Review of long-term immunogenicity following HPV vaccination: Gaps in current knowledge.

The licensed HPV vaccines are highly efficacious and induce high levels of neutralizing antibody levels, the assumed mediators of protection. However, a correlate of protection against HPV is lacking, and the evidence is still limited as to long-term persistence of antibodies, especially following reduced dosing schedules. The World Health Organization (WHO) urges immunization of young girls as part of the strategy to eliminate cervical cancer, thus long-lasting protection is required. The current review describes long-term follow-up regarding vaccine-induced seropositivity and antibody level development following the different vaccines and dosing schedules. Implications and opportunities of long-term vaccine-induced immune responses are discussed, such as the gaps in monitoring of long-term immunogenicity, the possibilities of reduced dosing schedules, and the importance of evidence for durable immunity.

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Determinants of HPV-vaccination uptake and subgroups with a lower uptake in the Netherlands.

BACKGROUND: In the Netherlands, the HPV-vaccine uptake was 52% during the 2009 catch-up campaign (birth cohorts 1993-1996). This increased to 61% in the regular immunization program (birth cohorts 2000-2001). However for birth cohorts 2003-2004 the uptake declined to 45.5%. With this study we aimed to gain insight into social, economic and cultural determinants that are associated with HPV-vaccination uptake and which subgroups with a lower HPV-vaccination uptake can be identified. In addition, we investigated whether the influence of these factors changed over time. METHODS: To study the determinants of HPV-vaccine uptake we performed a database study using different aggregation levels, i.e. individual level, postal code level and municipality level. All Dutch girls who were invited for HPV-vaccination through the National Immunization Program in the years 2012, 2014 and 2017 (i.e. birth cohorts 1999, 2001 and 2004, respectively) were included in the study population. We conducted multilevel logistic regression analyses to analyze the influence of the determinants on HPV-vaccination uptake, taking into account that the delivery of HPV-vaccine was nested within municipalities. RESULTS: Results showed that in particular having not received a MMR-vaccination, having one or two parents born in Morocco or Turkey, living in an area with lower socioeconomic status and higher municipal voting proportions for Christian political parties or populist parties with liberal-conservative views were associated with a lower HPV-vaccination uptake. Besides some changes in political preferences of the population and changes in the association between HPV uptake and urbanization level we found no clear determinants which could possibly explain the decrease in the HPV-vaccination uptake. CONCLUSIONS: In this study we identified current social, economic and cultural determinants that are associated with HPV-vaccination uptake and which low-vaccination subgroups can be identified. However, no clear determinants were found which could explain the decrease in the HPV-vaccination uptake. Tailored information and/or consultation for groups that are associated with a lower HPV-vaccination uptake might help to increase the HPV-vaccination uptake in the future.

How to increase awareness of additional vaccinations; the case of maternal pertussis vaccination.

BACKGROUND: Effective and safe vaccines are available outside national immunization programs (NIP). Increased awareness and vaccine uptake can improve public health. Before the inclusion of maternal pertussis vaccination (MPV) in the Dutch NIP in December 2019, extra communication efforts were undertaken. Here we examine the success of these efforts, investigating women's awareness of and their decision-making process regarding MPV. METHODS: Between December 2018 and January 2019, one year before the introduction of MPV in the NIP, and about three years after MPV was recommended by the Dutch Health Council, pregnant and non-pregnant women (i.e. child younger than two years) were invited to fill out an online questionnaire. Participant's decision-making processes regarding MPV were assessed with an adapted Precaution Adoption Process Model (PAPM), including stages of awareness, engagement, information-seeking, and vaccination behaviour. Furthermore, factors related to the decision-making process were examined. RESULTS: In total, 942 women were included, of whom 62% were non-pregnant. Most of the pregnant and nonpregnant women were aware of MPV during pregnancy (respectively 69 and 56%). Most aware women had heard about MPV through their midwife and the Public Health Institute (PHI) website. Women unaware of MPV reported a need for information, preferably from their midwives. Most aware women felt MPV was important to them (88%) and were classified as "engaged". Of the eligible and "engaged" pregnant women, 58% were vaccinated, versus 38% of "engaged" non-pregnant women. CONCLUSIONS: As the most preferred and trusted source of information, midwives are essential to increasing awareness of MPV. The PHI website is considered to be a reliable information source and is often consulted. To increase awareness, appropriate healthcare workers should be encouraged to actively inform target groups about available, additional vaccinations.

