Infant Vaccination Research Articles

The Impact of the U.S. Maternal Tdap Vaccination Program on Preventing Pertussis in Infants 2-<6 Months of Age: A Case-control Evaluation

Abstract Background To protect infants aged <2 months against pertussis, the United States recommends Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during each pregnancy. Data are limited on the strategy’s effectiveness against pertussis in infants aged ≥2 months. Methods Pertussis cases aged 2-<6 months with cough onset between 1/1/2011-12/31/2014 were identified in six U.S. states. Controls were 2-<6 months of age, hospital-matched, and selected by birth certificate. Mothers were interviewed to collect demographic and healthcare information. Provider-verified vaccination history was obtained for infants and mothers. Adjusted odds ratios (aORs) were calculated using conditional logistic regression; overall vaccine effectiveness (VE) was estimated as (1 - aOR) x 100. To describe maternal Tdap VE modified by infant DTaP (diphtheria and tetanus toxoids, and acellular pertussis) doses, case-control sets were unmatched and a time-to-event analysis conducted through a Generalized Linear Mixed Model. Results A total of 335 cases and 927 controls were enrolled. The overall adjusted VE estimate for Tdap during pregnancy was 45.6% (95% confidence interval [CI], 5.8% – 68.5%) and increased slightly, but not significantly against infant hospitalization (55.7% (-116.8% – 90.9%)). Although point estimates were not significant, VE was modified by infant DTaP doses (58.8% (-6.0% – 84.0%) for zero DTaP doses, 30.5% (-21.4% – 60.2%) for one DTaP dose, and 3.2% (-170.8% – 65.4%) for two DTaP doses). Conclusions Our study suggests that there is some benefit of maternal Tdap vaccination beyond the first two months of life, however, on-time vaccination of infants remains critical to maintain protection from pertussis.

Long-term dynamics of measles virus-specific neutralizing antibodies in children vaccinated before 12 months of age.

Measles is a highly contagious disease presenting a significant risk for unvaccinated infants and adults. Measles vaccination under the age of 12 months provides early protection, but has also been associated with blunting of antibody responses to subsequent measles vaccinations and assumed to have lower vaccine effectiveness. Our study included children who received an early measles, mumps and rubella (MMR) vaccination between 6 and 12 months of age (n=79, given in addition to the regular MMR vaccination schedule at 14 months and 9 years) and a group without additional early vaccination (n=44). We evaluated measles virus (MeV)-specific neutralizing antibodies before vaccination at 14 months and up to 6 years thereafter using a plaque reduction neutralization test according to the standard set by the WHO. We show a significant association between age of first MMR and MeV-specific neutralizing antibody levels later in life. Although most children who received early vaccination seroconverted after the first dose, children vaccinated before 8·5 months of age exhibited a markedly faster antibody decay and lost their protective neutralizing antibody levels over 6 years. Routine vaccination of infants under 8·5 months of age may lead to blunted MeV-specific antibody responses to subsequent MMR vaccination. Early MMR vaccination should only be considered during measles outbreaks or in other situations of increased risk of MeV infection.

