Background Pertussis is endemic with epidemic peaks affecting all age groups and is a severe disease in infants too young to be vaccinated. Maternal tetanus-diphtheria-acellular-pertussis (Tdap)-vaccination has an estimated vaccine effectiveness against pertussis disease of approximately 90% for infants up to 2 months, thus shortening the vulnerable period. Maternal vaccination protects through transplacental transfer of maternal antibodies via an active receptor-mediated process. This process may be impaired in fetuses with fetal growth restriction (FGR), primarily caused by placental insufficiency. In the Netherlands, term infants from mothers Tdap-vaccinated during pregnancy receive diphtheria, tetanus, and pertussis, inactivated poliovirus, Haemophilus influenzae type b, and hepatitis B (DTaP-IPV-Hib-HepB) vaccinations at age 3-5-12 months. Infants born preterm or from unvaccinated mothers are recommended to receive an extra dose at 2 months-of-age. For term FGR infants from vaccinated mothers this 3-5-12 month schedule may be suboptimal due to compromised placental function, including transplacental transfer of maternal antibodies. Consequently, protection from maternal vaccination up to their first vaccination may be less optimal compared to term infants who are appropriate for gestational age (AGA) or small for gestational age (SGA).Aim This study investigates whether following maternal Tdap vaccination, concentrations of passively acquired maternal IgG antibodies against Tdap vaccine antigens in 2-month-old FGR infants are at least as high as in 2-month-old term AGA- and SGA infants.Method This is a prospective, observational cohort study involving Tdap-vaccinated pregnant women carrying a fetus with signs of SGA or FGR. Blood samples will be collected from mothers (finger-stick) and their infants (umbilical cord) at birth, and at 2 months (heel-stick), to measure Tdap-specific IgG antibody concentrations. Additionally, questionnaire data on general health will be gathered at three different time points. Results will be compared with historical studies investigating transfer of maternal antibodies after Tdap vaccination during pregnancy in AGA preterms and terms.Discussion By comparing the concentrations of IgG antibodies against Tdap vaccine antigens among FGR, SGA, AGA preterms and terms, we will contribute to insights into the necessity of optimizing the immunization schedule for FGR infants.

Background Target trial emulation (TTE) is a framework to systematically address potential biases in causal inference when using observational data. We estimated vaccine effectiveness (VE) of the Omicron XBB.1.5 booster vaccination against SARS-CoV-2 infection between 2 October 2023 and 2 April 2024 using four TTE approaches. Methods A hypothetical target trial was designed where eligible participants would be randomly assigned to receive booster vaccination or not. Four approaches were used to emulate this hypothetical trial using data of an ongoing prospective cohort study in the Netherlands. The first and second approach defined time zero as the start of the booster vaccination rollout and considered vaccination as a time-varying variable. The first approach adjusted for confounders by regression adjustment, while the second used inverse probability weighting. The third and fourth approach used multiple time zeros. In the third approach, all persons who received a booster vaccination on a specific day were matched 1:1 to persons who were not (yet) vaccinated on that day. In the fourth approach, confounders were adjusted for using inverse probability weighting. Results Overall VE was 30% (95%CI:26–34), 28% (24–32), 28% (24–32) and 27% (24–31) in the first, second, third and fourth approach, respectively. VE decreased as time since vaccination increased, but this was somewhat less pronounced in the third approach. Conclusions Estimated VE was similar across the four approaches. The choice of approach should be based on the model assumptions, estimand of interest, and feasibility.

