Epstein-Barr virus and cytomegalovirus co-infections and mortality risk in patients with HIV-associated cryptococcal meningitis: a post-hoc analysis of a prospective nested cohort in the AMBITION-cm randomised controlled trial.

Background: HIV-associated cryptococcal meningitis case fatality remains greater than 25%. Co-prevalent infections might contribute to poor outcomes. We aimed to ascertain the prevalence and the clinical significance of Epstein-Barr virus (EBV) and cytomegalovirus co-infections in patients with cryptococcal meningitis to guide potential therapeutic interventions.

Cerebrospinal Fluid Mononuclear Cell Phenotype and Activation Predictors of 2-week and 1-year survival among Persons with HIV-Associated Cryptococcal Meningitis.

Background: Despite efforts to optimize therapy for HIV-associated cryptococcal meningitis (CM), survival outcomes remain poor. It is unclear how the cerebrospinal fluid (CSF) cellular immune phenotype and activation contribute to 2-week and 1-year survival following CM.

Methods: We compared baseline CSF mononuclear cell phenotype and activation among adults with HIV-associated cryptococcal meningitis who died within 2-weeks of CM diagnosis to survivors who were alive at 1-year.

Cerebral Perfusion Pressures and Implications on Clinical Outcomes and Medical Management in Cryptococcal Meningitis.

Background: In cryptococcal meningitis, increased intracranial pressure (ICP) is associated with worse outcomes and increased mortality. We sought to understand how changes in ICP and mean arterial pressure (MAP) affect cerebral perfusion pressure (CPP) and influence clinical outcomes.

Methods: We performed a secondary data analysis of a prospective cohort of Ugandan adults with HIV-associated cryptococcal meningitis.

Evaluating the Use of Lower Dose Flucytosine for the Treatment of Cryptococcal Meningitis: A Clinical Trial.

Background: Cryptococcosis is a leading cause of death among people living with HIV. Guidelines recommend combination therapy with amphotericin B and flucytosine, but standard flucytosine dosing of 100 mg/kg/day is associated with hematologic toxicity. The FLOOR trial investigated whether lower flucytosine dosing maintained therapeutic efficacy and reduced toxicity.

Experience of research nurses with oral encochleated amphotericin B for treatment of cryptococcal meningitis in a resource-limited setting.

Background: Besides the commonly used intravenous formulations of amphotericin B, an oral nanocrystal amphotericin B (MAT2203) formulation is being evaluated for efficacy to treat invasive fungal infections. This new experimental oral formulation has not been used before.

Methods: Herein, we describe our experiences with using oral amphotericin B for management of patients with HIV-associated cryptococcal meningitis in Uganda from a research nurse perspective.

Recent Antiretroviral Therapy Initiation Is Associated With Increased Mortality Risk in HIV-associated Cryptococcal Meningitis: An Analysis of Clinical Trial Data From Africa.

Background: More than half of people diagnosed with human immunodeficiency virus-associated cryptococcal meningitis are antiretroviral therapy (ART)-experienced. The impact of recent ART initiation (≤14 days) on outcomes from cryptococcal meningitis, and how to optimally manage ART in this patient population, are unknown.

Methods: We analyzed data from the recent Ambisome Therapy Induction Optimisation (AMBITION) trial to (1) examine whether patients diagnosed with cryptococcal meningitis within 14 days of ART initiation are at higher risk of mortality and (2) determine the impact of ART interruption at diagnosis of cryptococcal meningitis.

Prognostic Value of C-Reactive Protein in Adults With Tuberculous Meningitis: A Prospective Cohort Study.

We enrolled 135 adults with tuberculous meningitis (TBM), including 83% living with HIV. Participants with baseline C-reactive protein (CRP) ≥40 mg/L had 3 times higher odds of an 8-week modified Rankin scale ≥4 (adjusted odds ratio, 2.78; 95% CI: 1.

Global proteomic analysis of clinical strains reveals significant differences between latent and lethal infection.

Unlabelled: To predict the outcomes of disseminated fungal disease, a deeper understanding of host-pathogen interactions at the site of infection is needed to identify targets for clinical intervention and diagnostic development. is the causative agent of cryptococcosis, the largest infectious killer of individuals living with HIV. Cryptococcal infection begins in the lungs, with loss of immunological control leading to disseminated central nervous system disease and death.

Household economic impact of HIV-associated cryptococcal meningitis in five countries in Southern and Eastern Africa.

Introduction: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related mortality. Cryptococcal meningitis is a poverty-related disease and the majority of cases occur in settings where resources are limited and access to quality care is often linked to an individual's ability to pay for services. We have previously demonstrated the efficacy, safety and cost-effectiveness of a single, high-dose liposomal amphotericin-based treatment regimen within the AMBITION-cm trial.

Personalised risk-prediction tools for cryptococcal meningitis mortality to guide treatment stratification in sub-Saharan Africa: a prognostic modelling study based on pooled analysis of two randomised controlled trials.

Background: Cryptococcal meningitis is a major driver of global HIV-related mortality, and validated approaches to stratify mortality risk could help to target effective treatment strategies. We aimed to develop and validate models to predict risk of all-cause mortality in people with HIV-associated cryptococcal meningitis in sub-Saharan African countries.

