Publications by authors named "Hester E de Melker"

144 Publications

Associations between measures of social distancing and SARS-CoV-2 seropositivity: a nationwide population-based study in the Netherlands.

Clin Infect Dis 2021 Mar 27. Epub 2021 Mar 27.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan, MA Bilthoven, the Netherlands.

This large nationwide population-based seroepidemiological study provides evidence on the effectiveness of physical distancing (>1.5m) and indoor group size reductions on SARS-CoV-2 infection. Additionally, young adults may play an important role in viral spread, opposed to children up until 12 years of age with whom close contact is permitted.
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http://dx.doi.org/10.1093/cid/ciab264DOI Listing
March 2021

Impact of physical distancing measures against COVID-19 on contacts and mixing patterns: repeated cross-sectional surveys, the Netherlands, 2016-17, April 2020 and June 2020.

Euro Surveill 2021 02;26(8)

Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.

BackgroundDuring the COVID-19 pandemic, many countries have implemented physical distancing measures to reduce transmission of SARS-CoV-2.AimTo measure the actual reduction of contacts when physical distancing measures are implemented.MethodsA cross-sectional survey was carried out in the Netherlands in 2016-17, in which participants reported the number and age of their contacts the previous day. The survey was repeated among a subsample of the participants in April 2020, after strict physical distancing measures were implemented, and in an extended sample in June 2020, after some measures were relaxed.ResultsThe average number of community contacts per day was reduced from 14.9 (interquartile range (IQR): 4-20) in the 2016-17 survey to 3.5 (IQR: 0-4) after strict physical distancing measures were implemented, and rebounded to 8.8 (IQR: 1-10) after some measures were relaxed. All age groups restricted their community contacts to at most 5, on average, after strict physical distancing measures were implemented. In children, the number of community contacts reverted to baseline levels after measures were eased, while individuals aged 70 years and older had less than half their baseline levels.ConclusionStrict physical distancing measures greatly reduced overall contact numbers, which likely contributed to curbing the first wave of the COVID-19 epidemic in the Netherlands. However, age groups reacted differently when measures were relaxed, with children reverting to normal contact numbers and elderly individuals maintaining restricted contact numbers. These findings offer guidance for age-targeted measures in future waves of the pandemic.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.8.2000994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908067PMC
February 2021

Persistence of antibodies to SARS-CoV-2 in relation to symptoms in a nationwide prospective study.

Clin Infect Dis 2021 Feb 24. Epub 2021 Feb 24.

Centre for Immunology of Infectious Diseases and Vaccines , National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Background: Assessing the duration of immunity following infection with SARS-CoV-2 is a first priority to gauge the degree of protection following infection. Such knowledge is lacking especially in the general population. Here, we studied changes in Immunoglobulin (Ig) isotype seropositivity and IgG binding strength of SARS-CoV-2-specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample.

Methods: Participants from a prospective representative serological study in the Netherlands were included based on IgG seroconversion to the Spike S1 protein of SARS-CoV-2 (N=353), with up to three consecutive serum samples per seroconverted participant (N=738). IgM, IgA and IgG antibody concentrations to S1, and increase in IgG avidity in relation to time since onset of disease symptoms, were determined.

Results: While SARS-CoV-2-specific IgM and IgA antibodies declined rapidly after the first month post onset of disease, specific IgG was still present in 92% (95% confidence interval, CI, 89-95) of the participants after 7 months. The estimated 2-fold decrease of IgG antibodies was 158 days (95% CI 136-189). Concentrations sustained better in persons reporting significant symptoms compared to asymptomatic persons or those with mild upper respiratory complaints only. Similarly, avidity of IgG antibodies for symptomatic persons showed a steeper increase over time compared with persons with mild or no symptoms (p=0.022).

Conclusion: SARS-CoV-2-specific IgG antibodies persist and show increasing avidity over time, indicative of underlying immune maturation. These data support development of immune memory against SARS-CoV-2 providing insight into protection of the general unvaccinated part of the population.
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http://dx.doi.org/10.1093/cid/ciab172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929058PMC
February 2021

Short term impact of the COVID-19 pandemic on incidence of vaccine preventable diseases and participation in routine infant vaccinations in the Netherlands in the period March-September 2020.

Vaccine 2021 02 6;39(7):1039-1043. Epub 2021 Jan 6.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands.

We aimed to assess the impact of the COVID-19 pandemic on the incidence of vaccine-preventable diseases (VPDs) and participation in the routine infant vaccination programme in the Netherlands. The incidence of various VPDs initially decreased by 75-97% after the implementation of the Dutch COVID-19 response measures. The participation in the first measles-mumps-rubella vaccination among children scheduled for vaccination in March-September 2020 initially dropped by 6-14% compared with the previous year. After catch-up vaccination, a difference in MMR1 participation of -1% to -2% still remained. Thus, the pandemic has reduced the incidence of several VPDs and has had a limited impact on the routine infant vaccination programme.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787078PMC
February 2021

Immunogenicity, duration of protection, effectiveness and safety of rubella containing vaccines: A systematic literature review and meta-analysis.

