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Aims: To document progress with human papillomavirus (HPV) vaccine introduction in three closely related European countries, one with organized (the Netherlands) and two with opportunistic cervical cancer screening (Belgium and Luxembourg). Methods: Experts involved in cervical cancer screening and national immunization programs from the three countries were contacted to provide information on the decision-making process concerning the introduction of HPV vaccine. Sales statistics were obtained from Intercontinental Marketing Services. Results: Advisory boards in all three countries advised organized HPV vaccination of girls of 12 years with variable catch-up policies. In Belgium, the national health authority partially reimburses the HPV vaccine for girls of 12-15 years (recently extended until 18 years). In Luxembourg, 12-year-old girls are invited for free vaccination, but the HPV vaccine is also free of charge for female adolescents of 13-17 years. The number of vaccines reimbursed in Belgium in December 2007 to May 2008 corresponds with the amount required to fully vaccinate 29% of the female population aged 12-15 years. In Luxembourg, between March and November 2008, the immunization program delivered a quantity of HPV vaccines which theoretically covered 29% of females aged 12-17 years. In the Netherlands, nationwide HPV vaccination of girls of 12 years will start in September 2009. The sales of HPV vaccines (all ages combined) were by far the lowest in the Netherlands. Conclusion: Up to the end of 2008, HPV vaccination efforts reached less than a third of the target population in Belgium and Luxembourg. If the latest trend continues, the current policy is expected to reach to most half of the target population. Well-planned introduction of vaccination combined with an organized screening program and active surveillance are crucial for the program to achieve and monitor its desired aims. Such surveillance should include linkage between vaccination, screening and cancer registries. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This paper shows how to model seroprevalence data using change-point fractional polynomials (FPs). The inclusion of a change point in the FP framework allows to detect distortions arising from common (often untestable) assumptions made in the estimation of the age-specific prevalence and force of infection from cross-sectional data. The method is motivated using seroprevalence data on the parvovirus B19 and the varicella zoster virus in Belgium. [ABSTRACT FROM AUTHOR]

The burden of infectious diseases is influenced by the structure of the population at risk. Population ageing may have implications for the disease burden of future epidemics. Moreover, changing household structures induced by population ageing may influence the dynamics of disease transmission and burden of infections transmitted via close contact interactions. We aim to investigate the impact of demographic change on the disease transmission dynamics and future disease burden and illustrate this for COVID-19 and influenza-like illness (ILI). We simulate the Belgian population between 2020 and 2050 using an individual-based model with census data. The simulated population structures were used as input for an infectious disease model that distinguishes between exposure to infection in the household versus exposure in the community at large. We mimicked outbreaks of COVID-19 and ILI of varying total final size. The simulated population ages between 2020 and 2050, which also affects household size and composition. As the proportion of elderly people in the population increases, the overall attack rate slightly decreases because older age groups have fewer contacts and are therefore less likely to incur and transmit infections. Despite the lower per-person attack rate, the estimated disease burden increases as morbidity and mortality increases with the age at infection. The demographic changes induced by population ageing have an impact on the burden of future outbreaks of COVID-19 and ILI in Belgium. The shifting age distribution implies that the elderly, a population group with increased morbidity and mortality in case of infection, make up an increasing proportion of the total population. Population ageing also leads to an increasing proportion of single-person households and collective households (e.g. nursing homes) in the population. Since the household attack rate varies by household size and composition, the living arrangements of the elderly population influences the disease burden of future epidemics to some extent. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to unprecedented changes in behaviour. To estimate if these persisted, a final round of the CoMix social contact survey was conducted in four countries at a time when all societal restrictions had been lifted for several months. We conducted a survey on a nationally representative sample in the UK, Netherlands (NL), Belgium (BE), and Switzerland (CH). Participants were asked about their contacts and behaviours on the previous day. We calculated contact matrices and compared the contact levels to a pre-pandemic baseline to estimate R 0 . Data collection occurred from 17 November to 7 December 2022. 7477 participants were recruited. Some were asked to undertake the survey on behalf of their children. Only 14.4 % of all participants reported wearing a facemask on the previous day. Self-reported vaccination rates in adults were similar for each country at around 86 %. Trimmed mean recorded contacts were highest in NL with 9.9 (95 % confidence interval [CI] 9.0-10.8) contacts per person per day and lowest in CH at 6.0 (95 % CI 5.4-6.6). Contacts at work were lowest in the UK (1.4 contacts per person per day) and highest in NL at 2.8 contacts per person per day. Other contacts were also lower in the UK at 1.6 per person per day (95 % CI 1.4-1.9) and highest in NL at 3.4 recorded per person per day (95 % CI 43.0-4.0). The next-generation approach suggests that R 0 for a close-contact disease would be roughly half pre-pandemic levels in the UK, 80 % in NL and intermediate in the other two countries. The pandemic appears to have resulted in lasting changes in contact patterns expected to have an impact on the epidemiology of many different pathogens. Further post-pandemic surveys are necessary to confirm this finding., Competing Interests: Declaration of Competing Interest None to declare., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Open surveys complementing surveillance programs often yield opportunistically sampled data characterised by spatio-temporal imbalance. We set up our study to understand to what extent spatio-temporal statistical models using such data achieve in describing epidemiological trends. We used self-reported symptomatic COVID-19 data from two Belgian regions, Flanders and the Brussels-Capital Region. These data were collected in a large-scale open survey with spatio-temporally imbalanced participation rates. We compared incidence estimates of both self-reported symptoms and test-confirmed COVID-19 cases obtained through generalised linear mixed models correcting for spatio-temporal correlation. We additionally simulated symptom incidences under different sampling strategies to explore the impact of sample imbalance, sample size and disease incidence, on trend detection. Our study shows that spatio-temporal sample imbalance generally does not lead to bad model performances in spatio-temporal trend estimation and high-risk area detection. Except for low-incidence diseases, collecting large samples will often be more essential than ensuring spatio-temporally sample balance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results., Methods: We compared projections from the European COVID-19 Scenario Modelling Hub. Five teams modelled incidence in Belgium, the Netherlands, and Spain. We compared July 2022 projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model's quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data., Results: By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models' quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes., Conclusions: We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort's aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: When formulating and evaluating COVID-19 vaccination strategies, an emphasis has been placed on preventing severe disease that overburdens healthcare systems and leads to mortality. However, more conventional outcomes such as quality-adjusted life years (QALYs) and inequality indicators are warranted as additional information for policymakers., Methods: We adopted a mathematical transmission model to describe the infectious disease dynamics of SARS-COV-2, including disease mortality and morbidity, and to evaluate (non)pharmaceutical interventions. Therefore, we considered temporal immunity levels, together with the distinct transmissibility of variants of concern (VOCs) and their corresponding vaccine effectiveness. We included both general and age-specific characteristics related to SARS-CoV-2 vaccination. Our scenario study is informed by data from Belgium, focusing on the period from August 2021 until February 2022, when vaccination for children aged 5-11 years was initially not yet licensed and first booster doses were administered to adults. More specifically, we investigated the potential impact of an earlier vaccination programme for children and increased or reduced historical adult booster dose uptake., Results: Through simulations, we demonstrate that increasing vaccine uptake in children aged 5-11 years in August-September 2021 could have led to reduced disease incidence and ICU occupancy, which was an essential indicator for implementing non-pharmaceutical interventions and maintaining healthcare system functionality. However, an enhanced booster dose regimen for adults from November 2021 onward could have resulted in more substantial cumulative QALY gains, particularly through the prevention of elevated levels of infection and disease incidence associated with the emergence of Omicron VOC. In both scenarios, the need for non-pharmaceutical interventions could have decreased, potentially boosting economic activity and mental well-being., Conclusions: When calculating the impact of measures to mitigate disease spread in terms of life years lost due to COVID-19 mortality, we highlight the impact of COVID-19 on the health-related quality of life of survivors. Our study underscores that disease-related morbidity could constitute a significant part of the overall health burden. Our quantitative findings depend on the specific setup of the interventions under review, which is open to debate or should be contextualised within future situations., (© 2024. The Author(s).)

