Testing for Cryptococcosis at a Major Commercial Laboratory-United States, 2019-2021

Kaitlin Benedict; Jeremy A W Gold; Stephanie Dietz; Seher Anjum; Peter R Williamson; Brendan R Jackson

doi:10.1093/ofid/ofac253

Testing for Cryptococcosis at a Major Commercial Laboratory-United States, 2019-2021

Open Forum Infect Dis. 2022 May 16;9(7):ofac253. doi: 10.1093/ofid/ofac253. eCollection 2022 Jul.

Authors

Kaitlin Benedict¹, Jeremy A W Gold¹, Stephanie Dietz², Seher Anjum³, Peter R Williamson³, Brendan R Jackson¹

Affiliations

¹ Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
² Division of Health Informatics and Surveillance, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
³ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Background: Cryptococcosis is a serious opportunistic fungal disease, and the proportion of cases among patients with immunosuppressive conditions other than HIV or organ transplant has increased. Understanding laboratory testing patterns for cryptococcosis is useful for estimating its true burden and developing testing guidance.

Methods: We identified cryptococcosis tests (cryptococcal antigen [CrAg], cryptococcal antibody, and fungal cultures) performed at a major national commercial laboratory ordered during March 1, 2019-October 1, 2021, and analyzed test results, patient and provider features, reasons for testing, geography, and temporal trends.

Results: Among 29 180 serum CrAg tests, 4422 (15.2%) were positive, and among 10 724 cerebrospinal fluid (CSF) CrAg tests, 492 (4.6%) were positive. Frequent reasons for serum CrAg testing in nonhospital settings (10 882 tests) were HIV (44.6%) and cryptococcosis (17.0%); other underlying conditions were uncommonly listed (<10% total). Serum CrAg positivity declined from 25.6% in October 2019 to 11.3% in September 2021. The South had the highest positivity for serum CrAg tests (16.6%), CSF CrAg tests (4.7%), and fungal cultures (0.15%). Among 5009 cryptococcal antibody tests, 5 (0.1%) were positive.

Conclusions: Few outpatient serum CrAg tests were performed for patients with immunocompromising conditions other than HIV, suggesting potential missed opportunities for early detection. Given the high positive predictive value of CrAg testing, research is needed to improve early diagnosis, particularly in patients without HIV. Conversely, the low yield of antibody testing suggests that it may be of low value. The decline in CrAg positivity during the COVID-19 pandemic warrants further investigation.

Keywords: Cryptococcus; United States; antigens; cryptococcosis; fungal; laboratories.

Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.