Histoplasmosis remains a neglected yet deadly fungal infection, disproportionately affecting persons living with HIV/ AIDS and other immunocompromised populations in endemic regions. Despite the World Health Organization's designation of Histoplasma as a high-priority pathogen, the disease remains underdiagnosed and excluded from national surveillance systems, resulting in delayed treatment and high death rates. To coordinate a global response, the International Society for Human and Animal Mycology convened a Histoplasmosis Working Group during its 2025 congress in Brazil. Experts engaged in structured discussions across 5 domains: awareness, research, diagnostics and treatment, capacity building, and fungal biology. The group highlighted persistent diagnostic delays, underuse of antigen testing, and poor access to liposomal amphotericin B and itraconazole. Innovations such as lateral flow assays and molecular tools were discussed, alongside the need for biobanks and validated diagnostic algorithms. A global 90-90-90 target for histoplasmosis by 2030 was proposed to improve diagnosis, treatment, and survival.

INTRODUCTION:Advanced HIV disease (AHD) remains a leading cause of mortality in Latin America and the Caribbean (LAC), driven by late diagnosis, treatment gaps and structural barriers, particularly among key populations and children. Persistent disparities in healthcare access, stigma, and limited health system capacity highlight the need for targeted research to improve AHD outcomes in the region. METHODS:The modified Delphi process to prioritize AHD research questions in LAC was conducted between August and November 2024. Systematic reviews, expert consultations and two Delphi rounds involving 74 and 69 participants from 17 LAC countries assessed questions based on public health relevance, feasibility and equity. A subsequent in-person workshop with 24 experts refined and validated the results, organizing the prioritized questions into short-, medium- and long-term priorities. RESULTS:Seventy-seven high-priority research questions were identified, 60 focused on adults and 17 on children. These questions centred on opportunistic infections (OIs), HIV-related cancers and health system interventions. Tuberculosis was the most frequently addressed OI (44% of OI-related questions), followed by cryptococcosis, histoplasmosis and HIV-related malignancies. Short-term priorities included interventions to reduce late diagnosis, improve retention in care and strengthen health systems, particularly for vulnerable populations such as children, pregnant women and incarcerated individuals. CONCLUSIONS:This study presents a comprehensive research agenda for AHD in LAC, emphasizing interventions to address OIs, strengthen the health system and support at-risk populations. The prioritized questions provide a roadmap for researchers, policymakers and funders to allocate resources effectively, ultimately improving AHD outcomes and reducing HIV-related mortality. Strengthening regional collaboration and political commitment will be critical to translating research into actionable policies and interventions.

Introduction Data on cytomegalovirus (CMV) neurological disease in people living with HIV (PLHIV) are scarce in Brazil. This study aimed to describe the main clinical, laboratory, and outcome characteristics of PLHIV with CMV neurological disease. Methods Observational case series conducted in a tertiary hospital in São Paulo over 28 months. Inclusion criteria: (i) HIV-1 infection; (ii) presence of encephalitis, ventriculoencephalitis, and/or myeloradiculopathy; and (iii) detection of CMV DNA in cerebrospinal fluid by PCR. Descriptive statistics were performed. Results Twenty-six patients were included, 22 (85%) male, median age (IQR) 40 (35–47) years. Fourteen (54%) had been diagnosed with HIV-1 infection ≤ 6 months prior, and 11 (42%) were on ART at admission. Median (IQR) CD4+ count and HIV-1 viral load were 39 (19–53) cells/µL and 712,417 (165,528–2,032,500) copies/mL, respectively. Twenty (77%) patients presented at least one concomitant opportunistic infection (OI), and 13 (50%) had two or more, most commonly cerebral toxoplasmosis (50%, n =13). Encephalitis was the predominant presentation (77%, n = 20), followed by myeloradiculopathy (23%, n = 6) and ventriculoencephalitis (19%, n = 5). Thirteen (50%) had extra-neurological CMV disease, most commonly gastrointestinal involvement (27%, n = 7). Median (IQR) plasma CMV viral load (n = 20) was 65,382 (42,331–189,149) copies/mL. Median (IQR) time from admission to initiation of antiviral therapy (ganciclovir and/or foscarnet) and ART were 10 (3–20) and 14 (9–23) days, respectively. Median hospital stay was 53 (34–66) days. In-hospital and 90-day post-discharge mortality were 46% (n = 12) and 54% (n = 14), respectively. Conclusions Patients with CMV neurological disease presented severe immunosuppression; encephalitis was the most frequent presentation, and concomitant OIs were common. Extra-neurological CMV disease was identified in 50% of cases, and plasma CMV viral load was markedly elevated. Hospitalization was prolonged, and mortality was high.

