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• The development of 5-combined vaccine and others is of high priority in Japan. • The first vaccination of DPT-IPV should be given concomitantly with the Hib vaccine. • Gobik is the first DPT-IPV-Hib pentavalent vaccine approved in Japan. • Gobik simultaneously provide primary and booster immunizations as a single agent. 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. 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. 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. 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). [ABSTRACT FROM AUTHOR]

Maternal pertussis vaccination during the third trimester of pregnancy was implemented in 2015 in Spain, reaching a national coverage of 84% in 2019. In this ecological study, we investigated whether there was a change in the disease severity for pertussis in infants upon introduction of prenatal pertussis vaccination. We performed a time-trend analysis of infant pertussis hospitalizations during 2005–2019 in Spain using national register data. Annual hospitalization rates per 100,000 population and the mean length of hospitalization were calculated for infants < 3 months of age (target group benefiting from the prenatal vaccination) and a reference group aged 3–11 months. We compared overall rates and annual percent changes of the above variables in both groups for the time period before (2005–2014) and after vaccination introduction (2015–2019), using segmented Poisson regression. During the pre-vaccination period, infants aged 0–2 months had a 5-times higher rate of pertussis hospitalization and spent on average 50 % longer in hospital than the reference group. After the maternal vaccination introduction, the hospitalization rate decreased more rapidly in infants aged 0–2 months than in infants aged 3–11 months: annual reduction of 34 % (95 % CI: 31–38) versus 26 % (95 % CI: 21–31) in the hospitalization rate and 13 % (95 % CI: 11–15) versus 6 % (95 % CI: 2–9) in the mean hospital stay, respectively. In 2019, the mean hospital stay for pertussis was about 4.5 days in both groups. Maternal pertussis vaccination in Spain led to a reduction in disease severity in the target group as compared to older infants, highlighting the need for increased efforts on educating healthcare professionals on the importance of maternal vaccinations. [ABSTRACT FROM AUTHOR]

• PERTINENT, a four-year hospital-based European network for pertussis in infants aged 0–11 months. • Sole network for independent, multi-country pertussis vaccine effectiveness studies in Europe. • One vaccine dose in infants aged 2–5 months would halve the risk of being hospitalised for pertussis. • Dose-dependent increase of vaccine effectiveness against hospitalisation due to pertussis. • At least one dose of acellular vaccine in infants continues to offer good protection for pertussis. Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36–73). Adjusted VE was 48 % (95 %CI: 5–71) for dose one (416 eligible infants) and 76 % (95 %CI: 43–90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three. [ABSTRACT FROM AUTHOR]

• Cost-effectiveness analysis of booster fifth-dose DTaP vaccination. • Reflection of herd immunity from vaccinated adolescents to unvaccinated infants. • DTaP booster is expected to reduce pertussis cases in adolescents. • DTaP booster to adolescents would be cost-effective when the morbidity is high. In Japan, the introduction of a fifth diphtheria–tetanus–acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11–12 years old who are currently receiving the diphtheria–tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. We used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020–2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. The ICER from the payers' perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. The cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends. [ABSTRACT FROM AUTHOR]

Vaccinations for seasonal influenza and pertussis have been recommended for pregnant women in England since 2010 and 2012, respectively. Uptake rates are suboptimal with large regional variations. To improve uptake, from 2016 onwards maternity trusts were commissioned to offer pertussis (and other) vaccinations in addition to these being available in primary care. Since 2021, Covid-19 vaccination has also been recommended for pregnant women. Overall maternal vaccination rates are routinely available, but not the relative provision by maternity trusts. We aimed to describe the national picture of maternity trust provision of maternal vaccinations, including how the maternity trust vaccination programme has progressed. Cross-sectional survey plus comparisons with 2017–18 figures for maternity trust provision of pertussis vaccination, and with UKHSA data for total pertussis vaccination. Twelve NHS commissioners participated (from 13/06/22 to 31/03/23) providing data for 120 (of a total 124) maternity trusts across England. All 120 (100%) trusts were commissioned to deliver influenza, and 107 (89%) to deliver pertussis vaccinations, though not all actually administered the vaccines; 29% offered Covid-19 vaccinations. For 2021–22 we found a mean of 25% (range 0–81.3%) women were vaccinated for pertussis (a large increase compared with previous estimates for 2017–18); and 11% (range 0–74.2%) for influenza, via their maternity trust. Commissioners reported a negative impact of the pandemic on routine vaccination provision. There was indication of efficiency by vaccinating women attending for other appointments. There are diverse mechanisms for reporting pertussis and influenza vaccinations administered at maternity trusts back to primary care, which may be inefficient for maternity staff workload and accuracy of data transfer (especially for pertussis). A high proportion of maternity trusts provide both pertussis and influenza vaccinations, despite a negative impact of the pandemic. Reasons for large between-trust variation in vaccination rates should be explored to improve uptake and equity. [ABSTRACT FROM AUTHOR]

• HCPs play an important role in informing pregnant women about maternal vaccinations. • Strategies to increase MPV uptake should not only focus on providing information. • Decrease experienced barriers in pregnant women that are intended to accept the MPV. In December 2019, the maternal pertussis vaccination (MPV) became part of the Dutch National Immunization Program. This study aims to study MPV behavior and associated psychosocial, attitudinal and organizational factors of pertussis vaccination behavior during pregnancy in the Netherlands. We conducted a cross-sectional survey among pregnant women and recent mothers, up to six months post-partum. The primary outcome measure of this study was MPV behavior. Associations between psychosocial, attitudinal and organizational factors and MPV behavior were assessed using univariate and multivariate binary logistic regression analysis. In total 1348 participants filled out the questionnaire, including 1282 (95.1%) MPV acceptors and 66 (4.9%) MPV refusers. The most important factors associated with MPV behavior were: attitude (aOR: 10.19; 95%CI: 4.30–24.16), outcome expectations (aOR: 8.94; 95%CI: 3.60–22.21), omission bias (aOR: 0.11; 95%CI: 0.02–0.59) and physical accessibility (aOR: 7.44; 95%CI: 3.37–16.46). Pregnant women make their decision about the MPV primarily based on attitudinal and psychosocial factors, such as outcome expectations and attitude. A combination and variation of different messages, about the advantages (effectiveness) and disadvantages (side effects) of maternal vaccination, can be used in reaching pregnant women with a positive and negative attitude about the MPV. In addition, strategies to increase MPV uptake should not only focus on providing information, but also decrease experienced practical barriers, such as poor physical accessibility, in people that are intended to receive the MPV but are not getting vaccinated. [ABSTRACT FROM AUTHOR]

Pregnant women (PW) are at increased risk of complications due to seasonal influenza and Covid-19. Immunization during pregnancy against pertussis and respiratory syncytial virus (RSV) protects newborns from severe diseases. Our aim was to assess intentions to get vaccinated against seasonal influenza, COVID-19, pertussis and RSV in PW and to identify factors associated with intentions. Cross-sectional survey in PW followed at a University Hospital in France assessing their knowledge, and attitudes toward vaccination against influenza, Covid-19, and RSV during pregnancy. Primary outcome was intention to receive each vaccine or potential vaccine. Univariable and multivariable analysis were carried out to identify factors associated with intentions to get vaccinated for each vaccine. Among the 1199 PW followed during the study period, 310 completed the questionnaire. Intentions to get vaccinated were respectively 43.9 %, 36.8 %, 36.1 % and 39.4 % against influenza, Covid-19, pertussis and RSV. Overall confidence in vaccines using 5C-model, recommendation by a healthcare professional (HCP), good knowledge about diseases and vaccines and previous influenza vaccination were associated with flu vaccine acceptance with respective adjusted odds ratios and 95 % Confidence Intervals (aOR) 1.69 (1.09–2.61) by one-point increase in confidence score, 4.89 (2.24–10.7), 1.56 by one-point increase in knowledge score (1.26–1.93), 13.5 and (5.3–34.3). Confidence was also associated with Covid-19 and RSV vaccine acceptance with respective aOR and 95 % CI 2.63 (1.7–4.07) and 1.92 (1.3–2.84). For pertussis, previous flu vaccination or pertussis vaccination in the last 5 years were predictors of pertussis vaccine acceptance during the pregnancy with respective aOR and 95 % CI 1.97 (1.1–3.84) and 2.9 (1.6–5.18). Confidence is associated with seasonal influenza, COVID-19 and RSV vaccines acceptance in pregnant women. Receiving a recommendation from a HCP was strongly associated with acceptance of influenza vaccine. Recent vaccination against pertussis was not a barrier to pertussis vaccine acceptance during pregnancy. [ABSTRACT FROM AUTHOR]

