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The article discusses the World Health Organization guidelines for recommending cryptococcal antigen (CrAg) screening in blood for human immunodeficiency virus (HIV)-infected persons, who do not receive effective antiretroviral therapy. It mention the asymptomatic CrAg-positive patients being enrolled in the ORCAS study during fluconazole therapy.

Background: HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia.Methods: Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants.Results: Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001).Conclusion: Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary. [ABSTRACT FROM AUTHOR]

Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method. This cohort study enrolled HIV-infected Ugandans from August-September 2013 in Mbale, Uganda and collected stool and blood samples at enrollment. Real-time PCR quantified stool: Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica, and Giardia intestinalis infection. Generalized linear models assessed relationships between parasitic infection and clinical or demographic data. 35% of participants (71/202) tested positive for ≥1 helminth, mainly N. americanus (55/199, 28%), and 4.5% (9/202) were infected with ≥2 stool parasites. Participants with hookworm infection had lower average CD4+ cell counts (-94 cells/mcL, 95%CI: -141, -48 cells/mcL; p<0.001) after adjustment for sex, CD4+ nadir at clinic entry, and time on ART. The high prevalence of parasitic infection and correlation with decreased CD4+ concentrations highlight the need to re-examine the effects of invasive helminth co-infection in rural, HIV-infected populations in the era of widely available ART. Elucidating the relationship between hookworm infection and immune recovery could provide opportunities for health optimization, e.g. integrated deworming, in these vulnerable populations. [ABSTRACT FROM AUTHOR]

(1→3)-Beta-D-glucan was detected in high levels in cerebrospinal fluid, and to lesser extent in serum, among HIV-infected persons with cryptococcal meningitis.Background. (1→3)-β-d-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for patients infected with human immunodeficiency virus (HIV) and presenting with suspected cryptococcal meningitis.Methods. The Fungitell assay was used to measure BDG concentrations in cerebrospinal fluid (CSF) (n = 177) and serum (n = 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG's relationship with mortality.Results. The Fungitell BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). Cerebrospinal fluid BDG concentrations at diagnosis were median (interquartile range) 343 (200–597) pg/mL in cryptococcal patients and 37 (23–46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were ≥10 000 colony-forming units/mL. (1→3)-β-d-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho = 0.820; P < .001), CSF CRAG lateral flow assay titers (rho = 0.780, P < .001), and monocyte chemotactic protein-1 levels in CSF (P = .047). In patients with cryptococcal meningitis, BDG ≥500 pg/mL at diagnosis was associated with increased 10-week mortality.Conclusions. (1→3)-β-d-Glucan is detectable in the CSF of HIV-infected patients with Cryptococcus, and it may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike CRAG, making BDG potentially useful in diagnosing recurrent episodes. [ABSTRACT FROM PUBLISHER]