Safety evaluation of adverse events following vaccination with Havrix,Engerix-B or Twinrix during pregnancy

BackgroundVaccination of pregnant women against hepatitis A virus (HAV) or hepatitis B virus (HBV) may benefit the mother and the fetus but is not routinely recommended. However, the risk associated with vaccination should be weighed against the risk of HAV or HBV infection. Data on safety profiles after hepatitis A, B or combined AB immunization during pregnancy are limited.MethodsWe searched the GSK Worldwide Safety Database for adverse events (AEs) following immunization of pregnant women with HAV (Havrix, GSK), HBV (Engerix-B, GSK) or the combined hepatitis AB (Twinrix, GSK) vaccine since market authorization through 31 January 2018, covering at least 25 years. AE reports (spontaneous, post-marketing surveillance and clinical trial cases) in the GSK Worldwide Safety Database were identified using a systematic search and were reviewed by clinicians to ascertain pregnancy status at time of vaccination and characterize adverse pregnancy outcomes, including pregnancy-related AEs and AEs in infants regardless of the causality assessment.ResultsOverall, 613, 700 and 363 pregnancies with exposure to Havrix, Engerix-B and Twinrix, respectively, were reported. Of these, 378, 339 and 194 were analyzed. The most frequently identified pregnancy outcomes were live infants (288, 223 and 151), spontaneous abortions (43, 57 and 26) and elective terminations (25, 24 and 9). A total of 19, 29 and 10 cases of congenital anomalies were reported. Of these, 17, 20 and 7 were major birth defects. The most commonly reported pregnancy-related AE and AE in infants were premature delivery (28) and jaundice (11), respectively. No maternal deaths were reported. Congenital anomalies were reported in all recorded infant deaths.ConclusionsThis review did not indicate any concerning pattern of adverse pregnancy outcomes following exposure to any of the 3 vaccines during pregnancy.     

Safety and immunogenicity of HepB-CpG in women with documented pregnancies post-vaccination: A retrospective chart review

BackgroundThere are currently no published data on the use of HepB-CpG (HEPLISAV-B®) during pregnancy or in women with documented pregnancies in the post-vaccination period. We aimed to evaluate data from the clinical development program of HepB-CpG in women who became pregnant during study participation and follow up.MethodsWe identified all study participants in the HepB-CpG pivotal pre-licensure clinical trials that had documented pregnancies during study follow up. We measured immunogenicity among study participants in the HepB-CpG (Heplisav-B®) arm compared to the HepB-alum (Engerix-B®) arm of the studies by comparing seroprotection rates (SPRs; anti-HBs ≥ 10 mIU/mL) and geometric mean concentrations (GMCs) of anti-HBs, obtained with FDA approved anti-HBsAg antibody assays at prespecified time points up to 28 weeks of follow up. Pregnancy outcomes were ascertained by chart review of extracted medical records of study participants.ResultsWe identified 40 documented pregnancies in the HepB-CpG arm and 19 documented pregnancies in the HepB-alum arm. Among subjects with documentation of seroprotection rates, 97.2% (95% CI 85.5–99.9) were seroprotected in the HepB-CpG arm and 66.7% (95% CI 41.0–86.7) were seroprotected in the HepB-alum arm. In the HepB-CpG arm, thirty-six study participants from the pivotal trials had reported pregnancy outcomes, the majority, 21/36 (58%) had a healthy term delivery, with 3/36 (8%) with spontaneous abortions, 1/36 (3%) congenital anomaly, and 2/36 (6%) had preterm birth. In the HepB-alum arm, 10/17 (59%) had healthy term deliveries, with 2/17 (12%) had spontaneous abortions and 1/17 (6%) had congenital anomaly.ConclusionsThese limited data suggest that HepB-CpG is immunogenic in women who become pregnant after vaccination, and pregnancy outcomes appear to be similar to women who received HepB-alum prior to pregnancy. These results need to be further verified with larger prospective studies with HBV vaccine administration during pregnancy.     

Impact of the National Perinatal Hepatitis B Prevention Programme in the Republic of Korea: A retrospective registry-based cohort study

IntroductionHepatitis B is a major preventable cause of morbidity and mortality from chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We aimed to evaluate the performance and outcomes of the Korean Perinatal Hepatitis B Prevention Programme (PHBPP) and to investigate the impact of the current post-exposure immunoprophylaxis protocol.MethodsA retrospective cohort study was performed based on electronic data registry of infants born to hepatitis B virus (HBV)-infected mothers between July 2002 and 2013.ResultsDuring the study period, 159,983 Korean infants were registered with the PHBPP, with an overall programme coverage of 92.8%. Despite receiving timely post-exposure immunoprophylaxis, 8.6% of infants born to mothers aged <25 years and hepatitis B e antigen (HBeAg)-positive, and 0.7% of infants born to mothers aged ≥25 years and HBeAg-negative were infected. An estimated 14,123 infants were directly protected from perinatal HBV transmission by the PHBPP during the 11.5-year period, at a cost of 1157 US dollars per case averted. The incidence of paediatric hepatocellular carcinoma declined dramatically during the period.ConclusionsA substantial number of infants have been prevented from hepatitis B since the PHBPP was launched in the Republic of Korea. Continued efforts to promote the programme, an integrated approach to maximising its coverage, a risk-stratified strategy, and innovations in logistics could further reduce perinatal HBV transmission.     

Trivalent inactivated influenza vaccine (IIV3) during pregnancy and six-month infant development

ObjectiveDespite recommendations by professional organizations that all pregnant women receive inactivated influenza vaccine, safety concerns remain a barrier. Our objective was to assess the effect of trivalent influenza vaccines (IIV3) during pregnancy on parent report 6-month infant development.MethodsWe conducted a multi-site prospective birth cohort study during the 2010–2011 influenza season and followed pregnant women and their newborns through 6 months of age. Information on IIV3 during pregnancy was ascertained from the EHR and self-report. The Ages and Stages Questionnaire-3 (ASQ-3) was completed by the mother to assess 6-month infant neurodevelopment in five domains (communication, gross motor, fine motor, problem-solving, and personal adaptive skills). Scores for each domain above the cut-off point indicating typical development were categorized as “on schedule” while scores in the zones indicating the need for either monitoring or further assessment were categorized as “not on schedule”. Multivariable logistic regression was conducted.ResultsOf the 1225 infant-mother pairs, 65% received IIV3 during pregnancy. In bivariate analysis, infants of women who received IIV3 during pregnancy were moderately-less likely to need monitoring or further assessment in the personal social domain compared with infants of unvaccinated women (10.0% vs. 14.1%, p = 0.033; crude OR (cOR): 0.68(95%CI:0.48,0.97)). However, after controlling for potential confounders, the findings were no longer statistically significant (aOR:0.72,95%CI: 0.49,1.06,p = 0.46). No significant unadjusted or adjusted associations emerged in any other ASQ-3 domain.ConclusionThere was no significant association between IIV3 exposure during pregnancy and 6-month infant development. Studies of IIV3 during pregnancy to assess longer-term developmental outcomes are indicated.     

Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial

BackgroundPertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization.MethodsThis phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6–14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (27^0/7–36^6/7 weeks’ gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination.Results601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5–77.1%) versus placebo (90.0–99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related.ConclusionsPertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant’s ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience.Clinical Trial Registration: ClinicalTrials.gov: NCT02422264.     

