Survival of patients with unfavorable prognosis cutaneous melanoma with increased use of immunotherapy agents: a population-based study in Belgium.

BACKGROUND: Although metastatic cutaneous melanoma is associated with an unfavorable prognosis, innovative therapies including immunomodulating agents and targeted therapies have shown survival benefits in clinical trials. We assessed the impact of the introduction of innovative drugs into clinical practice on the survival of patients with metastatic cutaneous melanoma during the period 2004-2017, in Belgium. The evolution of associated expenses was also analyzed. METHODS: This is a retrospective population-based study using data from the national Belgian Cancer Registry, compulsory health insurance, and administrative survival data. The immunomodulating drugs were ipilimumab, nivolumab and pembrolizumab, while targeted therapies included vemurafenib, dabrafenib and trametinib. RESULTS: We did not identify a trend for improvement over time. Median survival (years) was 1.5 (95% CI: 1.1-1.8) in 2004-2008, 1.1 (95% CI: 0.8-1.5) in 2009-2013, and 1.6 (95% CI: 1.3-2.4) in 2014-2017, respectively. In contrast, survival improved in those with unknown primary tumor localization. In this group, median survival time was 2.0 (95% CI: 1.4-2.9) in the most recent period, while it was 1.1 (95% CI: 0.7-1.3) in 2009-2013, and 0.9 (95% CI: 0.6-1.2) in 2004-2008. The uptake of innovative drugs remained modest, with no drug being used by more than 30% of patients. Yearly expenditure was almost non-existent, and gradually increased, reaching several million euros in 2014-2017. CONCLUSION: Patients with metastatic cutaneous melanoma who were diagnosed between 2004 and 2017 showed no apparent improvement in survival. In contrast, increased survival was observed in the subgroup of patients with unknown primary tumor localization.

Efficacy and safety of the recombinant zoster vaccine: A systematic review and meta-analysis.

In this systematic review with meta-analysis, the efficacy, effectiveness, and safety of the new GSK recombinant zoster vaccine (RZV) were assessed.Twenty three publications reporting on 14 studies were selected, including 2 pivotal RCTs in older immunocompetent adults (ZOE-50 and ZOE-70), 4 RCTs on immunocompromised patients (haematopoietic stem cell transplantation (HSCT), haematological malignancies, solid tumour, and renal transplantation), and 8 observational studies. Vaccine efficacy of RZV against herpes zoster (HZ) and postherpetic neuralgia (PHN) was very high in immunocompetent older adults (respectively 94% and 91.2% in adults ≥50 years and 91.3% and 88.8% in adults ≥70 years). However, the number needed to vaccinate (NNV) was relatively high (between 32 and 36 for HZ and between 261 and 335 for PHN). Slow waning of the vaccine efficacy has been described after a median follow-up of 10 years after vaccination. In patients after HSCT, vaccine efficacy of RZV against HZ was lower compared to immunocompetent adults (68.2%), while vaccine efficacy of RZV against PHN was similar (89.3%). Higher incidences of HZ and PHN in patients after HSCT resulted in higher absolute reduction of cases and lower NNV (respectively 10 and 115). Observational studies confirmed a good vaccine effectiveness, albeit lower than in RCTs (ranging between 70% and 85%). No safety signal was identified neither in RCTs with immunocompetent or immunocompromised adults nor in observational studies and post-marketing surveillance. Increased reactogenicity after RZV vaccination, limited in extent and duration, did not result in low second dose compliance. Conclusion: Although vaccine efficacy in RCTs and effectiveness in the real world has been reported to be good, it needs to be stressed that high numbers of immunocompetent adults need to be vaccinated to prevent HZ and PHN. Due to higher incidence, more acceptable NNVs were calculated in immunocompromised adults after HSCT.

Belgian observational survival data (incidence years 2004-2017) and expenditure for innovative oncology drugs in twelve cancer indications.

