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Background: Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available. Methods: We performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572. Findings: In total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6–2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0–28·6) and that of medically attended RSV infection was 14·1% (12·3–16·0). Interpretation: RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections. Funding: Innovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.

This study assessed the costs and benefits of introducing routine varicella vaccination to healthy children in Germany. Three vaccination strategies were compared with that of no prevention: vaccination of all 15-month-old children: vaccination of susceptible 12-year-olds (adolescent); and a combination of strategies (children including catch-up). From a purely economic viewpoint, the adeolescent strategy was optimal: It was the only one that resulted in net direct cost savings. However, since this strategy may be less acceptable from a medical or organizational point of view and because total net savings were the highest, a second option was to begin immunization starting with the 15-month-old children and to use the catch-up strategy for 11 years (total benefit-to-cost ratio (BCR), 4.72:1; cost-effectiveness ratio (CER), DM 6915 per life-year saved) and from year 12 on to use the first strategy (BCR, 4.60:1; CER, DM 19,735 per life-year saved).

Individual-based models (IBMs) offer endless possibilities to explore various research questions but come with high model complexity and computational burden. Large-scale IBMs have become feasible but the novel hardware architectures require adapted software. The increased model complexity also requires systematic exploration to gain thorough system understanding. We elaborate on the development of IBMs for vaccine-preventable infectious diseases and model exploration with active learning. Investment in IBM simulator code can lead to significant runtime reductions. We found large performance differences due to data locality. Sorting the population once, reduced simulation time by a factor two. Storing person attributes separately instead of using person objects also seemed more efficient. Next, we improved model performance up to 70% by structuring potential contacts based on health status before processing disease transmission. The active learning approach we present is based on iterative surrogate modelling and model-guided experimentation. Symbolic regression is used for nonlinear response surface modelling with automatic feature selection. We illustrate our approach using an IBM for influenza vaccination. After optimizing the parameter spade, we observed an inverse relationship between vaccination coverage and the clinical attack rate reinforced by herd immunity. These insights can be used to focus and optimise research activities, and to reduce both dimensionality and decision uncertainty.

BackgroundThe SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries. This is important since insights derived from the study could be utilized in guiding the formulation of risk communication strategies.MethodsWe used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals.ResultsThe results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables. More specifically, participants who perceived COVID-19 to be a serious illness made fewer contacts compared to those who had low or neutral perceptions of the COVID-19 severity. Additionally, vaccinated individuals reported significantly higher number of contacts than the non-vaccinated. Further-more, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors.ConclusionOur multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant. Hence, insights derived from this study could be taken into account when designing, implementing and communicating COVID-19 interventions.

This paper documents the progress of human papillomavirus (HPV) vaccine introduction in Belgium. Information on vaccine use is based on sales statistics and reimbursement claims. From November 2007 to November 2008, the National Institute for Health and Disability Insurance reimbursed the HPV vaccine for girls aged between 12-15 years. In December 2008, the age limit was extended to include girls up to the age of 18. In November 2008, the total number of HPV vaccines sold exceeded 530,000 doses. The number of vaccines reimbursed in Belgium, for the period November 2007-November 2008, corresponds to the amount required to fully vaccinate 44% of all girls aged between 12-15 years. However, the trend was decreasing over the last 10 months. By the current reimbursement policy, we can expect that maximum half of the target population can be reached. In Flanders (one of the three Communities in Belgium), the intention is to start, from September 2010, with a free school-based HPV immunisation for girls in the first year of secondary school (12 years of age), complemented with vaccination by a physician of choice. This strategy ensures a higher HPV vaccine coverage which is expected to be as high as the current coverage in the hepatitis B vaccination programme (approximately 80%) offered to boys and girls in the same age group and under the same circumstances.

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., The COVID-19 pandemic caused many governments to impose policies restricting social interactions. Here, the authors implement an age-specific, individual-based model with data on social contacts for the Belgian population and investigate the effect of non-pharmaceutical interventions.

