Chantal Wb Boonacker

Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria

Background High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. Methodology/Principal Findings We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. Conclusions/Significance Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.

Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis

Childhood immune thrombocytopenia (ITP) is a rare autoimmune bleeding disorder. Most children recover within 6 to 12 months, but individual course is difficult to predict. We performed a systematic review and meta-analysis to identify predictors of chronic ITP. We found 1399 articles; after critical appraisal, 54 studies were included. The following predictors of chronic ITP in children, assessed in at least 3 studies, have been identified: female gender (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.04-1.31), older age at presentation (age ≥11 years; OR 2.47, 95% CI 1.94-3.15), no preceding infection or vaccination (OR 3.08, 95 CI 2.19-4.32), insidious onset (OR 11.27, 95% CI 6.27-20.27), higher platelet counts at presentation (≥20 × 10(9)/L: OR 2.15, 95% CI 1.63-2.83), presence of antinuclear antibodies (OR 2.87, 95% 1.57-5.24), and treatment with a combination of methylprednisolone and intravenous immunoglobulin (OR 2.67, 95% CI 1.44-4.96). Children with mucosal bleeding at diagnosis or treatment with intravenous immunoglobulin alone developed chronic ITP less often (OR 0.39, 95% CI 0.28-0.54 and OR 0.71, 95% CI 0.52-0.97, respectively). The protective effect of intravenous immunoglobulin is remarkable and needs confirmation in prospective randomized trials as well as future laboratory studies to elucidate the mechanism of this effect.

Effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial.

Objective To assess the effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections. Design Open randomised controlled trial. Setting 11 general hospitals and two academic centres. Participants 111 children aged 1-6 with recurrent upper respiratory tract infections selected for adenoidectomy. Intervention A strategy of immediate adenoidectomy with or without myringotomy or a strategy of initial watchful waiting. Main outcome measure Primary outcome measure: number of upper respiratory tract infections per person year calculated from data obtained during the total follow-up (maximum 24 months). Secondary outcome measures: days with upper respiratory tract infection per person year, middle ear complaints with fever in episodes and days, days with fever, prevalence of upper respiratory tract infections, and health related quality of life. Results During the median follow-up of 24 months, there were 7.91 episodes of upper respiratory tract infections per person year in the adenoidectomy group and 7.84 in the watchful waiting group (difference in incidence rate 0.07, 95% confidence interval −0.70 to 0.85). No relevant differences were found for days of upper respiratory tract infections and middle ear complaints with fever in episodes and days, nor for health related quality of life. The prevalence of upper respiratory tract infections decreased over time in both groups. Children in the adenoidectomy group had significantly more days with fever than the children in the watchful waiting group. Two children had complications related to surgery. Conclusion In children selected for adenoidectomy for recurrent upper respiratory tract infections, a strategy of immediate surgery confers no clinical benefits over a strategy of initial watchful waiting. Trial registration Dutch Trial Register NTR968: ISRCTN03720485.

Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis.

To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).

Cost Effectiveness of Pneumococcal Conjugate Vaccination against Acute Otitis Media in Children: A Review

While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on the cost effectiveness of pneumococcal conjugate vaccination against AOM in children.We searched PubMed, Cochrane and the Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects [DARE], NHS Economic Evaluation Database [NHS EED] and Health Technology Assessment database [HTA]) from inception until 18 February 2010. We used the following keywords with their synonyms: ‘otitis media’, ‘children’, ‘cost-effectiveness’, ‘costs’ and ‘vaccine’. Costs per AOM episode averted were calculated based on the information in this literature.A total of 21 studies evaluating the cost effectiveness of pneumococcal conjugate vaccines were included. The quality of the included studies was moderate to good. The cost per AOM episode averted varied from €168 to €4214, and assumed incidence rates varied from 20952 to 118000 per 100000 children aged 0–10 years. Assumptions regarding direct and indirect costs varied between studies. The assumed vaccine efficacy of the 7-valent pneumococcal CRM197-conjugate vaccine was mainly adopted from two trials, which reported 6–8% efficacy. However, some studies assumed additional effects such as herd immunity or only took into account AOM episodes caused by serotypes included in the vaccine, which resulted in efficacy rates varying from 12% to 57%. Costs per AOM episode averted were inversely related to the assumed incidence rates of AOM and to the estimated costs per AOM episode. The median costs per AOM episode averted tended to be lower in industry-sponsored studies.Key assumptions regarding the incidence and costs ofAOMepisodes have major implications for the estimated cost effectiveness of pneumococcal conjugate vaccination against AOM. Uniform methods for estimating direct and indirect costs of AOM should be agreed upon to reliably compare the cost effectiveness of available and future pneumococcal vaccines against AOM.