Background: The complex management of health needs in multimorbid patients, alongside limited cost data, presents challenges in developing cost-effective patient-care pathways. We estimated the costs of managing 171 dyads and 969 triads in Belgium, taking into account the influence of morbidity interactions on costs., Methods: We followed a retrospective longitudinal study design, using the linked Belgian Health Interview Survey 2018 and the administrative claim database 2017-2020 hosted by the Intermutualistic Agency. We included people aged 15 and older, who had complete profiles (N = 9753). Applying a system costing perspective, the average annual direct cost per person per dyad/triad was presented in 2022 Euro and comprised mainly direct medical costs. We developed mixed models to analyse the impact of single chronic conditions, dyads and triads on healthcare costs, considering two-/three-way interactions within dyads/triads, key cost determinants and clustering at the household level., Results: People with multimorbidity constituted nearly half of the study population and their total healthcare cost constituted around three quarters of the healthcare cost of the study population. The most common dyad, arthropathies + dorsopathies, with a 14% prevalence rate, accounted for 11% of the total national health expenditure. The most frequent triad, arthropathies + dorsopathies + hypertension, with a 5% prevalence rate, contributed 5%. The average annual direct costs per person with dyad and triad were €3515 (95% CI 3093-3937) and €4592 (95% CI 3920-5264), respectively. Dyads and triads associated with cancer, diabetes, chronic fatigue, and genitourinary problems incurred the highest costs. In most cases, the cost associated with multimorbidity was lower or not substantially different from the combined cost of the same conditions observed in separate patients., Conclusion: Prevalent morbidity combinations, rather than high-cost ones, made a greater contribution to total national health expenditure. Our study contributes to the sparse evidence on this topic globally and in Europe, with the aim of improving cost-effective care for patients with diverse needs., (© 2024. The Author(s).)

Background: Burden of disease estimates have become important population health metrics over the past decade to measure losses in health. In Belgium, the disease burden caused by COVID-19 has not yet been estimated, although COVID-19 has emerged as one of the most important diseases. Therefore, the current study aims to estimate the direct COVID-19 burden in Belgium, observed despite policy interventions, during 2020 and 2021, and compare it to the burden from other causes., Methods: Disability-adjusted life years (DALYs) are the sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to disease. DALYs allow comparing the burden of disease between countries, diseases, and over time. We used the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs related to COVID-19. Estimates of person-years for (a) acute non-fatal disease states were calculated from a compartmental model, using Belgian seroprevalence, social contact, hospital, and intensive care admission data, (b) deaths were sourced from the national COVID-19 mortality surveillance, and (c) chronic post-acute disease states were derived from a Belgian cohort study., Results: In 2020, the total number of COVID-19 related DALYs was estimated at 253,577 [252,541 - 254,739], which is higher than in 2021, when it was 139,281 [136,704 - 142,306]. The observed COVID-19 burden was largely borne by the elderly, and over 90% of the burden was attributable to premature mortality (i.e., YLLs). In younger people, morbidity (i.e., YLD) contributed relatively more to the DALYs, especially in 2021, when vaccination was rolled out. Morbidity was mainly attributable to long-lasting post-acute symptoms., Conclusion: COVID-19 had a substantial impact on population health in Belgium, especially in 2020, when COVID-19 would have been the main cause of disease burden if all other causes had maintained their 2019 level., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: During the COVID-19 pandemic, the CoMix study, a longitudinal behavioral survey, was designed to monitor social contacts and public awareness in multiple countries, including Belgium. As a longitudinal survey, it is vulnerable to participants' "survey fatigue", which may impact inferences., Methods: A negative binomial generalized additive model for location, scale, and shape (NBI GAMLSS) was adopted to estimate the number of contacts reported between age groups and to deal with under-reporting due to fatigue within the study. The dropout process was analyzed with first-order auto-regressive logistic regression to identify factors that influence dropout. Using the so-called next generation principle, we calculated the effect of under-reporting due to fatigue on estimating the reproduction number., Results: Fewer contacts were reported as people participated longer in the survey, which suggests under-reporting due to survey fatigue. Participant dropout is significantly affected by household size and age categories, but not significantly affected by the number of contacts reported in any of the two latest waves. This indicates covariate-dependent missing completely at random (MCAR) in the dropout pattern, when missing at random (MAR) is the alternative. However, we cannot rule out more complex mechanisms such as missing not at random (MNAR). Moreover, under-reporting due to fatigue is found to be consistent over time and implies a 15-30% reduction in both the number of contacts and the reproduction number ([Formula: see text]) ratio between correcting and not correcting for under-reporting. Lastly, we found that correcting for fatigue did not change the pattern of relative incidence between age groups also when considering age-specific heterogeneity in susceptibility and infectivity., Conclusions: CoMix data highlights the variability of contact patterns across age groups and time, revealing the mechanisms governing the spread/transmission of COVID-19/airborne diseases in the population. Although such longitudinal contact surveys are prone to the under-reporting due to participant fatigue and drop-out, we showed that these factors can be identified and corrected using NBI GAMLSS. This information can be used to improve the design of similar, future surveys., (© 2023. The Author(s).)

Background: Pneumococcal conjugate vaccines (PCVs) effectively reduce infection and asymptomatic carriage of Streptococcus pneumoniae vaccine serotypes. In 2016, Belgium replaced its infant PCV13 program by a 4-year period of PCV10. Concomitantly, S. pneumoniae serotype carriage was monitored together with the carriage of other nasopharyngeal pathogens in children attending day-care centers., Methods: From 2016 to 2019, a total of 3459 nasopharyngeal swabs were obtained from children aged 6-30 months. Culture and qPCR were used for the identification of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus and for serotyping and antimicrobial susceptibility assessment of S. pneumoniae strains., Results: S. pneumoniae colonization was frequent and stable over the study years. H. influenzae and M. catarrhalis were more frequently carried (P < .001) than S. pneumoniae, by, respectively, 92.3% and 91.0% of children. Prevalence of all PCV13 serotypes together increased significantly over time from 5.8% to 19.6% (P < .001) and was attributable to the increasing prevalence of serotype 19A. Coincidently, non-vaccine serotype 6C increased (P < .001) and the overall pneumococcal non-susceptibility to tetracycline and erythromycin. Non-susceptibility to cotrimoxazole decreased (P < .001)., Conclusions: The switch to a PCV program no longer covering serotypes 19A, 6A, and 3 was associated with a sustained increase of serotypes 19A and 6C in healthy children, similarly as in invasive pneumococcal disease. This resulted in a re-introduction of the 13-valent conjugate vaccine during the summer of 2019., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Background: The increasing availability of data on social contact patterns and time use provides invaluable information for studying transmission dynamics of infectious diseases. Social contact data provide information on the interaction of people in a population whereas the value of time use data lies in the quantification of exposure patterns. Both have been used as proxies for transmission risks within in a population and the combination of both sources has led to investigate which contacts are more suitable to describe these transmission risks., Methods: We used social contact and time use data from 1707 participants from a survey conducted in Flanders, Belgium in 2010-2011. We calculated weighted exposure time and social contact matrices to analyze age- and gender-specific mixing patterns and to quantify behavioral changes by distance from home. We compared the value of both separate and combined data sources for explaining seroprevalence and incidence data on parvovirus-B19, Varicella-Zoster virus (VZV) and influenza like illnesses (ILI), respectively., Results: Assortative mixing and inter-generational interaction is more pronounced in the exposure matrix due to the high proportion of time spent at home. This pattern is less pronounced in the social contact matrix, which is more impacted by the reported contacts at school and work. The average number of contacts declined with distance. On the individual-level, we observed an increase in the number of contacts and the transmission potential by distance when travelling. We found that both social contact data and time use data provide a good match with the seroprevalence and incidence data at hand. When comparing the use of different combinations of both data sources, we found that the social contact matrix based on close contacts of at least 4 h appeared to be the best proxy for parvovirus-B19 transmission. Social contacts and exposure time were both on their own able to explain VZV seroprevalence data though combining both scored best. Compared with the contact approach, the time use approach provided the better fit to the ILI incidence data., Conclusions: Our work emphasises the common and complementary value of time use and social contact data for analysing mixing behavior and analysing infectious disease transmission. We derived spatial, temporal, age-, gender- and distance-specific mixing patterns, which are informative for future modelling studies., (© 2022. The Author(s).)

