Challenges in Diagnosing and Managing Disseminated Mycobacterium avium and Talaromyces marneffei Co-infection: A Case Report

Challenges in Diagnosing and Managing Disseminated Mycobacterium avium and Talaromyces marneffei Co-infection: A Case Report | 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 Challenges in Diagnosing and Managing Disseminated Mycobacterium avium and Talaromyces marneffei Co-infection: A Case Report Hui-Hui Wu, Yu-Kun Zhao, Yun Lai, Chun-Lei Wan, Qiang Liao, Yi-Hong Zheng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4814788/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Oct, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 13 You are reading this latest preprint version Abstract Background Mycobacterium avium ( M. avium ) is emerging as an opportunistic pathogen and has been grouped with the nontuberculosis mycobacteria (NTM). Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), primarily affects elderly individuals with chronic lung disease and remains one of the leading causes of death in many regions worldwide. Distinguishing between NTM infection and drug-resistant TB is challenging due to similar manifestations and resistance to conventional anti-tuberculosis therapies (ATT). Talaromyces marneffei ( T. marneffei ) is a pathogenic fungus causing devastating infection, primarily in immunocompromised individuals. Few reports describe disseminated co-infection of M. avium and T. marneffei in HIV-uninfected persons. Case presentation: Herein, we present a case study of an HIV-negative Chinese woman who initially presented with chronic cough, sputum production, and recurrent low-grade fever, which was initially diagnosed as TB. After three years of anti-TB treatment, her situation progressed, and she developed multiple subcutaneous abscesses throughout the body, including the brain. Subsequent bacterial culture and genetic analysis confirmed the presence of NTM specifically identified as M. avium . However, despite receiving anti-NTM treatment, it remained ineffective until co-infection with T. marneffei was eventually diagnosed. Conclusions Early utilization of genetic diagnostic methods is necessary to detect the possibility of NTM infections, especially when patients do not respond adequately to ATT. It is also crucial to remain vigilant for co-infections when the disease progresses despite ongoing anti-NTM treatment. Mycobacterium avium Talaromyces marneffei Co-infection Tuberculosis Diagnosis Case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Nontuberculous mycobacteria (NTM) are increasingly recognized as critical opportunistic pathogens of humans, causing globally increasing opportunistic infections and mortality in immunocompromised populations and affecting otherwise healthy individuals. [ 1 , 2 ] While the lungs are most affected, the lymphatic system, skin, heart, soft tissues, bones, and joints are also frequently involved. [ 2 ] Diagnosing and treating NTM is challenging due to its similarity in symptoms and histopathological characteristics with tuberculosis (TB), as well as resistance to many antibiotics. [ 3 , 4 ] NTM are diverse and ubiquitous in the environment; however, only a few species pose severe threats by causing opportunistic infections in humans, such as Mycobacterium avium (M. avium) . M. avium is an emerging opportunistic pathogen worldwide that often causes nontuberculous infections in immunocompromised individuals. [ 5 ] Talaromyces marneffei ( T. marneffei ) is a pathogenic fungus causing talaromycosis, which has devastating impacts on persons with acquired immunodeficiency syndrome (AIDS) or other immunocompromised conditions. [ 6 ] To our knowledge, only three HIV-negative cases of disseminated M. avium and T. marneffei co-infection had been reported. [ 7 – 9 ] Unfortunately, prompt diagnosis of this co-infection was often missed, resulting in ineffective treatment and poor patient prognosis. Herein, we present a novel case of an HIV-negative Chinese woman who was initially misdiagnosed with TB and received ineffective anti-tuberculosis therapies (ATT) for three years. Subsequently, she developed pulmonary lesions along with bone lesions accompanied by subcutaneous abscesses and cerebral abscesses before ultimately being diagnosed with disseminated co-infection of M. avium and T. marneffei . Case presentation The patient, a 44-year-old Chinese woman, presented with chronic cough, sputum production, recurrent low-grade fevers, and chest pain. She had previously been diagnosed with secondary pulmonary tuberculosis, tuberculous pleuritis, sternal tuberculosis, and lymph node tuberculosis three years ago. A left upper lung lobe wedge resection and excision of chest wall masses were performed on her along with the administration of ATT, which proved to be ineffective. One month before she visited our institution, she sought medical attention at another hospital due to multiple subcutaneous abscesses on the head, trunk, and limbs. Cultures from an ulcer on her trunk revealed NTM infection, where M. avium was identified through DNA microarray chip array testing. Consequently, she was diagnosed with disseminated M. avium infection and treated using amikacin, moxifloxacin, clofazimine, clarithromycin, and linezolid. However, her condition did not improve after one month of treatment; instead, she gradually developed mental symptoms such as disorganized speech and hallucinations, leading to her subsequent evaluation and treatment at our hospital. On physical examination, the patient presented with pallor and cachexia. Subcutaneous abscesses and cutaneous ulcers accompanied by yellowish purulent discharge measuring 2 to 4 cm in diameter were observed on the head, chest, abdomen, and lower limbs (Fig. 1 ). Laboratory investigations revealed leukocytosis (white blood cell [WBC]: 18.62×10 9 /L, neutrophils ratio: 92%, lymphocytes ratio: 2.6%), anemia (hemoglobin [Hb]: 4.4 g/dL, red blood cell [RBC] count: 3.35×10 12 /L), hepatic and renal