The COVID-19 pandemic was in 2020 and 2021 for a large part mitigated by reducing contacts in the general population. To monitor how these contacts changed over the course of the pandemic in the Netherlands, a longitudinal survey was conducted where participants reported on their at-risk contacts every two weeks, as part of the European CoMix survey. The survey included 1659 participants from April to August 2020 and 2514 participants from December 2020 to September 2021. We categorized the number of unique contacted persons excluding household members, reported per participant per day into six activity levels, defined as 0, 1, 2, 3-4, 5-9 and 10 or more reported contacts. After correcting for age, vaccination status, risk status for severe outcome of infection, and frequency of participation, activity levels increased over time, coinciding with relaxation of COVID-19 control measures. Te authors would like to thank all participants of the CoMix survey. Te CoMix study in the Netherlands was made possible through funding from the European Union’s Horizon 2020 research and innovation programme— project EpiPose (Grant Agreement Number 101003688). Tis work refects only the authors’ view. Te European Commission is not responsible for any use that may be made of the information it contains. We are grateful to the EpiPose management team for coordinating the CoMix survey so data collection was made possible in the Netherlands.

Very few studies with inactivated hepatitis A vaccines were designed for long-term follow-up of antibody persistence. Based on the serological data from these vaccine trials, mathematical models were developed to predict the decrease of anti-hepatitis A virus (anti-HAV) antibodies after vaccination. This study was designed to compare Avaxim (0–6 months) to Havrix 720 (0–1–6 months). In this paper, both groups of vaccinees are described considering the age, gender, and weight of the subjects at enrollment. For mathematical modelling, two different approaches were used: one starting the calculations from the geometric mean titres (GMTs) at each point in time, the other basing the calculations on individual anti-HAV titres. Both vaccines are very immunogenic, although Avaxim shows a higher GMT at each point in time. When these data are used in mathematical models to predict the persistence of anti-HAV antibodies, both vaccines (Avaxim and Havrix 720) show similar long-term antibody kinetics. Antibody levels ≥ 20 mIU/ml are estimated to last on average for at least 10 years after completion of the full vaccination course. Ten years after the full course, approximately 53% of subjects are estimated to have antibody levels ≥ 20 mIU/ml. At 15 years, these levels will be maintained by about 34% of vaccinees. Avaxim and Havrix 720 show a similar long-term profile of persistence of anti-HAV. A mathematical model based on GMTs appeared to give equivalent results to a model based on individual serological data. The GMT method is easier to apply than the individual based method. However, the advantage of the latter method is the possibility of calculating confidence limits for the predicted values and making estimates of the percentage of subjects having a certain level of antibody titres at a certain time. J. Med. Virol. 60:1–7, 2000. © 2000 Wiley-Liss, Inc.

Despite long-standing two-dose measles-mumpsrubella (MMR) vaccination, measles outbreaks still occur in highly vaccinated European populations. For instance, large measles outbreaks occurred in France (2008–13), the United Kingdom (2012–13) and the Netherlands (2012). Based on a multicohort model approach, using spatial serological survey data, MMR vaccination coverage data and data on social contacts, we found effective reproduction numbers significantly higher than 1 for measles in Belgium. This indicates that at one of the expected re-introductions, a measles outbreak is likely to spread, especially when it occurs during school term. The predicted average effective reproduction number increased over a 30-year time span from 1.3 to 2.2 and from 1.9 to 3.2 for basic reproduction numbers of 12 and 18, respectively. The expected relative measles incidence was highest in infants under one year of age, in adolescents and young adults. In conclusion, gradually increasing proportions of susceptible adolescents and young adults provide through their highly active social life an avenue for measles to resurge in large outbreaks upon re-introduction in Belgium, especially during school terms. Infants form an important vulnerable group during future measles outbreaks. The authors would like to acknowledge the colleagues of the Flemish Agency for Care and Health, the Scientific Institute of Public Health and the measles elimination committee for fruitful discussions related to this research. NH acknowledges support of the University of Antwerp Scientific Chair in Evidence-based Vaccinology sponsored in 2009-2014 by a gift from Pfizer. SA acknowledges support by the Research Fund of Hasselt University (Grant BOF11NI31). ES and HG acknowledge support from a Methusalem research grant from the Flemish government. NG is beneficiary of a postdoctoral grant from the AXA Research Fund. Support from the IAP Research Network P7/06 of the Belgian State (Belgian Science Policy) is gratefully acknowledged. HT and EL are postdoctoral researchers for the Fund of Scientific Research - Flanders (FWO). The computational resources and services used in this work were provided by the Hercules Foundation and the Flemish Government - department EWI.

