{"doi":"10.3390/jof9010046","title":"Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality","abstract":"Cryptococcus is the leading cause of AIDS-related meningitis in sub-Saharan Africa. The clinical implications of a sterile cerebrospinal fluid (CSF) culture among individuals diagnosed with cryptococcal meningitis using CSF cryptococcal antigen (CrAg) are unclear. We prospectively enrolled 765 HIV-positive Ugandans with first-episode cryptococcal meningitis from November 2010 to May 2017. All persons were treated with amphotericin-based induction therapy. We grouped participants by tertile of baseline CSF quantitative Cryptococcus culture burden and compared clinical characteristics, CSF immune profiles, and 18-week mortality. We found 55 (7%) CSF CrAg-positive participants with sterile CSF cultures. Compared to the non-sterile groups, participants with sterile CSF cultures had higher CD4 counts, lower CSF opening pressures, and were more frequently receiving ART. By 18 weeks, 47% [26/55] died in the sterile culture group versus 35% [83/235] in the low culture tertile, 46% [107/234] in the middle tertile, and 56% [135/241] in the high tertile (p < 0.001). The sterile group had higher levels of CSF interferon-gamma (IFN-γ), IFN-α, interleukin (IL)-6, IL-17, G-CSF, GM-CSF, and chemokine CXCL2 compared with non-sterile groups. Despite persons with sterile CSF cultures having higher CD4 counts, lower CSF opening pressures, and CSF cytokine profiles associated with better Cryptococcus control (e.g., IFN-γ predominant), mortality was similar to those with higher fungal burdens. This unexpected finding challenges the traditional paradigm that increasing CSF fungal burdens are associated with increased mortality but is consistent with a damage-response framework model.","journal":"Journal of Fungi","year":2022,"id":263842,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9207,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":269372,"name":"Katherine Huppler Hullsiek","orcid":null,"position":1,"is_corresponding":false},{"id":453915,"name":"Anna Stadelman","orcid":null,"position":2,"is_corresponding":false},{"id":269371,"name":"Darlisha A Williams","orcid":null,"position":3,"is_corresponding":false},{"id":452980,"name":"Kenneth Ssebambulidde","orcid":"0000-0002-8125-0698","position":4,"is_corresponding":false},{"id":267652,"name":"Elizabeth C Okafor","orcid":"0000-0003-1495-4596","position":5,"is_corresponding":false},{"id":452981,"name":"Lillian Tugume","orcid":"0000-0002-1293-1545","position":6,"is_corresponding":false},{"id":292463,"name":"Edwin Nuwagira","orcid":"0000-0001-7526-9504","position":7,"is_corresponding":false},{"id":732100,"name":"Andrew Akampurira","orcid":null,"position":8,"is_corresponding":false},{"id":578702,"name":"Abdu K Musubire","orcid":"0000-0003-2410-5344","position":9,"is_corresponding":false},{"id":267660,"name":"Mahsa Abassi","orcid":"0000-0001-9601-3006","position":10,"is_corresponding":false},{"id":399943,"name":"Conrad Muzoora","orcid":"0000-0002-7866-5198","position":11,"is_corresponding":false},{"id":445888,"name":"Joshua Rhein","orcid":"0000-0002-0480-9646","position":12,"is_corresponding":false},{"id":267658,"name":"David R. Boulware","orcid":"0000-0002-4715-0060","position":13,"is_corresponding":false},{"id":397657,"name":"David B. Meya","orcid":"0000-0002-8854-0321","position":14,"is_corresponding":false},{"id":267647,"name":"Caleb P Skipper","orcid":"0000-0002-0000-8876","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:26:33.413850Z","pmid":"36675867","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}