Incidence of Acute Kidney Injury and Associated Mortality among Individuals with Drug-Susceptible Tuberculosis in Uganda.

BACKGROUND: Although tuberculosis (TB) is associated with significant mortality and morbidity, its impact on kidney function is not well understood and is often attributed to anti-TB drugs. We aimed to assess the incidence of acute kidney injury (AKI) in the immediate post-TB diagnosis period in Uganda, a TB/HIV-endemic country in sub-Saharan Africa. METHODS: We included patients enrolled in an observational cohort study of adults diagnosed with drug-susceptible TB followed longitudinally. Adults (≥ 18years) without known kidney disease were enrolled between 8/2022-7/2023 at three regional hospitals serving 12.5% of the Ugandan population. Our primary outcome was incidence of KDIGO-defined AKI within two weeks of TB diagnosis. Other outcomes included predictors of AKI and its association with 30-day survival. RESULTS: A total of 156 adults were included. The median (IQR) age was 39 (28-53) years, most were male (68.6%) and 49.4% had HIV. People with HIV had shorter time to TB diagnosis from symptom onset (21[7-30] days) compared to HIV-negative participants (60[23-90] days), p<0.001. The incidence of AKI was 33.3% (52/156), and was similar between people with and without HIV. Proteinuria or hematuria at enrollment was associated with higher odds of AKI (OR-2.68, 95%CI 1.09-6.70, p∼0.033). AKI was associated with significant risk of mortality (aHR-8.22, 95% CI, 1.94-34.72, p ∼0.004) independent of HIV status. CONCLUSION: The overall incidence of AKI in the immediate post-TB diagnosis period is high and associated with increased mortality risk. Our findings suggest monitoring kidney function should be routine for patients with TB, including prior to treatment initiation.

Mid-Upper Arm Circumference Is a Strong Predictor of Mortality Among Ugandan Adults With HIV-Associated Cryptococcal Meningitis: A Prospective Cohort Study.

Background: Mortality among adults diagnosed with HIV-associated cryptococcal meningitis remains high (24%-40%). We hypothesized that nutritional state, as measured by mid-upper arm circumference (MUAC), is a potentially modifiable risk factor for mortality. Methods: Ugandan adults hospitalized with HIV-associated cryptococcal meningitis had MUAC measurements performed at baseline. We compared MUAC measurements with baseline clinical and demographic variables and investigated associations with survival using Cox regression. Results: Of 433 participants enrolled, 41% were female, the median CD4 T-cell count (interquartile range [IQR]) was 15 (6-41) cells/µL, and 37% were antiretroviral therapy naïve. The median MUAC (IQR) was 24 (22-26) cm, the median weight (IQR) was 53 (50-60) kg, and MUAC correlated with weight (Pearson r = 0.6; P < .001). Overall, 46% (200/433) died during the 18-week follow-up. Participants in the lowest MUAC quartile (≤22 cm) had the highest mortality: 39% (46/118) at 2 weeks and 62% (73/118) at 18 weeks. A baseline MUAC ≤22 cm was associated with an 82% increased risk of 18-week mortality as compared with participants with an MUAC >22 cm (unadjusted hazard ratio, 1.82; 95% CI, 1.36-2.42; P < .001). Following adjustment for antiretroviral therapy status, CD4 count, hemoglobin, amphotericin dose, and tuberculosis status, the adjusted hazard ratio was 1.84 (95% CI, 1.27-2.65; P < .001). As a continuous variable, 18-week mortality was reduced by 10% for every 1-cm increase in MUAC. CSF Th17 immune responses were positively associated with MUAC quartile. Conclusions: MUAC measurement is a simple bedside tool that can identify adults with HIV-associated cryptococcal meningitis at high risk for mortality for whom an enhanced bundle of care, including nutritional supplementation, should be further investigated.

Self-Rated Competence of Ugandan Healthcare Workers to Obtain Informed Consent for Autopsy.

