Evaluation of new semi-quantitative cryptococcal antigen Immy (immunochromatographic) SQ (semi-quantitative) and Biosynex tests in plasma for detection of subclinical cryptococcal meningitis in HIV positive patients with CD4 <100

Abstract

Introduction: Blood cryptococcal antigen (CrAg) titres >160 are associated with concurrent subclinical cryptococcal meningitis (CM). When lumbar puncture (LP) is not immediately available in a CrAg screening programme, semi-quantitative CrAg assays may provide risk stratification for CM. Materials and methods: Two semi-quantitative assays (SQ [Immuno-Mycologics, Norman, OK, USA] and CryptoPS [Biosynex, Strasbourg, France]) were evaluated against a qualitative lateral flow assay (LFA) using 194 plasma samples from a cohort of HIV-seropositive individuals with CD4 counts <100 cells/μL. We compared SQ and CryptoPS results to titres for LFA-positive samples. Among patients with LP, we examined the association between semi-quantitative CrAg results and CM. We used a Cox proportional hazards model to determine the association between SQ score and mortality. Results: Of 194 participants, 60 (31%) had positive LFA results, of whom 41 (68%) had a titre of ≤160 and 19 (32%) a titre >160. Fifty individuals with antigenaemia had an LP; a clinically-useful SQ score that identified all ten cases of subclinical CM was ≥3 (100% sensitivity, 55% specificity). Patients with an SQ score of 3 or 4 also had a 2.2-fold increased adjusted hazards of 6-month mortality (95% CI, 0.79-6.34; p=0.13) versus those with score of <3. Nine of ten patients with subclinical CM had a strong-positive CryptoPS result versus 10/40 without subclinical CM (p<0.001). Conclusions: Semi-quantitative assays offered a sensitive though not specific means of gauging the risk of concurrent CM in this patient population.