Cryptococcal antigen in serum and cerebrospinal fluid for detecting cryptococcal meningitis in adults living with HIV: systematic review and meta-analysis of diagnostic test accuracy studies.

Cryptococcal antigen (CrAg) detection could direct timely initiation of antifungal therapy. We searched MEDLINE and EMBASE for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on HIV-positive adults with suspected cryptococcal meningitis (CM). With QUADAS-2, we evaluated risk of bias (RoB) of 11 included studies on 3,600 participants and used random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg was 99.8% (88.4 - 100) and 95.2% (88.7 - 98), respectively; of CSF CrAg was 98.8% (96.2 - 99.6) and 99.3% (96.7 - 99.9), respectively. Agreement between CSF CrAg and CSF culture was 97% (96 - 99). In HIV-adults with CM symptoms, serum CrAg-negativity may rule out CM, positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In first episode of CM, CSF CrAg-positivity is diagnostic