Clinician Staffing and Quality of Care in US Health Centers

Health centers are vital primary care safety nets for underserved populations, but optimal clinician staffing associated with quality care is unclear. Understanding the association of clinician staffing patterns with quality of care may inform care delivery, scope-of-practice policy, and resource allocation. To describe the association of clinician staffing models and ratios with quality-of-care metrics in health centers. This cross-sectional study of US health centers used data from the 2022 Health Resources and Services Administration Uniform Data System (UDS). Clinician staffing ratios, expressed as the fraction of full-time equivalents (FTEs) per 1000 visits of physicians, advanced practice registered nurses (APRNs), and physician associates (PAs) to total clinician FTEs at each health center. Percentage of eligible patients receiving the corresponding service or outcome for 14 individual clinical quality metrics collected by the UDS, including infant immunizations; screening for cancer, depression, tobacco use, hypertension, HIV, and glycated hemoglobin levels; weight and body mass index (BMI) assessment; and appropriate statin, aspirin, and/or antiplatelet therapy. This analysis of 791 health centers serving 16 114 842 patients (56.6% female) identified 5 clinician staffing models: balanced (similar FTEs of physicians, APRNs, and PAs; 152 [19.2%] of health centers), higher FTEs of APRNs than physicians (174 [22.0%]), higher FTEs of physicians than APRNs (160 [20.2%]), approximately equal FTEs of physicians and APRNs (263 [33.2%]), and large scale (42 [5.3%]). Adjusted linear models showed positive associations between physician FTEs per 1000 visits and cervical (β, 14.9; 95% CI, 3.1-26.7), breast (β, 15.7; 95% CI, 3.2-28.1), and colorectal (β, 18.3; 95% CI, 6.0-30.6) cancer screening. Generalized additive models showed nonlinear positive associations beginning at a physician FTE ratio of 0.45 (95% CI, 0.02-6.22) for infant vaccinations, 0.39 (95% CI, 0.05-2.21) for cervical cancer screening, 0.39 (95% CI, 0.02-1.67) for breast cancer screening, 0.47 (95% CI, 0.00-5.76) for HIV testing, and 0.70 (95% CI, 0.18-19.96) for depression in remission; APRN FTE ratio of 0.45 (95% CI, 0.17-7.46) for adult BMI assessment; and PA FTE ratio of 0.16 (95% CI, 0.11-3.88) for infant vaccinations. Staffing models were not associated with 7 of the 14 metrics analyzed. In this cross-sectional study of health centers, physician FTE ratio was associated with higher performance in cancer screening, infant vaccinations, and HIV testing; APRN FTE ratio was associated with higher performance in preventative health assessments; and PA FTE ratio was associated with higher performance in infant vaccination. These findings suggest that targeted staffing strategies may be associated with quality of care in certain domains and that tailored approaches to health center staffing based on community-specific needs are warranted.

Effect of 10-valent pneumococcal conjugate vaccine on trends of pneumococcal meningitis in children under five years, Uganda, 2003-2022.

Pneumococcal meningitis, a vaccine-preventable disease caused by Streptococcus pneumoniae (Spn) is the leading bacterial meningitis in under five children. In April 2014, Uganda introduced routine immunization with 10-valent Pneumococcal Conjugate Vaccine (PCV10) for infants. The target coverage for herd immunity is ≥ 90% with three doses (PCV10-dose 3). We assessed the effect of PCV10 introduction and coverage on the trends of pneumococcal meningitis in under five children. We analyzed laboratory-confirmed pediatric bacterial meningitis (PBM) data at two high-volume WHO-accredited sentinel surveillance hospitals in Kampala City and Gulu District, from 2003 to 2022. We used confirmed cases to estimate the minimum incidence of pneumococcal meningitis in the host districts and calculated annual incidence of pneumococcal meningitis per one million populations, and the proportion of confirmed PBM attributable to Spn. We divided the study period into 2003-2013 (pre-PCV10) and 2014-2022 (post-PCV10), and conducted interrupted time series analysis using autoregressive integrated moving average models for the effect of PCV10 on trends of pneumococcal meningitis and PBM attributable to Spn. We analyzed reported PCV10 data in DHIS2 from 2014 to 2022 for annual PCV10-dose 3 coverage. Among the 534 confirmed PBM cases, 331(62%) were pneumococcal meningitis; 227(69%) from Gulu District and 104(31%) from Kampala City. The majority (95%) of the isolates were not serotyped. The majority (57%) were male and unimmunized (98%); median age = 14(IQR = 6-27) months with most (55%) aged ≥ 12 months. The case-fatality rate was 9%. During Pre-PCV10 period, the overall incidence of pneumococcal meningitis in the host districts increased; slope change = 1.0 (95%CI = 0.99999, 1.00001) but declined in post-PCV10 period (2014-2022) by 92% from 86 cases /1,000,000 in 2014 to 7/1,000,000 in 2022, slope change= -1.00006 (95%CI=-1.00033, -0.99979). Whereas there was an immediate decline in the proportion of confirmed PBM attributable to Spn in the host districts, level change=-1.84611(95%CI=-1.98365,-1.70856), an upward trend was recorded from 2016 to 2022, slope change = 1.0 (95%CI = 0.99997, 1.00003). During 2015-2022, PCV10-dose 3 coverage was largely > 90% for Gulu District and 52-72% for Kampala City. The PCV10 routine immunization program reduced the incidence of pneumococcal meningitis in Kampala City and Gulu District. There was no effect on the confirmed PBM proportionately attributable to Spn. Kampala City persistently recorded PCV10-dose3 coverage < 90%. We recommend enhancing serotyping and periodic nasopharyngeal carriage surveys to ascertain the maximum vaccine effectiveness and monitor Spn serotypes, and strengthening routine immunization in Kampala City.

