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To compare the incidence of respiratory symptoms and short-term consequences between children with Down syndrome and children from the general population, we conducted a prospective parent-reported observational study. Children with Down syndrome (≤ 18 years) were included between March 2012 and June 2014. Caregivers received a baseline questionnaire with follow-up 1–2 years after inclusion. Caregivers received a weekly questionnaire about respiratory symptoms, fever, antibiotic prescriptions, doctor’s visits, and consequences for school and work attendance. Children with Down syndrome were compared to a cohort of the general population (“Kind en Ziek” study) with similar weekly questionnaires. A total of 9,011 childweeks were reported for 116 participants with Down syndrome (75% response rate). The frequency of respiratory symptoms was higher in children with Down syndrome than in children from the general population (30% vs 15.2%). In addition, symptoms subsided later (around 8 vs 5 years of age). The seasonal influence was limited, both in children with Down syndrome and children from the general population. Consequences of respiratory disease were significant in children with Down syndrome compared to children from the general population, with a higher rate of doctor’s visits (21.3% vs 11.8%), antibiotic prescriptions (47.8% vs 26.3%), and absenteeism from school (55.5% vs 25.4%) and work (parents, 9.4% vs 8.1%). Conclusion: Children with Down syndrome have a higher frequency of respiratory symptoms and symptoms last until a later age, confirming the impression of professionals and caregivers. Individualized treatment plans might prevent unfavorable consequences of chronic recurrent respiratory disease in children with Down syndrome. What is Known:• Children with Down syndrome have an altered immune system and are prone to a more severe course of respiratory tract infections.• The overall conception is that patients with Down syndrome suffer from respiratory tract infections more often. What is New:• Children with Down syndrome suffer from respiratory symptoms more frequently than children from the general population.• The respiratory symptoms in children with Down syndrome subside at a later age compared to children from the general population.

This study improves our understanding of the pathogenesis of tuberculous meningitis (TBM) and may direct future strategies for the prevention of immunopathology associated with TBM. Our data suggest that host biomarker signatures in the cerebrospinal fluid have promising diagnostic applications and require urgent investigation. Background. Tuberculous meningitis (TBM) is a severe complication of tuberculosis predominantly affecting young children. Early treatment is vital to prevent morbidity and mortality, emphasizing the importance of early diagnosis. The lack of sensitive methods for early diagnosis is the most common cause of delay. Attempts have been made to develop simplified tests for tuberculosis, but their diagnostic power remains poor. The clinical picture of TBM is mainly driven by the host's immune response to Mycobacterium tuberculosis; therefore, identification of disease-specific biomarkers may have diagnostic and therapeutic value and improve our understanding of its pathogenesis. Methods. We investigated disease-specific biomarkers of childhood TBM in a cohort of children aged 3 months–13 years with symptoms and signs suggestive of meningitis. Cerebrospinal fluid (CSF) and serum from 56 patients with and 55 patients without TBM were assessed for 28 soluble mediators. Results. Unsupervised hierarchical clustering analysis revealed a disease-specific pattern of biomarkers for TBM relative to other types of meningitis. A biomarker-based diagnostic prediction model for childhood TBM based on CSF concentrations of interleukin 13 (cutoff value, 37.26 pg/mL), vascular endothelial growth factor (cutoff value, 42.92 pg/mL), and cathelicidin LL-37 (cutoff value, 3221.01 pg/mL) is presented with a sensitivity of 0.52 and a specificity of 0.95. Conclusions. These data highlight the potential of biosignatures in the host's CSF for diagnostic applications and for improving our understanding of the pathogenesis of TBM to discover strategies to prevent immunopathological sequelae.

This report describes four patients with acute lymphoblastic leukaemia, suffering from posterior reversible encephalopathy syndrome during the induction period of treatment. A review of the literature on posterior reversible encephalopathy syndrome in paediatric leukaemia is given. The exact mechanism of posterior reversible encephalopathy syndrome is not clear and seems to be multifactorial. Hypertension is likely to play a major role in the development but could be also secondary. All patients in this case series presented after introduction of the new induction protocol for acute lymphoblastic leukaemia. Treatment of hypertension is likely to have a favourable role and posterior reversible encephalopathy syndrome is most often reversible. It is important to consider this diagnosis during the induction phase of leukaemia treatment in the presence of neurological symptoms. The incidence of PRES in the induction scheme should be investigated, in order to optimize the ALL treatment.

BackgroundGenetic variation in immune response genes is associated with susceptibility and severity of infectious diseases. Toll-like receptor (TLR) 9 polymorphisms are associated with susceptibility to develop meningococcal meningitis (MM). The aim of this study is to compare genotype distributions of twoTLR9polymorphisms between clinical severity variables in MM survivors.MethodsWe used DNA samples of a cohort of 390 children who survived MM. Next, we determined the genotype frequencies ofTLR9-1237 andTLR9+2848 polymorphisms and compared these between thirteen clinical variables associated with prognostic factors predicting adverse outcome of bacterial meningitis in children.ResultsTheTLR9 -1237 TC and CC genotypes were associated with a decreased incidence of a positive blood culture forNeisseria (N.) meningitidis(p = 0.014, odds ratio (OR) 0.5. 95% confidence interval (CI) 0.3 – 0.9). TheTLR9 +2848 AA mutant was associated with a decreased incidence of a positive blood culture forN. meningitidis(p = 0.017, OR 0.6, 95% CI 0.3 – 0.9). Cerebrospinal fluid (CSF) leukocytes per μL were higher in patients carrying theTLR9 -1237 TC or CC genotypes compared to carriers of the TT wild type (WT) (p = 0.024, medians: 2117, interquartile range (IQR) 4987 versus 955, IQR 3938). CSF blood/glucose ratios were lower inTLR9 -1237 TC or CC carriers than in carriers of the TT WT (p = 0.017, medians: 0.20, IQR 0.4 versus 0.35, IQR 0.5). CSF leukocytes/μL were higher in patients carrying theTLR9 +2848 AA mutant compared to carriers of GG or GA (p = 0.0067, medians: 1907, IQR 5221 versus 891, IQR 3952).ConclusionsWe identified TLR9 genotypes associated with protection against meningococcemia and enhanced local inflammatory responses inside the central nervous system, important steps in MM pathogenesis and defense.

Cutaneous zygomycosis is a rare but severe fungal infection with high risk of dissemination. Early recognition, deep surgical biopsy for diagnosis, aggressive treatment with repeated surgical debridement, and targeted pharmacotherapy are essential and can prevent dissemination and fatal outcome. We present case reports of 2 patients.