Utility of urine and serum lateral flow assays to determine the prevalence and predictors of cryptococcal antigenemia in HIV‐positive outpatients beginning antiretroviral therapy in Mwanza, Tanzania

Abstract

BackgroundDetection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV-positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre-emptively. Recently developed point-of-care cryptococcal antigen tests may be useful for screening, particularly in resource-limiting settings, but few studies have assessed their utility.MethodologyThe objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV-positive patients with CD4+ T-cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point-of-care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients’ files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations.ResultsAmong 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p<0.001 for both). Compared to the new LFA diluent for urine cryptococcal antigen, the standard diluent had higher sensitivity (100% versus 80%) but lower specificity (74% versus 92%) using serum cryptococcal antigen as a gold standard.ConclusionsOur findings suggest that HIV-positive outpatients with CD4 counts <200 cells/µL, rather than 100, should be screened for asymptomatic cryptococcal antigenemia given its association with mortality if untreated. Agreement of the urine LFA with the serum LFA was not sufficient to recommend routine screening with urine LFA.

Cryptococcal antigenemia and associated risk factors among ART‐naïve and ART‐experienced HIV‐infected peoples at selected health institutions of Mekelle, Northern Ethiopia

“…The findings from this study were similar to recent prevalence reports from Namibia (3.3%) (Sawadogo et al, ) and Tanzania (3.7%) (Letang et al, ) and slightly lower than the prevalence reported in South Africa (4.3%) (Longley et al, ). However, lower than the prevalence reported in two studies from Nigeria (12.7% and 8.9%) (Oladele et al, ; Osazuwa, Dirisu, Okuonghae, & Ugbebor, ) and two more from Tanzania (7.1% and 5.1%) (Magambo et al, ; Wajanga et al, ). We also compared our finding with studies in other developing countries like Indonesia (7.1%) (Ganiem et al, ), Vietnam (4%) (Smith et al, ), and Thailand (9.2%) (Pongsai, Atamasirikul, & Sungkanuparph, ).…”

Preheating of urine improves the specificity of urinary cryptococcal antigen testing using the lateral flow assay

“…Early studies on the CrAg LFA test showed high sensitivity and low specificity in urine. [7,8,9]. In other studies, the diluent was changed or the urine was frozen in order to improve specificity but the results didn’t reach the gold standard pattern (serum, CSF) [8,9].…”

Brief Report: Geographical Variation in Prevalence of Cryptococcal Antigenemia Among HIV-Infected, Treatment-Naive Patients in Nigeria: A Multicenter Cross-Sectional Study

“…Magambo and colleagues also noted a high prevalence of asymptomatic cryptococcal antigenemia in patients with CD4 count between 100 and 200. 19 This calls into question the use of 100 CD4 cells/mm 3 as a cutoff. However, very little data exists on the cost-effectiveness of screening patients with CD4 100-200 cells/mm 3 , and little is known about differences in development of CM and survival of patients in this range as compared with those with CD4<100 cells/mL.…”