Vaccine 2021 Feb 14;39(6):889-900. Epub 2021 Jan 14.

National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control (Cib), Bilthoven, the Netherlands.

Background: Rubella containing vaccines (RCV) prevent rubella virus infection and subsequent congenital rubella syndrome (CRS). To update the evidence on immunogenicity, duration of protection, effectiveness and safety of RCV, we conducted a systematic literature review.

Methods: We searched EMBASE and SCOPUS, using keywords for rubella vaccine in combination with immunogenicity (seroconversion and seropositivity), duration of protection, efficacy/effectiveness, and safety. Original research papers involving at least one dose of RCV (at any age), published between 1-1-2010 and 17-5-2019 were included. Where appropriate, meta-analyses were performed. Quality of included studies was assessed using GRADE methodology.

Results: We included 36 papers (32 randomized controlled trials (RCTs) and 4 observational studies) on immunogenicity (RA27/3 strain) in children and adolescent girls, 14 papers (5 RCTs and 9 observational studies) on duration of protection, one paper on vaccine effectiveness (VE) (BRDII strain), and 74 studies on safety, including three on safety in pregnancy. Meta-analysis of immunogenicity data showed 99% seroconversion (95% CI: 98-99%) after a single dose of RCV in children, independent of co-administration with other vaccines. Seroconversion after RCV1 below 9 months of age (BRDII strain, at 8 months) was 93% (95% CI: 92-95%). For duration of protection, the included studies showed a seropositivity of 88%-100% measured 1-20 years after one or two RCV doses. The single study on VE of BRDII strain, reported 100% VE after one and two doses. Among 34,332 individuals participating in the RCTs, 140 severe adverse events (SAEs) were reported as possibly related to RCV. Among the case reports on SAEs, the association with RCV was confirmed in one report (on fulminant encephalitis). Among 3,000 pregnant women who were inadvertently vaccinated, no SAEs were reported.

Conclusions: One and two doses of RCV are highly immunogenic for a long period of time, effective in preventing rubella and CRS, and safe.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.079DOI Listing
February 2021

Background incidence rates of adverse pregnancy outcomes in the Netherlands: Data of 2006-2018.

Eur J Obstet Gynecol Reprod Biol 2021 Jan 25;256:274-280. Epub 2020 Nov 25.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

Objective: Maternal vaccination is an effective and safe intervention to protect newborns against infectious diseases shortly after birth. We assessed background rates of adverse pregnancy outcomes before the implementation of a maternal pertussis immunisation programme in the Netherlands, to put into perspective the safety concerns about such outcomes following immunisation.

Study Design: In this retrospective cross-sectional study, annual numbers of pregnancy outcomes derived from the Dutch Perinatal Registry were used to calculate incidence rates per 10,000 in the 2006-2018 period. Births of ≥500 g birth weight and ≥24 + 0 w gestational age were included. Trends with moving-average-lines over the past 3 years were plotted, with 95 % confidence interval.

Results: From 2006 through 2018, yearly numbers of pregnancies ranged between 158,868-175,710. Numbers of newborns ranged between 161,307-178,874, of whom 160,838-178,177 were live-born. Most outcomes were stable over time. Between 2006-2011, occurrence of labour induction increased by 68 %, and postpartum hemorrhage increased by 25 %. Both stabilised from 2011 onwards. Perinatal mortality up to day 7 or 28 postpartum decreased by 38 % and 37 %, respectively. Occurrence of low Apgar score among preterm infants born before 37 + 0 w gestational age and among term infants increased by 19 % and 27 %, respectively.

Conclusion: Our study on background incidences showed notable increases over time in occurrence of labour induction, postpartum hemorrhage and low Apgar score, while showing a considerable decrease in overall perinatal mortality. These findings should be considered when interpreting data on adverse events occurring since the maternal pertussis immunisation programme was implemented.
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http://dx.doi.org/10.1016/j.ejogrb.2020.11.064DOI Listing
January 2021

Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in The Netherlands: Cross-Protective and Second-Order Herd Effects.

Clin Infect Dis 2021 Mar;72(5):e103-e111

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

Background: Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage.

Methods: We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform.

Results: A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6-14.5]), heterosexual men (13.0% per year [95% CI, 8.3-17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9-7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women).

Conclusions: Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.
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http://dx.doi.org/10.1093/cid/ciaa1770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935392PMC
March 2021

Nationwide seroprevalence of SARS-CoV-2 and identification of risk factors in the general population of the Netherlands during the first epidemic wave.

J Epidemiol Community Health 2020 Nov 28. Epub 2020 Nov 28.

