Enhanced Bordetella pertussisacquisition rate in adolescents during the 2012 epidemic in the Netherlands and evidence for prolonged antibody persistence after infection.

IntroductionIn 2012 a large epidemic of pertussis occurred in the Netherlands. We assessed pertussis toxin (PT) antibody levels in longitudinal serum samples from Dutch 10-18 year-olds, encompassing the epidemic, to investigate pertussis infection incidence.Methods: Blood was sampled in October 2011 (n = 239 adolescents), then 1 year (2012; n = 228) and 3 years (2014; n = 167) later. PT-IgG concentrations were measured by immunoassay and concentrations ≥50 IU/mL (seropositive) assumed indicative of an infection within the preceding year.Results: During the 2012 epidemic, 10% of participants became seropositive, while this was just 3% after the epidemic. The pertussis acquisition rate proved to be sixfold higher during the epidemic (97 per 1,000 person-years) compared with 2012-2014 (16 per 1,000 person-years). In 2012, pertussis notifications among adolescents nationwide were 228/100,000 (0.23%), which is at least 40 times lower than the seropositivity percentage. Remarkably, 17 of the 22 seropositive participants in 2011, were still seropositive in 2012 and nine remained seropositive for at least 3 years.Discussion: Longitudinal studies allow a better estimation of pertussis infections in the population. A PT-IgG concentration ≥50 IU/mL as indication of recent infection may overestimate these numbers in cross-sectional serosurveillance and should be used carefully

Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis in nicotinic acetylcholine receptor alpha7 subunit gene knockout mice

BACKGROUND: The alpha7 subunit of nicotinic acetylcholine receptors (alpha7nAChR) can negatively regulate the synthesis and release of proinflammatory cytokines by macrophages and fibroblast-like synoviocytes in vitro. In addition, stimulation of the alpha7nAChR can reduce the severity of arthritis in murine collagen-induced arthritis (CIA). OBJECTIVE: To provide more insight into the role of the alpha7nAChR in the pathogenesis of arthritis by investigating the effect of the absence of alpha7nAChR in CIA in alpha7-deficient (alpha7nAChR(-/-)) compared with wild-type (WT) mice. METHODS: CIA was induced in alpha7nAChR(-/-) and WT littermate mice at day 0 by immunisation with chicken collagen type II (cCII) followed by a booster injection with cCII on day 20. Mice were killed on day 44 or day 63 and arthritis activity as well as radiological and histological damage were scored. The effects on the immune response were evaluated by measurement of antigen-specific antibodies and cytokines, and evaluation of the effects on antigen-specific stimulated spleen cells. RESULTS: In alpha7nAChR(-/-) mice a significant increase in the incidence and severity of arthritis as well as increased synovial inflammation and joint destruction were seen. Exacerbation of CIA was associated with elevated systemic proinflammatory cytokines and enhanced T-helper cell 1 (Th1)-cytokine and tumour necrosis factor alpha production by spleen cells. Moreover, a specific decrease in the collagen-specific 'Th1-associated' IgG2a response was seen, whereas IgG1 titres were unaffected. CONCLUSIONS: The results presented here indicate that immune cell function in a model of rheumatoid arthritis is regulated by the cholinergic system and, at least in part, mediated by the alpha7nACh

Salivary antibody levels in adolescents in response to a meningococcal serogroup C conjugate booster vaccination nine years after priming : systemically induced local immunity and saliva as potential surveillance tool

