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1 mei 2012, Item does not contain fulltext, The burden of respiratory infections is mainly seen in primary healthcare. To evaluate the potential impact of new preventive strategies against respiratory infections, such as the implementation of pneumococcal conjugate vaccines for infants in 2006 in The Netherlands, we conducted a baseline retrospective cohort study of electronic primary-care patient records to assess consultation rates, comorbidities and antibiotic prescription rates for respiratory infections in primary care. We found that between 1995 and 2005, overall registered consultation rates for lower respiratory tract infections had increased by 42.4%, upper respiratory infections declined by 4.9%, and otitis media remained unchanged. Concomitantly, there was a steady rise in overall comorbidity (75.7%) and antibiotic prescription rates (67.7%). Since Dutch primary-care rates for respiratory infections changed considerably between 1995 and 2005, these changes must be taken into account to properly evaluate the effect of population-based preventive strategies on primary-care utilization.

Knowledge of the immunological correlates of Staphylococcus aureus and Streptococcus pneumoniae colonization is required for the search for future protein vaccines. We evaluated natural antibody lev

Background Significant differences in immune responses upon vaccination have been described, suggesting genetics are important in determining the magnitude of vaccine responses. The interleukin (IL)-4 pathway, including IL-4, IL-13 and the IL-4 receptor α chain (IL-4 Rα), is central to humoral responses and therefore could have an impact on vaccine responsiveness. Objective To investigate whether single nucleotide polymorphisms (SNPs) in the IL-4, IL-13 and IL-4 RA genes influence pneumococcal serotype-specific IgG antibody responses. Methods SNPs in the IL-4 gene (C −589T, G2979T), the IL-13 gene (G −1112A, Arg130Gln) and in the IL-4 RA gene (Ile50Val, Gln551Arg) were investigated in isolation and in combination, for their influence on serotype-specific IgG antibody responses upon combined pneumococcal conjugate and polysaccharide vaccinations in children with a history of recurrent otitis media. Results Lower antibody responses were observed for alleles previously associated with atopy, IL-4 −589T, IL-4 2979T and IL-4 Rα 551Gln. Effects were stronger in gene haplotype combinations or in multiple haplotype combination analyses. Conclusion This study highlights the importance of host genetic factors in vaccine responses. Furthermore, it supports the approach of studying the effect of combinations of multiple alleles, in haplotypes or in combinations of haplotypes, on complex phenotypes within a biological pathway.

Contains fulltext : 51717.pdf (publisher's version ) (Open Access), OBJECTIVE: Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS: DNA samples from 348 children with > or = 2 acute otitis media episodes, who were participating in a randomized, controlled vaccination trial, and 463 healthy adult controls were included. Polymorphisms in TNFA, IL1B, IL4, IL6, IL10, IL8, NOS2A, C1INH, PARP, TLR2, and TLR4 were genotyped. Genotype distributions in children with recurrent acute otitis media were compared with those in controls. Within the patient group, the number of acute otitis media episodes before vaccination and the clinical and immunologic response to pneumococcal conjugate vaccinations were analyzed. RESULTS: The IL6-174 G/G genotype was overrepresented in children with acute otitis media when compared with controls. In the patient group, TNFA promoter genotypes -238 G/G and -376 G/G and the TLR4 299 A/A genotype were associated with an otitis-prone condition. Furthermore, lower specific anticapsular antibody production after complete vaccination was observed in patients with the TNFA-238 G/G genotype or TNFA-863 A allele carriage. Finally, the IL10-1082 A/A genotype contributed to protection from the recurrence of acute otitis media after pneumococcal vaccination. CONCLUSIONS: Variation in innate immunoresponse genes such as TNFA-863A, TNFA-376G, TNFA-238G, IL10-1082 A, and IL6-174G alleles in the promoter sequences may result in altered cytokine production that leads to altered inflammatory responses and, hence, contributes to an otitis-prone condition.

Contains fulltext : 50782.pdf (publisher's version ) (Closed access), Innate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life.

Contains fulltext : 32756.pdf (publisher's version ) (Open Access), A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated the molecular epidemiology of 921 pneumococcal isolates retrieved from both the pneumococcal vaccine (PV) and control vaccine (CV) groups during the vaccination study. Within individuals a high turnover rate of pneumococcal restriction fragment end labeling genotypes, which was unaffected by vaccination, was observed. Comparison of the genetic structures before and after completion of the vaccination scheme revealed that, despite a shift in serotypes, there was clustering of 70% of the pneumococcal populations. The remaining isolates (30%) were equally observed in the PV and CV groups. In addition, the degree of genetic clustering was unaffected by vaccination. However, within the population genetic structure, nonvaccine serotype clusters with the serotypes 11, 15, and 23B became predominant over vaccine-type clusters after vaccination. Finally, overall pneumococcal resistance was low (14%), and, albeit not significant, a reduction in pneumococcal resistance as a result of pneumococcal vaccination was observed. Molecular surveillance of colonization in Dutch children shows no effect of pneumococcal conjugate vaccination on the degree of genetic clustering and the genetic structure of the pneumococcal population. However, within the genetic pneumococcal population structure, a clear shift toward nonvaccine serotype clusters was observed.

