Zoi Dorothea Pana

Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries

BackgroundMucormycosis has emerged as a rare but frequently fatal invasive fungal disease. Current knowledge on paediatric mucormycosis is based on case reports and small series reported over several decades. Contemporary data on a large cohort of patients is lacking.MethodsTwo large international registries (Zygomyco.net and FungiScope™) were searched for mucormycosis cases in ≤19 year-old patients. Cases enrolled between 2005 and 2014 were extracted, and dual entries in the two databases merged. Epidemiology, clinical characteristics, diagnostic procedures, therapeutic management and final outcome were recorded and analysed with SPSS v.12.ResultsSixty-three unique cases (44 proven and 19 probable) were enrolled from 15 countries (54 in European and 9 in non-European countries). Median age was 13 years [Interquartile Range (IQR) 7.7] with a slight predominance (54.1 %) of females. Underlying conditions were haematological malignancies (46 %), other malignancies (6.3 %), haematopoietic stem cell transplantation (15.9 %), solid organ transplantation, trauma/surgery and diabetes mellitus (4.8 % each) and a variety of other diseases (7.9 %); in 9.5%, no underlying medical condition was found. Neutropenia was recorded in 46 % of the patients. The main sites of infection were lungs (19 %), skin and soft tissues (19 %), paranasal sinus/sino-orbital region (15.8 %) and rhino-cerebral region (7.9 %). Disseminated infection was present in 38.1 %. Mucormycosis diagnosis was based on several combinations of methods; culture combined with histology was performed in 31 cases (49.2 %). Fungal isolates included Rhizopus spp. (39.7 %), Lichtheimia spp. (17.5 %), Mucor spp. (12.7 %), Cunninghamella bertholletiae (6.3 %) and unspecified (23.8 %). Treatment comprised amphotericin B (AmB) monotherapy in 31.7 % or AmB in combination with other antifungals in 47.7 % of the cases, while 14.3 % received no antifungals. Surgery alone was performed in 6.3 %, and combined with antifungal therapy in 47.6 %. Crude mortality at last contact of follow-up was 33.3 %. In regression analysis, disseminated disease and prior haematopoietic stem cell transplantation were associated with increased odds of death, whereas the combination of systemic antifungal therapy with surgery was associated with improved survival.ConclusionPaediatric mucormycosis mainly affects children with malignancies, presents as pulmonary, soft tissue, paranasal sinus or disseminated disease and is highly lethal. Outcome is improved when active antifungal therapy and surgery are combined.

Exserohilum infections: Review of 48 cases before the 2012 United States outbreak

Exserohilum species are soilborne fungi that have been uncommon causes of human disease. The ongoing outbreak in the United States warrants improved understanding of this pathogen. We systematically reviewed all cases of Exserohilum spp. infections published before the outbreak in 2012 in order to provide a better understanding of the organism and its wider spectrum of human disease. Cases of Exserohilum infections were retrieved by searching PubMed. Demographic data, underlying conditions, microbiology, clinical manifestations, therapy, and outcome were recorded and analyzed. Forty-eight evaluable cases were identified from 1975 to 2012. The number of reported cases increased more than twofold during the study period (P < 0.01). Most cases occurred in the southern United States, India, and Israel. Median age of patients was 25 years, with a male predominance. Most infections were due to E. rostratum (60.4%), followed by E. longirostratum (6.3%) and E. mcginnisii (2%), while 31.3% were unidentified species. The most frequent underlying conditions were immunosuppression (27.2%), trauma (16.6%), and atopy (12.5%). Exserohilum disease manifested as systemic (73%), cutaneous (25%), corneal (16.7%), and subcutaneous (10.4%) infection. Antifungal therapy consisted mainly of amphotericin B (44%) alone or combined with a triazole. Surgery was used in 48% of cases and was combined with antifungal therapy in 31%. The all-cause mortality was 23%, which was higher in patients with preexisting immunosuppression (56.2%; odds ratio 15.4; 95% confidence interval, 2.7-88.6). This review of the pre-outbreak reported cases highlights several aspects of epidemiology, clinical presentation, risk factors, and management of this unusual pathogen.

