Serum sphingolipids aid in diagnosing adult HIV-negative patients with pulmonary cryptococcosis: a clinical cohort study.

Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.

Clinical characteristics of tracheobronchial Talaromyces marneffei infection in non-HIV-infected patients in South China.

OBJECTIVES: Tracheobronchial Talaromyces marneffei (T. marneffei) infections among non-HIV-infected patients are rare. To improve understanding, we analysed the clinical features, immune mechanisms, treatment, and prognosis. METHODS: Data on hospitalized patients with tracheobronchial T. marneffei infections from September 2013 to May 2022 were collected. The clinical and imaging features were analysed. RESULTS: Nineteen patients were enrolled, with a median age of 52 years (45-62 years). The most common symptoms were cough, expectoration, fever, weight loss, and anaemia. The total white blood cell and neutrophil counts, erythrocyte sedimentation rate, C-reactive protein, procalcitonin and globulin were increased, and the serum albumin levels were decreased. Chest CT manifestations included patchy shadows, masses, obstructive atelectasis, cavities, pleural effusion, and hilar and mediastinal lymphadenopathy. The fibreoptic bronchoscopy findings included masses, polyps or nodules with mucosal oedema, hypertrophic bulges, lumen stenosis or obstruction, and purulent secretions. T. marneffei infection was confirmed in 10 patients by positive culture, in five by both culture and metagenomic next-generation sequencing (mNGS), in two by mNGS, in one by culture and pathology and in 1 by histopathology. BALF (15/19, 78.9%) had the highest culture positive rate, followed by sputum (3/19), bronchial mucosa (1/1), lung biopsy (1/2); 36.8% of the patients were coinfected with other pathogens. For induction therapy, 7, 6, 2, and 4 patients received voriconazole, amphotericin B, voriconazole combined with amphotericin B, and fluconazole therapy, respectively, and 26.3% received treatment combined with nebulization and/or administration of amphotericin B under fibreoptic bronchoscopy. Four patients were treated for underlying diseases or coinfection, 31.6% were cured, 42.1% improved, and 26.3% died. CONCLUSIONS: T. marneffei infection is common in the tracheobronchial airway tissue or secretions, and bronchoscopy has important diagnostic and treatment value. Antifungal therapy, including systemic therapy, involves triazoles and amphotericin administration, and aerosol inhalation and administration of amphotericin B under bronchoscopy are important.

T. marneffei infection involving the tracheobronchial region in airway tissue or secretions is high, and bronchoscopy has important value in diagnosing and treating these patientsThe use of triazoles and amphotericin and the aerosol inhalation and instillation of amphotericin B under bronchoscopy are essential to antifungal therapy.

Comparison of the clinical features of HIV-positive and HIV-negative hosts infected with Talaromyces marneffei: A multicenter, retrospective study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical features of rare disseminated Mycobacterium colombiense infection in nine patients who are HIV-negative in Guangxi, China.

OBJECTIVES: Localized or disseminated infection caused by different nontuberculous mycobacteria (NTM) species has been increasingly reported in recent years, but reports of Mycobacterium colombiense infection are extremely rare. Herein, we analyzed the clinical features of patients with disseminated M. colombiense infection. METHODS: Patients diagnosed with disseminated M. colombiense infection between February 4, 2016 and August 25, 2021 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. RESULTS: NTM infection was diagnosed in 248 HIV-negative patients. Of these, nine patients with disseminated M. colombiense infection were enrolled. Five of these patients were positive for anti-interferon-γ autoantibodies. The lung, lymph nodes, bones, and joints were the most commonly involved organs. Anemia, fever, lymphadenopathy, cough and expectoration, and ostealgia were the most common symptoms. The levels of white blood cells and neutrophils were increased in eight patients. M. colombiense was detected by both metagenomic next-generation sequencing (mNGS) and culture in four patients and only by mNGS in the remaining five patients. All patients received combination anti-NTM therapy; five underwent surgery. The condition of eight patients improved, and one died during the treatment. CONCLUSION: Patients infected with M. colombiense can present as disseminated infections, easily involving multiple organs, such as the lung, lymph nodes, bone, and joints, with fever, lymphadenopathy, and increased white blood cell and neutrophil counts. mNGS plays a crucial role in the early diagnosis of M. colombiense infection. Once diagnosed, timely and effective anti-NTM therapy, combined with local surgery if necessary, can improve the prognosis of patients with this condition.

Pathogen spectrum and immunotherapy in patients with anti-IFN-γ autoantibodies: A multicenter retrospective study and systematic review.

Background: Anti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data. Methods: This systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity. Results: We included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%). Conclusions: Intracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, Talaromyces marneffei, and Salmonella spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases.

Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated Talaromyces marneffei Infection.

High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1-3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203-89 605) ng/mL at diagnosis, 48 189.4 (15 537-83 375) ng/mL before IVCY therapy, and 10 721.2 (5637-13 245) ng/mL at the end of IVCY therapy (P < .05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896-45 626) ng/mL, and to 37 464.2 (19 872-58 321) ng/mL at 24 months (P < .05). Five patients discontinued antimicrobial therapy within 3-12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers.