A5006238054- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Infectious Diseases and Tuberculosis
- Nail Diseases and Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Tuberculosis Research and Epidemiology
- Bacterial Infections and Vaccines
- Orthopedic Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Syphilis Diagnosis and Treatment
- HIV/AIDS oral health manifestations
- Infectious Encephalopathies and Encephalitis
- Malaria Research and Control
- Mycobacterium research and diagnosis
- Food Security and Health in Diverse Populations
- HIV/AIDS Impact and Responses
- Healthcare Technology and Patient Monitoring
- Medical Imaging and Pathology Studies
- Congenital Diaphragmatic Hernia Studies
- Infectious Diseases and Mycology
- HIV/AIDS Research and Interventions
- Whipple's Disease and Interleukins
- Diabetes Management and Research
- Respiratory viral infections research
- COVID-19 epidemiological studies
Makerere University
2019-2024
Infectious Diseases Institute
2019-2024
Rutgers, The State University of New Jersey
2020-2021
University of Minnesota
2019
Uganda Virus Research Institute
2019
London School of Hygiene & Tropical Medicine
2019
University College London
2019
Hospital for Tropical Diseases
2019
University of the Witwatersrand
2019
University of Liverpool
2019
Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether treatment regimen that includes single high dose liposomal amphotericin B would be efficacious not known.
IntroductionTuberculous meningitis accounts for 1–5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance new Xpert MTB/RIF Ultra (Xpert Ultra) tuberculous diagnosis.MethodsIn this prospective validation study, we tested cerebrospinal fluid (CSF) adults presenting with suspected (ie, headache or altered mental status clinical signs meningism) Mulago National Referral Hospital and Mbarara Regional in Uganda. centrifuged CSF, resuspended cell...
Abstract Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK from Africa. We hypothesized that would increase serum CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, 10 mg/kg/day),...
Abstract The epidemiology of infectious causes meningitis in sub-Saharan Africa is not well understood, and a common cause this region, Mycobacterium tuberculosis (TB), notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB (TBM) its mimics. 368 HIV-infected Ugandan adults subacute were prospectively enrolled. Total...
Abstract Background Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. Methods In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) (MAT2203, Matinas Biopharma) vs intravenous (IV) human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), 2 efficacy with/without IV loading doses...
Diagnosis of extrapulmonary tuberculosis (TB) remains challenging. We sought to determine the prevalence disseminated TB by testing urine with TB-lipoarabinomannan (TB-LAM) lateral flow assay and Xpert MTB/RIF Ultra (Ultra) in hospitalized adults.We prospectively enrolled human immunodeficiency virus (HIV)-positive adults suspected meningitis Uganda during 2018-2020. Participants underwent standardized urine-based screening. Urine (60 mcL) was tested TB-LAM (Alere), remaining centrifuged...
Cryptococcal meningitis is a leading cause of in sub-Saharan Africa. Given the need for rapid point-of-care testing, we evaluated diagnostic performance Dynamiker cryptococcal antigen (CrAg) lateral flow assay (LFA). We assessed CrAg LFA compared to IMMY as reference standard. tested 150 serum, 115 plasma, and 100 cerebrospinal fluid (CSF) samples from HIV patients with symptomatic 113 serum suspected asymptomatic antigenemia. Compared LFA, sensitivity was 98% 100% CSF 96% patients....
There is an increasing recognition of patients presenting with cryptococcal meningitis despite having a negative CSF antigen (CrAg). In this report, we describe three cases advanced immunosuppression who presented to hospital "false negative" antigen, two whom had positive fungal culture. We the challenge CSF-CrAg and explore ways overcome using newer diagnostic techniques.
Abstract Background It is unknown whether persons with symptomatic cryptococcal meningitis detected during routine blood antigen (CrAg) screening have better survival than presenting overt meningitis. Methods We prospectively enrolled Ugandans HIV and from December 2018 to 2021. Participants were treated amphotericin-based combination therapy. compared outcomes between who CrAg screened then referred hospital those directly the Results Among 489 participants meningitis, 40% (194/489)...
Tuberculosis (TB) and cryptococcal meningitis are leading causes of morbidity mortality in advanced HIV disease. Data limited on TB co-infection among individuals with meningitis. We performed a retrospective analysis HIV-infected participants from 2010–2017. Baseline demographics were compared between three groups: ‘prevalent TB’ if treated >14 days prior to diagnosis, ‘concurrent ± 14 or ‘No at baseline’. used time-updated proportional-hazards regression models assess diagnosis as risk...
Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4 < 100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails ∼25%. Sertraline has vitro vivo activity against Cryptococcus is synergistic mice. We evaluated the efficacy safety of sertraline asymptomatic cryptococcal antigenemia. conducted a randomized trial CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard 800 mg for 2 weeks, then 400 10 200 through...
