Association between season of vaccination and antibody levels against infectious diseases.

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 children vs. 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 a P-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.

Quantifying the impact of mass vaccination programmes on notified cases in the Netherlands.

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.

Extent and origin of resistance to antituberculosis drugs in the Netherlands, 1993 to 2011.

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<0.001) and a decreasing trend among foreign-born (p=0.02) over the study period. Since 2005, the proportion of M. tuberculosis resistant strains among all strains tested has increased in both groups (p=0.03 and p=0.01, respectively). Overall, we found a significantly increasing trend when excluding streptomycin resistance (p<0.001). The trend was most markedly increased for isoniazid resistance (p = 0.01). Although resistance was mainly due to transmission of resistant strains, mostly outside the Netherlands or before 1993 (when DNA fingerprinting was not systematically performed), in some cases (n=45), resistance was acquired in the Netherlands. We conclude that antituberculosis drug resistance is increasing in the Netherlands, mostly related to migration from high TB-incidence countries, but also to domestic acquisition.

Time lag between immigration and tuberculosis rates in immigrants in the Netherlands: a time-series analysis.

SETTING AND OBJECTIVE: In low-incidence countries, most tuberculosis (TB) cases are foreign-born. We explored the temporal relationship between immigration and TB in first-generation immigrants between 1995 and 2012 to assess whether immigration can be a predictor for TB in immigrants from high-incidence countries. DESIGN: We obtained monthly data on immigrant TB cases and immigration for the three countries of origin most frequently represented among TB cases in the Netherlands: Morocco, Somalia and Turkey. The best-fit seasonal autoregressive integrated moving average (SARIMA) model to the immigration time-series was used to prewhiten the TB time series. The cross-correlation function (CCF) was then computed on the residual time series to detect time lags between immigration and TB rates. RESULTS: We identified a 17-month lag between Somali immigration and Somali immigrant TB cases, but no time lag for immigrants from Morocco and Turkey. CONCLUSION: The absence of a lag in the Moroccan and Turkish population may be attributed to the relatively low TB prevalence in the countries of origin and an increased likelihood of reactivation TB in an ageing immigrant population. Understanding the time lag between Somali immigration and TB disease would benefit from a closer epidemiological analysis of cohorts of Somali cases diagnosed within the first years after entry.

The race between initial T-helper expansion and virus growth upon HIV infection influences polyclonality of the response and viral set-point.

Infection with HIV is characterized by very diverse disease-progression patterns across patients, associated with a wide variation in viral set-points. Progression is a multifactorial process, but an important role has been attributed to the HIV-specific T-cell response. To explore the conditions under which different set-points may be explained by differences in initial CD4 and CD8 T-cell responses and virus inoculum, we have formulated a model assuming that HIV-specific CD4 cells are both targets for infection and mediators of a monoclonal or polyclonal immune response. Clones differ in functional avidity for HIV epitopes. Importantly, in contrast to previous models, in this model we obtained coexistence of multiple clones at steady-state viral set-point, as seen in HIV infection. We found that, for certain parameter conditions, multiple steady states are possible: with few initial CD4 helper cells and high virus inoculum, no immune response is established and target-cell-limited infection follows, with associated high viral load; when CD4 clones are initially large and virus inoculum is low, infection can be controlled by several clones. The conditions for the dependence of viral set-point on initial inoculum and CD4 T-helper clone availability are investigated in terms of the effector mechanism of the clones involved.

Similar seasonal peak in clustered and unique extra-pulmonary tuberculosis notifications: winter crowding hypothesis ruled out?

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.

Tuberculosis seasonality in the Netherlands differs between natives and non-natives: a role for vitamin D deficiency?

SETTING: The seasonality of tuberculosis (TB) incidence suggests that the risk of infection or development of disease has a seasonal component. OBJECTIVE: To investigate factors associated with seasonal patterns of TB disease in the Netherlands by splitting notifications according to origin (natives vs. non-natives) and disease site (pulmonary TB [PTB] vs. extra-pulmonary TB [EPTB]). We focus on the presence of a seasonal peak, as much debate has centred on factors enhancing transmission vs. disease development. DESIGN: Monthly notifications were derived from culture sample dates of all cases between 1993 and 2008. We fitted seasonal autoregressive integrated moving average (SARIMA) models to the time series. Seasonal decomposition revealed seasonal trends. To assess the seasonality of the peak, we repeated the analysis omitting December (trough) notifications. RESULTS: TB notifications show a seasonal pattern, with a peak in spring and a trough in winter, which is present in both PTB and EPTB and in both natives and non-natives. However, when excluding December notifications, seasonality only holds in non-native EPTB and non-native TB notifications. CONCLUSION: A seasonal peak in TB notifications (March-June) is apparent in non-natives, but is absent in natives. This peak is driven by the seasonality of EPTB notifications, which are highest in June-July. The contribution of winter crowding is discussed. Vitamin D deficiency, enhancing disease development at the end of winter-early spring, seems the most likely factor explaining the yearly peak in EPTB.

Immune Unresponsiveness to platelets. A case study.

Both 51Cr-survival studies with donor platelets and allogenic skin transplantations were performed in a patient with immune unresponsiveness to platelet antigens, i.e., HLA-and platelet-specific antigens. The patients, who suffered from hypoplastic anaemia, was successfully transfused with random donor platelets during 13 months. The serum of this patient contained only granulocyte-and mononuclear-cell-reactive antibodies, but no platelet-reactive antibodies. A nearly normal survival time of the donor platelets as well as a prolonged rejection time of a skin allograft of the same donor support the serological findings. The 51Cr-platelet survival time was not influenced by a leucocyte concentrate from the same donor, which was administered at the same time. Thus, in our patient, no increased platelet destruction could be induced via the so-called innocent bystander mechanism.