An open-label, phase IV randomised controlled trial of two schedules of a four-component meningococcal B vaccine in UK preterm infants

ObjectiveTo compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines.DesignAn open-label,...

A prospective, multicenter study of hepatitis B birth-dose vaccine with or without hepatitis B immunoglobulin in preventing mother-to-child transmission of hepatitis B virus in Ethiopia

BackgroundHistorically, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) was considered uncommon in Africa, leading to a reluctant attitude to birth-dose HBV vaccination on the continent. As a randomized trial would be unethical, real-life data are needed to assess the effect of HBV birth-dose vaccine in Africa. MethodsA multicenter, prospective, observational study of hepatitis B surface antigen (HBsAg)-positive pregnant women and their infants was carried out in Ethiopia, from January 2019 to May 2021. Pregnant women were screened for HBsAg and HIV as part of routine antenatal care and/or delivery, and HBsAg-positive HIV-negative pregnant women were included in the study. HBV birth-dose vaccine and hepatitis B immunoglobulin (HBIg) were recommended but not all newborns received it as it was not national policy. All infants, however, received the pentavalent HBV vaccine at 6, 10, and 14 weeks of age. Vaccination status was confirmed from delivery ward charts and infant vaccination certificates. Infants were tested for HBsAg at 9 months of age and a positive result was taken as evidence of MTCT. FindingsOf 290 HBsAg-positive pregnant women, 168 mother/infant pairs returned for their 9-month follow-up visit and were included in this analysis. Two of 112 (1.8 %) infants who received birth-dose vaccine with HBIg, and 2 of 23 (8.7 %) who received birth-dose vaccine alone were HBsAg positive at nine months of age, compared to 8 of 33 (24.2 %) who received neither vaccine nor HBIg at birth (p = 0.002). High maternal viral load (>200,000 IU/ml; adjusted odds ratio [AOR] 10.4; 95 % confidence interval [CI] 1.2–92.1) and not receiving HBV birth-dose vaccine nor HBIg (AOR 29.2; 95 % CI 4.0–211.3) were independent predictors of MTCT. InterpretationBirth-dose HBV vaccine with or without HBIg significantly reduced the risk of MTCT of HBV in Ethiopia. Improved coverage of birth-dose HBV vaccine should be an urgent priority.

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns.

The neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs) and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a novel glucopyranosyl lipid A (GLA)-stable emulsion (SE) adjuvant admixed with a first-in-infant CH505 transmitter-founder (CH505TF) gp120 immunogen designed to induce precursors for bnAbs against HIV. HVTN 135 is a phase I randomized, placebo-controlled trial of CH505TF+GLA-SE or placebo. Healthy infants in South Africa aged ≤5 days, born to mothers living with HIV but HIV nucleic acid negative at birth were randomized to five doses of CH505TF + GLA-SE or placebo at birth and 8, 16, 32, and 54 weeks. 38 infants (median age = 4 days; interquartile range 4, 4.75 days) were enrolled November 2020 to January 2022. Among 28 (10) infants assigned to receive CH505TF + GLA-SE (placebo), most (32/38) completed the 5-dose immunization series and follow-up (35/38). Solicited local and systemic reactions were more frequent in vaccine (8, 28.6% local; 16, 57.1% systemic) vs. placebo recipients (1, 10% local, p = 0.25; 4, 40.0% systemic, p = 0.38). All events were Grade 1 except two Grade 2 events (pain, lethargy). Serious vaccine-related adverse events were not recorded. This study illustrates the feasibility of conducting trials of novel adjuvanted HIV vaccines in HIV-exposed infants receiving standard infant vaccinations. The safety profile of the CH505TF + GLA-SE vaccine was reassuring. ClinicalTrials.gov NCT04607408. National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH). This paper summarizes the phase 1 trial design and safety profile of an experimental CH505TF immunogen + GLA-SE HIV vaccine in infants born to mothers living with HIV.

The Effect of Grasp Reflex Stimulation on Pain During Vaccine Administration.

The administration of vaccination, being an invasive procedure, can induce considerable pain in preterm infants. This study was conducted to evaluate the effect of grasp reflex stimulation on pain and crying time during hepatitis B vaccine administration in infants. This parallel randomized controlled trial was conducted between November 1, 2022, and April 1, 2023, at the Neonatal Intensive Care Unit of a public hospital in Turkey. The study included preterm infants whose parents provided both verbal and written consent. The control group (n =31) underwent a routine vaccination procedure, while the experimental group (n =28) underwent grasp reflex stimulation in addition to the routine vaccination procedure. Data were collected through the infant information form, stopwatch, and Premature Infant Pain Profile Scale-Revised (PIPP-R) form. The mean PIPP-R score during the procedure was 11.67±2.05 in the experimental group and 15.51±1.36 in the control group (P ≤.001). After the procedure, the mean PIPP-R score was 10.89±2.06 in the experimental group and 14.67±1.55 in the control group (P ≤.001). The mean duration of crying was 19.57±6.17 in the experimental group and 27.12±6.19 in the control group (P ≤.001). The mean PIPP-R and crying time of the control group were higher. Grasp reflex stimulation applied to preterm infants during vaccine administration decreased pain and crying time during and after the procedure. Grasp reflex stimulation can be applied as a care approach for procedures that may cause pain in infants and may help calm infants as part of pain management in nursing. The results of this study provide new information to the literature regarding the impact of grasp reflex stimulation on pain and the duration of crying induced by the hepatitis B vaccine in preterm infants. To our knowledge, this is the first study to confirm the effectiveness and feasibility of grasping reflex stimulation in hepatitis B vaccine administration in preterm infants. This study may contribute to future evidence-based studies. Grasping reflex stimulation can be tried as a parent-provided intervention in younger or older infants or in those who are critically ill.

A prospective, observational, multi-center, post-marketing safety surveillance study of the GSK combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) in South Korean infants

ABSTRACT In South Korea, a combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b invasive infections (DTaP-IPV/Hib) is available since 2018 for vaccination of infants from the age of 2 months. This prospective, observational, non-comparative, post-marketing study evaluated the real-world safety of DTaP-IPV/Hib primary vaccination in eligible South Korean infants from the age of 2 months between 2018 and 2022. Infants were followed up for 30 days after each vaccine dose to assess the proportion of infants experiencing any adverse event (AE), including adverse drug reactions (ADRs), unexpected AEs, and serious AEs/serious ADRs (SAEs/SADRs). Of 660 infants vaccinated during the study period, 646 were included in the total safety cohort. A total of 194 AEs were reported in 143 (22.1%) infants; 158 AEs occurred after the first dose in 130 (20.1%) infants, 21 after the second dose in 20 (13.4%) infants, and 11 after the third dose in ten (8.1%) infants. The most frequent AEs by Medical Dictionary for Regulatory Activities Preferred Terms terminology were pyrexia (13.3%), injection site swelling (5.1%), and irritability (1.7%). Most of the AEs were mild, resolved without a medical visit, and were classified as possibly related to vaccination. The incidence proportions of ADRs, unexpected AEs, and SAEs/SADRs were 19.4%, 4.3%, and 0.9%, respectively. All SAEs/SADRs resolved after hospitalization or emergency room visit, and one event was possibly related to vaccination. These results are in line with the approved label and other national/international studies, confirming the acceptable safety profile of DTaP-IPV/Hib in the South Korean pediatric population.

