Adverse events following immunization of co- and separate administration of DTaP-IPV/Hib vaccines: A real-world comparative study.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders.

Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

Epidemiological and bacterial profile of childhood meningitis in Tunisia.

The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi (16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. The most frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

Incidence of Bacteremia and Serious Bacterial Infections in Hyperpyrexic Infants Offered Universal Pneumococcal Conjugate Vaccine 13 and Haemophilus influenzae B Immunization.

BACKGROUND: High fevers, especially in young children, often alarm clinicians and prompt extensive evaluation based on perceptions of increased risk of serious bacterial infection (SBI), and even brain damage or seizure disorders. OBJECTIVE: The aim of this study was to determine the prevalence of SBI in infants aged 3-36 months with fever ≥40.5°C in a population of infants offered universal pneumococcal conjugate vaccine 13 and Haemophilus influenzae B immunization. METHODS: This study is a retrospective review of all infants aged 3-36 months with temperature ≥40.5°C presenting to a tertiary care pediatric emergency department over a 30-month period in an era of universal pneumococcal conjugate 13 and H. influenzae B immunization. RESULTS: SBI was recorded in 54 (21.8%) of 247 study infants, most commonly pneumonia 30 patients (12.1%) and urinary tract infection 16 patients (6.5%). Two patients had positive blood cultures, yielding a bacteremia rate of 0.8%. Patients with SBI had a significantly higher WBC count ( P < 0.0001) and C-reactive protein levels ( P < 0.0001), and were significantly more likely to be hospitalized ( P < 0.0001). DISCUSSION: Although SBI was common (21.8%) in our cohort of hyperpyrexic infants universally offered vaccination with pneumococcal conjugate 13 and H. influenzae B vaccines, bacteremia was a rare finding (0.8%).

Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded, randomized, parallel-group study.

OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).

Lung mucosal immunity to NTHi vaccine antigens: Antibodies in sputum of chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness in older adults. A major cause of COPD-related morbidity and mortality is acute exacerbation of COPD (AECOPD). Bacteria in the lungs play a role in exacerbation development, and the most common pathogen is non-typeable Haemophilus influenzae (NTHi). A vaccine to prevent AECOPD containing NTHi surface antigens was tested in a clinical trial. This study measured IgG and IgA against NTHi vaccine antigens in sputum. Sputum samples from 40 COPD patients vaccinated with the NTHi vaccine were collected at baseline and 30 days after the second dose. IgG and IgA antibodies against the target antigens and albumin were analyzed in the sputum. We compared antibody signals before and after vaccination, analyzed correlation with disease severity and between sputum and serum samples, and assessed transudation. Antigen-specific IgG were absent before vaccination and present with high titers after vaccination. Antigen-specific IgA before and after vaccination were low but significantly different for two antigens. IgG correlated between sputum and serum, and between sputum and disease severity. Sputum albumin was higher in patients with severe COPD than in those with moderate COPD, suggesting changes in transudation played a role. We demonstrated that immunization with the NTHi vaccine induces antigen-specific antibodies in sputum. The correlation between IgG from sputum and serum and the presence of albumin in the sputum of severe COPD patients suggested transudation of antibodies from the serum to the lungs, although local IgG production could not be excluded.Clinical Trial Registration: NCT02075541.

What is the context? Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory illness in older adults and the third leading cause of death worldwide.One bacterium in the lungs, non-typeable Haemophilus influenzae (NTHi), is responsible for acute exacerbation of the disease, characterized by an increase in airway wall inflammation and symptoms, leading to high morbidity and mortality.A vaccine targeting NTHi was previously developed but did not show efficacy in reducing exacerbations in COPD patients, probably because the vaccine did not elicit an immune response in the lung mucosae, where the bacteria are located.What is the impact? Parenteral immunization with new vaccines targeting NTHi is able to elicit immune defense at the level of lung mucosae.Now that antibodies can be measured in sputum, new vaccines against COPD exacerbations or other lung infections can be tested for efficacy in the actual target tissue.Also, lung immunity against specific pathogens can now be tested.What is new? We determined that antigen-specific antibodies were present in the lungs after vaccination; these were assessed in sputum after vaccination with NTHi surface antigens.NTHi-specific IgG were present in the lungs and appeared to have arrived there primarily by transudation, a type of leakage from the serum to the lung mucosae.Transudation appeared to be stronger in severe than in moderate COPD patients.

