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

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013.

Background and aimsThe Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25-1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.

Dutch national immunization schedule: compliance and associated characteristics for the primary series.

In the Netherlands, the recommended priming immunization schedule for diphtheria, tetanus, pertussis and polio (DTaP-IPV) is at 2, 3 and 4 months of age. We evaluated the compliance with the recommended schedule, as well as its characteristics. We included all infants born between 2007 and 2012 who received minimally one DTaP-IPV vaccination (n = 1,061,578). Infants complied with the schedule if they received the first vaccination between 6 and 9 weeks of age, and the second and third vaccination 2-6 weeks after the first and second vaccination. We examined associations between compliance and several characteristics using log-binomial regression. Compliance for the first, second and third vaccination was 81.6, 88.3 and 84.2%, respectively. Compliance with the total recommended schedule was 64.5%, and increased from 60.1% for 2007 to 68.5% for 2012. Compliance was higher for full-term infants (65.9%), infants with normal birth weight (66.0%) and when both parents were born in the Netherlands (66.8%). CONCLUSION: Delayed vaccination during the primary vaccination schedule occurs in one sixth of the Dutch children. Efforts to improve compliance should be focused in particular on preterm infants, infants with low birth weight and infants whose parents are not born in the Netherlands. What is Known: • A delayed start of vaccination leads to a longer period at risk for infectious diseases, e.g. pertussis • Delayed vaccination is associated with several factors including prematurity, low birth weight, family size, birth order, low socioeconomic status and health status of the child What is New: • Compliance with the recommended priming immunization schedule for diphtheria, tetanus, pertussis and polio was 64.5%, and increased from 60.1% for 2007 to 68.5% for 2012 • If the first vaccination was delayed, there was a higher chance that the following vaccinations were administered 'out-of-schedule' as well, resulting in even a higher age at second and third vaccination.

Negative attitude and low intention to vaccinate universally against varicella among public health professionals and parents in the Netherlands: two internet surveys.

BACKGROUND: Prior to introduction of universal varicella vaccination, it is crucial to gain insight into the willingness to vaccinate among the population. This is because suboptimal national vaccination coverage might increase the age of infection in children, which will lead to higher complication rates. We studied the attitude and intention to vaccinate against varicella among Dutch public health professionals who execute the National Immunisation Programme (NIP), and parents. METHODS: Medical doctors and nurses of regional public health services (RPHS) and child health clinics (CHC), and a random sample of parents received an internet survey on varicella vaccination. Separate logistic regression models were used to identify determinants for a positive attitude (professionals) or a positive intention (parents) to vaccinate against varicella within the NIP (free of charge). RESULTS: The questionnaire was completed by 181 RPHS professionals (67%), 260 CHC professionals (46%), and 491 parents (33%). Of professionals, 21% had a positive attitude towards universal varicella vaccination, while 72% preferred to limit vaccination to high-risk groups only. Of parents, 28% had a positive intention to vaccinate their child against varicella within the NIP. The strongest determinant for a positive attitude or intention to vaccinate against varicella among professionals and parents was the belief that varicella is a disease serious enough to vaccinate against. CONCLUSIONS: We showed that a majority of the Dutch public health professionals and parents in this study have a negative attitude or low intention to vaccinate universally against varicella, as a result of the perceived low severity of the disease. Most participating professionals support selective vaccination to prevent varicella among high-risk groups.

Vaccination coverage for measles, mumps and rubella in anthroposophical schools in Gelderland, The Netherlands.

BACKGROUND: Social clustering of unvaccinated children in anthroposophical schools occurs, as inferred from various measles outbreaks that can be traced to these schools. However, accurate vaccination coverage data of anthroposophical schools are not widely available. METHODS: In 2012, we performed a survey to estimate the vaccination coverage in three different grades of 11 anthroposophical schools in Gelderland, The Netherlands. We also gauged the opinion on childhood vaccination of the parents and compared these with the results of a national survey. In 2014, we were also able to obtain the registered total vaccination coverage per school from the national vaccination register to compare this with our survey data. RESULTS: The self-reported MMR vaccination coverage (2012) in the three grades of the schools in our study was 83% (range 45-100% per school). The registered total vaccination coverage (2014) was 78% (range 59-88% per school). The 95% confidence intervals of the two different vaccination coverages overlap for all schools. The parents in this study were less convinced about the beneficial effect of vaccinations and more worried about the possible side effects of vaccination compared with parents in general. CONCLUSION: Despite high overall vaccination coverage, the WHO goal to eliminate measles and rubella will not easily be achieved when social clustering of unvaccinated children in anthroposophical schools remains.

