Author Correction: Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox.

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Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox.

Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-γ-producing T-cell percentages and VZV-specific antibody titres. The protective effect of re-exposure to chickenpox is likely limited, as boosting only occurred in 17-25% of the VZV re-exposed grandparents and for less than one year.

Modelling multisera data: the estimation of new joint and conditional epidemiological parameters.

Testing humans for infectious diseases is often done by assessing the presence or absence of disease-specific antibodies in serum samples. For feasibility and economical reasons, these sera are often tested for more than one antigen. Studying diseases with similar transmission routes can govern new insights for disease dynamics. We use flexible marginal and conditional models to model multisera data on the Varicella-Zoster virus and the Parvo B19-virus in Belgium. Next form the derivation of the age-dependent marginal force of infection (FOI), we introduce new epidemiological parameters: the age-dependent joint and conditional FOI. These parameters allow us to study the association among the occurrence and acquisition of both infections. Furthermore, we show how to test for association and whether the infection-specific age-dependent FOI curves are proportional and consequently whether separable mixing in the population holds.

Estimating the impact of vaccination using age-time-dependent incidence rates of hepatitis B.

The objective of this study was to model the age-time-dependent incidence of hepatitis B while estimating the impact of vaccination. While stochastic models/time-series have been used before to model hepatitis B cases in the absence of knowledge on the number of susceptibles, this paper proposed using a method that fits into the generalized additive model framework. Generalized additive models with penalized regression splines are used to exploit the underlying continuity of both age and time in a flexible non-parametric way. Based on a unique case notification dataset, we have shown that the implemented immunization programme in Bulgaria resulted in a significant decrease in incidence for infants in their first year of life with 82% (79-84%). Moreover, we have shown that conditional on an assumed baseline susceptibility percentage, a smooth force-of-infection profile can be obtained from which two local maxima were observed at ages 9 and 24 years.

Modelling age-dependent force of infection from prevalence data using fractional polynomials.

The force of infection is one of the primary epidemiological parameters of infectious diseases. For many infectious diseases it is assumed that the force of infection is age-dependent. Although the force of infection can be estimated directly from a follow up study, it is much more common to have cross-sectional seroprevalence data from which the prevalence and the force of infection can be estimated. In this paper, we propose to model the force of infection within the framework of fractional polynomials. We discuss several parametric examples from the literature and show that all of these examples can be expressed as special cases of fractional polynomial models. We illustrate the method on five seroprevalence samples, two of Hepatitis A, and one of Rubella, Mumps and Varicella.

Pharmaco-economic evaluation of targeted hepatitis A vaccination for children of ethnic minorities in Amsterdam (The Netherlands).

OBJECTIVE: Estimate cost-effectiveness of vaccination against hepatitis A virus (HAV) for children of ethnic minorities in Amsterdam. BACKGROUND: Pharmaco-economic analysis is relevant for motivating reimbursement of vaccination costs in the framework of a programmatic approach to vaccination of ethnic minorities. DESIGN: Pharmaco-economic modeling. METHOD: In cost-effectiveness analysis, costs, benefits and health gains were estimated for a large-scale HAV-vaccination for children of Turkish and Maroccan origin. Analysis was performed from the societal perspective, as recommended in the Dutch guidelines for pharmaco-economic research. This implies that indirect costs of production losses are included in the analysis. Cost-effectiveness was expressed in net costs per adult HAV-infection averted in incremental and aggregate analysis. Incremental analysis compares targeted vaccination with the current limited-scale HAV-vaccination that exists, whereas aggregate analysis compares targeted vaccination with the sheer absence of vaccination. RESULTS: Net aggregate costs of targeted HAV-vaccination for Turkish and Maroccan children in Amsterdam amounts to 61.000. Cost-effectiveness was estimated, in aggregate and incremental analysis, at 13.500 and 11.100 respectively per adult HAV-infection averted. Uni- and multivariate sensitivity analyses show that major impact on cost-effectiveness may be expected from reductions in the vaccine price through economies of scale. Probabilistic sensitivity analysis indicates possible large fluctuations in cost-effectiveness from 1 year to another, related to varying incidence of disease. CONCLUSION: HAV-vaccination for children from ethnic minorities in Amsterdam is not cost saving, but may have a favourable cost-effectiveness. Such a vaccination program fits into the recent Dutch policy of specific vaccinations directed at groups of ethnic minorities, such as for hepatitis B.

Economic evaluation of options for measles vaccination strategy in a hypothetical Western European country.

In this study an analysis was made of economic costs and medical effects (by cost-effectiveness and cost-benefit analysis) associated with measles vaccination in a hypothetical Western European country. We analysed ten vaccination options in terms of past and future vaccination coverage. We show that several of the proposed strategies for improving measles vaccination coverage are preferable to maintaining the existing policies, regardless of past coverage and the viewpoint of the analysis. For society, very high coverage (95%) two-dose vaccination is most optimal, irrespective of past vaccination coverage. The addition of a one-time campaign (to reduce susceptibility in (pre-)adolescent age groups) to such a high coverage two-dose vaccination programme is cost-saving to the health-care payer and to society when coverage in the past was low (< or = 70%). Even when coverage in the past was high (90%) for more than a decade, this 'maximum strategy' could be implemented at an acceptable cost to the health-care payer (incremental direct costs per discounted life-year gained < 30,000 Euros), and at net savings to society.

Hepatitis B in St Petersburg, Russia (1994-1999): incidence, prevalence and force of infection.

Hepatitis B (HB) is thought to be an expanding health problem in Russia. The incidence of infection was estimated from mandatorily reported HB cases in St Petersburg. The two-sided t-test for independent samples and the LOESS (locally-weighted regression) smoother were used to compare the age at infection for symptomatic, asymptomatic and chronic infections, by gender. The force of infection was estimated from seroprevalence data (907 sera taken in 1999) using a newly developed nonparametric method based on local polynomials, as well as an earlier method based on isotonic regression and kernel smoothers. With the local polynomial method, pointwise confidence intervals (95%) were constructed by bootstrapping. On average, men contracted HB infection at a significantly younger age than women (in 1999, 21.8 vs 22.7 years, respectively). The overall male to female ratio was 1.92. In 1999 the overall incidence almost doubled compared with the preceding years and tripled among the age groups with highest incidence (15-29-year olds: 85% of cases in 1999). The incidence increase was associated with a lower average age at infection (24.1 years in 1994 vs 22.1 years in 1999). The age and gender-specific force of infection estimates generally confirmed the incidence estimates and emphasized the usefulness of local polynomials to do this. Hence HB transmission in St Petersburg occurs mainly in young adults. The dramatic increase of infections in 1999 was probably due to injecting drug use. Without intervention, HB virus is expected to continue to spread rapidly with a greater proportion of female infections caused by sexual transmission. These trends may also provide an indication for HIV transmission.

The difficult quest for data on "vanishing" vaccine-preventable infections in Europe: the case of measles in Flanders (Belgium).

We aimed to describe the impact of vaccination on the epidemiology of measles infection in Flanders (Belgium), to document probable vaccination coverage based on this evidence, compare these epidemiological data with those generated by a mathematical model and estimate the costs of morbidity from measles. In contrast to previous analyses, we included the costs of long-term care for sequelae due to encephalitis and subacute sclerosing panencephalitis (SSPE). We estimated the direct health care costs per average measles case at 227, 212, 210, 200 and 194 for the age groups of 0-4, 5-9, 10-14, 15-19 and > or=20 years, respectively. Excluding long-term care lowers these estimates by 22-51%, depending on the age group. By including indirect time costs, we arrive at total costs per measles case of 320, 305, 210, 200 and 625, respectively. In addition to registering vaccination coverage more rigorously in the future, it seems necessary to undertake seroprevalence studies to document the age-specific immunity to measles. By using such information, current vaccination strategies can be adapted to prevent future outbreaks and to help eliminate measles from Europe in an efficient way. We noted throughout that many of the data sources are flawed. Better and accessible data bases are required to improve the reliability of similar studies in the future.

[Pharmaco-economic aspects of vaccination against invasive pneumococcal infections in persons over 65 years of age; review of the literature on cost effectiveness analysis]. / Farmaco-economische aspecten van vaccinatie tegen invasieve pneumokokkeninfecties bij 65-plussers; literatuuroverzicht van kosteneffectiviteitsanalysen.

OBJECTIVE: To assess the cost-effectiveness of vaccination to prevent invasive pneumococcal disease in the elderly. DESIGN: Review of the literature. METHODS: Articles in Dutch or English reporting studies into the cost-effectiveness of vaccination for the prevention of invasive pneumococcal infection in persons over 65 years of age were retrieved from Medline (1980-2000; search terms: 'pneumococcal' and 'vaccine' in combination with 'costs' or 'economics') and on the basis of the reference lists in the articles found. The following aspects of the selected studies were assessed: the net costs per year of life gained, the incidence of invasive pneumococcal disease in the elderly, the mortality due to invasive pneumococcal infections, the effectiveness of the vaccine in the prevention of invasive pneumococcal infections, and the costs of the vaccine and its administration. Attention was also given to specific age categories and to the effects of varying certain crucial assumptions. RESULTS: We retrieved a total of five studies: one each for the USA, Canada, the Netherlands and Spain and a multinational study for five European countries. The cost-effectiveness of vaccination of the elderly against invasive pneumococcal infections varied from cost savings to [symbol: see text] 33,000,-per life-year gained. The Dutch study estimated the cost-effectiveness at [symbol: see text] 10,100,-per life-year gained (price level 1995). Almost all the studies selected based their estimate of the effectiveness of vaccination on the same case-control study from the USA. The potential effects on cost-effectiveness of more extensive influenza vaccination and of the inclusion of re-vaccination against pneumococci were not included in the analyses. CONCLUSION: The cost-effectiveness of vaccination against invasive pneumococcal infections in persons over 65 years of age (in the Netherlands as well as in several other countries) was below the previously accepted threshold of [symbol: see text] 20,000,-.