In 2019, maternal pertussis vaccination (MPV) during pregnancy was introduced in the Netherlands. New interventions to promote informed decision making (IDM) about vaccinations are highly needed, especially for new vaccinations. Decision aids (DAs) have the potential to support IDM. This study evaluates the effects of an online DA on IDM and MPV uptake. Pregnant individuals, recruited for the randomized controlled trial (RCT), who gave informed consent (N = 1,236) were randomly assigned to the control (N = 650; no information) or intervention condition (N = 586; DA at 18 weeks pregnancy). MPV uptake and IDM were primary outcomes, decisional certainty and psychological determinants of MPV uptake were secondary outcomes. Measures were taken at 18 weeks of pregnancy (baseline) and at 20 weeks of pregnancy (post-test); intervention use was logged. Data were analysed using intention-to-treat analyses, logistic regression, and linear mixed regression models. Uptake of MPV was high in our sample (92.3 %). No significant effect of the DA condition on MPV uptake was found compared to the control condition. We found that the DA increased IDM (β = 0.24, p <.004) and one of its components level of knowledge about MPV (β = 0.31, p <.004). We also found an increase in decisional certainty (β = 0.24, p <.004), perceived susceptibility (β = 0.24, p <.004), severity of pertussis (β = 0.41, p <.004), and positive affect about MPV (β = 0.15, p <.004). There was a positive association between dose of the intervention and MPV uptake (β = 0.05, p <.004). The DA seemed effective in promoting IDM about and determinants of MPV uptake. No main effect was found on MPV uptake, but MPV uptake was related to the level of exposure to the DA. People with high intentions towards MPV were overrepresented in the sample. However, effects on IDM were consistent among participants with different levels of MPV intention at baseline. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Vaccination mandates have long been an effective tool in increasing vaccination rates and reducing the potential for disease outbreaks. In the wake of COVID-19, opposition to mandates in the K-12 setting has garnered more attention, and policymakers opposed to them have become more active. This study sought to assess whether these efforts are supported by the U.S. public. We fielded a large, national survey (N = 16,461) from January to April of 2022 to assess U.S. public opinion about seven specific vaccination mandates (diphtheria, tetanus, & pertussis (DTaP); polio; chickenpox; measles, mumps, and rubella (MMR); hepatitis; human papillomavirus (HPV); and COVID-19) in K-12 educational settings. We found that Americans are overwhelmingly supportive of all vaccination mandates with support ranging from a high 90 percent of respondents for DTaP, polio, chickenpox, and MMR to a low of 68 percent for COVID-19. Individuals who deemed vaccines safe and important, those with trust in the National Institutes of Health and the Food and Drug Administration, urban residents, and ethnic and racial minorities tended to be consistently more supportive. Perceptions about vaccine effectiveness were positively associated with mandate support in most cases, as was trust in medical doctors. Respondents who believed that vaccines cause autism, those with better health and more trust in religious leaders tended to be consistently more opposed. Women were generally more supportive of mandates except for HPV and COVID-19. Ideology and partisanship affected opinion for COVID-19 as did trust in the Centers for Disease Control and Prevention. We found no effects for income or education. Vaccination mandates in K-12 have broad support among the American public, even in more controversial cases such as HPV and COVID-19. Vocal opposition and growing interest by policymakers to limit or undo vaccination mandates are not supported by the broader public. [ABSTRACT FROM AUTHOR]

The global COVID-19 public health crisis has resulted in extraordinary collaboration to expeditiously develop vaccines and therapeutics. The safety of these biologics is closely monitored by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Novel products may have limited safety data, and although serious medical outcomes associated with vaccination are rare, knowledge of background incidence rates of medical conditions in the US population puts reported adverse events (AEs) in perspective for further study. Although relatively minor vaccination skin reactions are common, rare instances of severe delayed hypersensitivity reactions such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome may occur. To aid in the assessment of these events, we performed a literature search in PubMed and Web of Science on the background incidence of EM, SJS, SJS/TEN, and TEN in the US population and on published reports of these conditions occurring post-vaccination. The US background annual incidence rates per million individuals of all ages ranged from 5.3 to 63.0 for SJS, from 0.4 to 5.0 for TEN, and from 0.8 to 1.6 for SJS/TEN. Since these conditions may overlap, some studies reported rates for EM/SJS/TEN combined, however we did not find studies with exclusive EM incidence rates. The published literature, including studies of reports submitted to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS), describes post-vaccination EM, SJS, SJS/TEN and/or TEN as rare occurrences. The vaccines most frequently associated with these conditions were measles, mumps, and rubella; diphtheria, tetanus, and pertussis; and varicella. The majority of VAERS reports of EM, SJS, SJS/TEN, or TEN occurred in children within 30 days of vaccination. This review summarizes background rates of these disorders in the general population and published AEs among vaccine recipients, to support safety surveillance of COVID-19 vaccines and other biologics. [ABSTRACT FROM AUTHOR]

Pertussis causes significant morbidity and mortality in infants aged <6 months. Maternal pertussis vaccination during pregnancy has been recommended in Canada since 2018 to reduce these negative outcomes. In the absence of routine immunization coverage data, our objective was to evaluate uptake in Toronto, Canada. We recruited mother-infant pairs at The Hospital for Sick Children, Toronto, between 2018 and 2020. We performed logistic regression to examine associations between demographics and self-reported pertussis vaccination. 76/243 mothers (31.3 %) reported receiving pertussis vaccination during their most recent pregnancy. Odds of receiving vaccination more than doubled with each 1-year increase in year of pregnancy (aOR: 2.2; 95 % CI: 1.3, 3.6; p < 0.01) and among those born in Canada as compared to those not (aOR: 2.0; 95 % CI: 1.1, 3.6; p = 0.02) Uptake of pertussis vaccination during pregnancy in Ontario has increased in recent years, however coverage remains lower than desirable. [ABSTRACT FROM AUTHOR]

• First study reporting societal economic burden of pertussis in UK adults ≥50 years. • Highest economic burden was among 55–59 years, comprising mostly of indirect costs. • Probabilistic sensitivity analysis showed 95% of simulations fell within 2 SDs. • Incidence values from the 2012 outbreak had the highest impact on total costs. • Findings could inform policy decisions and interventions for reducing disease burden. Pertussis is an endemic respiratory tract infection caused by Bordetella pertussis that may affect all individuals from infants to older adults. Pertussis incidence in adults is often underreported and in various countries, including the United Kingdom (UK), there are evidence gaps on pertussis-associated economic burden in the older adult population. We aimed to quantify the economic burden of pertussis in adults aged ≥50 years in the UK. A cost-of-illness study was conducted to estimate the cost of pertussis from a societal perspective. We utilized a sum diagnosis cost approach in which costs related to infection with pertussis were included. Medical, patient, and indirect costs were calculated individually and combined to calculate total costs. A framework was developed to assess costs for consecutive age groups from 50–54 years of age to ≥85 years of age. Sensitivity and scenario analyses were used to assess analysis uncertainty. The base-case analysis estimated the total annual economic burden of pertussis to be approximately £238 million (M). This comprised approximately £159 M in indirect costs, £66 M in medical costs, and £13 M in patient costs. Costs for the age group 55–59 years had the highest impact on the economic burden, with approximately £79 M in total annual costs. Visits to general practitioners and nurses were the largest contributors to medical costs (∼£37 M) followed by inpatient visits (∼£21 M). Transportation costs (∼£10 M) were the major patient costs. Productivity loss (∼£71 M) and leisure time loss (∼£72 M) had comparable contributions to annual indirect costs. Sensitivity and scenario analyses suggested that incidence rates, indirect costs, and underreporting estimates had the highest impact on outcomes. Total cost of pertussis in the UK among adults ≥50 years of age is substantial and highest for adults 55–59 years of age. Indirect costs were the main contributors to the economic burden. [ABSTRACT FROM AUTHOR]

