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Background: Due to the similar clinical, lung imaging, and pathological characteristics, talaromycosis is most commonly misdiagnosed as tuberculosis. This study aimed to identify the characteristics of talaromycosis pleural effusion (TMPE) and to distinguish TMPE from tuberculosis pleural effusion (TPE).Methods: We enrolled 19 cases each of TMPE and TPE from Guangxi, China. Patients' clinical records, pleural effusion tests, biomarker test results, and receiver operating characteristic curves were analyzed.Results: In total, 39.8% (65/163) of patients exhibited serous effusion, of whom 61 were non-human immunodeficiency virus (HIV)-infected patients; 68.85% of the non-HIV-infected patients (42/61) had TMPE. Thoracentesis was performed only in 19 patients, all of whom were misdiagnosed with tuberculosis and received long-term anti-tuberculosis treatment. In four of these patients, interleukin (IL)-23, IL-27, and interferon-gamma (IFN-γ) measurements were not performed since pleural effusion samples could not be collected because the effusion had been drained prior to the study. In the remaining 15 patients, pleural effusion samples were collected. Talaromyces marneffei was isolated from the pleural effusion and pleural nodules. Most TMPEs were characterized by yellowish fluid, with marked elevation of protein content and nucleated cell counts. However, neutrophils were predominantly found in TMPEs, and lymphocytes were predominantly found in TPEs (both p < 0.05). Adenosine deaminase (ADA) and IFN-γ levels in TMPEs were significantly lower than those in TPEs (all p < 0.05) and provided similar accuracies for distinguishing TMPEs from TPEs. IL-23 concentration in TMPEs was significantly higher than that in TPEs (p < 0.05), and it provided similar accuracy for diagnosing TMPEs. IL-27 concentrations in TMPEs were significantly lower than those in TPEs (all p < 0.05) but was not useful for distinguishing TMPE from TPE.Conclusions: Talaromycosis can infringe on the pleural cavity via the translocation of T. marneffei into the pleural space. Nonetheless, this phenomenon is still commonly neglected by clinicians. TMPE is a yellowish fluid with exudative PEs and predominant neutrophils. Higher neutrophil counts and IL-23 may suggest talaromycosis. Higher lymphocyte counts, ADA activity, and IFN-γ concentration may suggest tuberculosis. [ABSTRACT FROM AUTHOR]

Background: In recent years, talaromycosis is reportedly on the rise in human immunodeficiency virus (HIV)-uninfected patients. However, the misdiagnosis and mistreatment of talaromycosis is more likely in HIV-uninfected patients than in HIV-infected patients because talaromycosis can be easily mistaken for tuberculosis or any other opportunistic infection. Therefore, we used metagenomic next-generation sequencing (mNGS), a novel gene detection method, for the diagnosis of talaromycosis in HIV-uninfected patients.Case Presentation: We report five cases diagnosed as talaromycosis by mNGS in HIV-uninfected patients, which were further confirmed by tissue culture. There were 3 male and 2 female patients. Two patients had a history of rat contact. The misdiagnosis duration ranged from 88 to 245 days. While the results of tissue culture changed from repeated negative to positive, the mNGS result for Talaromyces marneffei was positive earlier in 4 patients. The reads of Talaromyces marneffei in mNGS ranged from 5 to 414. After antifungal therapy, one of the outcomes was death due to the longest duration of misdiagnosis, and the other outcomes were clinical improvement.Conclusions: mNGS is perhaps a rapid and effective diagnosis approach for the early confirmation of talaromycosis. Antifungal therapy is recommended once Talaromyces marneffei was revealed by mNGS. mNGS might reduce misdiagnosis duration and improve prognosis. Through these findings, we hope to provide some reference for talaromycosis in HIV-uninfected patients diagnosed early with the help of mNGS. [ABSTRACT FROM AUTHOR]

Background: Talaromyces marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation.Case Presentation: We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents' revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D).Conclusions: In T. marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections. [ABSTRACT FROM AUTHOR]