dysfunction (gamma-glutamyl transpeptidase [GGT]: 80 U/L, serum creatinine: 135 µmol/L), elevated erythrocyte sedimentation rate (ESR: 46 mm/h, normal range [NR]: 0–20 mm/h), increased C-reactive-protein levels (CRP: 103 mg/L, NR: 0–9 mg/L), elevated IgG levels (36.58 g/L, NR: 8.6-17.4g/L). The CD4 + lymphocyte count was below average at 368/µL (NR: 414–1440/µL). The anti-HIV test, TPPA (Treponema pallidum particle agglutination test), and TRUST (Tolulized red unheated serum test) were negative. Chest computed tomography (CT) showed bilateral lung infection with enlarged lymph nodes in the bilateral supraclavicular, neck, axillary, and mediastinal regions. Additionally, thickening of the left pleura, bilateral pleural effusion, and pericardial effusion were observed. Multiple areas of bone destruction involving the sternum, numerous ribs, vertebral bodies, and scapula were also seen (Fig. 2 ). Cephalic magnetic resonance imaging (MRI) revealed scattered lesions on the head and cheeks, along with abnormal enhancement in the left frontal lobe, suggestive of infectious lesions and multiple abscesses (Fig. 2 ). Histopathological examination of a skin abscess in the right upper abdomen revealed diffuse histiocytoid cells and lymphocytic and neutrophil infiltration in the dermis. A few small-sized fungal spore-like structures, which were positively stained with Gomori's methenamine silver (GMS), were identified in affected areas (Fig. 3 ). Subsequently, T. marneffei was isolated by culturing the pus from a scalp abscess (Fig. 4 ) and confirmed through polymerase chain reaction (PCR) sequencing. In addition, next-generation sequencing (NGS) of tissue from the left upper lobe confirmed that the initial pulmonary infection was caused by M. avium . Thus, the patient was diagnosed with disseminated M. avium and T. marneffei co-infection. She received treatment consisting of oral itraconazole 0.2 g, twice daily, clarithromycin 0.5 g, twice daily, moxifloxacin 0.4 g once daily, ethambutol 0.625 g once daily, and doxycycline 0.1 g once daily. Subcutaneous abscesses were managed through incision, drainage, and local wound care. After two weeks of treatment, the patient became afebrile, and partial improvement was observed in cutaneous lesions. Her mental state was improved. Laboratory examination showed a slight recovery of leukocytosis (WBC: 15.44×10 9 /L, neutrophil ratio: 90.4%). Liver and kidney function markers were improved (GGT: 39 U/L, serum creatinine: 103 µmol/L). The patient requested discharge for unknown reasons and was lost to follow-up. Discussion and Conclusions The Mycobacterium avium complex (MAC) is the most common type of NTM and comprises 12 species. [ 10 ] Mycobacterium avium and Mycobacterium intracellulare represent the two original members of this complex. MAC infections and TB share similar clinical manifestations, including fever, night sweats, weight loss, cough, and expectoration. They also share similar histopathological characteristics, which both exhibit acid-fast positive bacilli, necrotizing granulomas, and multinucleated Langhans giant cells. [ 3 , 11 ]. The prognosis for MAC infection remains poorly characterized. A recent review reported a 5-year all-cause mortality exceeding 25% in patients with MAC pulmonary disease and higher risks of complications and death from disseminated MAC infections [ 12 ]. Although culture is the gold standard for diagnosing MAC infections, its utility is limited due to low positivity rates caused by slow growth of pathogenic NTM (typically taking two months) and varying culture temperatures required for different NTM species [ 13 ]. T. marneffei is an emerging opportunistic pathogenic fungus often found in patients with AIDS or other immunodeficiency diseases. [ 14 ] In rare cases, co-infection of NTM and T. marneffei in HIV-negative patients can occur. [ 15 ] Due to the similarity in clinical manifestations, such as cough and skin lesions between NTM and T. marneffei infections, the misdiagnosis rate for either pathogen can be as high as 77%, leading to a poor prognosis. [ 16 ] A study indicates that co-infection of NTM and T. marneffei exhibits higher levels of inflammatory markers, more severe inflammatory anemia, and involvement of more sites than infection with either pathogen alone. Elevated levels of anti-IFN-γ autoantibodies, WBCs, neutrophils, IgG, IgM, IgA, serum globulin, ESR, and CRP, and low CD4 + T cell count are considered risk factors for T. marneffei and NTM co-infection. [ 15 , 17 ] Unfortunately, we did not test for anti-IFN-γ autoantibodies. However, our patient exhibited increased levels of WBCs, IgG, ESR, and CRP and a low CD4 + T cell count. Reviewing her medical records revealed a drop in hemoglobin from 5.4 g/dL to 4.4 g/dL, along with worsened symptoms when treated with anti-NTM medication. All these findings suggest inadequate disease control and the possibility of a co-infection. MAC, particularly M. avium , shows poor sensitivity to existing anti-TB drugs. [ 4 ] A standard anti-MAC regimen involves a combination of macrolides, rifamycin, and ethambutol (guideline-based three-drug therapy, GBT therapy) for a minimum of 12 months following sputum conversion. Other recommended treatments include aminoglycosides, fluoroquinolones, and isoniazid. [ 18 ] Nevertheless, the rates of treatment failure and recurrence for M. avium remain significantly high. [ 5 ] Amphotericin B and itraconazole are identified as the most effective drugs for treating T. marneffei , with a treatment course of 3–6 months. [ 19 ] Due to our patient's previous allergic reaction to rifampicin, she was treated as indicated above and exhibited a positive response after two weeks. Unfortunately, she was lost during the follow-up. We presented a rare case of disseminated M. avium and T. marneffei co-infection in an HIV-negative patient. The previous three cases of this co-infection typically presented with symptoms including fever, cough, chest pain, lymphadenopathy, and