Impact and effectiveness of the 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children under 5 years of age in the Netherlands.

BACKGROUND: In 2011, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) in the Netherlands. We report on impact and effectiveness against invasive pneumococcal disease (IPD) in children aged under 5 years by switching from PCV7 to PCV10. METHOD: We included IPD cases between 2004 and 2019 in children aged < 5 years reported via the national surveillance system. To assess the impact of the PCV10 vaccination program we compared IPD incidence 6-8 years after PCV10 introduction (2017-2019) to the two years just before the switch to PCV10 (2009-2011). We estimated vaccine effectiveness (VE) using the indirect cohort method, comparing vaccination status (at least two vaccine doses) in IPD-cases caused by PCV10 serotypes (cases) to non-PCV10 IPD cases (controls), in children eligible for PCV10. RESULTS: The overall incidence decreased from 8.7 (n = 162) in 2009-2011 to 7.3 per 100.000 (n = 127) in 2017-2019 (Incidence rate ratio (IRR) 0.83, 95%CI: 0.66; 1.05). IPD caused by the additional serotypes included in PCV10 declined by 93% (IRR 0.07, 95%CI: 0.02; 0.23). Incidence of non-PCV10 IPD showed a non-significant increase (IRR 1.25, 95%CI: 0.96; 1.63). Among 231 IPD-cases eligible for PCV10, the overall VE was 91% (95%CI: 67; 97) and did not differ by sex or age at diagnosis. Effectiveness against non-PCV10 serotype 19A IPD was non-significant with an estimate of 28% (95%CI:-179; 81). CONCLUSION: PCV10 is highly effective in protecting against IPD in Dutch children under 5 years with limited serotype replacement after switching from PCV7 to PCV10. We found no evidence for significant cross-protection of PCV10 against 19A serotype IPD.

[National Immunisation Programme: is vaccinating less an option?] / Rijksvaccinatieprogramma: is minder vaccineren een optie?

Many people are no longer familiar with the diseases that are part of the Dutch National Immunisation Programme (NIP). The protection given by the NIP has ensured that these diseases, most of them serious, have largely disappeared. The NIP has developed gradually, but in retrospect it was in 1957 that what we now know as the NIP started. Over the years, the NIP has gradually expanded to include various vaccines such as live attenuated vaccines, conjugate vaccines and vaccines that offer protection against chronic viral infections. Currently, the NIP offers protection against twelve different diseases. Occasionally the Netherlands still sees minor outbreaks of those diseases included in the NIP programme, generally among non-vaccinated people. It is important that the NIP is retained; stopping vaccination always leads to the return of the disease. The question is: can good protection be maintained with fewer injections? This subject is on the agenda of the Health Council Of The Netherlands for discussion in 2022.

Measuring vaccine effectiveness against persistent HPV infections: a comparison of different statistical approaches.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is endorsed by the World Health Organization as an intermediate endpoint for evaluating HPV vaccine effectiveness/efficacy. There are different approaches to estimate the vaccine effectiveness/efficacy against persistent HPV infections. METHODS: We performed a systematic literature search in Pubmed to identify statistical approaches that have been used to estimate the vaccine effectiveness/efficacy against persistent HPV infections. We applied these methods to data of a longitudinal observational study to assess their performance and compare the obtained vaccine effectiveness (VE) estimates. RESULTS: Our literature search identified four approaches: the conditional exact test for comparing two independent Poisson rates using a binomial distribution, Generalized Estimating Equations for Poisson regression, Prentice Williams and Peterson total time (PWP-TT) and Cox proportional hazards regression. These approaches differ regarding underlying assumptions and provide different effect measures. However, they provided similar effectiveness estimates against HPV16/18 and HPV31/33/45 persistent infections in a cohort of young women eligible for routine HPV vaccination (range VE 93.7-95.1% and 60.4-67.7%, respectively) and seemed robust to violations of underlying assumptions. CONCLUSIONS: As the rate of subsequent infections increased in our observational cohort, we recommend PWP-TT as the optimal approach to estimate the vaccine effectiveness against persistent HPV infections in young women. Confirmation of our findings should be undertaken by applying these methods after longer follow-up in our study, as well as in different populations.