The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial

The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-0·02 [95% CI -0·13 to 0·10]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-0·17 [-0·27 to -0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-0·42 [-0·50 to -0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-0·44 [-0·55 to -0·33]), and involved antibodies to the central NANP region (r=-0·39 [-0·49 to -0·28]) but not the C-terminal region (r=0·02 [-0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables. Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal antibodies. US National Institutes of Health, National Institute of Allergy and Infectious Diseases; PATH-Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), European Regional Development Fund and European Social Fund; Fundación Ramón Areces; Spanish Ministry of Science and Innovation; and Generalitat de Catalunya (CERCA Program).

Descriptive analysis of safety and immunogenicity profiles of a 15-valent pneumococcal conjugate vaccine between subcutaneous and intramuscular administration in a phase 1 study of healthy Japanese infants (V114-028)

IntroductionSubcutaneous (SC) administration is typically used for pediatric inactivated vaccines in Japan, whereas intramuscular (IM) administration is used outside Japan. We previously reported the safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), administered subcutaneously and intramuscularly in a Japanese phase 1 study (V114-028). Here, we report secondary descriptive analyses on V114 groups of the study to further assess the safety and immunogenicity profiles of V114 between the administration routes. MethodsA total of 133 healthy Japanese infants were randomized to receive V114-SC (n = 44), V114-IM (n = 45), or PCV13-SC (n = 44) at approximately 3, 4, 5, and 12–15 months of age. Adverse events (AEs) from Days 1–14 post-vaccination and vaccine-related serious AEs from Day 1 to 1-month post-dose 4 were reported. Serotype-specific immunoglobulin G (IgG) responses were measured across the vaccination series. ResultsProportions of participants with solicited systemic AEs (irritability, somnolence, decreased appetite, and urticaria) and pyrexia were generally comparable between the groups. Compared with V114-SC, patients receiving V114-IM had a lower incidence of irritability and somnolence, and higher incidence of decreased appetite. Proportion of participants with solicited injection-site erythema was lower with V114-IM (82.2%) than V114-SC (100.0%). Those with other solicited injection-site AEs (induration, swelling, and pain) were generally comparable between the groups, with lower observed proportions with V114-IM. Serotype-specific IgG responses were also generally comparable between the groups, including at pre-toddler dose. ConclusionsThese results suggest the utility of IM administration as an option for V114 vaccination in Japanese infants.

Safety of Rotavirus Vaccination in Infants That Were Exposed to Biologics In Utero: A Systematic Review

Safety of Rotavirus Vaccination in Infants That Were Exposed to Biologics In Utero: A Systematic Review

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

June 2024 ACIP Meeting Update: Influenza, COVID-19, RSV, and Other Vaccines.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met June 26 through 28, 2024. This update summarizes the proceedings of this meeting, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include COVID-19 and influenza vaccine recommendations for the 2024 to 2025 season, meningococcal vaccination considerations, information regarding preferred Haemophilus influenzae type B containing vaccines for American Indian and Alaskan Native infants, and updates regarding implementation and effectiveness of RSV immunization in pregnant people and infants.