Myositis autoantibodies, clinical features, and environmental exposures at illness onset are associated with disease course in juvenile myositis.

To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).

Parental experiences and attitudes regarding the management of acute otitis media--a comparative questionnaire between Finland and The Netherlands.

BACKGROUND Both treatment guidelines and the amount of antibiotics used for acute otitis media (AOM) vary across western countries. Parental expectations and their awareness of antimicrobial use and resistance, which may also be influenced by the guidelines, are not yet completely known. OBJECTIVE To compare parental experiences and opinions regarding the management of AOM in children with AOM in Finland and The Netherlands. METHODS We sent the questionnaires via public day care in Turku, Finland, and Utrecht, The Netherlands. We asked about family background, childs history of AOM and parental experiences and attitudes about AOM treatment and antimicrobial resistance. RESULTS Of 1151 participants, 83% in Finland and 49% in The Netherlands had had at least one episode of AOM. Antibiotics were used more frequently in Finland than in The Netherlands, 99% versus 78%, respectively. More Finnish parents reported to believe that antibiotics are necessary in the treatment of AOM as compared to Dutch parents. Use of analgesics for AOM was similar (80% in Finland and 86% in The Netherlands). One-third of the parents had discussed resistance with their doctor. According to parental experiences, antimicrobial resistance had caused more problems in Finland than in The Netherlands (20% versus 2%). Finally, 88% of parents in Finland and 65% in The Netherlands were worried that bacteria could become resistant to antibiotics. CONCLUSIONS Treatment practices and parental expectations seem to interact with each other. Therefore, if we aim to change AOM treatment practices, we have to modify both guidelines and parental expectations.

Trimethoprim-Sulfamethoxazole in Children With Chronic Otitis Media: A Randomized Comparison of Costs and Effects

Objective: To study the cost-effectiveness of a 6- to 12-week course of high-dose oral trimethoprim-sulfamethoxazole in children with chronic active otitis media (COM). Study Design: Cost-effectiveness study including both direct and indirect costs alongside a randomized placebo-controlled trial. Setting: Tertiary care university hospital in the Netherlands. Patients: One hundred one children aged 1 to 12 years with a documented history of COM for at least 3 months. Intervention: Six to 12 weeks of oral trimethoprim-sulfamethoxazole 18 mg/kg twice daily versus placebo. Main Outcome Measures: Incremental cost-effectiveness in terms of costs per number needed to treat (NNT) to cure 1 patient (incremental cost-effectiveness ratio [ICER]). Curation was defined as no otomicroscopic signs of otorrhea in either ear. Results: After 6 weeks of follow-up, the difference in mean cost per patient between the trimethoprim-sulfamethoxazole and placebo groups was Euro100 (US

Immediate Adenoidectomy vs Initial Watchful Waiting Strategy in Children With Recurrent Upper Respiratory Tract Infections: An Economic Evaluation

126). The NNT was 4 (clinical effect), and the corresponding ICER was Euro400 (US

Long-Term Follow-Up Study of Young Adults Treated for Unilateral Complete Cleft Lip, Alveolus, and Palate by a Treatment Protocol Including Two-Stage Palatoplasty: Speech Outcomes

504), that is, the average extra costs to cure 1 child from otorrhea is Euro400 (US