J. Fungi2016, 2(3), 23; doi:10.3390/jof2030023 - published 11 August 2016 Show/Hide Abstract
Abstract: The application of molecular technologies to aid diagnosis and management of infectious diseases has had a major impact and many assays are in routine use. Diagnosis of aspergillosis has lagged behind. Lack of standardization and limited commercial interest have meant that PCR was not included in consensus diagnostic criteria for invasive fungal disease. In the last ten years careful evaluation and validation by the Aspergillus European PCR initiative with the development of standardized extraction, amplification and detection protocols for various specimen types, has provided the opportunity for clinical utility to be investigated. PCR has the potential to not only exclude a diagnosis of invasive aspergillosis but in combination with antigen testing may offer an approach for the early diagnosis and treatment of invasive aspergillosis in high-risk populations, with the added benefit of detection of genetic markers associated with antifungal resistance.
Abstract: Invasive aspergillosis (IA) is a severe complication among hematopoietic stem cell transplant recipients or patients with hematological malignancies and neutropenia following anti-cancer therapy. Moreover, IA is increasingly observed in other populations, such as solid-organ transplant recipients, patients with solid tumors or auto-immune diseases, and among intensive care unit patients. Frequent delay in diagnosis is associated with high mortality rates. Cultures from clinical specimens remain sterile in many cases and the diagnosis of IA often only relies on non-specific radiological signs in the presence of host risk factors. Tests for detection of galactomannan- (GM) and 1,3-β-d-glucan (BDG) are useful adjunctive tools for the early diagnosis of IA and may have a role in monitoring response to therapy. However, the sensitivity and specificity of these fungal biomarkers are not optimal and variations between patient populations are observed. This review discusses the role and interpretation of GM and BDG testing for the diagnosis of IA in different clinical samples (serum, bronchoalveolar lavage fluid, cerebrospinal fluid) and different groups of patients (onco-hematological patients, solid-organ transplant recipients, other patients at risk of IA).
Abstract: Since the first description of an azole-resistant A. fumigatus strain in 1997, there has been an increasing number of papers describing the emergence of azole resistance. Firstly reported in the USA and soon after in Europe, it has now been described worldwide, challenging the management of human aspergillosis. The main mechanism of resistance is the modification of the azole target enzyme: 14-α sterol demethylase, encoded by the cyp51A gene; although recently, other resistance mechanisms have also been implicated. In addition, a shift in the epidemiology has been noted with other Aspergillus species (mostly azole resistant) increasingly being reported as causative agents of human disease. This paper reviews the current situation of Aspergillus azole resistance and its implications in the clinical setting.
J. Fungi2016, 2(2), 19; doi:10.3390/jof2020019 - published 13 June 2016 Show/Hide Abstract
Abstract: 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.
Abstract: Chronic pulmonary aspergillosis (CPA) is estimated to affect 3 million people worldwide making it an under recognised, but significant health problem across the globe, conferring significant morbidity and mortality. With variable disease forms, high levels of associated respiratory co-morbidity, limited therapeutic options and prolonged treatment strategies, CPA is a challenging disease for both patients and healthcare professionals. CPA can mimic smear-negative tuberculosis (TB), pulmonary histoplasmosis or coccidioidomycosis. Cultures for Aspergillus are usually negative, however, the detection of Aspergillus IgG is a simple and sensitive test widely used in diagnosis. When a fungal ball/aspergilloma is visible radiologically, the diagnosis has been made late. Sometimes weight loss and fatigue are predominant symptoms; pyrexia is rare. Despite the efforts of the mycology community, and significant strides being taken in optimising the care of these patients, much remains to be learnt about this patient population, the disease itself and the best use of available therapies, with the development of new therapies being a key priority. Here, current knowledge and practices are reviewed, and areas of research priority highlighted.