Centre for Infectious Disease Control, RIVM, Bilthoven, Netherlands

Background: We aimed to detect SARS-CoV-2 serum antibodies in the general population of the Netherlands and identify risk factors for seropositivity amidst the first COVID-19 epidemic wave.

Methods: Participants (n=3207, aged 2-90 years), enrolled from a previously established nationwide serosurveillance study, provided a self-collected fingerstick blood sample and completed a questionnaire (median inclusion date 3 April 2020). IgG antibodies targeted against the spike S1-protein of SARS-CoV-2 were quantified using a validated multiplex-immunoassay. Seroprevalence was estimated controlling for survey design, individual pre-pandemic concentration, and test performance. Random-effects logistic regression identified risk factors for seropositivity.

Results: Overall seroprevalence in the Netherlands was 2.8% (95% CI 2.1 to 3.7), with no differences between sexes or ethnic background, and regionally ranging between 1.3 and 4.0%. Estimates were highest among 18-39 year-olds (4.9%), and lowest in children 2-17 years (1.7%). Multivariable analysis revealed that persons taking immunosuppressants and those from the Orthodox-Reformed Protestant community had over four times higher odds of being seropositive compared to others. Anosmia/ageusia was the most discriminative symptom between seropositive (53%) and seronegative persons (4%, p<0.0001). Antibody concentrations in seropositive persons were significantly higher in those with fever or dyspnoea in contrast to those without (p=0.01 and p=0.04, respectively).

Conclusions: In the midst of the first epidemic wave, 2.8% of the Dutch population was estimated to be infected with SARS-CoV-2, that is, 30 times higher than reported. This study identified independent groups with increased odds for seropositivity that may require specific surveillance measures to guide future protective interventions internationally, including vaccination once available.
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http://dx.doi.org/10.1136/jech-2020-215678DOI Listing
November 2020

Changes in HPV Seroprevalence from an Unvaccinated toward a Girls-Only Vaccinated Population in the Netherlands.

Cancer Epidemiol Biomarkers Prev 2020 Nov 20;29(11):2243-2254. Epub 2020 Aug 20.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Background: In the Netherlands, bivalent human papillomavirus (HPV) vaccination was included in the National Immunization Program for 12-year-old girls in 2010 (vaccination coverage, 45%-60%). We examined possible changes in HPV seroprevalence in the HPV-unvaccinated Dutch population aged 0-89 years, comparing prevaccination data with data of approximately 6 years after implementation of national vaccination.

Methods: Serum samples of men and women were used from two cross-sectional population-based serosurveillance studies performed before (2006-07, = 6,384) and after (2016-17, = 5,645) implementation of HPV vaccination in the Netherlands. Seven high-risk HPV-specific antibodies (HPV16, 18, 31, 33, 45, 52, and 58) were tested in a virus-like particle-based multiplex immunoassay.

Results: Type-specific HPV seroprevalence increased in women between 2006-07 and 2016-17. Also, a higher seroprevalence for at least one type in women >15 years was found in 2016-17 (31.7%) compared with 2006-07 (25.2%). In men, overall HPV seroprevalence remained similar; however, a lower seroprevalence was found for HPV16 in 2016-17 (7.5%) compared with 2006-07 (10.6%).

Conclusions: Our results indicate an increase in high-risk HPV types in women and a rather stable exposure in men. No clear effects of the strategy of girls-only vaccination were observed in men, probably because of the short time after introduction combined with suboptimal coverage.

Impact: No herd immunity has been observed yet in a population with suboptimal HPV vaccination coverage.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0596DOI Listing
November 2020

Social-psychological determinants of maternal pertussis vaccination acceptance during pregnancy among women in the Netherlands.

Vaccine 2020 09 8;38(40):6254-6266. Epub 2020 Aug 8.

TNO Child Health, Netherlands Organization for Applied Scientific Research, P.O. Box 3005, 2316 ZL Leiden, the Netherlands.

Background: Maternal Pertussis Vaccination (MPV) during pregnancy became part of the National Immunization Program in the Netherlands late 2019. This study aims to identify social-psychological factors associated with MPV acceptance among Dutch women to add to the current understanding of vaccine hesitancy worldwide, and to inform the development of communication and information campaigns about MPV.

Methods: We conducted a cross-sectional study using an online survey among 611 women (174 pregnant women, 205 women who had given birth in the past two years and 232 women of 20-35 years old). The primary and secondary outcomes were vaccination intention and attitude towards MPV, respectively. Pearson's correlation and regression analyses were used to examine social-psychological and socio-demographic determinants of the outcomes.

Results: Vaccination intention was most explained by attitudes towards MPV, beliefs about safety, moral norm and the belief about the effectiveness of MPV (R = 0.79). Other factors associated were injunctive norm, anticipated regret of vaccinating, and decisional certainty. Attitudes towards MPV were further explained by descriptive norm, risk perceptions of side effects, and risk perceptions of the baby getting pertussis when not vaccinating, and fear of MPV and of the disease (R = 0.76). Finally, pregnant women had a significantly lower intention and less positive attitude towards MPV than non-pregnant women.

