{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:40:03Z","timestamp":1793040003666,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Invasive pulmonary aspergillosis (IPA) is a common complication in patients with severe fever with thrombocytopenia syndrome (SFTS); however, its diagnosis remains challenging due to non-specific clinical manifestations and limited diagnostic tools. This study aimed to develop and validate a machine learning (ML)-based early diagnostic model to identify IPA in SFTS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 374 SFTS patients with suspected IPA were retrospectively enrolled at Qishan Hospital between March 2022 and June 2025. Both the Least Absolute Shrinkage and Selection Operator (LASSO) and the Boruta algorithms were employed for feature selection. Seven ML algorithms were subsequently developed and evaluated using multiple evaluation metrics to compare their predictive performance. Optimal cutoff values were determined by the Youden index. The AUCs of the models were compared using the DeLong test. Feature contributions in the optimal model were interpreted using SHapley Additive exPlanations (SHAP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the seven algorithms, the Random Forest (RF) model demonstrated the best predictive performance. The final model incorporated five key features: sex, serum potassium, international normalized ratio (INR), galactomannan (GM) test positivity, and SFTSV RNA load. The RF model achieved an area under the receiver operating characteristic curve (AUC) of 0.871 (95% CI: 0.799-0.933), with a specificity of 0.829 (95% CI: 0.735-0.912), a sensitivity of 0.854 (95% CI: 0.738\u20130.953), and an F1 score of 0.795. Calibration was acceptable, with a Brier score of 0.140 (95% CI: 0.105 - 0.179), and clinical utility was confirmed through decision curve analysis (DCA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our ML model provides a non-invasive and cost-effective approach for the early identification of SFTS-associated IPA. It may serve as a valuable adjunct to existing diagnostic strategies and support timely diagnostic evaluation in high-risk patients. Further external validation is warranted before clinical implementation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1857200","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:41:18Z","timestamp":1785390078000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of an interpretable machine learning model for the early diagnosis of invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: a retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Shuwen","family":"Ding","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruize","family":"Ma","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Peng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Yantai City Hospital for Infectious Disease","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Yantai City Hospital for Infectious Disease","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihai","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.surg.2023.05.023","article-title":"Evaluating prediction model performance","volume":"174","author":"Cabot","year":"2023","journal-title":"Surgery"},{"key":"B2","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/s12276-021-00610-1","article-title":"Severe fever with thrombocytopenia syndrome virus: emerging novel phlebovirus and their control strategy","volume":"53","author":"Casel","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/jof12030229","article-title":"Aspergillosis: an update on epidemiology, risk factors, diagnosis, susceptibility, and treatment","volume":"12","author":"Castro-Fuentes","year":"2026","journal-title":"J. Fungi"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaf803","article-title":"Neurological manifestations and high viral load as independent predictors of mortality in severe fever with thrombocytopenia syndrome","volume":"13","author":"Chen","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"B5","doi-asserted-by":"publisher","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":"71","author":"Donnelly","year":"2019","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc Am."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaf712","article-title":"Relationship between cytokine level and viral load in severe fever with thrombocytopenia syndrome","volume":"12","author":"Guo","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1693567","article-title":"Pathogen profile of co-infections and mortality determinants among patients with severe fever with thrombocytopenia syndrome","volume":"15","author":"Hu","year":"","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00542-20","article-title":"The nonstructural protein NSs of severe fever with thrombocytopenia syndrome virus causes a cytokine storm through the hyperactivation of NF-\u03baB","volume":"41","author":"Khalil","year":"2021","journal-title":"Mol. Cell. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3390\/v16010128","article-title":"Current progress of severe fever with thrombocytopenia syndrome virus (SFTSV) vaccine development","volume":"16","author":"Kim","year":"2024","journal-title":"Viruses"},{"key":"B10","doi-asserted-by":"publisher","first-page":"797.e1","DOI":"10.1016\/j.cmi.2023.02.002","article-title":"The clinical value of aspergillus-specific IgG antibody test in the diagnosis of nonneutropenic invasive pulmonary aspergillosis","volume":"29","author":"Lu","year":"2023","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc Clin. Microbiol. Infect. Dis."},{"key":"B11","article-title":"Diagnosis and treatment scheme for severe fever with thrombocytopenia syndrome (2023 edition)","year":"2023"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1397733","article-title":"Clinical utility of metagenomic next-generation sequencing in the diagnosis of invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease patients in the intensive care unit","volume":"14","author":"Niu","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2262","article-title":"Epidemiology, prognosis and management of potassium disorders in covid-19","volume":"32","author":"Noori","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2025.101747","article-title":"Comprehensive epidemiological analysis of severe fever with thrombocytopenia syndrome in Japan 2013\u20132023: descriptive observational study","volume":"65","author":"Ohno","year":"2025","journal-title":"Lancet Reg. Health: West. Pac."