[No scientific lower threshold for compulsory vaccination]. / Geen wetenschappelijke ondergrens voor verplicht vaccineren.

The national vaccination rate in young children in the Netherlands has decreased in recent years. This has led to social and political discussions, for instance about compulsory vaccination for children in child-care. The national commission on child-care and vaccination has advised that vaccination should be made compulsory when the rate of vaccination has declined to a pre-determined lower threshold, to be determined by the government. A frequently quoted lower threshold is 95%. The idea behind this is the concept of a critical vaccination rate, a threshold needed for elimination of an infection in a large, well-mixed population. In this article we argue why the critical vaccination rate does not offer a scientific basis for a lower threshold to the national vaccination rate.

[Introduction of pertussis vaccination during pregnancy]. / Invoering van een kinkhoestvaccinatie voor zwangeren.

Pertussis is an endemic disease in the Netherlands. In order to protect infants under 6 months of age, women can be vaccinated during pregnancy with a DTaP(-IPV) booster vaccine. After this so-called maternal vaccination, pertussis antibodies are passed through the placenta to the unborn child, who will be protected after birth. The vaccine is offered as a part of the national vaccination programme (Rijksvaccinatieprogramma, RVP) since 16 December 2019. Children of maternally vaccinated women will follow a different vaccination schedule, namely the 3-5-11-months schedule. This schedule change applies to the DTaP-IPV-HiB-HepB combination vaccine and the 10-valent pneumococcal (PCV10) vaccine. High-risk groups and children of unvaccinated mothers will follow the 2-3-5-11 months schedule. Maternal vaccination is offered from 22 weeks of gestation in the Netherlands. This timing is logistically feasible. We have seen that women already got themselves actively vaccinated during pregnancy before the inclusion of the vaccine in the RVP.

Effect of vaccination on severity and infectiousness of measles during an outbreak in the Netherlands, 2013-2014.

An outbreak of measles in the Netherlands in 2013-2014 provided an opportunity to assess the effect of MMR vaccination on severity and infectiousness of measles.Measles is notifiable in the Netherlands. We used information on vaccination, hospitalisation, complications, and most likely source(s) of infection from cases notified during the outbreak. When a case was indicated as a likely source for at least one other notified case, we defined it as infectious. We estimated the age-adjusted effect of vaccination on severity and infectiousness with logistic regression.Of 2676 notified cases, 2539 (94.9%) were unvaccinated, 121 (4.5%) were once-vaccinated and 16 (0.6%) were at least twice-vaccinated; 328 (12.3%) cases were reported to have complications and 172 (6.4%) cases were hospitalised. Measles in twice-vaccinated cases led less often to complications and/or hospitalisation than measles in unvaccinated cases (0% and 14.5%, respectively, aOR 0.1 (95% CI 0-0.89), P = 0.03). Of unvaccinated, once-vaccinated and twice-vaccinated cases, respectively, 194 (7.6%), seven (5.1%) and 0 (0%) were infectious. These differences were not statistically significant (P > 0.05).Our findings suggest a protective effect of vaccination on the occurrence of complications and/or hospitalisation as a result of measles and support the WHO recommendation of a two-dose MMR vaccination schedule.

Comparison of antibody response between boys and girls after infant and childhood vaccinations in the Netherlands.

BACKGROUND: Infectious diseases can differ by sex in their incidence, prevalence, or severity of disease. These differences may be induced by sex-dependent immune responses and resulting protection, for example after vaccination. Therefore, this study aims to assess possible sex-differences in immunoglobulin levels (IgG) after infant and childhood vaccination. METHODS: Data from a national cross-sectional serosurvey conducted in 2006/2007 were used (Pienter 2). We compared IgG levels against measles, mumps, rubella, diphtheria, tetanus, poliomyelitis, pertussis, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup C (MenC) between girls and boys both short term (1 month to 1 year) and long term (1-3 year) after infant and childhood vaccinations, using linear regression analysis. Proportions of boys and girls reaching a protective IgG level were compared using Fishers exact test. RESULTS: Differences in IgG were found at specific time points after vaccination against measles, mumps, rubella, MenC, and polio. The geometric mean concentration or titer (GMC/T) girls:boys ratios ranged between 1.10 for polio type 1 <1 year after the first childhood booster to 1.90 for MenC <1 year after infant vaccination, indicating higher antibody levels in girls. No significant differences were found between boys and girls for diphtheria, tetanus, pertussis, and Hib at either time point. Proportions with protective levels differed only at 1-3 years after infant vaccination for mumps (82.5% boys vs. 91.9% girls, p = 0.046), and at the same time point for MenC (7.0% boys vs. 18.2% girls, p = 0.015), and polio type 1 (87.8% boys vs. 95.9% girls, p = 0.047). CONCLUSION: Differences in IgG between boys and girls were generally small and not consistent, neither between pathogens nor within pathogens. If differences were observed, girls were favored over boys. On the whole, the results suggest that there are no major sex differences in protection from the studied pathogens in the Netherlands.

Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus vaccination strategies in a high-income, low-endemic setting.

BACKGROUND AND OBJECTIVE: Since 2013, a biennial rotavirus pattern has emerged in the Netherlands with alternating high and low endemic years and a nearly 50% reduction in rotavirus hospitalization rates overall, while infant rotavirus vaccination has remained below 1% throughout. As the rotavirus vaccination cost-effectiveness and risk-benefit ratio in high-income settings is highly influenced by the total rotavirus disease burden, we re-evaluated two infant vaccination strategies, taking into account this recent change in rotavirus epidemiology. METHODS: We used updated rotavirus disease burden estimates derived from (active) surveillance to evaluate (1) a targeted strategy with selective vaccination of infants with medical risk conditions (prematurity, low birth weight, or congenital conditions) and (2) universal vaccination including all infants. In addition, we added herd protection as well as vaccine-induced intussusception risk to our previous cost-effectiveness model. An age- and risk-group structured, discrete-time event, stochastic multi-cohort model of the Dutch pediatric population was used to estimate the costs and effects of each vaccination strategy. RESULTS: The targeted vaccination was cost-saving under all scenarios tested from both the healthcare payer and societal perspective at rotavirus vaccine market prices (€135/child). The cost-effectiveness ratio for universal vaccination was €51,277 at the assumed vaccine price of €75/child, using a societal perspective and 3% discount rates. Universal vaccination became cost-neutral at €32/child. At an assumed vaccine-induced intussusception rate of 1/50,000, an estimated 1707 hospitalizations and 21 fatal rotavirus cases were averted by targeted vaccination per vaccine-induced intussusception case. Applying universal vaccination, an additional 571 hospitalizations and <  1 additional rotavirus death were averted in healthy children per vaccine-induced intussusception case. CONCLUSION: While universal infant rotavirus vaccination results in the highest reductions in the population burden of rotavirus, targeted vaccination should be considered as a cost-saving alternative with a favorable risk-benefit ratio for high-income settings where universal implementation is unfeasible because of budget restrictions, low rotavirus endemicity, and/or public acceptance.

No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls.

INTRODUCTION: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue. METHODS: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014 (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined. RESULTS: The cohort consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and 16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07-5.49). CONCLUSIONS: Fatigue ≥6 m and 3-6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.

Quantifying the impact of mass vaccination programmes on notified cases in the Netherlands.

Vaccination programmes are considered a main contributor to the decline of infectious diseases over the 20th century. In recent years, the national vaccination coverage in the Netherlands has been declining, highlighting the need for continuous monitoring and evaluation of vaccination programmes. Our aim was to quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands. We collected and digitised previously unavailable monthly case notifications of diphtheria, poliomyelitis, mumps and rubella in the Netherlands over the period 1919-2015. Poisson regression models accounting for seasonality, multi-year cycles, secular trends and auto-correlation were fit to pre-vaccination periods. Cases averted were calculated as the difference between observed and expected cases based on model projections. In the first 13 years of mass vaccinations, case notifications declined rapidly with 82.4% (95% credible interval (CI): 74.9-87.6) of notified cases of diphtheria averted, 92.9% (95% CI 85.0-97.2) cases of poliomyelitis, and 79.1% (95% CI 67.1-87.4) cases of mumps. Vaccination of 11-year-old girls against rubella averted 49.9% (95% CI 9.3-73.5) of cases, while universal vaccination averted 68.1% (95% CI 19.4-87.3) of cases. These findings show that vaccination programmes have contributed substantially to the reduction of infectious diseases in the Netherlands.