Conclusions: Communication about MPV should address the most important determinants of MPV intention and attitude, i.e. beliefs about safety and effectiveness and moral norms. Furthermore, such information may benefit from taking into account affective feelings of pregnant women such as anticipated regret and fear towards MPV. Further research could explore this. The timing of communication about MPV can be important as determinants of MPV acceptance may vary depending on pregnancy status.
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http://dx.doi.org/10.1016/j.vaccine.2020.07.047DOI Listing
September 2020

Measles vaccination in infants younger than 9 months.

Lancet Infect Dis 2020 04;20(4):403

National Institute for Public Health and the Environment, Bilthoven 3720, Netherlands. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30135-3DOI Listing
April 2020

High varicella zoster virus susceptibility in Caribbean island populations: Implications for vaccination.

Int J Infect Dis 2020 May 26;94:16-24. Epub 2020 Feb 26.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3720 MA Bilthoven, The Netherlands. Electronic address:

Objectives: Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN).

Methods: Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0-90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model.

Results: Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households.

Conclusions: VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions.
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http://dx.doi.org/10.1016/j.ijid.2020.02.047DOI Listing
May 2020

High seroprevalence of multiple high-risk human papillomavirus types among the general population of Bonaire, St. Eustatius and Saba, Caribbean Netherlands.

Vaccine 2020 03 19;38(13):2816-2826. Epub 2020 Feb 19.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Background: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on lifetime cumulative HPV exposure and contributing risk factors, but has not been available yet for Caribbean Netherlands (CN), comprising the islands Bonaire, St. Eustatius and Saba. Therefore, a cross-sectional population-based serosurveillance study was performed in this (recently girls-only HPV-vaccinated) population in 2017.

Methods: Blood samples from participants (n = 1,823, 0-90 years) were tested for seven high-risk (hr)-HPV-specific IgG-antibodies using a VLP-based multiplex-immunoassay. Risk factors for HPV-seropositivity were analysed among persons unvaccinated aged ≥ 15 years who ever had sex (n = 1,080).

Results: Among unvaccinated individuals aged ≥ 15 years, overall seropositivity was high (34%), with over half of them being seropositive for ≥ 2 hr-HPV types, and HPV16 and 52 being most prevalent (13%). Seroprevalence was substantial higher in unvaccinated women (51%) than men (18%), predominantly peaking in women aged 20-59 years, and was highest on St. Eustatius (38%). Besides age and sex, sexual risk factors were associated with HPV-seropositivity.

Conclusions: In accordance with the Caribbean region, seroprevalence of multiple hr-HPV types was high in CN. These data corroborate the decision regarding introduction of a sex-neutral HPV-vaccination program and the relevance for considering a population-based cervical cancer screening program.
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http://dx.doi.org/10.1016/j.vaccine.2020.02.017DOI Listing
March 2020

Is there an association between socioeconomic status and immune response to infant and childhood vaccination in the Netherlands?

Vaccine 2020 04 14;38(18):3480-3488. Epub 2020 Feb 14.

National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Introduction: Socioeconomic status (SES) is a well-known determinant of health, but its relation with vaccine-induced immunity is less documented. We explored the association between SES and immunoglobulin G (IgG) levels against vaccine-preventable diseases in vaccinated children in the Dutch National Immunization Programme.

Methods: Data from a population-wide cross-sectional serosurvey in the Netherlands (2006-2007) were used. We compared geometric mean IgG concentrations/titers (GMC/T ratios) against measles, mumps, rubella, Haemophilus influenzae type b (Hib), Neisseria meningococcus type C, diphtheria, tetanus, poliovirus types 1,2,3 and pertussis in children of high versus low SES by linear regression analysis. We included 894 children (0-12 years) at one of two timeframes: 1 month to 1 year, or 1-3 years after vaccination. Mother's educational level and net household income served as binary indicators of SES.

Results: Of 58 possible associations of vaccine-induced antibody responses with educational level and 58 with income, 10 (9%) were statistically significant: 2 favouring (that is, with higher IgG levels at) high educational level (for Hib 1 m-1y after vaccination (GMC/T ratio: 2.99, 95%CI: 1.42-6.30) and polio 2 1 m-1y after the 9-year booster dose (1.14, 1.01-1.27)) and 8 favouring low income (polio 1, 2 and 3 1 m-1y after the 11-month booster (0.74, 0.58-0.94; 0.79, 0.64-0.97; 0.72, 0.55-0.95), polio 3 and pertussis 1-3y after the 11-month booster (0.70, 0.56-0.88; pertussis-prn: 0.60, 0.37-0.98; pertussis-ptx: 0.66, 0.47-0.95), mumps and rubella 1-3y after first vaccination (0.73, 0.55-0.97; 0.70, 0.55-0.90), and rubella 1 m-1y after second vaccination (0.83, 0.55-0.90)). After adjustment for multiple testing, none of the differences remained significant. There was no association between SES and proportion of children with protective IgG levels.