BACKGROUND: The Food and Drug Administration and European Medicines Agency typically approve market access for cancer drugs based on surrogate end-points, which do not always translate into substantiated improvements in outcomes that matter the most to patients, i.e. survival and quality of life. These drugs often, also, have a high price tag. We assessed whether there was an increase in cancer drug expenditure for a broad selection of indications, and whether this correlates with increased overall survival. METHODS: This cohort study used Belgian Cancer Registry data from 125,692 patients (12 cancer indications, incidence period 2004-2017), which was linked to reimbursement and survival data. This reliably represents the Belgian situation. One-to-five year observed survival probability, median survival time, oncology drug expenditure and mean oncology drug cost per patient were reviewed. FINDINGS: In almost all indications, total expenditure and average treatment cost for oncology drugs increased over the years (2004-2017). In contrast, mixed findings are observed for the evolution in overall survival probability and median survival time. While an absolute improvement in the 3-year survival probability of about 10% is noticed in non-small-cell lung cancer and chronic myeloid leukaemia, improvements in about half of the other indications are limited or even absent. INTERPRETATION: The Belgian observational data indicate that assuming 'innovative' oncology drugs always add value in terms of improved survival is often unjustified. The literature also highlights the problem of using surrogate end-points, and the lack of comparative evidence showing an added value of oncology drugs for both survival and quality of life at market approval or during the post-marketing phase. Comparative studies should be conducted in the pre-marketing phase that are suitable for registration purposes, aid reimbursement decisions and support physicians and patients when making treatment decisions.

Survival in stage IV ovarian cancer with increased use of debulking surgery and bevacizumab.

OBJECTIVES: Advanced ovarian cancer has a poor prognosis, with a 5 year survival probability of <30%. Attempts to improve survival have focused on debulking surgery and systemic therapy. We assessed the evolution of treatment patterns and survival of patients with advanced epithelial ovarian cancer with specific attention to changes in survival after introducing bevacizumab. METHODS: Population based data from the Belgian Cancer Registry were coupled with administrative reimbursement data from the compulsory health insurance organizations and the national database where date of death is registered, based on the patient's unique national number. Patients with epithelial ovarian cancer stage IV diagnosed in 2004-17 were included. The proportion of patients who underwent debulking surgery and received bevacizumab was calculated per incidence year. Survival was compared for the three incidence periods (2004-08, 2009-13, 2014-17) and before and after the introduction of bevacizumab. RESULTS: 2034 patients with stage IV epitheial ovarian cancer were included. From 2012 onwards, uptake of bevacizumab increased, with 50% of patients with stage IV ovarian cancer diagnosed in 2017 receiving bevacizumab. The proportion of stage IV patients who underwent debulking surgery also increased over time, from 21.1% in 2004-08 to 50.4% and 45.4% in 2009-13 and 2014-17, respectively. The 3 year observed survival probability fluctuated between 27% and 42% without a trend over time. The increase in debulking surgery was associated with improved survival (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79 to 0.98) but the introduction of bevacizumab was not (HR 0.94, 95% CI 0.85 to 1.03). For patients diagnosed in 2004, the mean cost per patient treated with oncological drugs was about €12 500, which doubled to about €25 000 for patients diagnosed in 2014 or later. CONCLUSIONS: Despite a rise in the use of debulking surgery and the introduction of bevacizumab into clinical practice, no improvement in 3 year survival probability was observed for patients with advanced ovarian cancer in Belgium.

An evaluation of managed entry agreements in Belgium: A system with threats and (high) potential if properly applied.

OBJECTIVE: To evaluate the strengths and weaknesses of managed entry agreements (MEAs) in Belgium. METHODS: All Belgian MEAs signed between 2010 and 2015 (n = 71) were studied, including the re-evaluations of 16 reimbursement requests for which the initial MEA had ended. The analysis was supported by the findings from a systematic literature review and structured interviews with Belgian stakeholders. RESULTS: The current application of MEAs provides the short-term advantage of getting a positive reimbursement decision with lower confidential prices. However, it is not clear whether the negotiated prices are in line with the added value of the interventions. Furthermore, the contracts do not provide incentives for manufacturers to gather evidence or to set public prices at an acceptable level. CONCLUSIONS: Based on our analysis of the Belgian MEAs and discussions with Belgian stakeholders, an overview of various issues and pitfalls related to the current application of the system is given. Recommendations are made related to providing correct incentives to deliver good evidence, establishing a correct link between identified uncertainties/problems and the type and content of the MEA, reducing the risk of making the system non-transparent, the importance of international collaboration, etc. in order to optimize the potential of this system. These recommendations are addressed to both the Belgian policymakers and stakeholders in other countries making use of MEAs.

Economic evaluation of pneumococcal vaccines for adults aged over 50 years in Belgium.

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.

Belgian guidelines for economic evaluations: second edition.

OBJECTIVES: The aim of this study was to present the updated methodological guidelines for economic evaluations of healthcare interventions (drugs, medical devices, and other interventions) in Belgium. METHODS: The update of the guidelines was performed by three Belgian health economists following feedback from users of the former guidelines and personal experience. The updated guidelines were discussed with a multidisciplinary team consisting of other health economists, assessors of reimbursement request files, representatives of Belgian databases and representatives of the drugs and medical devices industry. The final document was validated by three external validators that were not involved in the previous discussions. RESULTS: The guidelines give methodological guidance for the following components of an economic evaluation: literature review, perspective of the evaluation, definition of the target population, choice of the comparator, analytic technique and study design, calculation of costs, valuation of outcomes, definition of the time horizon, modeling, handling uncertainty and discounting. We present a reference case that can be considered as the minimal requirement for Belgian economic evaluations of health interventions. CONCLUSIONS: These guidelines will improve the methodological quality, transparency and uniformity of the economic evaluations performed in Belgium. The guidelines will also provide support to the researchers and assessors performing or evaluating economic evaluations.

Should chronic hepatitis B be treated as early as possible?

OBJECTIVES: We studied the cost-effectiveness of tenofovir and entecavir in e antigen positive (CHBe+) and negative (CHBe-) chronic hepatitis B. METHODS: Using a multicenter survey including 544 patients we measured patient quality of life and attributable costs by clinical disease stage. Natural disease progression was studied in 278 patients in a single center. A Markov model was constructed to follow hypothetical cohorts of treated and untreated 40-year-old CHBe+ and CHBe- patients and 50-year-old patients with compensated cirrhosis. RESULTS: We did not find an improvement in quality of life when viral load was reduced under treatment. Transition rates to liver cirrhosis were found to be age-dependent. Assuming equal effectiveness, tenofovir dominates the entecavir strategy because of its lower price in Belgium. The incremental cost-effectiveness ratio (ICER) of tenofovir after 20 years is more favorable for treating Caucasian cirrhotic patients (mean ICER €29,000/quality-adjusted life-year [QALY]) compared with treating non-cirrhotic patients (mean ICER €110,000 and 131,000/QALY for CHB e+ and e-, respectively). Within the non-cirrhotic patients the ICER decreases with increasing cohort starting age from 30 to 50 years. CONCLUSIONS: Results of long-term models for tenofovir or entecavir treatment of CHB need to be interpreted with caution as long-term trials with hard end points are lacking. Especially the effect on HCC remains highly uncertain. Based on cost-effectiveness considerations such antiviral treatment should be targeted at patients with cirrhosis or at risk of rapid progression to this disease stage.

Calculating an intervention's (cost-)effectiveness for the real-world target population: the potential of combining strengths of both RCTs and observational data.

Economic evaluations most often use results from randomised controlled trials (RCTs) to model effectiveness. Inconsiderate application of the absolute treatment effect from RCTs may result in unrealistic estimates of an intervention's benefit for the real-world target population. The baseline risk of events in this target population may differ significantly from the baseline risk in the RCT population. An approach to handle this problem is to combine observational data with evidence from RCTs. Reliable administrative or register data can provide an estimate of the real-world baseline risks. In combination with the relative treatment effect from well-performed RCTs this results in an estimate of the absolute benefit for the relevant target population. Applying this approach, one must remain cautious about the validity of the assumption of a constant relative treatment effect.

Using threshold values for cost per quality-adjusted life-year gained in healthcare decisions.

BACKGROUND: In many countries, the incremental cost-effectiveness ratio (ICER) is used to assess whether an intervention is worth its costs. At the same time, policy makers often feel uncomfortable with refusing reimbursement of any intervention purely on the basis of the fact that the ICER exceeds a specific threshold value. Reluctance to define a single threshold value for the ICER seems to have been stronger in social security systems than in national healthcare services systems. This study explores how basic differences between healthcare systems impact upon the potential usefulness of an ICER threshold value. METHODS: This study is a narrative review of literature about the theoretical foundations of the ICER threshold value approach and its practical relevance in different types of healthcare systems. RESULTS: A single ICER threshold value cannot be maintained, defined, or measured and should not be used as a policy-making tool. None of the solutions presented up until now to make the ICER threshold approach a valuable policy-making tool overcome the important weaknesses of the approach. CONCLUSIONS: ICERs and ICER threshold values are insufficient for assessing interventions' value for money. Rather, they should be considered as one element in the decision-making process. Complete rationalization of the decision-making process by means of quantitative decision criteria is undesirable and not feasible. Increasing transparency in the criteria used for a decision and explicitness about the relative importance of each criterion should, therefore, be the major goal.

Tiotropium's cost-effectiveness for the treatment of COPD: a cost-utility analysis under real-world conditions.

BACKGROUND: Tiotropium is reimbursed since March 2004 in Belgium for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Questions however remain on this product's value for money. The purpose of this study is to calculate tiotropium's cost-effectiveness under real-world conditions. METHODS: Strengths of both observational and RCT data were combined in a model. A large longitudinal (2002-2006) observational dataset of regular tiotropium users (56,321 patients) was analysed to retrieve the baseline risk for exacerbations and exacerbation-related hospitalisations the year before the first delivery of tiotropium. The relative treatment effect from the UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial was then applied to this baseline risk to reflect the effect of tiotropium treatment and calculate the intervention's incremental cost-effectiveness ratio (ICER). RESULTS: After 1000 Latin Hypercube simulations, the incremental benefit expressed as quality-adjusted life years (QALY) gained is on average 0.00048 (95% confidence interval (CI) 0.00009-0.00092). In combination with a substantial mean incremental cost of €373 per patient (95% CI 279-475), this results in an unfavourable average ICER of €1,244,023 (95% CI 328,571-4,712,704) per QALY gained. Results were most sensitive to the treatment effect on hospitalisations. Based on our large observational database, up to 89% of the patients were not hospitalised for COPD in the year before the first tiotropium delivery. CONCLUSIONS: The main cause for tiotropium's unfavourable cost-effectiveness ratio is a combination of a relative high price for tiotropium, a low number of hospitalisations without tiotropium treatment (on average 0.14/year) and a non-significant treatment effect (on average 0.94) with respect to avoiding exacerbation-related hospitalisations. From an economic point of view, a revision of reimbursement modalities (e.g. with a lower price) would be justified and would entail a more efficient use of resources.

Cost-effectiveness of human papillomavirus vaccination in Belgium: do not forget about cervical cancer screening.

OBJECTIVES: The cost-effectiveness of adding a human papillomavirus (HPV) vaccination program in 12-year-old females to the recommended cervical cancer screening in Belgium is examined. Moreover, the health and economic consequences of a potential decline in screening uptake after initiation of a HPV vaccination program are investigated. METHODS: A static Markov model is developed to estimate the direct effect of vaccination on precancerous lesions and cervical cancers. RESULTS: Vaccination is estimated to avoid 20 percent of the cervical cancers occurring in a 12-year-old girls' cohort and to cost 32,665 euro per quality-adjusted life-year (QALY) gained (95 percent credibility interval [CrI]: 17,447 euro to 68,078 euro), assuming a booster injection after 10 years, a limited duration of protection and discounting costs and effects at 3 percent and 1.5 percent, respectively. Assuming lifelong protection, HPV vaccination is estimated to cost 14,382 euro (95 percent CrI: 9,238 euro to 25,644 euro) per QALY gained, while avoiding 50 percent of the cervical cancer cases. In the base-case, a 10 percent reduction in screening compliance after vaccination obliterates the effect of vaccination on cervical cancer cases avoided, whereas further declines in the level of screening compliance even turned out to be detrimental for the cohort's health, inducing a mean loss in QALYs and life-year gained compared with the situation prevaccination. CONCLUSIONS: An HPV vaccination program should only be considered if the level of screening after vaccination can be maintained.

Cost effectiveness of implantable cardioverter-defibrillators for primary prevention in a Belgian context.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy was traditionally applied in patients who survived a cardiac arrest or who experienced a symptomatic ventricular tachyarrhythmia. Its use in primary prevention (i.e. in patients who have yet to experience a serious arrhythmic event, but who are considered at high risk for sudden cardiac death) has become more common, and policy makers question whether ICD therapy should be reimbursed in these instances. OBJECTIVE: To assess the cost effectiveness of primary prevention ICD therapy versus conventional therapy from the perspective of the Belgian health insurance system. METHOD: A lifetime 1-month cycle Markov model was constructed and populated with clinical and effectiveness data from the SCD-HeFT study and real-world Belgian cost data expressed in year 2005 values. Probabilistic modelling and sensitivity analyses were performed. RESULTS: ICD therapy results in 1.22 life-years gained (LYG) or 1.03 QALYs gained. The lifetime cost-effectiveness and cost-utility ratios were euro 59,989 (95% CI 35 873, 113 518) per LYG and euro 71 428 (95% CI 40 225, 134 623) per QALY gained, respectively. A cost-effectiveness ratio

Varicella vaccination in Europe: are we ready for a universal childhood programme?

Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

Introduction of emerging medical devices on the market: a new procedure in Belgium.

When new medical technologies enter the market, there is often uncertainty about the added value for the patient and for society, hampering well-considered decision making about reimbursement. Current Belgian legislation already offered opportunities for the managed uptake of possibly innovative emerging implants. However, it has also some shortcomings such as the lack of a clear research design, rendering the scientific evaluation of clinical effectiveness, cost-effectiveness, and patient or organizational issues more difficult. Against this background, a new procedure was elaborated by the Belgian health insurance institute and the Belgian Health Care Knowledge Centre.

Convincing or confusing? Economic evaluations of childhood pneumococcal conjugate vaccination--a review (2002-2006).

We review 15 economic analyses of pneumococcal conjugate vaccines, published between 2002 and 2006, in terms of methodology, assumptions, results and conclusions. We found a great diversity in assumptions (eg, vaccine efficacy parameters, incidence rates for both invasive and non-invasive disease) mainly due to local variation in data and opinions. Accordingly, the results varied greatly, from total net savings to over euro 100,000 per discounted QALY gained. The cost of the vaccination program (determined by price per dose and schedule (4 or 3 doses, or fewer)), and likely herd immunity impacts are highly influential though rarely explored in these published studies. If the net long-term impact (determined by a mixture of effects related to herd immunity, serotype replacement, antibiotic resistance and cross reactivity) remains beneficial and if a 3-dose schedule confers near-equivalent protection to a 4-dose schedule, the cost-effectiveness of PCV7 vaccination programs can be viewed as attractive in developed countries.

An economic evaluation of varicella vaccination in Italian adolescents.

An economic evaluation was performed to assess five varicella vaccination scenarios targeted to 11-year-old Italian adolescents. The scenarios were: "compulsory vaccination" of all adolescents, recommended vaccination of susceptible adolescents on the basis of an "anamnestic screening", a "blood test" or a combination of both ("both tests") and vaccination of adolescents in the private sector, at the parents' charge ("private vaccination"). Probabilities and unit costs were taken from published sources and experts opinion. The accuracy of the anamnestic screening (81.6% sensitivity and 87.3% specificity) was derived from a separate descriptive study among 344 Italian adolescents. The costs and benefits of each scenario were simulated using a Markov model and cost-effectiveness, budget-impact and cost-benefit analyses were conducted. Of all considered scenarios, "both tests" and "anamnestic screening" were the most appealing options with an estimated net direct cost of 5058 and 8929 per life-year gained (compared to no vaccination) versus 14,693-42,842 for the other scenarios. These two scenarios further resulted in substantial net savings for society (over 600,000 per cohort, BCR: 2.17). The need for a serological confirmation was highly dependent on the sensitivity of the anamnestic screening, which is believed to increase once such a program is launched. For practical considerations, "anamnestic screening" seems to be the most convenient option.