Background: High-titer anti-interferon (IFN)-γ autoantibodies are strongly associated with intracellular pathogens such as nontuberculous mycobacteria and Talaromyces marneffei, but they are not as commonly associated with Talaromyces marneffei co-infected with Mycobacterium tuberculosis.Case Presentation: Herein, we report a case of an HIV-negative Chinese man with a severe, disseminated co-infection of Talaromyces marneffei and Mycobacterium tuberculosis, who had a high-titer of anti IFN-γ autoantibodies and a CFI heterozygous nonsense gene mutation. The patient rapidly developed sepsis and died. Through by flow cytometry for CD4+ T cells' intracellular phosphorylated STAT-1 and Th1 cells (CD4+ IFN-γ+ cells), we found that the patient's serum can inhibited IFN γ-induced CD4+ T cells' STAT-1 phosphorylation and Th1 cell differentiation in normal peripheral blood mononuclear cells, but this phenomenon was not observed in normal control's serum. In addition, the higher serum concentration in the culture medium, the more obvious inhibition of Th1 cell differentiation.Conclusions: For HIV-negative individuals with relapsing, refractory, fatal double or multiple intracellular pathogen infections, especially Talaromyces marneffei, clinicians should be aware that if they might be dealing with adult-onset immunodeficiency syndrome due to high-titer anti-IFN-γ autoantibodies. Systematic genetic and immunological investigations should also be performed. [ABSTRACT FROM AUTHOR]

Background: Talaromyces marneffei (TM) primarily infects patients with co-morbidities that cause immunodeficiency, but non-secretory myeloma (NSMM) is rare. TSM and NSMM are associated with fever, osteolysis, and swollen lymph nodes, thereby making it difficult for clinicians to make differential diagnosis. In this case, we describe TM infection coexisting with NSMM.Case Presentation: We retrospectively reviewed the case of a male (without human immunodeficiency virus infection) with fever, thoracalgia, swollen lymph nodes, and subcutaneous nodules who presented to the First Affiliated Hospital of Guangxi Medical University in February 2014. Chest computed tomography revealed patchy infiltration and positron emission tomography/computed tomography showed increased metabolic activity in the lower-right lung, lymph nodes, left ninth rib, and right ilium. Pathological examination of the lung, lymph nodes, subcutaneous nodules, and bone marrow showed no malignancy, he was diagnosed with community-acquired pneumonia. His clinical symptoms did not improve after anti-bacterial, anti-Mycobacterium tuberculosis, and anti-non-M. tuberculosis treatment. Later, etiological culture and pathological examination of the subcutaneous nodule proved TM infection, and the patient was re-diagnosed with disseminated TSM, which involved the lungs, lymph nodes, skin, bone, and subcutaneous tissue. After antifungal treatment, the patient showed significant improvement, except for the pain in his bones. Imaging showed aggravated osteolysis, and bone marrow biopsy and immunohistochemistry indicated NSMM. Thus, we conclusively diagnosed the case as NSMM with TSM (involving the lungs, lymph nodes, skin, and subcutaneous tissue). His condition improved after chemotherapy, and he was symptom-free for 7 years.Conclusion: TM infection is rare in individual with NSMM. Since they have clinical manifestation in common, easily causing misdiagnosis and missed diagnosis, multiple pathological examinations and tissue cultures are essential to provide a differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.Methods: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.Results: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy.Conclusion: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions. [ABSTRACT FROM AUTHOR]

Background: Talaromyces marneffei is an invasive, and thermal dimorphic pathogenic fungus, whose infection is life threatening in human. Although immunocompromised patients, such as patients with human immunodeficiency virus infection and recipients of organ transplant, are susceptible hosts, infections have been recently reported in people with normal immune function. Patients with cancer may also be susceptible hosts but no case of T. marneffei infection has been reported in patients with lung cancer. In this case, we describe T. marneffei infection coexisting with primary pulmonary lymphoepithelioma-like carcinoma (LELC) in an HIV-negative patient.Case Presentation: A 50-year-old, previously healthy female presented with a 1-month history of cough and fever. CT scans showed a mass in the left lower lung, left pleural thickening, pleural effusion, and multiple swollen lymph nodes throughout the body. Based on the pathology of the left lung lesion, she was diagnosed with left primary pulmonary LELC complicated with T. marneffei. She received both anti-tumor and anti-fungal treatments. A subsequent CT re-examination demonstrated that the mass was absorbed remarkably after treatment. Follow up showed no tumor progression and no relapse of T. marneffei infection.Conclusion: This case suggested that clinicians should pay more attention to the potential hosts of T. marneffei infection, especially those with lung cancer. Early diagnosis and treatment can improve the prognosis of T. marneffei infection coexisting with lung cancer. [ABSTRACT FROM AUTHOR]