{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:08:28Z","timestamp":1773137308804,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Several studies have evaluated the serum galactomannan (GM) antigen assay in pediatric patients, and there is convincing evidence for its usefulness as a diagnostic tool for invasive Aspergillus infections in patients with acute leukemias or post allogeneic hematopoietic cell transplantation (HCT). Less is known about the utility of the assay in monitoring responses to treatment in patients with established invasive aspergillosis (IA). Here, we present the long-term kinetics of serum galactomannan in two severely immunocompromised adolescents with invasive pulmonary aspergillosis (IPA) who were cured after complicated clinical courses. We also review the utility of the GM antigen assay in serum as a prognostic tool around the time of diagnosis of IA and as a biomarker to monitor disease activity in patients with established IA and assess responses to systemic antifungal therapy.<\/jats:p>","DOI":"10.3390\/jof9020157","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:23:49Z","timestamp":1674617029000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long-Term Kinetics of Serum Galactomannan during Treatment of Complicated Invasive Pulmonary Aspergillosis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-2605","authenticated-orcid":false,"given":"Athanasios","family":"Tragiannidis","sequence":"first","affiliation":[{"name":"Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology\/Oncology, Children\u2019s University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"2nd Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Linke","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology\/Oncology, Children\u2019s University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos L.","family":"Correa-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidrun","family":"Herbr\u00fcggen","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology\/Oncology, Children\u2019s University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-9290","authenticated-orcid":false,"given":"Frieder","family":"Schaumburg","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1188-393X","authenticated-orcid":false,"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology\/Oncology, Children\u2019s University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.1128\/iai.62.12.5424-5433.1994","article-title":"Chemical and immunological characterization of the extracellular galactomannan of Aspergillus fumigatus","volume":"62","author":"Kobayashi","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1473-3099(04)01045-X","article-title":"Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis","volume":"4","author":"Donnelly","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10928-017-9509-1","article-title":"Prognostic value of galactomannan: Current evidence for monitoring response to antifungal therapy in patients with invasive aspergillosis","volume":"44","author":"Kovanda","year":"2017","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1093\/cid\/ciw592","article-title":"Galactomannan, \u03b2-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis","volume":"63","author":"Lehrnbecher","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"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","volume":"12","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/cid\/ciw444","article-title":"Executive Summary: Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin. Microbiol Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1200\/JCO.2016.71.7017","article-title":"Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update","volume":"35","author":"Lehrnbecher","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1016\/S1470-2045(20)30723-3","article-title":"8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation","volume":"22","author":"Groll","year":"2021","journal-title":"Lancet. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1086\/528714","article-title":"Strong correlation between serum aspergillus galactomannan index and outcome of aspergillosis in patients with hematological cancer: Clinical and research implications","volume":"46","author":"Miceli","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3389\/fmicb.2018.00661","article-title":"Galactomannan, a Surrogate Marker for Outcome in Invasive Aspergillosis: Finally Coming of Age","volume":"9","author":"Mercier","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/cid\/cir786","article-title":"Invasive aspergillosis in children with acquired immunodeficiencies","volume":"54","author":"Tragiannidis","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1093\/jpids\/pix046","article-title":"Epidemiology of Invasive Fungal Disease in Children","volume":"6","author":"Pana","year":"2017","journal-title":"J. Pediatr. Infect. Dis Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/myc.13029","article-title":"Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation","volume":"63","author":"Linke","year":"2020","journal-title":"Mycoses"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Leeflang, M.M., Debets-Ossenkopp, Y.J., Wang, J., Visser, C.E., Scholten, R.J., Hooft, L., Bijlmer, H.A., Reitsma, J.B., Zhang, M., and Bossuyt, P.M. (2015). Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane. Database Syst. Rev., 34.","DOI":"10.1002\/14651858.CD007394.pub2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1093\/jpids\/pix054","article-title":"Role of Molecular Biomarkers in the Diagnosis of Invasive Fungal Diseases in Children","volume":"6","author":"Huppler","year":"2017","journal-title":"J. Pediatric. Infect. Dis Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1093\/cid\/cix198","article-title":"Pharmacodynamics of Isavuconazole for Invasive Mold Disease: Role of Galactomannan for Real-Time Monitoring of Therapeutic Response","volume":"64","author":"Kovanda","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1080\/14737159.2018.1488589","article-title":"Galactomannan antigenemia as a biomarker for therapeutic response of invasive aspergillosis: Implications for clinical trial design and patient care","volume":"18","author":"McCarthy","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/jac\/dkab317","article-title":"When to change treatment of acute invasive aspergillosis: An expert viewpoint","volume":"77","author":"Slavin","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1128\/AAC.45.3.857-869.2001","article-title":"Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: Correlation with galactomannan antigenemia","volume":"45","author":"Petraitiene","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1128\/AAC.46.1.12-23.2002","article-title":"Antifungal