice. Recommendations in many countries state that preterm infants (PTIs) should receive the same routine immunization schedule and timing as for full-term births, according to their chronological age. Data regarding hexavalent vaccine safety in PTIs are still limited. We conducted a post-marketing surveillance study of the DTaP2-IPV-HB-Hib vaccine administered to PTIs in Apulia region, Italy. We identified PTIs by selecting the hospital discharge records of infants born between January and June 2017 using the DRG and ICD-9-CM codes for preterm birth, and we matched these data with records included in the regional immunization registry. We analyzed coverage and timeliness of vaccination. To investigate adverse events (AEs) after the first dose, we interviewed via phone the parents of PTIs vaccinated with at least one dose of the DTaP2-IPV-HB-Hib vaccine. At the time of our analysis (31.12.2017), 866/936 (92.5%) PTIs received the first dose of hexavalent vaccine and 539/936 (57.6%) were vaccinated by the third month of age, as recommended; 700/866 (80.8%) received the DTaP2-IPV-HB-Hib vaccine. The parents of 339 PTIs vaccinated with the DTaP2-IPV-HB-Hib vaccine reported local pain as the most common reaction (35.7% of the children). Erythema, swelling, induration and nodule were also reported in about 25% of the children. Systemic adverse events were generally rarer than local reactions. No serious AEs were reported. Our findings showed that more than 40% of PTIs received delayed hexavalent vaccination. This study showed a reassuring safety profile of the vaccine in the preterm population and may be considered as a pilot for further real-world studies.

•Anti-HBs concentration <10mIU/mL in many children 10y after priming with hexavalents.•Immune memory persists in >80% of children 10y after priming with hexavalent vaccines.•A 3-dose priming with Hexavac was less immunogenic than similar Infanrix hexa priming. The strategy of vaccinating infants to prevent hepatitis B virus infection in adolescence or adulthood requires durable immunity. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children primed with three doses of either Hexavac® or Infanrix hexa® 10years earlier during infancy. This open-label, controlled, multicentre study conducted in Italy, enrolled 751 healthy pre-adolescents (aged 11–13years) who were given either Hexavac (n=409) or Infanrix hexa (n=342) at 3, 5 and 11months of life. All participants received a challenge dose of a monovalent hepatitis B vaccine (HBVaxPro® 5µg). The concentrations of antibodies to hepatitis B surface antigen (anti-HBs) were measured before and 1month after the challenge dose. The analysis was descriptive and no formal hypothesis was tested. One month post-challenge, 331 participants in the Hexavac cohort [83.6%, 95% CI: 79.6; 87.1] and 324 in the Infanrix hexa cohort [96.4%, 95% CI: 93.8; 98.1] had anti-HBs concentrations ≥10mIU/mL. Before the challenge dose, an anti-HBs concentration of ≥10mIU/mL was found in 94 children in the Hexavac cohort [23.9%, 95% CI: 19.7; 28.4] and in 232 children in the Infanrix hexa cohort [69%, 95% CI: 63.8; 74.0]. Among children with a pre-challenge anti-HBs concentration of <10mIU/mL, 236 [78.7%, 95% CI: 73.6; 83.2] in the Hexavac cohort and 92 [88.5%, 95% CI: 80.7; 93.9] in the Infanrix hexa cohort achieved protective anti-HBs antibody concentrations. No evidence of active hepatitis B disease was observed in either group, and the HBVaxPro challenge dose was well tolerated. These data confirm that immune memory persists in a high percentage of children (>80%) at least 10years after a two-dose primary and booster vaccination schedule with a hexavalent vaccine (Hexavac or Infanrix hexa). Trial registration: EudraCT Number: 2013-001602-28; clinicaltrials.gov: NCT02012998