Search

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: 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: 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: 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]

Background: Papillomaviruses (PVs) and polyomaviruses (PyVs) infect diverse vertebrates including human and cause a broad spectrum of outcomes from asymptomatic infection to severe disease. There has been no PV and only one PyV detected in tree shrews, though the genomic properties of tree shrews are highly similar to those of the primates. Methods: Swab and organ samples of tree shrews collected in the Yunnan Province of China, were tested by viral metagenomic analysis and random PCR to detect the presence of PVs and PyVs. By PCR amplification using specific primers, cloning, sequencing and assembling, genomes of two PVs and one PyV were identified in the samples. Results: Two novel PVs and a novel PyV, named tree shrew papillomavirus 1 and 2 (TbelPV1 and TbelPV2) and polyomavirus 1 (TbelPyV1) were characterized in the Chinese tree shrew (Tupaia belangeri chinensis). The genomes of TbelPV1, TbelPV2, and TbelPyV1 are 7410 bp, 7526 bp, and 4982 bp in size, respectively. The TbelPV1 genome contains 7 putative open-reading frames (ORFs) coding for viral proteins E1, E2, E4, E6, E7, L1, and L2; the TbelPV2 genome contains 6 ORFs coding for viral proteins E1, E2, E6, E7, L1, and L2; and the TbelPyV1 genome codes for the typical small and large T antigens of PyV, as well as the VP1, VP2, and VP3 capsid proteins. Genomic comparison and phylogenetic analysis indicated that TbelPV1 and TbelPV2 represented 2 novel PV genera of Papillomaviridae, and TbelPyV1 represented a new species of genus Alphapolyomavirus. Our epidemiologic study indicated that TbelPV1 and TbelPV2 were both detected in oral swabs, while TbelPyV1 was detected in oral swabs and spleens. Conclusion: Two novel PVs (TbelPV1 and TbelPV2) and a novel PyV (TbelPyV) were discovered in tree shrews and their genomes were characterized. TbelPV1, TbelPV2, and TbelPyV1 have the highest similarity to Human papillomavirus type 63, Ursus maritimus papillomavirus 1, and Human polyomavirus 9, respectively. TbelPV1 and TbelPV2 only showed oral tropism, while TbelPyV1 showed oral and spleen tropism. [ABSTRACT FROM AUTHOR]

Background/Objective: With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. Methods: A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. Result: The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). Conclusion: Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection. [ABSTRACT FROM AUTHOR]

Background: The incidence of Penicillium marneffei infection has recently increased. This fungus can cause fatal systemic mycosis in both immunocompetent and immunocompromised patients without HIV infection.Methods: We retrospectively analysed Penicilliosis patients between January 1, 2003 and August 1, 2014 at the First Affiliated Hospital of Guangxi Medical University. HIV-negative patients with Penicilliosis were divided into two groups: patients with underlying disease (Group D) and patients without underlying disease (Group ND). HIV-positive patients were excluded. The relationships between overall survival and the study variables were assessed using univariate and multivariate analyses.Results: During 11 years, Penicillium marneffei infection was diagnosed in 109 patients. Sixty-six (60.55 %) patients were HIV-positive and excluded from these cases. Forty-three patients were HIV-negative were enrolled. Among these patients, 18 (41.86 %) patients were in Group D, and 25 (58.14 %) were in Group ND. The most common underlying disease was diabetes. There were no statistically significant differences between the two groups in clinical characteristics, except for immune state and prognosis. Group ND had higher lymphocyte cell counts, CD4 cell counts, and CD4 T-cell percentages than Group D (P < 0.05). Patients in Group D had higher recurrence and mortality rates than Group ND (P < 0.05). In the univariate analysis, only underlying disease, CD4 cell percentage, and T lymphocyte cell percentage were significantly associated with overall survival.Conclusions: Penicillium marneffei can infect HIV-negative patients and can cause fatal systemic mycosis. There were no clear differences in clinical manifestations among HIV-negative patients with and without underlying disease. However, Penicillium marneffei in HIV-negative patients in with underlying diseases may cause immune function decline and a deficiency in T-cell-mediated immunity. Underlying disease, CD4 cell percentage, and T lymphocyte cell percentage may be potential risk factors affecting prognosis. Timely, effective, and longer courses of antifungal treatments are important in improving prognoses. [ABSTRACT FROM AUTHOR]

Background: Penicillium marneffei is the only dimorphic member of the genus and is an emerging pathogenic fungus that can cause fatal systemic mycosis. Penicillium marneffei disseminates hematogenously to other locations. Penicillium marneffei infection most commonly involves the skin, lungs, and reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes, pericardium, liver, and spleen. Involvement of the mesenteric and central nervous systems has also been reported. Infection involving the trachea has not been previously reported.Case Presentation: We herein report a previously healthy 28-year-old male farmer from Guangxi Province without HIV who became infected with P. marneffei. The infection primarily affected the trachea, resulting in structural damage to the cartilage, tracheal stenosis, and tracheal absence. The infection also involved the lungs and lymph nodes. After antifungal treatment and surgery, his symptoms, signs, and lung imaging findings showed significant improvement. This is the first such case report.Conclusion: Penicillium marneffei infection in normal hosts is characterized by an insidious onset, various clinical manifestations, and common misdiagnosis, leading to high mortality rates. Penicillium marneffei hematogenously disseminates throughout the whole body. This is the first reported case of P. marneffei infection involving the main trachea with subsequent structural damage to the tracheal cartilage, severe tracheostenosis, and tracheal absence. [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: Viruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. Results: We present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28–34%, genus level). PHP also outperformed these two alignment-free methods much (24–38% vs 18–20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. Conclusions: The Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies. [ABSTRACT FROM AUTHOR]