Background: Lyme borreliosis (LB) is the most common tick-borne disease in Europe and North America, yet its economic burden remains largely unknown. This study aimed to estimate the economic cost associated with the different clinical manifestations of LB in Belgium., Methods: An incidence approach and societal perspective were used to estimate the total cost-of-illness for LB in Belgium. Costs were calculated for patients with erythema migrans (EM) or disseminated/late LB, including patients who developed post-treatment Lyme disease syndrome (PTLDS). Direct medical, direct non-medical (transportation & paid help) and indirect non-medical costs (productivity losses) were included in the analysis. Ambulatory cost data were collected through a prospective cohort study from June 2016 to March 2020, in which patients with LB were followed up 6 to 12 months after diagnosis. Hospitalization costs were retrieved from the Minimal Clinical Data registry, a mandatory registry for all Belgian hospitals, linked to the Minimal Financial Data registry. Costs were expressed in 2019 euros., Results: The total annual cost associated with clinical manifestations of LB in Belgium was estimated at €5.59 million (95% UI 3.82-7.98). Of these, €3.44 million (95% UI 2.05-5.48) or 62% was related to disseminated/late LB diagnoses and €2.15 million (95% UI 1.30-3.26) to EM. In general, direct medical costs and productivity losses accounted for 49.8% and 46.4% of the total costs, respectively, while direct non-medical costs accounted for only 3.8%. The estimated mean costs were €193 per EM patient and €5,148 per disseminated/late LB patient. While patients with PTLDS seemed to have somewhat higher costs compared to patients without PTLDS, the number of patients was too small to have representative estimates., Conclusions: We estimate the total annual direct medical costs, direct non-medical and indirect non-medical costs associated with LB to exceed €5.5 million per year, almost evenly distributed between EM (40%) and disseminated/late LB (60%). EM costs 26 times less per patient but occurs also 16 times more frequently than disseminated/late LB. The cost burden remains limited by comparison to other infectious diseases due to the relative lower incidence., (© 2022. The Author(s).)

Presence of SARS-CoV-2 was monitored in nasopharyngeal samples from young children aged 6-30 months attending day-care centres (DCCs) in Belgium from May 2020-February 2022. SARS-CoV-2 carriage among DCC children was only detected from November 2021, after emergence of Delta and Omicron variants, in 9 of the 42 DCCs screened. In only one DCC, two children tested positive for SARS-CoV-2 at the same sampling time point, suggesting limited transmission of SARS-CoV-2 in Belgian DCCs among young children during the studied period.

Background: A new adjuvanted subunit vaccine (HZ/su), with higher vaccine efficacy than live-attenuated vaccine (ZVL), has been licensed in Europe since March 2018. Therefore, Belgian decision-makers might need to re-assess their recommendations for vaccination against herpes zoster (HZ)., Methods: We conducted a cost-effectiveness analysis, using a Markov decision tree, of vaccinating 50- to 85-year-old immunocompetent Belgian cohorts with no vaccination, HZ/su, ZVL, and ZVL with booster after 10 years. Due to the uncertainty in vaccine waning of HZ/su vaccine beyond 4 years, we used a logarithmic and 1-minus-exponential function to model respectively a long and short duration of protection. We used a lifetime time horizon and implemented the health care payer perspective throughout the analysis., Results: HZ/su had the greatest impact in avoiding health and economic burden. However, it would never become cost-effective at a willingness-to-pay threshold of €40,000 per quality-adjusted life year (QALY) gained at its market price set by the manufacturer in the USA. Depending on the waning function assumed for HZ/su, the price per dose needs to drop 60% or 83% such that vaccination with HZ/su, assuming respectively a long or short duration of protection, would become cost-effective in 50- and 80-year-old individuals. At €40,000 per QALY gained, ZVL or ZVL with booster was never found cost-effective compared with HZ/su, even if only administration cost was considered., Conclusion: HZ/su is cost-effective in the 50-year-old age cohort at the unofficial Belgian threshold of €40,000 per QALY gained, if its price drops to €55.40 per dose. This result is, however, very sensitive to the assumed duration of protection of the vaccine, and the assumed severity and QALY loss associated with HZ and post-herpetic neuralgia (PHN)., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time., Competing Interests: The authors have declared that no competing interests exist.

BackgroundTo control epidemic waves, it is important to know the susceptibility to SARS-CoV-2 and its evolution over time in relation to the control measures taken.AimTo assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the first national lockdown in Belgium, we performed a nationwide seroprevalence study, stratified by age, sex and region using 3,000-4,000 residual samples during seven periods between 30 March and 17 October 2020.MethodsWe analysed residual sera from ambulatory patients for IgG antibodies against the SARS-CoV-2 S1 protein with a semiquantitative commercial ELISA. Weighted seroprevalence (overall and by age category and sex) and seroincidence during seven consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity.ResultsThe weighted overall seroprevalence initially increased from 1.8% (95% credible interval (CrI): 1.0-2.6) to 5.3% (95% CrI: 4.2-6.4), implying a seroincidence of 3.4% (95% CrI: 2.4-4.6) between the first and second collection period over a period of 3 weeks during lockdown (start lockdown mid-March 2020). Thereafter, seroprevalence stabilised, however, significant decreases were observed when comparing the third with the fifth, sixth and seventh period, resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid-October 2020 a weighted overall seroprevalence of 4.2% (95% CrI: 3.1-5.2).ConclusionDuring lockdown, an initially small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.

Purpose: Health-related quality of life outcomes are increasingly used to monitor population health and health inequalities and to assess the (cost-) effectiveness of health interventions. The EQ-5D-5L has been included in the Belgian Health Interview Survey, providing a new source of population-based self-perceived health status information. This study aims to estimate Belgian population norms for the EQ-5D-5L by sex, age, and region and to analyze its association with educational attainment., Methods: The BHIS 2018 provided EQ-5D-5L data for a nationally representative sample of the Belgian population. The dimension scores and index values were analyzed using logistic and linear regressions, respectively, accounting for the survey design., Results: More than half of respondents reported problems of pain/discomfort, while over a quarter reported problems of anxiety/depression. The average index value was 0.84. Women reported more problems on all dimensions, but particularly on anxiety/depression and pain/discomfort, resulting in significantly lower index values. Problems with mobility, self-care, and usual activities showed a sharp increase after the age of 80 years. Consequently, index values decreased significantly by age. Lower education was associated with a higher prevalence of problems for all dimensions except anxiety/depression and with a significantly lower index value., Conclusion: This paper presents the first nationally representative Belgian population norms using the EQ-5D-5L. Inclusion of the EQ-5D in future surveys will allow monitoring over time of self-reported health, disease burden, and health inequalities., (© 2021. The Author(s).)