Immunization status and factors influencing hepatitis B vaccination of preterm infants in three provinces of China, 2019 to 2021

BackgroundPremature infants have less physiologic reserve and often delayed vaccination compared to full-term infants. The birth dose of hepatitis B vaccine (HepB-BD) is an essential measure to achieve the goal of "zero infections" of hepatitis B virus in all newborns. However, there are few investigations of hepatitis B vaccination of preterm infants, leading to uncertainty of coverage and insufficient knowledge of factors influencing timely vaccination of this important population.MethodsWe obtained hepatitis B vaccine (HepB) vaccination histories of premature infants born during 2019–2021 in three provinces from the respective provincial immunization information systems. Extracted data included date of birth, sex, region, and dates of HepB administration. We conducted descriptive analyses that included basic characteristics of the study subjects, HepB-BD administration, and full-series HepB vaccination. Factors potentially influencing HepB-BD and full series vaccination were analyzed by logistic regression.ResultsThere were 1623 premature infants included in the analytic data set. Overall HepB-BD coverage was 71.41%; coverage among premature infants born to mothers with unknown hepatitis B surface antigen (HBsAg) status was 69.57%; coverage was higher at county-level-and-above hospitals (72.02%) than hospitals below county level (61.11%). Full-series HepB coverage was 94.15%; full-series coverage among preterm infants weighing less than 2000 g at birth was 76.92%. Logistic regression showed that the HepB-BD vaccination rate was positively associated with being born to an HBsAg-positive mother and being preterm with high birth weight. Regression analysis for factors influencing full-series HepB coverage showed that being born prematurely was positively associated with full-series coverage and being premature with a very low birth weight was negatively associated with full-series coverage.ConclusionsHepB-BD coverage levels in three provinces of China were less than the target of 90%, especially among premature infants born to mothers with unknown HBsAg status and at hospitals below the county level. Screening of pregnant women should be a universal normal standard. Hepatitis B vaccination training should be strengthened in hospitals to improve the HepB-BD vaccination rate of premature infants and to effectively prevent mother-to-child transmission of hepatitis B virus.

Time interval distribution of hepatitis B vaccine immunization among infants in China from 2017 to 2021

ABSTRACT Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third doses is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from the Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28 and 61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61 and 214 days after the second dose 87,067 (64.1%) infants were vaccinated with the third dose between 151 and 180 days after the second dose. The time interval distribution varied across the four provinces or municipalities (p < .001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine and training for obstetricians and related personnel.

The Divergent Effect of Different Infant Vaccination Schedules of the 13-Valent Pneumococcal Conjugate Vaccine on Serotype-Specific Immunological Memory.

Pneumococcal vaccination schedules are traditionally assessed based on the antibody response. The Memory B Cell (MBC) response has been less studied, despite its role in the magnitude and longevity of protection. We compared the immune response to different vaccination schedules with the 13-valent Pneumococcal Conjugate Vaccine (PCV13) and investigated the relationship between MBCs and the antibody response. Total and pneumococcal serotype (PS)-specific MBCs, their subsets and PS-specific IgG antibodies induced by a 3 + 0 (group A), 2 + 1 (group B) or 3 + 1 (group C) schedule in healthy infants were studied before and 1 month after the last PCV13. The relatively immature IgM+IgD+ MBC subset was the predominant subset in all groups but was larger in group A compared to group B and group C, indicating that age might be a significant parameter of the composition of the MBC pool. PS-specific MBCs at baseline were higher in group A, but they increased significantly only in the groups receiving the booster schedules (groups B and C). PS-specific IgM-only MBCs at baseline positively corelated with the antibody response and the PS-specific swIg MBCs post-immunization. Our findings illustrate the importance of a booster dose for the enrichment of PS-specific immunological memory. IgM-only MBCs and swIg MBCs may serve as additional correlates of vaccine-induced protection.