Vaccination is an evidence-based strategy to prevent or reduce the severity of infectious diseases (ID). Here, we aimed to describe the experience of implementing a vaccination clinic specifically targeting liver, heart, lung, and combined dual organ transplantation at a single transplantation center in Denmark. In this cohort of 242 solid organ transplant (SOT) candidates, we investigated seroprotection and the proportion of recommended vaccinations documented before transplantation. Furthermore, we registered completed vaccinations after ID consultations. The median age in our cohort was 53 years (IQR, 42–60), 60% were males (n = 135), and liver transplants (n = 138; 57%) were the most frequently planned organ transplants. Before the consultation to the vaccination clinic, influenza and pneumococcal vaccines had the highest proportion of documented vaccination (58% and 37%, respectively). Serological protection was more frequently observed for measles, mumps, or rubella (MMR, approximately 90% for each), while only 30% (n = 72) of SOT candidates showed seroprotection against pneumococcal disease. All SOT candidates required at least one of the recommended vaccines, and over 90% required three or more. At least 10% of patients in our cohort needed a live attenuated vaccine for either MMR or yellow fever. The most frequently administered vaccine was the tetanus–diphtheria-acelullar pertussis (Tdap) booster (n = 217; 90%), influenza vaccination was either administered (n = 16; 7%) or recommended (n = 226; 93%), PCV13 was administered (n = 155; 64%) or recommended (n = 27; 11%), and PPSV23 was either administered (n = 18; 7.4%) or recommended (n = 140; 58%). All SOT candidates adhered completely to their vaccination schedules. Based on our findings, we recommend prioritizing vaccination before transplantation by providing ID consultations for SOT candidates. [ABSTRACT FROM AUTHOR]

• The average on-schedule/timely vaccination decreased in Beijing, during 2020–2021. • The on-schedule vaccination of DTaP4 and MPSV-A1,2 decreased significantly. • The timely vaccination of for DTaP1-3 and "Four Vaccines"decreased significantly. The routine immunization program for children is a primary strategy and a core part of vaccination. Achieving and maintaining high level of vaccination coverage are important to reduce morbidity and mortality caused by vaccine-preventable diseases. In Beijing, annual coverage surveys have been conducted since 2005. It is necessary and possible to assess the level and trend of routine vaccination coverage of children in Beijing as well as the disruption of coronavirus disease 2019 (COVID-19) pandemic and provide the reference for the further improve the vaccination coverage. The data of 61,521 children aged 1–3 years in the vaccination coverage surveys during 2005–2021 were analyzed by Beijing Center for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the data and the difference of vaccination coverage within the time period. More than 99 % of participants had immunization cards and electronic immunization records. The concordance rate of both records were also over 99 %. During 2011–2019, the rates of on-time and in-time vaccination of each routine vaccine reached 96 % or more and increased significantly (all P values <0.05), compared with that of 2005–2010. All rates of the investigated vaccine, except for Bacillus Calmette-Guérin vaccine (BCG) and the first dose of hepatitis B vaccine (HepB), decreased in 2020–2021 significantly (all P values <0.05). For the causes of failing to vaccinate on time, delayed vaccination accounted for 47.82 %. The top two vaccines to be missed were the first dose of hepatitis A vaccine and the 4th dose of diphtheria-tetanus-acellular pertussis vaccine, accounting for 21.41 % and 20.79 %, respectively. The main reason for zero-dose/drop-out vaccination was "Guardians regarded the immunization service time as inappropriate", accounting for 72.27 %. The coverage level and service quality of routine immunization in Beijing were relatively high. However, as influenced by COVID-19 epidemics, both on-time and in-time vaccination rates decreased significantly, except for BCG and HepB. Under the background of COVID-19 pandemic, the keys to maintain high level of vaccination coverage include flexible immunization service time to ensure the guardians bringing their children for vaccination timely, and more attention from providers to the doses after children's first birthday. [ABSTRACT FROM AUTHOR]

• In Australia, maternal influenza and pertussis vaccine coverage increased steadily between 2016–2020. • Maternal vaccine coverage was lower for influenza than pertussis. • Independent predictors of lower maternal vaccine coverage included younger age, lower socio-economic status, prior pregnancies, and public hospital model of care. Respiratory infections including influenza and pertussis are associated with significant morbidity and mortality in mothers and newborns. Vaccination during pregnancy against influenza and pertussis is recommended for all women but data on uptake in Australia is limited. We conducted a retrospective population-based cohort study in Australia's largest state, New South Wales (NSW), using a Perinatal Data Collection (PDC). Data included demographic, pregnancy, and birth details including pertussis and influenza vaccination during pregnancy for all women giving birth between 01 January 2016 and 31 December 2020. We used descriptive statistics to assess uptake of influenza and pertussis vaccination during pregnancy and Poisson loglinear regression to estimate associations between maternal characteristics and vaccine receipt. During 2016–2020, there were 477,776 births (mean maternal age 32.25 years). In 176,255 (36.9%) births the mother received both vaccines; 202,922 (42.5%) influenza and 315,620 (66.1%) pertussis vaccine. From 2016 to 2020, reported coverage increased from 26.7% to 58.7% for influenza and 43.1% to 78.8% for pertussis, respectively. After adjustment, characteristics associated with lower likelihood of receiving influenza and pertussis vaccination included: younger age (<30 years), being born in Australia/New Zealand, from lower socio-economic strata, having previous pregnancies, being later to first antenatal care, utilising the public hospital care model, smoking, having chronic hypertension and BMI > 25 kg/m2. While reported coverage of both influenza and pertussis vaccine in birthing women in NSW has increased over time, disparities in coverage exist and they highlight areas where evidence-based interventions to improve maternal vaccination could be targeted. [ABSTRACT FROM AUTHOR]

Countries routinely offering acellular pertussis vaccine, where long-term protection is not sustained, have the challenge of selecting an optimal schedule to minimise disease among young infants. We conducted a narrative systematic review and synthesis of information to evaluate different pertussis immunisation strategies at controlling pertussis disease, hospitalisation, deaths, and vaccine effectiveness among young infants. We conducted a review of the literature on studies about the primary, booster, and/or maternal vaccination series and synthesised findings narratively. Countries offering the first three doses of vaccine within six-months of life and a booster on or before the second year or life were defined as accelerated primary and booster schedules, respectively. Countries offering primary and booster doses later were defined as extended primary and booster schedules. All search results were screened, and articles reviewed and reconciled, by two authors. The Risk of Bias in Non-randomised Studies of Intervention tool was used to evaluate the risk of bias. A total of 98 studies were included in the analyses and the following recurring themes were described: timing of vaccination, vaccine coverage, waning immunity/vaccine effectiveness, direct and indirect effectiveness, switching from an accelerated to extended schedule, impact of changes in testing. The risk of bias was generally low to moderate for most studies. Comparing schedules is challenging and there was insufficient evidence to that one schedule was superior to another. Countries must select a schedule that maintains high vaccine coverage and reduced the risk of delaying the delivery vaccines to protect infants. [ABSTRACT FROM AUTHOR]

• In 2007, Mexico switched pertussis vaccines from whole-cell (wP) to acellular (aP). • There was increased pertussis notifications over the period 2000–2019 in Mexico. • Effectiveness was comparable (>95%) for 3 and 4 doses of wP and aP vaccines. • Vaccine coverage was >90% for dose 1, but decreased for each subsequent dose. • There is high protection against pertussis in children up to 4 years in Mexico. The national immunization program in Mexico includes a 3-dose primary series of pertussis vaccine and a toddler booster dose. In Mexico, whole-cell pertussis vaccines (wP) were switched in 2007 to acellular pertussis vaccines (aP). This retrospective study using Mexican National Databases of Health and population surveillance (2000–2019) assessed the incidence of pertussis, infant pertussis vaccination coverage, and vaccine effectiveness (VE) against clinically-diagnosed and/or laboratory-confirmed pertussis in children aged 6.5–18.5 or 24.5 months for the primary series, and children aged 18.5 or 24.5–48.5 months for the toddler booster. The incidence of pertussis sharply increased in 2012 and was highest in 2012, 2015, and 2016 (0.84–0.94/100,000 person-years). Coverage was highest for the first dose in the primary series, decreasing for each subsequent dose. The VE against notified pertussis was 96.4% (95% CI: 94.7, 97.6) for the first three doses of wP vaccine (2000–2007) and 95.7% (95% CI: 95.1, 96.2) for the first three doses of aP vaccine (2008–2019). Our findings suggested high levels of vaccine effectiveness overall were achieved for the aP and wP vaccines in Mexico between 2000 and 2019. [ABSTRACT FROM AUTHOR]

