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

      de Boer, Pieter T; van Lier, Alies; de Melker, Hester; van Wijck, Albert J M; Wilschut, Jan C; van Hoek, Albert Jan; Postma, Maarten J (2018-12-06)
      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. 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. 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. 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.
    • The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses.

      Zimmermann, Petra; Perrett, Kirsten P; Messina, Nicole L; Donath, Susan; Ritz, Nicole; van der Klis, Fiona R M; Curtis, Nigel (2019-08-01)
      In total, 471 healthy infants were included. At 7 and 13 months of age, antibodies to the primary course of routine vaccines given at 6 weeks, 4 and 6 months of age (pertussis (pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN)), polio (type 1, 2, 3), Haemophilus influenzae type b (Hib), pneumococcus (serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)) were measured, and at 13 months of age, antibodies to the 12-month routine vaccines (Hib, meningococcus C, measles, mumps and rubella). The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared between infants whose mothers did or did not receive dTpa or TIV immunisation during pregnancy.
    • Effectiveness of Early Measles, Mumps, and Rubella Vaccination Among 6-14-Month-Old Infants During an Epidemic in the Netherlands: An Observational Cohort Study.

      Woudenberg, Tom; van der Maas, Nicoline A T; Knol, Mirjam J; de Melker, Hester; van Binnendijk, Rob S; Hahné, Susan J M (2017-04-15)
      Routinely, the first measles, mumps, and rubella (MMR) vaccine dose is given at 14 months of age in the Netherlands. However, during a measles epidemic in 2013-2014, MMR vaccination was also offered to 6-14-month-olds in municipalities with <90% MMR vaccination coverage. We studied the effectiveness of the early MMR vaccination schedule.
    • Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus.

      Marinelli, Isabella; van Lier, Alies; de Melker, Hester; Pugliese, Andrea; van Boven, Michiel (2017)
      Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002-2011, n=7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.
    • Health and Economic Impact of a Tender-Based, Sex-Neutral Human Papillomavirus 16/18 Vaccination Program in the Netherlands.

      Qendri, Venetia; Bogaards, Johannes A; Berkhof, Johannes (2017-07-15)
      Uptake of human papillomavirus (HPV) vaccine among girls in the Dutch immunization program has plateaued at around 60%. Vaccinating boys may be an appealing complementary strategy for the prevention of HPV-related diseases, especially since tender negotiations and reduced dosing schemes have driven down the cost of vaccination.
    • In Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants.

      van Erp, Elisabeth A; van Kasteren, Puck B; Guichelaar, Teun; Ahout, Inge M L; de Haan, Cornelis A M; Luytjes, Willem; Ferwerda, Gerben; Wicht, Oliver (2017-11-01)
      Respiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mainly below 6 months of age, when neutralizing matAb levels are present. To investigate this discrepancy, we asked if disease severity is related to antibody properties other than neutralization. Some antibody effector functions are mediated via their Fc binding region. However, it has been shown that this binding may lead to antibody-dependent enhancement (ADE) of infection or reduction of neutralization, both possibly leading to more disease. In this study, we first showed that high levels of ADE of RSV infection occur in monocytic THP-1 cells in the presence of RSV antibodies and that neutralization by these antibodies was reduced in Vero cells when they were transduced with Fc gamma receptors. We then demonstrated that antibodies from cotton rats with formalin-inactivated (FI)-RSV-induced pulmonary pathology were capable of causing ADE. Human matAbs also caused ADE and were less neutralizing in vitro in cells that carry Fc receptors. However, these effects were unrelated to disease severity because they were seen both in uninfected controls and in infants hospitalized with different levels of RSV disease severity. We conclude that ADE and reduction of neutralization are unlikely to be involved in RSV disease in infants with neutralizing matAbs.IMPORTANCE It is unclear why severity of RSV disease peaks at the age when infants have neutralizing levels of maternal antibodies. Additionally, the exact reason for FI-RSV-induced enhanced disease, as seen in the 1960s vaccine trials, is still unclear. We hypothesized that antibodies present under either of these conditions could contribute to disease severity. Antibodies can have effects that may lead to more disease instead of protection. We investigated two of those effects: antibody-dependent enhancement of infection (ADE) and neutralization reduction. We show that ADE occurs in vitro with antibodies from FI-RSV-immunized RSV-infected cotton rats. Moreover, passively acquired maternal antibodies from infants had the capacity to induce ADE and reduction of neutralization. However, no clear association with disease severity was seen, ruling out that these properties explain disease in the presence of maternal antibodies. Our data contribute to a better understanding of the impact of antibodies on RSV disease in infants.
    • The influence of neonatal Bacille Calmette-Guérin (BCG) immunisation on heterologous vaccine responses in infants.

      Zimmermann, Petra; Donath, Susan; Perrett, Kirsten P; Messina, Nicole L; Ritz, Nicole; Netea, Mihai G; Flanagan, Katie L; van der Klis, Fiona R M; Curtis, Nigel (2019-06-19)
    • Influenza-like Illness Incidence Is Not Reduced by Influenza Vaccination in a Cohort of Older Adults, Despite Effectively Reducing Laboratory-Confirmed Influenza Virus Infections.

      van Beek, Josine; Veenhoven, Reinier H; Bruin, Jacob P; van Boxtel, Renée A J; de Lange, Marit M A; Meijer, Adam; Sanders, Elisabeth A M; Rots, Nynke Y; Luytjes, Willem (2017-08-15)
      Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed.
    • The intention of Dutch general practitioners to offer vaccination against pneumococcal disease, herpes zoster and pertussis to people aged 60 years and older.

      Lehmann, Birthe A; Eilers, Renske; Mollema, Liesbeth; Ferreira, José; de Melker, Hester E (2017-06-07)
      Increasing life expectancy results in a larger proportion of older people susceptible to vaccine preventable diseases (VPDs). In the Netherlands, influenza vaccination is routinely offered to people aged 60 years and older. Vaccination against pneumococcal disease, herpes zoster and pertussis is rarely used. These vaccines will be evaluated by the Dutch Health Council and might be routinely offered to older people in the near future. Possible expansion of the program depends partly on the willingness of general practitioners (GPs) to endorse additional vaccinations. In this study, we assessed predictors of GPs' attitude and intention to vaccinate people aged 60 years and older.
    • Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness.

      van der Maas, Nicoline A T; Sanders, Elisabeth A M; Versteegh, Florens G A; Baauw, Albertine; Westerhof, Anneke; de Melker, Hester E (2019-10-29)
    • Timeliness of immunisations in preterm infants in the Netherlands.

      Rouers, Elsbeth D M; Berbers, Guy A M; van Dongen, Josephine A P; Sanders, Elisabeth A M; Bruijning-Verhagen, Patricia (2019-09-16)
    • Trends in governmental expenditure on vaccination programmes in the Netherlands, a historical analysis.

      van Wijhe, Maarten; de Boer, Pieter T; de Jong, Herman J; van Vliet, Hans; Wallinga, Jacco; Postma, Maarten J (2019-09-10)
    • Vaccinating children against influenza increases variability in epidemic size.

      Backer, J A; van Boven, M; VAN DER Hoek, W; Wallinga, J (2018-10-10)
      Seasonal influenza causes a high disease burden. Many influenza vaccination programmes target the elderly and persons at high risk of complications. Some countries have recommended or even implemented a paediatric vaccination programme. Such a programme is expected to reduce influenza transmission in the population, offering direct protection to the vaccinated children and indirect protection to the elderly. We study the impact of a child vaccination programme with an age- and risk-structured transmission model, calibrated to data of 11 influenza seasons in the Netherlands. The model tracks the build-up of immunes and susceptibles in each age cohort over time, and it allows for seasonal variation in vaccine match and antigenic drift. Different vaccination strategies are evaluated for three target age groups (2-3, 2-12 and 2-16 year olds) over the full range of vaccination coverages (0-100%). The results show that the paediatric vaccination programme has only a limited impact on the elderly age groups, which account for most influenza morbidity and mortality. This is due to two notable changes in infection dynamics. First, an age shift is observed: influenza infections are reduced in vaccinated children, but are increased in young adults with limited natural immunity after years of vaccination. These young adults assume the role of driving the epidemic. Second, a year with low influenza activity can be followed by a large epidemic due to build-up of susceptibles. This variation of the infection attack rate increases with increasing vaccination coverage. The increased variability in the infection attack rate implies that health care facilities should be prepared for rare but larger peaks in influenza patients. Moreover, vaccinating the group with the highest transmission potential, results in a larger dependency on a secure vaccine supply. These arguments should be taken into account in the decision to introduce mass vaccination of school-aged children against influenza.
    • Vaccine preferences and acceptance of older adults.

      Eilers, R; de Melker, H E; Veldwijk, J; Krabbe, P F M (2017-05-15)
      Expanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination.
    • Variation in loss of immunity shapes influenza epidemics and the impact of vaccination.

      Woolthuis, Rutger G; Wallinga, Jacco; van Boven, Michiel (2017-09-19)
      Protective antibody immunity against the influenza A virus wanes in 2-7 years due to antigenic drift of the virus' surface proteins. The duration of immune protection is highly variable because antigenic evolution of the virus is irregular. Currently, the variable nature of the duration of immunity has had little attention in analyses of the impact of vaccination, including cost-effectiveness studies.