Uptake of perinatal immunoprophylaxis for infants born to women with a record of hepatitis B in Victoria (2009–2017)

BackgroundMother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains one of the leading causes of transmission worldwide. An estimated 90 % of infants who are exposed to HBV and do not receive appropriate post exposure immunoprophylaxis will go on to develop chronic hepatitis B (CHB). In Australia, universal birth dose vaccination was adopted in 2000 and universal antenatal screening for hepatitis B was introduced in the 1990 s, however up to 10 % of women may have missed screening. There is no coordinated care or data collection that systematically reports the access to interventions to prevent mother-to-child transmission (PMTCT) for women with CHB. Therefore, the incidence rate of MTCT is unknown.MethodsWe conducted retrospective data linkage of perinatal records, public health notification and hospital admission data to identify women with a record of HBV infection who had given birth to a live infant(s) in Victoria between 2009 and 2017. We assessed uptake of birth dose vaccination and hepatitis B immunoglobulin (HBIG) and explored factors associated with administration of birth dose recorded as administered within 7 days.ResultsAmong 690,052 live births, 6118 births (0.90 %) were linked to 4196 women with a record of HBV infection. 89.4 % of all Victorian infants (n = 616,879), and 96.8 % of infants linked to women with a positive record of CHB (n = 5,925) received birth dose within 7 days. Infants born in private hospitals had reduced odds of receiving birth dose when compared to public hospitals births (Victorian population, aOR = 0.67, 95 %CI = 0.66, 0.69; CHB linked records aOR = 0.17, 95 %CI = 0.11, 0.25).Of the 6118 infants linked to a positive maternal record of CHB, discrepant recording of maternal CHB status between the three datasets was identified in 72.4% of records and HBIG administration was recorded for only 2.3% of births.ConclusionAn approach that involves coordinated care and integrates data collection for women with CHB and their infants is required to support the elimination of MTCT of hepatitis B in Victoria.     

Assessing the feasibility of passive surveillance for maternal immunization safety utilizing archival medical records in Kinshasa,Democratic Republic of the Congo

IntroductionSince the establishment of the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions in 2015, there has been an urgent need for field validation of pharmacovigilance feasibility in low- and middle-income countries. In this study, we assess the availability and quality of archival medical records at ten randomly selected high-traffic maternity wards in Kinshasa province, Democratic Republic of Congo (DRC).MethodsA retrospective cohort of mother-child pairs was established from all recorded births taking place at study sites between July 1, 2019 to February 28, 2020 through digitization of medical records. Adverse birth outcomes and maternal vaccination status, where available and linkable, were defined according to GAIA. Basic demographic information on mothers and newborns was also tabulated; birth outcomes were assessed for both intra-site prevalence and a pooled prevalence.ResultsA total of 7,697 mother-newborn pair records were extracted, with 37% of infants screening positive as cases of adverse outcomes. Maternal vaccination information was linkable to 67% of those cases. In total, 51% of stillbirths, 98% of preterm births, 100% of low birthweight infants, 90% of small for gestational age infants, 100% of microcephalic infants, and 0% of neonatal bloodstream infections were classifiable according to GAIA standards following initial screening. Forty percent of case mothers had some indication of tetanus vaccination prior to delivery in their medical records, but only 26% of case mothers met some level of GAIA definition for maternal vaccination during the pregnancy of interest.ConclusionsArchival birth records from delivery centers can be feasibly utilized to screen for stillbirth and maternal tetanus vaccination, and to accurately classify preterm birth, low birthweight, small for gestational age, and congenital microcephaly. Assessment of other neonatal outcomes were limited by inconsistent postpartum infant follow-up and records keeping.     

