Pediatric Invasive Aspergillosis Research Articles

Pediatric Invasive Aspergillosis: a Retrospective Review of 59 Cases.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.

Epidemiology and outcomes of invasive aspergillosis among pediatric immunocompromised patients: A 12-year single-center experience.

This study explores the epidemiology, outcomes and predictors of mortality of invasive aspergillosis (IA) at a high-volume pediatric center for immunocompromised hosts. Much of our understanding of pediatric IA is extrapolated from the adult literature. Our study found that IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the hematopoietic cell transplantation study cohort.

The role of galactomannan test results in the diagnosis of pediatric invasive aspergillosis

Background Invasive aspergillosis (IA) is an important cause of morbidity and mortality in immunosuppressed children. Early detection of the infection can improve prognosis in this patient population. Objectives To investigate the utility of Aspergillus galactomannan antigen assay (GM-EIA) as a diagnostic tool for IA in at-risk paediatric patients. Patients/Methods For the study, 659 GM-EIA results from 59 patients diagnosed with IA and 3368 GM-EIA results from 351 subjects without evidence for IA (controls) were reviewed retrospectively. Three cut-off values (i.e. ≥0.5, ≥1, ≥1.5) were specified to determine GM-EIA positivity. Results The median age was 6.3 years for boys and 14.5 years for girls. There was a significant difference between the girls and boys in terms of age (p < 0.01). For proven/probable/possible IA patients, sensitivity of 67.8% and specificity of 59.8% were detected when the ≥0.5 cut-off value was used for GM-EIA-positivity. The specificity increased to 80% at the cut-off of ≥1 and to 88% at the cut-off of ≥1.5. False positivity rates were 9.14, 3, and 1.45% at the ≥0.5, ≥1 and ≥1.5 cut-offs respectively. In the proven/probable IA group, sensitivity and negative predictive values were 86.9 and 97.2% at the ≥0.5 cut-off, 85.7 and 97.9%, at the ≥1 cut-off and 84.2 and 98.1% at ≥1.5 cut-off respectively. The positive likelihood ratio was 7.57 and the odds ratio was 42.67 at ≥1.5 cut-off. Conclusion The GM-EIA may be used for both screening and diagnostic purposes in paediatric patients using a cut-off value of ≥1.5 for GM-EIA positivity.

Pediatric Invasive Aspergillosis.

Invasive aspergillosis (IA) is a disease of increasing importance in pediatrics due to growth of the immunocompromised populations at risk and improvements in long-term survival for many of these groups. While general principles of diagnosis and therapy apply similarly across the age spectrum, there are unique considerations for clinicians who care for children and adolescents with IA. This review will highlight important differences in the epidemiology, clinical manifestations, diagnosis, and therapy of pediatric IA.

Diagnostic value of galactomannan detection for invasive aspergillosis infections in pediatric patients with Meta-analysis

Objective To evaluate the diagnostic value of galactomannan (GM) detection for invasive aspergillosis infections in pediatric patients , a Meta-analysis was performed. Methods According to selection criteria, studies indexed by PubMed,EMBASE,Medline,CNKI and Wanfang Data on GM testing in pediatric aspergillosis were included from January 2001 to November 2012 . The methodological quality was assessed by QUADAS, sources of heterogeneity investigated, pooled effect quantities evaluated, and summary receiver operative curves (ROC) and subgroup analysis performed. Stata12.0 was used to analyze diagnostic parameters, such as, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve (AUC). Results Thirteen articles with 16 sets of data were included. The weighted sensitivity and specificity with 95% confidence interval were 0.71(0.60-0.79) and 0.94(0.89-0.96), respectively. Under different cut-off values , sensitivities of GM assay in diagnosis of pediatric aspergillosis were 0.71（0.54-0.84） for 0.5, 0.77（0.64-0.87） for 0.8 ,0.72（0.58-0.84） for 1.0 and 0.59（0.39-0.76） for 1.5, and its responding specificities were 0.94（0.89-0.97）, 0.89（0.82-0.93）, 0.89（0.81-0.94） and 0.91（0.88-0.94）. Conclusion Under the cut-off value of 0.8, the GM assay is a useful method in the detection of pediatric invasive aspergillosis.（Chin J Lab Med，2014,37：772-775） Key words: Aspergillosis; Mannans; Meta-analysis; Child

The Role of Biomarkers for Diagnosis of and Therapeutic Decisions Related to Invasive Aspergillosis in Children

Invasive aspergillosis (IA) is a feared opportunistic infection for many immuncompromised children resulting in significant morbidity and mortality. Timely diagnosis based on traditional testing modalities and clinical evaluation has proven to be challenging. Assays designed to measure IA biomarkers such as galactomannan (GM) and beta-D-glucan (BG) represent a potential significant improvement in the ability to diagnose pediatric IA. However, as with any new diagnostic tool, clinicians need to be aware of the operating characteristics of these assays in order to apply them in the appropriate settings. Published adult and pediatric data regarding GM and BG testing are reviewed and guidance regarding the appropriate utility of these assays in children is offered.

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.

