The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial.

BACKGROUND: Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring's response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 -May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens. CONCLUSIONS/SIGNIFICANCE: Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant's vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring's response to vaccines. TRIAL REGISTRATION: ISRCTN.com ISRCTN32849447

Participation in and attitude towards the national immunization program in the Netherlands: data from population-based questionnaires

Contains fulltext : 108971.pdf (publisher's version ) (Open Access)BACKGROUND: Knowledge about the determinants of participation and attitude towards the National Immunisation Program (NIP) may be helpful in tailoring information campaigns for this program. Our aim was to determine which factors were associated with nonparticipation in the NIP and which ones were associated with parents' intention to accept remaining vaccinations. Further, we analyzed possible changes in opinion on vaccination over a 10 year period. METHODS: We used questionnaire data from two independent, population-based, cross-sectional surveys performed in 1995-96 and 2006-07. For the 2006-07 survey, logistic regression modelling was used to evaluate what factors were associated with nonparticipation and with parents' intention to accept remaining vaccinations. We used multivariate multinomial logistic regression modelling to compare the results between the two surveys. RESULTS: Ninety-five percent of parents reported that they or their child (had) participated in the NIP. Similarly, 95% reported they intended to accept remaining vaccinations. Ethnicity, religion, income, educational level and anthroposophic beliefs were important determinants of nonparticipation in the NIP. Parental concerns that played a role in whether or not they would accept remaining vaccinations included safety of vaccinations, maximum number of injections, whether vaccinations protect the health of one's child and whether vaccinating healthy children is necessary. Although about 90% reported their opinion towards vaccination had not changed, a larger proportion of participants reported to be less inclined to accept vaccination in 2006-07 than in 1995-96. CONCLUSION: Most participants had a positive attitude towards vaccination, although some had doubts. Groups with a lower income or educational level or of non-Western descent participated less in the NIP than those with a high income or educational level or indigenous Dutch and have been less well identified previously. Particular attention ought to be given to these groups as they contribute in large measure to the rate of nonparticipation in the NIP, i.e., to a greater extent than well-known vaccine refusers such as specific religious groups and anthroposophics. Our finding that the proportion of the population inclined to accept vaccinations is smaller than it was 10 years ago highlights the need to increase knowledge about attitudes and beliefs regarding the NIP

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

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

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721