BACKGROUND:Diagnostic self-testing for SARS-CoV-2 may lead to selection bias in test-negative case-control designs (TND) for COVID-19 vaccine effectiveness (VE) at the primary care level. We investigated whether SARS-CoV-2 self-testing among those with acute respiratory infection (ARI) after the acute pandemic phase was associated with primary care healthcare seeking in the general Dutch population. METHODS:We pooled questionnaire data from three study rounds (June 2022, November 2022, and April 2023) of the nationwide PIENTER Corona cohort study. Among 3152 participants aged ≥18 years, we selected the first self-reported ARI episode with cough, sore throat, dyspnoea, and/or coryza since March 2022. We performed log-binomial regression analyses adjusted for age, sex, education, and comorbidities to assess the associations between COVID-19 vaccination, SARS-CoV-2 self-testing, and general practitioner (GP) consultation, and between GP consultation and the prior self-test result. RESULTS:Vaccinated (vs. unvaccinated) participants with an ARI episode more often self-tested [adjusted risk ratio (RR) 1.13, 95% confidence interval (CI) 1.04-1.27]. Vaccination (RR 0.78, 95% CI 0.48-1.44) and the self-test result overall (RR 0.86, 95% CI 0.69-1.08) were both not associated with GP consultation. However, with point estimates in opposite directions, vaccinated individuals seemed less likely (RR 0.86, 95% CI 0.68-1.08) and unvaccinated seemed more likely (RR 1.57, 95% CI 0.36-6.28) to consult a GP after a positive self-test. CONCLUSION:Findings from this Dutch-population-based cohort suggest that GP consultations between March 2022 and May 2023 may have differed by self-test result and vaccination status, indicating that selection bias in the TND COVID-19 VE estimates from testing before GP consultation could be a valid concern. More research in various settings is needed.

INTRODUCTION:This study aimed to assess whether the occurrence, severity, and duration of AE following COVID-19 booster vaccination were associated with subsequent booster uptake during the 2022-2024 autumn booster campaigns in the Netherlands. METHODS:We included participants from the Vaccine Study COVID-19 (VASCO), an ongoing prospective cohort study, who were eligible for booster vaccination in 2022-2024. Participants completed a questionnaire on AE one month after booster vaccination. Logistic regression was performed to assess the association between the occurrence, severity, and duration of local and systemic AE, and revaccination during the subsequent year. We adjusted for demographics and prior SARS-CoV-2 infection. RESULTS:In 2022 and 2023, 11,010 and 14,824 participants were vaccinated and completed the AE questionnaire. Of these, 73.7% and 87.0% were revaccinated in subsequent years. The occurrence of systemic AE in 2022 was associated with a lower odds of revaccination in 2023 (OR: 0.84 [95%CI, 0.76-0.93]). The likelihood of revaccination declined with increasing severity- moderate (0.79 [0.66-0.94]) and severe AE (0.45 [0.34-0.60]) - and longer duration (>5 days: 0.72 [0.54-0.95]) of systemic AE. Also, severe local AE (0.38 [0.23-0.60]) and seeking medical care for AE (0.50 [0.34-0.73]) were associated with reduced vaccination uptake. Similar associations were observed for revaccination in 2024. CONCLUSION:This study found a lower likelihood of subsequent COVID-19 booster uptake after experiencing systemic AE, particularly when severe or prolonged, or when experiencing a severe local AE. These findings underscore the need to address experienced AE in communication strategies, as this may influence the success of vaccination campaigns.

This study assessed whether systematically using finetype data in national surveillance of invasive meningococcal disease serogroup B (IMD-B) in the Netherlands could improve cluster detection in order to prevent further cases through public health actions. We analysed 2005-2023 data, including 1,642 IMD-B cases with complete finetype and municipality information (95%; N = 1729). Using a generalized linear model, we calculated expected baselines for each finetype, including temporal trends. Using SaTScan™, we applied Poisson scan-statistics with a 365-day window to identify spatiotemporal clusters, comparing results to epidemiological and core-genome multi-locus sequence typing (cgMLST) data. Of 453 finetypes, 308 (68%) occurred once; diversity was high (Gini-Simpson index 0.96). We identified 42 spatiotemporal clusters across 37 finetypes, comprising 132 cases (8%), with a median cluster size of two (range 2-21) and duration of 45 days (range 6-356). Between zero and five clusters were detected yearly. Among 18 cases with known epidemiological links, 14 (78%) were within detected spatiotemporal clusters. CgMLST data from eight clusters supported some clusters but rejected others. Systematic cluster detection using finetype could reveal missed epidemiological links, potentially enabling public health action. However, its impact in preventing additional IMD-B cases is likely limited due to small cluster sizes, though meaningful given the severity of IMD-B. Simple finetype mapping may provide a resource-efficient alternative to SaTScan™.