Japanese encephalitis vaccination in pregnancy among U.S. active duty military women

IntroductionJapanese encephalitis (JE) vaccine is an inactivated vaccine that has shown no risks in pregnancy in animal models, but epidemiologic studies are lacking. U.S. military service members located in JE endemic regions are required to be vaccinated; understanding the potential adverse events (AEs), including AEs that may occur in pregnancy, is needed. Here, we assessed pregnancy and infant health outcomes in association with JE vaccination in pregnancy.MethodsThe study population consisted of 192,570 pregnancies to active duty women (2003–2014), captured in the Department of Defense Birth and Infant Health Research program. JE vaccine in pregnancy, vaccine count, formulation, trimester, and whether first career dose coincided with pregnancy were compared with unexposed pregnancies to assess risk of pregnancy and infant health outcomes. Adjusted risk estimates and 95% confidence intervals (CIs) were calculated by multivariable models.ResultsOf the 192,570 identifed pregnancies, 513 were exposed to the JE vaccine; 474 exposures occurred in the first trimester. For all outcomes, elevated risk estimates ranging from 1.53 to 1.70, were observed with receipt of >1 JE vaccine in pregnancy, though 95% CIs were wide and encompassed the null. First dose of JE vaccination in pregnancy was associated with a 1.87 (95% CI: 1.12–3.13) times increased risk of low birthweight (LBW) when excluding pregnancies exposed to other non-routinely recommended vaccinations in pregnancy. All other associations were null in both main and subset analyses.ConclusionsThe overall results of these analyses provide reassuring findings for the safety of JE vaccination in pregnancy. Higher counts of JE vaccine received in pregnancy yielded large yet non-statistically significant risk estimates for all outcomes, though likely driven by lack of pregnancy awareness. An association was observed with LBW in subset analyses, but it was limited to women receiving their first JE vaccine and not observed in the larger main analyses.     

Prenatal tetanus-diphtheria-acellular pertussis vaccine effectiveness at preventing infant pertussis

ObjectiveTo evaluate the effectiveness of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine containing five pertussis components (Tdap5; Adacel®, Sanofi) when given during pregnancy at preventing pertussis in infants less than 2 months of age.MethodsThe US Centers for Disease Control and Prevention (CDC), in collaboration with the Emerging Infections Program (EIP) Network, undertook a case-control study evaluating the effectiveness of Tdap vaccination in pregnancy against pertussis in infants less than 2 months of age based on data collected by the EIP Network from 2011 through 2014. The dataset from the CDC/EIP Network study was used to conduct this product-specific vaccine effectiveness analysis of Tdap5 vaccination in pregnancy to prevent disease in young infants. The main outcome of interest was vaccine effectiveness in infants whose pregnant parents were vaccinated with Tdap5 between 27 and 36 weeks’ gestation, in accordance with the ideal timing for Tdap vaccination in pregnancy recommended by the US Advisory Committee on Immunization Practices. Odd ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression, and vaccine effectiveness was calculated as (1–OR) × 100 %.ResultsThere were 160 infant pertussis cases and 302 matched controls included in this Tdap5-specific study. Tdap5 effectiveness in preventing pertussis in infants whose pregnant parents were vaccinated between 27 and 36 weeks’ gestation was 92.5 % (95 % CI, 38.5 %–99.1 %). Effectiveness of Tdap5 against pertussis-related hospitalization in infants whose pregnant parents were vaccinated between 27 and 36 weeks’ gestation could not be calculated due to lack of discordance among matched cases and controls. Vaccination of the parents after pregnancy or less than 14 days before delivery did not protect infants from pertussis.ConclusionsTdap5 vaccination in pregnancy between 27 and 36 weeks’ gestation is highly effective at protecting young infants from pertussis.Study registration: ClinicalTrials.gov, NCT05040802.     

Kinetics of pneumococcal antibodies among HIV-exposed,uninfected infants in Botswana

BackgroundStreptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants.MethodsWe conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes.ResultsAt birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55–93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age.ConclusionsBoth HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.     

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months

BackgroundPERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2–11 months, VE of vaccination in pregnancy and of primary vaccination (PV).MethodsFrom December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants’ age group.ResultsOf 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35–91%] and 88% [95%CI: 57–96%].Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33–90] and 95% [95%CI: 69–99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27–86] and 94% [95%CI: 59–99].ConclusionOur findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2–11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.     