Disparate kinetics in immune response of two different Haemophilus influenzae type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule.

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.710­1.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group ­ Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.

Preferences of healthcare providers in Switzerland for attributes of pediatric hexavalent vaccines: a discrete-choice experiment.

OBJECTIVE: To understand the preferences of healthcare providers (HCPs) in Switzerland for pediatric hexavalent vaccine attributes. METHODS: A discrete-choice experiment included a series of choices between 2 hypothetical pediatric hexavalent vaccines with varying attributes: device type (including preparation time and risk of dosage errors), proportion of infants seroprotected against Haemophilus influenzae type b (Hib) at 11-12 months (pre-booster), packaging size, years on the market, and the thermostability at room temperature. Odds ratios (ORs) and conditional relative attribute importance (CRAI) were calculated using random-parameters logit. RESULTS: HCPs (150 pediatricians and 40 nursing staff) in Switzerland were unlikely to choose a vaccine conferring 50% (OR 0.00; 95% CI 0.00-0.00) or 70% (OR 0.01; 95% CI 0.00-0.01) of infants with Hib seroprotection at 11-12 months (pre-booster) compared with a vaccine conferring 90% seroprotection. The odds of choosing a vaccine available on the market for more than 3 years were nearly 5 times the odds of choosing a vaccine available on the market for less than 1 year (OR 4.76; 95% CI 1.87-7.65). The odds of choosing a vaccine in a prefilled syringe were nearly 3 times the odds of choosing a reconstituted vaccine (OR 2.77; 95% CI 1.39-4.15), and the odds of choosing a vaccine with a smaller package size were nearly 2 times the odds of choosing a vaccine with larger package size (OR 1.89; 95% CI 1.23-2.55). HCPs were equally likely to choose vaccines that can stay at room temperature for 6 versus 3 days (OR 1.07; 95% CI 0.73-1.42). According to CRAI, the most important attribute was Hib seroprotection, followed by years on the market, device type, and packaging size. CONCLUSION: Hib seroprotection at 11-12 months was the most important hexavalent vaccine attribute to HCPs in this study.

High Prevalence of Non-typeable Haemophilus influenzae and Haemophilus haemolyticus Among Vaccinated Children with Community-Acquired Pneumonia in Vietnam.

Among 467 children under five hospitalized with community-acquired pneumonia, the prevalence of Haemophilus influenzae or Haemophilus haemolyticus was 60.8%, all cases were non-typable H. influenzae (NTHi) or H. haemolyticus. NTHi/H. haemolyticus PCR detection was associated with about twice the risk for severe disease. The results highlight the need for increased awareness and research efforts to investigate the role of NTHi/H. haemolyticus in severe CAP among children.

A phase 4, open-label study to evaluate the safety and immunogenicity of DTaP5-HBV-IPV-Hib in children previously vaccinated with DTaP2-HBV-IPV-Hib or DTaP5-HBV-IPV-Hib (V419-016).