A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated the molecular epidemiology of 921 pneumococcal isolates retrieved from both the pneumococcal vaccine (PV) and control vaccine (CV) groups during the vaccination study. Within individuals a high turnover rate of pneumococcal restriction fragment end labeling genotypes, which was unaffected by vaccination, was observed. Comparison of the genetic structures before and after completion of the vaccination scheme revealed that, despite a shift in serotypes, there was clustering of 70% of the pneumococcal populations. The remaining isolates (30%) were equally observed in the PV and CV groups. In addition, the degree of genetic clustering was unaffected by vaccination. However, within the population genetic structure, nonvaccine serotype clusters with the serotypes 11, 15, and 23B became predominant over vaccine-type clusters after vaccination. Finally, overall pneumococcal resistance was low (14%), and, albeit not significant, a reduction in pneumococcal resistance as a result of pneumococcal vaccination was observed. Molecular surveillance of colonization in Dutch children shows no effect of pneumococcal conjugate vaccination on the degree of genetic clustering and the genetic structure of the pneumococcal population. However, within the genetic pneumococcal population structure, a clear shift toward nonvaccine serotype clusters was observed.

Contains fulltext : 58738.pdf (publisher's version ) (Closed access)

Item does not contain fulltext, Recurrent otitis media may be related to defects in specific antibody production, as suggested previously. This might be reflected in lower antibody responses to vaccinations administered in the context of the national childhood vaccination program in children suffering from recurrent otitis media. In a cross-sectional study we determined the levels of antidiphtheria, antitetanus, anti- Haemophilus influenzae type b (anti-Hib) and antimeasles antibodies in sera of 163 children with two or more episodes of acute otitis media per year and in 143 children with repeated periods of persistent otitis media with effusion each lasting at least 3 months. The control group consisted of 521 age-matched healthy children, who were free of recurrent respiratory tract infections. Children with recurrent acute otitis media, including highly otitis-prone children, showed higher antidiphtheria and antitetanus antibody titers compared to controls. No differences were observed in anti-Hib and antimeasles antibody levels between children with recurrent acute otitis media and controls, nor did any of the antibody levels in children with persistent otitis media with effusion differ from those in controls. Therefore, the results of our study do not point toward a generalized immunological hyporesponsiveness in children with recurrent acute otitis media and persistent otitis media with effusion. Determination of antibody responses to regular vaccines is not indicative for otitis-proneness.

Contains fulltext : 58666.pdf (publisher's version ) (Closed access)

Contains fulltext : 58936.pdf (publisher's version ) (Closed access)

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Item does not contain fulltext, BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Long term effects of recurrent episodes of otitis media, rapid emergence of drug resistant bacteria associated with AOM worldwide and huge estimated direct and indirect annual costs associated with otitis media have emphasized the need for an effective vaccination program to prevent episodes of AOM. OBJECTIVES: The object of this review was to assess the effect of pneumococcal vaccination in preventing AOM in children up to 12 years of age. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infection Group specialised register (last update, 26th April 2001), the Cochrane Library (Issue 4, 2000), MEDLINE (January 1966-August 2000) and reference list of all studies and review articles retrieved. We also contacted two vaccine manufacturers and first or corresponding authors of some included studies. SELECTION CRITERIA: Randomised controlled clinical trials of pneumococcal vaccination with prevention of AOM as outcome in children aged 12 years or younger and a follow-up of at least six months. DATA COLLECTION AND ANALYSIS: Five reviewers independently assessed trial quality and two reviewers extracted data. Two study authors were contacted. MAIN RESULTS: Eight trials on pneumococcal polysaccharide vaccine (PPV) and two trials on pneumococcal conjugate vaccine (PCV) were included. The highest efficacy of PPV was found in children aged 24 months and older: the rate ratio after adjustment for study was 0.833 [95%CI: 0.625-0.970]. The PPV has little effect on the prevention of AOM in children without documented prior episodes of AOM and only a moderate effect in the group of children with documented AOM episodes prior to vaccination. The results of the two PCV trials in healthy infants, which followed children from the age of two months until two years of age, could not be pooled because of lack of data. Both studies showed that the risk of recurrent disease decr