Following the onset of the ongoing COVID-19 pandemic throughout the world, a large fraction of the global population is or has been under strict measures of physical distancing and quarantine, with many countries being in partial or full lockdown. These measures are imposed in order to reduce the spread of the disease and to lift the pressure on healthcare systems. Estimating the impact of such interventions as well as monitoring the gradual relaxing of these stringent measures is quintessential to understand how resurgence of the COVID-19 epidemic can be controlled for in the future. In this paper we use a stochastic age-structured discrete time compartmental model to describe the transmission of COVID-19 in Belgium. Our model explicitly accounts for age-structure by integrating data on social contacts to (i) assess the impact of the lockdown as implemented on March 13, 2020 on the number of new hospitalizations in Belgium; (ii) conduct a scenario analysis estimating the impact of possible exit strategies on potential future COVID-19 waves. More specifically, the aforementioned model is fitted to hospital admission data, data on the daily number of COVID-19 deaths and serial serological survey data informing the (sero)prevalence of the disease in the population while relying on a Bayesian MCMC approach. Our age-structured stochastic model describes the observed outbreak data well, both in terms of hospitalizations as well as COVID-19 related deaths in the Belgian population. Despite an extensive exploration of various projections for the future course of the epidemic, based on the impact of adherence to measures of physical distancing and a potential increase in contacts as a result of the relaxation of the stringent lockdown measures, a lot of uncertainty remains about the evolution of the epidemic in the next months., (Copyright © 2021. Published by Elsevier B.V.)

Background: In response to the ongoing COVID-19 pandemic, several countries adopted measures of social distancing to a different degree. For many countries, after successfully curbing the initial wave, lockdown measures were gradually lifted. In Belgium, such relief started on May 4th with phase 1, followed by several subsequent phases over the next few weeks., Methods: We analysed the expected impact of relaxing stringent lockdown measures taken according to the phased Belgian exit strategy. We developed a stochastic, data-informed, meta-population model that accounts for mixing and mobility of the age-structured population of Belgium. The model is calibrated to daily hospitalization data and is able to reproduce the outbreak at the national level. We consider different scenarios for relieving the lockdown, quantified in terms of relative reductions in pre-pandemic social mixing and mobility. We validate our assumptions by making comparisons with social contact data collected during and after the lockdown., Results: Our model is able to successfully describe the initial wave of COVID-19 in Belgium and identifies interactions during leisure/other activities as pivotal in the exit strategy. Indeed, we find a smaller impact of school re-openings as compared to restarting leisure activities and re-openings of work places. We also assess the impact of case isolation of new (suspected) infections, and find that it allows re-establishing relatively more social interactions while still ensuring epidemic control. Scenarios predicting a second wave of hospitalizations were not observed, suggesting that the per-contact probability of infection has changed with respect to the pre-lockdown period., Conclusions: Contacts during leisure activities are found to be most influential, followed by professional contacts and school contacts, respectively, for an impending second wave of COVID-19. Regular re-assessment of social contacts in the population is therefore crucial to adjust to evolving behavioral changes that can affect epidemic diffusion.

Background: Each year, up to 10% of unvaccinated adults contracts seasonal influenza, with half of this proportion developing symptoms. As a result, employers experience significant economic losses in terms of employee absenteeism. Influenza vaccines can be instrumental in reducing this burden. Workplace vaccination is expected to reduce employee absenteeism more than linearly as a result of positive externalities. It remains unclear whether workplace influenza vaccination yields a positive return on investment., Methods: We simulated the spread of influenza in the seasons 2011-12 up to 2017-18 in Belgium by means of a compartmental transmission model. We accounted for age-specific social contact patterns and included reduced contact behavior when symptomatically infected. We simulated the impact of employer-funded influenza vaccination at the workplace and performed a cost-benefit analysis to assess the employers' return on workplace vaccination. Furthermore, we look into the cost-benefit of rewarding vaccinated employees by offering an additional day off., Results: Workplace vaccination reduced the burden of influenza both on the workplace and in the population at large. Compared to the current vaccine coverage - 21% in the population at large - an employee vaccine coverage of 90% could avert an additional 355 000 cases, of which about 150 000 in the employed population and 205 000 in the unemployed population. While seasonal influenza vaccination has been cost-saving on average at about €10 per vaccinated employee, the cost-benefit analysis was prone to between-season variability., Conclusions: Vaccinated employees can serve as a barrier to limit the spread of influenza in the population, reducing the attack rate by 78% at an employee coverage of 90%. While workplace vaccination is relatively inexpensive (due to economies of scale) and convenient, the return on investment is volatile. Government subsidies can be pivotal to encourage employers to provide vaccination at the workplace with positive externalities to society as a whole., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In 2010-2011, we conducted a social contact survey in Flanders, Belgium, aimed at improving and extending the design of the first social contact survey conducted in Belgium in 2006. This second social contact survey aimed to enable, for the first time, the estimation of social mixing patterns for an age range of 0 to 99 years and the investigation of whether contact rates remain stable over this 5-year time period., Methods: Different data mining techniques are used to explore the data, and the age-specific number of social contacts and the age-specific contact rates are modelled using a generalized additive models for location, scale and shape (GAMLSS) model. We compare different matrices using assortativeness measures. The relative change in the basic reproduction number (R 0 ) and the ratio of relative incidences with 95% bootstrap confidence intervals (BCI) are employed to investigate and quantify the impact on epidemic spread due to differences in sex, day of the week, holiday vs. regular periods and changes in mixing patterns over the 5-year time gap between the 2006 and 2010-2011 surveys. Finally, we compare the fit of the contact matrices in 2006 and 2010-2011 to Varicella serological data., Results: All estimated contact patterns featured strong homophily in age and sex, especially for small children and adolescents. A 30% (95% BCI [17%; 37%]) and 29% (95% BCI [14%; 40%]) reduction in R 0 was observed for weekend versus weekdays and for holiday versus regular periods, respectively. Significantly more interactions between people aged 60+ years and their grandchildren were observed on holiday and weekend days than on regular weekdays. Comparing contact patterns using different methods did not show any substantial differences over the 5-year time period under study., Conclusions: The second social contact survey in Flanders, Belgium, endorses the findings of its 2006 predecessor and adds important information on the social mixing patterns of people older than 60 years of age. Based on this analysis, the mixing patterns of people older than 60 years exhibit considerable heterogeneity, and overall, the comparison of the two surveys shows that social contact rates can be assumed stable in Flanders over a time span of 5 years.

The COVID-19 pandemic caused many governments to impose policies restricting social interactions. A controlled and persistent release of lockdown measures covers many potential strategies and is subject to extensive scenario analyses. Here, we use an individual-based model (STRIDE) to simulate interactions between 11 million inhabitants of Belgium at different levels including extended household settings, i.e., "household bubbles". The burden of COVID-19 is impacted by both the intensity and frequency of physical contacts, and therefore, household bubbles have the potential to reduce hospital admissions by 90%. In addition, we find that it is crucial to complete contact tracing 4 days after symptom onset. Assumptions on the susceptibility of children affect the impact of school reopening, though we find that business and leisure-related social mixing patterns have more impact on COVID-19 associated disease burden. An optimal deployment of the mitigation policies under study require timely compliance to physical distancing, testing and self-isolation.