• High variability of in vivo potency assays for wP (pertussis), IPV and menB vaccines. • Low precision makes in vivo assays unsuitable to monitor manufacturing consistency. • Large differences between individual mice likely contribute to menB assay variability. For the batch release of vaccines, potency release assays are required. Non-animal in vitro tests have numerous advantages and are preferred; however, several vaccines are still released using in vivo assays. Their major drawback is the inherent variability with its practical implications. We quantified the variability of in vivo potency release assays for whole-cell pertussis, inactivated polio and meningococcal B (MenB) vaccines which showed large CV (Coefficient of Variation) ranging from 34% to 125%. As inherent variability might potentially be attributed to the highly variable immune system between individual animals, we evaluated the antibody titres to four MenB antigens in 344 individual outbred mice. These varied strongly, with more than 100-fold differences in antibody titres in responsive mice. Furthermore, within individual mice there was generally no correlation between the strengths of the responses to the four antigens. A mouse with a very low or no response to one antigen in many cases exhibited a strong response to another antigen. The large differences between individual animals is likely a considerable contributor to the inherent variability of in vivo potency assays. Our data again support the notion that it is preferred to move away from in vivo potency assays for monitoring batch to batch consistency as part of vaccine batch release testing. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has disrupted the distribution of routine immunizations globally. Multi-country studies assessing a wide spectrum of vaccines and their coverage rates are needed to determine global performance in achieving vaccination goals. Global vaccine coverage data for 16 antigens were obtained from WHO/UNICEF Estimates of National Immunization Coverage. Tobit regression was performed for all country-antigen pairs for which data were continuously available between 2015–2020 or 2015–2021 to predict vaccine coverage in 2020/2021. Vaccines for which multi-dose data were available were assessed to determine whether vaccine coverage for subsequent doses were lower than that of first doses. Vaccine coverage was significantly lower-than-predicted for 13/16 antigens in 2020 and all assessed antigens in 2021. Lower-than-predicted vaccine coverage was typically observed in South America, Africa, Eastern Europe, and Southeast Asia. There was a statistically significant coverage drop for subsequent doses of the diphtheria-tetanus-pertussis, pneumococcus, and rotavirus vaccines compared to first doses in 2020 and 2021. The COVID-19 pandemic exerted larger disruptions to routine vaccination services in 2021 than in 2020. Global efforts will be needed to recoup vaccine coverage losses sustained during the pandemic and broaden vaccine access in areas where coverage was previously inadequate. [ABSTRACT FROM AUTHOR]

A syringe for the long-term, room-temperature storage and injection of vaccines is described. Stabilisation was achieved by drying from a trehalose-containing buffer which formed an inert soluble glass distributed in the internal interconnected voids in an absorbent, compliant, reticulated, medical-grade, porous sponge. The sponge is stored inside the barrel of a syringe and the vaccines are re-solubilised by the aspiration of water. The syringe contains the sponge throughout the filling and drying processes in manufacture, and in transport, stockpiling and finally injection. The active vaccine is delivered to the patient in the normal injection process by depressing the plunger, which compresses the sponge to completely expel the dose. Full recovery of vaccine potency, after 7–10 months @ 45 °C, was shown by complete protection against supra-lethal doses of active toxins in immunised Guinea pigs. [ABSTRACT FROM AUTHOR]

• ACIP recommends that pregnant women receive Tdap, ideally at 27–36 weeks' gestation. • Tdap5 vaccination during 27–36 weeks' gestation protects infants from pertussis. • Tdap vaccination of mothers after pregnancy did not protect infants from pertussis. To 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. The 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 %. There 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. Tdap5 vaccination in pregnancy between 27 and 36 weeks' gestation is highly effective at protecting young infants from pertussis. Study registration: ClinicalTrials.gov , NCT05040802. [ABSTRACT FROM AUTHOR]

• Vaccination of pregnant women is recommended to reduce pertussis in infants. • A novel agent-based mathematical model was developed to examine several phenomena. • Maternal vaccination results in reduction in future pertussis cases in infants. • Immunological blunting has moderate effect on maternal vaccination effectiveness. • Interruption of exposure pathways reduces pertussis disease in infants. The re-emergence of pertussis has occurred in the past two decades in developed countries. The highest morbidity and mortality is seen among infants. Vaccination in pregnancy is recommended to reduce the pertussis burden in infants. We developed and validated an agent-based model to characterize pertussis epidemiology in Alberta. We computed programmatic effectiveness of pertussis vaccination during pregnancy (PVE) in relation to maternal vaccine coverage and pertussis disease reporting thresholds. We estimated the population preventable fraction (PFP) of different levels of maternal vaccine coverage against counterfactual "no-vaccination" scenario. We modeled the effect of immunological blunting and measured protection through interruption of exposure pathways. PVE was inversely related to duration of passive immunity from maternal immunization across most simulations. In the scenario of 50% maternal vaccine coverage, PVE was 87% (95% quantiles 82–91%), with PFP of 44% (95% quantiles 41–45%). For monthly age intervals of 0–2, 2–4, 4–6 and 6–12, PVE ranged between 82 and 99%, and PFP ranged between 41 and 49%. At 75% maternal vaccine coverage, PVE and PFP were 90% (95% quantiles 86–92%) and 68% (95% quantiles 65–69%), respectively. At 50% maternal vaccine coverage and 10% blunting, PVE and PFP were 86% (95% quantiles 77–87%) and 43% (95% quantiles 39–44%), respectively, while at 50% blunting, the corresponding values of PVE and PFP were 76% (95% quantiles 70–81%) and 38% (95% quantiles 35–40%). PVE attributable to interruption of exposure pathways was 54–57%. Our model predicts significant reduction in future pertussis cases in infants due to maternal vaccination, with immunological blunting slightly moderating its effectiveness. The model is most sensitive to maternal vaccination coverage. The interruption of exposure pathways plays a role in the reduction of pertussis burden in infants due to maternal immunization. The effect of maternal immunization on population other than infants remains to be elucidated. [ABSTRACT FROM AUTHOR]

Since 2012, reports of primary ovarian insufficiency (POI) temporally associated with receipt of human papillomavirus (HPV) vaccine have been published leading to questions about a potential causal association. A Vaccine Safety Datalink study did not find an increased risk for POI after vaccination. We reviewed the Vaccine Adverse Event Reporting System (VAERS) to describe POI reports. We searched VAERS, a U.S. passive surveillance system, for domestic POI reports received from 01/01/1990 to 12/31/2017 after any vaccination. The search used both Medical Dictionary for Regulatory Activity Preferred Terms and a text-based search for POI and its symptoms. All reports were reviewed, and the American College of Obstetricians and Gynecologists (ACOG) guidelines for POI diagnosis were applied. Data mining for disproportionate reporting was conducted. Six hundred fifty-two reports met the search criteria and clinical review identified 19 POI reports. Most reports (n = 16) were received between 2013 and 2017. The median age at vaccination was 14.5 years (range 10–25 years) and the median interval between first dose of vaccination and reporting the event to VAERS was 43 months (range 4–132 months; mean 59.6 months). Four reports met ACOG diagnostic criteria; one with an underlying cause (47XXX chromosomal abnormality) reported. Eleven reports documented menstrual irregularity ≥ 3 months; 5 had ≥ 1 laboratory test result used to diagnose POI. Eighteen of 19 reports described receipt of HPV vaccine with or without other vaccines. Other vaccines reported were meningococcal conjugate vaccine, hepatitis A, varicella and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis. Disproportionate reporting was found for three relevant coding terms after HPV vaccination. POI is rarely reported to VAERS. Most reports contained limited diagnostic information and were submitted after published cases of POI following HPV vaccination. Results of our review do not suggest a safety concern. [ABSTRACT FROM AUTHOR]

Older adults are at increased risk for adverse health outcomes when having an influenza, pneumococcal disease, pertussis, or herpes zoster infection. Despite the ability of vaccinations to prevent these adverse outcomes, vaccination coverage is low in the European Union. This study aimed to explore the sociodemographic, lifestyle, and health-related characteristics associated with vaccination willingness for these vaccine-preventable diseases. Cross-sectional data from wave 6 (years 2013–2017) of the population-based Doetinchem Cohort Study was analysed, with 3063 participants aged 46–86 years included. The outcome was the self-reported willingness to get vaccinated against influenza, pneumococcal disease, pertussis, and herpes zoster (willing, neutral, not willing). Multinomial logistic regression was used to investigate the socio-demographic, lifestyle and health characteristics associated with vaccination willingness. For influenza 36 % was willing to get vaccinated, 35 % was neutral and 28 % was not willing to get vaccinated. The willingness to get vaccinated for the relatively unfamiliar vaccine-preventable diseases was lower: 26 % for pneumococcal disease (neutral: 50 %, not willing: 23 %), 26 % for pertussis (neutral 53 %, not willing: 22 %), and 23 % for herpes zoster (neutral 54 %, not willing: 24 %). A relative lower willingness was found among those 46–64 years old (compared to those 65 years or older). Women, having a high SES, being employed and having a good health were all associated with lower willingness to get vaccinated, which was the case for all vaccine-preventable diseases. Older adults were generally more willing to get vaccinated against influenza than for the three less familiar diseases. Characteristics of those less willing may be used to improve strategies to increase vaccination coverage. Additional studies are needed to investigate the willingness to get vaccinated during and after the COVID-19 pandemic that may have changed the feel of urgency for vaccination. [ABSTRACT FROM AUTHOR]