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 <0.001). Compared with nurses/midwives, doctors had 73% lower odds of having a high competence score (adjusted OR: 0.27, 95% CI: 0.08-0.94, 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.

Organ donation and HIV: Awareness and willingness to be a living donor among people with HIV in Uganda.

BACKGROUND: HIV+-to-HIV+ organ transplantation has demonstrated promise and is now authorized for research purposes in certain countries. However, organ transplantation is dependent on the availability of organ donors. We assessed the awareness and willingness to donate organs among people with HIV (PWH) in Uganda. METHODS: We conducted a multicenter cross-sectional study between October 2023 and January 2024 in four large HIV clinics in Northern Uganda. The study population consisted of PWH. A structured questionnaire was used to collect data regarding awareness, willingness, and beliefs regarding organ donation. Organ donation was defined as the willingness to be a living donor of a solid organ. We conducted multivariable logistic regression to assess for an association between willingness to donate organs and selected exposures. Data were analyzed in Stata version 15.0. Results are expressed as adjusted odds ratio (AOR) with 95% confidence intervals (CI). RESULTS: A total of 232 participants were recruited. The mean age ± standard deviation of the participants was 42.2±11.8 years. All participants were on antiretroviral therapy. Sixty-two (26.7%) had a CD4 count less than or equal to 200 cells/mm3. The majority (80.6%, n = 187) had ever heard of organ donation. Slightly more than a third (34.9%, n = 81) were willing to donate organs. Factors associated with willingness to be a living organ donor included being female (AOR: 1.56; 95% CI: 1.15-2.11), having a tertiary education level (AOR: 1.79; 95% CI: 1.03-3.11), average monthly income >500 000 UGX (135.1USD) (AOR: 5.5; 95% CI: 1.97-15.40), ever heard about organ donation (AOR: 5.4; 95% CI: 1.67-17.8), and attending an organ donation campaign (AOR: 2.0; 95% CI: 1.07-3.74). CONCLUSIONS: Awareness about organ donation was high but the willingness to be a living organ donor was low among PWH in Uganda. There is a need to sensitize the community about the need and benefits of organ donation with the involvement of media and the healthcare workers.

Frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa: a scoping review.

BACKGROUND: Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. OBJECTIVE: To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa. METHODS: We conducted a scoping review of autopsy studies conducted in Africa. DATA SOURCES: PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online. STUDY ELIGIBILITY CRITERIA: The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens. DATA SYNTHESIS: Data were summarized using descriptive statistics and no meta-analysis was performed. RESULTS: We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%). CONCLUSIONS: Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.

Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis.

Background: Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis from being normal to markedly elevated. However, the clinical implications of CSF protein levels in cryptococcal meningitis remain unclear. Methods: We analysed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into ≥100 mg/dL (n=249) and <100 mg/dL (n=641). We described baseline clinical variables and mortality by CSF protein levels. Results: Approximately one-third of individuals had a baseline CSF protein ≥100 mg/dL. Those with CSF protein ≥100 mg/dL were more likely to present with Glasgow coma scale scores <15 (P<0.01), self-reported seizures at baseline (P=0.02), higher CD4 T-cells (p<0.001), and higher CSF white cells (p<0.001). Moreover, those with a baseline CSF protein ≥100 mg/dL also had a lower baseline CSF fungal burden (p<0.001) and a higher percentage of sterile CSF cultures at day 14 (p=0.02). Individuals with CSF protein ≥100 mg/dL demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules pro-inflammatory cytokines, type-1 T-helper cell cytokines, type-3 chemokines, and immune-exhaustion marker (p<0.05). 18-week mortality risk in individuals with a CSF protein <100 mg/dL was 34% higher, (unadjusted Hazard Ratio 1.34; 95% CI, 1.05 to 1.70; p=0.02) than those with ≥100 mg/dL. Conclusion: In cryptococcal meningitis, individuals with CSF protein ≥100 mg/dL more frequently presented with seizures, altered mental status, immune activation, and favourable fungal outcomes. Baseline CSF protein levels may serve as a surrogate marker of immune activation and prognosis.