High Effectiveness of the Bivalent Human Papillomavirus (HPV) Vaccine Against Incident and Persistent HPV Infections up to 6 Years After Vaccination in Young Dutch Women.

Background: Monitoring vaccine effectiveness (VE) in vaccination programs is of importance for assessing the impact of immunization. This study aimed to estimate the VE of the bivalent human papillomavirus (HPV) vaccine against incident and 12-month persistent infections up to 6 years after vaccination. Methods: In 2009-2010, girls eligible for the vaccination catch-up campaign (ie, those aged 14-16 years) were enrolled into a prospective cohort. Annually, participants completed a questionnaire and submitted a self-collected vaginal swab sample for HPV testing by the SPF10-LiPA25 assay. We compared sociodemographic characteristics and infection rates between vaccinated and unvaccinated girls. The VE was adjusted for characteristics related to HPV vaccination status. We used combined end points for VE estimation. Results: In total, 1635 women, of whom 54% were fully vaccinated, were included for VE estimation. The adjusted VE against HPV16 and 18 persistent infections amounted to 97.7% (95% confidence interval [CI], 83.5%-99.7%). We found a VE against HPV31, 33, and 45 persistent infections of 61.8% (95% CI, 16.7%-82.5%). We found no indications that the protection against vaccine or cross-protective types changes over time. Conclusion: Our findings of nearly full protection against vaccine-type persistent infections and significant cross-protection to nonvaccine types in a population-based cohort study confirm the effectiveness of the bivalent HPV vaccine as estimated in trials. We found no indications for waning protection up to 6 years after vaccination.

Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands.

BACKGROUND: The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the impact of PCVs on community-acquired pneumonia (CAP) hospitalization rates in all age-groups. METHODS: A time series analysis using Poisson regression was performed on 155,994 CAP hospitalizations. Hospitalization rates were calculated using the total number of hospitalizations as denominator. The time trend in the pre-PCV period (1999-2006) was extrapolated to predict the hospitalization rate in the post-PCV period (2006-2014) if PCV had not been implemented. Rate ratios over time were calculated by comparing observed and predicted time trends. RESULTS: In children <5 years of age, the observed hospitalization rates during the post-PCV period were significantly lower than predicted if PCV had not been implemented (0-6 months: 0.62, 95% CI: 0.41-0.96; 6 months - 1 year: 0.67, 95% CI: 0.50-0.90; 2-4 years: 0.78, 95% CI: 0.61-0.97). In all other age-groups, rate ratios declined over time but did not reach statistical significance. CONCLUSIONS: After introduction of PCV, CAP hospitalizations declined in young children but no clear impact of PCV on CAP hospitalizations was seen in other age-groups.

Severe underestimation of pertussis related hospitalizations and deaths in the Netherlands: A capture-recapture analysis.

OJECTIVE: Despite vaccination, pertussis has remained endemic, sometimes leading to severe disease. We aimed to quantify the completeness of reporting (CoR) of pertussis hospitalizations and deaths in the Netherlands. STUDY DESIGN: CoR was estimated using capture-recapture analyses. Hospitalizations (2007-2014) from the National Registration Hospital Care (hospital data) were matched to the notifiable Infectious Disease case registry (notifications) providing (month and) year of birth, gender and postal code. Deaths (1996-2014) from Statistics Netherlands (death registry) were matched to notifications using gender, age, year of death and notification date. Cases <2years (y) and ≥2y were analysed separately. Chao's estimator estimated the total population, which was used to calculate CoR. RESULTS: Using strict matching criteria, we found 461 matches among 876 (hospital data) and 757 (notifications) hospitalizations <2y. The population estimate of hospitalized infants was 1446, resulting in CoR between 52% and 61%. For hospitalizations ≥2y (246; hospital data and 264; notifications) 43 matches were found, with a population estimate of 1512 and CoR between 16.5% and 22%. Among thirteen (death registry) and eight (notifications) deaths <2y, seven cases overlapped. The population estimate was 16. CoR of the two sources was 50-81%. With two (death registry) and eight (notifications) deaths ≥2y without overlap, the population estimate was 26 and CoR 8-31%. CONCLUSION: Results showed substantial underestimation of pertussis hospitalizations and deaths. This has to be taken into account in evaluation of current and future immunization programs.

