Multicentric analysis of childhood tuberculosis in Turkey.

Only a few series of pediatric tuberculosis (TB) have been reported in the last 20 years. The purpose of this study was to evaluate the clinical, radiological, microbiological, and treatment characteristics of childhood TB. A total of 539 children with childhood TB diagnosed over a 12-year period (1994-2005) in 16 different centers in Turkey participated in the study. The medical records of all childhood TB patients were investigated. A total of 539 children (274 males, 265 females) with childhood TB aged 10 days-17 years participated in the study. Age distribution was nearly equal among all age groups. We detected the index case in 39.8% of the patients. More than one index case was detected in 17.3% of the patients. A minimum 15-mm induration is accepted on tuberculin skin test (TST) following Bacillus Calmette-Guérin (BCG) vaccination. The TST was positive in 55.3% of the patients. Acid-fast bacillus smear was positive in 133, and polymerase chain reaction for Mycobacterium tuberculosis was positive in 45 patients. In 75 patients (13.9%), cultures yielded M. tuberculosis. One hundred fifty-one patients (28%) did not present for followup, and families of 5 patients (0.9%) discontinued the treatment. Pulmonary TB (n=285) and meningeal TB (n=85) were the most frequent diseases. In 29% of the patients, there was poor adherence to treatment or patients were lost to follow-up. We have demonstrated that household contact screening procedures play a major and important role, especially considering the high ratio of cases with contact index cases. We also recommend that the positive TST values should be reviewed according to the local cut-off data and should be specified in as many countries as possible. In view of the considerably high percentages of patients lost to follow-up and treatment discontinuation observed in our study, we suggest that application of directly observed treatment short-course (DOTS) is preferable.

The effect of cetirizine on IFN-gamma and IL-10 production in children with allergic rhinitis.

Cetirizine, one of the most commonly used antihistamines for the treatment of allergic diseases, possesses some anti-inflammatory properties. Despite its common use, the effect of cetirizine on the production of cytokines from peripheral blood mononuclear cells (PBMCs) needs further clarification. The aim of this study was to investigate whether cetirizine changes interleukin (IL)-10, (IF)-gamma and IL-4 production from PBMCs in children with allergic rhinitis. Thirteen children with allergic rhinitis sensitized to house dust mite (HDM) were treated with cetirizine for four weeks. Blood samples were drawn just prior to the treatment, on the last day of the treatment and two weeks following the cessation of treatment The cytokine production from PBMCs was tested in the presence or absence of HDM allergen and measured by ELISA assay. An augmentation in IL-10 production was observed in PBMCs at the 4th week of cetirizine treatment (p<0.05). Furthermore, a significant increase in IFN-gamma production was observed following the therapy. IL-4 release did not change at all time points tested. In addition, IFN-gamma/IL-4 ratio increased following cetirizine treatment. Cetirizine induced a shift in the human Th1/Th2 cytokine balance toward a Th1 type response by increasing IFN-gamma production and augmenting suppressor cytokine release (IL-10). We concluded that apart from its known antihistaminic properties, cetirizine may modulate allergic inflammation while the patients are on regular treatment schedules.

TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha production.

Previous studies suggested that abnormal regulation of TNF-alpha production may have a role in the pathogenesis of rheumatic fever (RF). Polymorphism at the promoter region of TNF-alpha gene (-308 A) has recently been shown to be associated with rheumatic heart disease (RHD) in Mexican patients. Although this polymorphism has long been shown to affect TNF-alpha gene expression in cell lines, its role in production of the cytokine in RF patients has not been studied. We therefore investigated TNF-alpha G-308A single nucleotide polymorphism and its effect on TNF-alpha production in 71 Turkish RF patients and 89 ethnically matched healthy controls. The TNF-alpha-308A allele frequency was found to be significantly higher in RF patients (RHD+arthritis) than in healthy controls [p<0.0032 Odds ratio (OR)=3.4, 95% confidence interval (CI) (1.5-7.7)]. When RHD patients were analyzed as a separate group, significant difference persisted [p<0.0055, OR=3.3, 95% CI (1.5-7.6)]. More importantly, ELISPOT analysis demonstrated that existence of A allele was associated with higher TNF-alpha production compared with G allele. Our data suggest that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop RF disease.