Background: Changes in serotype distribution have been described after the switch from the 13-valent pneumococcal conjugate vaccine (PCV13) to the 10-valent pneumococcal conjugate vaccine (PCV10) in Belgium., Aim: To describe serotype's invasive disease potential and the detailed evolution of serotype distribution and antimicrobial susceptibility of pneumococcal isolates (carriage and IPD) in children up to 30 months of age over a period during and after the vaccine switch (2015-2018)., Methods: S. pneumoniae strains isolated from the nasopharynx of healthy children attending day-care centres (DCCs) and strains from normally sterile sites of children with IPD were serotyped (Quellung-reaction) and antimicrobial susceptibility testing was performed. Invasive disease potential was defined as the serotype-specific odds ratio (OR)., Results: The highly invasive (OR > 1) serotypes 12F, 1, 3, 24A/B/F, 33F, 19A, and 9N were not frequently carried (<7.5% of carriage strains). Different serotypes dominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). PCV13 vaccine serotypes increased in carriage (5.4% (25/463) in period 1 vs 10.3% (69/668) in period 3) and in IPD (7.3% (8/110 in period 1 vs 23.9% (34/142) in period 3) due to an increase (p < 0.01) in serotype 19A. The penicillin non-susceptibility of 19A was lower (p = 0.02) in carriage (6.8%) than in IPD (23.5%). Erythromycin and tetracycline non-susceptibility were more frequent (p < 0.01) in IPD (26.0%; 23.0%) compared to carriage strains (18.2%; 14.5%) and penicillin non-susceptibility increased over the three year study period (carriage: 13.4%, 19.8%, 18.5%, p = 0.05; IPD: 11.8%, 15.0%, 20.4%, p = 0.02)., Conclusion: Only some of the serotypes with high invasive disease potential (serotype 1, 3, 19A) in Belgium are included in PCV10 and/or PCV13. This reinforces the need for continuous monitoring, both in healthy children as in children with IPD, to better understand the dynamics of pneumococcal disease, to optimise the composition and implementation of PCVs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The standard framework of economic evaluation of health programs, which is increasingly used for policy funding decisions, is insufficiently equipped to reflect the full range of health and economic benefits conferred by vaccines and thus undervalues vaccination., Methods: In 2019, a group of Belgian health economic and clinical experts, supported by 2 senior international vaccination experts (1 American, 1 Belgian), convened 4 roundtable meetings to highlight which particular value elements of vaccination remain neglected in economic evaluations., Results: They concluded that the standard economic evaluation framework fails to reflect the full value of vaccination with respect to prevention of complications linked to some vaccine-preventable diseases, health gains for caregivers, herd effects, changes in exposure to and distribution of serotypes, the effect on antimicrobial resistance, productivity gains for caregivers and patients, and the distributive implications of vaccination programs., Conclusions: Here, suggestions are made regarding how these shortcomings can be addressed in future economic evaluations of vaccines and how a more level playing field between vaccines and other health programs can be created., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has shown how a newly emergent communicable disease can lay considerable burden on public health. To avoid system collapse, governments have resorted to several social distancing measures. In Belgium, this included a lockdown and a following period of phased re-opening. A representative sample of Belgian adults was asked about their contact behaviour from mid-April to the beginning of August, during different stages of the intervention measures in Belgium. Use of personal protection equipment (face masks) and compliance to hygienic measures was also reported. We estimated the expected reproduction number computing the ratio of [Formula: see text] with respect to pre-pandemic data. During the first two waves (the first month) of the survey, the reduction in the average number of contacts was around 80% and was quite consistent across all age-classes. The average number of contacts increased over time, particularly for the younger age classes, still remaining significantly lower than pre-pandemic values. From the end of May to the end of July , the estimated reproduction number has a median value larger than one, although with a wide dispersion. Estimated [Formula: see text] fell below one again at the beginning of August. We have shown how a rapidly deployed survey can measure compliance to social distancing and assess its impact on COVID-19 spread. Monitoring the effectiveness of social distancing recommendations is of paramount importance to avoid further waves of COVID-19.

When estimating important measures such as the herd immunity threshold, and the corresponding efforts required to eliminate measles, it is often assumed that susceptible individuals are uniformly distributed throughout populations. However, unvaccinated individuals may be clustered in a variety of ways, including by geographic location, by age, in schools, or in households. Here, we investigate to which extent different levels of within-household clustering of susceptible individuals may impact the risk and persistence of measles outbreaks. To this end, we apply an individual-based model, Stride, to a population of 600,000 individuals, using data from Flanders, Belgium. We construct a metric to estimate the level of within-household susceptibility clustering in the population. Furthermore, we compare realistic scenarios regarding the distribution of susceptible individuals within households in terms of their impact on epidemiological measures for outbreak risk and persistence. We find that higher levels of within-household clustering of susceptible individuals increase the risk, size and persistence of measles outbreaks. Ignoring within-household clustering thus leads to underestimations of required measles elimination and outbreak mitigation efforts.

Although COVID-19 has been spreading throughout Belgium since February, 2020, its spatial dynamics in Belgium remain poorly understood, partly due to the limited testing of suspected cases during the epidemic's early phase. We analyse data of COVID-19 symptoms, as self-reported in a weekly online survey, which is open to all Belgian citizens. We predict symptoms' incidence using binomial models for spatially discrete data, and we introduce these as a covariate in the spatial analysis of COVID-19 incidence, as reported by the Belgian government during the days following a survey round. The symptoms' incidence is moderately predictive of the variation in the relative risks based on the confirmed cases; exceedance probability maps of the symptoms' incidence and confirmed cases' relative risks overlap partly. We conclude that this framework can be used to detect COVID-19 clusters of substantial sizes, but it necessitates spatial information on finer scales to locate small clusters., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

BackgroundThe current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium.AimThis observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D.MethodsA total of 2,615 nasopharyngeal swabs from children (6-30 months old) attending day care were collected in three periods over 2016-2018. Children's demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A).ResultsThe carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017-2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017-2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017-2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%).ConclusionsDuring and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.

Cytomegalovirus (CMV) infection is endemic worldwide but its seroprevalence varies widely. The goal of this study was to estimate the age-specific seroprevalence of CMV infection in Belgium based on two cross-sectional serological datasets from 2002 and 2006. The seroprevalence was estimated relying on diagnostic test results based on cut-off values pre-specified by the manufacturers of the tests as well as relying on mixture models applied to continuous pathogen-specific immunoglobulin G antibody titre concentrations. The age-specific seroprevalence of hepatitis A virus (HAV), based on three Belgian cross-sectional serological datasets from 1993, 2002 and 2006, was used as a comparator since individuals acquire lifelong immunity upon recovery, implying an increasing seroprevalence with age. The age group weighted overall CMV seroprevalence derived from the mixture model was 32% (95% confidence interval (CI) 31-34%) in 2002 and 31% (95% CI 30-32%) in 2006. We demonstrated that CMV epidemiology differs from the immunizing infection HAV. This was the first large-scale study of CMV and HAV serial datasets in Belgium, estimating seroprevalence specified by age and birth cohort.