Community-Acquired Bacterial Meningoencephalitis: The New Guideline

Updating the vaccination recommendations against meningococci and pneumococci, in particular the introduction of the B vaccine as the standard vaccination for infants from January 2024 and the adaptation of the pneumococcal vaccination strategy for infants and adults aged 60 and over with the latest conjugate vaccines (PCV13, PCV15, PCV20).Emphasis on the need for rapid diagnostic lumbar puncture and simultaneous serum and cerebrospinal fluid analysis to increase diagnostic precision. The introduction of procalcitonin (PCT) in serum as an additional biomarker to differentiate between bacterial and viral meningitis.The use of multiplex PCR as a supplement, not a replacement, for standard diagnostics to speed up pathogen identification.Adaptation of antibiotic recommendations based on the current resistance situation, in particular for meningococcal meningitis, consideration of penicillin G only after resistance testing.Clarification of the areas and duration of use of dexamethasone in bacterial meningitis, particularly in pneumococcal meningitis and the controversial data situation in Listeria meningitis.New findings on the safe use of heparin in septic sinus thrombosis without increased risk of hemorrhage.

Otitis media sequelae and hearing in adolescence after administration of an 11-valent conjugate pneumococcal vaccine in infancy: a prospective cohort study with long-term follow-up of the ARIVAC trial

Pneumococcal conjugate vaccines (PCVs) have been shown in randomised controlled trials and epidemiological studies to prevent acute otitis media caused by vaccine serotype pneumococci, although their role in preventing complications of acute otitis media is less clear. We hypothesised that the 11-valent PCV would reduce the long-term sequelae of acute otitis media, including moderate-to-severe ear disease and hearing loss. This prospective cohort study, referred to as 11PCV study, included follow-up after 16-20 years of children previously enrolled in 2000-04, at age 6 weeks to 6 months, in the randomised, placebo-controlled, ARIVAC trial of 11-valent PCV for the prevention of radiographical pneumonia. The ARIVAC trial and this 11PCV study were conducted at six study centres in Bohol, Philippines. Ear disease was classified using video-otoscopy review and observations derived from the ear exam. The final classification of the worst ear disease was mild (ie, acute otitis media, otitis media with effusion, healed perforation, or tympanosclerosis), moderate (ie, dry perforation or adhesive otitis media), or severe (chronic suppurative otitis media). Hearing loss was assessed following a standard schema and classified according to the worst ear as mild (>15 to 30 dB puretone average) or moderate-to-profound (>30 dB pure tone average). We calculated the relative and absolute risk reduction in the primary outcome of moderate-to-severe ear disease and the secondary outcomes of mild or moderate-to-profound hearing loss in adolescents who previously received the 11-valent PCV compared with those who received placebo during infancy in ARIVAC. Of the 15 593 children assessed for eligibility in ARIVAC, 12 194 were randomly assigned and 8926 were alive and could be located for enrolment in this 11PCV study between Sept 19, 2016, and Dec 13, 2019. 8321 (4188 in the vaccine group and 4133 in the placebo group) completed follow-up of the 11PCV study by March 30, 2020, and had sufficient data to classify ear disease and be included in the primary outcome analysis. The primary outcome of the absolute risk reduction in moderate-to-severe ear disease in the vaccine group (310 [7·4%] of 4188) versus those in the placebo group (356 [8·6%] of 4133) was 1·2% (95% CI 0·0-2·4; p=0·046) and the relative risk reduction was 14·1% (0·0 to 26·0). There were no differences in secondary outcomes of mild hearing loss or moderate-to-profound hearing loss between the vaccine and placebo groups. The absolute risk reduction for moderate-to-severe ear disease in adolescence of 1·2% (12 per 1000 children) was almost three times higher than the 0·45% reduction (4·5 per 1000 children) in radiographical pneumonia in the first 2 years of life shown in ARIVAC. Administration of 11-valent PCV in infancy was associated with absolute and relative risk reductions in the sequelae of acute otitis media 16-20 years after the original ARIVAC trial. Bill & Melinda Gates Foundation.

Modelling the potential impact of global hepatitis B vaccination on the burden of chronic hepatitis B in the United States.

About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non-US-born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B-related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B-related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings.