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Vaccination has reduced the disease burden of vaccine-preventable diseases. However, the extent to which seasonal cycles of immunity could influence vaccine-induced immunity is not well understood. A national cross-sectional serosurveillance study performed in the Netherlands (Pienter-2) yielded data to investigate whether season of vaccination was associated with antibody responses induced by DT-IPV (diphtheria, tetanus and poliomyelitis), MMR (measles, mumps and rubella) and meningococcus C (MenC) vaccines in children. In total, 434 children met the inclusion criteria to study DT-IPV immunity, 811 for MMR and 311 for MenC. Differences in log(antibody levels) by season of vaccination were investigated with linear multivariable regression analyses. Seroconversion rates varied according to season of vaccination for rubella (90% of autumn-vaccinated childrenvs.99% of winter-vaccinated had concentrations above cut-off levels). Summer-vaccinated boys showed a slower decline of tetanus antibodies (6% per month), in comparison with winter-vaccinated boys. In conclusion, season of vaccination showed little association with immunological protection. However, a number of associations were seen with aP-value of about 0.03; and adding data from a just-completed nationwide serological study might add more power to the current study. Further immunological and longitudinal investigations could help understand the mechanisms of seasonal influence in vaccine-induced responses.

Vaccination programmes are considered a main contributor to the decline of infectious diseases over the 20th century. In recent years, the national vaccination coverage in the Netherlands has been declining, highlighting the need for continuous monitoring and evaluation of vaccination programmes. Our aim was to quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands. We collected and digitised previously unavailable monthly case notifications of diphtheria, poliomyelitis, mumps and rubella in the Netherlands over the period 1919–2015. Poisson regression models accounting for seasonality, multi-year cycles, secular trends and auto-correlation were fit to pre-vaccination periods. Cases averted were calculated as the difference between observed and expected cases based on model projections. In the first 13 years of mass vaccinations, case notifications declined rapidly with 82.4% (95% credible interval (CI): 74.9–87.6) of notified cases of diphtheria averted, 92.9% (95% CI 85.0–97.2) cases of poliomyelitis, and 79.1% (95% CI 67.1–87.4) cases of mumps. Vaccination of 11-year-old girls against rubella averted 49.9% (95% CI 9.3–73.5) of cases, while universal vaccination averted 68.1% (95% CI 19.4–87.3) of cases. These findings show that vaccination programmes have contributed substantially to the reduction of infectious diseases in the Netherlands.

Given the role of the CD4 T helper cells in the development of memory CTL precursors, it seems beneficial to boost the CD4 T helper response in the context of vaccination against the human immunodeficiency virus (HIV). However, CD4 T cells are also the preferred targets of infection by HIV. Here, we address the question as to whether it is advantageous to stimulate the CD4 T helper cell response, as this will increase the pool of potential target cells of infection. To do so we formulated a mathematical model describing the interactions between virus-infected cells, susceptible cells, HIV-specific CD4 helper T cells, and CTL precursor (CTLp) and effector cells (CTLe). The effect of increased initial CD4 helper and CTLp numbers on the outcome of infection, as well as the effect on viral set point of increased CD4 T helper growth rate, CTL responsiveness and the rate at which CTLp and CTLe are produced were studied. We found that only when the virus has a low basic reproductive number does the number of CTLp and CD4 T helper cells at the moment of infection influence the outcome of infection. In this situation, high initial T helper and CTL numbers can switch the outcome from full-blown infection to virus control. However, this holds for virus with infectivity in a limited range, and current estimates of virus infectivity suggest that it is higher. In that case, only a vaccination protocol that increases CTL responsiveness, ideally in combination with the rate of production of CD4 T helper cells, may offer a solution as it can reduce the viral set point considerably. If brought under a certain level, the viral population might be unable to replicate any further. However, changing these parameters of the immune response is only beneficial when infection is controlled by CTL in the long term. When a CD4 lymphoproliferative response is mounted but the CTL response is not maintained, increasing the CD4 T helper growth rate is deleterious.

The elimination of tuberculosis (TB) is threatened by an apparent increase in the level of resistance in Mycobacterium tuberculosis. In the Netherlands, where the majority of TB patients are migrants, resistance may also be increasing. We conducted a retrospective study, using 18,294 M. tuberculosis isolates from TB cases notified between 1993 and 2011. We investigated the trends in antituberculosis drug resistance, focusing on the country of birth of the patients and whether resistance had developed during treatment or was the result of transmission of resistant M. tuberculosis strains. For both scenarios, we determined whether this had happened in or outside the Netherlands. Antituberculosis drug resistance was found in 13% of all cases analysed and showed an increasing trend among patients who had been born in the Netherlands (p

BACKGROUND: The incidence of extra-pulmonary tuberculosis (EPTB) in the Netherlands shows a seasonal trend, with a peak in spring and a trough in autumn. Possible causes of this peak are winter crowding and a seasonal decrease in immune competence in spring. A third explanation may be a reporting bias. OBJECTIVE: To investigate the role of winter crowding by a time-series analysis of notification data. DNA fingerprinting clustering status can differentiate between recent and remote infections. Seasonality in clustered cases would reflect enhanced transmission in winter and/or seasonally lowered immunity, while seasonality in unique cases would only reflect seasonally lowered immunity. METHODS: We fitted (seasonal) auto-regressive moving average models to culture-positive TB notifications in the Netherlands (1993–2008) to assess seasonality. We then used seasonal trend Loess decompositions to derive the seasonal pattern, and compared the heights of the seasonal peaks. RESULTS: Clustered and unique EPTB notifications showed a seasonal trend that was absent in clustered and unique PTB notifications. The seasonal peak in clustered EPTB cases was not significantly higher than in unique EPTB cases. CONCLUSIONS: The similar timing and height of the seasonal peak of clustered and unique EPTB cases suggests that winter crowding is unlikely to cause the seasonal trend in notifications.