Acute gastroenteritis (AGE) remains a common condition in both low- and high-income countries. In Belgium, however, there is currently a lack of information on the societal health and economic impact of AGE. We conducted a retrospective study using mortality and cause-of-death data, hospital data, primary care data, health interview survey data and other published data. We estimated the burden of illness during a 5-year period (2010-2014) in Belgium in terms of deaths, patients admitted to hospitals, patients consulting their general practitioner (GP) and cases occurring in the community. We further quantified the health impact in terms of disability-adjusted life years (DALYs) and the economic impact in terms of cost-of-illness estimates. We estimated 343 deaths, 27 707 hospitalised patients, 464 222 GP consultations and 10 058 741 episodes occurring in the community (0.91 cases/person) on average per year. AGE was associated with 11 855 DALYs per year (107 DALY per 100 000 persons). The economic burden was estimated to represent direct costs of €112 million, indirect costs of €927 million (90% of the total costs) and an average total cost of €103 per case and €94 per person. AGE results in a substantial health and economic impact in Belgium, justifying continued mitigation efforts.

Airborne infectious diseases such as influenza are primarily transmitted from human to human by means of social contacts, and thus easily spread within households. Epidemic models, used to gain insight into infectious disease spread and control, typically rely on the assumption of random mixing within households. Until now, there has been no direct empirical evidence to support this assumption. Here, we present the first social contact survey specifically designed to study contact networks within households. The survey was conducted in Belgium (Flanders and Brussels) from 2010 to 2011. We analysed data from 318 households totalling 1266 individuals with household sizes ranging from two to seven members. Exponential-family random graph models (ERGMs) were fitted to the within-household contact networks to reveal the processes driving contact between household members, both on weekdays and weekends. The ERGMs showed a high degree of clustering and, specifically on weekdays, decreasing connectedness with increasing household size. Furthermore, we found that the odds of a contact between older siblings and between father and child are smaller than for any other pair. The epidemic simulation results suggest that within-household contact density is the main driver of differences in epidemic spread between complete and empirical-based household contact networks. The homogeneous mixing assumption may therefore be an adequate characterization of the within-household contact structure for the purpose of epidemic simulations. However, ignoring the contact density when inferring based on an epidemic model will result in biased estimates of within-household transmission rates. Further research regarding the implementation of within-household contact networks in epidemic models is necessary.

Around 30% of individuals will develop herpes zoster (HZ), caused by the varicella zoster virus (VZV), during their life. While several risk factors for HZ, such as immunosuppressive therapy, are well known, the genetic and molecular components that determine the risk of otherwise healthy individuals to develop HZ are still poorly understood. We created a computational model for the Human Leukocyte Antigen (HLA-A, -B, and -C) presentation capacity of peptides derived from the VZV Immediate Early 62 (IE62) protein. This model could then be applied to a HZ cohort with known HLA molecules. We found that HLA-A molecules with poor VZV IE62 presentation capabilities were more common in a cohort of 50 individuals with a history of HZ compared to a nationwide control group, which equated to a HZ risk increase of 60%. This tendency was most pronounced for cases of HZ at a young age, where other risk factors are less prevalent. These findings provide new molecular insights into the development of HZ and reveal a genetic predisposition in those individuals most at risk to develop HZ.

Streptococcus pneumoniae causes a high disease burden including pneumonia, meningitis and septicemia. Both a polysaccharide vaccine targeting 23 serotypes (PPV23) and a 13-valent conjugate vaccine (PCV13) are indicated for persons aged over 50 years. We developed and parameterized a static multi-cohort model to estimate the incremental cost-effectiveness and budget-impact of these vaccines at different uptake levels. Using three different vaccine efficacy scenarios regarding non-invasive pneumococcal pneumonia and extensive uni- and multivariate sensitivity analyses, we found a strong preference for PPV23 over PCV13 in all age groups at willingness to pay levels below €300 000 per quality adjusted life year (QALY). PPV23 vaccination would cost on average about €83 000, €60 000 and €52 000 per QALY gained in 50-64, 65-74 and 75-84 year olds, whereas for PCV13 this is about €171 000, €201 000 and €338 000, respectively. Strategies combining PPV23 and PCV13 vaccines were most effective but generally less cost-effective. When assuming a combination of increased duration of PCV13 protection, increased disease burden preventable by PCV13 and a 75% reduction of the PCV13 price, PCV13 could become more attractive in <75 year olds, but would remain less attractive than PPV23 from age 75 years onwards. These observations are independent of the assumption that PPV23 has 0% efficacy against non-invasive pneumococcal pneumonia. Pneumococcal vaccination would be most cost-effective in Belgium, when achieving high uptake with PPV23 in 75-84 year olds, as well as by negotiating a lower market-conform PPV23 price to improve uptake and cost-effectiveness.

Objective: The objective of this study was to study the independent environmental triggers of ST-elevation myocardial infarction (STEMI) in a multifactorial environmental population model., Methods and Results: Daily counts of all STEMI patients who underwent urgent percutaneous coronary intervention over the period 2006-2009 in Belgium were associated with average daily meteorological data and influenza-like illness incidence data. The following meteorological measures were investigated: particulate matter less than 10 μM (PM10) and less than 2.5 μM (PM(2.5)), ozone, black smoke, temperature and relative humidity. During the study period a total of 15,964 STEMI patients (mean age 63, 75% male) were admitted with a daily average admission rate of 11 ± 4 patients. A multivariate Poisson regression analysis showed that only the temperature was significantly correlated with STEMI, with an 8% increase in the risk of STEMI for each 10°C decrease in temperature (adjusted incidence risk ratio (IRR) 0.92, 95% CI 0.89-0.96). The effects of temperature were consistent among several subpopulations but the strongest effect was seen in diabetic patients (IRR 0.85, 95% CI 0.78 -0.95). There was a trend for an incremental risk of STEMI for each 10 μg/m³ PM(2.5) increase and during influenza epidemics with IRR of 1.02 (95% CI 1.00-1.04) and 1.07 (95% CI 0.98-1.16), respectively., Conclusion: In a global environmental model, low temperature is the most important environmental trigger for STEMI, whereas air pollution and influenza epidemics only seem to have a modest effect.

Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0-9 years) and adults (25-54 years) have the highest potential to cause a major zoonotic outbreak.

Background: Generic medicines offer an opportunity for governments to contain pharmaceutical expenditures, since generics are generally 10%-80% lower in price than brand medicines. Belgium has a small generic market that takes up 15% of the total pharmaceutical market in packages sold., Objective: To determine the knowledge of consumers about the different available packages of a common over-the-counter medicine (acetaminophen) with regard to price advantage, quality, and effectiveness in a country with a small generic market., Methods: We conducted an online survey in the general Flemish population using a questionnaire with 25 statements. The questionnaire also contained 2 informative interventions. First, we showed the price per package and per tablet that the patient would pay in the pharmacy. Second, we provided the respondent with general information about generic medication (equivalence, effectiveness, price, and recognition). Before and after the interventions, we probed for preferences and knowledge about the different packages. Multivariate logistic models were used to examine the independent effects of consumer characteristics on responses to the survey statements., Results: We obtained a sample of 1,636 respondents. The general attitude towards generic medication was positive-only 5% would rather not use a generic. Nevertheless, only 17% of the respondents were able to recognize a generic medicine. Older consumers (aged 60 years and above) were more often confused about the different packages (OR = 2.59, 95% CI = 1.76-3.80, P ≤ 0.001). Consumers without a higher education degree tended to be more doubtful about the difference in effectiveness and quality between the different brands (OR = 0.59, 95% CI = 0.44-0.79, P ≤ 0.001). Consumer recognition of the name of the active substance of acetaminophen was poor. When different brands were displayed, possible price advantage seemed to be an important motive to switch to a cheaper brand. Consumers generally found medicines to be too expensive; however, consumers with medical or paramedical training had a different opinion., Conclusions: Two main recommendations can be made to increase the knowledge and enhance the trust in cheaper equivalent medicines. First, highlighting the name of the active substance on the label of medicine packages can reduce confusion and avoid health risks, especially among older consumers. Second, new investments or reallocation of budgets should be considered in order to provide consumers with authoritative information on the bioequivalence and price differences between the different available brands. This would be a cost-effective and potentially cost-saving investment for health care payers.