INTRODUCTION: Treatment for acute myeloid leukemia (AML) presents a significant economic burden to patients, health care insurers and society, and is expected to remain so in the near future. There are few studies describing the costs of AML in the literature. However, the high cost of treating AML and the demographic evolution of the world population, indicate that such studies are needed to support ongoing efforts to allocate resources efficiently in health care. OBJECTIVE: To describe and compare the costs of AML therapies daily used at the Antwerp University Hospital in adult patients receiving chemotherapy with/without stem cell transplantation and in patients receiving immunotherapy using dendritic cell vaccination. DESIGN AND METHODS: This monocentric study compares direct hospital medical costs of treatment for AML between 2005 and 2010, allocated and charged according to the hospital analytic accounting system. Information on use of medical resources was collected from electronic medical records. Professional and facility charges associated with inpatient and outpatient management were collected using electronic billing information. Drug costs and drug administration costs were based on list prices published by the Belgian reimbursement authority (RIZIV/INAMI). The cost analysis distinguished between group 1, patients treated with induction and consolidation therapy alone; group 2, patients treated with induction and consolidation therapy plus allogeneic hematopoietic stem cell transplantation (HSCT) and group 3, patients treated with induction and consolidation therapy plus immunotherapy using dendritic cells engineered to express the Wilms’ tumor protein (Van Tendeloo et al. Proc Natl Acad Sci USA. 2010;107(31):13824-9). RESULTS AND DISCUSSION: 51 adult patients who were treated for newly diagnosed AML were included. Costs on medical and nursing care at the hematology ward, pharmaceutical prescriptions, transfer episodes to the intensive care ward, laboratory tests and medical imaging were analyzed. The cost of dendritic cell vaccine preparation was € 20 450 per patient. The median cost in group 1 (15 patients) was € 32,648 (range: € 4,759 - € 140,383). Only 1 patient in group 1 went into remission after induction therapy and received consolidation therapy. All patients in group 1 died within 5 year after diagnosis, 13 patients died within 1 year and 5 died within 1 month. The median cost in group 2 (26 patients) was € 184,554 (range: € 87,932 - € 449,155). The median post-consolidation treatment cost in group 2 was € 110,430 (range: € 31,364 - € 255,948). Five-year survival in group 2 was 19%. Seventeen patients in group 2 died within 1 year after HSCT. The median cost in group 3 (10 patients) was € 88,635 (range: € 23,392 - € 215,119). The median post-consolidation treatment cost in group 3 was € 40,748 (range: € 26,907- € 156,870). Five-year survival in group 3 was 30%. Four patients in group 3 died within 1 year after vaccination. CONCLUSION: This study comparing different post-consolidation therapies confirmes the high cost of treating AML and suggests that savings to the healthcare system could be achieved by sustaining complete remission status for longer periods. Dendritic cell vaccination is one of the new therapeutic options to attain a long remission status. Disclosures No relevant conflicts of interest to declare.

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. (C) 2020 Elsevier Ltd. All rights reserved. We thank Herman Van Oyen and Toon Braeye from the Belgian population health institute (Sciensano) for reading and commenting on our manuscript. This research received funding from the Flemish Government (AI Research Program). Authors NH and PB acknowledge funding from the European Union’s Horizon 2020 research and innovation programme - project EpiPose (No. 101003688 ). Authors TN, NH, PVD, and PB acknowledge funding from the Research Foundation Flanders (No. G0G1920N).

Since 2005, the world has faced several public health emergencies of international concern arising from infectious disease outbreaks. Of these, the COVID-19 pandemic has had by far the greatest health and economic consequences. During these emergencies, responses taken by one country often have an impact on other countries. The implication is that coordination between countries is likely to achieve better outcomes, individually and collectively, than each country independently pursuing its own self-interest. During the COVID-19 pandemic, gaps in multilateral cooperation on research and information sharing, vaccine development and deployment, and travel policies have hampered the speed and equity of global recovery. In this Health Policy article, we explore how multilateral collaboration between countries is crucial to successful responses to public health emergencies linked to infectious disease outbreaks. Responding to future global infectious disease threats and other health emergencies will require the creation of stronger mechanisms for multilateral collaboration before they arise. A change to the governance of multilateral institutions is a logical next step, with a focus on providing equal ownership and leadership opportunities to all member countries. Europe can be an example and advocate for stronger and better governed multilateral institutions. (C) 2021 The Author(s). Published by Elsevier Ltd.

Methods We related sales figures to coinciding price evolutions, and broke the costs down by their bearer. On the one hand we analysed a data extraction from IMS Health for Belgium for the period 2007-2013. The IMS Health database contains sales figures of a representative sample of community pharmacies including the number of packages sold (per CNK number) per month. On the other hand, we studied the corresponding unit price tables of the Belgian centre for Pharmaco-therapeutic Information (BCFI, an independent source).