A Rare Case of Aspergillosis Complicated by Endocarditis, Arterial Thrombosis, and Stroke in an Immunocompetent Patient: Successful Treatment with Early Intervention and Antifungal Therapy

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Abstract

Abstract Disseminated aspergillosis is a rare but highly lethal condition in immunocompetent patients. This report describes a patient's rapid progression from primary lumbar infection to infective endocarditis, arterial thrombosis, and stroke in just two days. Successful early intervention with lesion clearance and antifungal therapy highlights the importance of prompt and comprehensive treatment.
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A Rare Case of Aspergillosis Complicated by Endocarditis, Arterial Thrombosis, and Stroke in an Immunocompetent Patient: Successful Treatment with Early Intervention and Antifungal Therapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Case of Aspergillosis Complicated by Endocarditis, Arterial Thrombosis, and Stroke in an Immunocompetent Patient: Successful Treatment with Early Intervention and Antifungal Therapy Lin-feng Liu, Jian-wen Xiang, Chen-wei Pan, Lingli Zhou, Sheng Wang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5797160/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Disseminated aspergillosis is a rare but highly lethal condition in immunocompetent patients. This report describes a patient's rapid progression from primary lumbar infection to infective endocarditis, arterial thrombosis, and stroke in just two days. Successful early intervention with lesion clearance and antifungal therapy highlights the importance of prompt and comprehensive treatment. disseminated Aspergillus infection immunocompetence rapid progression Figures Figure 1 Introduction Aspergillus is a fungus commonly found in soil, decaying organic matter, and vegetation, making it widely present in the environment( 1 ). Invasive aspergillosis, primarily affecting the lungs, is the most common Aspergillus infection in immunocompromised individuals( 2 ). Disseminated aspergillosis, a severe form of invasive aspergillosis, affects multiple organs and has a high fatality rate( 3 ). The occurrence of disseminated aspergillosis is closely associated with immunosuppression, including conditions such as hematological malignancies, organ transplantation, and prolonged steroid use( 4 , 5 ). Although disseminated aspergillosis in immunocompetent patients has been documented, rapid systemic progression remains rare( 6 – 8 ). Diagnosing disseminated aspergillosis in immunocompetent individuals is challenging, and some cases are only identified post-mortem( 9 , 10 ). Here, we present a case involving structural lung changes and lumbar pain that rapidly progressed to endocarditis, heart failure, lower limb arterial thrombosis, stroke, and splenic infarction. We hypothesize that the source of the Aspergillus infection is linked to underlying structural lung disease. Case Presentation A 40-year-old woman presented with a month-long history of fever and lumbar pain. Initial treatment with anti-infectives did not significantly improve her symptoms. Lumbar spine CT showed L5-S1 disc protrusion, and MRI indicated disc degeneration and lumbar hyperostosis(Figure A ). Despite pain relief, neurotrophic therapy, and acupuncture, her lower back pain persisted. Her medical history included tuberculosis 15 years ago, leading to left lung atelectasis(Figure B). She had no other chronic conditions or history of immunosuppressive therapy. Upon admission, blood tests showed elevated WBC (12.72 x 10^9/l), NEUT% (78%), CRP (95.8 mg/l), and ESR (65 mm/h). Elevated ( 1 , 3 ) β-D glucan levels and a positive galactomannan (GM) test suggested Aspergillus infection, prompting further blood next-generation sequencing (mNGS), which confirmed Aspergillus fumigatus. Lumbar debridement on September 25, 2023, revealed necrotic tissue and pus, with pathology confirming Aspergillus fumigatus(Figure C/D). Treatment was adjusted to include voriconazole. On October 12, 2023, the patient developed fever, tachycardia, chest pain, and limb weakness. Cardiac ultrasound revealed a mitral valve mass, and MRI showed cerebral infarction. A multidisciplinary team diagnosed infective endocarditis, heart failure, and acute cerebral infarction, leading to valve replacement surgery, temporary pacemaker implantation, and myocardial pathology examination(Figure E/F). Upon ICU return, within 6 hours, the patient developed right lower limb ischemia due to arterial embolism, necessitating urgent thrombectomy