{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:32:30Z","timestamp":1788294750204,"version":"build-2803163510"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T00:00:00Z","timestamp":1699660800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["AI73896"],"award-info":[{"award-number":["AI73896"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["AI93257"],"award-info":[{"award-number":["AI93257"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["U19AI110818"],"award-info":[{"award-number":["U19AI110818"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013114","name":"Broad Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013114","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cryptococcal meningitis is the second most common cause of death in people living with HIV\/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and the genetic diversity of these infecting isolates can also be geographically linked. Here, we employ whole genome sequences for 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis obtained via a large clinical trial, across both Malawi and Cameroon, to enable population genetic comparisons of isolates between countries. We see that isolates from Cameroon are highly clonal, when compared to those from Malawi, with differential rates of disruptive variants in genes with roles in DNA binding and energy use. For a subset of patients (22) from Cameroon, we leverage longitudinal sampling, with samples taken at days 7 and 14 post-enrollment, to interrogate the genetic changes that arise over the course of infection, and the genetic diversity of isolates within patients. We see disruptive variants arising over the course of infection in several genes, including the phagocytosis-regulating transcription factor GAT204. In addition, in 13% of patients sampled longitudinally, we see evidence for mixed infections. This approach identifies geographically linked genetic variation, signatures of microevolution, and evidence for mixed infections across a clinical cohort of patients affected by cryptococcal meningitis in Central Africa.<\/jats:p>","DOI":"10.1093\/mmy\/myad116","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T22:21:02Z","timestamp":1699568462000},"source":"Crossref","is-referenced-by-count":4,"title":["Genetic diversity and microevolution in clinical <i>Cryptococcus<\/i> isolates from Cameroon"],"prefix":"10.1093","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-6028","authenticated-orcid":false,"given":"Poppy","family":"Sephton-Clark","sequence":"first","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-6555","authenticated-orcid":false,"given":"Elvis","family":"Temfack","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Douala General Hospital , Douala , Cameroon"},{"name":"Institut Pasteur, Molecular Mycology Unit, CNRS UMR 2000 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Tenor","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena L","family":"Toffaletti","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine , Durham, North Carolina , 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tihana","family":"Bicanic","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, St George\u2019s University of London , London , UK"},{"name":"Clinical Academic Group in Infection, St George\u2019s University Hospital , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Harrison","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, St George\u2019s University of London , London , UK"},{"name":"MRC Centre for Medical Mycology, University of Exeter , Exeter , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lortholary","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Tropical Medicine, Paris Cit\u00e9 University, Necker-Enfants Malades Hospital, AP-HP, IHU Imagine , Paris , France"},{"name":"Mycology Department and National Reference Center for Invasive Mycoses and Antifungals, Institut Pasteur , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Kouanfack","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang , Dschang , Cameroon"},{"name":"Day Hospital, Hospital Central Yaound\u00e9 , Yaound\u00e9 , Cameroon"},{"name":"Research Center for Emerging and Re-emerging Diseases, Cameroon Baptist Convention Health Services (CBCHS) , Yaound\u00e9 , Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-960X","authenticated-orcid":false,"given":"Christina A","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard , Cambridge, Massachusetts , 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