{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:49:12Z","timestamp":1773190152858,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We identified cryptococcosis tests (cryptococcal antigen [CrAg], cryptococcal antibody, and fungal cultures) performed at a major national commercial laboratory ordered during March 1, 2019\u2013October 1, 2021, and analyzed test results, patient and provider features, reasons for testing, geography, and temporal trends.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 29\u2009180 serum CrAg tests, 4422 (15.2%) were positive, and among 10\u2009724 cerebrospinal fluid (CSF) CrAg tests, 492 (4.6%) were positive. Frequent reasons for serum CrAg testing in nonhospital settings (10\u2009882 tests) were HIV (44.6%) and cryptococcosis (17.0%); other underlying conditions were uncommonly listed (&amp;lt;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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofac253","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T13:46:04Z","timestamp":1652708764000},"source":"Crossref","is-referenced-by-count":6,"title":["Testing for Cryptococcosis at a Major Commercial Laboratory\u2014United States, 2019\u20132021"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-2493","authenticated-orcid":false,"given":"Kaitlin","family":"Benedict","sequence":"first","affiliation":[{"name":"Mycotic Diseases Branch, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy A W","family":"Gold","sequence":"additional","affiliation":[{"name":"Mycotic Diseases Branch, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Dietz","sequence":"additional","affiliation":[{"name":"Division of Health Informatics and Surveillance, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seher","family":"Anjum","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Immunology, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R","family":"Williamson","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Immunology, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan R","family":"Jackson","sequence":"additional","affiliation":[{"name":"Mycotic Diseases Branch, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"2022073010015624600_ofac253-B1","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2022073010015624600_ofac253-B2","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/cid\/ciab268","article-title":"MSG07: an international cohort study comparing epidemiology and outcomes of patients with Cryptococcus neoformans or Cryptococcus gattii infections","volume":"73","author":"Baddley","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B3","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1086\/649858","article-title":"Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America","volume":"50","author":"Perfect","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B4","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/cid\/cix867","article-title":"Comparative epidemiology and outcomes of human immunodeficiency virus (HIV), non-HIV non-transplant, and solid organ transplant associated cryptococcosis: a population-based study","volume":"66","author":"George","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B5","doi-asserted-by":"crossref","first-page":"e56269","DOI":"10.1371\/journal.pone.0056269","article-title":"Epidemiology of cryptococcal meningitis in the US: 1997\u20132009","volume":"8","author":"Pyrgos","year":"2013","journal-title":"PLoS One"},{"key":"2022073010015624600_ofac253-B6","doi-asserted-by":"crossref","first-page":"e43582","DOI":"10.1371\/journal.pone.0043582","article-title":"Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative\/non-transplant","volume":"7","author":"Bratton","year":"2012","journal-title":"PLoS One"},{"key":"2022073010015624600_ofac253-B7","article-title":"Increased cryptococcal meningitis mortality among HIV negative, non-transplant patients: a single US center cohort study","volume":"7","author":"Motoa","year":"2020","journal-title":"Ther Adv Infect Dis"},{"key":"2022073010015624600_ofac253-B8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/qjmed\/hcl014","article-title":"Cryptococcosis in apparently immunocompetent patients","volume":"99","author":"Lui","year":"2006","journal-title":"QJM"},{"key":"2022073010015624600_ofac253-B9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/cid\/ciz193","article-title":"A multicenter, longitudinal cohort study of cryptococcosis in human immunodeficiency virus-negative people in the United States","volume":"70","author":"Marr","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B10","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/cid\/ciy776","article-title":"Estimation of direct healthcare costs of fungal diseases in the United States","volume":"68","author":"Benedict","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B11","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1093\/cid\/cis725","article-title":"Reconsidering cryptococcal antigen screening in the U.S. among persons with CD4&lt;100 cells\/mcL","volume":"55","author":"Rajasingham","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B12","article-title":"Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America","author":"Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV"},{"key":"2022073010015624600_ofac253-B13","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cmi.2019.11.016","article-title":"Diagnostic test accuracy of the BioFire\u00ae FilmArray\u00ae meningitis\/encephalitis panel: a systematic review and meta-analysis","volume":"26","author":"Tansarli","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"2022073010015624600_ofac253-B14","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1128\/CMR.15.3.465-484.2002","article-title":"Current