BACKGROUND: In several countries large-scale immunization of children and young adults with Meningococcal serogroup C (MenC) conjugate vaccines has induced long-standing herd protection. Salivary antibodies may play an important role in mucosal protection against meningococcal acquisition and carriage. AIM: To investigate antibody levels in (pre)adolescents primed 9 years earlier with a single dose of MenC-polysaccharide tetanus toxoid conjugated (MenC-TT) vaccine and the response to a booster vaccination, with special focus on age-related differences and the relation between salivary and serum antibody levels. METHODS: Nine years after priming, healthy 10- (n=91), 12- (n=91) and 15-year-olds (n=86) received a MenC-TT booster vaccination. Saliva and serum samples were collected prior to and 1 month and 1 year after vaccination. MenC-polysaccharide(MenC-PS)-specific antibody levels were measured using a fluorescent-bead-based multiplex immunoassay. RESULTS: Before the booster, MenC-PS-specific IgG and IgA levels in saliva and serum were low and correlated with age at priming. The booster induced a marked increase in salivary MenC-PS-specific IgG (>200-fold), but also in IgA (∼10-fold). One year after the booster, salivary IgG and IgA had remained above pre-booster levels in all age groups (∼20-fold and ∼3-fold, respectively), with persistence of highest levels in the 15-year-olds. MenC-PS-specific IgG and IgA levels in saliva strongly correlated with the levels in serum. CONCLUSION: Parenteral MenC-TT booster vaccination induces a clear increase in salivary MenC-PS-specific IgG and IgA levels and persistence of highest levels correlates with age. The strong correlation between serum and salivary antibody levels indicate that saliva may offer an easy and reliable tool for future antibody surveillance

Sex-Related Differences in the Immune Response to Meningococcal Vaccinations During Adolescence.

BACKGROUND: Immune responses to pediatric vaccinations have been reported to differ according to sex. Such sex-differential responses may become more pronounced during adolescence due to hormonal differences. We investigated whether the vaccine response following primary vaccination against meningococcal serogroup A (MenA), MenW and MenY and booster vaccination against MenC differed between girls and boys using data from two clinical studies. METHODS: Children aged 10, 12, and 15 years, who had been primed with MenC vaccination between 14 months and 6 years of age, received a booster MenC vaccination or MenACWY vaccination. Polysaccharide-specific IgG concentrations and functional antibody titers [determined with the serum bactericidal antibody (SBA) assay] were measured at baseline, 1 month, 1 year, and 3 years (only MenC group) after vaccination. We calculated geometric mean concentrations and titers (GMC and GMT) ratios for girls vs. boys adjusted for age group. Additionally, we compared the proportion protected individuals between girls and boys at all timepoints. RESULTS: This study included 342 girls and 327 boys from two clinical trials. While MenAWY antibody levels did not differ consistently 1 month after vaccination, all GMC- and GMT-ratios were in favor of girls 1 year after vaccination [range: 1.31 (1.02–1.70) for MenA IgG to 1.54 (1.10–2.16) for MenW IgG]. Overall, MenC antibody levels were slightly higher in girls at all postvaccination timepoints (GMC- and GMT-ratios: 1.16/1.17 at 1 month, 1.16/1.22 at 1 year and 1.12/1.15 3 years postvaccination). Higher MenC antibody levels were observed in 12- and 15-year-old girls compared to boys of the same age, whereas 10-year-old boys and girls had similar antibody levels. The percentage of participants protected (SBA titer ≥ 8) was very high (95–100%) at all timepoints, and did not differ significantly between boys and girls. CONCLUSION: Antibody responses were higher in girls than in boys for all serogroups at most timepoints after primary MenAWY vaccination and booster MenC vaccination. The differences in average titers were however small and the percentage participants with protective titers was very high for both sexes

Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming : A Role for Priming Age?

BACKGROUND: Antibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels. METHODS: Measurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier. RESULTS: The number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster. CONCLUSIONS: Circulating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC

The Department of Maori Affairs housing programme, 1935-1967 : a thesis presented in fulfillment of the requirements for the degree of Master of Arts in history at Massey University

The Department of Maori Affairs housing programme was established in the 1930s through the Maori Housing Act (1935) and the Maori Housing Amendment Act (1938). A special housing programme was required because a large proportion of the Maori population lived in 'deplorable' housing conditions, and it was'... impossible for the average Maori to finance a new home'1 1. J M McEwen, 'Urbanisation and the Multi-Racial Society', in R H Brookes and I H Kawharu (eds.), Administration in New Zealand's Multi-Racial Society (Wellington, 1967), p. 76. through lending institutions because they could provide neither security nor regular payments. The purposes of this study are twofold. First, to examine successive governments' Maori housing policies in the period 1935 to 1967, and discuss how these were implemented by the Department of Maori Affairs. Second, to assess their effectiveness as a provider of housing for the Maori population