Conclusion: In this explorative study, we found no consistent association between SES and immune response to vaccination in the Netherlands and no association with protective IgG levels. Additional studies in other settings should confirm this finding.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.071DOI Listing
April 2020

Persisting Antibody Response 9 Years After Bivalent Human Papillomavirus (HPV) Vaccination in a Cohort of Dutch Women: Immune Response and the Relation to Genital HPV Infections.

J Infect Dis 2020 05;221(11):1884-1894

Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294 unvaccinated girls (1993-1994) who provide a vaginal self-swab sample, serum sample, and questionnaire yearly, we report a high, persisting antibody response up to 9 years after vaccination for vaccine types HPV-16 or HPV-18. Antibodies against nonvaccine HPV types 31, 33, 45, 52, and 58 were lower but still significantly higher than in unvaccinated individuals. This was also reflected in the seroprevalence. We compared participant characteristics and antibody levels between vaccinated women with and those without HPV infections 1 year before infection (204 incident and 64 persistent infections), but we observed no consistent difference in type-specific antibody levels. Having a high-risk HPV infection was associated with sexual risk behavior and smoking 1 year before infection. Although high antibody levels are necessary for protection, our study suggests that on the individual level other factors such as HPV exposure or antibody avidity could be important.
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http://dx.doi.org/10.1093/infdis/jiaa007DOI Listing
May 2020

Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness.

BMC Infect Dis 2019 Oct 29;19(1):919. Epub 2019 Oct 29.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, PObox 1, 3720BA, Bilthoven, The Netherlands.

Background: Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history.

Methods: Medical record data of 0-2y old patients hospitalized for pertussis during 2005-2014 were linked to vaccination data. Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course. We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington.

Results: Of 1187 records, medical data from 676 were retrieved. Of these, 12% concerned preterms, whereas they are 8% of Dutch birth cohorts. Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001). Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01). Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU). Preterms had longer ICU stays (15d vs 9d; p = 0.004). Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated. After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms. Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93-96%) and 73% (95% CI 20-91%) in terms and preterms, respectively. Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively).

Conclusions: Infants hospitalized for pertussis suffer from severe disease. Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination. These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.
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http://dx.doi.org/10.1186/s12879-019-4563-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820906PMC
October 2019

Evaluation of the surveillance system for invasive meningococcal disease (IMD) in the Netherlands, 2004-2016.

BMC Infect Dis 2019 Oct 17;19(1):860. Epub 2019 Oct 17.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Postbus 1, 3720 BA, Bilthoven, The Netherlands.

Background: Enhanced surveillance for confirmed cases of invasive meningococcal disease (IMD) was introduced in the Netherlands in 2003, in which reference laboratory data (NRLBM) are linked with notification data (OSIRIS). The quality of surveillance information is important for public health decision making. Our objective was to describe the system and evaluate it for data completeness and timeliness.

Methods: Cases reported in the surveillance system from 2004 to 2016 were included. For the notification data, we used information on serogroup, vaccination status, mortality, and country of infection as indicators for record completeness. Notification times to regional and national level were calculated using the reported dates available in the notification database.

Results: A total of 2123 cases were reported in the years 2004-2016, of which 1.968 (93%) were reported by the reference laboratory and 1.995 (94%) in the notification system. Of all cases, 1.840 cases (87%) were reported in both systems and could be linked. The serogroup was known in 86% of the notified cases, and was significantly higher (94%) in the years 2013-2016. Information on vaccination status, mortality and country of infection was available in 88, 99 and 97% of notified cases, respectively. Regional notification of cases occurred within one working day for 86% of cases and 98% were notified nationally within three days.

Conclusions: A well performing IMD surveillance system was demonstrated and serogroup completeness has improved over the years. Underlining the need for reporting to both the clinical and laboratory surveillance system remains important to further improve the overall performance in supporting public health response and vaccination policy.
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http://dx.doi.org/10.1186/s12879-019-4513-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796335PMC
October 2019

Seroepidemiology of Measles, Mumps and Rubella on Bonaire, St. Eustatius and Saba: The First Population-Based Serosurveillance Study in Caribbean Netherlands.

Vaccines (Basel) 2019 Oct 1;7(4). Epub 2019 Oct 1.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3720 MA Bilthoven, The Netherlands.