Mannose-binding lectin levels in children with asthma.

Mannose-binding lectin (mbl), one of the important components of innate immunity, can activate the lectin pathway of the complement system. After binding mannose containing carbohydrate structures of foreign antigen, mbl initiates and regulates the inflammatory responses. Asthma is a complex inflammatory disease of the lung involving many components of the immune system. Our objective was to investigate the serum mbl levels of asthmatic children in comparison with healthy controls. Serum mbl levels were determined by nephelometric assay in 72 asthmatic children (5-15 yr old) and 30 healthy age-matched controls. Mbl levels of asthmatic children were measured both during acute attack and after complete remission. There was no significant difference between the mbl levels during acute attack (median 4.1 mg/l) or quiescence of symptoms (median 3.6 mg/l). Serum mbl levels both during acute attack or quiescence of symptoms was significantly higher in asthmatic children than in the healthy controls (median 2.8 mg/l, p < 0.0001 for each). Furthermore, mbl levels of asthmatic children positively correlated with peripheral blood eosinophils (r = 0.377, p < 0.001), which is a systemic component of airway inflammation in asthma. Our findings indicate that mbl may be implicated in the pathogenesis of asthma by contributing to airway inflammation or by increasing the risk of developing asthma.

Rapid decline of anti-pneumococcal antibody levels in nephrotic children.

Nephrotic children are at increased risk for pneumococcal infections. Antibody responses to the currently recommended pneumococcal polysaccharide vaccine have been variable and maintenance of adequate antibody levels over time has not been well documented. In this study, we determined total IgG antibody levels against pneumococcal polysaccharides before and 1, 6, 12 and 36 months after 23-valent pneumococcal polysaccharide vaccine (PPV) administration in nine children with steroid-responsive nephrotic syndrome during remission while off corticosteroids. The baseline antibody levels were between 4 and 86 mg/l. Four weeks after vaccination, the titer increased at least twofold in all patients with a mean arithmetic value of 165.4 mg/l. At the 6th month, the levels decreased in six out of nine subjects to a mean of 94.6 mg/l. At the 36th month, the control antibody levels were below the baseline or below the early postvaccination values in four out of nine subjects. Only two patients had stable high concentrations through the study period. Our data show that nephrotic patients may not retain their antibody levels despite reasonably good initial responses to the pneumococcal vaccine and that susceptibility to infections may continue in vaccinated children.

Netherton syndrome associated with idiopathic congenital hemihypertrophy.

Netherton syndrome is a rare genodermatosis comprised of anichthyosiform dermatitis, hair shaft defects, and atopic features. Other problems associated with Netherton syndrome are delayed growth and development, immune abnormalities, recurrent infections, and intermittent aminoaciduria. We describe an 18-month-old girl with Netherton syndrome who had idiopathic congenital hemihypertrophy on her right side with contralateral benign nephromegaly in addition to the characteristic clinical signs of the syndrome. To our knowledge, this is the first case of Netherton syndrome associated with idiopathic congenital hemihypertrophy to be reported.

Apoptosis of cord blood neutrophils and their response to colony-stimulating factors.

Neutrophil production and functions are immature in newborns. Although neutrophil kinetics during neonatal period have been widely studied, little is known about the effect of apoptosis on these defects. In this study, we examine the apoptosis of neonatal neutrophils and the effects of colony-stimulating factors (CSF) on this process. The study was performed using three different methodologies (morphological analysis, surface Fas expression, and mitochondrial 7A6 antigen expression) and the results were compared with adult controls. Neonatal neutrophils more rapidly underwent apoptosis in comparison to adult neutrophils. The above-mentioned three different methods gave similar results. Granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) decreased the apoptosis of neutrophils in newborns and adults. This effect was significantly more pronounced in adults than newborns in morphological analysis. Increased apoptosis may contribute to qualitative and quantitative defects of neutrophils during neonatal period and may be an explanation for the proneness of newborn to develop neutropenia during systemic infections.