Since the cessation of real-time monitoring of COVID-19 hospitalizations in early 2024, the burden of and vaccine effectiveness (VE) against severe COVID-19 in the Netherlands was largely unknown. Recently, hospitalization data from 2024 were made available and were linked to the population registry, vaccination registry and healthcare use data (for classification into medical risk groups). We analyzed the number and incidence of COVID-19 hospitalizations in 2023 and 2024 by age and medical risk group. VE against hospitalization of the autumn booster of 2023 (by time since vaccination, 25 September 2023 to 16 September 2024) and of the autumn booster of 2024 (16 September to 31 December 2024) were estimated by medical risk group among persons aged 60 years and older using Cox proportional hazards models with calendar time as underlying time scale and vaccination status as time-varying exposure. Models were adjusted for age, sex, region and household socio-economic status. From around age 60 onward, intermediate and high medical risk groups had a markedly higher incidence than younger age groups, increasing with age. Persons in the low medical risk group had a low incidence up to the age of 80. In 2024, incidence was lower than in 2023. For both autumn booster rounds, estimated VE against hospitalization was moderate at 55-67% in the first 3 months post-vaccination. In the high medical risk group, 2023 VE decreased fast and was no longer significant at 6 months post-vaccination. For both years, estimates of the number of averted hospitalizations and number needed to vaccinate to prevent one hospitalization indicated that significant health benefit can be achieved by vaccinating the intermediate and high medical risk groups aged 60 years and older. Efforts to increase the moderate vaccine uptake among risk groups could potentially prevent a considerable disease-and healthcare burden.

Importance:Household contacts of patients with invasive group A streptococcus (iGAS) disease have an increased risk of iGAS. In the Netherlands, the iGAS public health policy was changed in January 2023, offering antibiotic prophylaxis to household contacts of all patients with iGAS rather than only those presenting with necrotizing fasciitis or streptococcal toxic shock syndrome. Objective:To estimate risk of iGAS in the general population and among household and other contacts of primary patients with iGAS, before and after the policy change. Design, Setting, and Participants:This nationwide, population-based, open cohort study, linked population registry data with iGAS laboratory data for the study period (April 2022 to December 2024). The study population consisted of all persons included in the Dutch population registry at any time during the study period. The case definition was an iGAS isolate submitted to the Netherlands Reference Laboratory for Bacterial Meningitis, with disease onset in the study period. Exposure:For contacts of primary patients with iGAS, exposure risk period was defined as the 30 days after culture date of the index patient. Exposure under the new policy was defined as all person-time after January 20, 2023. Main Outcomes and Measures:Incidence rate ratios (IRR) of iGAS during the 30-day risk period compared with unexposed person-time were estimated. Secondary attack rates among household contacts were estimated with an odds ratio (OR) to compare attack rates before and after the policy change. Estimates were adjusted for age group, sex, household socioeconomic status, and year quarter. Results:A total of 19 006 247 persons (9 467 251 male [49.8%]; 6 308 794 [33.2%] aged 20-45 years) contributed 51 067 977 person-years to the analysis. A total of 3644 iGAS isolates from 3630 unique persons were included, of which 14 were household secondary cases. The IRR for household contacts during the risk period was 235.25 (95% CI, 94.35-586.59) before and 74.00 (95% CI, 35.17-155.71) after the policy change, compared with unexposed person-time. The secondary attack rate among household contacts was 0.219% (7 individuals) before and 0.047% (7 individuals) after the policy change (adjusted OR, 0.17; 95% CI, 0.03-0.83). Conclusions and Relevance:In this nationwide cohort study, there was a reduction in secondary iGAS risk among household contacts after implementation of an expanded antibiotic prophylaxis policy, which suggests that antibiotic prophylaxis for household contacts of patients with iGAS prevents secondary iGAS infection.

INTRODUCTION:There is evidence that pre-booked appointments (PBA) for vaccination can enhance uptake, but might also result in reactance. We assessed the effect of PBA versus self-scheduling on uptake of COVID-19 vaccination during the 2023 autumn campaign in the Netherlands. METHODS:Persons aged ≥60 years were personally invited by mail. Those born between 01-01-1934 and 01-05-1952 (i.e., age 71.7-90.0 on 31-12-2023) received a letter with a PBA, while the others received a letter inviting them to self-schedule an appointment. National registries of sociodemographic determinants and COVID-19 vaccination were linked by a unique personal identifier. A regression discontinuity design was applied to estimate the local average treatment effect at 71.7 and 90.0 years of age among non-institutionalised adults with ≥1 prior COVID-19 vaccination. Stratified analyses were done for sociodemographic subgroups. RESULTS:The autumn 2023 vaccination coverage among non-institutionalised persons aged ≥60 years with ≥1 prior registered COVID-19 vaccination (N = 4.0 million) was 55.0%. PBA resulted in a 3.3 (95% CI 2.6-4.1) and 4.7 (95% CI 3.7-5.7) percentage point higher uptake at 71.7 and 90.0 years, respectively. Subgroup analyses showed predominantly positive results. However, statistically significant interactions between several determinants of vaccination and the PBA effect indicate that the effect size differed between subgroups. DISCUSSION:This nationwide quasi-experimental study shows that PBA is effective in increasing uptake. However, differences of the PBA effect between subgroups should be taken into account to increase equity of the vaccination programme.

