1,721,098 research outputs found
Een kwantitatieve analyse van varicella-zoster virus infectie: van immunologie tot epidemiologie
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Een kwantitatieve analyse van varicella-zoster virus infectie: van immunologie tot epidemiologie
No full textnot availabl
Cost‑Efectiveness Analysis of Herpes Zoster Vaccination in 50‑ to 85‑Year‑Old Immunocompetent Belgian Cohorts: A Comparison between No Vaccination, the Adjuvanted Subunit Vaccine, and Live‑Attenuated Vaccine
No full textBackground 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 euro40,000 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 euro40,000 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 euro40,000 per QALY gained, if its price drops to euro55.40 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).This work was supported in part by Research Foundation-Flanders (JB), the Methusalem financing program of the Flemish government (ZP). The funding agreements ensured the authors’ independence in designing the study, interpreting the data, and writing and publishing the report.
We would like to thank the colleagues from the SIMID group for their input during our monthly meetings
An ODE-based mixed modelling approach for B- and T-cell dynamics induced by Varicella-Zoster Virus vaccines in adults shows higher T-cell proliferation with Shingrix than with Varilrix
No full textAbstract: Clinical trials covering the immunogenicity of a vaccine aim to study the longitudinal dynamics of certain immune cells after vaccination. The corresponding immunogenicity datasets are mainly analyzed by the use of statistical (mixed effects) models. This paper proposes the use of mathematical ordinary differential equation (ODE) models, combined with a mixed effects approach. ODE models are capable of translating underlying immunological post vaccination processes into mathematical formulas thereby enabling a testable data analysis. Mixed models include both population-averaged parameters (fixed effects) and individual-specific parameters (random effects) for dealing with inter- and intra-individual variability, respectively. This paper models B-cell and T-cell datasets of a phase I/II, open-label, randomized, parallel-group study (NCT00492648) in which the immunogenicity of a new Herpes Zoster vaccine (Shingrix) is compared with the original Varicella Zoster Virus vaccine (Varilrix). Since few significant correlations were found between the B-cell and T-cell datasets, each dataset was modeled separately. By following a general approach to both the formulation of several different models and the procedure of selecting the most suitable model, we were able to propose a mathematical ODE mixed-effects model for each dataset. As such, the use of ODE-based mixed effects models offers a suitable framework for handling longitudinal vaccine immunogenicity data. Moreover, this approach allows testing for differences in immunological processes between vaccines or schedules. We found that the Shingrix vaccination schedule led to a more pronounced proliferation of T-cells, without a difference in T-cell decay rate compared to the Varilrix vaccination schedule. (C) 2019 Elsevier Ltd. All rights reserved
Estimating transmission parameters using social contact data and serological data
No full textIn order to restrict the damage caused by an epidemic, intervention strategies are needed to reduce the transmission of infected-specific antigens. To this purpose, the estimation of age-dependent transmission rates is required. In the past, different mixing patterns were imposed to the so-called Who-Acquires-Infection-From-Whom matrix (WAIFW) to make them estimable from seroprevalence data (Anderson and May, 1991). These mixing assumptions, however are rather artificial and result in large differences on the estimation of the basic reproduction number R0, a basic quantity in infectious disease epidemiology. More recently, an alternative approach has come up, originating from assuming transmission rates for directly transmitted airborne infections are proportional to rates of conversational contact making (Wallinga et al., 2006). In this paper, we shown how transmission parameters can be estimated using serological data on varicella zoster virus (VZV) and social contact data from Belgium. We elaborate on the methodology as presented by Walling et al. (2006), by explicitly accounting for the different sources of variability, using a continuous rather than discrete modeling approach and by testing the proportionality assumption. A cross-sectional survey on social contacts was conducted in Belgium from March to June 2006. Contacted persons had to record their contacts during one day including characteristics as age, gender, location and duration of the contact. Moreover, a distinction between two types of contact was made: non-close contacts, defined as a two-way conversation of at least three words in each others proximity, and close contacts that involve any sort of physical skin-to-skin touching. The 'social contact matrix' is estimated using a bivariate smoothing approach based on thin plate regression splines. Using the mass action principle, these estimated contact rates are contrasted to seroprevalence data to obtain transmission parameters. A first analysis focuses on the constant proportionality assumption: transmission rates are proportional to contact rates up to a constant q. Five contact types which are likely to be responsible for VZV transmission are considered. According to the AIC-criterion, close contacts lasting longer than 15 minutes are most capable of explaining the observed serological profile. A non-parametric bootstrap approach is applied to assess sampling variability and to account for age uncertainty. Secondly, we explore whether the proportionality factor q depends on the age of the susceptible person, the age of the infected person or both. This consideration makes logical sense, since transmission dynamics might also be influenced by age differences in susceptibility, infectivity, hygiene, etc. Age dependence is modeled using discrete structures as well as loglinear regression models. For VZV in Belgium, extending the model to age-dependent proportionality entails an improvement in fit. Concepts of model selection uncertainty are illustrated for the set of candidate models and a model averaged estimate is calculated for the set of candidate models and a model averaged estimate is calculated for the basic reproduction number R0
Estimating transmission parameters using social contact data and serological data
No full textIn order to restrict the damage caused by an epidemic, intervention strategies are needed to reduce the transmission of infected-specific antigens. To this purpose, the estimation of age-dependent transmission rates is required. In the past, different mixing patterns were imposed to the so-called Who-Acquires-Infection-From-Whom matrix (WAIFW) to make them estimable from seroprevalence data (Anderson and May, 1991). These mixing assumptions, however are rather artificial and result in large differences on the estimation of the basic reproduction number R0, a basic quantity in infectious disease epidemiology. More recently, an alternative approach has come up, originating from assuming transmission rates for directly transmitted airborne infections are proportional to rates of conversational contact making (Wallinga et al., 2006). In this paper, we shown how transmission parameters can be estimated using serological data on varicella zoster virus (VZV) and social contact data from Belgium. We elaborate on the methodology as presented by Walling et al. (2006), by explicitly accounting for the different sources of variability, using a continuous rather than discrete modeling approach and by testing the proportionality assumption. A cross-sectional survey on social contacts was conducted in Belgium from March to June 2006. Contacted persons had to record their contacts during one day including characteristics as age, gender, location and duration of the contact. Moreover, a distinction between two types of contact was made: non-close contacts, defined as a two-way conversation of at least three words in each others proximity, and close contacts that involve any sort of physical skin-to-skin touching. The 'social contact matrix' is estimated using a bivariate smoothing approach based on thin plate regression splines. Using the mass action principle, these estimated contact rates are contrasted to seroprevalence data to obtain transmission parameters. A first analysis focuses on the constant proportionality assumption: transmission rates are proportional to contact rates up to a constant q. Five contact types which are likely to be responsible for VZV transmission are considered. According to the AIC-criterion, close contacts lasting longer than 15 minutes are most capable of explaining the observed serological profile. A non-parametric bootstrap approach is applied to assess sampling variability and to account for age uncertainty. Secondly, we explore whether the proportionality factor q depends on the age of the susceptible person, the age of the infected person or both. This consideration makes logical sense, since transmission dynamics might also be influenced by age differences in susceptibility, infectivity, hygiene, etc. Age dependence is modeled using discrete structures as well as loglinear regression models. For VZV in Belgium, extending the model to age-dependent proportionality entails an improvement in fit. Concepts of model selection uncertainty are illustrated for the set of candidate models and a model averaged estimate is calculated for the set of candidate models and a model averaged estimate is calculated for the basic reproduction number R0
Using empirical social contact data to model person to person infectious disease transmission: An illustration for varicella
No full textWith the aim to improve dynamic models for infections transmitted predominantly through non-sexual social contacts, we compared three popular model estimation methods in how well they fitted seroprevalence data and produced estimates for the basic reproduction number R0 and the effective vaccination level required for elimination of varicella. For two of these methods, interactions between age groups were parameterized using empirical social contact data whereas for the third method we used the current standard approach of imposing a simplifying structure on the ‘Who Acquires Infection From Whom’ (WAIFW) matrix. The first method was based on solving a set of differential equations to obtain an equilibrium value of the proportion of susceptibles. The second method was based on finding a solution for the age-specific force of infection using the formula of the mass action principle by means of iteration. Both solutions were contrasted with observed age-specific seroprevalence data. The best fit of the WAIFW matrix was obtained with contacts involving touching, and lasting longer than 15 min per day. Plausible values for R0 for varicella in Belgium ranged from 7.66 to 13.44. Both approaches based on empirical social contact data provided a better fit to seroprevalence data than the current standard approach.This study was made as part of ‘SIMID’, a strategic basic research project funded by the institute for the Promotion of Innovation by Science and Technology in Flanders (IWT), project number
060081. We also gratefully acknowledge support from IAP research Network P6/03 of the Belgian Government (Belgian Science Policy). The work benefited from discussions held as part of POLYMOD, a European Commission project funded within the Sixth Framework Programme, Contract No. SSP22-CT-2004-502084
Cost-effectiveness of vaccination against herpes zoster in adults aged over 60 years in Belgium
No full textAim: To assess the cost-effectiveness of vaccinating all or subgroups of adults aged 60 to 85 years against herpes zoster. Methods: A deterministic compartmental static model was developed (in freeware R), in which cohorts can acquire herpes zoster according to their age in years. Surveys and database analyses were conducted to obtain as much as possible Belgian age-specific estimates for input parameters. Direct costs and Quality-Adjusted Life-Year (QALY) losses were estimated as a function of standardised Severity Of Illness (S01) scores (i.e. as a function of the duration and severity of herpes zoster disease). Results: Uncertainty about the average SOIscore for a person with herpes zoster, the duration of protection from the vaccine, and the population that can benefit from the vaccine, exerts a major impact on the results: under assumptions least in favour of vaccination, vaccination is not cost-effective ( i.e. incremental cost per QALY gained > (sic) 48,000 for all ages considered) at the expected vaccine price of 90 per dose. At the same price, but under assumptions most in favour of vaccination, vaccination is found to be costeffective (i.e. incremental cost per QALY gained < (sic) 5500 for all ages considered). Vaccination of age cohort 60 seems more cost-effective than vaccination of any older age cohort in Belgium. Discussion: If the vaccine price per dose drops to (sic) 45, HZ vaccination of adults aged 60-64 years is likely to be cost-effective in Belgium, even under assumptions least in favour of vaccination. Unlike previous studies, our analysis acknowledged major methodological and model uncertainties simultaneously and presented outcomes for 26 different target ages at which vaccination can be considered (ages 60-85). (C) 2011 Elsevier Ltd. All rights reserved.We thank Judith Breuer (Department of infection and Immunity, University College London, UK) and John Edmunds (Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, UK) for providing data from the Scott et al. study. We also thank two anonymous referees for their thoughtful comments on a previous version of this manuscript. This study was co-funded by the Belgian Health Care Knowledge Center,the Institute for the Promotion of Innovation by Science and Technology in Flanders (strategic basic research project, Simulation models of infectious disease transmission and control processes (SIMID)), and the IAP research network nr P6/03 of the Belgian Government (Belgian Science Policy). NH acknowledges support from the University of Antwerp scientific chair in Evidence-Based Vaccinology, financed in 2009–2011 by a gift from Pfizer
Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies
No full textIntroductionStudying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research. MethodsWe adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients. ResultsStarting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population's characteristics. ConclusionThe results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines.Funding
BO acknowledges funding received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 851752-CELLULOEPI) and Research Foundation Flanders (FWO) (grant agreement 1861219N). NH and IGF acknowledge support from the EBOVAC3 project which has received funding from the IMI2 Joint Undertaking under grant agreement No 800176 (IMI-EU).
Acknowledgments
We thank Nina Keersmaekers for her contribution in the early stages of this work. Also, we acknowledge that the resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation - Flanders (FWO) and the Flemish Government
Within-host modeling to measure dynamics of antibody responses after natural infection or vaccination: A systematic review
No full textWithin-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models.TheEBOVAC3projecthasreceivedfundingfromtheIMI2Joint UndertakingundergrantagreementNo800176(IMI-EU).This JointUndertakingreceivessupportfromtheEuropeanUnion’s Horizon2020researchandinnovationprogramme,EuropeanFederationofPharmaceuticalIndustriesandAssociations(EFPIA)and theCoalitionforEpidemicPreparednessInnovations(CEPI).This projecthasreceivedfundingfromtheEuropeanResearchCouncil (ERC)undertheEuropeanUnion’sHorizon2020researchand innovationprogramme(GrantagreementNo.851752)andthe FWOseniorclinicalinvestigatorofBensonOgunjimi(1861219N ResearchFoundationFlanders).
Acknowledgements
IGFandNHacknowledgesupportfromtheEBOVAC3project whichhasreceivedfundingfromtheIMI2JointUndertakingunder grantagreementNo800176(IMI-EU).ThisJointUndertaking receivessupportfromtheEuropeanUnion’sHorizon2020research andinnovationprogramme,EuropeanFederationofPharmaceuticalIndustriesandAssociations(EFPIA)andtheCoalitionfor Epidemic PreparednessInnovations(CEPI).BOacknowledges fundingreceivedfromtheEuropeanResearchCouncil(ERC)under theEuropeanUnion’sHorizon2020researchandinnovationprogramme(grantagreement851752-CELLULO-EPI)andResearch FoundationFlanders(FWO)(grantagreement1861219N)
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