Conrad Muzoora

Background: Hepatitis B virus (HBV) is a global health problem endemic in Sub-Saharan Africa, with 65% of global cases occurring in the WHO Western Pacific and African regions. HBV is a known primary cause of kidney disease that progresses throughout the illness. Early detection of kidney disease and antiviral initiation can slow its progression. Our study aimed to identify the prevalence of kidney disease and associated factors in adults with chronic HBV. Methods: We conducted a cross-sectional study from November 2023 to December 2024 in Mbarara, Uganda, recruiting adults with chronic hepatitis B. Data collected: socio-demographics, comorbidities, coinfections, and hepatitis B-related data. Spot urine and blood were collected for dipstick, urine neutrophil gelatinase–associated lipocalin (NGAL), and creatinine with estimated glomerular filtration rate (eGFR). We defined kidney disease as the presence of (1) urine NGAL >132 ng/mL, (2) eGFR 2 , or (3) eGFR between 60 and 2 with proteinuria or hematuria. We utilized logistic regression to determine factors associated with kidney disease. Results: We enrolled 157 participants with a mean age of 35.8 (standard deviation, ±12.5) years, and 50% (79/156) were males. Overall kidney disease prevalence was 27% (43/157; 95% confidence interval (CI): 20.6–35.1%). Prevalence based on urine NGAL was 17.2% (27/157; 95% CI: 11.6–24.0), eGFR 2 was 5.7% (9/157; 95% CI: 2.7–10.6), and eGFR between 60 and 2 with either proteinuria or hematuria was 9.6% (15/157; 95% CI: 5.4–15.3). Being female was associated with higher odds of kidney disease (adjusted odds ratio, 2.49; 95% CI: 1.16–5.36; P = 0.019). Conclusion: Nearly one-third of adults with chronic Hepatitis B in Uganda had kidney disease, with NGAL increasing the detection by 12% over creatinine and urine dipstick alone. We recommend frequent monitoring of kidney function in adults with chronic HBV.

: 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. We used a comprehensive diagnostic algorithm to determine microbiological etiologies of cases. Participants were followed through hospital discharge, and mortality was summarized by meningitis etiology. We enrolled 1,577 participants with suspected meningitis, of whom 96% (n = 1,511/1,577) had HIV infection and 51% (n = 772/1,577) were antiretroviral therapy naive. The median CD4 cell count was 39 cells/µL (interquartile range: 14–97 cells/µL). Cryptococcal meningitis was the most frequently diagnosed etiology of meningitis (62%) followed by TB meningitis (21%). Inpatient mortality was highest among participants diagnosed with possible TB meningitis (32%) followed by probable TB meningitis (29%) and bacterial meningitis (24%). Among the 4% (n = 66/1,577) of HIV-seronegative participants, TB meningitis was the most frequently (38%) diagnosed cause of meningitis. Despite improvements in access to HIV therapy, cryptococcal meningitis and tuberculous meningitis persist as the most common etiologies of meningitis in Uganda. Improved access to meningitis diagnostics and treatments is critically needed to mitigate the morbidity and mortality, particularly in the resource-limited settings of HIV and TB endemic regions.

We examined the self-rated competence of Ugandan healthcare workers (HCWs) in obtaining informed consent for autopsies, considering the challenges of low autopsy acceptance rates globally. In September and October 2023, we conducted a nationwide cross-sectional study of HCWs, who provided informed consent to participate and completed an online, self-administered questionnaire. Participants’ self-rated competence in obtaining informed consent for autopsy was assessed through Likert scale questions. Knowledge and practices were also assessed. All scores were converted to percentages, with scores ≥80% indicating higher competence. We enrolled 216 HCWs (including 145 [67.1%] doctors), with a mean age of 31.6 ± 7.2 years. Overall, 55.6% (n = 120) had ever assisted in obtaining consent for autopsy, 43.6% (n = 100) had ever obtained consent for autopsy themselves, and 13.4% (n = 29) had ever attended training on obtaining consent for autopsy. The mean competency score was 59.8 ± 17.0% (perfect score, 100%), with 29 (13.4%) participants demonstrating high competence. Healthcare workers with adequate knowledge had higher competence scores (odds ratio [OR]: 15.0, 95% CI: 6.17–36.58, P P = 0.040). Fewer than one in five Ugandan HCWs demonstrated high self-rated competence or possessed adequate knowledge regarding informed consent for autopsies, and only a few had received specialized training on how to obtain consent for an autopsy. Therefore, there is a pressing need for enhanced training and increased awareness among Ugandan HCWs in obtaining informed consent for autopsies.

"Diagnosis Of Chronic Pulmonary Aspergillosis" published on 17 Apr 2023 by The American Society of Tropical Medicine and Hygiene.

Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen). An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance. A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment. ISRCTN, ISRCTN72509687 . Registered on 13 July 2017.

Background: The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef’s most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. Results: Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naïve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p < 0.0001) than clones from other subtypes. Subtype C Nefs displayed the lowest in vitro functionality. Inter-subtype differences in HLA class I downregulation remained statistically significant after controlling for differences in age, sex, and clinical parameters (p < 0.0001). The synthesized consensus subtype B Nef showed higher activities compared to consensus C Nef, which was most pronounced in cells expressing lower protein levels. Nef clones exhibited substantial inter-subtype diversity: cohort consensus residues differed at 25% of codons, while a similar proportion of codons exhibited substantial inter-subtype differences in major variant frequency. These amino acids, along with others identified in intra-subtype analyses, represent candidates for mediating inter-subtype differences in Nef function. Conclusions: Results support a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation.

Background. Therapy for human immunodeficiency virus (HIV)–associated cryptococcal meningitis in many centers in Africa is fluconazole administered a