INTRODUCTION:We estimated vaccine effectiveness (VE) of JN.1 COVID-19 vaccination against SARS-CoV-2 infection by (sub)variant between 23 September 2024 and 23 February 2025. METHODS:JN.1 vaccine-eligible participants of an ongoing prospective cohort study (VAccine Study COvid-19; VASCO) were included: individuals aged ≥60 years, and individuals aged <60 years with a medical risk condition or who were healthcare workers. In VASCO, questionnaire and serology data are regularly collected and self-tests are provided. SARS-CoV-2 infection was based on reported positive self-tests and/or anti-nucleoprotein serology results. The variant of infection was determined by whole genome sequencing of viral genetic material in positive self-tests. VE against infection was estimated using Cox regression with JN.1-vaccination as time-varying exposure, and VE against JN.1 subvariants KP.3.1.1 and XEC using multinomial logistic regression with matching of infected and uninfected participants by calendar week. Models were adjusted for age group, sex, education level, medical risk condition and SARS-CoV-2 infection history. RESULTS:Of 4490 JN.1-vaccine eligible participants <60 years, 1283 (29%) were vaccinated. Of 19,349 participants ≥60 years, 14,400 (74%) were vaccinated. During follow-up 2142 infections occurred, of which the majority was self-reported (72%). VE was 16% (95%CI: -11-36) in participants <60 years and 13% (95%CI: 2-23) in participants ≥60 years. VE against KP.3.1.1 (n = 251;27%) did not differ significantly from the VE against XEC (n = 195;5%)(OR:1.3; 0.8-2.1). CONCLUSION:We found that, during a 5-month study period with low incidence, JN.1-vaccination provided limited added protection in preventing SARS-CoV-2 infection. The observed VE estimates indicate potentially lower protection against XEC than KP.3.1.1, but the power to detect such a difference was low.

BACKGROUNDInvasive Haemophilus influenzae type b (iHib) disease incidence in < 5-year-olds decreased after vaccine introduction but increased between 2011 and 2023 in the Netherlands. The National Immunisation Programme changed products in 2011 (from DTaP-IPV/Hib to DT3aP-HBV-IPV/Hib) and 2018 (to DT5aP-HBV-IPV-Hib) and schedule from 3 + 1 to 2 + 1 doses in 2020.AIMWe aimed to estimate overall, product- and schedule-specific vaccine effectiveness (VE) against iHib disease to inform vaccination strategies.METHODSWe conducted a matched case-control study extracting iHib cases born ≥ 2005 and aged 6-119 months from 2005-2023 national reference laboratory data. We selected 10 controls per case matched on birth date and sex from the population register and obtained vaccination data from the vaccination registry. Using conditional logistic regression, we estimated matched odds ratios (mOR) and VE among 6-10-month-olds (eligible only for the primary series) and 11-119-month-olds.RESULTSWe included 250 iHib cases and 2,487 controls. Among children aged 11-119 months, VE against iHib of the full schedule was 96% (95% CI: 88-99), 95% (95% CI: 91-97) and 98% (95% CI: 94-99) for any DTaP-IPV/Hib, DT3aP-HBV-IPV/Hib and DT5aP-HBV-IPV-Hib, respectively. It was 97% (95% CI: 93-99) for 2 + 1, 96% (95% CI: 93-98) for 3 + 1 doses, and > 95% for the respective primary series. No differences in VE by time since vaccination were observed between products or schedules.CONCLUSIONChanges in VE against iHib after recent product or schedule changes do not explain the increasing iHib incidence. The high VE supports pursuing optimal vaccination coverage.

