Evaluation of serum cryptococcal antigen testing using two novel semi-quantitative lateral flow assays in persons with cryptococcal antigenemia.

Introduction: Early cryptococcal disease can be detected via circulating antigen in blood before fulminant meningitis develops—where early antifungal therapy improves survival. Two semi-quantitative cryptococcal antigen (CrAg) lateral flow assays have been developed, but with undefined diagnostic performance. Method: Cryopreserved serum samples from HIV-infected Ugandans obtained as part of a prospective CrAg-screening cohort were tested in duplicate for CrAg by the CrAgSQ (IMMY) and CryptoPS (Biosynex) lateral flow assays. Case-controlled diagnostic performance was measured using the FDA-approved CrAg LFA (IMMY) as a reference standard via McNemar9s test. Results: Of 99 serum samples tested, 57 were CrAg+ by the CrAg LFA reference standard. By CrAgSQ, 57 were read positive, with 98% sensitivity (56/57; 95%CI, 0.91–0.99) and 98% specificity (41/42; 95%CI, 0.88–0.99) (McNemar9s, P=.99). The CrAgSQ false negative (n=1) had a titer Conclusion: The new semi-quantitative CrAg LFAs allow for a rapid estimation of titer level in easy-to-perform platforms. The CrAgSQ demonstrated better qualitative sensitivity and specificity over CryptoPS in comparison to the reference standard. The exact grade of the CrAgSQ has some subjectivity with inter-reader variability; however, qualitative reads were generally concordant for both assays.