DTaP5-HBV-IPV-Hib (Vaxelis®) is a hexavalent combination vaccine (HV) indicated in infants and toddlers for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. Switching between HVs during the childhood vaccination series is sometimes necessary due to, for example, vaccine availability, health-care provider preference, and/or tender awards. The purpose of this study was to describe the safety, tolerability, and immunogenicity of a booster dose of Vaxelis® in participants who previously received a primary infant series of either DTaP2-HBV-IPV-Hib (Hexyon®) or Vaxelis®. Healthy participants approximately 11-13 months of age who previously received a two-dose primary series of Hexyon® (HHV group) or Vaxelis® (VVV group) all received a Vaxelis® booster dose. Immunogenicity was evaluated by measuring antibody levels to individual vaccine antigens approximately 30 days following booster vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). The proportions of participants with antibody-specific responses for antigens contained in both Vaxelis® and Hexyon® at 30 days post-toddler-booster vaccination with Vaxelis® were comparable between groups, and higher in the VVV group for Vaxelis® antigens PRN and FIM2/3. The overall proportions of participants with AEs were generally comparable between groups. Following a booster dose of Vaxelis®, immune responses were comparable between groups for all shared antigens, and higher in the VVV group for antigens found only in Vaxelis®. The booster was well tolerated in both groups. These data support the use of Vaxelis® as a booster in mixed HV regimens.

Efficacy and Prolonged Safety of Haemophilus influenzae Type b Conjugate Vaccines.

OBJECTIVE: The purpose of this study was to find data proving the influence of the Haemophilus influenzae type b (Hib) conjugate vaccination on the frequency of invasive Hib illness. METHODOLOGY: A systematic literature search was conducted on the PubMed database to identify peerreviewed publications pertaining to the epidemiology of Haemophilus influenzae meningitis, both before and after the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines. The search query employed a combination of relevant keywords, including "invasive," "Haemophilus," "influenzae," "meningitis," and specific serotype b (Hib). Additionally, terms related to epidemiology, burden, risk factors, impact, Hib vaccine, Hib conjugate vaccine, combination vaccine, vaccine production, efficacy, immunisation coverage, surveillance, review, clinical aspects, outcomes, and various age groups (adults and children) were incorporated. RESULT: The search encompassed articles published till now. Subsequently, relevant research papers concerning Haemophilus influenzae meningitis were subjected to a comprehensive review and analysis. CONCLUSION: The Hib conjugate vaccination has shown to be extremely effective when administered to the entire population. However, changes to the immunisation protocol appear to be required in order to effectively manage invasive Hib illness.

Non-specific effects of Pneumococcal and Haemophilus vaccines in children aged 5 years and under: a systematic review.

OBJECTIVE: To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under. DATA SOURCES: A key word literature search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, the European Union Clinical Trials Register and ClinicalTrials.gov up to June 2023. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs), quasi-RCT or cohort studies. PARTICIPANTS: Children aged 5 or under. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were independently screened by two reviewers, with a third where disagreement arose. Risk of bias assessment was performed by one reviewer and confirmed by a second. Results were tabulated and a narrative description performed. RESULTS: Four articles were identified and included in this review. We found a reduction in hospitalisations from influenza A (44%), pulmonary tuberculosis (42%), metapneumovirus (45%), parainfluenza virus type 1-3 (44%), along with reductions in mortality associated with pneumococcal vaccine. No data on the Haemophilus vaccine was found. CONCLUSIONS AND IMPLICATIONS: In this systematic review, we demonstrate that there is a reduction in particular viral infections in children aged 5 years and under who received the 9-valent pneumococcal conjugate vaccine which differ from those for which the vaccine was designed to protect against. While limited studies have demonstrated a reduction in infections other than those which the vaccine was designed to protect against, substantial clinical trials are required to solidify these findings. PROSPERO REGISTRATION NUMBER: CRD42020146640.

