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      Culture-independent diagnostic approaches for invasive aspergillosis in solid organ transplant recipients

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          Abstract

          Prompt and accurate diagnosis of invasive aspergillosis (IA) is crucial for immunocompromised patients, including those who have received a solid organ transplant (SOT). Despite their low sensitivity, microscopic detection and conventional culture are considered the 'gold standard' methods. In conjunction with conventional culture, culture-independent assays such as serum galactomannan testing and Aspergillus polymerase chain reaction (PCR) have been incorporated into the diagnostic process for IA. The recently revised consensus definitions from the European Organization for Research and Treatment of Cancer and the Mycosis Study Group have adjusted the threshold for positive galactomannan testing based on the sample type, and have excluded 1,3-β-D-glucan testing as a mycological criterion. Following extensive standardization efforts, positive Aspergillus PCR tests using serum, plasma, or bronchoalveolar lavage fluid have been added. However, there are limited studies evaluating the clinical utility of these culture-independent assays for the early diagnosis of IA in SOT recipients. Therefore, further research is required to determine whether these assays could aid in the early diagnosis of IA in SOT recipients, particularly in relation to the organ transplanted. In this review, we examine the culture-independent diagnostic methods for IA in SOT recipients, as well as the clinical utility of these assays.

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          Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium

          Abstract Background Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. Methods To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups’ findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. Results There is no change in the classifications of “proven,” “probable,” and “possible” IFD, although the definition of “probable” has been expanded and the scope of the category “possible” has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. Conclusions These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
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            Revised definitions of invasive fungal disease from the 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) Consensus Group.

            Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. After the introduction of the original 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) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
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              Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis.

              A double-sandwich enzyme-linked immunosorbent galactomannan assay has been approved for surveillance for invasive aspergillosis in immunocompromised patients. We undertook a meta-analysis to assess the accuracy of a galactomannan assay for diagnosing invasive aspergillosis. Studies of the galactomannan assay that used the European Organization for Research and Treatment of Cancer or similar criteria as a reference standard and provided data to calculate sensitivity and specificity were included. Pooled sensitivity and specificity and summary measures of accuracy, Q* (the upper left-most point on the summary receiver-operating characteristic curve), mean D (a log odds ratio), and Youden index were calculated. Subgroup analyses were performed to explore heterogeneity. Twenty-seven studies from 1966 to 28 February 2005 were included. Overall, the galactomannan assay had a sensitivity of 0.71 (95% confidence interval [CI], 0.68-0.74) and specificity of 0.89 (95% CI, 0.88-0.90) for proven cases of invasive aspergillosis. The Youden index, mean D, and Q* were 0.54 (95% CI, 0.41-0.65), 2.74 (95% CI, 21.12-3.36), and 0.80 (95% CI, 0.74-0.86), respectively, indicating moderate accuracy. Subgroup analyses showed that the performance of the test differed by patient population and type of reference standard used. Significant heterogeneity was present. The galactomannan assay has moderate accuracy for diagnosis of invasive aspergillosis in immunocompromised patients. The test is more useful in patients who have hematological malignancy or who have undergone hematopoietic cell transplantation than in solid-organ transplant recipients. Further studies with attention to the impact of antifungal therapy, rigorous assessment of false-positive test results, and assessment of the utility of the test under nonsurveillance conditions are needed.
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                Author and article information

                Journal
                Korean J Transplant
                Korean J Transplant
                Korean Journal of Transplantation
                The Korean Society for Transplantation
                2671-8790
                2671-8804
                30 September 2023
                30 September 2023
                30 September 2023
                : 37
                : 3
                : 155-164
                Affiliations
                [1]Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
                Author notes
                Corresponding author: Yeon-Joon Park Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea, E-mail: yjpk@ 123456catholic.ac.kr
                Author information
                https://orcid.org/0000-0003-1505-846X
                https://orcid.org/0000-0003-2182-5821
                Article
                kjt-37-3-155
                10.4285/kjt.23.0043
                10583980
                37751964
                c10381cc-3bd2-481b-82da-e602b6213d7f
                Copyright © 2023 The Korean Society for Transplantation

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 July 2023
                : 17 August 2023
                : 28 August 2023
                Funding
                Funding/Support This study was supported by research grant from the Korean Society for Transplantation (2023-00-03004-008).
                Categories
                Review Article

                invasive aspergillosis,galactomannan,polymerase chain reaction,transplant

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