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• Inflammatory markers are indicators of co-infections. • Age is an important predisposing factor for Talaromyces marneffei infection in patients who are HIV-negative. • Persistent infection is more likely to occur in patients with Talaromyces marneffei infection who are HIV-negative. • Mycobacterium tuberculosis is the most common co-infection in HIV-negative hosts. Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians. We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022. A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative. TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative. [ABSTRACT FROM AUTHOR]

Background: Anti-IFN-γ autoantibodies (AIGAs) are closely related to the disseminated infection of multiple pathogens. Mycobacterium phlei (M. phlei) is a nonpathogenic nontuberculous mycobacteria (NTM), and M. phlei infection of the bone is extremely rare. We report a rare case of high-titer AIGAs presenting with Sweet's syndrome (SS) accompanied by opportunistic coinfection with multiple pathogens during 12 years of follow-up. The patient in this case also developed disseminated M. phlei infection with osteolytic destruction after treatment for SS. Case Presentation: A 68-year-old Chinese woman was admitted to our hospital in August 2009 due to fever and cough with expectoration for 3 months. The patient was successively infected with Klebsiella pneumoniae, herpes zoster virus and Candida. Chest computed tomography (CT) showed recurrent consolidations in different lung fields. After 15 months of antimicrobial treatment, the patient experienced partial recovery. In September 2010, the patient was pathologically diagnosed with SS due to the presence of multiple rashes. After prednisone and thalidomide treatment, the rashes subsided, and the pulmonary lesions had completely absorbed. In May 2011, the patient was diagnosed with disseminated tuberculosis and was administered anti-tuberculosis therapy for 3 months without improvement. NTM was subsequently cultured from her sputum and chest wall pus, and she improved after 20 months of anti-NTM therapy. In March 2016, the patient developed osteolytic destruction of the C7-T2 vertebral bodies with a back abscess. NTM was eventually cultured from the dorsal abscess pus and further identified as M. phlei. High-titer AIGAs were detected in the patient's serum. After another round of aggressive anti-NTM therapy, the patient was finally cured. Conclusion: Patients with AIGA-associated anti-cytokine autoantibody disease can present with multiple opportunistic infections and SS involving the lung. AIGA-associated immunodeficiency leads to infection with nonpathogenic M. phlei, which is refractory, can cause relapse, and even leads to osteolytic destruction. [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]

To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) co-infections in HIV-negative patients. A multicenter retrospective study in 13 hospitals, and a systematic literature review were performed of original articles published in English related to TM/NTM co-infections. HIV-negative patients with TM and NTM co-infections comprised Group 1; TM-only infection Group 2; NTM-only infection Group 3; and healthy volunteers Group 4. Univariate logistic analysis was used to estimate the potential risk factors of TM/NTM co-infections. A total of 22 cases of TM and NTM co-infections were enrolled. Of these, 17 patients (77.3%) had a missed diagnosis of one of the TM or NTM pathogens. The anti-IFN-γ autoantibodies (AIGAs) titer, white blood cell (WBC), neutrophil counts (N), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), globulin, and immunoglobulin G (IgG) levels of Group 1 were higher than those of the other groups, whereas the levels of CD4+T cells was lower than those of other groups. There was a significant negative correlation between the AIGA titers and the number of CD4+T cells (P < 0.05). Factors including the ratio of the actual values to the cut-off values of AIGAs, WBC, N, HGB, CD4+T cells, IgG, IgM, IgA, serum globulin, ESR, and CRP were taken as potential risk factors for TM and NTM co-infection. Most patients with TM and NTM co-infection had a missed diagnosis of one of the TM or NTM pathogens. The levels of AIGAs, WBC, N, ESR, and CRP in TM and NTM co-infections were remarkably higher than in mono-infection. High-titer AIGAs may be a potential risk factor and susceptibility factor for co-infection of TM and NTM in HIV-negative hosts. [ABSTRACT FROM AUTHOR]

A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces marneffei and Burkholderia cepacia infection. The patient's lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections. [ABSTRACT FROM AUTHOR]