Estado de vacunación en pacientes con riesgo de enfermedades invasoras por bacterias capsuladas en un hospital pediátrico de Buenos Aires / Vaccination status in patients at risk for invasive disease with encapsulated bacteria at a children's hospital in the City of Buenos Aires

Introducción. El Ministerio de Salud contempla vacunas específicas para personas con riesgo elevado de infecciones invasoras por bacterias capsuladas (BC). En la actualidad se desconoce el cumplimiento del programa. El objetivo fue evaluar el estado de vacunación para BC en ≤ 18 años con factores de riesgo. Población y métodos. Estudio observacional, analítico, mediante encuesta a padres de ≤ 18 años con VIH, asplenia y/o déficit de complemento que concurrieron al vacunatorio de un hospital pediátrico de octubre de 2020 a septiembre de 2021. Se recabaron datos sociodemográficos y clínicos. Se evaluó el estado de vacunación para BC: neumococo, meningococo y Haemophilus influenzae b (Hib), calendario regular y antigripal. Se administró la escala de reticencia a la vacunación (ERV): rango 10-50. Se analizó la asociación entre las variables estudiadas y la vacunación para BC mediante regresión logística (OR, IC95%). Se utilizó la base datos REDCap® y STATA vs14®. Resultados. Participaron 104 sujetos, media 9,9 años (DE 4,4). Asplenia: 91,3 %, VIH: 7,6 % y déficit de complemento: 0,9 %. Nivel socioeconómico: pobreza relativa: 38,4 %, seguido por clase media: 37,5 %. Estado de vacunación completa para meningococo: 45 %, neumococo: 42 %, Hib: 97 %. El 77,9 % tenía al día el calendario regular y el 61,5 %, el antigripal. Media ERV: 41,9 (DE 3,2). No se encontraron asociaciones significativas entre las variables y el estado de vacunación para BC. Conclusiones. Un elevado porcentaje no tenía vacunación completa para BC, tampoco el calendario regular y antigripal. La confianza en la vacunación de los cuidadores fue elevada.

Introduction. The Ministry of Health has established specific vaccines for people at high risk for invasive infections with encapsulated bacteria (EB). There is currently no information about compliance with the vaccination schedule. Our objective was to assess EB vaccination status in subjects ≤ 18 years with risk factors. Population and methods. Observational, analytical study with a survey to parents of subjects aged ≤ 18 years with HIV, asplenia and/or complement deficiency attending a vaccination center at a children's hospital between October 2020 and September 2021. Sociodemographic and clinical data were collected. Their vaccination status for the EB pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib), their regular vaccination and flu vaccination schedules were assessed. The vaccine hesitancy scale (VHS) was administered: range 10­50. The association between the study variables and EB vaccination was analyzed using logistic regression (OR, 95% CI). The REDCap® database and the STATA® v.14 software were used. Results. A total of 104 subjects participated; mean age: 9.9 years (SD: 4.4). Asplenia: 91.3%, HIV: 7.6%, and complement deficiency: 0.9%. Socioeconomic level: relative poverty: 38.4%, followed by middle class: 37.5%. Complete vaccination status: meningococcal vaccine 45%, pneumococcal vaccine: 42%, Hib: 97%. The regular vaccination and flu vaccination schedules were up-to-date in 77.9% and 61.5% of cases, respectively. Mean VHS score: 41.9 (SD: 3.2). No significant associations were observed between variables and EB vaccination status. Conclusions. A high percentage of subjects had not completed neither their EB vaccination nor their regular or their flu vaccination schedules. Caregivers' confidence in vaccines was high.

Childhood vaccination coverage and regional differences in Swiss birth cohorts 2012-2021: Are we on track?

