Clinical features of Candidiasis in patients with inherited interleukin 12 receptor ß1 deficiency.

BACKGROUND: Interleukin 12Rß1 (IL-12Rß1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rß1 deficiency. RESULTS: Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. CONCLUSIONS: Patients who are deficient in IL-12Rß1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

Takayasu arteritis in a 4-year-old girl: case report and brief overview of the pediatric literature.

Takayasu arteritis (TA) is a large vessel vasculitis that involves the aorta, its major branches and pulmonary arteries. Diagnosis of TA during childhood remains challenging due to the non-specific symptoms. We report a four-year-old girl presenting with fever, fatigue, weight loss, and elbow pain who was later diagnosed as childhood TA. On admission, she had fever, hypertension, decreased pulses, bruits, hepatosplenomegaly, and increased erythrocyte sedimentation rate and C-reactive protein level. Computed tomography angiography showed luminal narrowing and wall thickening in ascending aorta, brachiocephalic, left common carotid and left vertebral arteries and descending aorta. Oral corticosteroid (prednisone, 2 mg/kg/day) was instituted, later followed by oral methotrexate (12.5 mg/m2/week). TA is rare in children; however, childhood TA must be considered in children who present with non-specific systemic symptoms, hypertension and increased acute phase reactants.

Clinical and epidemiological features of Turkish children with 2009 pandemic influenza A (H1N1) infection: experience from multiple tertiary paediatric centres in Turkey.

BACKGROUND: In April 2009 a novel strain of human influenza A, identified as H1N1 virus, rapidly spread worldwide, and in early June 2009 the World Health Organization raised the pandemic alert level to phase 6. Herein we present the largest series of children who were hospitalized due to pandemic H1N1 infection in Turkey. METHODS: We conducted a retrospective multicentre analysis of case records involving children hospitalized with influenza-like illness, in whom 2009 H1N1 influenza was diagnosed by reverse-transcriptase polymerase chain reaction assay, at 17 different tertiary hospitals. RESULTS: A total of 821 children with 2009 pandemic H1N1 were hospitalized. The majority of admitted children (56.9%) were younger than 5 y of age. Three hundred and seventy-six children (45.8%) had 1 or more pre-existing conditions. Respiratory complications including wheezing, pneumonia, pneumothorax, pneumomediastinum, and hypoxemia were seen in 272 (33.2%) children. Ninety of the patients (11.0%) were admitted or transferred to the paediatric intensive care units (PICU) and 52 (6.3%) received mechanical ventilation. Thirty-five children (4.3%) died. The mortality rate did not differ between age groups. Of the patients who died, 25.7% were healthy before the H1N1 virus infection. However, the death rate was significantly higher in patients with malignancy, chronic neurological disease, immunosuppressive therapy, at least 1 pre-existing condition, and respiratory complications. The most common causes of mortality were pneumonia and sepsis. CONCLUSIONS: In Turkey, 2009 H1N1 infection caused high mortality and PICU admission due to severe respiratory illness and complications, especially in children with an underlying condition.

Viral etiology in hospitalized children with acute lower respiratory tract infection.

This study was performed to investigate the viral etiological agents, age distribution and clinical manifestations of lower respiratory tract infection (LRTI) in hospitalized children. The viral etiology and clinical findings in 147 children (1 month to 5 years of age) hospitalized with acute LRTI were evaluated. Cell culture was used for isolation of influenza viruses and direct fluorescent antibody assay for parainfluenza viruses (PIVs), respiratory syncytial virus (RSV) and adenoviruses (ADVs). Reverse-transcriptase polymerase chain reaction was employed for human metapneumovirus (hMPV). One hundred and six of all patients (72.1%) were male, and 116 children (79.8%) were < or = 2 years. A viral etiology was detected in 54 patients (36.7%). RSV was the most frequently isolated (30 patients, 55.6%), and PIV (27.8%), hMPV (13%), influenza-A (9.3%), and ADV (5.6%) were also shown. Dual infection was detected in six patients. There were no statistically significant differences between the two groups (with isolated virus or no known viral etiology) with respect to symptoms, clinical findings, laboratory work-up, or radiological data. Length of hospital stay was also not different. Determination of the etiology of acute LRTI in children less than 5 years of age seems impossible without performing virological work-up, whether viral or nonviral in origin.

Multicenter prospective study on the burden of rotavirus gastroenteritis in Turkey, 2005-2006: a hospital-based study.

Rotavirus is the main cause of gastroenteritis and dehydration requiring hospitalization among infants and children. Despite the high diarrhea-related mortality rate, there are limited studies describing the prevalence of rotavirus in Turkey. The disease burden of rotavirus gastroenteritis in Turkey was assessed by active, prospective surveillance conducted in accordance with a modified World Health Organization generic protocol from 1 June 2005 through 1 June 2006. A total of 411 children aged <5 years who were hospitalized for gastroenteritis in 4 centers were enrolled. Rotavirus was identified in 53% of samples from the 338 children tested; the range for individual centers was 32.4%-67.4%. Overall, 83.8% of rotavirus-positive children were aged <2 years. Rotavirus gastroenteritis occurred year-round but peaked in the winter. G1P[8] was the most widely prevalent strain (76% of strains), followed by G2P[4] (12.8%). G9P[8] was reported in samples from 3.9% of children. These data support the need for a rotavirus vaccine in Turkey.