Disease Burden of Invasive Meningococcal Disease in the Netherlands Between June 1999 and June 2011 : A Subjective Role for Serogroup and Clonal Complex

BACKGROUND: Several countries consider the implementation of a meningococcal serogroup B vaccine for young children and/or serogroup C or ACWY conjugate vaccine for adolescents. Representative information on clinical course of invasive meningococcal disease (IMD) is useful to evaluate cost-effectiveness of vaccination. Information on the relation between infecting meningococcal clonal complex (CC), disease course and outcome of IMD is scarce. METHODS: A retrospective study using Dutch surveillance data on IMD from June 1999 to June 2011. Clinical information was retrieved from hospital records. The effect of age, comorbidity, clinical manifestation, serogroup, and CC on disease course and outcome was assessed in multivariable analyses. Meningococcal CCs were assessed by multilocus sequence typing. RESULTS: Clinical information was retrieved for 879 IMD cases: 48% of patients presented with meningitis, 17% with septic shock, and 22% with septic shock plus meningitis. Development of septic shock was not related to CC or serogroup. Median (interquartile range) duration of hospital admission was 10 (8-13) days. Intensive care unit admittance (38%) was higher for patients aged ≥10 years and patients with septic shock (P-values ≤.001). Case-fatality rate (8%) and development of sequelae (29%) was dependent on age and clinical manifestation (P-values ≤.001) and not affected by comorbidity, CC, or serogroup. CONCLUSIONS: IMD still coincides with a considerable disease burden and mortality. Disease course and outcome depend mainly on age and clinical manifestation and less on meningococcal CC or serogroup

Disease Burden of Invasive Meningococcal Disease in the Netherlands Between June 1999 and June 2011 : A Subjective Role for Serogroup and Clonal Complex

BACKGROUND: Several countries consider the implementation of a meningococcal serogroup B vaccine for young children and/or serogroup C or ACWY conjugate vaccine for adolescents. Representative information on clinical course of invasive meningococcal disease (IMD) is useful to evaluate cost-effectiveness of vaccination. Information on the relation between infecting meningococcal clonal complex (CC), disease course and outcome of IMD is scarce. METHODS: A retrospective study using Dutch surveillance data on IMD from June 1999 to June 2011. Clinical information was retrieved from hospital records. The effect of age, comorbidity, clinical manifestation, serogroup, and CC on disease course and outcome was assessed in multivariable analyses. Meningococcal CCs were assessed by multilocus sequence typing. RESULTS: Clinical information was retrieved for 879 IMD cases: 48% of patients presented with meningitis, 17% with septic shock, and 22% with septic shock plus meningitis. Development of septic shock was not related to CC or serogroup. Median (interquartile range) duration of hospital admission was 10 (8-13) days. Intensive care unit admittance (38%) was higher for patients aged ≥10 years and patients with septic shock (P-values ≤.001). Case-fatality rate (8%) and development of sequelae (29%) was dependent on age and clinical manifestation (P-values ≤.001) and not affected by comorbidity, CC, or serogroup. CONCLUSIONS: IMD still coincides with a considerable disease burden and mortality. Disease course and outcome depend mainly on age and clinical manifestation and less on meningococcal CC or serogroup

Meningococcal serogroup C immunogenicity, antibody persistence and memory B-cells induced by the monovalent meningococcal serogroup C versus quadrivalent meningococcal serogroup ACWY conjugate booster vaccine : A randomized controlled trial

BACKGROUND: Adolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster. METHODS: Healthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year. RESULTS: Of 501 participants, 464 (92.6%) were included in the 'according to protocol' cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds. CONCLUSION: Both MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease in the long-term