painful skin erythema. [ 7 – 9 ] In addition to most of these symptoms, our patient uniquely developed the rare complication of cutaneous and cerebral abscesses. The presented case has prompted several clinical reflections. Firstly, diagnosing M. avium /NTM infections and TB is difficult because of the similar clinical manifestations and histopathological characteristics. Thus, genetic diagnostic methods such as DNA microarray or NGS are essential, especially when anti-TB treatment is ineffective. Second, vigilance is required for potential opportunistic pathogens co-infection even in HIV-negative patients, significantly when symptoms worsen, inflammatory markers escalate, anemia deteriorates, and anti-IFN-γ autoantibodies are detected. Furthermore, multiple histopathological examinations and pathogen cultures from various sites can be beneficial in clarifying the diagnosis. It is easy to misdiagnose and miss diagnose disseminated M. avium and T. marneffei co-infection in HIV-negative patients, leading to a poor prognosis. Therefore, it is imperative to employ timely genetic diagnostic methods, conduct multiple cultures and pathological examinations, and maintain a vigilant approach toward identifying co-infections. Abbreviations NTM Nontuberculous mycobacteria TB Tuberculosis M. avium Mycobacterium avium T. marneffei Talaromyces marneffei AIDS Acquired immunodeficiency syndrome ATT Anti-tuberculosis therapies WBC White blood cell Hb Hemoglobin RBC Red blood cell GGT Gamma-glutamyl transpeptidase ESR Erythrocyte sedimentation rate NR Normal range CRP C-reactive-protein TPPA Treponema pallidum particle agglutination test TRUST Tolulized red unheated serum test CT Computed tomography MRI Magnetic resonance imaging GMS Gomori's methenamine silver PCR Polymerase chain reaction NGS Next-generation sequencing MAC Mycobacterium avium complex GBT therapy Guideline-based three-drug therapy Declarations Ethics approval and consent to participate The study protocol was conducted per the Declaration of Helsinki. It was approved by the Ethics Committee of the First Affiliated Hospital of Gannan Medical University (No: LLSL-2023171). Consent for publication Both the patient and her father gave written and oral informed consent to publish the clinical details and images. The consent form was obtained from the hospital during the patient's inpatient stay. Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding None. Authors’ contributions HHW and YKZ conceived the study, participated in the patient's clinical management, reviewed the literature on the item, and drafted the manuscript. YL and CLW participated in the clinical management of the patient. QL, YHZ, and SL contributed to the diagnosis and gene chip detection. JFL made the correct diagnosis, participated in the patient's clinical management, conceived the study, reviewed the literature on the item, and drafted the manuscript. YKZ reviewed drafts of the paper. All authors read and approved the final manuscript. Acknowledgments We sincerely appreciate Prof. Di-qing Luo's invaluable assistance in processing the photographs. References Dahl VN, Mølhave M, Fløe A, van Ingen J, Schön T, Lillebaek T, et al. Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review. Int J Infect Dis. 2022; 125: 120-131. doi: 10.1016/j.ijid.2022.10.013. Bhanushali J, Jadhav U, Ghewade B, Wagh P. Unveiling the Clinical Diversity in Nontuberculous Mycobacteria (NTM) Infections: A Comprehensive Review. Cureus. 2023;15(11):e48270. doi: 10.7759/cureus.48270. Kendall BA, Varley CD, Choi D, Cassidy PM, Hedberg K, Ware MA, et al. Distinguishing tuberculosis from nontuberculous mycobacteria lung disease, Oregon, USA. Emerg Infect Dis. 2011; 17(3): 506-509. doi: 10.3201/eid1703.101164. Dartois V, Dick T. Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease. Nat Rev Drug Discov. 2024; 23(5): 381-403. doi: 10.1038/s41573-024-00897-5. Mattoo R. Targeting emerging Mycobacterium avium infections: perspectives into pathways and antimicrobials for future interventions. Future Microbiol. 2021;16:753-764. doi: 10.2217/fmb-2021-0016. Wang F, Han R, Chen S. An Overlooked and Underrated Endemic Mycosis-Talaromycosis and the Pathogenic Fungus Talaromyces marneffei. Clin Microbiol Rev. 2023;36(1):e0005122. doi: 10.1128/cmr.00051-22. Su SS, Zhang SN, Ye JR, Xu LN, Lin PC, Xu HY, et al. Disseminated Talaromyces marneffei And Mycobacterium avium Infection Accompanied Sweet's Syndrome In A Patient With Anti-Interferon-gamma Autoantibodies: A Case Report. Infect Drug Resist. 2019; 12: 3189-3195. doi: 10.2147/IDR.S218836. Yu G, Xu X, Ye B. Disseminated Mycobacterium avium and Talaromyces marneffei co-infection. Med Clin (Barc). 2021;157(9):458. doi: 10.1016/j.medcli.2020.12.026. Tang BS, Chan JF, Chen M, Tsang OT, Mok MY, Lai RW, et al. Disseminated penicilliosis, recurrent bacteremic nontyphoidal salmonellosis, and burkholderiosis associated with acquired immunodeficiency due to autoantibody against gamma interferon. Clin Vaccine Immunol. 2010;17(7):1132-8. doi: 10.1128/CVI.00053-10. Hamed KA, Tillotson G. A narrative review of nontuberculous mycobacterial pulmonary disease: microbiology, epidemiology, diagnosis, and management challenges. Expert Rev Respir Med. 2023; 17(11): 973-988. doi: 10.1080/17476348.2023.2283135. Gopalaswamy R, Shanmugam S, Mondal R, Subbian S. Of tuberculosis and nontuberculous mycobacterial infections - a comparative analysis of epidemiology, diagnosis and treatment. J Biomed Sci. 2020;27(1):74. doi: 10.1186/s12929-020-00667-6. Diel R, Lipman M, Hoefsloot W. High mortality in patients with Mycobacterium avium complex lung disease: a systematic review. BMC Infect Dis. 2018; 18(1): 206. doi: 10.1186/s12879-018-3113-x. van Ingen J. Diagnosis of nontuberculous mycobacterial infections. Semin Respir Crit Care Med. 2013; 34(1): 103-109. doi: 10.1055/s-0033-1333569. He L, Mei X, Lu S, Ma J, Hu Y, Mo D, et al. Talaromyces marneffei infection in non-HIV-infected patients in mainland China. Mycoses. 