Vaccine preferences and acceptance of older adults.

BACKGROUND: Expanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination. METHODS: A discrete choice experiment was conducted to generate choice data that was analyzed using a mixed multinomial logit statistical model. RESULTS: Important factors that were associated with vaccination acceptance in older adults are high mortality risk of the infectious disease, high susceptibility of getting the infectious disease, and high vaccine effectiveness. Age, influenza vaccination in 2013 and self-perceived health score were identified as personal factors that affect vaccine preference. Potential vaccination rates of older adults were estimated at 68.1% for pneumococcal vaccination, 58.1% for herpes zoster vaccination, 53.9% for pertussis vaccination and 54.3% for influenza vaccination. For persons aged 50-65, potential vaccination rates were estimated at 58.1% for pneumococcal vaccination, 49.5% for herpes zoster vaccination, 43.9% for pertussis vaccination and 42.2% for influenza vaccination. For persons aged 65 and older, these were respectively 76.2%, 67.5%, 57.5% and 65.5%. DISCUSSION: Our results suggest that older adults are most likely to accept pneumococcal vaccination of the four vaccines. Information provision accompanied with the implementation of a new vaccine has to be tailored for the individual and the vaccine it concerns. Special attention is needed to ensure high uptake among persons aged 50-65years.

Performance of a bedside test for tetanus immunity: results of a cross-sectional study among three EDs in the Netherlands in 2012-2013.

INTRODUCTION: Despite sustained high vaccination coverage and a national guideline by the Health Council (HC-guideline) on tetanus postexposure prophylaxis (T-PEP), tetanus sporadically occurs in the Netherlands. This study aims to assess the added value of a bedside test for tetanus immunity (Tetanos Quick Stick (TQS); Ingen BioSciences Group, France), in the context of routine T-PEP in two adult cohorts: those born before introduction of tetanus toxoid vaccination in the National Immunization Programme (NIP) in 1957 (pre-NIP-cohort; n=196) and those born after (NIP-cohort; n=405). METHODS: Adults included at the time of visiting one of three participating EDs received T-PEP as per routine recommendations. Subsequently, a nurse performed the TQS and filled in a questionnaire. We compared the indication for T-PEP based on TQS results with those based on the HC-guideline and with actually administration of T-PEP, stratified by cohort. RESULTS: Among the pre-NIP and NIP-cohort, 16% and 9%, respectively, received T-PEP, while this was not indicated based on the HC-guideline. Furthermore, 8% and 7%, respectively, did not get T-PEP, although it was indicated by the guideline. Comparing the indication derived from the HC-guideline with TQS result found that 22% (pre-NIP-cohort) and 8% (NIP-cohort) were not eligible for T-PEP according to the HC-guideline but had a negative TQS. Conversely, 36% (pre-NIP-cohort) and 73% (NIP-cohort) were eligible for T-PEP according to the HC-guideline but had positive TQS, indicating sufficient tetanus protection. CONCLUSION: Use of the TQS would allow better targeting of T-PEP. Furthermore, stricter adherence to the HC-guideline can prevent overimmunisation and decrease the risk of tetanus.

[Infection prevention in newborns through maternal vaccination: current insights and developments]. / Infectiepreventie bij zuigelingen door maternale vaccinatie.

- In the first few months of life, newborns are vulnerable to infections.- Vaccination of the pregnant mother leads to transplacental antibody transfer, resulting in the best possible protection of the newborn.- Maternal vaccination has long been given for the prevention of tetanus in developing countries, and for the prevention of pertussis and influenza in developed countries, such as the United States, England and Belgium. These vaccinations give newborns good protection and, to date, no adverse effects are known for the foetus or the pregnancy.- Currently, phase 3 trials during pregnancy are ongoing following maternal vaccination against group B streptococci and respiratory syncytial virus. Here, again, no risks to mother or child have been reported.- Recently, the Dutch Health Council advised that all pregnant women in the Netherlands be vaccinated against pertussis in a vaccination programme.- This paper gives an overview of effectiveness, safety and practicalities of maternal vaccination.