The role of cerebrospinal fluid (CSF) lactate in tuberculosis meningitis (TBM) diagnosis and prognosis is unclear. aim this study was to evaluate the performance CSF alone combination with glucose predicting a TBM 14-day survival. HIV-positive Ugandan adults were investigated for suspected meningitis. baseline tests included smear microscopy; Gram stain; cell count; protein; point-of-care glucose, lactate, cryptococcal antigen (CrAg) assays. Where CrAg negative or there suspicion TBM, Xpert...
The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. assay's PCR cycle threshold (Ct) values represent number of cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) load. We measured relationship between cerebrospinal fluid (CSF) TB load with mortality.We prospectively enrolled...
Abstract Background Sodium abnormalities are frequent in central nervous system infections and may be caused by cerebral salt wasting, syndrome of inappropriate antidiuretic hormone secretion, or medication adverse events. In cryptococcal meningitis (CM), the prevalence baseline hyponatremia whether adversely impacts survival is unknown. Methods We conducted a secondary analysis data from 2 randomized trials human immunodeficiency virus–infected adult Ugandans with CM. grouped serum sodium...
Abstract Background The EnACT trial was a phase 2 randomized clinical conducted in Uganda, which evaluated novel orally delivered lipid nanocrystal (LNC) amphotericin B combination with flucytosine for the treatment of cryptococcal meningitis. When (5FC) is used as monotherapy cryptococcosis, 5FC can induce resistant Cryptococcus mutants. Oral uses drug delivery mechanism, and we assessed whether resistance to develops during oral LNC–amphotericin therapy. Methods We enrolled Ugandans HIV...
Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal monotherapy at 3 mg/kg previously failed to meet noninferiority criteria compared deoxycholate its registrational clinical trial. We aimed compare quantitative and mortality between among persons human immunodeficiency virus (HIV)-related meningitis receiving adjunctive 100 mg/kg/day....
Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to (CM). In April 2016, national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral Uganda. We report the evaluation cascade focusing on linkage care, fluconazole for 10 weeks and 6 months follow up, ART initiation subset facilities.We conducted retrospective, cross-sectional...
As part of the END TB strategy, World Health organization (WHO) recommends provision tuberculosis preventive therapy (TPT) to all people at high risk developing active disease. Patients with HIV-associated cryptococcal meningitis are severely immunocompromised and therefore should be eligible for TPT. In this commentary we discuss challenges associated starting in patients HIV a clinical setting, highlight benefit, existing gaps research opportunities patient population.
Abstract Background Intravenous (IV) amphotericin B is the gold standard treatment of severe mycoses. A new orally absorbed, less-toxic formulation has been developed (Matinas Biopharma). We evaluated efficacy this novel anti-fungal agent amongst adults with cryptococcal meningitis. Methods conducted a phase II randomized clinical trial testing oral encochleated (cAMB) versus IV for first episode meningitis in Kampala, Uganda from December 2020 to August 2021. Participants were HIV-positive,...
Introduction: Tuberculous meningitis accounts for 1-5% of tuberculosis (TB) cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance new Xpert MTB/Rif Ultra (Ultra) TB diagnosis. Methods: In a prospective diagnostic accuracy study, we tested cerebrospinal fluid (CSF) adults presenting with sub-acute Mulago and Mbarara Hospitals, Uganda. centrifuged CSF, resuspended cell pellet in 2mL CSF 0.5ml aliquots Ultra, Xpert, mycobacterial growth indicator tube (MGIT)...
Abstract Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis; however, its clinical implications remain unclear. We analyzed data from 890 adults with meningitis randomized into two trials Uganda between 2015 and 2021. CSF was grouped &lt; 100 mg/dl (72%, n = 641) ≥ (28%, 249). described baseline variables 18-week mortality by groups. Those were more likely to present Glasgow coma scale score 15 (P .01), self-reported seizures at...
Abstract Given extensive improvements in access to antiretroviral therapy (ART) over the past 12 years, HIV and cryptococcal meningitis landscapes have dramatically changed since 2010. We sought evaluate changes clinical presentation outcomes of people presenting with HIV-associated between 2010 2022 Uganda. analyzed three prospective cohorts HIV-infected Ugandans during 2010–2012, 2013–2017, 2018–2022. summarized baseline demographics, characteristics at presentation, 2-week 16-week...
Abstract Background Tuberculous meningitis (TBM) mortality averages at 27% but may reach 70% in HIV co-infection. High MRC severity grade, lower cerebrospinal fluid (CSF) white blood cell count (WBC) count, low weight, CD4 and plasma sodium were linked to Vietnam. Prognostic factors African adults with HIV-associated TBM are unknown. We sought determine the baseline predictive of death HIV-positive Ugandan TBM. Methods prospectively enrolled patients who received treatment classified as...