status of nonculture methods for diagnosis of invasive fungal infections","volume":"15","author":"Yeo","year":"2002","journal-title":"Clin Microbiol Rev"},{"key":"2022073010015624600_ofac253-B15","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/myc.12882","article-title":"Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies","volume":"62","author":"Bahr","year":"2019","journal-title":"Mycoses"},{"key":"2022073010015624600_ofac253-B16","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.3201\/eid1806.111228","article-title":"Recognition and diagnosis of Cryptococcus gattii infections in the United States","volume":"18","author":"Iverson","year":"2012","journal-title":"Emerg Infect Dis"},{"key":"2022073010015624600_ofac253-B17","first-page":"585","article-title":"Prevalence and correlates of cryptococcal antigen positivity among AIDS patients\u2014United States, 1986\u20132012","volume":"63","author":"McKenney","year":"2014","journal-title":"Morb Mortal Wkly Rep"},{"key":"2022073010015624600_ofac253-B18","article-title":"Evaluation of a cryptococcal antigen lateral flow assay and cryptococcal antigen positivity at a large public hospital in Atlanta, Georgia","volume":"8:XXX\u2013XX","author":"Harrington","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2022073010015624600_ofac253-B19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.17294\/2330-0698.1717","article-title":"Cryptococcal antigen testing in an integrated medical system: Eastern Wisconsin","volume":"7","author":"Klumph","year":"2020","journal-title":"J Patient Cent Res Rev"},{"key":"2022073010015624600_ofac253-B20","doi-asserted-by":"crossref","first-page":"100563","DOI":"10.1016\/j.eclinm.2020.100563","article-title":"Potential missed opportunities for diagnosis of cryptococcosis and the association with mortality: a cohort study","volume":"27","author":"Salazar","year":"2020","journal-title":"EClinicalMedicine"},{"key":"2022073010015624600_ofac253-B21","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/clinids\/18.5.789","article-title":"Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis","volume":"18","author":"Powderly","year":"1994","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1310\/NQXR-ULMG-MM1B-3T2B","article-title":"Clinical utility of monitoring serum cryptococcal antigen (sCRAG) titers in patients with AIDS-related cryptococcal disease","volume":"1","author":"Aberg","year":"2000","journal-title":"HIV Clin Trials"},{"key":"2022073010015624600_ofac253-B23","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrneurol.2016.167","article-title":"Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy","volume":"13","author":"Williamson","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"2022073010015624600_ofac253-B24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/cid\/cit641","article-title":"Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid","volume":"58","author":"Kabanda","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2022073010015624600_ofac253-B25","article-title":"HIV in the United States by region","author":"Centers for Disease Control and Prevention"},{"key":"2022073010015624600_ofac253-B26","article-title":"Cryptococcus species other than Cryptococcus neoformans and Cryptococcus gattii: are they clinically significant?","volume":"7:XXX\u2013XX","author":"Cano","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2022073010015624600_ofac253-B27","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1128\/JCM.02447-06","article-title":"False-positive culture results from patient tissue specimens due to contamination of RPMI medium with Cryptococcus albidus","volume":"45","author":"Winston","year":"2007","journal-title":"J Clin Microbiol"},{"key":"2022073010015624600_ofac253-B28","doi-asserted-by":"crossref","first-page":"a019760-a","DOI":"10.1101\/cshperspect.a019760","article-title":"Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis","volume":"4","author":"Kwon-Chung","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2022073010015624600_ofac253-B29","article-title":"Testing practices for fungal respiratory infections and SARS-CoV-2 among infectious disease specialists, United States","volume":"7:605","author":"Benedict","year":"2021","journal-title":"J Fungi (Basel)"},{"key":"2022073010015624600_ofac253-B30","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.15585\/mmwr.mm6936a4","article-title":"Delay or avoidance of medical care because of COVID-19-related concerns - United States, June 2020","volume":"69","author":"Czeisler","year":"2020","journal-title":"Morb Mortal Wkly Rep"},{"key":"2022073010015624600_ofac253-B31","article-title":"Impact of COVID-19 on commercial laboratory testing in the United States. Paper presented at: Conference on Retroviruses and Opportunistic Infections","author":"Delaney","year":"2021"},{"key":"2022073010015624600_ofac253-B32","article-title":"Coronavirus disease 2019\u2013associated invasive fungal infection","volume":"8:XXX\u2013XX.","author":"Baddley","year":"2021","journal-title":"Open Forum Infect Dis"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofac253\/43711959\/ofac253.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/9\/7\/ofac253\/45029081\/ofac253.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/9\/7\/ofac253\/45029081\/ofac253.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T10:04:34Z","timestamp":1659175474000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofac253\/6586373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,16]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofac253","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,1]]},"published":{"date-parts":[[2022,5,16]]},"article-number":"ofac253"}}