2021; 64(10): 1170-1176. doi: 10.1111/myc.13295. Qiu Y, Huang J, Li Y, Zeng W, Pan M, Cen J, et al. Talaromyces marneffei and nontuberculous mycobacteria co-infection in HIV-negative patients. Sci Rep. 2021; 11(1): 16177. doi: 10.1038/s41598-021-95686-0. Yang ZM, Huang J, Chen XM, Meng X, Qiu Y, Zeng W, et al. [Advances in clinical characteristics of talaromycosis combined with other opportunistic infections]. Zhonghua Jie He He Hu Xi Za Zhi. 2023; 46(5): 503-506. Chinese. doi: 10.3760/cma.j.cn112147-20220807-00659. Qiu Y, Tang M, Zeng W, Feng X, Pan M, Li W, et al. Clinical findings and predictive factors for positive anti-interferon-gamma autoantibodies in patients suffering from a nontuberculosis mycobacteria or Talaromyces marneffei infection: a multicenter prospective cohort study. Sci Rep. 2022; 12(1): 9069. doi: 10.1038/s41598-022-13160-x. Wang PH, Shu CC, Chen CY, Wei YF, Cheng SL. The role of treatment regimen and duration in treating patients with Mycobacterium avium complex lung disease: A real-world experience and case-control study. J Microbiol Immunol Infect. 2024; 57(1): 164-174. doi: 10.1016/j.jmii.2023.11.006. Le T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, et al. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med. 2017; 376(24): 2329-2340. doi: 10.1056/NEJMoa1613306. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 31 Oct, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 11 Aug, 2025 Reviews received at journal 03 Aug, 2025 Reviews received at journal 24 Jul, 2025 Reviewers agreed at journal 20 Jul, 2025 Reviewers agreed at journal 20 Jul, 2025 Reviewers agreed at journal 17 Jul, 2025 Reviews received at journal 27 Aug, 2024 Reviewers agreed at journal 22 Aug, 2024 Reviewers invited by journal 22 Aug, 2024 Editor invited by journal 29 Jul, 2024 Editor assigned by journal 29 Jul, 2024 Submission checks completed at journal 29 Jul, 2024 First submitted to journal 27 Jul, 2024 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. 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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-4814788","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":343707918,"identity":"59dce1c7-4e88-4281-8bf7-65a97b52d922","order_by":0,"name":"Hui-Hui Wu","email":"","orcid":"","institution":"First Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Hui-Hui","middleName":"","lastName":"Wu","suffix":""},{"id":343707919,"identity":"79583345-d5cf-4541-ae7e-f024842f9eab","order_by":1,"name":"Yu-Kun Zhao","email":"","orcid":"","institution":"First Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Yu-Kun","middleName":"","lastName":"Zhao","suffix":""},{"id":343707920,"identity":"3f245a8f-c170-4a4a-92f3-18063be92dd4","order_by":2,"name":"Yun Lai","email":"","orcid":"","institution":"The First Affiliated Hospital of Gannan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"Lai","suffix":""},{"id":343707922,"identity":"931162c7-394b-4b1f-9dfe-1ff20c365483","order_by":3,"name":"Chun-Lei Wan","email":"","orcid":"","institution":"The First Affiliated Hospital of Gannan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chun-Lei","middleName":"","lastName":"Wan","suffix":""},{"id":343707924,"identity":"2b86bf84-137c-49c8-b9c9-94cae50a35c6","order_by":4,"name":"Qiang Liao","email":"","orcid":"","institution":"The Second Affiliated Hospital of Gannan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Liao","suffix":""},{"id":343707925,"identity":"57f60e7b-2754-42b8-a316-24add2990ab8","order_by":5,"name":"Yi-Hong Zheng","email":"","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-Hong","middleName":"","lastName":"Zheng","suffix":""},{"id":343707927,"identity":"a2070db7-59b3-45c9-a7bf-ec0828006546","order_by":6,"name":"Sha Lu","email":"","orcid":"","institution":"Sun Yat-sen Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sha","middleName":"","lastName":"Lu","suffix":""},{"id":343707929,"identity":"ef7bcfee-f6d6-4da2-ac20-49ef751b6f45","order_by":7,"name":"Jing-Fa Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIie3PPQrCQBCG4U8CSbNxO4kI5goT0ipeZYOthaVlQEklpjV4iZSWE7bNDWwULyDYiKTwD2yzpeC+3cA8DAPYbD9YF1AMDOE6DvNlYUDcD4khPTeptrUZeRWjn4tY+ysTEqiTnt8pJC0u7KcIZY9bidLFhqJS+yX394iKnTIg/rrpvElUQ9HBjNCk1OLISWZKxI2SYinAlRERx+eVlKa541KV1kH7L9KbTa+ioXEm9fnaLEahHLQQQCh0su8UtK2/8hhoTBZtNpvtb3sAfvBInJrHpq4AAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Gannan Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jing-Fa","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2024-07-28 02:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4814788/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4814788/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-11895-2","type":"published","date":"2025-10-31T15:57:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63803053,"identity":"5e1c5e4a-f596-4f86-85d1-76eb07a1bf99","added_by":"auto","created_at":"2024-09-02 13:21:57","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1110275,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eManifestations of skin lesions. \u003c/strong\u003e(a, d) Multiple subcutaneous abscesses measuring 2 to 4 cm in diameter were distributed over the head and lower limb. (b) Some of the lesions had ruptured with discharge of yellowish fluid. (c) Multiple coin-sized ulcerations and erosions with crusts and purulent discharge were found on the chest.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4814788/v1/b2e0c588b4d977a8018d5039.jpg"},{"id":63803056,"identity":"a3b06451-136f-4ed7-8a55-1767cf96182d","added_by":"auto","created_at":"2024-09-02 13:21:57","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":225693,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMedical images show pulmonary infection, bone destruction, and brain abscess.