[Investigation of phenotypic and genotypic characteristics of vancomycin-resistant Enterococcus faecium isolates]. / Vankomisine dirençli Enterococcus faecium suslarinin fenotipik ve genotipik olarak incelenmesi.

The purpose of the present study was to investigate the phenotypic and genotypic characteristics and the probable clonal dissemination of 13 vancomycin-resistant enterococcus (VRE) strains isolated between February-August 2006 from 11 patients at the Hospital of Istanbul Faculty of Medicine. The in vitro activities of antibiotics were determined by disk diffusion method in accordance with the CLSI (Clinical and Laboratory Standards Institute) guidelines and the minimum inhibitory concentration (MIC) values by E-test. Multiplex polymerase chain reaction (PCR) was performed for detection of vanA, vanB and vanC genes and RAPD-PCR (Randomly amplified polymorphic DNA-PCR) for investigating a clonal relationship among the isolates. All isolates exhibited resistance to vancomycin, teicoplanin, ampicillin, and high-level resistance to streptomycin. VanA phenotype and the relevant vanA gene, characterised by resistance to both vancomycin and teicoplanin, were detected in all isolates which were all E. faecium. Molecular investigation by RAPD-PCR showed these strains to belong to four different patterns, each containing 1 to 5 isolates. According to these results, the spread of VRE within our hospital was considered as a polyclonal dissemination.

Neuro-Behçet disease presenting as secondary pseudotumor syndrome: case report.

Behçet's disease is a multisystemic, recurrent, inflammatory disorder, which has a three-symptom complex comprising uveitis, oral aphtae and genital ulcerations. It is rare in childhood. The prevalence of neurologic involvement in BD is range of 10-49%, and shows a wide spectrum from isolated headache to subacute encephalopathy and severe psychosis. We report a 12-year-old Behçet's disease patient with secondary pseudotumor syndrome due to cerebral vein thrombosis and aim to review the literature.

Pulmonary arterial pressure in infants with laryngomalacia.

OBJECTIVE: Persistent upper airway obstruction may lead to increased pulmonary arterial pressure in childhood. Laryngomalacia is one of the most common causes of transient upper airway obstruction by laryngeal blockage in infants. The aim of the study is to evaluate the pulmonary arterial pressures in infants with laryngomalacia during infancy period. METHODS: Fifteen infants with laryngomalacia and 30 healthy controls were enrolled into this study. The pulmonary arterial pressures were measured by using Doppler echocardiography. Infants were also evaluated by clinical investigations, telecardiography and electrocardiography. RESULTS: Our results showed that infants with laryngomalacia may have significantly higher pulmonary arterial pressure than healthy subjects. Pressures of patient group were significantly decreased at the end of infancy period. CONCLUSIONS: Increased pulmonary arterial pressure levels due to laryngomalacia are reversible by during developmental process. Therefore, in symptomatic period, evaluation of infants with laryngomalacia by using Doppler echocardiography may be useful for monitoring pulmonary arterial pressure and following up the clinical outcome.

Tuberculous liver abscess in an immunocompetent child with pulmonary tuberculosis as a cause of fever of unknown origin.

Infectious diseases are the leading cause of FUO. A case of prolonged fever with hepatic and pulmonary tuberculosis as a final diagnosis is herein presented. A 4-year-old, otherwise healthy boy presented with an axillary temperature of up to 39.5ºC for the previous 3 weeks. His medical history revealed an occasional increase in body temperature up to 38.5ºC for the last 6 months. Physical examination revealed coarse breath sounds on the basal lung area. Chest X-ray showed mediastinal lymphadenomegaly and computed tomography revealed paratracheal conglomerated lymph nodes and a groundglass appearance on the right lung. There were multiple contrast-enhanced, hypoechoic nodules with central necrosis in the liver parenchyma on abdominal magnetic resonance imaging. Open liver biopsy yielded chronic granulomatous inflammation compatible with pathological findings of tuberculosis infection. The culture specimen was positive for Mycobacterium tuberculosis. The patient improved rapidly after antituberculous therapy was initiated. Tuberculosis, especially in its disseminated form, poses a distinct diagnostic challenge in cases of prolonged fever with unproven etiology, and thus persistence should be exercised in disclosing the cause of such fevers.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005-2012 in Turkey. A multicenter prospective surveillance study.

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

Distribution of Streptococcus pneumoniae serotypes that cause parapneumonic empyema in Turkey.