Methods: For this prediction modelling study, we pooled individual-level data from the ACTA (ISRCTN45035509) and AMBITION-cm (ISRCTN72509687) randomised controlled trials.

Diagnostic accuracy of the re-engineered urinary FujiLAM2 assay amongst hospitalized adults with advanced HIV disease.

Background: A nonsputum-based, point-of-care tuberculosis (TB) diagnostic test is a global health priority. The impact of urinary mycobacterial lipoarabinomannan (LAM) testing has been limited by the diagnostic performance of current assays. We assessed the diagnostic accuracy of the re-engineered TB-LAM SILVAMP (FujjLAM2) assay (Fujifilm, Japan) to diagnose TB amongst hospitalized adults living with advanced HIV disease.

Etiology and Outcomes of Meningitis among Adults in Three Ugandan Referral Hospitals, 2018-2023: A Prospective Cohort Study in a High-HIV Endemic Setting.

Studies describing the global burden of meningitis often exclude HIV- or tuberculosis (TB)-related etiologies, thereby presenting a limited view of meningitis etiology in low- and middle-income countries. This study provides an updated evaluation of the etiology of meningitis and treatment outcomes in Uganda given advancements in molecular and TB diagnostics. We conducted a prospective observational cohort study from December 2018 to October 2023, for which adults with suspected meningitis were recruited from three referral hospitals in Uganda.

The diagnostic role of elevated serum cryptococcal antigen titers in patients with suspected cryptococcal meningitis when lumbar puncture is contraindicated: A case report.

Cryptococcal meningitis is one of the major causes of death in sub-Saharan Africa among individuals with advanced HIV, and it is typically diagnosed through lumbar puncture (LP). However, LP may be contraindicated in some cases, causing a clinical dilemma and potential delay in treatment. We present the case of a 60-year-old female, newly diagnosed with HIV, who presented with a reduced level of consciousness and a positive serum cryptococcal antigen (CrAg) test (high titer = 1:320).

Diagnostic Accuracy of the Updated FujiLAM II Assay to Detect Tuberculosis in Outpatients With Advanced HIV Disease.

Background: An urgent need exists for point-of-care diagnostics to detect tuberculosis (TB) among people with advanced human immunodeficiency virus (HIV) disease. The Fujifilm SILVAMP TB LAM (FujiLAM II) is a novel point-of-care assay that detects mycobacterial lipoarabinomannan (LAM) antigen in the urine to identify TB. We present a validation of the FujiLAM II assay on prospectively collected urine samples from outpatient adults with advanced HIV disease in Uganda.

The hypervirulent Type-1/Type-17 phenotype of clinical isolates is specific to A/J mice.

is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Both host- and pathogen-specific factors are known to affect patient outcome, and recent studies showed that strain-specific differences in clinical isolates can influence virulence in A/J mice. However, it is unclear how the immunologic and genetic background of inbred mouse strains affects disease outcome during infection.

Neurocognitive Impairment Among Cryptococcal Meningitis Survivors in Uganda, a Prospective Cohort Study.

Background: Neurocognitive impairment in HIV-associated cryptococcal meningitis survivors remains poorly characterized. We sought to identify risk factors associated with sustained neurocognitive impairment.

Methods: Cryptococcal meningitis survivors from the ASTRO-CM trial underwent neurocognitive assessment at 12 weeks.

Experiences, challenges, gaps, and strategies for counselling persons presenting with advanced HIV-associated meningitis in Uganda.

Background: Advanced HIV disease (AHD) is still a significant problem in Uganda despite the test-and-treat strategy and the increased access to antiretroviral therapy (ART). Meningitis remains a major cause of morbidity and mortality in people with AHD. HIV counselling is essential and plays an important role in managing persons with AHD-related meningitis.

Impact of cerebrospinal fluid leukocyte infiltration and activated neuroimmune mediators on survival with HIV-associated cryptococcal meningitis.

Introduction: Cryptococcal meningitis remains a prominent cause of death in persons with advanced HIV disease. CSF leukocyte infiltration predicts survival at 18 weeks; however, how CSF immune response relates to CSF leukocyte infiltration is unknown.

Methods: We enrolled 401 adults with HIV-associated cryptococcal meningitis in Uganda who received amphotericin and fluconazole induction therapy.

Increasing postgraduate medical mycology research dissertations at Uganda's higher institution of learning.

Objectives: Postgraduate medical mycology research may also be affected by funding. This study reports the positive impact of funding on postgraduate medical mycology research at Makerere University, Uganda.

Methods: This retrospective study was conducted on postgraduate medical microbiology dissertation topics from 2023 to 2024 using data collected between September and November 2024.

Pulmonary granuloma formation during latent infection in C3HeB/FeJ mice involves progression through three immunological phases.

is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs.

Pulmonary granuloma formation during latent infection in C3HeB/FeJ mice involves progression through three immunological phases.

Unlabelled: is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs.

Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.

Studies across various pathogens highlight the importance of pathogen genetic differences in disease manifestation. In the human fungal pathogen Cryptococcus neoformans, sequence type (ST) associates with patient outcome. We performed a meta-analysis of four genomic studies and identified overlapping gene regions associated with virulence, suggesting the importance of these gene regions in cryptococcal disease in diverse clinical isolates.