• Measles VC (at least one dose) in HCW in 2019 was 73.3% (CI95%: 71.0–75.5). • Pertussis VC (booster during adulthood) was 53.5 % (49.9–57.0). • Varicella VC was 26.4 % (23.0–30.2) and influenza VC 34.8 % (32.8–37.4). • 14.6 % and 10.1 % of HCW were susceptible to measles and varicella. • Higher influenza and pertussis VC in wards with a staff vaccination contact person. Vaccine recommendations for healthcare workers (HCW) aim to protect them and reduce transmission to susceptible patients. We conducted a national randomised survey in 2019 whose main objectives were to estimate national vaccination coverage (VC) for measles, pertussis, varicella, and influenza in HCW working in healthcare facilities (HCF) in France, and to identify determinants associated with higher VC. We performed a cross-sectional survey of physicians, nurses, midwives and nursing assistants in HCF using a random stratified three-stage sampling design. Data were collected during face-to-face interviews using a tablet computer and complemented with information from the individual HCW vaccination records. We investigated possible determinants of higher VC using univariate and multivariate Poisson regressions and estimated the prevalence ratio (PR). We included 8594 HCW working in 167 HCF. Self-declared VC was 73.3% (CI95%: 71.0–75.5) for measles in HCW with no history of measles (at least one dose), 53.5% (49.9–57.0) for pertussis (booster dose during adulthood), 26.4% (23.0–30.2) for varicella in HCW with no history of varicella (at least one dose) and 34.8% (32.8–37.4) for influenza. Taking into account the history of each disease and related VC, 14.6% and 10.1 % of HCW were susceptible to measles and varicella. VC varied by profession, age group, ward and sex. Higher influenza VC was observed in HCW working in wards where i) there was a staff vaccination contact person (PRa: 1.2, CI95% 1.1–1.4), ii) staff vaccination was organized in the ward (1.4: 1.2–1.6), iii) information on influenza vaccines was provided (1.2: 1.1–1.4), and iv) the ward manager supported the HCW vaccination campaign (1.3: 1.1–1.6). Over a 10-year period, VC for HCW working in HCF improved in France. However, vaccination objectives were not achieved for measles (95%) or influenza (80%). Vaccination efforts should be continued, especially in wards with at-risk patients. [ABSTRACT FROM AUTHOR]

Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017–2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1–6.4%) compared to up to 28% before the SIA (range: 7.3–28.1%). We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children. [ABSTRACT FROM AUTHOR]

• In 2018, about 8,883,931 and 12,566,478 children aged under 5 years old in Nigeria had not received routine DTP1 and MCV1, respectively. • MCV and DTP zero-dose prevalence shared similar patterns, with highest prevalence districts concentrated in the northeast and northwest but also found elsewhere. • Measles incidence, though mitigated by campaigns, is related to subnational routine MCV1 coverage. • Residual zero-dose prevalence following vaccination campaigns should be analysed and reported. • Targeted campaigns or routine immunization interventions in higher zero-dose prevalence districts are needed to reduce disease risk. Geographically precise identification and targeting of populations at risk of vaccine-preventable diseases has gained renewed attention within the global health community over the last few years. District level estimates of vaccination coverage and corresponding zero-dose prevalence constitute a potentially useful evidence base to evaluate the performance of vaccination strategies. These estimates are also valuable for identifying missed communities, hence enabling targeted interventions and better resource allocation. Here, we fit Bayesian geostatistical models to map the routine coverage of the first doses of diphtheria-tetanus-pertussis vaccine (DTP1) and measles-containing vaccine (MCV1) and corresponding zero-dose estimates in Nigeria at 1x1 km resolution and the district level using geospatial data sets. We also map MCV1 coverage before and after the 2019 measles vaccination campaign in the northern states to further explore variations in routine vaccine coverage and to evaluate the effectiveness of both routine immunization (RI) and campaigns in reaching zero-dose children. Additionally, we map the spatial distributions of reported measles cases during 2018 to 2020 and explore their relationships with MCV zero-dose prevalence to highlight the public health implications of varying performance of vaccination strategies across the country. Our analysis revealed strong similarities between the spatial distributions of DTP and MCV zero dose prevalence, with districts with the highest prevalence concentrated mostly in the northwest and the northeast, but also in other areas such as Lagos state and the Federal Capital Territory. Although the 2019 campaign reduced MCV zero-dose prevalence substantially in the north, pockets of vulnerabilities remained in areas that had among the highest prevalence prior to the campaign. Importantly, we found strong correlations between measles case counts and MCV RI zero-dose estimates, which provides a strong indication that measles incidence in the country is mostly affected by RI coverage. Our analyses reveal an urgent and highly significant need to strengthen the country's RI program as a longer-term measure for disease control, whilst ensuring effective campaigns in the short term. [ABSTRACT FROM AUTHOR]

Immunity gaps caused by COVID-19-related disruptions highlight the importance of catch-up vaccination. Number of countries offering vaccines in second year of life (2YL) has increased, but use of 2YL for catch-up vaccination has been variable. We assessed pre-pandemic use of 2YL for catch-up vaccination in three countries (Pakistan, the Philippines, and South Africa), based on existence of a 2YL platform (demonstrated by offering second dose of measles-containing vaccine (MCV2) in 2YL), proportion of card availability, and geographical variety. We conducted a secondary data analysis of immunization data from Demographic and Health Surveys (DHS) in Pakistan (2017–2018), the Philippines (2017), and South Africa (2016). We conducted time-to-event analyses for pentavalent vaccine (diphtheria-tetanus-pertussis-Hepatitis B- Haemophilus influenzae type b [Hib]) and MCV and calculated use of 2YL and MCV visits for catch-up vaccination. Among 24–35-month-olds with documented dates, coverage of third dose of pentavalent vaccine increased in 2YL by 2%, 3%, and 1% in Pakistan, Philippines, and South Africa, respectively. MCV1 coverage increased in 2YL by 5% in Pakistan, 10% in the Philippines, and 3% in South Africa. In Pakistan, among 124 children eligible for catch-up vaccination of pentavalent vaccine at time of a documented MCV visit, 45% received a catch-up dose. In the Philippines, among 381 eligible children, 38% received a pentavalent dose during an MCV visit. In South Africa, 50 children were eligible for a pentavalent vaccine dose before their MCV1 visit, but only 20% received it; none with MCV2. Small to modest vaccine coverage improvements occurred in all three countries through catch-up vaccination in 2YL but many missed opportunities for vaccination continue to occur. Using the 2YL platform can increase coverage and close immunity gaps, but immunization programmes need to change policies, practices, and monitor catch-up vaccination to maximize the potential. [ABSTRACT FROM AUTHOR]

The reported number of pertussis cases declined after the implementation of COVID-19 prevention and control measures, however, the burden of pertussis among adults in China remains largely unknown. Additionally, the waning of natural antibody level has also rarely been assessed. A total of 762 healthcare workers (HCWs) who had underwent the health examinations in 2021 and 2022 were included. Serum anti-PT IgG and IgA levels were determined by ELISA. Recent B. pertussis infection was defined as anti-PT IgG ≥100 IU/ml and/or anti-PT IgA ≥10 IU/ml. In 2021, the seroprevalence of recent B. pertussis infection was 10.1 %, and those HCWs in outpatient department had a higher percentage (18.6 %), and geometric mean concentration (GMC) (6.3 IU/ml) than those in other departments. This seroprevalence decreased to 2.4 % in 2022, although the difference remained significant. In the 77 subjects with recent B. pertussis infection in 2021, anti-PT IgG was undetectable in 18 cases the following year. Majority (68/76) of the subjects with anti-PT IgA ≥10 IU/ml in 2021 no longer had detected this antibody in 2022. Among 95 pertussis cases, approximately 60.0 % of cases reported no history of cough. Among those with a documented cough history, 36 cases with suspected pertussis courses who had never been diagnosed. Prolonged cough with nocturnal exacerbation (29/38) was the most commonly reported clinical symptom, and whoop was confirmed in six cases. Uroclepsia and syncopes during the cough attacks were reported by three and one subjects, respectively. One case presented with subconjunctival hemorrhage and tensionic purpura during the course. The results suggested a high prevalence of B. pertussis infection among HCWs. The presence of unrecognized adult pertussis cases and the rapid waning of antibody indicate the need to improve clinical management for suspected pertussis in adults, and to updated immunization schedule after childhood program. [ABSTRACT FROM AUTHOR]