Epileptic seizures after octreotide administration in a 6.5-year-old female with ALL and L-asparaginase associated pancreatitis: a possible drug interaction.

INTRODUCTION Octreotide is a synthetic somatostatin analogue which has been suggested for use in the management of acute pancreatitis, though its safety and effectiveness in the pediatric setting has not been extensively studied. CASE REPORT we present a rare case of a 6.5-year-old female with acute lymphoblastic leukemia (ALL) and L-asparaginase (L-asp) induced pancreatitis, who developed epileptic seizures, possibly associated with octreotide administration. Her imaging and laboratory findings ruled out a leukemic involvement or infection of CNS. The EEG revealed repetitive sharp waves maximal on the frontal and temporal areas of the right hemisphere. The child was treated with diazepam and she continued with systemic anticonvulsant treatment with levetiracetam. After 2 weeks of conservative treatment, pancreatitis resolved and she continued her chemotherapy protocol. Levetiracetam treatment lasted 8 months. 7 months after the first episode, EEG was reported as normal, and the child completed the chemotherapy protocol without any further severe complications. CONCLUSIONS Larger and well designed studies are needed to warrant the safety of octreotide in pediatric population.

The first case of congenital leishmaniasis in a female infant in Greece.

Good communication skills are an essential part of the doctor– patient interaction, both on the part of the doctor and the patient, and the patient’s care givers when the patient is a child. In Australian hospitals, interpreter services are routine for people who do not speak English. However, there are many people who speak a reasonable standard of English as a second language (ESL) but may have some difficulty in understanding complex explanations and instructions. This is particularly the case in stressful situations such as medical encounters. The 2006 Australian Census data show that Italian, Greek, Cantonese, Arabic and Mandarin speakers total 6.4% of the population. This is of importance to Australian doctors talking to patients, as well as interacting with colleagues who do not have English as a first language (EFL). There can be important repercussions in poor understanding in the doctor–patient consultation. We wish to present an observation that was noted as part of the PhD of AK into the differences between EFL or native English speakers, and English as a second (or subsequent) language (ESL) or non-native English speakers in the doctor– patient consultation. Ethics approval was obtained from the University of Melbourne. Families being seen for routine paediatric ophthalmic consultations were invited to participate and signed informed consent. A clinician, DM, and his patients were observed and tape-recorded in a clinical setting, and patients and doctors were interviewed independently at the end of consultations. Prior to the clinical consultation, patients had already been seen by an orthoptist who takes a history and performs a visual acuity and eye movement examination, as well as provides eye drops as required. On entering the ophthalmologist’s room, the doctor introduced himself to the patients and care givers, and asked if it was okay for the researcher to join them in the room. The doctor directed simple questions to verbal children such as, ‘Would you like to sit in the chair with mummy or daddy, or by yourself?’ Parents quickly conceded the child’s wish and sat with the child or in a chair next to the child. Further simple questions about history, discussion of management and compliance, and understanding of the disease were usually directed to the child. When the doctor was no longer getting adequate answers, he transferred the discussion to the parents by requesting the child’s permission to ask the parents: ‘Could we ask your Mum and Dad if X?’ This overhearing cue usually resulted in the parents answering the question without the need to repeat the question. However, in some cases, the question had to be asked again directly to the parents. Most parents with EFL took the cue, whereas all parents with ESL missed the cue. This scenario was so consistent that statistical analysis was performed (data provided). Similar observations can be seen outside the patient consultation setting. For example, a student in the presence of Dr X (EFL) and Dr Y (ESL) was told, ‘You could ask Dr X or Dr Y to help you’. Without a further question, Dr X (EFL) responded, while Dr Y (ESL) needed to be asked specifically again. Although study of language usually does not lend itself to rigorous Fisherian analysis, this observation may be of use to clinicians who have patients or staff with ESL, to appreciate if they are fully understanding and likely to act on what they have heard. Further research in this clinical area would be of value. For now, when it is recognised that care givers have some difficulty interpreting information, it may be necessary to take additional time to ensure that all aspects of a treatment plan for a child are understood.