and decompression. Intraoperative pathology of the thrombus was performed(Figure G/H), followed by postoperative care with antifungal therapy (isavuconazole), anticoagulation, mechanical ventilation, and monitoring. Head CT revealed cerebral hemorrhage and infarction, while abdominal imaging showed splenic infarction. Despite the critical condition and the family's decision against further invasive procedures, including bronchoscopy, the patient gradually improved and was discharged after two months. At the eight-month follow-up, the patient showed significant improvement in limb function and reduction in lumbar pain, with fungal markers nearing normal levels. Discussion Chronic lung changes (e.g., those caused by tuberculosis) are important risk factors for Aspergillus infection, particularly in conditions such as chronic obstructive pulmonary disease (COPD) and pneumoconiosis( 11 – 13 ). These structural changes impair lung function, creating an environment conducive to Aspergillus colonization and invasion, which can lead to severe outcomes. Although the patient's immune function was normal, individual factors such as structural lung abnormalities, prior infections, and potential genetic susceptibility may increase vulnerability to Aspergillus infection. Further research is needed to identify specific genetic markers or risk factors to help predict susceptibility and prevent severe infections in similarly high-risk groups. Aspergillus infection typically presents with nonspecific symptoms, making diagnosis challenging in immunocompetent patients. Comprehensive diagnostic approaches are crucial for timely identification of such infections. Diagnostic tools such as next-generation sequencing (NGS) and PCR are critical for identifying these difficult-to-diagnose infections, as evidenced by similar cases( 9 , 14 ). One unique aspect of this case was the consistent identification of Aspergillus across multiple sites, including spinal, myocardial, and lower limb arterial pathology, as well as blood NGS. This multi-site detection highlights the extensive dissemination of the infection and provides strong evidence for accurate diagnosis, which is rarely achieved in clinical practice. One limitation in this case was the lack of a lung biopsy, making it difficult to confirm the exact source of the Aspergillus infection. This also underscores the importance of considering invasive diagnostics in unclear cases to ensure accurate treatment. This case demonstrates that even immunocompetent individuals with structural lung disease are at risk for rapidly progressing Aspergillus infection, emphasizing the necessity of early and comprehensive treatment. For patients with disseminated aspergillosis, clearance of Aspergillus often requires prolonged treatment, as it can spread hematogenously to multiple organs, making the disease course unpredictable. Timely evaluation and adjustment of treatment strategies are crucial for improving patient outcomes( 2 ). This case also shows that Aspergillus infection in immunocompetent patients can rapidly spread to multiple organs, causing endocarditis, arterial thrombosis, and stroke. These severe complications emphasize the need for prompt diagnosis and active multi-system management. Given the severity of these complications, early recognition and multi-system management are essential for reducing mortality. In conclusion, although disseminated aspergillosis is rare in immunocompetent patients, it can lead to rapid multi-organ involvement and high mortality. Early recognition, timely multidisciplinary consultation, and proactive intervention are crucial for improving prognosis. Declarations Declarations and Competing Interests: The authors declare that they have no financial or personal conflicts of interest that could have influenced the findings presented in this paper. Clinical Trial Number : Not applicable. Data Availability: As this study is a case report, the data are not publicly available due to patient privacy and ethical considerations. However, relevant information can be made available from the corresponding author upon reasonable request. Consent for Publication: Written informed consent was obtained from the patient (or their legal guardian) for the publication of this case report, including any accompanying images. Funding: The authors declare no specific grants for this research from any funding agency. Ethical approval statement : Written informed consent was obtained from the patient for publication of this case report and accompanying images. References Thompson GR, 3rd, Young JH. Aspergillus Infections. The New England journal of medicine. 