Vaccine uptake determinants in The Netherlands.

BACKGROUND: Combining existing data on background characteristics with data from immunization registers might give insight into determinants of vaccine uptake, which can help to improve communication strategies and invitation policy of National Immunisation Programmes. METHODS: The study population consisted of children born in 2005 as registered in the Dutch national immunization register Præventis. A hierarchical logistic regression model was used to quantify associations between individual vaccination status and proxy variables for ethnic background (individual level), socio-economic status (postcode level) and religious objection to vaccination (municipal level). RESULTS: Most children whose both parents were not born in The Netherlands had a somewhat lower full vaccine uptake, for example, children whose both parents were born in Turkey [odds ratio = 0.7 (0.6-0.8)] or in Morocco [odds ratio = 0.8 (0.7-0.9)]. The partial uptake was also relatively high (3.7-8.0%) compared with children whose both parents were born in The Netherlands (3.1%). Municipalities with higher religious objection to vaccination and postcode areas with lower socio-economic status were also associated with a lower full uptake. CONCLUSIONS: Despite the high vaccination coverage in The Netherlands, we were able to identify determinants of vaccine uptake by combining existing data sets. This might be an example for other countries. The impact of ethnic background and socio-economic status is not as well known in The Netherlands as the effect of religious objection to vaccination, and deserves more attention. Groups that have a relatively high partial uptake deserve special attention because they do not reject vaccination in general.

Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013.

BACKGROUND: Vaccine uptake within the Dutch National Immunisation Programme (NIP) has slightly declined since the COVID-19 pandemic. We studied psychosocial factors of vaccine uptake, namely parental intention, attitudes, beliefs, trust and deliberation (i.e., self-evidence), before (2013) and two years into the pandemic (2022). METHODS: In 2022 and 2013, parents with a young child (aged < 3.5 years) participated in online surveys on vaccination (n = 1000 and 800, (estimated) response = 12.2 % and 37.2 %, respectively). Psychosocial factors were measured on 7-point Likert scales. Multivariate logistic regression analysis was used to study differences between parents in 2022 and 2013 in 'negative' scores (≤2) of psychosocial factors. RESULTS: In both 2022 and 2013, most parents with a young child expressed positive intention (2022 = 83.1 %, 2013 = 87.0 %), attitudes (3 items: 2022 = 66.7 %-70.9 %, 2013 = 62.1 %-69.8 %) and trust (2022 = 51.8 %, 2013 = 52.0 %) towards the NIP and considered vaccinating their child as self-evident (2022 = 57.2 %, 2013 = 67.3 %). Compared to parents in 2013, parents in 2022 had significantly higher odds of reporting negative attitudes towards vaccination (3 items combined: OR = 2.84, 95 % CI = 1.09, 7.37), believing that vaccinations offer insufficient protection (OR = 4.89, 95 % CI = 3.19, 7.51), that the NIP is not beneficial for the protection of their child's health (OR = 2.23, 95 % CI = 1.15, 4.35), that vaccinating their child does not necessarily protect the health of other children (OR = 2.24, 95 % CI = 1.16, 4.33) or adults (OR = 2.22, 95 % CI = 1.32, 3.75) and that vaccinations could cause severe side effects (OR = 2.20, 95 % CI = 1.35, 3.58), preferring natural infection over vaccination (OR = 3.18, 95 % CI = 2.24, 4.51) and reporting low trust towards the NIP (OR = 1.73, 95 % CI = 1.08, 2.79). CONCLUSIONS: Although most parents had positive intention, attitudes and trust towards vaccination and perceived vaccinating their child as self-evident, proportions of parents with negative scores were slightly larger in 2022 compared to 2013. Monitoring these determinants of vaccine uptake and developing appropriate interventions could contribute to sustaining high vaccine uptake.

Assessment of vaccine candidates for persons aged 50 and older: a review.