Voriconazole Antifungal Prophylaxis in Children With Malignancies: A Nationwide Study

Background: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. Materials and Methods: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients’ demographics, outcome, and adverse event (AE) data were recorded. Results: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. Conclusions: VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Loeffler Endocarditis in a Pediatric Patient

Loefler endocarditis is a potential fatal adverse event of hypereosinophilic syndrome. We report a case of a 5-year-old girl diagnosed with peripheral hypereosinophilia refractory to corticosteroid therapy who developed eosinophilia-related endocarditis. Echocardiography revealed infiltration of the left ventricular free wall and the posterior mitral leaflet causing moderate mitral regurgitation. Genetic tests failed to recognize FIPiLi-PDGRFA genotype; however imatinib, a tyrosine kinase inhibitor was initiated. After a 4-week period of treatment there was a complete resolution of eosinophilia and a complete recovery of cardiac manifestation. This case highlights the introduction of imatinib for the treatment of hypereosinophilic syndrome refractory to corticosteroid therapy even in the absence of FIPiLi-PDGRFA genotype in pediatric patients.

Rare Fungal Infections in Children: An Updated Review of the Literature

An increasing trend of reports of rare fungal diseases has been observed to be mainly associated with the substantial increase of high-risk immunocompromised children, as well as with the selective pressure of antifungal drugs. On the other hand, recent reports have shown that several species of these rare fungi may also cause infections in immunocompetent children without obvious underlying conditions. The clinical spectrum of these infections, and most importantly their outcome, varies greatly, implying for a rather heterogenic group of pediatric infections. Various types of superficial and subcutaneous fungal infections, as well as systemic and disseminated life-threatening infections, have been reported. Prompt diagnosis and appropriate treatment of rare fungal diseases in children remains a great challenge. Several treatment options have been used, ranging from localized to combination treatment with extensive surgical excision and long-term antifungal therapy. We review contemporary data of rare fungal infections in pediatric patients focusing on epidemiology, mycology, management and outcome, published during the last three years.

AN UNUSUAL CASE OF MYCOPLASMA PNEUMONIAE-ASSOCIATED AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A 10-YEAR-OLD FEMALE CHILD

Dr Sonia Radice Dr Carla Carnovale Dr Stefania Antoniazzi Professor Gianvincenzo Zuccotti Dr Valentina Perrone Dr Antonella Piazza Professor Emilio Clementi Unit of Clinical Pharmacology CNR Institute of Neuroscience Department of Clinical Sciences Department of Paediatrics University Hospital ‘Luigi Sacco’ Università di Milano Milan Family Paediatricians Territorial Health Service of Monza/Brianza Monza E. Medea Scientific Institute Lecco, Italy

Toxoplasmosis in Transplant Recipients, Europe, 2010–2014

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010–2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management.

Performance of QuantiFERON®-TB Gold In-Tube assay in children receiving disease modifying anti-rheumatic drugs

BackgroundTo evaluate the performance of the Quantiferon®-TB Gold In-Tube (QFT-IT) interferon (IFN)-γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece.MethodsA total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF-α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated.ResultsAgreement between TST and QFT-IT results was moderate (k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN-γ assay was increased by a factor of 27.6 (P=0.002), whereas there was no positive TST. There was a significant difference in the mitogen-induced IFN-γ secretion among various treatments (P=0.038). TNF-α inhibitors were associated with increased mitogen-induced IFN-γ secretion compared to monotherapy with conventional DMARDs (P=0.008). All children screened prior to anti-TNF-α treatment exhibited a negative QFT-IT and no active TB disease was detected during a 2-year follow-up.ConclusionsQFT-IT may be a more reliable test than TST for detection of LTBI in children with rheumatic diseases receiving anti-rheumatic treatment. Drug regimen might influence the mitogen-induced IFN-γ secretion and the effect of TNF-α inhibitors might vary according to the specific agent administered.