Immunity against Neisseria meningitidis Serogroup C in the Dutch Population before and after Introduction of the Meningococcal C Conjugate Vaccine

Contains fulltext : 88187.pdf (publisher's version ) (Open Access)BACKGROUND: In 2002 a Meningococcal serogroup C (MenC) conjugate vaccine, with tetanus toxoid as carrier protein, was introduced in the Netherlands as a single-dose at 14 months of age. A catch-up campaign was performed targeting all individuals aged 14 months to 18 years. We determined the MenC-specific immunity before and after introduction of the MenC conjugate (MenCC) vaccine. METHODS AND FINDINGS: Two cross-sectional population-based serum banks, collected in 1995/1996 (n = 8539) and in 2006/2007 (n = 6386), were used for this study. The main outcome measurements were the levels of MenC polysaccharide(PS)-specific IgG and serum bactericidal antibodies (SBA) after routine immunization, 4-5 years after catch-up immunization or by natural immunity. There was an increasing persistence of PS-specific IgG and SBA with age in the catch-up immunized cohorts 4-5 years after their MenCC immunization (MenC PS-specific IgG, 0.25 microg/ml (95%CI: 0.19-0.31 microg/ml) at age 6 years, gradually increasing to 2.34 microg/ml,(95%CI: 1.70-3.32 microg/ml) at age 21-22 years). A comparable pattern was found for antibodies against the carrier protein in children immunized above 9 years of age. In case of vaccination before the age of 5 years, PS-specific IgG was rapidly lost. For all age-cohorts together, SBA seroprevalence (> or =8) increased from 19.7% to 43.0% in the pre- and post-MenC introduction eras, respectively. In non-immunized adults the SBA seroprevalence was not significantly different between the pre- and post-MenC introduction periods, whereas PS-specific IgG was significantly lower in the post-MenC vaccination (GMT, age > or =25 years, 0.10 microg/ml) era compared to the pre-vaccination (GMT, age > or =25 years, 0.43 microg/ml) era. CONCLUSION: MenCC vaccination administered above 5 years of age induced high IgG levels compared to natural exposure, increasing with age. In children below 14 months of age and non-immunized cohorts lower IgG levels were observed compared to the pre-vaccination era, whereas functional levels remained similar in adults. Whether the lower IgG poses individuals at increased risk for MenC disease should be carefully monitored. Large-scale introduction of a MenCC vaccine has led to improved protection in adolescents, but in infants a single-dose schedule may not provide sufficient protection on the long-term and therefore a booster-dose early in adolescence should be considered

Age-Related Immunity to Meningococcal Serogroup C Vaccination: An Increase in the Persistence of IgG2 Correlates with a Decrease in the Avidity of IgG

Contains fulltext : 97618.pdf (publisher's version ) (Open Access)Background All children and adolescents between 1 and 19 years of age in The Netherlands received a single meningococcal serogroup C conjugate (MenCC) vaccine in 2002. During follow-up 4–5 years later, the persistence of MenC polysaccharide-specific IgG was found to be dependent on age of vaccination with higher IgG levels in the oldest immunized age categories. Methods and Findings Two cross-sectional population-based serum banks, collected in 1995/1996 and in 2006/2007, were used for this study. We measured MenC polysaccharide-specific IgM, the IgG1 and IgG2 subclasses and determined the avidity of the IgG antibodies. We report that the age-related persistence of IgG after immunization with the MenCC vaccine seemed to result from an increase of IgG2 levels with age, while IgG1 levels remained stable throughout the different age-cohorts. Furthermore, an age-related increase in IgM levels was observed, correlating with the persistence of IgG antibodies with age. It is noteworthy that the increase in IgG2 correlated with a reduced IgG-avidity with age. Conclusion These date indicate that the classical characteristics of a T-cell-dependent antibody response as elicited by protein based vaccines might not be completely applicable when conjugate vaccines are administered to older children and adolescents up to 18 years of age. The response elicited by the MenCC vaccine seemed to be more a mixture of both T cell dependent and T cell independent responses in terms of humoral immunological characteristics

Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model

BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. METHODS/PRINCIPAL FINDINGS: We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY) and €6371/QALY (range: 4139-9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. CONCLUSIONS/SIGNIFICANCE: To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies

Serologische bevindingen en gezondheidsklachten bij standmedewerkers werkzaam op de Westfriese Flora 1999 in Bovenkarspel. Een onderzoek in het kader van de Veteranenziekte epidemie

This study was aimed at contributing to finding the source of a epidemic of Legionnaire's disease (LD) in visitors of the Westfriese Flora 1999 (West-Frisian Flower-show). The Westfriese Flora is a yearly flower exhibition combined with an agricultural and consumer products fair. The study targeted all persons without LD who had been working on the Westfriese Flora as volunteer, employee to the exhibition-organization or exhibitor. These persons were asked to fill in a questionnaire on their health status before and after the exhibition and their whereabouts during the exhibition. They were also asked to have a paired blood-sample taken to be tested for antibodies against L. pneumophila. No clear relations between health complaints and specific places or other factors, like drinking tap-water, were seen. However, antibody levels were clearly increased in those working in hall 3, but not in those working at other places and therefore the main LD spreading source should be sought in hall 3. The exact location, however, can not be inferred from this study with any certainty. From the two potential sources in hall 3 (a whirlpoolspa and a bubblemat) our data seem to indicate the whirlpoolspa as the more likely source, but this is not conclusive. From these findings we conclude that exposure to L. pneumophila seems to cause a slight elevation of antibody titers in those who do not develop LD, but that this increase is not accompanied by a demonstrable amount of milder forms of disease (apart from LD).Dit onderzoek bedoelt een bijdrage te leveren aan het vinden van de bron van de epidemie van Veteranenziekte onder bezoekers van de Westfriese Flora 1999. De onderzoekspopulatie bestond uit alle standmedewerkers op de Floraen de medewerkers en vrijwilligers van de Flora-organisatie die geen veteranenziekte hadden ontwikkeld. Deze personen kregen een vragenlijst toegestuurd met vragen over hun gezondheid voor en na de Flora, en hun verblijf (duur en plaats) op de Flora. Zij werden ook gevraagd tweemaal een bloedmonster te laten nemen voor onderzoek naar antistoffen tegen L. pneumophila. Er werd geen verband gevonden tussen gezondheidsklachten en het werken op specifieke plaatsen op de Flora, noch met enkele andere factoren (zoals het drinken van kraanwater op de Flora). De hoeveelheid antilichamen tegen L. pneumophila in bloed daarentegen was duidelijk hoger in personen die werkten in hal 3, waar een deel van de consumentenbeurs was gehuisvest. Er waren geen verschillen in de concentratie van antilichamen binnen de groep personen die op andere plekken werkten. Hieruit kan worden geconcludeerd dat de belangrijkste bron van L. pneumophila zich in hal 3 heeft bevonden. Met behulp van ruimtelijke smoothing technieken kon de hoogte van de concentraties antilichamen worden weergegeven op de plattegrond kaart van de consumentenbeurs. Daaruit kan de exacte locatie van de bron binnen hal 3 echter niet worden afgeleid.kten in hal 3 gaat niet samen te gaan met aantoonbaar meer op legionellosis lijkende gezondheidsklachten (afgezien van het optreden van veteranenziekten)