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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. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities. Methods: We conducted a retrospective, cross-sectional survey of patients with CD4 < 100 at seven urban and seven rural facilities after 1 year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a pre-emptive fluconazole prescription for the first 10 weeks. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap. Results: We evaluated 359 patient records between April 2016 to March 2017; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of < 50 cell/μL. Overall, CrAg screening had been performed in 255/359 (71.0, 95% CI, 66.0–75.7) of patients' records reviewed, with a higher proportion among urban facilities (170/209 (81.3, 95% CI, 75.4–86.4)) than rural facilities (85/150 (56.7, 95% CI, 48.3–64.7)). Among those who were CrAg screened, 56/255 (22.0, 95% CI, 17.0–27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9, 95% CI, 71.7–92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0, 95% CI, 7.6–30.8%) of these were still receiving antifungal therapy at 6 months follow up. At least one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening. Conclusion: There was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening.. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation. [ABSTRACT FROM AUTHOR]

Given extensive improvements in access to antiretroviral therapy (ART) over the past 12 years, the HIV and cryptococcal meningitis landscapes have dramatically changed since 2010. We sought to evaluate changes in clinical presentation and clinical outcomes of people presenting with HIV-associated cryptococcal meningitis between 2010 and 2022 in Uganda. We analyzed three prospective cohorts of HIV-infected Ugandans with cryptococcal meningitis during 2010-2012, 2013-2017, and 2018-2022. We summarized baseline demographics, clinical characteristics at presentation, and 2-week and 16-week mortality. Overall, 2022 persons had confirmed cryptococcal meningitis between 2010 and 2022. In the most recent 2018-2022 cohort, 48% presented as ART-naïve, and the median CD4 cell count was 26 cells/µl. Participants in the 2018-2022 cohort had the lowest cerebrospinal fluid (CSF) opening pressure (median 22 cmH2O) and the highest percentage with sterile CSF quantitative cultures (21%) compared with earlier cohorts (P < .001 for both), signifying a less severely ill population presenting with cryptococcal meningitis. Two-week mortality was lowest among participants with cryptococcal meningitis enrolled in a clinical trial in the 2018-2022 cohort at 13% compared to 26% in both 2010-2012 and 2013-2017 (P < .001). While AIDS-related deaths have dramatically declined over the past 12 years, cryptococcosis persists, presenting challenges to HIV program implementation. Two-week mortality has improved in the most recent cohort, likely due to the establishment of cryptococcal screening programs, better supportive care including scheduled lumbar punctures, and the availability of flucytosine-an essential component of antifungal therapy., (© The Author(s) 2025. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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 HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into < 100 mg/dl (72%, n = 641) and ≥ 100 mg/dl (28%, n = 249). We described baseline clinical variables and 18-week mortality by CSF protein groups. Those with CSF protein ≥ 100 mg/dl were more likely to present with Glasgow coma scale score < 15 (P < .01), self-reported seizures at baseline (P = .02), higher CD4 T-cell count (P < .001), and higher CSF white blood cells (P < .001). Moreover, those with a baseline CSF protein ≥ 100 mg/dl also had a lower baseline CSF fungal burden (P < .001) and a higher percentage of sterile CSF cultures at day 14 (P = .02). Individuals with CSF protein ≥ 100 mg/dl demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules, pro-inflammatory cytokines, T-helper cell type 1 and 17 cytokines, and immune-exhaustion marker (P < .05). 18-week mortality risk in individuals with a CSF protein < 100 mg/dl was 34% higher (unadjusted Hazard Ratio 1.34; 95% Confidence Interval, 1.05-1.70; P = .02) than those with CSF protein ≥ 100 mg/dl. In HIV-associated cryptococcal meningitis, individuals with baseline CSF protein ≥ 100 mg/dl more frequently presented with neurological symptoms, higher CSF inflammatory cytokines, reduced fungal burden, and lower mortality risk. The findings underscore the prognostic significance of baseline CSF protein levels in predicting disease severity and mortality risk in cryptococcal meningitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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.)

Background: The integrated approach to malaria prevention, which advocates for the use of several malaria prevention methods at households, is being explored to complement other existing strategies. We implemented a pilot project that promoted the integrated approach to malaria prevention in two rural communities in Wakiso district, Uganda., Objectives: This paper presents the impact evaluation findings of the project carried out 2 years after implementation with a focus on changes in knowledge and practices on malaria prevention., Methods: The project evaluation was cross-sectional in design and employed both quantitative and qualitative data collection methods. The quantitative survey was conducted among 540 households (household heads being participants) while the qualitative component involved 4 focus group discussions among community health workers (CHWs). Chi-square test was used to compare quantitative results from the evaluation with those of the baseline while thematic analysis was employed for qualitative data., Results: There was a statistically significant positive change in malaria prevention practices in the evaluation compared with the baseline regarding indoor residual spraying (χ2 = 7.9, p = 0.019), mosquito screening of windows and ventilators (χ2 = 62.3, p = 0.001), and closing windows of houses before 6:00 pm (χ2 = 60.2, p < 0.001). The CHWs trained during the project were found to be highly knowledgeable on the various malaria prevention methods in the integrated approach, and continued to promote their use in the community., Conclusion: Findings of the impact evaluation give promise that utilisation of integrated malaria prevention can be enhanced if use of multiple methods is promoted in communities.

Background: Besides use of insecticide-treated mosquito nets (ITNs) and indoor residual spraying (IRS), other complimentary measures including suitable housing structures, and environmental management that reduce breeding of malaria vectors, can be implemented at households to prevent the disease. However, most studies on malaria prevention have focused mainly on ITNs and IRS. The aim of this study was therefore to assess malaria prevention practices beyond ITNs and IRS, and associated environmental risk factors including housing structure in rural Wakiso district, Uganda., Methods: A clustered cross-sectional survey was conducted among 727 households in Wakiso district. Data were collected using an interviewer-administered questionnaire and observational checklist. The questionnaire assessed participants' household practices on malaria prevention, whereas the checklist recorded environmental risk factors for malaria transmission, and structural condition of houses. Poisson regression modeling was used to identify factors associated with use of mosquito nets by households., Results: Of the 727 households, 471 (64.8%) owned at least one mosquito net. Use of mosquito nets by households was higher with increasing education level of participants-primary (aPR = 1.27 [95% CI: 1.00-1.60]), secondary (ordinary level) (aPR = 1.47 [95% CI: 1.16-1.85]) and advanced level / tertiary (aPR = 1.55 [95% CI: 1.19-2.01]), and higher household income (aPR = 1.09 [95% CI: 1.00-1.20]). Additionally, participants who were not employed were less likely to have mosquito nets used in their households (aPR = 0.83 [95% CI: 0.70-0.98]). Houses that had undergone IRS in the previous 12 months were 42 (5.8%), while 220 (43.2%) households closed their windows before 6.00 pm. Environmental risk factors found at households included presence of vessels that could potentially hold water for mosquito breeding 414 (56.9%), and stagnant water in compounds 144 (19.8%). Several structural deficiencies on houses that could promote entry of mosquitoes were found such as lack of screening in ventilators 645 (94.7%), and external doors not fitting perfectly into walls hence potential for mosquito entry 305 (42.0%)., Conclusion: There is need to increase coverage and utilisation of ITNs and IRS for malaria prevention in Wakiso district, Uganda. In addition, other malaria prevention strategies such as environmental management, and improving structural condition of houses are required to strengthen existing malaria prevention approaches., Competing Interests: The authors have declared that no competing interests exist.