Vaccine exposure during pregnancy among privately and publicly insured women in the United States, 2016–2018

BackgroundVaccine use during pregnancy affects maternal and infant health. Many women do not receive vaccines recommended during pregnancy; conversely, inadvertent exposure to vaccines contraindicated or not recommended during pregnancy may occur. We assessed exposure to two recommended vaccines and two vaccines not recommended during pregnancy among privately and Medicaid-insured women in the United States.MethodsThis study includes a retrospective cohort of pregnancies in women aged 12–55 years resulting in live birth, spontaneous abortion, or stillbirth identified in the IBM® MarketScan® Commercial, Blue Health Intelligence® (BHI®) Commercial, and IBM MarketScan Multi-State Medicaid Databases from August 1, 2016, to December 31, 2018. Gestational age at vaccination was determined using a validated algorithm. We examined vaccines (1) recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) (tetanus, diphtheria, and acellular pertussis [Tdap]; inactivated influenza) and (2) not recommended (human papillomavirus [HPV]) or contraindicated (measles, mumps, and rubella [MMR]).ResultsWe identified 496,771 (MarketScan Commercial), 858,961 (BHI), and 289,573 (MarketScan Medicaid) pregnancies (approximately 75% aged 20–34 years). Across these three databases, 52.1%, 50.3%, and 31.3% of pregnancies, respectively, received Tdap, most often at a gestational age of 28 weeks, and influenza vaccination occurred in 32.1%, 30.8%, and 18.0% of pregnancies, respectively. HPV vaccination occurred in < 0.2% of pregnancies, mostly in the first trimester among women aged 12–19 years, and MMR was administered in < 0.1% of pregnancies. Use of other contraindicated vaccines per ACIP (e.g., varicella, live attenuated influenza) was rare.ConclusionMaternal vaccination with ACIP-recommended vaccines was suboptimal among privately and Medicaid-insured patients, with lower vaccination coverage among Medicaid-insured pregnancies than their privately insured counterparts. Inadvertent exposure to contraindicated vaccines during pregnancy was rare. This study evaluated only vaccinations reimbursed among insured populations and may have limited generalizability to uninsured populations.     

Signals and trends of Guillain–Barré syndrome after the introduction of live-attenuated vaccines for influenza in the US and South Korean adverse event reporting systems

BackgroundWith the advent of live-attenuated, quadrivalent, and cell-cultured vaccines for influenza, there have been discussions on the safety of these vaccines compared to conventional vaccines (such as inactivated, trivalent, and egg-cultured vaccines) because of the development of neurological adverse events (AEs). This study aimed to compare the trends and safety signals in the AE reporting systems of the US and South Korea and, more particularly, to evaluate the association between influenza vaccination and Guillain–Barré syndrome (GBS).MethodsIn total, 400,535 AE reports from the US Vaccine Adverse Event Reporting System (VAERS) and 28,766 AE reports from the Korea Adverse Event Reporting System (KAERS) between 2005 and 2017 were assessed. Disproportionality analysis was performed to detect the safety signals and examine the potential risk of GBS with influenza vaccination using the case/non-case approach.ResultsIn both databases, GBS was the most frequently reported AE following influenza immunization. Using the case/non-case approach, the adjusted reporting odds ratio (ROR) of GBS was 3.57 (95% confidence interval [CI], 3.16–4.03) and 3.09 (95% CI, 0.83–11.45) in the VAERS and KAERS data, respectively. People vaccinated with live-attenuated vaccines reported 2.30 times (95% CI, 1.74–3.05) more cases of GBS than those vaccinated with other types of vaccines.ConclusionsOur analysis of the VAERS and KAERS reports for AEs following immunization (AEFI) for influenza shows the need for cautious monitoring regarding the development of GBS after influenza vaccination, particularly, after live-attenuated vaccination. However, owing to potential reporting bias caused by limited AEFI reports after the introduction of new types of influenza vaccines, further prospective safety studies are needed.     

