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The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

Histoplasmosis, an invasive fungal infection endemic in the Americas, Africa, and Asia, with a few cases reported among immigrants to Europe, was classified as an AIDS-defining disease in 1987 (1,2). [...]

Objectives Methods Results Conclusions To evaluate the performance of Xpert MTB/RIF Ultra testing in urine samples as part of a TB screening strategy in patients with advanced HIV disease (AHD).We conducted a multicentre prospective cohort study across three HIV reference hospitals in Brazil, between January and December 2023. The study included adult hospitalized patients with AHD, defined by a CD4 count of <200 cells/μL in the last 3 months or clinical presentation suggestive of opportunistic infection, without effective antiretroviral treatment. Participants underwent systematic tuberculosis (TB) screening using urine Xpert MTB/RIF Ultra and TB lipoarabinomannan (TB‐LAM) tests. The diagnosis performance of urine Xpert MTB/RIF Ultra was assessed including sensitivity, specificity, and positive and negative predictive values. Disease characterization was based on the Global Tuberculosis Dictionary. Survival at 30 and 90 days was also evaluated.Urine molecular testing was performed on 133 patients. Xpert MTB/RIF Ultra showed a sensitivity of 20.7% in bacteriologically confirmed TB cases and 21.2% in cases that included both clinically diagnosed and bacteriologically confirmed TB. The addition of urine Xpert MTB/RIF Ultra to TB‐LAM led to the detection of three additional cases, representing a 6.3% increase from the 48 cases detected by TB‐LAM. Xpert MTB/RIF Ultra had a specificity of 96.9% and no rifampicine resistance mutations were detected. Overall mortality was 16/133 (12.0%) at 30 days and 25/127 (19.7%) at 90 days.There was a high overlap between urine TB‐LAM and Xpert MTB/RIF Ultra results, with the addition of Xpert MTB/RIF providing limited additional benefit for TB screening in patients with AHD. [ABSTRACT FROM AUTHOR]

The rapid diagnosis of opportunistic infections (OIs) is critical for improving the health outcomes of people living with HIV/AIDS (PLWHA). This study aimed to describe the feasibility of implementing a package for the rapid diagnosis of tuberculosis, histoplasmosis, and cryptococcosis in patients with advanced HIV/AIDS disease in Porto Alegre, Brazil. The research involved two focus groups with health professionals, four in-depth interviews with healthcare managers, and twelve interviews with PLWHA. The corpus was analyzed using Descending Hierarchical Classification (DHC). The study found that the rapid test diagnosis intervention was generally well-received by patients and health professionals, improving diagnosis and treatment outcomes. However, it also identified several areas for improvement, including the need for expanded psychosocial support and enhanced coordination between health services. The findings have important implications for the development and implementation of policies and programs aimed at enhancing the diagnosis and treatment of OIs among PLWHA with advanced diseases. Further research should explore social determinants of HIV/AIDS mortality to offer valuable insights into improving prevention and treatment strategies. By prioritizing patient-centered care and improving coordination between health services, policymakers and health professionals can improve the health outcomes of PLWHA with advanced disease in Porto Alegre and other similar settings. [ABSTRACT FROM AUTHOR]

Background Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. Methods Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. Results A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P =.69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P =.82). Conclusions One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access. [ABSTRACT FROM AUTHOR]

Background Evidence for efficacy of single, high-dose liposomal amphotericin B (LAmB) in HIV-associated cryptococcal meningitis and histoplasmosis is growing. No systematic review has examined the safety of this regimen across multiple studies. Methods We systematically searched Medline, Scopus, and the Cochrane Library from inception to April 2023 for studies reporting grade 3 and 4 adverse events (AEs) with single high-dose LAmB vs traditional amphotericin regimens for HIV-associated fungal infections. Results Three trials (n = 946) were included. Compared with traditional regimens, single high-dose LAmB was associated with equivalent risk of grade 3 and 4 AEs (risk ratio [RR], 0.75; 95% CI, 0.53–1.06) and lower overall risk of grade 4 AEs (RR, 0.68; 95% CI, 0.55–0.86), grade 4 renal (RR, 0.43; 95% CI, 0.20–0.94) and grade 4 hematological AEs (RR, 0.46; 95% CI, 0.32–0.65). Conclusions Single, high-dose LAmB is associated with a lower risk of life-threatening AEs compared with other World Health Organization–endorsed amphotericin B–based regimens in invasive HIV–related fungal infection. [ABSTRACT FROM AUTHOR]