INTRODUCTION:With still high circulation of pertussis and risk for severe disease in young children, insight into vaccine effectiveness (VE) of infant pertussis vaccination is important. In the Netherlands, NIP period 1 corresponds to the period during which the DT3aP-IPV-Hib-HBV vaccine and the 3 + 1 dose schedule were used, and NIP period 2 to the period during which the DT5aP-IPV-Hib-HBV vaccine was used, maternal Tdap vaccination was implemented, and both the 3 + 1 and 2 + 1 dose schedules were used. We estimated the VE of full infant vaccination against pertussis. METHODS:We conducted a case-control study including all laboratory-confirmed pertussis cases aged 12-35 months, notified between 2013 and 2024, each matched to four controls by year and month of birth. Conditional logistic regression including age group and NIP period as interaction terms was used to estimate stratum-specific odds ratios (ORs) with 95% confidence intervals (CIs). We compared these estimates to those obtained by the screening method, applying logistic regression with the log-odds of the national vaccination coverage in the corresponding birth cohorts of cases as an offset. VE was calculated as (1-OR)*100 for both methods. RESULTS:We included 1156 cases and 4624 controls. Among cases, 27% were fully vaccinated, 4% partly vaccinated and 69% unvaccinated; among controls these percentages were 89%, 6% and 5% respectively. Overall VE of the case-control study was 98.2% (95% CI: 97.6-98.6). VE decreased with increasing time since vaccination (p < 0.001) and this was slightly more pronounced for NIP period 1 compared to period 2 (p < 0.001). Estimates using the screening method were slightly lower, with overall VE being 96.4% (95% CI: 95.9-96.8), but similar trends were observed. CONCLUSION:Full infant pertussis vaccination is highly effective up to 36 months of age. These findings, consistent across both methods, emphasize importance of high infant pertussis vaccination uptake.

While previous population-based studies have assessed post-acute sequelae after coronavirus disease 2019 (COVID-19), none have investigated health-related quality of life (HRQoL) and (extreme) fatigue after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the pre-vaccination era. Using a nationwide seroepidemiological study, we investigated endpoints linked to post-COVID-19 condition in the general Dutch population up to one year after infection, including symptomatic and asymptomatic infections among unvaccinated individuals early in the pandemic. Participants that were not (yet) vaccinated and aged ≥ 15 years were selected from the February 2021 round of the PIENTER Corona cohort study. We assessed associations between time since serologically-identified SARS-CoV-2 infection and health utility, mental health, physical health and fatigue. To enable comparison across the full range of each outcome, we defined cut-off points for multivariable logistic regression models at every 5

Background:The protective effect of HPV vaccination against cervical cancer has been demonstrated in registry linkage studies. The start age of screening in those studies was lower than 25 years. We estimated the vaccine effectiveness of bivalent HPV16/18 vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands where routine screening starts at age 30 years. Methods:We linked the vaccination status of women born in year 1993 who were eligible for HPV vaccination at age 16 years with histopathological results recorded in the nationwide pathology databank (Palga). Cumulative risks of invasive cervical cancer and CIN3+ were estimated for fully vaccinated (3 doses or 2 doses ≥150 days apart), partially vaccinated, and unvaccinated women. Vaccine effectiveness estimates were adjusted for differences in screening participation between the vaccine groups. Findings:A total of 103,059 women were included, of whom 47,130 were fully vaccinated, 5,098 were partially vaccinated, and 50,831 were unvaccinated. Five (0·011%) cancers were observed in fully vaccinated, two (0·039%) in partially vaccinated, and 42 (0·083%) in unvaccinated women. The vaccine effectiveness in fully vaccinated women was 91·5% (95% CI 78·9, 96·6) against cancer and 81·2% (95% CI 78·4, 83·7) against CIN3+. The vaccine effectiveness in partially vaccinated women was 48·1% (95% CI -56·8, 82·8) against cancer and 58·4% (95% CI 45·3, 68·3) against CIN3+. Interpretation:The high effectiveness of bivalent HPV vaccination against cervical cancer and CIN3+ and the low cancer incidence supports a screening start age of 30 years in vaccinated women. Research in context:Evidence before this study: We searched Pubmed and Google Scholar with the search terms ("Cervical Cancer") AND ("HPV" OR "human papillomavirus") AND ("vaccination"). Articles published in English were searched until January 2, 2025. Studies from Sweden, Denmark, and Scotland were identified linking individual vaccination, screening and cancer registry data. The start age of screening in these studies was 23-25 years. They showed a strong effectiveness in preventing cervical cancer following the introduction of bivalent and quadrivalent HPV vaccination.Added value of this study: We observed a very low absolute incidence of cervical cancer in vaccinated women and a much lower incidence of cervical cancer and CIN3+ in women vaccinated at age 16 compared with unvaccinated women, in a setting where routine screening starts at age 30. By linking the vaccination registry to the nationwide pathology databank, we were able to adjust for screening non-attendance in the incidence of cancer and CIN3+ over a 15 year period.Implications of all the available evidence: Our study supports a start age of screening of at least 30 years in women vaccinated at a young age. Avoiding screening before age 30 in these women is expected to substantially reduce the harms associated with screening and treatment.

