Selda Hancerli Torun

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life‐threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single‐gene inborn errors of IFN‐γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Invasive aspergillosis in hematopoietic stem cell and solid organ transplantation

Invasive aspergillosis (IA) is currently an important cause of morbidity and mortality in hematopoietic stem cell transplant and solid organ transplant recipients. A high index of suspicion and careful clinical and radiological examinations are the keys to identifying infected patients early. Chest computerized axial tomography is extremely useful in diagnosing pulmonary aspergillosis. Microbiologic or histologic identification of infection, however, remain essential. Successful management of invasive fungal infections depends on timely and appropriate treatment. There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials. In contrast to adult patients, large prospective comparitive studies have not been performed in pediatric patients with IA. Moreover, pediatric subgroups have not been analyzed in published studies that include a broader age range. Clinicians treating pediatric IA are largely left with the results of uncontrolled trials, observatory surveys, salvage therapy data and extrapolations from adult studies to guide their treatment choices. The aim of this article is to state the main characteristics of IA in both pediatric and adult populations.

Atypical presentation of human bocavirus: Severe respiratory tract infection complicated with encephalopathy.

Human bocavirus (HBOV) has been reported as a worldwide distributed respiratory pathogen. It has also been associated with encephalitis recently by detection of the virus in cerebrospinal fluid (CSF) of patients presented with encephalitis. This retrospective study aimed to present clinical features of HBOV infections in children with respiratory symptoms and describe unexplained encephalopathy in a subgroup of these patients. Results of 1,143 pediatric nasal samples from mid‐December 2013 to July 2014 were reviewed for detection of HBOV. A multiplex real time polymerase chain reaction assay was used for viral detection. Medical records of the patients were retrospectively analyzed. HBOV was detected in 30 patients (2.6%). Median age was 14 months (5–80). Clinical diagnoses were upper respiratory tract infection (n = 10), bronchopneumonia (n = 9), acute bronchiolitis (n = 5), pneumonia (n = 4), acute bronchitis (n = 1), and asthma execarbation (n = 1). Hospitalization was required in 16 (53.3%) patients and 10 (62.5%) of them admitted to pediatric intensive care unit (PICU). Noninvasive mechanical ventilation modalities was applied to four patients and mechanical ventilation to four patients. Intractable seizures developed in four patients while mechanically ventilated on the 2nd–3rd days of PICU admission. No specific reason for encephalopathy was found after a thorough investigation. No mortality was observed, but two patients were discharged with neurological sequela. HBOV may lead to respiratory infections in a wide spectrum of severity. This report indicates its potential to cause severe respiratory infections requiring PICU admission and highlights possible clinical association of HBOV and encephalopathy, which developed during severe respiratory infection. J. Med. Virol. 87:1831–1838, 2015.

Clinical and Epidemiological Characteristics of Pandemic Influenza A/(H1N1) in Hospitalized Pediatric Patients at a University Hospital, Istanbul, Turkey

Abstract Background: The aim of this study was to describe the clinical and epidemiological characteristics of pandemic influenza in hospitalized children. Methods: A total of 114 patients with suspected H1N1 virus infection were hospitalized, and nasal swabs were sent to National Influenza Reference Laboratory for confirmation of pandemic influenza A (H1N1) virus infection by rRT–PCR assay. Results: Forty-six female and 68 male patients were included in the study. Age of the patients ranged from 40 days to 16 years. Clinical and/or radiological pneumonia were detected in 96% of all. Sixteen patients required mechanical ventilation due to hypoxemia. Previously healthy children required mechanical ventilation and oxygen therapy more than patients with chronic diseases. Elevated levels of CRP and LDH in patients with respiratory distress and patients who required mechanical ventilation were statistically significant. Conclusion: Our study showed that progress of pandemic influenza infection in previously healthy children is as severe as their counterparts with chronic underlying diseases.

Role of Autoantibodies to N-Methyl-d-Aspartate (NMDA) Receptor in Relapsing Herpes Simplex Encephalitis A Retrospective, One-Center Experience

Post–herpes simplex virus encephalitis relapses have been recently associated with autoimmunity driven by autoantibodies against N-methyl-d-aspartate (NMDA) receptors. Because it offers different treatment options, determination of this condition is important. Between 2011 and 2014, 7 children with proven diagnosis of herpes simplex virus encephalitis were identified in a university hospital of Istanbul. Two patients had neurologic relapse characterized mainly by movement disorders 2 to 3 weeks after initial encephalitis. The first patient received a second 14 days of acyclovir treatment together with antiepileptic drugs and left with severe neurologic sequelae. The second patient was found to be NMDA receptors antibody positive in the cerebrospinal fluid. She was treated with intravenous immunoglobulin and prednisolone. She showed substantial improvement, gradually regaining lost neurologic abilities. Post–herpes simplex virus encephalitis relapses may frequently be immune-mediated rather than a viral reactivation, particularly in children displaying movement disorders like choreoathetosis. Immunotherapy may provide benefit for this potentially devastating condition, like the case described in this report.

Caspofungin therapy in immunocompromised children and neonates

The prevalence of invasive fungal infections is increasing and the infections are becoming a major problem in immunocompromised children and neonates. Fortunately, there has been a recent surge in the development of new antifungal agents. Caspofungin, the first licensed echinocandin, is a novel class of antifungal and is approved for use in children 3 months of age or older for the treatment of invasive candidiasis, salvage therapy for invasive aspergillosis and as empirical therapy for febrile neutropenia. This article reviews the published data on the use of caspofungin in immunocompromised children and neonates with invasive fungal infections.

Evaluation of Candida species and antifungal susceptibilities among children with invasive candidiasis

AIM Non-albicans Candida species and resistant microorganisms have been more commonly isolated in invasive candidiasis in recent years. The aim of this study was to evaluate the distrubution of Candida spp and antifungal resistance in our clinic. MATERIAL AND METHODS Fifty-four Candida isolates and antifungal susceptibility results obtained from patients diagnosed as having invasive candidiasis between December 2012 and June 2016 were included. Clinical and laboratory data were retrospectively analyzed. E-test method was used in order to determine antifungal susceptibilities of Candida spp for amphotericin B, fluconazole, voriconazole, ketoconazole, itraconazole, anidulafungin, caspofungin, and flucytosine. RESULTS The clinical diagnoses of the patients were candidemia (n=27, 50%), catheter-related blood stream infection (n=1, 1.8%), urinary tract infection (n=13, 24%), surgical site infection (n=4, 7.4%), intraabdominal infection (n=3, 5.5%), empyema (n=2, 3.7%), and pneumonia (n=4, 7.4%). The most common isolated agent was C. albicans (n=27, 50%) and the others were C. parapsilosis (n=13, 24%), C. tropicalis (n=6, 11.1%), C. glabrata (n=3, 5.6%), C. lusitaniae (n=2, 3.7%), and unspecified Candida spp. (n=3, 5.6%). Fluconazole resistance was 7.4% among all isolates. Resistance against itraconazole, ketoconazole, anidulafungin, voriconazole and caspofungin were 33.3%, 12.5%, 11.1%, 5%, and 2.5%, respectively. Isolates presented intermediate resistance against itraconazole (41.7%), voriconazole (5.6%), and amphotericin B (3.7%) to varying extents. All of the isolates were susceptible to flucytosine. CONCLUSIONS In our clinic, C. albicans and non-albicans Candida species were equally distributed and antifungal susceptibilities against major antifungal agents such as fluconazole, amphotericin B, and caspofungin were found considerably high.

Characteristics of isolated spinal cord involvement in neurobrucellosis with no corresponding MRI activity: A case report and review of the literature.

Brucellosis is the most common zoonotic infection that affects camels, sheep, and goats as primary hosts and humans as secondary hosts [1,2]. Brucellosis is transmitted through the consumption of uncooked meat or unpasteurized dairy products or by direct contact with tissue or blood from infected animals, and is more common in countries with poor public health [3]. According to the World Health Organization, N500,000 new cases occur each year worldwide [2]. Herein, we present an adolescent boy with isolated spinal cord involvement due to brucellosis with normal imaging.We also determined the clinical characteristics of similar cases through review of reports in the literature.

Brucella infection in a child with progressive familial intrahepatic cholestasis type 2 who had undergone liver transplantation.

Brucellosis is considered the most widespread zoonosis in the world. In endemic regions of brucellosis, childhood brucellosis includes up to one‐third of all cases of human brucellosis. Brucellosis constitutes a public health problem in Turkey. A boy aged 12 yr who had PFIC2 had undergone deceased‐donor liver transplantation in 2008 at the age of seven. The boy presented with fatigue, fever, and pain in the right leg and hip and was admitted to the hospital. Brucella melitensis grew in the blood culture, and the SAT was positive at a titer of 1:640. The patient was treated with oral doxycycline and rifampicin for eight wk. After treatment, the patient recovered and his blood cultures became negative. The patients mother also had a high Brucella agglutination titer of 1:320 positive and was treated in the internal medicine department with spiramycin and doxycycline. Brucella infection should be suspected in liver transplant recipients with fever of unknown origin, especially in recipients who live in an endemic area.

Acquired Immune Deficiency Syndrome in Differential Diagnosis of Hyper-IgE-Immunoglobulinemia: Pediatric Case Report.

Acquired immune deficiency syndrome can be encountered with hypereosinophilia and hyperimmunoglobulin E (hyper-IgE) values, though these levels are rarely so high to be compared with hyperimmunoglobulin E syndrome. A 9-year-old boy presented with the complaint of fatigue, weakness, weight loss and generalized pruritic rash lasting for a year. He had frequent respiratory tract infections, wheezing episodes and urticarial skin lesions before that. On admission, he was cachectic and he had generalized lymphadenopathy, hepatosplenomegaly, oral moniliasis and pruritic rash all over his body. Laboratory evaluation revealed marked lymphopenia and hypergammaglobulinemia with extremely high IgE values (IgE: 59 300 kU/l). He was diagnosed with stage 4 human immunodeficiency virus (HIV) infection and started on antiretroviral treatment. In conclusion, HIV infection can be presented with increased IgE values.