2021;385(16):1496-509. Patterson TF, Thompson GR, 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. Lehrnbecher T, Frank C, Engels K, Kriener S, Groll AH, Schwabe D. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect. 2010;61(3):259-65. Herbrecht R, Bories P, Moulin JC, Ledoux MP, Letscher‐Bru V. Risk stratification for invasive aspergillosis in immunocompromised patients. Annals of the New York Academy of Sciences. 2012;1272(1):23-30. Koehler P, Bassetti M, Chakrabarti A, Chen SCA, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21(6):e149-e62. Cheon S, Yang MK, Kim C-J, Kim TS, Song K-H, Woo SJ, et al. Disseminated Aspergillosis in the Immunocompetent Host: A Case Report and Literature Review. Mycopathologia. 2015;180(3-4):217-22. McLaughlin J, Libre E, Morgan A, Djurkovic S. Disseminated invasive aspergillosis in an immunocompetent patient. Cleveland Clinic journal of medicine. 2019;86(6):369-70. Kankam SB, Saffar H, Shafizadeh M, Afhami S, Khoshnevisan A. Intraventricular CNS aspergillosis in a patient with prior history of COVID-19: Case report and review of literature. Ann Med Surg (Lond). 2022;80:104122. Guirao-Arrabal E, García-López C, Anguita-Santos F, de la Cruz-Sabido J, Chueca N, Ruíz-Escolano E, et al. Disseminated aspergillosis in an immunocompetent patient treated with corticosteroids: value of PCR for diagnosis. Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia. 2019;32(3):273-5. Guglielmetti S, Jaccard CM, Mühlethaler K, Bigler A, Springe D, Ebnöther L, et al. Delayed Diagnosis of a Diffuse Invasive Gastrointestinal Aspergillosis in an Immunocompetent Patient. Case Reports in Critical Care. 2020;2020:1-5. El-Baba F, Gao Y, Soubani AO. Pulmonary Aspergillosis: What the Generalist Needs to Know. The American journal of medicine. 2020;133(6):668-74. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. The European respiratory journal. 2007;30(4):782-800. Chabi ML, Goracci A, Roche N, Paugam A, Lupo A, Revel MP. Pulmonary aspergillosis. Diagn Interv Imaging. 2015;96(5):435-42. Dorado G, Gálvez S, Rosales TE, Vásquez VF, Hernández P. Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing - Review. Biomolecules. 2021;11(8). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5797160","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":403485046,"identity":"e1e51a59-f953-4cb2-9a96-9436ab7c9ab9","order_by":0,"name":"Lin-feng Liu","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lin-feng","middleName":"","lastName":"Liu","suffix":""},{"id":403485047,"identity":"cf73ec6a-c91d-49ae-9265-2b3f2216efb4","order_by":1,"name":"Jian-wen Xiang","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jian-wen","middleName":"","lastName":"Xiang","suffix":""},{"id":403485048,"identity":"50463ab8-a402-413e-9f37-ee57c35911b3","order_by":2,"name":"Chen-wei Pan","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chen-wei","middleName":"","lastName":"Pan","suffix":""},{"id":403485049,"identity":"0b88bbcd-41c6-471f-ba2f-6f359217baef","order_by":3,"name":"Lingli Zhou","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lingli","middleName":"","lastName":"Zhou","suffix":""},{"id":403485050,"identity":"e92f81fb-25af-4b33-a788-c1bf54ed739c","order_by":4,"name":"Sheng Wang","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Wang","suffix":""},{"id":403485051,"identity":"27354ddd-7b57-4574-9c30-adc19c77c15f","order_by":5,"name":"Qi-feng Zhao","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qi-feng","middleName":"","lastName":"Zhao","suffix":""},{"id":403485052,"identity":"29ca9da4-6564-45fa-a8a7-dcf86c83fed8","order_by":6,"name":"Peng Ai","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Ai","suffix":""},{"id":403485053,"identity":"c29b0044-e38e-4391-8c75-5f8a215455ed","order_by":7,"name":"Yu Hao","email":"","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Hao","suffix":""},{"id":403485054,"identity":"d185c826-bd02-48e9-b715-5bbf8838b9b9","order_by":8,"name":"Yu-qiang Gong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIie2RMQrCQBBFNyykGk27NolHGEmbgwg2GwKpFHKAFAGLlGlzDCFgvWHAVkvLVNYB24AuVnaZUnBf/R+fmS+Ew/GjmBETCKSkgWt4fVvk4ar2c+QqkmCkGK+wVqx8tM1OBlCmHYFAUSa7WWVzzwuj0E/PtDCDuOSHalZp92gQwSpLjV5FTEWjSrsjoGIpkbKKrYlRchWER9FXqENF9smac0tUZ91zml4QNETDWCaMlpv+GlDPxT8tjWFv7nA4HP/KG94FQ603qLFIAAAAAElFTkSuQmCC","orcid":"","institution":"Second Affiliated Hospital \u0026 Yuying Children's Hospital of Wenzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yu-qiang","middleName":"","lastName":"Gong","suffix":""}],"badges":[],"createdAt":"2025-01-09 14:08:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5797160/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5797160/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74243732,"identity":"2e8ef097-53fd-4aed-8dab-711465bd6133","added_by":"auto","created_at":"2025-01-20 09:46:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8450481,"visible":true,"origin":"","legend":"\u003cp\u003eFigure A reveals abnormal signals in the T12/S1 vertebral endplate and intervertebral space, suggesting possible infection or L5/S1 disc herniation. Figure B shows low-density occlusion in the left central bronchus, leading to left lung atelectasis, pleural thickening, and calcification.