AIMS: Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to estimate vaccination coverage and timeliness in Swiss children over a decade. Furthermore, we evaluated the impact of COVID-19, regional variations, and the adherence to the amended vaccination schedule in 2019. METHODS: Retrospective observational study with Swiss health insurance claims data including birth cohorts 2012-2021 of children continuously observed until ages 13, 25, and 48 months respectively. We used population-weighted proportions and time-to-event analyses to describe coverage and timeliness of diphtheria/tetanus/pertussis/poliomyelitis/haemophilus influenzae type b (DTaP-IPV-Hib), measles/mumps/rubella (MMR), hepatitis B (HBV), pneumococcal (PCV), and meningococcal (MCV) vaccinations according to the national schedule. The potential impact of COVID-19 and vaccination schedule adherence were evaluated descriptively. Logistic regression was used to investigate regional factors potentially associated with non-vaccination. RESULTS: 120,073 children, representing between 12 and 17 % of all Swiss children born in corresponding years, were included. Coverage remained stable or improved over the years. The 2019 amendment of the national immunization schedule was associated with an increase of ~10 % points in full coverage in Swiss children for DTaP-IPV-Hib, MMR and HBV despite the concurrent COVID-19 pandemic. Nonetheless, full vaccination coverage remained below 90 % with many vaccination series being delayed or not completed. The comparison across the different vaccines revealed large differences in coverage. Moreover, we observed large regional differences in non-vaccination with children living in rural and German-speaking areas more likely to be entirely unvaccinated. CONCLUSION: Full vaccination coverage in Swiss children is still below 90 % with many vaccinations administered delayed. Given regional differences, missed or delayed booster vaccinations, and differences in vaccine-specific acceptability, more effort may be needed to achieve national vaccination targets.

Análisis económico de las vacunas del primer año de vida con componente pertussis en el contexto de la ini-ciativa mundial de erradicación de la poliomielitis en Argentina / Vaccination in children under 1 year with pertussis component in the context of the global initiative for the eradication of poliomyelitis in Argentina: economic analysis

INTRODUCCIÓN: La Iniciativa Mundial de Erradicación de la Polio promueve la introducción de vacuna de polio inactivada (IPV) en sus programas, con la posterior retirada de Sabin (bOPV). OBJETIVO: Construir un modelo de económico que compare diferentes esquemas de vacunación para la prevención de polio y tosferina en el primer año de vida. Material y MÉTODOS: Análisis de cuatro escenarios de vacunación del esquema primario para Argentina, en base a los precios de las vacunas, costos del programa y reactogenicidad de vacuna celular o acelular para Bordetella pertussis: - Escenario 1 (caso base): dos dosis de IPV, una dosis de bOPV y tres dosis de vacuna pentavalente (DTwP-HB-Hib); - Escenario 2: tres dosis IPV y de pentavalente; - Escenario 3: tres dosis de hexavalente (DTaP-HepB-IPV-Hib); - Escenario 4: dos dosis de hexavalente más una dosis de pentavalente más IPV. RESULTADOS: El costo incremental en base al escenario 1 fue de USD 3.716.671; 19.696.668 y 14.383.341 para los escenarios 2, 3 y 4, respectivamente. Para la reactogenicidad, la diferencia fue de USD -14.178.240 comparado el caso base con el escenario 3. DISCUSIÓN: La inversión de incorporación de full IPV y costos asociados se modifica según tipo de vacuna y reactogenicidad asociada al componente B. pertussis.

BACKGROUND: Global Polio Eradication Initiative promotes the introduction of inactivated polio vaccine (IPV) in its programs, with withdrawal of Sabin (bOPV). There is no an economic analysis of the investment related to the incorporation of IPV vaccines together with a whole cell Bordetella pertussis vaccine or combined with acellular hexavalent. AIM: An economic model that compares different vaccination schemes for the prevention of polio and pertussis in the first year of life was carried out. METHODS: Four vaccination scenarios for the primary scheme based on Argentina demographic and costs data were developed: - Scenario 1 (base case): two doses of IPV, one dose of bOPV and three doses of pentavalent (DTwP-HepB-Hib) vaccine; - Scenario 2: three doses of IPV plus three doses of pentavalent; - Scenario 3: three doses of hexavalent; - Scenario 4: two doses of hexavalent plus one dose of pentavalent plus IPV. RESULTS: The incremental cost based on scenario 1 was USD 3.716.671; 19.696.668 and 14.383.341 for scenarios 2, 3 and 4 respectively. In terms of reactogenicity savings was -14.178.240 compared base case with scenario 3. DISCUSSION: Full IPV introduction investment and costs associated were modified according to the type of vaccine and reactogenicity related with the B. pertussis component.