efficacy of caspofungin (MK-0991) in experimental pulmonary aspergillosis in persistently neutropenic rabbits: Pharmacokinetics, drug disposition, and relationship to galactomannan antigenemia","volume":"46","author":"Petraitiene","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1128\/AAC.00673-10","article-title":"The initial 96 hours of invasive pulmonary aspergillosis: Histopathology, comparative kinetics of galactomannan and (1->3) \u03b2-d-glucan and consequences of delayed antifungal therapy","volume":"54","author":"Hope","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1128\/AAC.04723-14","article-title":"Pharmacodynamics of amphotericin B deoxycholate, amphotericin B lipid complex, and liposomal amphotericin B against Aspergillus fumigatus","volume":"59","author":"Petraitis","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/mmy\/myv034","article-title":"Effects of host response and antifungal therapy on serum and BAL levels of galactomannan and (1\u21923)-\u03b2-D-glucan in experimental invasive pulmonary aspergillosis","volume":"53","author":"Petraitiene","year":"2015","journal-title":"Med. Mycol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1093\/jac\/dkw098","article-title":"Pharmacodynamics of isavuconazole in experimental invasive pulmonary aspergillosis: Implications for clinical breakpoints","volume":"71","author":"Kovanda","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1574","DOI":"10.1128\/AAC.01574-20","article-title":"Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy","volume":"65","author":"Gastine","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/cncr.22863","article-title":"Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis: A study of 56 patients with hematologic cancer","volume":"110","author":"Woods","year":"2007","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/cncr.24022","article-title":"Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients","volume":"115","author":"Maertens","year":"2009","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1439-0507.2010.02009.x","article-title":"Serum galactomannan strongly correlates with outcome of invasive aspergillosis in acute leukaemia patients","volume":"54","author":"Park","year":"2011","journal-title":"Mycoses"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.7326\/M13-2508","article-title":"Combination antifungal therapy for invasive aspergillosis: A randomized trial","volume":"162","author":"Marr","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1086\/339324","article-title":"Invasive aspergillosis in allogeneic stem cell transplant recipients: Increasing antigenemia is associated with progressive disease","volume":"34","author":"Boutboul","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1128\/JCM.02281-09","article-title":"Prognostic features of galactomannan antigenemia in galactomannan-positive invasive aspergillosis","volume":"48","author":"Koo","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1128\/JCM.00750-11","article-title":"Prospective evaluation of clinical and biological markers to predict the outcome of invasive pulmonary aspergillosis in hematological patients","volume":"50","author":"Bergeron","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1128\/JCM.06513-11","article-title":"Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis","volume":"50","author":"Chai","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Neofytos, D., Railkar, R., Mullane, K.M., Fredricks, D.N., Granwehr, B., Marr, K.A., Almyroudis, N.G., Kontoyiannis, D.P., Maertens, J., and Fox, R. (2015). Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129022"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1007\/s00330-016-4717-4","article-title":"Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis","volume":"27","author":"Vehreschild","year":"2017","journal-title":"Eur. Radiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mercier, T., Wera, J., Chai, L.Y.A., Lagrou, K., and Maertens, J. (2020). A Mortality Prediction Rule for Hematology Patients with Invasive Aspergillosis Based on Serum Galactomannan Kinetics. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020610"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0140-6736(15)01159-9","article-title":"Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): A phase 3, randomised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa020191","article-title":"Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis","volume":"347","author":"Herbrecht","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1086\/590566","article-title":"Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria","volume":"47","author":"Segal","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/cid\/cir441","article-title":"Earlier response assessment in invasive aspergillosis based on the kinetics of serum Aspergillus galactomannan: Proposal for a new definition","volume":"53","author":"Nucci","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/myc.13097","article-title":"Usefulness of serum galactomannan in initiating and modifying antifungal therapy in children with cancer and persistent high-risk febrile neutropenia","volume":"63","author":"Valenzuela","year":"2020","journal-title":"Mycoses"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Han, S.B., Kim, S.K., Lee, J.W., Yoon, J.-S., Chung, N.-G., Cho, B., Jeong, D.C., Kang, J.H., Kim, H.-K., and Lee, D.-G. (2015). Serum galactomannan index for early prediction of mortality in immunocompromised children with invasive pulmonary aspergillosis. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1014-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1128\/AAC.03023-15","article-title":"Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy","volume":"60","author":"Huurneman","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1099\/jmm.0.000512","article-title":"Effect of involved Aspergillus species on galactomannan in bronchoalveolar lavage of patients with invasive aspergillosis","volume":"66","author":"Hedayati","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/ofid\/ofac112","article-title":"Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases","volume":"9","author":"Thompson","year":"2022","journal-title":"Open Forum Infect. Dis."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/2\/157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:54Z","timestamp":1760120094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/2\/157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,24]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jof9020157"],"URL":"https:\/\/doi.org\/10.3390\/jof9020157","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,24]]}}}