Background: Setting fair health care priorities counts among the most difficult ethical challenges our societies are facing., Objective: To elicit through a discrete choice experiment the Belgian adult population's (18-75 years; N = 750) preferences for prioritizing health care and investigate whether these preferences are different for prevention versus cure., Methods: We used a Bayesian D-efficient design with partial profiles, which enables considering a large number of attributes and interaction effects. We included the following attributes: 1) type of intervention (cure vs. prevention), 2) effectiveness, 3) risk of adverse effects, 4) severity of illness, 5) link between the illness and patient's health-related lifestyle, 6) time span between intervention and effect, and 7) patient's age group., Results: All attributes were statistically significant contributors to the social value of a health care program, with patient's lifestyle and age being the most influential ones. Interaction effects were found, showing that prevention was preferred to cure for disease in young adults, as well as for severe and lethal disease in people of any age. However, substantial differences were found in the preferences of respondents from different age groups, with different lifestyles and different health states., Conclusions: Our study suggests that according to the Belgian public, contextual factors of health gains such as patient's age and health-related lifestyle should be considered in priority setting decisions. The studies, however, revealed substantial disagreement in opinion between different population subgroups., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Risk groups with increased vulnerability for influenza complications such as pregnant women, persons with underlying illnesses as well as persons who come into contact with them, such as health care workers, are currently given priority (along with other classic target groups) to receive seasonal influenza vaccination in Belgium. We aimed to evaluate this policy from a health care payer perspective by cost-effectiveness analysis in the three specific target groups above, while accounting for effects beyond the target group. Increasing the coverage of influenza vaccination is likely to be cost-effective for pregnant women (median €6589 per quality-adjusted life-year (QALY) gained [€4073-€10,249]) and health care workers (median €24,096/QALY gained [€16,442-€36,342]), if this can be achieved without incurring additional administration costs. Assuming an additional physician's consult is charged to administer each additional vaccine dose, the cost-effectiveness of vaccinating pregnant women depends strongly on the extent of its impact on the neonate's health. For health care workers, the assumed number of preventable secondary infections has a strong influence on the cost-effectiveness. Vaccinating people with underlying illnesses is likely highly cost-effective above 50 years of age and borderline cost-effective for younger persons, depending on relative life expectancy and vaccine efficacy in this risk group compared to the general population. The case-fatality ratios of the target group, of the secondary affected groups and vaccine efficacy are key sources of uncertainty., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Dermoscopy is a technique which improves melanoma detection. Optical dermoscopy uses a handheld optical device to observe the skin lesions without recording the images. Sequential digital dermoscopy imaging (SDDI) allows storage of the pictures and their comparison over time. Few studies have compared optical dermoscopy and SDDI from an economic perspective., Objective: The present observational study focused on patients with one-to-three atypical melanocytic lesions, i.e. lesions considered as suspicious by optical dermoscopy. It aimed to calculate the "extra-costs" related to the process of melanoma detection. These extra-costs were defined as the costs of excision and pathology of benign lesions and/or the costs of follow-up by SDDI. The objective was to compare these extra-costs when using optical dermoscopy exclusively versus optical dermoscopy with selective use of SDDI., Methods: In a first group of patients, dermatologists were adequately trained in optical dermoscopy but worked without access to SDDI. They excised all suspicious lesions to rule out melanoma. In a second group, the dermatologists were trained in optical and digital dermoscopy. They had the opportunity of choosing between immediate excision or follow-up by SDDI (with delayed excision if significant change was observed). The comparison of extra-costs in both groups was made possible by a decision tree model and by the division of the extra-costs by the number of melanomas diagnosed in each group. Belgian official tariffs and charges were used., Results: The extra-costs in the first and in the second group were respectively €1,613 and €1,052 per melanoma excised. The difference was statistically significant., Conclusions: Using the Belgian official tariffs and charges, we demonstrated that the selective use of SDDI for patients with one-to-three atypical melanocytic lesions resulted in a significant cost reduction.

Aims: The present observational case-control study assessed the cost-effectiveness of contemporary vascular closure devices (VCDs) for the prevention of vascular complications in an all-comers transfemoral percutaneous coronary intervention (PCI) population., Methods and Results: A total of 8,292 consecutive PCI patients were enrolled from a single-centre prospective registry from January 2005 to December 2010. VCDs were available from July 2007 and, from that time point, VCDs were implanted in 1,780 of the 5,394 patients (33%). Vascular complications occurred in 221 (2.7%) patients. The use of VCDs was independently associated with a 53% risk reduction (OR 0.47, 95% CI: 0.3-0.7) in vascular complications (3.0% vs. 1.5%) and with a 65% risk reduction (IRR 0.37, 95% CI: 0.32-0.43) in the post-PCI length of hospital stay (LOS) (mean 2.8 vs. 1.5 days). Mainly due to the reduced LOS, the patients with VCDs accrued vascular direct medical costs (VCD, diagnosis and treatment of vascular complications, post-PCI LOS) that were on average 498€ less than those accrued by the non-VCD patients. The cost-effectiveness was present across all vascular risk profiles., Conclusions: In this large, all-comers transfemoral PCI population, the use of VCDs was independently associated with a reduction in the rate of vascular complications and the post-PCI length of hospital stay and proved to be cost-saving across all vascular risk profiles.

Mumps is a potentially severe viral infection. The incidence of mumps has declined dramatically in high-income countries since the introduction of mumps antigen-containing vaccines. However, recent large outbreaks of mumps in highly vaccinated populations suggest waning of vaccine-induced immunity and primary vaccine failure. In this paper we present a simple method for identifying geographic regions with high outbreak potential, demonstrated using 2006 mumps seroprevalence data from Belgium and Belgian vaccination coverage data. Predictions of the outbreak potential in terms of the effective reproduction number in future years signal an increased risk of new mumps outbreaks. Literature reviews on serological information for both primary vaccine failure and waning immunity provide essential information for our predictions. Tailor-made additional vaccination campaigns would be valuable for decreasing local pockets of susceptibility, thereby reducing the risk of future large-scale mumps outbreaks.

Background: In any country, part of the population is sceptical about the utility of vaccination. To develop successful vaccination programmes, it is important to study and understand the defining characteristics of vaccine sceptics. Research till now mainly focused either on the underlying motives of vaccine refusal, or on socio-demographic differences between vaccine sceptics and non-sceptics. It remained till now unexplored whether both groups differ in terms of basic psychological dispositions., Methods: We held a population survey in a representative sample of the population in Flanders, Belgium (N = 1050), in which we investigated whether respondents' attitude to vaccination was associated with their basic disposition toward other community members or society in general, as measured by the Triandis and Gelfand social orientation scale., Results: We found that sceptics and non-sceptics have a different social orientation, even when several variables are controlled for. More specifically, vaccine sceptics scored significantly lower on both horizontal individualism and horizontal collectivism, indicating a lower disposition to see others as equals., Conclusion: These findings need confirmation in the context of different countries. Such insights can be valuable to optimize the design of effective communication strategies on vaccination programmes.