The National Immunization Program (NIP) on Bonaire, St. Eustatius and Saba (i.e., Caribbean Netherlands (CN)) includes the measles-mumps-rubella (MMR) vaccine since 1988/89. Seroepidemiological data is an important tool to evaluate the NIP, hence a cross-sectional representative population-based serosurveillance study was conducted for the first time in CN in mid-2017. Participants ( = 1829, aged 0-90 years) donated a blood sample and completed a health-related questionnaire. MMR-specific IgG antibodies were determined using a bead-based multiplex immunoassay and risk factors were analyzed using logistic regression models. Overall seroprevalence was high for measles (94%), but lower for mumps and rubella (both 85%). In NIP eligibles, including women of childbearing age, rubella seroprevalence (88%) exceeded the threshold for protection (85%); however, for measles (89%) this protective level (95%) was not met. MMR seropositivity was lowest in children who became CN resident at 11-17 years of age (especially for measles (72%)), mostly originating from Latin America and other non-Western countries. Interestingly, rubella seroprevalence was lowest in non-NIP eligible adults from Dutch overseas territories and Suriname (75%). Taken together, MMR immunity is generally good in CN, nonetheless some risk groups were identified. Additionally, we found evidence for a unique island epidemiology. In light of recent regional measles outbreaks, disease monitoring remains of utmost importance.
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http://dx.doi.org/10.3390/vaccines7040137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963433PMC
October 2019

Long-term HPV-specific immune response after one versus two and three doses of bivalent HPV vaccination in Dutch girls.

Vaccine 2019 11 28;37(49):7280-7288. Epub 2019 Sep 28.

Center for Infectious Disease Control, National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, 3720 MA Bilthoven, the Netherlands.

Background: In view of further reduction of HPV vaccination schedules, gaining more insight into humoral and cellular immune responses after a single HPV vaccine is of great interest. Therefore, these responses were evaluated after different doses of the bivalent (2v) HPV-vaccine in girls.

Methods: Blood was collected yearly up to seven years post-vaccination with one-, two- or three-doses of the 2vHPV vaccine (N = 890). HPV-type-specific IgG and IgA-antibody levels, IgG-isotypes and avidity indexes were measured by a virus-like-particle-based multiplex-immuno-assay for two vaccine and five non-vaccine HPV types. HPV-type-specific memory B-cell numbers- and T-cell cytokine responses were determined in a subpopulation.

Results: HPV-type-specific antibody concentrations were significantly lower in one- than in two- and three-dose vaccinated girls but remained stable over seven years. The lower antibody response coincided with reduced HPV-type-specific B- and T-cell responses. There were no differences in both the IgG subtypes and the avidity of the HPV16-specific antibodies between the groups.

Conclusions: One-dose of the 2vHPV vaccine is immunogenic, but results in less B- and T-cell memory and considerable lower antibody responses when compared with more doses. Therefore, at least of some of girls receiving the one-dose of the vaccination might be at higher risk for waning immunity to HPV in the long-term.
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http://dx.doi.org/10.1016/j.vaccine.2019.09.066DOI Listing
November 2019

The Clinical Picture and Severity of Invasive Meningococcal Disease Serogroup W Compared With Other Serogroups in the Netherlands, 2015-2018.

Clin Infect Dis 2020 05;70(10):2036-2044

Centre for Infectious Disease Control Netherlands (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven.

Background: An increase in invasive meningococcal disease (IMD) serogroup W (IMD-W) cases caused by sequence type-11 clonal complex (cc11) was observed from October 2015 in the Netherlands. We compared the clinical picture and disease outcome of IMD-W cases with other serogroups, adjusting for host characteristics.

Methods: We included IMD cases reported from January 2015 to June 2018 in the Netherlands and assessed clinical manifestation and symptoms at disease onset and calculated case fatality rates (CFRs). We used logistic regression to compare clinical manifestations and mortality of IMD-W with IMD caused by meningococci serogroup B, Y, or C, adjusting for age, gender, and comorbidities.

Results: A total of 565 IMD cases were reported, of which 204 were IMD-W, 270 IMD-B, 63 IMD-Y, and 26 IMD-C. Most IMD-W isolates belonged to cc11 (93%; 175/188). Compared with other serogroups, IMD-W patients were diagnosed more often with septicemia (46%) or pneumonia (12%) and less often with meningitis (17%, P < .001). IMD-W cases presented more often with respiratory symptoms (45%, P < .001); 16% of IMD-W patients presented with diarrhea without IMD-specific symptoms (P = .061). The CFR for IMD-W was 16% (32/199, P < .001). The differences between IMD-W and other serogroups remained after adjusting for age, gender, and comorbidities.

Conclusions: The atypical presentation and severe outcome among IMD-W cases could not be explained by age, gender, and comorbidities. Almost all our IMD-W cases were caused by cc11. More research is needed to identify the bacterial factors involved in clinical presentation and severity of IMD-W cc11.
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http://dx.doi.org/10.1093/cid/ciz578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201410PMC
May 2020

Effect of measles vaccination in infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis.

Lancet Infect Dis 2019 11 20;19(11):1246-1254. Epub 2019 Sep 20.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands. Electronic address:

Background: Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses.

Methods: For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines.

