{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:19:18Z","timestamp":1772461158521,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Heinz Ansmann Foundation","award":["U01AI125003"],"award-info":[{"award-number":["U01AI125003"]}]},{"name":"Hirsch Institute for Tropical Medicine","award":["U01AI125003"],"award-info":[{"award-number":["U01AI125003"]}]},{"name":"The U.S. National Institute of Allergy and Infectious Diseases","award":["U01AI125003"],"award-info":[{"award-number":["U01AI125003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg\/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7\/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6\/71); p &lt; 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.<\/jats:p>","DOI":"10.3390\/jof9080836","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T10:30:48Z","timestamp":1691577048000},"page":"836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Disseminated Cryptococcosis Is a Common Finding among Human Immunodeficiency Virus-Infected Patients with Suspected Sepsis and Is Associated with Higher Mortality Rates"],"prefix":"10.3390","volume":"9","author":[{"given":"Tafese Beyene","family":"Tufa","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital and Medical Faculty of the Heinrich, Heine University, 40225 D\u00fcsseldorf, Germany"},{"name":"Hirsch Institute of Tropical Medicine, Asella P.O. Box 04, Ethiopia"},{"name":"College of Health Sciences, Arsi University, Asella P.O. Box 04, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Martin","family":"Orth","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital and Medical Faculty of the Heinrich, Heine University, 40225 D\u00fcsseldorf, Germany"},{"name":"Hirsch Institute of Tropical Medicine, Asella P.O. Box 04, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1157-8700","authenticated-orcid":false,"given":"Tobias","family":"Wienemann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hospital Hygiene, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University, Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1626-4855","authenticated-orcid":false,"given":"Bjoern-Erik Ole","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital and Medical Faculty of the Heinrich, Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-2698","authenticated-orcid":false,"given":"Colin R.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hospital Hygiene, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University, Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-0060","authenticated-orcid":false,"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6288-8821","authenticated-orcid":false,"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital and Medical Faculty of the Heinrich, Heine University, 40225 D\u00fcsseldorf, Germany"},{"name":"Hirsch Institute of Tropical Medicine, Asella P.O. Box 04, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6755-4492","authenticated-orcid":false,"given":"Torsten","family":"Feldt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital and Medical Faculty of the Heinrich, Heine University, 40225 D\u00fcsseldorf, Germany"},{"name":"Hirsch Institute of Tropical Medicine, Asella P.O. Box 04, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ijid.2020.04.004","article-title":"Presentation and outcome of suspected sepsis in a high-HIV burden, high antiretroviral coverage setting","volume":"96","author":"Chaka","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S1473-3099(22)00499-6","article-title":"The global burden of HIV-associated cryptococcal infection in adults in 2020: A modelling analysis","volume":"22","author":"Rajasingham","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"989265","DOI":"10.3389\/fmed.2022.989265","article-title":"Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis","volume":"9","author":"Muzazu","year":"2022","journal-title":"Front. Med. (Lausanne)"},{"key":"ref_4","unstructured":"World Health Organization (2023, May 21). Guidelines for Diagnosing, Preventing and Managing Cryptococcal Disease among Adults, Adolescents and Children Living with HIV. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/357088."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e01238-18","DOI":"10.1128\/JCM.01238-18","article-title":"Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing","volume":"57","author":"Rajasingham","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e31-6","DOI":"10.1097\/QAI.0000000000000147","article-title":"Cryptococcal meningitis management in Tanzania with strict schedule of serial lumber punctures using intravenous tubing sets: An operational research study","volume":"66","author":"Meda","year":"2014","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ofy122","DOI":"10.1093\/ofid\/ofy122","article-title":"Detrimental Outcomes of Unmasking Cryptococcal Meningitis with Recent ART Initiation","volume":"5","author":"Rhein","year":"2018","journal-title":"Open Forum. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fuchs, A., Tufa, T.B., H\u00f6rner, J., Hurissa, Z., Nordmann, T., Bosselmann, M., Abdissa, S., Sorsa, A., Orth, H.M., and Jensen, B.O. (2021). Clinical and microbiological characterization of sepsis and evaluation of sepsis scores. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247646"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Seymour","year":"2016","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third Inter-national Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"943","DOI":"10.21037\/jtd.2017.03.125","article-title":"SIRS, qSOFA and new sepsis definition","volume":"9","author":"Marik","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S343","DOI":"10.1093\/cid\/ciab789","article-title":"Minimally Invasive Tissue Sampling: A Tool to Guide Efforts to Reduce AIDS-Related Mortality in Resource-Limited Settings","volume":"73","author":"Letang","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3201\/eid2001.130906","article-title":"Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast","volume":"20","author":"Boulware","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","unstructured":"(2022). WHO Fungal Priority Pathogens List to Guide Research Daphag, World Health Organization."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13756-022-01053-7","article-title":"Prevalence and characterization of antimicrobial resistance among gram-negative bacteria isolated from febrile hospitalized patients in central Ethiopia","volume":"11","author":"Tufa","year":"2022","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1080\/21505594.2016.1158359","article-title":"Bloodstream infections in HIV-infected patients","volume":"7","author":"Taramasso","year":"2016","journal-title":"Virulence"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.7883\/yoken.65.28","article-title":"Epidemiology of bloodstream infections and predictive factors of mortality among HIV-infected adult patients in Thailand in the era of highly active antiretroviral therapy","volume":"65","author":"Kiertiburanakul","year":"2012","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1093\/cid\/cix613","article-title":"Inadequacy of High-Dose Fluconazole Monotherapy Among Cerebrospinal Fluid Cryptococcal Antigen (CrAg)-Positive Human Immunodeficiency Virus-Infected Persons in an Ethiopian CrAg Screening Program","volume":"65","author":"Beyene","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lakoh, S., Rickman, H., Sesay, M., Kenneh, S., Burke, R., Baldeh, M., Jiba, D.F., Tejan, Y.S., Boyle, S., and Koroma, C. (2020). Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: A prospective study. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4862-x"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/QAI.0000000000001899","article-title":"Laboratory-Reflex Cryptococcal Antigen Screening Is Associated with a Survival Benefit in Tanzania","volume":"80","author":"Faini","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/cid\/ciac675","article-title":"Cryptococcal Antigenemia in Advanced Human Immunodefi-ciency Virus Disease: Pathophysiology, Epidemiology, and Clinical Implications","volume":"76","author":"Wake","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhao, T., Xu, X.L., Nie, J.M., Chen, X.H., Jiang, Z.S., Liu, S.Q., Yang, T.T., Yang, X., Sun, F., and Lu, Y.Q. (2021). Establishment of a novel scoring model for mortality risk prediction in HIV-infected patients with cryptococcal meningitis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06417-9"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/hiv.12679","article-title":"Serum cryptococcal antigen titre as a diagnostic tool and a predictor of mortality in HIV-infected patients with cryptococcal meningitis","volume":"20","author":"Chen","year":"2019","journal-title":"HIV Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/S0140-6736(15)60164-7","article-title":"Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: An open-label, randomised controlled trial","volume":"385","author":"Mfinanga","year":"2015","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/cid\/civ936","article-title":"Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study","volume":"62","author":"Longley","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1845","DOI":"10.1016\/S2214-109X(22)00450-8","article-title":"Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: An economic analysis of the AMBITION-cm trial","volume":"10","author":"Lawrence","year":"2022","journal-title":"Lancet Glob. Health"},{"key":"ref_27","unstructured":"(2023, May 21). National Consolidated Guidelines for Comprehensive HIV Prevention, Care and Treatment, Ethiopian HIV Prevention, Care and Treatment Guideline, Available online: https:\/\/www.afro.who.int\/publications\/national-consolidated-guidelines-comprehensive-hiv-prevention-care-and-treatment."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"695240","DOI":"10.3389\/fcimb.2021.695240","article-title":"ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates with High and Low Fluconazole IC (50)","volume":"11","author":"Gerlach","year":"2021","journal-title":"Front. Cell Infect. Microbiol."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/8\/836\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:28:29Z","timestamp":1760128109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/8\/836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["jof9080836"],"URL":"https:\/\/doi.org\/10.3390\/jof9080836","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]}}}