\u003c/p\u003e\n\u003cp\u003eFigure C demonstrates hexamine silver staining in the spinal column, and Figure D shows HE staining of the spine, both identifying fungal organisms in the L5/S1 disc, with morphology indicative of Aspergillus infection. PAS and silver nitrate stains are positive, with fungal bodies marked (Figure C red arrow indicates the fungal body, original magnification ×400; bar = 100 μm).\u003c/p\u003e\n\u003cp\u003eFigures E and F, showing hexamine silver and HE staining of the cardiac muscle, reveal infective endocarditis with hyaline and mucinous degeneration of the mitral valve and vegetation, local necrosis, granulation, and neutrophil infiltration, with positive PAS and silver nitrate staining confirming Aspergillus. (Figure E red arrow indicates the fungal body, original magnification ×400; bar = 100 μm).\u003c/p\u003e\n\u003cp\u003eFigures G and H illustrate hexamine silver and HE staining of the right lower limb artery, identifying a mixed thrombus containing Aspergillus organisms. The morphology aligns with Aspergillus infection (Figure G red arrow indicates the fungal body, original magnification ×400; bar = 100 μm).\u003c/p\u003e","description":"","filename":"figure.png","url":"https://assets-eu.researchsquare.com/files/rs-5797160/v1/f9702658775b9fb948efaf8f.png"},{"id":74349401,"identity":"3223f8ef-734c-4334-84fa-a6d8390baa44","added_by":"auto","created_at":"2025-01-21 10:24:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":12097743,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5797160/v1/6dd5b919-cb7a-48b4-9fa2-21eeb89f0103.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case of Aspergillosis Complicated by Endocarditis, Arterial Thrombosis, and Stroke in an Immunocompetent Patient: Successful Treatment with Early Intervention and Antifungal Therapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAspergillus is a fungus commonly found in soil, decaying organic matter, and vegetation, making it widely present in the environment(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Invasive aspergillosis, primarily affecting the lungs, is the most common Aspergillus infection in immunocompromised individuals(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Disseminated aspergillosis, a severe form of invasive aspergillosis, affects multiple organs and has a high fatality rate(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The occurrence of disseminated aspergillosis is closely associated with immunosuppression, including conditions such as hematological malignancies, organ transplantation, and prolonged steroid use(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Although disseminated aspergillosis in immunocompetent patients has been documented, rapid systemic progression remains rare(\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Diagnosing disseminated aspergillosis in immunocompetent individuals is challenging, and some cases are only identified post-mortem(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Here, we present a case involving structural lung changes and lumbar pain that rapidly progressed to endocarditis, heart failure, lower limb arterial thrombosis, stroke, and splenic infarction. We hypothesize that the source of the Aspergillus infection is linked to underlying structural lung disease.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 40-year-old woman presented with a month-long history of fever and lumbar pain. Initial treatment with anti-infectives did not significantly improve her symptoms. Lumbar spine CT showed L5-S1 disc protrusion, and MRI indicated disc degeneration and lumbar hyperostosis(Figure A ). Despite pain relief, neurotrophic therapy, and acupuncture, her lower back pain persisted. Her medical history included tuberculosis 15 years ago, leading to left lung atelectasis(Figure B). She had no other chronic conditions or history of immunosuppressive therapy.