Economic evaluations of varicella vaccination programmes: a review of the literature.

Chickenpox infections are generally mild but due to their very high incidence among healthy children they give rise to considerable morbidity and occasional mortality. With the development of a varicella vaccine in the early 1970s and its progressive licensing in many countries, interest in the efficiency of varicella immunisation programmes grew. The objective of this review was to discuss the methodological aspects and results of published economic evaluations of varicella vaccination. From this, we attempted to make recommendations. A computerised search was carried out; 17 full economic evaluations of varicella vaccination were retrieved. The review identified the methodological divergences and similarities between the articles in four areas: study design, epidemiological data, economic data and model characteristics. We assessed to what extent the applied methods conform to general guidelines for the economic evaluation of healthcare interventions and compared the studies' results. The desirability of a universal vaccination programme depends on whose perspective is taken. Despite variability in data and model assumptions, the studies suggest that universal vaccination of infants is attractive to society because large savings occur from averted unproductive days for parents. For the healthcare payer, universal vaccination of infants does not generate savings. Vaccination of susceptible adolescents has been proposed by some authors as a viable alternative; the attractiveness of this is highly dependent on the negative predictive value of anamnestic screening. Targeted vaccination of healthcare workers and immunocompromised individuals appears relatively cost effective. Findings for other target groups are either contradictory or provide insufficient evidence for any unequivocal recommendations to be made. High sensitivity to vaccine price was reported in most studies. This review highlights that some aspects of these studies need to be further improved before final recommendations can be made. First, more transparency, completeness and compliance to general methodological guidelines are required. Second, because of the increasing severity of varicella with age, it is preferable and in some cases essential to use dynamic models for the assessment of universal vaccination strategies. Third, most studies focused on the strategy of vaccinating children only while their results depended heavily on disputable assumptions (regarding vaccine effectiveness and impact on herpes zoster). Since violation of these assumptions could have important adverse public health effects, we suggest pre-adolescent vaccination as a more secure alternative. This option deserves more attention in future analyses.

The seroepidemiology of primary varicella-zoster virus infection in Flanders (Belgium).

UNLABELLED: The age-specific seroprevalence of varicella-zoster virus (VZV) antibodies was assessed in a sample of the Flemish (Belgian) population. ELISA tests were used to analyse 1673 sera from subjects aged 1 to 44 years (October 1999-April 2000). Chickenpox infections in Flanders appear to affect children at a younger age than in other European countries since 47.37% (95% CI: 37.33-57.41) is already immune at 2 years of age. For older age-groups, the prevalence is similar to that of most European countries: 80.19% (95% CI: 72.60-87.78) at 5 years, 92.52% (95% CI: 87.54-97.51) at 9 years and 100%> or =40 years. The accuracy of non-positive recollections of varicella histories among Flemish 10 to 17-year olds was examined on the basis of a second (residual) serum bank. In this group, VZV seroprevalence was almost always 100% (or nearly 100%), irrespective of age, degree of reliability (negative or uncertain answers) or level of ascertainment (child personally or parents). The limited size of this second data set did not allow for an accurate assessment of the negative predictive value of such recollections. CONCLUSION: since varicella-zoster virus predominantly affects very small children and is generally perceived as benign, the required high coverage rate of a universal childhood varicella vaccination programme may be hard to attain. Adolescent strategies can minimise the population risks involved but the accuracy of non positive antecedents of chickenpox needs to be documented to assess the efficiency of such strategies.