{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:14:20Z","timestamp":1789164860227,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"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\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS086312"],"award-info":[{"award-number":["R01 NS086312"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23 NS110470"],"award-info":[{"award-number":["K23 NS110470"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI055433"],"award-info":[{"award-number":["T32 AI055433"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI145437"],"award-info":[{"award-number":["R01AI145437"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2TR002492"],"award-info":[{"award-number":["KL2TR002492"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["D43TW009345"],"award-info":[{"award-number":["D43TW009345"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43TW009345"],"award-info":[{"award-number":["D43TW009345"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012737","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["HHSN261201800006I"],"award-info":[{"award-number":["HHSN261201800006I"]}],"id":[{"id":"10.13039\/100012737","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"}]},{"name":"DHHS cooperative agreement","award":["1NU58DP006270"],"award-info":[{"award-number":["1NU58DP006270"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells\/\u03bcL; IQR: 9\u201376) and lower CSF white blood cell (WBC; 4 cells\/\u03bcL; IQR: 4\u201385) counts than paradoxical IRIS (CD4: 78 cells\/\u03bcL; IQR: 47\u2013142; WBC: 45 cells\/\u03bcL; IQR: 8\u2013128). Among those with CSF WBC &amp;lt;5 cells\/\u03bcL, 86% (43\/50) had relapse. Among those with CD4 counts &amp;lt;50 cells\/\u03bcL, 91% (39\/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Poor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT01802385.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac853","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T21:32:50Z","timestamp":1666906370000},"page":"1080-1087","source":"Crossref","is-referenced-by-count":12,"title":["Recurrence of Symptoms Following Cryptococcal Meningitis: Characterizing a Diagnostic Conundrum With Multiple Etiologies"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9431-8938","authenticated-orcid":false,"given":"Nathan C","family":"Bahr","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Kansas Medical Center , Kansas City, Kansas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb P","family":"Skipper","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Huppler-Hullsiek","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Ssebambulidde","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bozena M","family":"Morawski","sequence":"additional","affiliation":[{"name":"Cancer Data Registry of Idaho, Idaho Hospital Association , Boise, Idaho , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole W","family":"Engen","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Nuwagira","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mbarara University of Science and Technology , Mbarara , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson M","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, Massachusetts , USA"},{"name":"Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth S","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M","family":"Lofgren","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Abassi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota , 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