\u003c/p\u003e \u003cp\u003eUpon admission, blood tests showed elevated WBC (12.72 x 10^9/l), NEUT% (78%), CRP (95.8 mg/l), and ESR (65 mm/h). Elevated (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) β-D glucan levels and a positive galactomannan (GM) test suggested Aspergillus infection, prompting further blood next-generation sequencing (mNGS), which confirmed Aspergillus fumigatus. Lumbar debridement on September 25, 2023, revealed necrotic tissue and pus, with pathology confirming Aspergillus fumigatus(Figure C/D). Treatment was adjusted to include voriconazole.\u003c/p\u003e \u003cp\u003eOn October 12, 2023, the patient developed fever, tachycardia, chest pain, and limb weakness. Cardiac ultrasound revealed a mitral valve mass, and MRI showed cerebral infarction. A multidisciplinary team diagnosed infective endocarditis, heart failure, and acute cerebral infarction, leading to valve replacement surgery, temporary pacemaker implantation, and myocardial pathology examination(Figure E/F).\u003c/p\u003e \u003cp\u003eUpon ICU return, within 6 hours, the patient developed right lower limb ischemia due to arterial embolism, necessitating urgent thrombectomy and decompression. Intraoperative pathology of the thrombus was performed(Figure G/H), followed by postoperative care with antifungal therapy (isavuconazole), anticoagulation, mechanical ventilation, and monitoring. Head CT revealed cerebral hemorrhage and infarction, while abdominal imaging showed splenic infarction. Despite the critical condition and the family's decision against further invasive procedures, including bronchoscopy, the patient gradually improved and was discharged after two months.\u003c/p\u003e \u003cp\u003eAt the eight-month follow-up, the patient showed significant improvement in limb function and reduction in lumbar pain, with fungal markers nearing normal levels.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eChronic lung changes (e.g., those caused by tuberculosis) are important risk factors for Aspergillus infection, particularly in conditions such as chronic obstructive pulmonary disease (COPD) and pneumoconiosis(\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). These structural changes impair lung function, creating an environment conducive to Aspergillus colonization and invasion, which can lead to severe outcomes. Although the patient's immune function was normal, individual factors such as structural lung abnormalities, prior infections, and potential genetic susceptibility may increase vulnerability to Aspergillus infection. Further research is needed to identify specific genetic markers or risk factors to help predict susceptibility and prevent severe infections in similarly high-risk groups.\u003c/p\u003e \u003cp\u003eAspergillus infection typically presents with nonspecific symptoms, making diagnosis challenging in immunocompetent patients. Comprehensive diagnostic approaches are crucial for timely identification of such infections. Diagnostic tools such as next-generation sequencing (NGS) and PCR are critical for identifying these difficult-to-diagnose infections, as evidenced by similar cases(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). One unique aspect of this case was the consistent identification of Aspergillus across multiple sites, including spinal, myocardial, and lower limb arterial pathology, as well as blood NGS. This multi-site detection highlights the extensive dissemination of the infection and provides strong evidence for accurate diagnosis, which is rarely achieved in clinical practice. One limitation in this case was the lack of a lung biopsy, making it difficult to confirm the exact source of the Aspergillus infection. This also underscores the importance of considering invasive diagnostics in unclear cases to ensure accurate treatment.\u003c/p\u003e \u003cp\u003eThis case demonstrates that even immunocompetent individuals with structural lung disease are at risk for rapidly progressing Aspergillus infection, emphasizing the necessity of early and comprehensive treatment. For patients with disseminated aspergillosis, clearance of Aspergillus often requires prolonged treatment, as it can spread hematogenously to multiple organs, making the disease course unpredictable. Timely evaluation and adjustment of treatment strategies are crucial for improving patient outcomes(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis case also shows that Aspergillus infection in immunocompetent patients can rapidly spread to multiple organs, causing endocarditis, arterial thrombosis, and stroke. These severe complications emphasize the need for prompt diagnosis and active multi-system management. Given the severity of these complications, early recognition and multi-system management are essential for reducing mortality.