Disseminated histoplasmosis remains a major cause of morbidity and mortality among people living with advanced HIV disease (AHD), particularly in Latin America, where delayed diagnosis and limited access to optimal antifungal therapy persist. Accurate tools to assess disease severity and predict mortality are essential to guide clinical decision-making, including hospitalization, intensive care unit admission, and treatment strategies. We conducted a retrospective observational cohort study of hospitalized adults with AHD (CD4 ≤ 200 cells/mm³) and a first episode of probable or proven disseminated histoplasmosis at a tertiary referral center in São Paulo, Brazil, between 2013 and 2023. Disease severity at admission was assessed using four tools: the World Health Organization (WHO) severity classification, the Histoplasmosis Fatality Score (HFS), the Sequential Organ Failure Assessment (SOFA), and the quick SOFA (qSOFA). The primary outcome was in-hospital mortality. Eighty-nine individuals were included; most were male (77.5%), with a median age of 39 years and profound immunosuppression (median CD4 count 24 cells/mm³). In-hospital mortality was 34.8%. Individuals who died had significantly higher HFS and SOFA scores. In multivariable analysis, HFS, SOFA score, and serum creatinine were independently associated with in-hospital mortality, whereas qSOFA was not. HFS showed the best discriminatory performance (AUC 0.798; 95% CI 0.707-0.889). The combination of HFS and elevated creatinine further improved discrimination (AUC 0.840; 95% CI 0.758-0.922), outperforming the WHO classification, SOFA, and qSOFA in predicting in-hospital mortality. These findings support the use of HFS as a practical and reliable tool for stratifying disease severity, optimizing resource allocation, and guiding clinical decision-making in high-burden settings.

This study investigates cerebrospinal fluid (CSF) biomarkers associated with HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH) in Brazil. Among 79 HIV-positive participants and 7 negative controls, elevated levels of inflammatory cytokines and soluble CD14 (sCD14) were found. The sCD14 showed promise as a diagnostic marker, and combined with other proinflammatory markers, may improve early detection and monitoring of HAND.

Neurological manifestations associated with COVID-19 remain partially described, mainly in low- and middle-income countries where diagnostic tools are limited. To address this, we assembled medical centers in Brazil with the goal of describing neurological syndromes associated with COVID-19 during the first wave of the pandemic. From June 1st, 2020 to June 1st, 2021, non-consecutive adult patients with new onset of six neurological syndromes up to 60 days after confirmed COVID-19 were included. Data were compiled from four tertiary centers and compared with general local COVID-19 data, as well as with a previous cohort focused on vascular syndrome. 197 patients were included, presenting with vascular syndromes (81), encephalopathy (68), encephalitis (19), Guillain-Barré syndrome (13), other neuropathies (12), and myelitis (4). The incidence curve of neurocovid mirrored that of COVID-19. Neurological syndromes were present regardless of COVID-19 severity. The median time from COVID-19 to onset of neurological symptoms was 14 days, suggesting a post-infectious immune-mediated mechanism. Patients were 10 times more likely to die (χ2 (1) = 356.55, p < 0.01, OR = 10.89) and 38 times more likely to be hospitalized than other COVID-19 patients (χ2 (1) = 1167.9, p < 0.01, OR = 38.22). Those developing vascular syndromes patients were 3 times more likely to require ICU (χ2 (1) = 37.12, p < 0.01, OR = 3.78) and 4 times more likely to die (χ2 (1) = 58.808, p < 0.01, OR = 4.73) than patients with vascular syndromes due to different etiologies. Our study corroborates the association of neurological syndromes with COVID-19. The incidence correlated with local waves of COVID-19, and patients with neurocovid exhibited a higher susceptibility to adverse outcomes compared to other COVID-19 patients. Among all neurological syndromes, vascular syndromes were the most common, and their severity surpassed that of vascular syndromes not attributed to COVID-19.

BACKGROUND:Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES:Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS:This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS:The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. CONCLUSIONS:We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

Chagas’ disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas’ disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.