Findings: Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96-99; I=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89-100; I=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low.

Interpretation: Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain.

Funding: WHO.
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http://dx.doi.org/10.1016/S1473-3099(19)30396-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838663PMC
November 2019

Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis.

Lancet Infect Dis 2019 11 20;19(11):1235-1245. Epub 2019 Sep 20.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands. Electronic address:

Background: Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months.

Methods: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.

Findings: Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33-0·66; I=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low.

Interpretation: MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity.

Funding: WHO.
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http://dx.doi.org/10.1016/S1473-3099(19)30395-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838664PMC
November 2019

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease.

Vaccine 2019 10 6;37(43):6558-6565. Epub 2019 Sep 6.

Centre for Infectious Disease Control Netherlands (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Electronic address:

Introduction: In 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes.

Methods: Pneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype.

Results: Compared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016-2018 in children <5 years (69%), 18-49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016-2018 declined in children <5 years (RR:0.68, 95%CI:0.42-1.11), 5-17 year olds (RR:0.58, 95%CI:0.29-1.14) and 18-49 year olds (RR:0.72, 95%CI:0.57-0.90), but not in 50-64 year olds (RR:0.94, 95%CI:0.81-1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93-1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70-0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96-1.36).

Conclusion: Twelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes.
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http://dx.doi.org/10.1016/j.vaccine.2019.08.025DOI Listing
October 2019

Risk of Measles and Diphtheria Introduction and Transmission on Bonaire, Caribbean Netherlands, 2018.

Am J Trop Med Hyg 2019 07;101(1):237-241

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

Endemic transmission of measles has been reestablished in Venezuela, and outbreaks of diphtheria remain ongoing across Latin America (LA). Hence, a large cross-sectional population-based serosurveillance study was conducted on Bonaire, one of the Dutch Leeward Antilles, to assess specific age and population groups at risk. Participants (aged 0-90 years) donated a blood sample and completed a questionnaire ( = 1,129). Antibodies against measles and diphtheria were tested using bead-based multiplex immunoassays. Our data revealed that immunity against measles is suboptimal, especially for those aged less than 5 years from Suriname, Aruba, and former Dutch Antilles (SADA), and adolescents from LA; and against diphtheria for persons aged more than 30 years, particularly among females and residents from SADA and LA. As refugees arrive persistently, health authorities on the Dutch Leeward Antilles should be on alert to detect early cases and prevent subsequent transmission. Ultimately, there is an urgent need for serosurveillance studies in the Caribbean region.
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http://dx.doi.org/10.4269/ajtmh.18-0824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609202PMC
July 2019

Disease burden of varicella versus other vaccine-preventable diseases before introduction of vaccination into the national immunisation programme in the Netherlands.

Euro Surveill 2019 May;24(18)

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.

IntroductionEstimating burden of disease (BoD) is an essential first step in the decision-making process on introducing new vaccines into national immunisation programmes (NIPs). For varicella, a common vaccine-preventable disease, BoD in the Netherlands was unknown.AimTo assess national varicella BoD and compare it to BoD of other vaccine-preventable diseases before their introduction in the NIP.MethodsIn this health estimates reporting study, BoD was expressed in disability-adjusted life years (DALYs) using methodology from the Burden of Communicable Diseases in Europe (BCoDE)-project. As no parameters/disease model for varicella (including herpes zoster) were available in the BCoDE toolkit, incidence, disease progression model and parameters were derived from seroprevalence, healthcare registries and published data. For most other diseases, BoD was estimated with existing BCoDE-parameters, adapted to the Netherlands if needed.ResultsIn 2017, the estimated BoD of varicella in the Netherlands was 1,800 (95% uncertainty interval (UI): 1,800-1,900) DALYs. Herpes zoster mainly contributed to this BoD (1,600 DALYs; 91%), which was generally lower than the BoD of most current NIP diseases in the year before their introduction into the NIP. However, BoD for varicella was higher than for rotavirus gastroenteritis (1,100; 95%UI: 440-2,200 DALYs) and meningococcal B disease (620; 95%UI: 490-770 DALYs), two other potential NIP candidates.ConclusionsWhen considering the introduction of a new vaccine in the NIP, BoD is usually estimated in isolation. The current approach assesses BoD in relation to other vaccine-preventable diseases' BoD, which may help national advisory committees on immunisation and policymakers to set vaccination priorities.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.18.1800363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505181PMC
May 2019

Cost-effectiveness of screening for chronic hepatitis B and C among migrant populations in a low endemic country.

PLoS One 2018 8;13(11):e0207037. Epub 2018 Nov 8.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

Background: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective.

Methods: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed.

Results: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections.

Conclusions: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207037PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224111PMC
April 2019

Persistence of immune response following bivalent HPV vaccination: A follow-up study among girls routinely vaccinated with a two-dose schedule.

Vaccine 2018 11 28;36(49):7580-7587. Epub 2018 Oct 28.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

Background: In this cohort study, we examined antibody levels and avidity after a two-dose schedule (0, 6 months) of the bivalent HPV-vaccine in girls routinely vaccinated in the Dutch HPV-vaccination program, up to 2 years following vaccination.

Methods: A blood sample at 7, 12 and 24 months after the first dose and questionnaire data were collected (n = 56). HPV type-specific antibody concentrations (lU/ml) against seven types (HPV16/18/31/33/45/52/58) were assessed using a validated virus-like particles (VLP) multiplex immunoassay. Avidity was tested using a modification of this assay.

Results: Seropositivity for vaccine types HPV 16 and 18 was 100% up to month 24, but declined for HPV-types 31/33/45/52/58, although not statistically significant for HPV45. All Geometric Mean Concentrations (GMCs) declined by months 12 and 24, but remained high for HPV16/18. Between month 7 and 12, GMCs declined more for other types. High avidity antibodies were induced up to 24 months for vaccine types (75%, 76-78% and 81-82% at months 7, 12 and 24, respectively), but for other types antibody avidity was 16-29% at month 7, 20-32% at month 12 and 19-32% at month 24.

Conclusions: GMCs declined over time for HPV-types 16/18/31/33/45/52/58, but remained high for vaccine-types HPV16/18 up to 24 months of follow-up. Antibody avidity was >75% for vaccine types but <35% for other HPV-types. Further follow-up of this cohort will provide insight into antibody and avidity kinetics over time.
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http://dx.doi.org/10.1016/j.vaccine.2018.10.018DOI Listing
November 2018

Systematically Developing a Web-Based Tailored Intervention Promoting HPV-Vaccination Acceptability Among Mothers of Invited Girls Using Intervention Mapping.

Front Public Health 2018 28;6:226. Epub 2018 Sep 28.

Child Health, Netherlands Organization for Applied Scientific Research (TNO), Leiden, Netherlands.

Currently, the eHealth field calls for detailed descriptions of theory-based interventions in order to support improved design of such interventions. This article aims to provide a systematic description of the design rationale behind an interactive web-based tailored intervention promoting HPV-vaccination acceptability. The 6-step Intervention Mapping (IM) protocol was used to describe the design rationale. After the needs assessment in Step 1, intervention objectives were formulated in Step 2. In Step 3, we translated theoretical methods into practical applications, which were integrated into a coherent intervention in Step 4. In Step 5, we anticipated future implementation and adoption, and finally, an evaluation plan was generated in Step 6. Walking through the various steps of IM resulted in a detailed description of the intervention. The needs assessment indicated HPV-vaccination uptake remaining lower than expected. Mothers play the most important role in decision-making about their daughter's immunization. However, they generally feel ambivalent after they made their decisions, and their decisions are based on rather unstable grounds. Therefore, intervention objectives were to improve HPV-vaccination uptake and informed decision-making, and to decrease decisional conflict among mothers of invited girls. Computer-tailoring was chosen as the main method; virtual assistants were chosen as a practical application to deliver interactive tailored feedback. To maximize compatibility with the needs of the target group, a user-centered design strategy by means of focus groups and online experiments was applied. In these, prototypes were tested and sequentially refined. Finally, efficacy, effectiveness, and acceptability of the intervention were tested in a randomized controlled trial. Results showed a significant positive effect of the intervention on informed decision-making, decisional conflict, and nearly all determinants of HPV-vaccination uptake ( < 0.001). Mothers evaluated the intervention as highly positive. Using IM led to an innovative effective intervention for promoting HPV-vaccination acceptability. The intervention maps will aid in interpreting the results of our evaluation studies. Moreover, it will ease the comparison of design rationales across interventions, and may provide leads for the development of other eHealth interventions. This paper adds to the plea for systematic reporting of design rationales constituting the process of developing interventions.
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http://dx.doi.org/10.3389/fpubh.2018.00226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190841PMC
September 2018

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

Ned Tijdschr Geneeskd 2018 09 20;162. Epub 2018 Sep 20.

Centrum Infectieziektebestrijding, RIVM, Bilthoven, Nederland.

Objective: To quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands.

Design: Estimates based on model projections of historical morbidity data.

Method: 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.

Results: In the first 13 years of mass vaccinations, case notifications declined rapidly with 18,900 (95%-CI: 12,000-28,600) notified cases of diphtheria averted, 5100 (95%-CI: 2200-13,500) cases of poliomyelitis, and 1800 (95%-CI: 1000-3200) cases of mumps. Vaccination of 11-year-old girls against rubella averted 13700 (95%-CI: 1400-38,300) cases, while universal rubella vaccination averted 700 (95%-CI: 80-2300) cases.

Conclusion: These findings show that vaccination programmes have contributed substantially to the reduction of infectious diseases in the Netherlands.
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September 2018