Changes in childhood vaccination during the coronavirus disease 2019 pandemic in Japan

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has greatly affected daily life. COVID-19 often causes asymptomatic or mild disease in children; however, delayed routine childhood immunization is a concern, as it could increase the risk of vaccine-preventable disease. No study has evaluated the status of childhood vaccinations in Japan during the COVID-19 pandemic.MethodsThis retrospective observational study evaluated the number of vaccine doses administered to children in 4 Japanese cities (2 cities in the Tokyo metropolitan area and 2 cities far from Tokyo) during the period from 2016 to 2020. Vaccine doses administered between January and September 2020 during the COVID-19 pandemic were compared, by month, with those given during 2016–2019. Age-stratified demographic data were collected to determine whether factors other than change in the child population over time affected vaccination trends.ResultsIn all cities the decrease in vaccine doses administered was most apparent in March and April 2020, i.e., just before or coincident with the declaration of a nationwide COVID-19 emergency on April 7, 2020. The decrease started as early as February in the Tokyo metropolitan area. As child age increased, the decrease became more apparent. Before the lift of national emergency on May 25, catch-up of the vaccination was observed in all age groups in all cities. Vaccine doses persistently increased in older age groups but not in infants. The overall vaccination trends did not differ significantly among the 4 cities.ConclusionsThe COVID-19 pandemic significantly affected routine childhood immunization in Japan. Thus, a nationwide electronic surveillance system and announcements for guardians to encourage timely routine immunization are warranted.     

Disparities in COVID-19 vaccine uptake among health care workers

BackgroundCOVID-19 vaccine uptake by healthcare workers (HCWs) is critical to protect HCWs, the patients they care for, and the healthcare infrastructure. Our study aims to examine the actual COVID-19 vaccination rate among HCWs and identify risk factors associated with vaccine nonacceptance.Study Design and MethodsA retrospective analysis of COVID-19 vaccinations for HCWs at a large multi-site US academic medical center from 12/18/2020 through 05/04/2021. Comparisons between groups were performed using unpaired student t-test for continuous variables and the chi-square test for categorical variables. A logistic regression analysis was used to assess the associations between vaccine uptake and risk factor(s).ResultsOf the 65,270 HCWs included in our analysis, the overall vaccination rate was 78.6%. Male gender, older age, White and Asian race, and direct patient care were associated with higher vaccination rates (P <.0001). Significant differences were observed between different job categories. Physicians and advanced practice staff, and healthcare professionals were more likely to be vaccinated than nurses and support staff.ConclusionsOur data demonstrated higher initial vaccination rates among HCWs than the general population national average during the study period. We observed significant disparities among different high-risk HCWs groups, especially among different job categories, black HCWs and younger HCWs despite their high risk of contracting the infection. Interventions to address lower vaccination rate and vaccine hesitancy should be built with these disparities and differences in mind to create more targeted interventions.     

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6–8 weeks old healthy infants: A phase III,randomized, single blind,non-inferiority study

BackgroundA liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6–8 weeks old healthy infants.MethodsA total of 405 healthy infants aged 6–8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4–6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period.ResultsOut of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4–6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated.ConclusionAfter assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6–8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine.Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.     

Disparities in infant mortality from all-infectious,vaccine-preventable,and non-vaccine preventable diseases in relation to parental education

