Laboratory-Reflex Cryptococcal Antigen Screening Is Associated With a Survival Benefit in Tanzania

Abstract

26This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. ABSTRACTBackground: Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12month survival/retention in CrAg-positive persons not treated with fluconazole was 0%.Methods: HIV testing was offered to all ART-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4<150 cells/µL. CrAgpositive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox regression models. Results:We screened 560 individuals for CrAg. The median CD4 count was 61 cells/µL (IQR 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/µL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs. 5.3%, p=0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100persons-year, respectively, p=0.25). Independent predictors of 6-month death/lost to follow-up A C C E P T E D 27 were low CD4, cryptococcal meningitis (adjusted hazard ratio (aHR) 2.76, 95% CI 1.31-5.82)), and no ART initiation (aHR 3.12, 95%CI 2.16-4.50). Conclusions:Implementing laboratory-reflex CrAg screening among outpatients and hospitalized-individuals resulted in a rapid detection of cryptococcosis and a survival benefit.These results provide a model of a feasible, effective and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis

“…Thirteen studies reported the prevalence of TB disease among patients who were CrAg positive, using different TB screening approaches [ 9 , 11 , 19–22 , 26 , 28 , 33 , 41 , 46 , 57 , 72 ]. Among 234 patients screened CrAg positive, 45 also were diagnosed with TB, giving an overall prevalence of coexistent disease of 19.2% (95% CI, 14.4%–24.9%).…”

Short‐course amphotericin B in addition to sertraline and fluconazole for treatment of HIV‐associated cryptococcal meningitis in rural Tanzania

“…The median CD4 cell count was 31 cells/µL (IQR 13‐59), and the median baseline CSF fungal burden was a relatively low 19 000 CFU/mL (IQR, 800‐110 000). In the presence of a district‐wide CrAg screening programme testing peripheral blood, the time from entry into HIV care to lumbar puncture and CSF CrAg result was a median of 1 (IQR, 0, 2) days …”

“…In the presence of a district-wide CrAg screening programme testing peripheral blood, the time from entry into HIV care to lumbar puncture and CSF CrAg result was a median of 1 (IQR, 0, 2) days. 13 The 2-week survival was 64% (18/28) for patients receiving fluconazole + sertraline and 89% (16/18) for those receiving additional amphotericin (P = .09). The 10-week survival was 21% (6/28) with fluconazole + sertraline alone, and 10-week survival was significantly higher at 61% (11/18) with 5 days of added amphotericin (P = .012).…”

“…Cryptococcal antigen (CrAg) screening of all HIV‐infected persons, both inpatients and outpatients with CD4 <150 cells/μL, was systematically implemented using the CrAg lateral flow assay (LFA; IMMY) at the hospital and six other HIV primary care treatment centres within the Kilombero district from November 2015 onwards. CrAg‐positive persons were referred to hospital for management . We included CSF CrAg‐positive persons and excluded current sertraline use, liver cirrhosis, pregnancy, breastfeeding or unable to receive lumbar punctures.…”

“…We enrolled HIV-infected adults with a first episode of crypto- 13 We included CSF CrAg-positive persons and excluded current sertraline use, liver cirrhosis, pregnancy, breastfeeding or unable to receive lumbar punctures. Quantitative CSF cultures were performed using five serial dilutions of 100 μL of CSF, as described.…”