In 2022, an increase in invasive group A streptococcal (iGAS) infections was observed in the Netherlands. A particular increase was seen among children; therefore, we aimed to assess risk factors for iGAS infection in children aged 6 months to 5 years. A prospective case-control study was conducted between February and May 2023. We approached parents of notified iGAS cases to complete a questionnaire on exposures during 4 weeks prior to disease onset. Controls were recruited via social media and matched to cases on sex and birthyear. Conditional logistic regression was performed to estimate odds ratios (OR) of exposures. For the analysis, we included 18 cases and 103 controls. Varicella prior to onset of iGAS disease was reported in two (11%) cases and one (1%) control (OR: 12.0, 95% CI: 1.1-139.0). Exposure to group A streptococcal (GAS)-like illnesses such as impetigo, pharyngitis, and scarlet fever was reported in 8 (44%) cases and 15 (15%) controls (OR: 7.1, 95% CI: 1.8-29.0). Our findings are in line with previous studies by identifying varicella as a risk factor for iGAS among young children and highlight the association with non-invasive GAS infections in the community as a possible source of transmission.

The increase in the older adult population over the coming decades emphasizes the importance of vaccinations to prevent infectious diseases among this population. Acceptance of vaccination is crucial for a successful vaccination program and insight in the motives of acceptation is therefore important. This study explores specifically the association between experiencing influenza-like illness (ILI) and other determinants for older adults on seasonal influenza vaccination acceptance. Furthermore, differences in acceptance of pneumococcal, influenza, herpes zoster and pertussis vaccines between various age groups were studied. Three prospective observational studies (2011/2012, 2012/2013 and 2014/2015) were performed in community-dwelling older adults (≥ 60 years) to monitor ILI. During home visits, throat/nose swabs, a blood sample and a questionnaire on demographics and general health were collected. An additional questionnaire was added to the 2014/2015 study on motives and intention of older adults to accept seasonal influenza and other vaccinations, including knowledge statements on vaccination in general (n = 1647). Random Forest analyses were used to identify predictors of intention to accept seasonal influenza vaccination. Univariate analyses showed that males, persons with limited contact with children, people who have received seasonal influenza vaccination in 2014/2015, persons reporting co-morbidity, persons reporting a lower perceived health and persons with more knowledge about vaccination have a significantly higher intention to accept seasonal influenza vaccination. The univariate and prediction analyses showed no association between having experienced ILI and the intention to receive seasonal influenza vaccination. Previous influenza vaccination had by far the most predictive value; when excluding this factor, age and perceived health were the best predictors. Except for pertussis vaccination, persons aged ≥ 70 years had a higher intention to vaccinate compared to persons aged 60–69 years. Our study showed that there is no association between having experienced ILI and the intention to receive seasonal influenza vaccination. Instead, previous influenza vaccination had the highest predictive value. Therefore, efforts should be made to make vaccination a habit to ensure annual vaccination. Healthcare workers, such as general practitioners (GPs) could play an important role in this because of frequent contact between older adults and GPs and the perceived importance of the advice of the GP. NTR4818 (30-09-2014).