\u003c/strong\u003e (a) Chest computed tomography (CT) showed a bilateral lung infection with severe destruction of pulmonary tissue in the left lung. Thickening of the left pleura, bilateral pleural effusion, and pericardial effusion were noted. (b) Multiple areas of bone destruction involving the sternum, ribs, vertebral bodies, and scapula were identified. (c) T2-weighted cephalic magnetic resonance imaging (MRI) revealed a round, high-signal density mass with surrounding edema, suggesting an abscess in the left frontal lobe. (d) T1-weighted cephalic 3D spoiled gradient-recalled echo sequence (SPGR) image showed a round-shaped, low-signal density mass in the exact site of the left frontal lobe.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4814788/v1/84148b3b01d3b3e2faa64cc8.jpg"},{"id":63804385,"identity":"5beb5112-1142-475b-86bf-afdfe82985a4","added_by":"auto","created_at":"2024-09-02 13:29:57","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1586085,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathology of subcutaneous abscess.\u003c/strong\u003e (a) The dermis of the lesions exhibited inflammation with infiltration of acute and chronic inflammatory cells. (HE, ×100) (b) Gomori's methenamine silver (GMS) staining revealed a few small-sized fungal spore-like structures (indicated by red arrows) in the affected area. (GMS, ×200)\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4814788/v1/ee1bca252ba598690695cfaa.jpg"},{"id":63803054,"identity":"d0a270eb-ca82-4f32-8708-91bc18549762","added_by":"auto","created_at":"2024-09-02 13:21:57","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":858680,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA culture of pus from a scalp abscess was positive for \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eTalaromyces marneffei\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e. \u003c/strong\u003e(a) Two colonies produced a red-wine-colored pigment that diffused into Sabouraud dextrose agar medium. (b) The reverse side of the colony.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4814788/v1/fa1be2413c46495b466434b0.jpg"},{"id":95040685,"identity":"ebe25ca3-b82f-4426-8eb8-20eab9cbc9a8","added_by":"auto","created_at":"2025-11-03 16:10:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4343705,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4814788/v1/db57f83e-0daf-4761-9a66-2eb6423d6e99.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Challenges in Diagnosing and Managing Disseminated Mycobacterium avium and Talaromyces marneffei Co-infection: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eNontuberculous mycobacteria (NTM) are increasingly recognized as critical opportunistic pathogens of humans, causing globally increasing opportunistic infections and mortality in immunocompromised populations and affecting otherwise healthy individuals. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] While the lungs are most affected, the lymphatic system, skin, heart, soft tissues, bones, and joints are also frequently involved. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Diagnosing and treating NTM is challenging due to its similarity in symptoms and histopathological characteristics with tuberculosis (TB), as well as resistance to many antibiotics. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] NTM are diverse and ubiquitous in the environment; however, only a few species pose severe threats by causing opportunistic infections in humans, such as \u003cem\u003eMycobacterium avium (M. avium)\u003c/em\u003e. \u003cem\u003eM. avium\u003c/em\u003e is an emerging opportunistic pathogen worldwide that often causes nontuberculous infections in immunocompromised individuals. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] \u003cem\u003eTalaromyces marneffei\u003c/em\u003e (\u003cem\u003eT. marneffei\u003c/em\u003e) is a pathogenic fungus causing talaromycosis, which has devastating impacts on persons with acquired immunodeficiency syndrome (AIDS) or other immunocompromised conditions. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] To our knowledge, only three HIV-negative cases of disseminated \u003cem\u003eM. avium\u003c/em\u003e and \u003cem\u003eT. marneffei\u003c/em\u003e co-infection had been reported. [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Unfortunately, prompt diagnosis of this co-infection was often missed, resulting in ineffective treatment and poor patient prognosis. Herein, we present a novel case of an HIV-negative Chinese woman who was initially misdiagnosed with TB and received ineffective anti-tuberculosis therapies (ATT) for three years. Subsequently, she developed pulmonary lesions along with bone lesions accompanied by subcutaneous abscesses and cerebral abscesses before ultimately being diagnosed with disseminated co-infection of \u003cem\u003eM. avium\u003c/em\u003e and \u003cem\u003eT. marneffei\u003c/em\u003e.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe patient, a 44-year-old Chinese woman, presented with chronic cough, sputum production, recurrent low-grade fevers, and chest pain. She had previously been diagnosed with secondary pulmonary tuberculosis, tuberculous pleuritis, sternal tuberculosis, and lymph node tuberculosis three years ago. A left upper lung lobe wedge resection and excision of chest wall masses were performed on her along with the administration of ATT, which proved to be ineffective. One month before she visited our institution, she sought medical attention at another hospital due to multiple subcutaneous abscesses on the head, trunk, and limbs. Cultures from an ulcer on her trunk revealed NTM infection, where \u003cem\u003eM. avium\u003c/em\u003e was identified through DNA microarray chip array testing. Consequently, she was diagnosed with disseminated \u003cem\u003eM. avium\u003c/em\u003e infection and treated using amikacin, moxifloxacin, clofazimine, clarithromycin, and linezolid. However, her condition did not improve after one month of treatment; instead, she gradually developed mental symptoms such as disorganized speech and hallucinations, leading to her subsequent evaluation and treatment at our hospital.