BACKGROUND: The increasing life expectancy in most European countries has resulted in growth of the population 50 and older. This population is more susceptible to infectious diseases because of immunosenescence, co-morbidity and general frailty. Thus, to promote healthy aging, vaccination against vaccine-preventable-diseases could be one strategy. In addition to its possible individual benefits, vaccination may also yield social benefits, such as a lower overall cost of healthcare. Most European countries, however, offer only influenza vaccine although vaccines for pneumococcal disease, herpes zoster, pertussis, and hepatitis A are also available. Our aim is to review the knowledge of these vaccines for persons aged 50 and older and explore the arguments for expanding current vaccination programmes beyond just influenza. METHODS: The evaluation model of Kimman et al. was used to assess herpes zoster, pneumococcal disease, pertussis and hepatitis A in terms of four domains: pathogen, vaccine, disease outcomes and cost-effectiveness. The sources were Dutch surveillance systems, seroprevalence studies and the international literature. RESULTS: Herpes zoster, pneumococcal disease and pertussis are prevalent among persons aged 50 and older. Vaccines vary in effectiveness and have mild and self-limiting side effects. Vaccination against pneumococcal disease and pertussis causes adaptation of the responsible pathogen. For pertussis and hepatitis A, the vaccine is not registered specifically for the elderly population. Vaccination against herpes zoster and pertussis could improve quality of life, while vaccination against pneumococcal disease and hepatitis A prevents mortality. However, only vaccination against herpes zoster and pneumococcal disease appear to be cost-effective. CONCLUSIONS: Vaccination can improve the health of the elderly population. As our review shows, however, the data are too incomplete to accurately judge its potential impact. More research is needed to determine how vaccination can most effectively improve the health of the growing population 50 years and older.

The impact of demographic change on the estimated future burden of infectious diseases: examples from hepatitis B and seasonal influenza in the Netherlands.

BACKGROUND: For accurate estimation of the future burden of communicable diseases, the dynamics of the population at risk - namely population growth and population ageing - need to be taken into account. Accurate burden estimates are necessary for informing policy-makers regarding the planning of vaccination and other control, intervention, and prevention measures. Our aim was to qualitatively explore the impact of population ageing on the estimated future burden of seasonal influenza and hepatitis B virus (HBV) infection in the Netherlands, in the period 2000-2030. METHODS: Population-level disease burden was quantified using the disability-adjusted life years (DALY) measure applied to all health outcomes following acute infection. We used national notification data, pre-defined disease progression models, and a simple model of demographic dynamics to investigate the impact of population ageing on the burden of seasonal influenza and HBV. Scenario analyses were conducted to explore the potential impact of intervention-associated changes in incidence rates. RESULTS: Including population dynamics resulted in increasing burden over the study period for influenza, whereas a relatively stable future burden was predicted for HBV. For influenza, the increase in DALYs was localised within YLL for the oldest age-groups (55 and older), and for HBV the effect of longer life expectancy in the future was offset by a reduction in incidence in the age-groups most at risk of infection. For both infections, the predicted disease burden was greater than if a static demography was assumed: 1.0 (in 2000) to 2.3-fold (in 2030) higher DALYs for influenza; 1.3 (in 2000) to 1.5-fold (in 2030) higher for HBV. CONCLUSIONS: There are clear, but diverging effects of an ageing population on the estimated disease burden of influenza and HBV in the Netherlands. Replacing static assumptions with a dynamic demographic approach appears essential for deriving realistic burden estimates for informing health policy.

Hospitalization due to varicella in the Netherlands.

BACKGROUND: In the Netherlands, incidence of physician's consultations and hospitalizations for varicella is low compared to other countries. Better knowledge about the severity of varicella among Dutch hospitalized patients is needed. Therefore, a medical record research was conducted among hospitalized patients with diagnosis varicella. METHODS: Hospital admissions due to varicella in 2003-2006 were obtained from the National Medical Register. Retrospectively, additional data were retrieved from the medical record of patients hospitalized with varicella in 23 Dutch hospitals using a standardized form. Analyses were performed using descriptive statistics. RESULTS: The study population (N = 296) was representative for all varicella admissions in the Netherlands (N = 1,658) regarding age, sex, duration of admission and type of diagnosis. Complications were recorded in 76% of the patients (37% had at least one relatively severe complication). Bacterial super infections of skin lesions (28%), (imminent) dehydration (19%), febrile convulsions (7%), pneumonia (7%) and gastroenteritis (7%) were most frequently reported. No varicella-related death occurred within the study population and 3% of the patients had serious rest symptoms. CONCLUSIONS: It is not likely that the severity of varicella among hospitalized patients in the Netherlands differs from other countries. A considerable part of the varicella complications among hospitalized patients was rather moderate and can be treated effectively, although in a third of the hospitalized cases with complications, severe complications occurred. These data are relevant in the decision-making process regarding whether or not to introduce routine varicella vaccination in the Netherlands.