\u003c/p\u003e \u003cp\u003eIn conclusion, although disseminated aspergillosis is rare in immunocompetent patients, it can lead to rapid multi-organ involvement and high mortality. Early recognition, timely multidisciplinary consultation, and proactive intervention are crucial for improving prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclarations and Competing Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no financial or personal conflicts of interest that could have influenced the findings presented in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this study is a case report, the data are not publicly available due to patient privacy and ethical considerations. However, relevant information can be made available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient (or their legal guardian) for the publication of this case report, including any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no specific grants for this research from any funding agency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval statement\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and accompanying images.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eThompson GR, 3rd, Young JH. Aspergillus Infections. The New England journal of medicine. 2021;385(16):1496-509.\u003c/li\u003e\n\u003cli\u003ePatterson TF, Thompson GR, 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60.\u003c/li\u003e\n\u003cli\u003eLehrnbecher T, Frank C, Engels K, Kriener S, Groll AH, Schwabe D. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect. 2010;61(3):259-65.\u003c/li\u003e\n\u003cli\u003eHerbrecht R, Bories P, Moulin JC, Ledoux MP, Letscher‐Bru V. Risk stratification for invasive aspergillosis in immunocompromised patients. Annals of the New York Academy of Sciences. 2012;1272(1):23-30.\u003c/li\u003e\n\u003cli\u003eKoehler P, Bassetti M, Chakrabarti A, Chen SCA, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21(6):e149-e62.\u003c/li\u003e\n\u003cli\u003eCheon S, Yang MK, Kim C-J, Kim TS, Song K-H, Woo SJ, et al. Disseminated Aspergillosis in the Immunocompetent Host: A Case Report and Literature Review. Mycopathologia. 2015;180(3-4):217-22.\u003c/li\u003e\n\u003cli\u003eMcLaughlin J, Libre E, Morgan A, Djurkovic S. Disseminated invasive aspergillosis in an immunocompetent patient. Cleveland Clinic journal of medicine. 2019;86(6):369-70.\u003c/li\u003e\n\u003cli\u003eKankam SB, Saffar H, Shafizadeh M, Afhami S, Khoshnevisan A. Intraventricular CNS aspergillosis in a patient with prior history of COVID-19: Case report and review of literature. Ann Med Surg (Lond). 2022;80:104122.\u003c/li\u003e\n\u003cli\u003eGuirao-Arrabal E, Garc\u0026iacute;a-L\u0026oacute;pez C, Anguita-Santos F, de la Cruz-Sabido J, Chueca N, Ru\u0026iacute;z-Escolano E, et al. Disseminated aspergillosis in an immunocompetent patient treated with corticosteroids: value of PCR for diagnosis. Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia. 2019;32(3):273-5.\u003c/li\u003e\n\u003cli\u003eGuglielmetti S, Jaccard CM, M\u0026uuml;hlethaler K, Bigler A, Springe D, Ebn\u0026ouml;ther L, et al. Delayed Diagnosis of a Diffuse Invasive Gastrointestinal Aspergillosis in an Immunocompetent Patient. Case Reports in Critical Care. 2020;2020:1-5.\u003c/li\u003e\n\u003cli\u003eEl-Baba F, Gao Y, Soubani AO. Pulmonary Aspergillosis: What the Generalist Needs to Know. The American journal of medicine. 2020;133(6):668-74.\u003c/li\u003e\n\u003cli\u003eBulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. The European respiratory journal. 2007;30(4):782-800.\u003c/li\u003e\n\u003cli\u003eChabi ML, Goracci A, Roche N, Paugam A, Lupo A, Revel MP. Pulmonary aspergillosis. Diagn Interv Imaging. 2015;96(5):435-42.\u003c/li\u003e\n\u003cli\u003eDorado G, G\u0026aacute;lvez S, Rosales TE, V\u0026aacute;squez VF, Hern\u0026aacute;ndez P. Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing - Review. Biomolecules. 2021;11(8).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"disseminated Aspergillus infection, immunocompetence, rapid progression","lastPublishedDoi":"10.21203/rs.3.rs-5797160/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5797160/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDisseminated aspergillosis is a rare but highly lethal condition in immunocompetent patients. 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