{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:40:38Z","timestamp":1793691638294,"version":"4.5.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T00:00:00Z","timestamp":1551052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T00:00:00Z","timestamp":1551052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23 AI108293"],"award-info":[{"award-number":["K23 AI108293"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since rapid cryptococcal antigen lateral flow assays (CrAg LFA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-based CrAg LFA testing. Among newly-diagnosed HIV-infected adults in South Africa, a trained nurse performed clinic-based testing of urine, fingerprick capillary and venous whole blood with rapid CrAg LFA (Immy Diagnostics, Norman, USA). We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay (EIA). We assessed diagnostic accuracy using EIA as the gold-standard, and performed additional validation testing on serum and among hospitalized adults with cryptococcal meningitis. Among 5,618 participants enrolled, 1,296 were HIV-infected and screened for cryptococcal antigenemia. Overall CrAg prevalence by serum EIA was 3.6% (95% CI 2.0\u20136.0%) for adults with CD4\u2009&lt;\u2009200 cells\/mm<jats:sup>3<\/jats:sup>, and 5.7% (95% CI 2.8\u201310.2%) for adults with CD4\u2009&lt;\u2009100 cells\/mm<jats:sup>3<\/jats:sup>. Using expanded screening guidelines (CD4\u2009&lt;\u2009200 cells\/mm<jats:sup>3<\/jats:sup>), CrAg LFA testing of venous whole blood, fingerprick capillary blood, and urine had diagnostic sensitivities of 46% (95% CI 19\u201375%), 38% (95% CI 14\u201368%), and 54% (95% CI 25\u201381%), and specificities of 97%, 97%, and 86%, respectively. When tested on serum samples, CrAg LFA had sensitivity of 93% (95% CI 66\u2013100%) and specificity of 100% (95% CI 88\u2013100%). All venous and fingerprick whole blood CrAg LFA tests were positive among 30 hospitalized adults with cryptococcal meningitis. Two independent readers had strong agreement for all LFA results (p\u2009&lt;\u20090.0001). When performed at the point-of-care by trained nurses, CrAg LFA testing was feasible, had the highest accuracy on serum specimens, and may accelerate treatment of HIV-associated cryptococcal infections.<\/jats:p>","DOI":"10.1038\/s41598-018-37478-7","type":"journal-article","created":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T11:03:08Z","timestamp":1551092588000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Validation of clinic-based cryptococcal antigen lateral flow assay screening in HIV-infected adults in South Africa"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3300-3817","authenticated-orcid":false,"given":"Paul K.","family":"Drain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meighan","family":"Krows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Govere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Thulare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole L.","family":"Wallis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett I.","family":"Gosnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahomed-Yunus","family":"Moosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid V.","family":"Bassett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Celum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,25]]},"reference":[{"key":"37478_CR1","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","volume":"17","author":"R Rajasingham","year":"2017","unstructured":"Rajasingham, R. et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 17, 873\u2013881 (2017).","journal-title":"Lancet Infect Dis."},{"key":"37478_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-67","volume":"10","author":"JN Jarvis","year":"2010","unstructured":"Jarvis, J. N. et al. Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases. BMC Infect Dis. 10, 67 (2010).","journal-title":"BMC Infect Dis."},{"key":"37478_CR3","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1097\/00002030-200205030-00009","volume":"16","author":"N French","year":"2002","unstructured":"French, N. et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 16, 1031\u20131038 (2002).","journal-title":"AIDS."},{"key":"37478_CR4","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1111\/j.1365-3156.2007.01874.x","volume":"12","author":"CA Liechty","year":"2007","unstructured":"Liechty, C. A. et al. Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health. 12, 929\u2013935 (2007).","journal-title":"Trop Med Int Health."},{"key":"37478_CR5","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1086\/597262","volume":"48","author":"JN Jarvis","year":"2009","unstructured":"Jarvis, J. N. et al. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment clinic in South Africa. 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AIDS. 29, 2473\u20132478 (2015).","journal-title":"AIDS."},{"key":"37478_CR8","doi-asserted-by":"publisher","first-page":"ofv046","DOI":"10.1093\/ofid\/ofv046","volume":"2","author":"E Letang","year":"2015","unstructured":"Letang, E. et al. Cryptococcal antigenemia in immunocompromised HIV patients in rural Tanzania: a preventable cause of early mortality. Open Forum Infect Dis. 2, ofv046 (2015).","journal-title":"Open Forum Infect Dis."},{"key":"37478_CR9","unstructured":"Pett, S. L. et al CrAg status and effects on benefits from enhanced prophylaxis in the REALITY trial. Conference on Retroviruses and Opportunistic Infections. Poster #784 (2018)."},{"key":"37478_CR10","unstructured":"World Health Organization. Rapid Advice: Diagnosis, prevention and management of Cryptococcal disease in HIV-infected adults, adolescents and children. Geneva: WHO (2011)."},{"key":"37478_CR11","unstructured":"World Health Organization. Guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children, March 2018. Geneva: World Health Organization. License: CC BY-NC-SA3.0 IGO."},{"key":"37478_CR12","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1097\/QAI.0b013e31824c837e","volume":"59","author":"R Rajasingham","year":"2012","unstructured":"Rajasingham, R., Meya, D. B. & Boulware, D. R. Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. Journal of acquired immune deficiency syndromes. 59, e85\u201391 (2012).","journal-title":"Journal of acquired immune deficiency syndromes."},{"key":"37478_CR13","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1093\/cid\/cir613","volume":"53","author":"JN Jarvis","year":"2011","unstructured":"Jarvis, J. N. et al. Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis. 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CD4 cell count threshold for cryptococcal antigen screening of HIV-infected individuals. Clin Infect Dis. In press."},{"key":"37478_CR20","doi-asserted-by":"publisher","first-page":"e75585","DOI":"10.1371\/journal.pone.0075585","volume":"8","author":"T Beyene","year":"2013","unstructured":"Beyene, T., Woldeamanuel, Y., Asrat, D., Ayana, G. & Boulware, D. R. Comparison of cryptococcal antigenemia between antiretroviral na\u00efve and antiretroviral experienced HIV positive patients at two hospitals in Ethiopia. PloS ONE. 8, e75585 (2013).","journal-title":"PloS ONE."},{"key":"37478_CR21","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1128\/CVI.00536-12","volume":"20","author":"J Hansen","year":"2013","unstructured":"Hansen, J. et al. Large-scale evaluation of the immune-mycologics lateral flow and enzyme-linked immunoassay for detection of cryptococcal antigen in serum and cerebrospinal fluid. 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Clin Infect Dis. 66, 686\u2013692 (2018).","journal-title":"Clin Infect Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37478-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37478-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37478-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T06:26:15Z","timestamp":1671258375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37478-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,25]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["37478"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-37478-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,25]]},"assertion":[{"value":"4 September 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"2687"}}