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

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

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

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

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

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

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

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

Burden of four vaccine preventable diseases in older adults.

BACKGROUND: Implementation of additional targeted vaccinations to prevent infectious diseases in the older adults is under discussion in different countries. When considering the added value of such preventive measures, insight into the current disease burden will assist in prioritization. The aim of this study was derive the first estimates of the disease burden in adults aged 50 years or over in the Netherlands for influenza, pertussis, pneumococcal disease and herpes zoster. METHODS: The average annual disease burden for these four diseases in the Netherlands was calculated for the period 2010-2013 using the disability-adjusted life years (DALY) measure. Disease models and parameters were obtained from previous research. Where possible we adapted these models specifically for older adults and applied age-specific parameters derived from literature. The disease burden based on these adapted models and parameters was compared with the disease burden based on the general population models. RESULTS: The estimated average annual disease burden was from high to low: pneumococcal disease (37,223 DALYs/year), influenza (7941 DALYs/year), herpes zoster (942 DALYs/year), and pertussis (812 DALYs/year). The adaptation of models and parameters specifically for the elderly resulted in a higher disease burden compared to the use of general population models. CONCLUSIONS: Among older adults, the disease burden in the period 2010-2013 was highest for pneumococcal disease, mostly because of high mortality, followed by influenza. Disease burden of herpes zoster and pertussis was relatively low and consisted mostly of years lived with disability. Better information on the course of infectious diseases and long-term consequences would enable more accurate estimation of disease burden in older adults.

Distribution of Health Effects and Cost-effectiveness of Varicella Vaccination are Shaped by the Impact on Herpes Zoster.

INTRODUCTION: Varicella zoster virus (VZV) is the etiological agent of varicella and herpes zoster (HZ). It has been hypothesised that immune boosting of latently infected persons by contact with varicella reduces the probability of HZ. If true, universal varicella vaccination may increase HZ incidence due to reduced VZV circulation. To inform decision-making, we conduct cost-effectiveness analyses of varicella vaccination, including effects on HZ. METHODS: Effects of varicella vaccination are simulated with a dynamic transmission model, parameterised with Dutch VZV seroprevalence and HZ incidence data, and linked to an economic model. We consider vaccination scenarios that differ by whether or not they include immune boosting, and reactivation of vaccine virus. RESULTS: Varicella incidence decreases after introduction of vaccination, while HZ incidence may increase or decrease depending on whether or not immune boosting is present. Without immune boosting, vaccination is expected to be cost-effective or even cost-saving. With immune boosting, vaccination at 95% coverage is not expected to be cost-effective, and may even cause net health losses. CONCLUSIONS: Cost-effectiveness of varicella vaccination depends strongly on the impact on HZ and the economic time horizon. Our findings reveal ethical dilemmas as varicella vaccination may result in unequal distribution of health effects between generations.

The pathogen- and incidence-based DALY approach: an appropriate [corrected] methodology for estimating the burden of infectious diseases.

In 2009, the European Centre for Disease Prevention and Control initiated the 'Burden of Communicable Diseases in Europe (BCoDE)' project to generate evidence-based and comparable burden-of-disease estimates of infectious diseases in Europe. The burden-of-disease metric used was the Disability-Adjusted Life Year (DALY), composed of years of life lost due to premature death (YLL) and due to disability (YLD). To better represent infectious diseases, a pathogen-based approach was used linking incident cases to sequelae through outcome trees. Health outcomes were included if an evidence-based causal relationship between infection and outcome was established. Life expectancy and disability weights were taken from the Global Burden of Disease Study and alternative studies. Disease progression parameters were based on literature. Country-specific incidence was based on surveillance data corrected for underestimation. Non-typhoidal Salmonella spp. and Campylobacter spp. were used for illustration. Using the incidence- and pathogen-based DALY approach the total burden for Salmonella spp. and Campylobacter spp. was estimated at 730 DALYs and at 1,780 DALYs per year in the Netherlands (average of 2005-2007). Sequelae accounted for 56% and 82% of the total burden of Salmonella spp. and Campylobacter spp., respectively. The incidence- and pathogen-based DALY methodology allows in the case of infectious diseases a more comprehensive calculation of the disease burden as subsequent sequelae are fully taken into account. Not considering subsequent sequelae would strongly underestimate the burden of infectious diseases. Estimates can be used to support prioritisation and comparison of infectious diseases and other health conditions, both within a country and between countries.

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

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

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

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

Assessment of serological evidence for mumps virus infection in vaccinated children.

It is estimated that at least one-third of mumps virus infections in non-vaccinated individuals are asymptomatic. Little information is available whether this proportion is the same among those vaccinated. We validated a commercial oral fluid mumps IgG-specific Enzyme Immunoassays (EIA) with vaccinated control groups to identify symptomatic and asymptomatic mumps virus infections in vaccinated individuals during a mumps outbreak in The Netherlands. A vaccinated control group was required to define a new cutoff value for the assay, because of the presence of low but significant levels of IgG antibodies in oral fluid as a result of mumps vaccination in the past. With a new cutoff, calculated using receiver operator characteristic analysis, we identified an attack rate of 7-10% compared to 2.7% based on clinical symptoms among vaccinated children. This finding has important implications when studying transmission patterns, strain virulence, as well as mumps vaccine effectiveness to protect from infection rather than disease.

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

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