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.

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.

Assessing the potential effects and cost-effectiveness of programmatic herpes zoster vaccination of elderly in the Netherlands.

BACKGROUND: Herpes zoster (HZ) is a painful disease affecting a considerable part of the elderly. Programmatic HZ vaccination of elderly people may considerably reduce HZ morbidity and its related costs, but the extent of these effects is unknown. In this article, the potential effects and cost-effectiveness of programmatic HZ vaccination of elderly in the Netherlands have been assessed according to a framework that was developed to support evidence-based decision making regarding inclusion of new vaccines in the Dutch National Immunization Program. METHODS: An analytical framework was used combining a checklist, which structured relevant data on the vaccine, pathogen and disease, and a cost-effectiveness analysis. The cost-effectiveness analysis was performed from a societal perspective, using a Markov-cohort-model. Simultaneous vaccination with influenza was assumed. RESULTS: Due to the combination of waning immunity after vaccination and a reduced efficacy of vaccination at high ages, the most optimal cost-effectiveness ratio (21716 euro per QALY) for HZ vaccination in the Netherlands was found for 70-year olds. This estimated ratio is just above the socially accepted threshold in the Netherlands of 20000 euro per QALY. If additional reduction of postherpetic neuralgia was included, the cost-effectiveness ratio improved (approximately 10000 euro per QALY) but uncertainty for this scenario is high. CONCLUSIONS: Vaccination against HZ at the age of 70 years seems marginally cost-effective in the Netherlands. Due to limited vaccine efficacy a considerable part of the disease burden caused by HZ will remain, even with optimal acceptance of programmatic vaccination.

MenACWY vaccination campaign for adolescents in the Netherlands: Uptake and its determinants.

BACKGROUND: Between 2015 and 2018 the incidence of meningococcal disease serogroup W increased tenfold in the Netherlands with the highest case fatality among adolescents and young adults. In 2018-2019 a national mass vaccination campaign, with recall after non-attendance, was implemented targeting 14-18-years old adolescents. This study estimated the MenACWY-vaccine uptake and investigated its determinants. METHODS: The uptake before the start of the vaccination campaign was estimated from the number of vaccines administered by Municipal Health Services and dispensed by public pharmacies, and within the campaign from the national vaccination register. Possible determinants of uptake after the first invitation and recall were investigated among the first group invited for vaccination (born in May-December 2004) using random forest classification analysis. RESULTS: The uptake was 86% (of which 1.9% before the campaign) among all eligible adolescents and 88% among the first group invited, including 5% uptake achieved after the recall. The most important predictor of vaccination after the first invitation was parents' country of birth (lower uptake when parents were born abroad, range: 52%-Morocco to 88%-Netherlands). The most important predictors among those recalled were, respectively, distance to vaccination location (lower uptake with larger distance, range: 4-6%), percentage of votes for the conservative Christian (reformed) party in the municipality (lower uptake with higher percentage, range: 4-5%) and parents' country of birth (higher uptake when parents were born abroad, range: 4%-Netherlands to 11%-Syria). CONCLUSIONS: The MenACWY vaccination campaign for adolescents achieved a high uptake, with little vaccine use before the campaign. Parents' country of birth, votes for the conservative reformed political party and distance to the vaccination location were the most important predictors of vaccination. The recall strategy enhanced the uptake and was valuable to diminish immunization disparities. Future vaccination campaigns should put more effort into reaching adolescents with immigrant parents.

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

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.

Intention to vaccinate universally against varicella, rotavirus gastroenteritis, meningococcal B disease and seasonal influenza among parents in the Netherlands: an internet survey.

OBJECTIVE: For the decision-making process regarding introduction of new vaccines into the National Immunisation Programme (NIP), advance insight into the potential acceptance among the population is relevant. We studied the intention of parents to have their child vaccinated against four diseases not currently covered by the NIP in the Netherlands. The results on varicella have been published before; this article adds the results on vaccination against rotavirus gastroenteritis, meningococcal B disease, and seasonal influenza. RESULTS: We invited a random sample from the national immunisation register of 1500 parents for an internet survey which was completed by 491 parents (33% response). The intention to vaccinate was highest for meningococcal B disease (83% positive intention), followed by rotavirus gastroenteritis (38%), and lowest for varicella (28%) and seasonal influenza (15%). Prediction analyses were performed to determine which out of seven questionnaire statements was most informative in predicting the intention to vaccinate. Main drivers of intention were the perceived importance of vaccination against the particular disease and the perception of whether or not the disease is severe enough to justify vaccination. The results of this study can be informative in the decision-making process whether or not to introduce new vaccines into the NIP.

Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus.

Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002-2011, n=7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.

A novel measles outbreak control strategy in the Netherlands in 2013-2014 using a national electronic immunization register: A study of early MMR uptake and its determinants.

BACKGROUND: During a large measles outbreak in the Netherlands in 2013-2014, infants aged 6-14months living in municipalities with low (<90%) measles-mumps-rubella (MMR) coverage were individually invited for an early MMR using the national electronic immunization register, Præventis. We estimated uptake of early MMR prior to and during the 2013-2014 outbreak and assessed determinants for early MMR vaccination. METHODS: We obtained vaccination records from Præventis, and defined early MMR as vaccination before 415days (13months) of age. A multi-level multivariable logistic regression model, restricted to infants with three diphtheria-pertussis-tetanus-polio (DPTP) vaccinations was used to examine the association between early MMR uptake and sex, parents' country of birth, socioeconomic status (SES; at postcode level) and voting proportions for the Reformed Political Party (SGP; at municipal level), used as a proxy for religious objections towards vaccination. RESULTS: In the 29 municipalities with low MMR coverage, uptake of early MMR was 0.5-2.2% prior to the outbreak. Between July 2013 and March 2014, 5,800 (57%) invited infants received an early MMR. Among infants with three DPTP, 70% received an early MMR. Only 1% of infants without prior DPTP received an early MMR. Lower early MMR uptake was associated with a higher SGP voter-ship (OR 0.89 per 5% increase, 95%CI 0.83-0.96), parents' with unknown country of birth (OR 0.66 95%CI 0.47-0.93) and compared with very high SES, high SES had significantly lower early MMR uptake (OR 0.66 95%CI 0.50-0.87). DISCUSSION: This is the first study describing use of Præventis during an outbreak and to assess determinants of early MMR uptake. More than half of invited infants obtained an early MMR. SES, parents' with unknown country of birth and religious objections towards vaccination were found to be associated with lower early MMR uptake. In future outbreaks, these determinants could be used to tailor intervention strategies.

A Software Tool for Estimation of Burden of Infectious Diseases in Europe Using Incidence-Based Disability Adjusted Life Years.

The burden of disease framework facilitates the assessment of the health impact of diseases through the use of summary measures of population health such as Disability-Adjusted Life Years (DALYs). However, calculating, interpreting and communicating the results of studies using this methodology poses a challenge. The aim of the Burden of Communicable Disease in Europe (BCoDE) project is to summarize the impact of communicable disease in the European Union and European Economic Area Member States (EU/EEA MS). To meet this goal, a user-friendly software tool (BCoDE toolkit), was developed. This stand-alone application, written in C++, is open-access and freely available for download from the website of the European Centre for Disease Prevention and Control (ECDC). With the BCoDE toolkit, one can calculate DALYs by simply entering the age group- and sex-specific number of cases for one or more of selected sets of 32 communicable diseases (CDs) and 6 healthcare associated infections (HAIs). Disease progression models (i.e., outcome trees) for these communicable diseases were created following a thorough literature review of their disease progression pathway. The BCoDE toolkit runs Monte Carlo simulations of the input parameters and provides disease-specific results, including 95% uncertainty intervals, and permits comparisons between the different disease models entered. Results can be displayed as mean and median overall DALYs, DALYs per 100,000 population, and DALYs related to mortality vs. disability. Visualization options summarize complex epidemiological data, with the goal of improving communication and knowledge transfer for decision-making.

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

BACKGROUND: Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. METHODS AND FINDINGS: The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961) and influenza (8670 DALYs/year; 95% UI: 8468-8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the National Immunisation Programme. The average disease burden per individual varied from 0.2 (95% UI: 0.1-0.4) DALYs per 100 infections for giardiasis, to 5081 and 3581 (95% UI: 3540-3611) DALYs per 100 infections for rabies and variant Creutzfeldt-Jakob disease, respectively. CONCLUSIONS: For guiding and supporting public health policy decisions regarding the prioritisation of interventions and preventive measures, estimates of disease burden and the comparison of burden between diseases can be informative. Although the collection of disease-specific parameters and estimation of incidence is a process subject to continuous improvement, the current study established a baseline for assessing the impact of future public health initiatives.