Pediatric Invasive Aspergillosis

Invasive aspergillosis (IA) remains an infectious disease that causes numerous subspecialists, young and old alike, to cower with fear and lose sleep at night. The more seasoned pediatricians see those nondescript scattered pulmonary nodules on a CT and remember the thief that has stolen so many of their oncologic success stories during eras where they tried every antifungal therapy permutation, including several that were not antifungals at all. The more-junior specialists are amazed at our seeming ineptitude when confronted by such a devastating killer, marveling at how, despite all the advances in medicine today, we still cannot diagnose this disease in a timely fashion nor consistently treat it. Although the terror remains the same, the face of the demon has changed. This brief primer will highlight some of the important concepts for the current management of IA.

The Role of Bronchoalveolar Lavage Galactomannan in the Diagnosis of Pediatric Invasive Aspergillosis

: Molecular biomarkers such as the galactomannan assay are of increasing interest in clinical settings for diagnosis of invasive aspergillosis (IA). The use of bronchoalveolar lavage galactomannan (BAL GM) is being validated in adult populations, but has not been systematically evaluated in pediatric patients. : A retrospective analysis was performed of patients for whom GM assays from BAL were submitted between November 1, 2006 and November14, 2007 at Childrens Hospital Los Angeles. Medical charts were reviewed and patients were categorized as having no, possible, probable, and proven IA, per established definitions. : Of 85 pediatric patients who had a BAL GM submitted during the study, 59 were immunocompromised. Three patients were identified as having proven IA, 6 had probable IA, 37 had possible IA, and 39 had no evidence of IA; 38 had a concurrent serum GM performed. A positive, linear correlation was established between BAL and serum GM, using OD index values (rho = 0.48, P = 0.002). Among immunocompromised patients, receiver operating characteristic curves demonstrated an optimal BAL GM OD cut-off value of 0.87, that yielded a sensitivity for probable/proven IA of 78% and a specificity of 100%. At 0.87, the positive and negative predictive values among immunocompromised patients were 58% and 96%, respectively. : We found a correlation between BAL GM values and a diagnosis of IA. We also noted a linear relationship between serum and BAL GM values. Receiver operating characteristic curves obtained from our pediatric data validate the current cut off for serum and suggest a possible cut off for BAL specimens.

Assessment of Aspergillus -Specific T Cells for Diagnosis of Invasive Aspergillosis in a Leukemic Child with Liver Lesions Mimicking Hepatosplenic Candidiasis

A child with acute myeloid leukemia presented with multiple liver lesions mimicking hepatosplenic candidiasis during the neutropenic phase following the induction chemotherapy. All the available diagnostic tools showed repeatedly negative results, including galactomannan. An enzyme-linked immunospot (ELISPOT) assay showed a high number of Aspergillus-specific T cells producing interleukin-10 [TH2(IL-10)] and a low number of Aspergillus-specific T cells producing gamma interferon [TH1(IFN-gamma)], revealing invasive aspergillosis (IA) before the confirmatory biopsy. A progressive skewing from the predominance of TH2(IL-10) to a predominance of TH1(IFN-gamma) was observed close to the complete resolution of the infection and foreshadowed the outcome. The ELISPOT assay holds promise for diagnosing pediatric IA.

Pediatric Invasive Aspergillosis: A Multicenter Retrospective Analysis of 139 Contemporary Cases

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised children. Invasive aspergillosis has been well characterized in adults; however, the incidence and analysis of risk factors, diagnostic tools, treatments, and outcomes have not been well described for a large cohort of pediatric patients. We conducted the largest retrospective review of contemporary cases of proven and probable pediatric invasive aspergillosis diagnosed at 6 major medical centers (January 1, 2000, to July 1, 2005). Aspergillus fumigatus was the species most frequently recovered (52.8%) for the 139 patients analyzed. The majority of the children had a malignancy with or without hematopoietic stem cell transplant. Significant risk factors that impacted survival were immunosuppressive therapies and allogeneic stem cell transplant. The most common clinical site of invasive aspergillosis was the lungs (59%), and the most frequent diagnostic radiologic finding was nodules (34.6%). Only 2.2% of children showed the air crescent sign, 11% demonstrated the halo sign, and cavitation was seen in 24.5% of patients. Before the diagnosis of invasive aspergillosis, 43.1% of patients received fluconazole, and 39.2% received liposomal amphotericin B. After the diagnosis of invasive aspergillosis, 57% were treated with a lipid formulation of amphotericin B; however, 45.8% received > or = 3 concomitant antifungal agents. Analysis did not show superiority of any 1 antifungal related to overall mortality. A total of 52.5% (73 of 139) died during treatment for invasive aspergillosis. Of all the interventions implemented, surgery was the only independent predictor of survival. Our analyses revealed common findings between adult and pediatric invasive aspergillosis. However, one key difference is diagnostic radiologic findings. Unlike adults, children frequently do not manifest cavitation or the air crescent or halo signs, and this can significantly impact diagnosis. Immune reconstitution, rather than specific antifungal therapy, was found to be the best predictor of survival.

New findings and unique aspects in pediatric aspergillosis

There is a paucity of specific data on pediatric invasive aspergillosis. While the underlying predisposing patient diseases and treatments differ in children and adults, it also appears that there is a heterogeneity of invasive aspergillosis disease that extends to children. These aspects extend in some reports to the Aspergillus spp. distribution as well as the fundamental pathophysiology of the disease in different age groups. For instance, the newer diagnostic tools hold great promise for adult patients but it appears that they have limited usefulness in children. Only through dedicated pediatric study will clinicians fully discover the nuances and unique findings in children with this deadly disease.