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/v13071213","article-title":"Clinical update of severe fever with thrombocytopenia syndrome","volume":"13","author":"Seo","year":"2021","journal-title":"Viruses"},{"key":"B16","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.jmii.2020.12.016","article-title":"Proven invasive pulmonary aspergillosis in the early clinical course of severe fever with thrombocytopenia syndrome: importance of an early diagnosis","volume":"54","author":"Seong","year":"2021","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"B17","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12883-024-03664-6","article-title":"Severe fever with thrombocytopenia syndrome with central nervous system symptom onset: a case report and literature review","volume":"24","author":"Shan","year":"2024","journal-title":"BMC Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/myc.13410","article-title":"Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: a systematic review and meta-analysis","volume":"65","author":"Shi","year":"2022","journal-title":"Mycoses"},{"key":"B19","doi-asserted-by":"publisher","first-page":"S574","DOI":"10.21037\/jtd.2019.01.25","article-title":"Developing prediction models for clinical use using logistic regression: an overview","volume":"11","author":"Shipe","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1038\/s41598-023-28851-2","article-title":"Investigation of predictors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome","volume":"13","author":"Song","year":"2023","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1298050","article-title":"The pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome patients with co-infections","volume":"13","author":"Song","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2026.2667562","article-title":"Diagnostic value of pentraxin 3 in plasma and bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in non-neutropenic patients: a prospective multicenter clinical study","volume":"15","author":"Sun","year":"","journal-title":"Emerging Microbes Infect."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1560288","article-title":"Incidence and predictors of pulmonary aspergillosis in patients with lung cancer: a systematic review and meta-analysis","volume":"12","author":"Teng","year":"2025","journal-title":"Front. Med."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1448710","article-title":"Clinical factors associated with invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: analysis of a 6-year clinical experience","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.iccn.2025.104118","article-title":"Association between hyperkalemia and outcomes in hospitalized patients with acute kidney injury","volume":"90","author":"Wang","year":"2025","journal-title":"Intensive Crit. Care Nurs."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2026.1743506","article-title":"Establishing and validating a predictive model for long-term control outcomes following orthokeratology lenses wear: a five-year cohort study","volume":"14","author":"Wang","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8040158","article-title":"Vascular leak and hypercytokinemia associated with severe fever with thrombocytopenia syndrome virus infection in mice","volume":"8","author":"Westover","year":"2019","journal-title":"Pathogens"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1186\/s12879-025-12018-7","article-title":"Prediction models for encephalitis and in-hospital death associated with severe fever with thrombocytopenia syndrome","volume":"25","author":"Wu","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1335664","article-title":"Clinical value of coagulation parameters in predicting the severity of severe fever with thrombocytopenia syndrome","volume":"15","author":"Xia","year":"2024","journal-title":"Front. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1748830","article-title":"Characteristics of T-lymphocyte subsets in patients with severe fever with thrombocytopenia syndrome complicated with invasive pulmonary aspergillosis: a retrospective study","volume":"16","author":"Xu","year":"","journal-title":"Front. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1186\/s12879-025-12218-1","article-title":"Establishment and validation of a nomogram for predicting severe fever with thrombocytopenia syndrome complicated by invasive pulmonary aspergillosis","volume":"25","author":"Yan","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2026.1833723","article-title":"Establishment and validation of a machine learning-based predictive model for in-hospital mortality risk in acute myocardial infarction patients complicated with diabetes mellitus","volume":"13","author":"Zeng","year":"","journal-title":"Front. Cardiovasc. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1186\/s12879-025-10900-y","article-title":"Clinical characteristics and outcomes of disseminated intravascular coagulation in patients with severe fever with thrombocytopenia syndrome","volume":"25","author":"Zhang","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.31083\/FBL40723","article-title":"Single-cell analyses highlight the proinflammatory contribution of low-density neutrophils in the acute phase of severe fever with thrombocytopenia syndrome","volume":"30","author":"Zhao","year":"2025","journal-title":"Front. Biosci.-Landmark"},{"key":"B35","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12879-025-10503-7","article-title":"Severe fever with thrombocytopenia syndrome complicated with aspergillus endocarditis and multiple organ infarctions after glucocorticoid treatment in an immunocompetent man: a case report","volume":"25","author":"Zhao","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1007\/s40121-023-00808-y","article-title":"A reservoir computing with boosted topology model to predict encephalitis and mortality for patients with severe fever with thrombocytopenia syndrome: a retrospective multicenter study","volume":"12","author":"Zheng","year":"2023","journal-title":"Infect. Dis. Ther."}],"updated-by":[{"DOI":"10.3389\/fcimb.2026.2027760","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T00:00:00Z","timestamp":1792972800000}}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1857200\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:07:29Z","timestamp":1793038049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1857200\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":36,"alternative-id":["10.3389\/fcimb.2026.1857200"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1857200","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"article-number":"1857200"}}