\u003c/p\u003e \u003cp\u003eOn physical examination, the patient presented with pallor and cachexia. Subcutaneous abscesses and cutaneous ulcers accompanied by yellowish purulent discharge measuring 2 to 4 cm in diameter were observed on the head, chest, abdomen, and lower limbs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Laboratory investigations revealed leukocytosis (white blood cell [WBC]: 18.62\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, neutrophils ratio: 92%, lymphocytes ratio: 2.6%), anemia (hemoglobin [Hb]: 4.4 g/dL, red blood cell [RBC] count: 3.35\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L), hepatic and renal dysfunction (gamma-glutamyl transpeptidase [GGT]: 80 U/L, serum creatinine: 135 \u0026micro;mol/L), elevated erythrocyte sedimentation rate (ESR: 46 mm/h, normal range [NR]: 0\u0026ndash;20 mm/h), increased C-reactive-protein levels (CRP: 103 mg/L, NR: 0\u0026ndash;9 mg/L), elevated IgG levels (36.58 g/L, NR: 8.6-17.4g/L). The CD4\u0026thinsp;+\u0026thinsp;lymphocyte count was below average at 368/\u0026micro;L (NR: 414\u0026ndash;1440/\u0026micro;L). The anti-HIV test, TPPA (Treponema pallidum particle agglutination test), and TRUST (Tolulized red unheated serum test) were negative.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eChest computed tomography (CT) showed bilateral lung infection with enlarged lymph nodes in the bilateral supraclavicular, neck, axillary, and mediastinal regions. Additionally, thickening of the left pleura, bilateral pleural effusion, and pericardial effusion were observed. Multiple areas of bone destruction involving the sternum, numerous ribs, vertebral bodies, and scapula were also seen (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Cephalic magnetic resonance imaging (MRI) revealed scattered lesions on the head and cheeks, along with abnormal enhancement in the left frontal lobe, suggestive of infectious lesions and multiple abscesses (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistopathological examination of a skin abscess in the right upper abdomen revealed diffuse histiocytoid cells and lymphocytic and neutrophil infiltration in the dermis. A few small-sized fungal spore-like structures, which were positively stained with Gomori's methenamine silver (GMS), were identified in affected areas (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Subsequently, \u003cem\u003eT. marneffei\u003c/em\u003e was isolated by culturing the pus from a scalp abscess (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) and confirmed through polymerase chain reaction (PCR) sequencing. In addition, next-generation sequencing (NGS) of tissue from the left upper lobe confirmed that the initial pulmonary infection was caused by \u003cem\u003eM. avium\u003c/em\u003e.\u003c/p\u003e\u003cp\u003eThus, the patient was diagnosed with disseminated \u003cem\u003eM. avium\u003c/em\u003e and \u003cem\u003eT. marneffei\u003c/em\u003e co-infection. She received treatment consisting of oral itraconazole 0.2 g, twice daily, clarithromycin 0.5 g, twice daily, moxifloxacin 0.4 g once daily, ethambutol 0.625 g once daily, and doxycycline 0.1 g once daily. Subcutaneous abscesses were managed through incision, drainage, and local wound care. After two weeks of treatment, the patient became afebrile, and partial improvement was observed in cutaneous lesions. Her mental state was improved. Laboratory examination showed a slight recovery of leukocytosis (WBC: 15.44\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, neutrophil ratio: 90.4%). Liver and kidney function markers were improved (GGT: 39 U/L, serum creatinine: 103 \u0026micro;mol/L). The patient requested discharge for unknown reasons and was lost to follow-up.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThe Mycobacterium avium complex (MAC) is the most common type of NTM and comprises 12 species. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] \u003cem\u003eMycobacterium avium\u003c/em\u003e and \u003cem\u003eMycobacterium intracellulare\u003c/em\u003e represent the two original members of this complex. MAC infections and TB share similar clinical manifestations, including fever, night sweats, weight loss, cough, and expectoration. They also share similar histopathological characteristics, which both exhibit acid-fast positive bacilli, necrotizing granulomas, and multinucleated Langhans giant cells. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prognosis for MAC infection remains poorly characterized. A recent review reported a 5-year all-cause mortality exceeding 25% in patients with MAC pulmonary disease and higher risks of complications and death from disseminated MAC infections [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Although culture is the gold standard for diagnosing MAC infections, its utility is limited due to low positivity rates caused by slow growth of pathogenic NTM (typically taking two months) and varying culture temperatures required for different NTM species [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eT. marneffei\u003c/em\u003e is an emerging opportunistic pathogenic fungus often found in patients with AIDS or other immunodeficiency diseases. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] In rare cases, co-infection of NTM and \u003cem\u003eT. marneffei\u003c/em\u003e in HIV-negative patients can occur. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Due to the similarity in clinical manifestations, such as cough and skin lesions between NTM and \u003cem\u003eT. marneffei\u003c/em\u003e infections, the misdiagnosis rate for either pathogen can be as high as 77%, leading to a poor prognosis. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] A study indicates that co-infection of NTM and \u003cem\u003eT. marneffei\u003c/em\u003e exhibits higher levels of inflammatory markers, more severe inflammatory anemia, and involvement of more sites than infection with either pathogen alone. Elevated levels of anti-IFN-γ autoantibodies, WBCs, neutrophils, IgG, IgM, IgA, serum globulin, ESR, and CRP, and low CD4\u0026thinsp;+\u0026thinsp;T cell count are considered risk factors for \u003cem\u003eT. marneffei\u003c/em\u003e and NTM co-infection. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Unfortunately, we did not test for anti-IFN-γ autoantibodies. However, our patient exhibited increased levels of WBCs, IgG, ESR, and CRP and a low CD4\u003csup\u003e+\u003c/sup\u003eT cell count. Reviewing her medical records revealed a drop in hemoglobin from 5.4 g/dL to 4.4 g/dL, along with worsened symptoms when treated with anti-NTM medication. All these findings suggest inadequate disease control and the possibility of a co-infection.\u003c/p\u003e \u003cp\u003eMAC, particularly \u003cem\u003eM. avium\u003c/em\u003e, shows poor sensitivity to existing anti-TB drugs. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] A standard anti-MAC regimen involves a combination of macrolides, rifamycin, and ethambutol (guideline-based three-drug therapy, GBT therapy) for a minimum of 12 months following sputum conversion. Other recommended treatments include aminoglycosides, fluoroquinolones, and isoniazid. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Nevertheless, the rates of treatment failure and recurrence for \u003cem\u003eM. avium\u003c/em\u003e remain significantly high. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Amphotericin B and itraconazole are identified as the most effective drugs for treating \u003cem\u003eT. marneffei\u003c/em\u003e, with a treatment course of 3\u0026ndash;6 months. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Due to our patient's previous allergic reaction to rifampicin, she was treated as indicated above and exhibited a positive response after two weeks. Unfortunately, she was lost during the follow-up.\u003c/p\u003e \u003cp\u003eWe presented a rare case of disseminated \u003cem\u003eM. avium\u003c/em\u003e and \u003cem\u003eT. marneffei\u003c/em\u003e co-infection in an HIV-negative patient. The previous three cases of this co-infection typically presented with symptoms including fever, cough, chest pain, lymphadenopathy, and painful skin erythema. [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] In addition to most of these symptoms, our patient uniquely developed the rare complication of cutaneous and cerebral abscesses. The presented case has prompted several clinical reflections. Firstly, diagnosing \u003cem\u003eM. avium\u003c/em\u003e /NTM infections and TB is difficult because of the similar clinical manifestations and histopathological characteristics. Thus, genetic diagnostic methods such as DNA microarray or NGS are essential, especially when anti-TB treatment is ineffective. Second, vigilance is required for potential opportunistic pathogens co-infection even in HIV-negative patients, significantly when symptoms worsen, inflammatory markers escalate, anemia deteriorates, and anti-IFN-γ autoantibodies are detected. Furthermore, multiple histopathological examinations and pathogen cultures from various sites can be beneficial in clarifying the diagnosis.\u003c/p\u003e \u003cp\u003eIt is easy to misdiagnose and miss diagnose disseminated \u003cem\u003eM. avium\u003c/em\u003e and \u003cem\u003eT. marneffei\u003c/em\u003e co-infection in HIV-negative patients, leading to a poor prognosis. Therefore, it is imperative to employ timely genetic diagnostic methods, conduct multiple cultures and pathological examinations, and maintain a vigilant approach toward identifying co-infections.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNTM\u0026nbsp;Nontuberculous mycobacteria\u003c/p\u003e\n\u003cp\u003eTB Tuberculosis\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eM. avium Mycobacterium avium\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eT. marneffei Talaromyces marneffei\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAIDS Acquired immunodeficiency syndrome\u003c/p\u003e\n\u003cp\u003eATT Anti-tuberculosis therapies\u003c/p\u003e\n\u003cp\u003eWBC White blood cell\u003c/p\u003e\n\u003cp\u003eHb Hemoglobin\u003c/p\u003e\n\u003cp\u003eRBC Red blood cell\u003c/p\u003e\n\u003cp\u003eGGT Gamma-glutamyl transpeptidase\u003c/p\u003e\n\u003cp\u003eESR Erythrocyte sedimentation rate\u003c/p\u003e\n\u003cp\u003eNR Normal range\u003c/p\u003e\n\u003cp\u003eCRP C-reactive-protein\u003c/p\u003e\n\u003cp\u003eTPPA Treponema pallidum particle agglutination test\u003c/p\u003e\n\u003cp\u003eTRUST Tolulized red unheated serum test\u003c/p\u003e\n\u003cp\u003eCT Computed tomography\u003c/p\u003e\n\u003cp\u003eMRI Magnetic resonance imaging\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGMS Gomori\u0026apos;s methenamine silver\u003c/p\u003e\n\u003cp\u003ePCR Polymerase chain reaction\u003c/p\u003e\n\u003cp\u003eNGS Next-generation sequencing\u003c/p\u003e\n\u003cp\u003eMAC Mycobacterium avium\u003cem\u003e\u0026nbsp;\u003c/em\u003ecomplex\u003c/p\u003e\n\u003cp\u003eGBT therapy \u0026nbsp;Guideline-based three-drug therapy\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was conducted per the Declaration of Helsinki. It was approved by the Ethics Committee of the First Affiliated Hospital of Gannan Medical University\u0026nbsp;(No: LLSL-2023171).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth the patient and her father gave written and oral informed consent to publish the clinical details and images. The consent form was obtained from the hospital during the patient's inpatient stay.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHHW and YKZ conceived the study, participated in the patient's clinical management, reviewed the literature on the item, and drafted the manuscript. YL and CLW participated in the clinical management of the patient. QL, YHZ, and SL contributed to the diagnosis and gene chip detection. JFL made the correct diagnosis, participated in the patient's clinical management, conceived the study, reviewed the literature on the item, and drafted the manuscript. YKZ reviewed drafts of the paper. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely appreciate Prof. Di-qing Luo's invaluable assistance in processing the photographs.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDahl VN, M\u0026oslash;lhave M, Fl\u0026oslash;e A, van Ingen J, Sch\u0026ouml;n T, Lillebaek T, et al. 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[Advances in clinical characteristics of talaromycosis combined with other opportunistic infections]. \u003cem\u003eZhonghua Jie He He Hu \u003c/em\u003e\u003cem\u003eXi Za Zhi. \u003c/em\u003e2023; 46(5): 503-506. Chinese. doi: 10.3760/cma.j.cn112147-20220807-00659.\u003c/li\u003e\n\u003cli\u003eQiu Y, Tang M, Zeng W, Feng X, Pan M, Li W, et al. Clinical findings and predictive factors for positive anti-interferon-gamma autoantibodies in patients suffering from a nontuberculosis mycobacteria or Talaromyces marneffei infection: a multicenter prospective cohort study. \u003cem\u003eSci Rep. \u003c/em\u003e2022; 12(1): 9069. doi: 10.1038/s41598-022-13160-x.\u003c/li\u003e\n\u003cli\u003eWang PH, Shu CC, Chen CY, Wei YF, Cheng SL. The role of treatment regimen and duration in treating patients with Mycobacterium avium complex lung disease: A real-world experience and case-control study. \u003cem\u003eJ\u003c/em\u003e\u003cem\u003e Microbiol Immunol Infect. \u003c/em\u003e2024; 57(1): 164-174. doi: 10.1016/j.jmii.2023.11.006.\u003c/li\u003e\n\u003cli\u003eLe T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, et al. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. \u003cem\u003eN Engl J Med.\u003c/em\u003e 2017; 376(24): 2329-2340. doi: 10.1056/NEJMoa1613306.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Mycobacterium avium, Talaromyces marneffei, Co-infection, Tuberculosis, Diagnosis, Case report","lastPublishedDoi":"10.21203/rs.3.rs-4814788/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4814788/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e \u003cem\u003eMycobacterium avium\u003c/em\u003e (\u003cem\u003eM. avium\u003c/em\u003e) is emerging as an opportunistic pathogen and has been grouped with the nontuberculosis mycobacteria (NTM). Tuberculosis (TB), caused by \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e (Mtb), primarily affects elderly individuals with chronic lung disease and remains one of the leading causes of death in many regions worldwide. Distinguishing between NTM infection and drug-resistant TB is challenging due to similar manifestations and resistance to conventional anti-tuberculosis therapies (ATT). \u003cem\u003eTalaromyces marneffei\u003c/em\u003e (\u003cem\u003eT. marneffei\u003c/em\u003e) is a pathogenic fungus causing devastating infection, primarily in immunocompromised individuals. Few reports describe disseminated co-infection of \u003cem\u003eM. avium\u003c/em\u003e and \u003cem\u003eT. marneffei\u003c/em\u003e in HIV-uninfected persons.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eHerein, we present a case study of an HIV-negative Chinese woman who initially presented with chronic cough, sputum production, and recurrent low-grade fever, which was initially diagnosed as TB. After three years of anti-TB treatment, her situation progressed, and she developed multiple subcutaneous abscesses throughout the body, including the brain. Subsequent bacterial culture and genetic analysis confirmed the presence of NTM specifically identified as \u003cem\u003eM. avium\u003c/em\u003e. However, despite receiving anti-NTM treatment, it remained ineffective until co-infection with \u003cem\u003eT. marneffei\u003c/em\u003e was eventually diagnosed.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEarly utilization of genetic diagnostic methods is necessary to detect the possibility of NTM infections, especially when patients do not respond adequately to ATT. It is also crucial to remain vigilant for co-infections when the disease progresses despite ongoing anti-NTM treatment.\u003c/p\u003e","manuscriptTitle":"Challenges in Diagnosing and Managing Disseminated Mycobacterium avium and Talaromyces marneffei Co-infection: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-02 13:21:52","doi":"10.21203/rs.3.rs-4814788/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-11T10:49:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-03T23:29:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-24T19:04:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"257153952887658478892454921633285266020","date":"2025-07-20T23:25:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327236833569445783295214190925963252952","date":"2025-07-20T21:42:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59480647942757582892837573133839565471","date":"2025-07-17T11:01:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-27T10:00:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"67495751416971821053098577791574797568","date":"2024-08-22T07:56:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-22T07:51:55+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-29T11:59:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-29T06:46:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-29T06:45:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-07-28T02:03:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0eeff00e-e1ef-43ac-b679-7389b2f8be67","owner":[],"postedDate":"September 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:06:59+00:00","versionOfRecord":{"articleIdentity":"rs-4814788","link":"https://doi.org/10.1186/s12879-025-11895-2","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-10-31 15:57:53","publishedOnDateReadable":"October 31st, 2025"},"versionCreatedAt":"2024-09-02 13:21:52","video":"","vorDoi":"10.1186/s12879-025-11895-2","vorDoiUrl":"https://doi.org/10.1186/s12879-025-11895-2","workflowStages":[]},"version":"v1","identity":"rs-4814788","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4814788","identity":"rs-4814788","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}