In New Zealand, approximately half reported pertussis cases are adult. Studies indicate underestimated pertussis burden in this population and probable reservoir for childhood pertussis. Pertussis is linked to chronic obstructive pulmonary disease (COPD) development and increased risk with pre-existing COPD. While acellular pertussis vaccines are available for adults, data on pertussis disease burden in adults and association with COPD remain limited. To estimate pertussis incidence in New Zealand adult health service user (HSU) population aged ≥ 18 between 2008–2019 and inform adult pertussis vaccination strategies by assessing disease burden and risk factors in different adult populations. Retrospective observational cohort study using an HSU cohort, formed by linking administrative health data using unique National Health Index identifier. For primary analysis, annual incidence rates were calculated using pertussis hospitalisations and notifications. In secondary analysis, Cox proportional hazards survival analyses explored association between pertussis in adults and chronic comorbidities. The cohort had 2,907,258 participants in 2008 and grew to 3,513,327 by 2019, with 11,139 pertussis cases reported. Highest annual incidence rate of 84.77 per 100,000 PYRS in 2012, notably affecting females, those aged 30–49 years, and European or Māori ethnicity. Adjusting for sociodemographic variables found no significant risk of prior pertussis notification leading to comorbidity diagnosis (Adjusted-HR: 0.972). However, individuals with prior comorbidity diagnosis had 16 % greater risk of receiving pertussis notification or diagnosis (Adjusted-HR: 1.162). Study found significant pertussis burden among the HSU adult cohort and highlighted higher risk of pertussis for those with recent comorbidity diagnoses. Vaccination for pertussis should be recommended for individuals with comorbidities to reduce infection risk and disease severity. GPs must have capability to test for pertussis, given it is notifiable disease with implications for individuals, their families, and broader population. High-quality disease surveillance is crucial for informing policy decisions. [ABSTRACT FROM AUTHOR]

We recently reported a near disappearance of B. pertussis and a decline in anti- B. pertussis antibodies during the peak implementation of Coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPI) in 2021 in British Columbia (BC), Canada. During 2021–2023, incidence of reported B. pertussis cases remained low in BC at < 1/100,000 population. This study determined how serological evidence of B. pertussis changed after the gradual relaxation of NPI between 2021–2023. Randomly selected blood samples from school staff 25–51 years old (n = 65) were collected yearly between 2021–2023 in the Vancouver metropolitan area, BC, Canada, and tested for anti-pertussis toxin (PT) IgG levels. Serological evidence of B. pertussis infection (thereafter "seroconversion") was defined as a quantifiable anti-PT IgG levels in subjects with anti-PT IgG levels below lower limit of quantification in the preceding year or a > 4-fold increase in anti-PT IgG levels between two subsequent years. Samples were also tested for anti-diphtheria toxoid (DT) IgG, and similar seroconversion criteria were applied to exclude seroconversion due to vaccination with tetanus-diphtheria-acellular-pertussis (Tdap). Three subjects met seroconversion criteria for anti-PT IgG between 2021 and 2022 and 9 between 2022 and 2023, yielding a seroconversion rate of 4.6 /100 person-years and 14.9/100 person-years, P = 0.127, respectively. None of the subjects met the criteria for vaccination with Tdap. The geometric mean concentration of anti-PT IgG showed a statistically significant decrease in 2022 compared with 2021, 4.8 IU/mL IU/ml (95 % confidence interval [CI], 3.8–5.9) vs. 6.4 IU/ml (95 % CI, 4.9–8.2; p = 0.001), followed by a statistically significant increase in 2023 compared with 2022 6.5 IU/ml (95 % CI, 4.9–8.5) vs. 4.8 IU/ml (95 % CI, 3.8–5.9; p = 0.0006), respectively. Serological evidence of B. pertussis increased between 2022 and 2023 despite low reported cases, which suggests that B. pertussis circulation resumed after relaxing of COVID-19 NPI. [ABSTRACT FROM AUTHOR]

• Evaluated children's antibody responses prior to and following the receipt of the dTaP5-IPV preschool booster, to all of the antigenic component of the vaccine (pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, pertactin, diphtheria toxoid and tetanus toxoid). • Evaluated and compared the impact of two antenatal pertussis-containing vaccines, dTaP3-IPV and dTaP5-IPV, on children's own vaccine responses to the receipt of the dTaP5-IPV preschool booster. • Evaluated the blunting effect of antenatal pertussis vaccination on children's own vaccine responses persisting up to around the age of 3 and a half years old. • The first study to evaluate on the impact of antenatal pertussis vaccination on children's own vaccine responses beyond the age of 2 years old. An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study. Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP 3 -IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP 5 -IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP 5 -IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared. Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP 3 -IPV and dTaP 5 -IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP 3 -IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22–0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups. The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose. ClinicalTrials.gov registration number: NCT03578120 [ABSTRACT FROM AUTHOR]

• In Japan, Prenatal DTaP vaccination lacks required safety information. • Pertussis seroprevalence is approximately 70% among pregnant Japanese women. • Maternal antibody titers in early pregnancy reflect infant antibody titers. • Preconception DTaP vaccination is one way to obtain maternal immunity. • A national survey to evaluate the safety information of prenatal DTaP is necessary. An increasing number of countries have been introducing acellular pertussis vaccination during pregnancy for the prevention of neonatal pertussis. In response to the fact that infantile pertussis cases of 0–5 months age groups remained unchanged despite the universal vaccination program, prenatal pertussis vaccination has been a rising issue in Japan. Hence, we investigated the seroprevalence of pertussis, diphtheria, and tetanus antibodies in Japanese pregnant women and neonates, and evaluated the necessity of diphtheria-tetanus-acellular pertussis (DTaP) vaccination during the preconception or prenatal period. Maternal PT-IgG (EIA) and FHA-IgG (EIA) for the first trimester, within 1 week after delivery, and cord blood were collected, along with colostrum pertussis-IgA (ELISA), diphtheria-IgG (EIA), tetanus-IgG (EIA), and blood samples from the first trimester. The maternal seroprevalence of PT-IgG and FHA-IgG was 69 % and 75 %, respectively. All tested participants were positive for diphtheria-IgG and tetanus-IgG (100 %). First trimester PT-IgG/FHA-IgG antibody titers were significantly associated with cord blood PT-IgG/FHA-IgG titers (P < 0.001). We found that pertussis seroprevalence among pregnant Japanese women was approximately 70 %. The antibody seropositivity rate of pertussis was lower than that of diphtheria and tetanus. Fetal acquired passive immunity against pertussis is higher when the level of maternal antibody in the first trimester is sufficient. At least 30 % of study population did not reach to the threshold value to provide sufficient pertussis immunity for the neonates and themselves. The acellular pertussis vaccine (DTaP) approved in Japan lacks safety information for pregnancy, hence, a solution for prompt administration of prenatal acellular pertussis vaccination might be introducing DTaP in the preconception period. [ABSTRACT FROM AUTHOR]

• We conducted the serological investigation of Bordetella pertussis in among populations of different ages in China during the COVID-19 pandemic. • To the best of our knowledge, this is the first study to evaluate the immunity of pertussis with anti-PT, anti-FHA, and anti-PRN antibodies in China. • The prevalence of pertussis had decreased during the COVID-19 pandemic, but there was still a certain proportion of adolescents and adults exhibiting evidence of recent pertussis infection. • The waning of antibody levels after pertussis vaccination were occurred, and an extra booster dose is highly recommended at the age of 6 years by replacing DT with DTP. In recent years, the resurgence of pertussis has posed a public health challenge in many countries. This study aimed to evaluate the immunity levels against pertussis among populations of different ages in China. We conducted a cross-sectional serological survey in Zhejiang Province, China in 2020. Serum IgG antibodies against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA), and pertactin (anti-PRN) were quantitatively measured. The geometric mean concentration (GMC) of three antibodies was calculated. An anti-PT level < 5 IU/mL was considered undetectable, ≥20 IU/mL as seropositive and ≥80 IU/mL as an indicator of recent infection. Mathematical models were fitted for anti-PT concentrations over time in children after four doses of the pertussis vaccination. A total of 4459 participants aged 0–59 years were included in the analyses. The overall positivity rate of anti-PT was 29.80% with the highest (81.44%) rate in the 1–2 years old and the lowest (4.72%) in 10–14 years old. The GMCs of anti-PT, anti-FHA and anti-PRN for the whole participants were 9.67 (95%CI: 9.25–10.10),18.93 (18.24–19.67), and 8.99 (8.61–9.38) IU/mL, respectively. Over 50% of subjects aged ≥ 7 years had undetectable anti-PT IgG antibodies (<5IU/mL). The proportions of the populations with anti-PT IgG ≥ 80 IU/mL were approximately 0.9%, 0.3% and 1.1% among the 10–14, 15–29, and 40–59 years old groups, respectively. The power regression equation of the attenuation model after last dose of pertussis vaccine was y = 41.088x-1.238 (R2 = 0.935, p < 0.001). The fitted anti-PT concentrations was only 5.60 IU/mL at 5 years following the last vaccination dose. The prevalence of pertussis decreased during the study period in the COVID-19 pandemic; however, there was still a certain proportion of adolescents and adults with evidence of recent infection. The decline in antibody levels after pertussis vaccination was observed, and booster doses are in urgent need in China. [ABSTRACT FROM AUTHOR]

• Resurgence of VPDs has been observed in England. The number of NHS 2ndry care episodes relating to 6 VPDs is reported here. • We show that these VPDs are associated with substantial cost and resource use burden on the healthcare system. • Notably an unexpectedly high number of polio cases was observed here whereas the PHE surveillance data report only one case. This study examined healthcare resource use (HCRU) for selected vaccine-preventable diseases (VPD) in secondary care in England. The hospital episode statistics (HES) dataset covering all secondary care interactions within the English National Health Service (NHS) from 2015 to 2021 was used to identify and track HCRU for patients with a primary or secondary diagnosis for pertussis and Haemophilus influenzae type b (Hib), or a primary diagnosis only for hepatitis B, diphtheria, poliomyelitis, or tetanus. The first documented diagnosis during the study period (01/04/2015–31/03/2021) was the index event. 7,274 patients with a total of 5,554,343 patient-days (mean follow up 1,491 days) were included. The total number of hospital admissions was 27,092 and total inpatient cost was £4,987,770, with hepatitis B making up ∼80 % of this. Mean outpatient hospital appointments per patient were highest for tetanus (4.00), but total outpatient A&E cost burden was highest for Hib (£643,343 [mean per attendance £144.57]). For patients 0–9 years of age (n = 1,917), pertussis (n = 1,547) and Hib (n = 313) were by far the most commonly coded diseases. Hepatitis B was the most common disease in adults of working age and Hib was most prevalent in adults of retirement age. Surprisingly, poliomyelitis was observed in the database potentially due to historic diagnoses and/or coding inaccuracy. Other discrepancies with surveillance data were noted. VPDs impose a large burden on the NHS, but there is potential to reduce this and improve public health by optimising vaccination schedules, improving access and ensuring high coverage rates. [ABSTRACT FROM AUTHOR]

Pertussis vaccination (Tdap -Tetanus-diphtheria-acellular pertussis) for pregnant women has been recommended since November 2017 in Singapore. In this prospective test-negative case-control study from 2018 to 2019, we aimed to evaluate vaccine effectiveness (VE) against pertussis infection and pertussis-related intensive care unit (ICU) admission according to Tdap (Tetanus-diphtheria-acellular pertussis) during pregnancy and/or infant pertussis vaccination. A total of 58 children (26 cases, 32 controls) were recruited with 4 ICU admissions. The median age was 3 months (interquartile range [IQR] 1.50–4.56 months). Overall, 25.9 % of mothers had received antenatal Tdap vaccination and 43.1 % of infants received pertussis vaccination, majority only 1 dose. Tdap in pregnancy alone without infant vaccine or with 0–1 infant dose had a VE of 97.62 % (95 % confidence interval [CI] 53.25–99.88 %), 98.17 % (95 %CI 66.61–99.9 %) respectively, against pertussis infection and 71.9 % (95 %CI 0.0–98.64), 75.86 % (95 % CI 0.0–98.78) respectively, against ICU admissions. Conclusion: Maternal Tdap vaccination was highly protective against infant pertussis and should be routinely recommended for all pregnant women. [ABSTRACT FROM AUTHOR]

• PERTINENT is a European active hospital-based surveillance system for pertussis in infants. • We measured the effectiveness of maternal and primary vaccination in infants <2 and 2–11 months. • Maternal vaccination reduced severe pertussis incidence in infants too young for vaccination. • Infants' vaccination reduced severe pertussis irrespective of the mother's vaccination status. • Only network allowing for independent multi-country pertussis vaccine effectiveness studies. PERTINENT 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). From 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. Of 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]. Our 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. [ABSTRACT FROM AUTHOR]

• The consistency approach is an avenue for vaccine batch release without animal testing. • In vitro testing of adjuvant biological activity contributes to animal-free potency testing of vaccines. • The aluminium-based vaccines and adjuvants tested showed in vitro NLRP3 inflammasome activation. • Benchmark dose modelling showed the activation to be due to the adjuvant only. • In vitro inflammasome activation may be used to measure adjuvant biological activity. Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine to identify critical quality attributes that inform the use of a comprehensive set of non-animal tests to release the vaccine, together with the principle that the quality of subsequent batches follows from their consistent production. Many vaccine antigens are by themselves not able to induce a protective immune response. The antigens are therefore administered together with adjuvant, most often by adsorption to aluminium salts. Adjuvant function is an important component of vaccine potency, and an important quality attribute of the final product. Aluminium adjuvants are capable of inducing NLRP3 inflammasome activation. The aim of this study was to develop and evaluate an in vitro assay for NLRP3 inflammasome activation by aluminium-adjuvanted vaccines. We evaluated the effects of Diphtheria-Tetanus-acellular Pertussis combination vaccines from two manufacturers and their respective adjuvants, aluminium phosphate (AP) and aluminium hydroxide (AH), in an in vitro assay for NLRP3 inflammasome activation. All vaccines and adjuvants tested showed a dose-dependent increase in IL-1β production and a concomitant decrease in cell viability, suggesting NLRP3 inflammasome activation. The results were analysed by benchmark dose modelling, showing a similar 50% effective dose (ED50) for the two vaccine batches and corresponding adjuvant of manufacturer A (AP), and a similar ED50 for the two vaccine batches and corresponding adjuvant of manufacturer B (AH). This suggests that NLRP3 inflammasome activation is determined by the adjuvant only. Repeated freeze-thaw cycles reduced the adjuvant biological activity of AH, but not AP. Inflammasome activation may be used to measure adjuvant biological activity as an important quality attribute for control or characterization of the adjuvant. [ABSTRACT FROM AUTHOR]

• Maternal pertussis vaccination (MPV) uptake is subjected to vaccine hesitancy. • 56% of the women would be undecided about accepting if being offered the MPV. • Decision-making needs in the orientation stage are associated with intention. • Acceptors score high on Trust in the vaccine and vaccine-providing authorities. • Contemplating religious arguments is important to orthodox protestant women. [ABSTRACT FROM AUTHOR]

Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or transmission. It is well established that the alum adjuvant is a potential weakness of the acellular vaccines because the immunity provided by it is short-term. We aimed to evaluate the potential of CpG 1018® adjuvant to improve antibody responses and enhance protection against B. pertussis challenge in a murine model. A titrated range of Tdap vaccine doses were evaluated in order to best identify the adjuvant capability of CpG 1018. Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), or the whole bacterium were increased due to the inclusion of CpG 1018. In B. pertussis intranasal challenge studies, we observed improved protection and bacterial clearance from the lower respiratory tract due to adding CpG 1018 to 1/20th the human dose of Tdap. Further, we determined that Tdap and Tdap + CpG 1018 were both capable of facilitating clearance of strains that do not express pertactin (PRN-), which are rising in prevalence. Functional phenotyping of antibodies revealed that the inclusion of CpG 1018 induced more bacterial opsonization and antibodies of the Th1 phenotype (IgG2a and IgG2b). This study demonstrates the potential of adding CpG 1018 to Tdap to improve immunogenicity and protection against B. pertussis compared to the conventional, alum-only adjuvanted Tdap vaccine. [ABSTRACT FROM AUTHOR]

The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia. The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test. 441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p < 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents. A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden. [ABSTRACT FROM AUTHOR]