Background: Haemophilia is a rare hereditary haemorrhagic disease that requires regular intravenous injections of clotting factor (CF) concentrates. This study sought to estimate the health and economic burden of haemophilia in Belgium. This is the first study of its type to be conducted, and reflects the Belgian authorities' growing interest for haemophilia as part of their priority planning for rare and chronic diseases., Methods: A probabilistic model was developed in order to estimate the lifetime haemophilia burden for the 2011 birth-year Belgian cohort. The health burden was initially expressed in terms of disability-adjusted life years (DALYs), the number of healthy life years lost due to living with disability and dying prematurely. An incidence perspective was used in line with World Health Organization recommendations. The economic burden calculated from direct and indirect haemophilia-related costs was expressed in euros. Data were drawn from the literature if none were available from federal institutions or health insurance. Disability weights for DALY calculation were derived using generic quality-of-life tools such as SF-6D from the SF-36 (36-item Short-Form Health Survey; for adults) and KINDL (generic quality-of-life instrument; for children) compared to population norms. Analyses were stratified according to haemophilia type and severity., Results: In Belgium, haemophilia resulted in 145 undiscounted and unweighted DALYs in total (95% credible interval [CrI] = 90-222), which represents an average of 11 DALYs per incident case with haemophilia (95% CrI = 8-15) during his life, varying according to haemophilia severity (17 DALYs for severe haemophilia, 12 DALYs for moderate, and 4 DALYs for mild). Mean total lifetime costs reached €7.8 million per people with haemophilia, 94.3% being direct costs and 5.7% indirect costs. Clotting factors accounted for 82.5% of direct costs., Conclusions: Haemophilia represents both an economic and health burden, especially regarding individual health on an individual patient level. Initiatives to counteract this burden should be clearly identified and given full support, as this burden is likely to increase in the future, especially from an economic perspective. Our study may also contribute towards a better global evaluation of haemophilia in the future.

Objectives: Many European countries have engaged in awareness campaigns to decrease outpatient antibiotic use and several measures have been proposed, e.g. the number of defined daily doses (DDDs) or packages per 1000 inhabitants per day, producing conflicting findings. Therefore, we set out to explore what measure is most appropriate., Methods: Outpatient data on each dispensed and reimbursed medicinal package in Belgium between 2002 and 2009 were aggregated at the level of the active substance in accordance with the Anatomical Therapeutic Chemical classification and expressed as the numbers of DDDs (WHO, version 2010), packages, treatments and insured individuals per 1000 inhabitants, insured individuals and patient contacts, per day, and in July-June years. Using these measures, time trends of outpatient antibiotic use were compared and explored in detail., Results: Expressed per 1000 inhabitants per day, outpatient antibiotic use increased between 2002-03 and 2008-09 in DDDs, whereas in packages, treatments and insured individuals it decreased. The same was true for use expressed per 1000 insured individuals or when allowing for the decreasing number of patient contacts. Increasing numbers of DDDs per package (more items per package and higher doses per unit for amoxicillin and co-amoxiclav) explain these discrepancies., Conclusions: The number of packages is a more appropriate measure than the number of DDDs when assessing outpatient antibiotic use over time and the impact of awareness campaigns in countries dispensing 'complete packages'. We recommended the use of different complementary measures or caution when interpreting trends based only on DDDs.

Hepatitis B virus (HBV) can be eliminated by effective universal vaccination. In Belgium, a free-of-charge HBV vaccination programme in infants with catch-up in adolescents was introduced in 1999. To evaluate the effects in <20-year-olds, seroprotection (anti-HBs >11 mIU/ml, according to the assay) and markers of infection (anti-HBc, HBsAg) were assessed in 2443 residual sera collected 7-8 years after implementation of the programme. The maximal prevalence of a solely anti-HBs seroprotective ('vaccinated') serostatus was 82·9% at age 1 year and 60·5% at age 13 years. A clear increase was found in age cohorts targeted by the campaign after a similar serosurvey conducted 4 years earlier. The prevalence of HBV infection remained unchanged at a low level (1·8% in 2006) similar to pre-vaccination data (1993-1994). We conclude that universal HBV vaccination has achieved overall high levels of vaccine-induced immunity, despite regional variations, which may give rise to pockets of susceptible young adults in the future.

Background: In Belgium, a co-insurance system is applied in which patients pay a portion of the cost for medicines, called co-payment. Co-payment is intended to make pharmaceutical consumers more responsible, increase solidarity, and avoid or reduce moral hazards., Objective: Our objective was to study the possible influence of co-payment on sales volume and generic market share in two commonly used medicine groups: cholesterol-lowering medication [statins (HMG-CoA reductase inhibitors) and fibrates] and acid-blocking agents (proton pump inhibitors and histamine H2 receptor antagonists)., Methods and Data: The data were extracted from the Pharmanet database, which covers pharmaceutical consumption in all Belgian ambulatory pharmacies. First, the proportion of sales volume and costs of generic products were modelled over time for the two medicine groups. Second, we investigated the relation between co-payment and contribution by the national insurance agency using change-point linear mixed models., Results: The change-point analysis suggested several influential events. First, the generic market share in total sales volume was negatively influenced by the abolishment of the distinction in the maximum co-payment level for name brands and generics in 2001. Second, relaxation of the reimbursement conditions for generic omeprazole stimulated generic sales volume in 2004. Finally, an increase in co-payment for generic omeprazole was associated with a significant decrease in omeprazole sales volume in 2005. The observational analysis demonstrated several changes over time. First, the co-payment amounts for name-brand and generic drugs converged in the observed time period for both medicine groups under study. Second, the proportion of co-payment for the total cost of simvastatin and omeprazole increased over time for small packages, and more so for generic than for name-brand products. For omeprazole, both the proportion and the amount of co-payment increased over time. Third, over time the prescription of small packages shifted to an emphasis on larger packages., Conclusions: As maximum co-payment levels decreased over time, they overruled the reference pricing system in Belgium. The changes in co-payment share over time also significantly affected sales volume, but whether physicians or patients are the decisive actors on the demand side of pharmaceutical consumption remains unclear.

Objectives: Bacterial resistance to antibiotics, driven by antibiotic consumption, imposes a major threat to the effective treatment of bacterial infections. In addition to reducing the amount of antibiotics prescribed, avoiding broad-spectrum antibiotics could extend the lifetime of the current arsenal of antibiotic substances. Therefore, we documented prescriber and patient characteristics associated with the choice between amoxicillin and broader-spectrum alternatives (co-amoxiclav or moxifloxacin) in recent years in Belgium., Methods: Complete reimbursement claims data (2002-09) for antibiotic prescriptions in outpatient care, including patient and prescriber characteristics, were collected for both young children (1-5 years) and the adult population (30-60 years). A backwards selection procedure within generalized estimating equations retained the most relevant determinants., Results: The age, gender and social category of the patient were found to be predictive of the extent to which amoxicillin was prescribed instead of the broader-spectrum alternatives, with female patients generally taking a higher proportion of amoxicillin than male patients. The age category of 40-44-year-old prescribers exhibited a preference for broad-spectrum antibiotics compared with both younger and older age groups. Significant interactions between the region and the prescriber's qualification (general practitioner or paediatrician) on the choice of antibiotic for children were found., Conclusions: Patient (age, gender and social category) and prescriber characteristics (age, gender, region and qualification) had an influence on whether amoxicillin or the alternative broad-spectrum antibiotics were prescribed. These findings should help policy makers to better target future campaigns to promote prudent prescribing of antibiotics.