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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. [ABSTRACT FROM AUTHOR]

Background Increased intracranial pressure (ICP) frequently complicates cryptococcal meningitis. Therapeutic lumbar punctures (LPs) have acute survival benefits in the first week, and we sought to understand the longer-term survival impact of therapeutic LPs. Methods We prospectively enrolled human immunodeficiency virus (HIV)–seropositive adults with cryptococcal meningitis from 2013 to 2017 in Uganda. We assessed the association between clinical characteristics, CSF parameters, and 14- and 30-day mortality by baseline ICP. We also assessed 30-day mortality by number of follow-up therapeutic LPs performed within 7 days. Results Our analysis included 533 participants. Participants with baseline ICP >350 mm H2O were more likely to have Glasgow Coma Scale (GCS) score <15 (P  < .001), seizures (P  < .01), and higher quantitative cryptococcal cultures (P  < .001), whereas participants with ICP <200 mm H2O were more likely to have baseline sterile CSF cultures (P  < .001) and CSF white blood cell count ≥5 cells/µL (P  = .02). Thirty-day mortality was higher in participants with baseline ICP >350 mm H2O and ICP <200 mm H2O as compared with baseline ICP 200–350 mm H2O (hazard ratio, 1.55 [95% confidence interval, 1.10–2.19]; P  = .02). Among survivors at least 7 days, the 30-day relative mortality was 50% higher among participants who did not receive any additional therapeutic LPs compared to those with ≥1 additional follow-up LP (33% vs 22%; P  = .04), irrespective of baseline ICP. Conclusions Management of increased ICP remains crucial in improving clinical outcomes in cryptococcal meningitis. Guidelines should consider an approach to therapeutic LPs that is not dictated by baseline ICP. [ABSTRACT FROM AUTHOR]

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 of baseline hyponatremia and whether hyponatremia adversely impacts survival is unknown. Methods We conducted a secondary analysis of data from 2 randomized trials of human immunodeficiency virus–infected adult Ugandans with CM. We grouped serum sodium into 3 categories: <125, 125–129, and 130–145 mmol/L. We assessed whether baseline sodium abnormalities were associated with clinical characteristics and survival. Results Of 816 participants with CM, 741 (91%) had a baseline sodium measurement available: 121 (16%) had grade 3–4 hyponatremia (<125 mmol/L), 194 (26%) had grade 2 hyponatremia (125–129 mmol/L), and 426 (57%) had a baseline sodium of 130–145 mmol/L. Hyponatremia (<125 mmol/L) was associated with higher initial cerebrospinal fluid (CSF) quantitative culture burden (P  < .001), higher initial CSF opening pressure (P  < .01), lower baseline Glasgow Coma Scale score (P  < .01), and a higher percentage of baseline seizures (P  = .03). Serum sodium <125 mmol/L was associated with increased 2-week mortality in unadjusted and adjusted survival analyses (adjusted hazard ratio, 1.87 [95% confidence interval, 1.26–2.79]; P  < .01) compared to those with sodium 130–145 mmol/L. Conclusions Hyponatremia is common in CM and is associated with excess mortality. A standardized management approach to correctly diagnose and correct hyponatremia in CM needs to be developed and tested. [ABSTRACT FROM AUTHOR]

Background Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. Methods We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Results Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P  < .0001), seizures (P  = .0005), elevated intracranial opening pressure (P  = .03), higher CSF white cells (P  = .007), and lower CSF glucose (P  = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P  =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55–7.51; P  = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Conclusions Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate. [ABSTRACT FROM AUTHOR]

• TB survivors experienced a high mortality rate of 28.5 per 1000 person-years. • Deceased individuals lost a median of 23.8 years. • Hospitalization and unemployment at treatment initiation predicted mortality after cure. • Social protection measures and follow-up of TB survivors could improve survival. To determine the incidence of mortality and its predictors among pulmonary tuberculosis (PTB) survivors treated at a rural Ugandan tertiary hospital. We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the World Health Organisation's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1000 population, crude all-cause mortality rate per 1000 person-years, and median years of potential life lost for deceased individuals. Using Cox proportional hazard models, we investigated predictors of mortality. Of 334 PTB survivors enrolled, 38 (11.4%) had died. The cumulative incidence of all-cause mortality was 113.7 per 1000 population, and the crude all-cause mortality rate was 28.5 per 1000 person-years. The median years of potential life lost for deceased individuals was 23.8 years (IQR: 9.6-32.8). Hospitalization (adjusted hazard ratio (aHR): 4.3, 95% CI: 1.1-16.6) and unemployment (aHR: 7.04, 95% CI: 1.5-31.6) at TB treatment initiation predicted mortality. PTB survivors experience post high mortality rates after TB cure. Survivors who were hospitalized and unemployed at treatment initiation were more likely to die after cure. Social protection measures and long-term follow-up of previously hospitalized patients could improve the long-term survival of TB survivors. [ABSTRACT FROM AUTHOR]