{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:32:28Z","timestamp":1791952348549,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,6,8]],"date-time":"2019-06-08T00:00:00Z","timestamp":1559952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["ACF-2015-16-003"],"award-info":[{"award-number":["ACF-2015-16-003"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St George\u2019s Hospital Research Charity"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI118511"],"award-info":[{"award-number":["R01AI118511"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ratanji Dalal Research Scholarship"},{"name":"South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa"},{"DOI":"10.13039\/501100000403","name":"Meningitis Research Foundation","doi-asserted-by":"publisher","award":["1604.0"],"award-info":[{"award-number":["1604.0"]}],"id":[{"id":"10.13039\/501100000403","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cryptococcal antigen (CrAg) screening and treatment with preemptive fluconazole reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advanced human immunodeficiency virus (HIV) disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a cohort study to investigate causes of morbidity and mortality during 6 months of follow-up among asymptomatic CrAg-positive and CrAg-negative (ratio of 1:2) patients living with HIV with CD4 counts &amp;lt;100 cells\/\u00b5L attending 2 hospitals in Johannesburg, South Africa. When possible, minimally invasive autopsy (MIA) was performed on participants who died.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty-seven CrAg-positive and 134 CrAg-negative patients were enrolled. Death occurred in 17\/67 (25%) CrAg-positive and 12\/134 (9%) CrAg-negative participants (hazard ratio for death, adjusted for CD4 count, 3.0; 95% confidence interval, 1.4\u20136.7; P = .006). Cryptococcal disease was an immediate or contributing cause of death in 12\/17 (71%) CrAg-positive participants. Postmortem cryptococcal meningitis and pulmonary cryptococcosis were identified at MIA in all 4 CrAg-positive participants, 3 of whom had negative cerebrospinal fluid CrAg tests from lumbar punctures (LPs) at the time of CrAg screening.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cryptococcal disease was an important cause of mortality among asymptomatic CrAg-positive participants despite LPs to identify and treat those with subclinical cryptococcal meningitis and preemptive fluconazole for those without meningitis. Thorough investigation for cryptococcal disease with LPs and blood cultures, prompt ART initiation, and more intensive antifungals may reduce mortality among asymptomatic CrAg-positive patients identified through screening.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz485","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T19:11:22Z","timestamp":1559934682000},"page":"1683-1690","source":"Crossref","is-referenced-by-count":54,"title":["Cryptococcal-related Mortality Despite Fluconazole Preemptive Treatment in a Cryptococcal Antigen Screen-and-Treat Program"],"prefix":"10.1093","volume":"70","author":[{"given":"Rachel M","family":"Wake","sequence":"first","affiliation":[{"name":"Centre for Healthcare-associated Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases, Johannesburg, South Africa"},{"name":"Institute of Infection & Immunity, St George\u2019s University of London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelesh P","family":"Govender","sequence":"first","affiliation":[{"name":"Centre for Healthcare-associated Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases, Johannesburg, South Africa"},{"name":"School of Pathology, University of the Witwatersrand, Johannesburg, South Africa"},{"name":"Division of Medical Microbiology, University of Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvier","family":"Omar","sequence":"first","affiliation":[{"name":"Department of Anatomical Pathology, University of the Witwatersrand, South Africa"},{"name":"Department of Pathology, National Health Laboratory Services, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Nel","sequence":"first","affiliation":[{"name":"Department of Anatomical Pathology, University of the Witwatersrand, South Africa"},{"name":"Department of Pathology, National Health Laboratory Services, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Haeri","family":"Mazanderani","sequence":"first","affiliation":[{"name":"Centre for HIV & STIs, National Institute for Communicable Diseases, Johannesburg, South Africa"},{"name":"Department of Medical Virology, University of Pretoria, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron S","family":"Karat","sequence":"first","affiliation":[{"name":"Tuberculosis Centre, London School of Hygiene & Tropical Medicine, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazir A","family":"Ismail","sequence":"first","affiliation":[{"name":"Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline T","family":"Tiemessen","sequence":"first","affiliation":[{"name":"Centre for HIV & STIs, National Institute for Communicable Diseases, Johannesburg, South Africa"},{"name":"Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N","family":"Jarvis","sequence":"first","affiliation":[{"name":"Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom"},{"name":"Botswana-UPenn Partnership, Gaborone"},{"name":"Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Harrison","sequence":"first","affiliation":[{"name":"Institute of Infection & Immunity, St George\u2019s University of London, United 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