Streptococcus pneumoniae is the most common etiological cause of complicated pneumonia, including empyema. In this study, we investigated the serotypes of S. pneumoniae that cause empyema in children. One hundred fifty-six children who were diagnosed with pneumonia complicated with empyema in 13 hospitals in seven geographic regions of Turkey between 2010 and 2012 were included in this study. Pleural fluid samples were collected by thoracentesis and tested for 14 serotypes/serogroups using a Bio-Plex multiplex antigen detection assay. The serotypes of S. pneumoniae were specified in 33 of 156 samples. The mean age ± the standard deviation of the 33 patients was 6.17 ± 3.54 years (range, 0.6 to 15 years). All of the children were unvaccinated according to the vaccination reports. Eighteen of the children were male, and 15 were female. The serotypes of the non-7-valent pneumococcal conjugated vaccine (non-PCV-7), serotype 1, serotype 5, and serotype 3, were detected in eight (14.5%), seven (12.7%), and five (9.1%) of the samples, respectively. Serotypes 1 and 5 were codetected in two samples. The remaining non-PCV-7 serotypes were 8 (n = 3), 18 (n = 1), 19A (n = 1), and 7F/A (n = 1). PCV-7 serotypes 6B, 9V, 14, 19F, and 23F were detected in nine (16.3%) of the samples. The potential serotype coverages of PCV-7, PCV-10, and PCV-13 were 16.3%, 45.4%, and 60%, respectively. Pediatric parapneumonic empyema continues to be an important health problem despite the introduction of conjugated pneumococcal vaccines. Active surveillance studies are needed to monitor the change in S. pneumoniae serotypes that cause empyema in order to have a better selection of pneumococcal vaccines.

Blue rubber bleb nevus syndrome: successful treatment with sirolimus.

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder with characteristic vascular malformations of the skin, gastrointestinal system, and, less often, other organ systems. The characteristic cutaneous lesions consist of deep-blue, soft, rubbery blebs, which are easily compressible. The most serious complication is abundant gastrointestinal bleeding. We describe the case of an 8-year-old girl with diagnosed BRBNS who had multiple venous malformations all over her body, importantly, throughout the gastrointestinal tract, mouth, esophagus, stomach, small bowel, and colon. She presented with recurrent massive gastrointestinal bleeding and soft tissue hematoma despite prednisolone and α-interferon therapy. We started low-dose sirolimus as an antiangiogenic agent. The vascular masses were reduced rapidly and there was no gastrointestinal bleeding and muscular hematoma after sirolimus therapy. There was no drug adverse reaction at 20-month follow-up. To the best of our knowledge, this is the first report related to the use of sirolimus in a patient with BRBNS.

Serotypes of Streptococcus pneumoniae isolates from children with invasive pneumococcal disease in Turkey: baseline evaluation of the introduction of the pneumococcal conjugate vaccine nationwide.

Before use of the pneumococcal conjugate vaccine PCV7 became widespread in Turkey, 202 invasive pneumococcus isolates were analyzed. The most common serotypes were 19F and 6B. In children ≤2 years of age, the potential coverage rate of PCV7 was 69.5%. The most frequent non-PCV7 serotypes were 19A, 3, 1, 6A, and 8.

IL-12Rß1 deficiency in two of fifty children with severe tuberculosis from Iran, Morocco, and Turkey.

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rß1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rß1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rß1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rß1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rß1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity.

Lymphadenitis caused by H1N1 vaccination: case report.

A patient admitted to hospital for a supraclavicular painful mass. Ultrasonography showed soliter lymphadenopathy. He underwent H1N1 vaccination 1 week before this lymphadenopathy developed. Groosly the mass measured 1cmx0.8cmx0.8cm. It was round, yellow to brown, slightly soft. In pathologic examination, we detected edema in capsule of lymph node. The basic architecture was preserved. There was mottled appearance caused by marked proliferation of immunoblasts which were positive with CD 30. Also large, unusual immunoblasts which closely resemble mononuclear hodgkin cells were present. These unusual immunoblasts were positive with CD 30, too. For differential diagnosis, at first we should regard hodgkin lymphoma. We suggested that lymphadenitis may be a side effect of H1N1 vaccination.

Congenital tuberculosis in premature twins after in vitro fertilisation.

Genital tuberculosis is a major cause of infertility in countries where tuberculosis is endemic. With recent advances in assisted reproductive technology, women with tuberculous endometritis may become pregnant and ultimately have children with congenital tuberculosis. In vitro fertilisation represents a useful treatment for infertility. Congenital tuberculosis is a rare and severe, rapidly progressive, disease. Making an early diagnosis of congenital tuberculosis is difficult, because it can mimic many neonatal illnesses. To the best of our knowledge, we report the first cases of premature twins with congenital tuberculosis following in vitro fertilisation. After the diagnosis of genital tuberculosis in the mother, the twins were screened and diagnosed for tuberculosis. The twins dramatically improved after anti-tuberculosis therapy. We also wish to draw attention to the importance of searching for genital tuberculosis as the possible cause of congenital infection, even if the mother is asymptomatic.