BackgroundThe burden of infectious diseases in infants is substantial. Parental education has been considered as a critical factor for predicting infant mortality. However, even though some studies have been done about relationship between infectious disease and parent’s education level, no researches have been conducted specifically about vaccine-preventable and non-vaccine-preventable disease mortality by parent’s educational level.PurposeThis study aimed to compare infant mortality rates from all-infectious diseases, vaccine-preventable and non-vaccine-preventable diseases by mother’s and father’s education levels.MethodsWe used 2017 US Linked Birth and Infant Death Data from National Center for Health Statistics, which included 3,153,574 live births and 13,870 deaths.To identify the association between each mother’s and father’s education level and all-infectious disease, vaccine-preventable disease, and non-vaccine-preventable disease infant mortality, logistic regression analyses were conducted by using educational level 1 as the reference. All-infectious diseases, vaccine-preventable and non-vaccine-preventable diseases were identified by vaccination recommendation of 2017 CDC guideline. Education levels were classified into four groups: level 1, through 12th grade with no diploma; Level 2, high school graduate or GED completed; Level 3, some college credit but no degree or associate degree; and Level 4, bachelor’s degree, master’s degree, doctorate or professional degree.ResultsHigher parents’ education level was appreciably associated with lower infant mortality from all-cause, all-infectious diseases, vaccine-preventable diseases, and non-vaccine-preventable diseases. Moreover, each mother’s and father’s education level was correlated to infant mortality due to vaccine-preventable diseases on the whole education level, while all-infectious disease and non-vaccine-preventable disease mortality is related with parent’s education level only if their education level is fairly high. In other words, the adjusted odds for vaccine-preventable disease mortality were significantly lower than that for all-infectious and non-vaccine-preventable disease mortality at education level 2 and 3 and still smaller at education level 4.ConclusionThese finding implies that each mother’s and father’s higher education level was associated with lower infant mortality rate from all-infectious diseases, vaccine-preventable diseases, and non-vaccine-preventable diseases. Furthermore, each level of mother’s and father’s education was more likely to be related to infant mortality by vaccine-preventable diseases than that of infant mortality by all-infectious diseases, and non-vaccine-preventable diseases.     

Efficacy,safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: A phase IIb randomized study

BackgroundNative American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs.MethodsIn this phase IIb, double-blind, controlled trial, 6–12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12–15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children.Results1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: −11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (−9.5, 14.0) and 5.2% (−8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between −4.4% (−39.2, 21.8) and 2.0% (−18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants.ConclusionsThe dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated.Clinical trials registrationNCT01545375 (www.clinicaltrials.gov)     

Development of a cumulative metric of vaccination adherence behavior and its application among a cohort of 12-month-olds in western Kenya

ObjectivesThe timely receipt of the recommended vaccination regimen, i.e. vaccination maintenance, is an underexplored, but important, indicator of public health. There is currently no standardized method for quantifying cumulative vaccination maintenance, however, and no simple way to explore predictors of adherence to vaccination schedules. We therefore sought to (1) develop a Vaccination Maintenance Score (VMS) and (2) apply this score to determine the predictors of vaccination behavior among infants in western Kenya (n = 245).MethodsWomen in western Kenya were enrolled during pregnancy and surveyed repeatedly through one year postpartum. Data were collected on a range of sociodemographic and health indicators and vaccinations. For each infant, we analyzed receipt of 11 vaccines recommended by the Kenyan Ministry of Health. We operationalized VMS as the total number of vaccines received on schedule. Vaccines that were not received or received off schedule were scored 0. VMS was modeled using multivariable tobit regression models.ResultsWe found that 85.7% of infants were fully immunized, but only 42.4% had optimal VMS, i.e. scored 11. The median (IQR) VMS was 10 (3). In multivariable regression, each one-point increase in maternal quality of life score (range: 0–32) was associated with a 0.22-point increase in VMS; each additional child in the household was associated with a 0.34-point increase in VMS; and initiating breastfeeding at birth was associated a 2.01-point increase in VMS.ConclusionsCoverage of the recommended vaccinations (85.7%) was nearly twice as high as cumulative timely receipt (42.4%). The VMS satisfies a need for a location-specific but easily adaptable metric of vaccination adherence behavior. It can be used to complement traditional methods of vaccination coverage and timeliness to better understand underlying behaviors that influence vaccination events, and thereby inform interventions to improve vaccination rates and decrease the burden of vaccine-preventable disease.Clinical Trial RegistrationNCT02974972 and NCT02979418.