Cryptococcal Antigen Screening Evaluated Among People Living with HIV

Cryptococcosis is a potentially fatal fungal disease caused by a few species of Cryptococcus (most often Cryptococcus neoformans or Cryptococcus gattii). Cryptococcosis is believed to be acquired by inhalation of the infectious propagule from the environment.

Most people in the USA who develop cryptococcal infections are HIV-positive. However, occasionally persons with no apparent immune system problems develop cryptococcosis. Cryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide.


An international team of scientists led by the University of Washington (Seattle, WA, USA) evaluated laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa. The team included 3,105 (39.4%) of 7,877 people screened were HIV-positive, of whom 908 had CD⁴ ≤200 cells/mm³ and were included in the analyses. The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, OK, USA).

The investigators reported that Lab reflex and clinic-based testing significantly increased CrAg screening and diagnosis of CrAg-positive PLHIV. As compared to clinician-directed testing, clinic-based CrAg testing increased the number of PLHIV diagnosed with cryptococcal meningitis (4.5% compared to 1.5%), initiation of fluconazole pre-emptive therapy (7.2% compared to 2.5%), and initiation of ART (96.8% compared to 91.3%). Comparing clinic-based testing to lab reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% compared to 4.1%) or mortality (8.1% compared to 9.9%).

The authors concluded that Lab reflex and clinic-based CrAg testing facilitated diagnosis of HIV-associated cryptococcosis and fluconazole initiation, but did not reduce cryptococcal meningitis or mortality. In this non-randomized cohort, clinical outcomes were similar between lab reflex testing and clinic-based point-of-care CrAg testing. The study was published on May 10, 2021 in the Journal of Acquired Immune Deficiency Syndromes.

Related Links:
University of Washington
Immy Diagnostics