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Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019–January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre–coronavirus disease 2019 period). [ABSTRACT FROM AUTHOR]

Background Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence. Methods We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate. Results 724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/μL; IQR: 9–76) and lower CSF white blood cell (WBC; 4 cells/μL; IQR: 4–85) counts than paradoxical IRIS (CD4: 78 cells/μL; IQR: 47–142; WBC: 45 cells/μL; IQR: 8–128). Among those with CSF WBC <5 cells/μL, 86% (43/50) had relapse. Among those with CD4 counts <50 cells/μL, 91% (39/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS. Conclusions Poor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results. Clinical Trials Registration NCT01802385. [ABSTRACT FROM AUTHOR]

Background Diagnosis of extrapulmonary tuberculosis (TB) remains challenging. We sought to determine the prevalence of disseminated TB by testing urine with TB-lipoarabinomannan (TB-LAM) lateral flow assay and Xpert MTB/RIF Ultra (Ultra) in hospitalized adults. Methods We prospectively enrolled human immunodeficiency virus (HIV)-positive adults with suspected meningitis in Uganda during 2018–2020. Participants underwent standardized urine-based TB screening. Urine (60 mcL) was tested with TB-LAM (Alere), and remaining urine was centrifuged with the cell pellet resuspended in 2 mL of urine for Xpert Ultra testing. Results We enrolled 348 HIV-positive inpatients with median CD4 of 37 cells/mcL (interquartile range, 13–102 cells/mcL). Overall, 26% (90 of 348; 95% confidence interval [CI], 21%–30%) had evidence of disseminated TB by either urine assay. Of 243 participants with both urine TB-LAM and Ultra results, 20% (48 of 243) were TB-LAM-positive, 12% (29 of 243) were Ultra-positive, and 6% (14 of 243) were positive by both assays. In definite and probable TB meningitis, 37% (14 of 38) were TB-LAM-positive and 41% (15 of 37) were Ultra-positive. In cryptococcal meningitis, 22% (40 of 183) were TB-LAM-positive and 4.4% (6 of 135) were Ultra-positive. Mortality trended higher in those with evidence of disseminated TB by either assay (odds ratio = 1.44; 95% CI, 0.83–2.49; P  = .19) and was 6-fold higher in those with definite TB meningitis who were urine Ultra-positive (odds ratio = 5.67; 95% CI, 1.13–28.5; P  = .04). Conclusions In hospitalized Ugandans with advanced HIV disease and suspected meningitis, systematic screening with urine TB-LAM and Ultra found a high prevalence of urine TB test positivity (26%). In those with TB meningitis, urine tests were positive in over one third. There was little concordance between Ultra and TB-LAM, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether persons with symptomatic cryptococcal meningitis detected during routine blood cryptococcal antigen (CrAg) screening have better survival than persons presenting with overt meningitis., Methods: We prospectively enrolled Ugandans with HIV and cryptocococcal meningitis from December 2018 to December 2021. Participants were treated with amphotericin-based combination therapy. We compared outcomes between persons who were CrAg screened then referred to hospital with those presenting directly to the hospital with symptomatic meningitis., Results: Among 489 participants with cryptococcal meningitis, 40% (194/489) received blood CrAg screening and were referred to hospital (median time to referral 2 days; interquartile range [IQR], 1-6). CrAg-screened persons referred to hospital had lower 14-day mortality than non-CrAg-screened persons who presented directly to hospital with symptomatic meningitis (12% vs 21%; hazard ratio, .51; 95% confidence interval, .32-.83; P = .006). Fewer CrAg-screened participants had altered mental status versus non-CrAg-screened participants (29% vs 41%; P = .03). CrAg-screened persons had lower quantitative cerebrospinal fluid (CSF) culture burden (median [IQR], 4570 [11-100 000] vs 26 900 [182-324 000] CFU/mL; P = .01) and lower CSF opening pressures (median [IQR], 190 [120-270] vs 225 [140-340] mmH2O; P = .004) compared with non-CrAg-screened persons., Conclusions: Survival from cryptococcal meningitis was higher in persons with prior CrAg screening than those without CrAg screening. Altered mental status was the most potent predictor for mortality in a multivariate model. We suggest that CrAg screening detects cryptococcal meningitis at an earlier stage, as evidenced by a favorable baseline risk profile and notably fewer persons with altered mental status., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cryptococcal antigen (CrAg) screening and pre-emptive antifungal therapy for people with CD4 cell counts <100 cells/μl are recommended by the World Health Organization and several national HIV guidelines. We sought to evaluate CrAg screening program implementation across Uganda, in relation to health center level and distance from the capital. We conducted a cross-sectional study of 22 health centers across southern Uganda from April to June 2019. We reviewed laboratory records regarding number of CD4 cell count tests performed, proportion of outpatients with CD4 counts <200 cells/μl, and number of CrAg screening tests performed. We administered surveys to health center staff to understand barriers to advanced HIV care. We observed no significant difference in health center level and performance of CrAg screening; with each subsequent health center level, there was 1.17-fold (95% CI: 0.92-1.41) higher odds of CrAg screening performed per level. CrAg screening uptake was not associated with distance from the capital city (odds ratio = 0.96, 95% CI: 0.89-1.04). Qualitative data from surveys indicated that limitations to uptake of CrAg screening were secondary to dysfunctional CD4 machines, lack of provider awareness of CrAg screening guidelines, and inadequate/intermittent supply of CrAg tests. There were no significant associations between CrAg screening uptake and level of health center or distance of health center from the capital city. We identified systemic barriers to CrAg screening related to inadequate CD4 testing, insufficient knowledge regarding national screening guidelines, and irregular laboratory testing supplies., Lay Summary: The objective of this study was to evaluate cryptococcal antigen (CrAg) screening program implementation in Uganda, by type of healthcare center and by distance from the capital city. CrAg screening uptake was not associated with distance from the capital city, or the type of healthcare center., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)