Introdução Doença citomegálica neurológica continua causando elevada morbidade e mortalidade em pessoas com aids avançada. Atualmente não existe consenso sobre o uso de pontos de corte de carga viral plasmática do citomegalovírus (CMV), no diagnóstico das complicações neurológicas causadas por esse vírus na aids avançada. Objetivo Avaliar o desempenho da carga viral plasmática do CMV no diagnóstico de doença neurológica citomegálica em pessoas com aids avançada. Método Estudo observacional, de coorte e retrospectivo, realizado em centro terciário de São Paulo, Brasil. Foram incluídos pacientes admitidos no hospital, durante o período de um ano, e que apresentaram os seguintes critérios: (i) diagnóstico confirmado de infecção por HIV-1; (ii) contagem de linfócitos T-CD4+ ≤ 100 células/µL; e (iii) coleta de carga viral plasmática do CMV na admissão hospitalar. Posteriormente foram identificados os pacientes com lesão de órgão-alvo citomegálica confirmada, incluindo a neurológica (encefalite e/ou polirradiculopatia). Calculou-se desempenho da carga viral do CMV (sensibilidade -Se-, especificidade -Es-, valor preditivo positivo -VPP-, valor preditivo negativo -VPN-, acurácia -Ac-, razão de verossimilhança positiva -RVP-, e razão de verossimilhança negativa -RVN- em pacientes com doença neurológica citomegálica, utilizando diversos pontos de corte de carga viral do CMV. Resultados No período do estudo foram internadas 830 PVHIV e 245 (29.5%) delas foram incluídos. A mediana (IQR) de idade dos pacientes foi 38 (30-46) anos e 183 (74.7%) deles foram do sexo masculino. Durante a internação, 17 (6.9%) pacientes tiveram lesão de órgão-alvo pelo CMV: 6 (2.4%) apresentaram doença neurológica e 11 (4.5%) tiveram doença não neurológica. A presença de carga viral plasmática de CMV ≥ 1.000 UI/mL mostrou Se = 83.3%, Es = 78.7%, VPP = 8.9%, VPN = 99.5, Ac = 78.8%, RVP = 3.9 e RVN = 0.2 no diagnóstico de doença neurológica. Por outro lado, a presença de carga viral plasmática de CMV ≥ 30.000 UI/mL mostrou Se = 83.3%, Es = 97.5%, VPP = 45.4%, VPN = 99.6, Ac = 97.1%, RVP = 33.3 e RVN = 0.03 no diagnóstico de doença neurológica. Conclusão O resultado do desempenho da carga viral plasmática de CMV ≥ 30.000 UI/mL sugere o uso potencial desse valor de corte no diagnóstico da doença neurológica citomegálica na prática clínica diária. Maiores estudos são necessários para confirmar esse achado e suas implicações terapêuticas.

Introduction: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. Methods: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. Results: Twelve RCTs ( n = 7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95% CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95% CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. Conclusions: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non- clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non- hospitalized COVID-19 patients. (c) 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Purpose: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. Methods: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. Findings: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, >= 4 weeks compared to < 1 week treatment ( P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. Implications: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the com- parative safety of AMB lipid formulations versus AMB deoxycholate.

Four cases of people living with HIV/AIDS (PLWHA) with calcified cerebral toxoplasmosis associated with perilesional edema causing a single episode of neurological manifestations have recently been reported. Here, we describe the first detailed description of perilesional edema associated with calcified cerebral toxoplasmosis causing three episodes of neurological manifestations in a PLWHA, including seizures in two of them. These recurrences occurred over approximately a decade. Throughout this period, the patient showed immunological and virological control of the HIV infection, while using antiretroviral therapy regularly. This case broadens the spectrum of an emerging presentation of calcified cerebral toxoplasmosis, mimicking a well-described finding of neurocysticercosis in immunocompetent hosts.

BackgroundThe radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis.MethodsAll patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan.ResultsWe included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044).ConclusionIn this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

Epidemiological studies on predisposing conditions and outcomes of progressive multifocal leukoencephalopathy (PML) cases have been carried out exclusively in high-income countries. We aim to report and compare the main characteristics and outcomes of patients with PML and several underlying diseases in a referral center in a middle-income country. We performed a retrospective cohort study of PML cases admitted to a tertiary care hospital in São Paulo, Brazil during 2000–2022. Demographic and PML-specific variables were recorded. One-year case-fatality rate and factors associated with death were identified using a multivariate Cox proportional hazards regression model. Ninety-nine patients with PML were included. HIV infection (84.8