• Access to pregnancy vaccines in the United Kingdom was disrupted by the COVID-19 pandemic. • UK pregnant women reported difficulties & feeling less safe accessing vaccine appointments for themselves & for their babies during COVID-19. • Ethnic minority women were more likely to report difficulties accessing vaccine appointments during COVID-19 therefore services must ensure equitable access during the ongoing pandemic. COVID-19 changed access to healthcare, including vaccinations, in the United Kingdom (UK). This study explored UK women's experiences of accessing pertussis vaccination during pregnancy and infant vaccinations during COVID-19. An online cross-sectional survey was completed, between 3rd August-11th October 2020, by 1404 women aged 16+ years who were pregnant at some point after the first UK lockdown from March 23rd, 2020. Ten follow-up semi-structured interviews were conducted. Most women surveyed were pregnant (65.7%) and a third postnatal (34.3%). Almost all women (95.6%) were aware that pertussis vaccination is recommended in pregnancy. Most pregnant (72.1%) and postnatal women (84.0%) had received pertussis vaccination; however, access issues were reported. Over a third (39.6%) of women had a pregnancy vaccination appointment changed. COVID-19 made it physically difficult to access pregnancy vaccinations for one fifth (21.5%) of women and physically difficult to access infant vaccinations for almost half of women (45.8%). Nearly half of women (45.2%) reported feeling less safe attending pregnancy vaccinations and over three quarters (76.3%) less safe attending infant vaccinations due to COVID-19. The majority (94.2%) felt it was important to get their baby vaccinated during COVID-19. Pregnant women from ethnic-minorities and lower-income households were less likely to have been vaccinated. Minority-ethnicity women were more likely to report access problems and feeling less safe attending vaccinations for both themselves and their babies. Qualitative analysis found women experienced difficulties accessing antenatal care and relied on knowledge from previous pregnancies to access vaccines in pregnancy. During the ongoing and future pandemics, healthcare services should prioritise equitable access to routine vaccinations, including tailoring services for ethnic-minority families who experience greater barriers to vaccination. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21–1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12–1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94–1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64–0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

Testing for inactivation of pertussis toxin and reversion to toxicity in aP vaccines has historically relied on the murine histamine sensitization test, that lacks mechanistic understanding, suffers from standardization problems and is associated with severe animal suffering. Though the regulatory requirements for in vivo testing of acellular pertussis (aP) vaccine products have been waived in Europe, it is still common practice globally. Easy and quantitative in vitro methods are therefore urgently needed. One of the alternatives under development is our reporter cell line - CHO-CRE cells - that carries a cAMP-reporter construct. After exposure to pertussis toxin, cells are stimulated with a low concentration of forskolin to allow detection of pertussis toxin dependent changes in intracellular cAMP levels. Here, the results of two prevalidation studies with purified pertussis toxin and pertussis toxin spiked aP vaccines are described that were performed according to the principles of the ICH Q2(R1) guidelines for a content assay. We confirmed the assay's specificity, accuracy, precision, linearity and range. The cAMP-PTx reporter assay allows for objective, reliable and quantitative assessment of pertussis toxin levels in aP vaccines and can thereby boost broad and global replacement of the histamine sensitization test. [ABSTRACT FROM AUTHOR]

Immunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans -placental transfer of anti- B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic. Paired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti- B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti- B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p < 0.016 using Bonferroni correction. Annual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2–10.9) vs. 8.4 IU/ml (5.1–13.9; p = 0.004); 18.8 IU/ml (10.9–32.2) vs. 23.6 IU/ml (13.2–42.1; p < 0.001); and 37.1 IU/ml (18.1–75.9) vs. 47.2 IU/ml (24.8–89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018–2019, 8.4 IU/ml (95% CI, 5.1–13.9) vs. 5.4 IU/ml (95% CI, 3.8–7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2–42.1) vs. 20.1 IU/ml (95% CI, 13.4–30.2; p = 0.656), and 47.2 IU/ml (24.8–89.9) vs. 17.3 IU/ml (95% CI, 10.5–28.7; p = 0.021), respectively. B. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19. [ABSTRACT FROM AUTHOR]

• We modelled expected DTP1, DTP3, and MCV1 coverage in 2020 based on historical trends from publicly-available vaccination coverage data. • We report a 2·9% (95 % CI : [2·2%; 3·6%]) global decline in DTP3 coverage from an expected 89·2% to a reported 86·3%; and similar results for DTP1 and MCV1. • These declines translate to levels of coverage last observed in 2005, thus suggesting a potential 15-years setback in RI improvements. • These declines are less than previous modelling – compatible with the hypothesis that coverage fell more acutely in early 2020 and then rebounded. Whilst COVID-19 vaccination strategies continue to receive considerable emphasis worldwide, the extent to which routine immunisation (RI) has been impacted during the first year of the pandemic remains unclear. Understanding the existence, extent, and variations in RI disruptions globally may help inform policy and resource prioritisation as the pandemic continues. We modelled historical, country-specific RI trends using publicly available vaccination coverage data for diphtheria, tetanus and pertussis-containing vaccine first-dose (DTP1) and third-dose (DTP3) from 2000 to 2019. We report a 2·9% (95 % CI : [2·2%; 3·6%]) global decline in DTP3 coverage from an expected 89·2% to a reported 86·3%; and a 2·2% decline in DTP1 coverage (95 % CI : [1·6%; 2·8%]). These declines translate to levels of coverage last observed in 2005, thus suggesting a potential 15-years setback in RI improvements. Further research is required to understand which factors – e.g., health seeking behaviours or non-pharmaceutical interventions – linked to the COVID-19 crisis impacted vaccination coverage. [ABSTRACT FROM AUTHOR]

To determine pertussis and influenza vaccination coverage during pregnancy among women delivering in all the maternities of Geneva (Switzerland), during the COVID-19 pandemic. All women delivering in all the maternity centres of the canton of Geneva from 1st November 2020 to 30th November 2020 (beginning of the flu vaccination season) and from 8th March 2021 to 7th April 2021 (end of the flu vaccination season) had their records checked upon admission to the labour ward regarding pertussis and influenza vaccination during pregnancy. Reasons for non-vaccination were recorded. Univariate and multivariate analyses were done to identify predictors of vaccine uptake. 951 women delivered in Geneva during the two study periods, of which 950 were included in the study. 86.2% were vaccinated against pertussis, with no significant difference between the study periods (87.5% vs 85% at the beginning and end of the flu vaccination season respectively). 49.8% were vaccinated against influenza, with no significant difference between the study periods (48.8% vs 50.7% beginning and end of the flu vaccination season respectively). The influenza vaccine was 5 times more likely not to be proposed (8.9% vs. 1.7%) and 3 times more likely to be refused (26.6% vs. 8%) than the pertussis vaccine. Main reason for refusal was a lack of maternal desire for both vaccines, but not vaccine fear. Maternal parity ≥ 1 was significantly associated with pertussis vaccine uptake at univariate analysis. Women were significantly more likely to accept the influenza vaccine if they had a university degree or if they did not deliver in a midwife-only run delivery unit in both univariate and multivariate analysis. In Geneva, most gynaecologists offer pertussis immunization during antenatal care and uptake is high, but more efforts must be done to increase influenza vaccination coverage. Education level impacts maternal flu vaccination uptake, but other social disparities did not. [ABSTRACT FROM AUTHOR]

• Vaccine hesitant parents tend to see vaccine hesitant providers. • Provider vaccine hesitancy is associated with children's higher odds of non-timely vaccination. • Parental vaccine hesitancy is associated with children's higher odds of non-timely vaccination. • A higher the degree of parental and provider vaccine hesitancy is associated with increased odds of non-timely vaccination. Although medical providers are a trusted vaccination information source for parents, they do not universally support vaccination. Complementary medicine (CM) providers are particularly likely to hold vaccine hesitant (VH) views, and VH parents often consult with them. Little research compares VH of parents and providers, and if and how each is associated with uptake of recommended childhood vaccines. We defined non-timely receipt as recommended vaccines given > 1 month later than officially recommended, based on vaccination records. We administered versions of the Parent Attitudes about Childhood Vaccines (PACV) 5-item survey instrument to 1256 parents and their children's pediatricians (N = 112, 40 CM-oriented, 72 biomedical [not CM-oriented]) to identify moderately (PACV-score 5–6) and highly (PACV-score 7+) hesitant providers/parents. We obtained multivariable adjusted odds ratios to test relationships between parental VH and provider type/VH, and between non-timely receipt of selected childhood vaccines and parental VH and provider type/VH. No biomedical providers were VH, 9 CM providers were moderately VH, and 17 were highly VH. Parents seeing moderately and highly hesitant providers had adjusted odds ratio (AOR) for being VH = 6.6 (95% confidence interval (CI), 3.1–14.0) and AOR = 31.3 (95% CI 16.8–58.3), respectively. Across all vaccine uptake endpoints, children of moderately and highly hesitant parents had 1.9–3.8 and 7.1–12.3 higher odds of non-timely vaccination, and children seeing highly hesitant CM providers had 4.9–9.4 higher odds. Children seeing moderately hesitant CM providers had 3.3 higher odds of non-timely vaccination for the 1st dose of measles and 3.5 higher odds for 1st dose of polio/pertussis/tetanus. VH by both parents and providers each is associated with non-timely childhood vaccination. As VH parents are more likely to consult with VH providers, interventions aimed at increasing timely vaccination need to primarily target VH providers and their clients. [ABSTRACT FROM AUTHOR]