Background:The protective effect of HPV vaccination against cervical cancer has been demonstrated in registry linkage studies. The start age of screening in those studies was lower than 25 years. We aimed to estimate the effectiveness of bivalent HPV16/18 vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands, where routine screening starts at age 30 years. Methods:We linked the vaccination status of women born in 1993 who were eligible for HPV vaccination at age 16 years with histopathological results recorded until April 1, 2024, in the nationwide pathology databank (Palga). Cumulative risks of invasive cervical cancer and CIN3+ were estimated for fully vaccinated (3 doses or 2 doses ≥150 days apart), partially vaccinated, and unvaccinated women. Cumulative risk ratios (CRRs) were adjusted for differences in screening participation between vaccine groups. Findings:A total of 103,059 women were included, of whom 47,130 were fully vaccinated, 5098 partially vaccinated, and 50,831 unvaccinated. Five cancers (0·011%) were observed in fully vaccinated, two (0·039%) in partially vaccinated, and 42 (0·083%) in unvaccinated women. The CRR for fully vaccinated women compared with unvaccinated women was 0·085 (95% confidence interval 0·025, 0·24) for cancer and 0·19 (0·16, 0·23) for CIN3+. The CRR for partially vaccinated women was 0·52 (0·12, 1·71) for cancer and 0·42 (0·30, 0·57) for CIN3+. Interpretation:The risk of cervical cancer and CIN3+ was strongly reduced in vaccinated women indicating that vaccine protection extends at least until age 30. Funding:The Dutch Ministry of Health, Welfare, and Sport.

Background:Post-COVID-19 condition (PCC) risk may have changed due to vaccination status, virus variants, prior infections, and other factors. We aimed to estimate PCC prevalence for one year in individuals infected with SARS-CoV-2 during autumn 2023, controlling for pre-infection symptoms and prevalence in recently uninfected participants. Methods:VASCO, a Dutch ongoing prospective cohort, collects three-monthly questionnaires and six-monthly SARS-CoV-2 serology. Participants indicated severity of 23 symptoms on a five-point Likert scale, and of fatigue and concentration problems on the Checklist Individual Strength. We matched participants who did with those who did not report a SARS-CoV-2 infection between September 25, 2023 and January 7, 2024, and censored follow-up time for both upon serological or antigen test evidence of infection. We estimated PCC-prevalence as the excess prevalence of at least one PCC-related symptom between matched infected and uninfected participants at 90, 180, 270, and 360 days post-infection. Additionally, participants could self-attribute long-term symptoms to SARS-CoV-2. Findings:We 1:1 matched 5621 infected to 5621 uninfected participants. The PCC prevalence, estimated as the marginal mean excess prevalence of PCC-related symptoms between infected and uninfected participants, was 0.2% (95% confidence interval: -1.9 to 2.3, p = 0.84) at 90 days, 0.5% (-1.6 to 2.6, p = 0.63) at 180 days, 0.7% (-1.3 to 2.8, p = 0.48) at 270 days, and 0.0% (-2.1 to 2.1, p = 0.99) at 360 days. Excess prevalence of new mild and severe long-term symptoms self-attributed to SARS-CoV-2 between infected and uninfected participants were both elevated at 90 days (mild: 7.2% (5.1-9.2), severe: 0.6% (0.4-0.8)) and 180 days (mild: 3.2% (2.0-4.4), severe: 0.3% (0.2-0.4)) post-infection (all p-values <0.0001), but no longer thereafter. Interpretation:This double-controlled study, incorporating pre- versus post-infection and uninfected symptom data, found a low risk of PCC among a community-dwelling adult population infected during the autumn 2023 SARS-CoV-2 wave. The prevalence of PCC-related symptoms in infected and uninfected individuals was not significantly different at 90-360 days post-infection. The excess prevalences of self-attributed long-term symptoms were elevated at 90 and 180 days post-infection but no longer from 270 days onwards. These findings suggest that the 2023 wave inferred a lower PCC risk than during the pandemic period. Funding:Funded by the Dutch Ministry of Health, Welfare and Sport.

Inleiding Maternale kinkhoestvaccinatie (MKV) beschermt zuigelingen de eerste maanden na de geboorte tegen kinkhoest. Er is weinig bekend over antistofoverdracht na ‘vroege MKV’ (20-24weken zwangerschapsduur), wat belangrijk is voor de bescherming van prematuren. Deze studie onderzocht kinkhoest-specifieke antistoffen bij 2 maanden in premature en voldragen zuigelingen na vroege MKV. Methode Vanaf 2019 kregen zwangeren een vroege MKV in studieverband of via het Rijksvaccinatieprogramma. Vanaf 2020 werden tijdig gevaccineerde vrouwen geïncludeerd, die werden opgenomen wegens een dreigende vroeggeboorte. Bloed van moeder en kind werd verzameld bij de bevalling en bij het kind op de leeftijd van 2 maanden. MKV-specifieke antistofconcentraties werden vergeleken met die van een referentie groep van voldragen zuigelingen met MKV tussen 30-33 weken zwangerschapsduur (‘late MKV’). Resultaten Na vroege MKV was de geometrische gemiddelde concentratie (GMC) van anti-Pertussis Toxine (PT) op de leeftijd van 2 maanden 14,7IU/ml (95%BI 10,6-20,4) in voldragen zuigelingen en 11,2IU/ml (95%BI 8,1-15,3) in prematuren. In voldragen zuigelingen na late MKV was dit 27,3IU/ml (95%BI 20,1-37,1). Beschouwing Premature en voldragen zuigelingen hebben na vroege MKV op de leeftijd van 2 maanden significant lagere anti-PT antistoffen dan voldragen zuigelingen na late MKV. Internationale data laten geen tekenen van minder goede bescherming van vroege MKV zien. Verder onderzoek moet uitwijzen of dit ook specifiek voor prematuren geldt.

BACKGROUND:The impact of human papillomavirus (HPV) vaccination programs depends on the degree of indirect protection against new infections achieved among unvaccinated women. We estimated the indirect effect of bivalent HPV vaccination by comparing the HPV-type incidence in unvaccinated female participants between a cohort offered vaccination in 2009/2010 and a cohort of similar-aged women offered vaccination in 2014. METHODS:We compared the incidence rates of HPV types in the HAVANA cohort (follow-up from 2010/2011 until 2015/2016) with those from the HAVANA-2 cohort (2017-2022) using two regression approaches to estimate the indirect effect of HPV vaccination. First, we calculated the incidence ratio (IRR) for a vaccine or cross-protective type in HAVANA-2 versus HAVANA by Poisson regression and compared it to the IRR for a non-cross-protective type. The indirect vaccine effect is defined as 1-ratio of the IRRs. Second, we performed Cox regression with infection by vaccine or cross-protective type as the endpoint and calculated the hazard ratio (HR) for HAVANA-2 versus HAVANA after adjusting for time-varying sociodemographic variables. The indirect effect is defined as 1-HR. RESULTS:We included 661 unvaccinated participants in HAVANA and 927 in HAVANA-2. We observed a significant reduction in incident HPV16 infections of 70.9% (95% CI 48.3-83.7%) with Poisson regression and of 73.1% (95% CI 53.3-84.5%) with Cox regression. For HPV45, significant decreases of 67.3% (95% CI 8.8-88.3%) and 69.8% (95% CI 15.2-89.3%) were observed. For HPV18, HPV31, and HPV33, the indirect effect was not statistically significant. CONCLUSIONS:Large indirect effects of the bivalent HPV vaccination program were observed for HPV16 and HPV45 infections.

We assessed the validity of serum total anti-nucleoprotein Immunoglobulin (N-antibodies) to identify SARS-CoV-2 (re)infections by estimating the persistence of N-antibody seropositivity and boosting following infection. From a prospective Dutch cohort study (VASCO), we included adult participants with ≥2 consecutive self-collected serum samples, 4-8 months apart, between May 2021-May 2023. Sample pairs were stratified by N-seropositivity of the first sample and by self-reported infection within the sampling interval. We calculated the proportions of participants with N-seroconversion and fold-increase (1.5, 2, 3, 4) of N-antibody concentration over time since infection and explored determinants. We included 67,632 sample pairs. Pairs with a seronegative first sample (70%) showed 89% N-seroconversion after reported infection and 11% when no infection was reported. In pairs with a seropositive first sample (30%), 82%-65% showed a 1.5- to 4-fold increase with a reported reinfection, and 19%-10% without a reported reinfection, respectively. After one year, 83% remained N-seropositive post-first infection and 93%-61% showed a 1.5-fold to 4-fold increase post-reinfection. Odds for seroconversion/fold increase were higher for symptomatic infections and Omicron infections. In the current era with limited antigen or PCR testing, N-serology can be validly used to detect SARS-CoV-2 (re)infections at least up to a year after infection, supporting the monitoring of COVID-19 burden and vaccine effectiveness.