{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:47:29Z","timestamp":1792280849609,"version":"4.4.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Cryptococcal meningitis is one of the most devastating infections, particularly in HIV-infected individuals. The increased use of immunosuppressants led to an increase in the incidence of cryptococcosis in HIV-uninfected individuals. This study aimed to compare the characteristics between groups. Methods: This retrospective cohort study was conducted from 2011 to 2021 in northern Thailand. Individuals diagnosed with cryptococcal meningitis aged \u226515 years were enrolled onto the study. Results: Out of 147 patients, 101 were individuals infected with HIV and 46 were non-infected. Factors associated with being infected with HIV included age &lt; 45 years (OR 8.70, 95% CI 1.78\u201342.62), white blood cells &lt; 5000 cells\/cu.mm. (OR 7.18, 95% CI 1.45\u201335.61), and presence of fungemia (OR 5.86, 95% CI 1.17\u201342.62). Overall, the mortality rate was 24% (18% in HIV-infected vs. 37% in HIV-uninfected individuals, p-value = 0.020). Factors associated with mortality included concurrent pneumocystis pneumonia (HR 5.44, 95% CI 1.55\u201319.15), presence of alteration of consciousness (HR 2.94, 95% CI 1.42\u20136.10), infection caused by members of C. gattii species complex (HR 4.19, 95% CI 1.39\u201312.62), and anemia (HR 3.17, 95% CI 1.17\u20138.59). Conclusions: Clinical manifestations of cryptococcal meningitis differed between patients with and without HIV-infection in some aspects. Increasing awareness in physicians of this disease in HIV-uninfected individuals may prompt earlier diagnosis and timely treatment.<\/jats:p>","DOI":"10.3390\/pathogens12030427","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T02:01:47Z","timestamp":1678327307000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cryptococcal Meningitis: Differences between Patients with and without HIV-Infection"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-1210","authenticated-orcid":false,"given":"Chutithep","family":"Teekaput","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Faculty of Medicine Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saowaluck","family":"Yasri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romanee","family":"Chaiwarith","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrneurol.2016.167","article-title":"Cryptococcal meningitis: Epidemiology, immunology, diagnosis and therapy","volume":"13","author":"Williamson","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","article-title":"Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\/AIDS","volume":"23","author":"Park","year":"2009","journal-title":"AIDS"},{"key":"ref_3","first-page":"551","article-title":"Central nervous system infections in HIV-infected patients hospitalized at King Chulalongkorn Memorial Hospital","volume":"94","author":"Kongsiriwattanakul","year":"2011","journal-title":"J. Med. Assoc. Thai."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s40588-017-0064-8","article-title":"Cryptococcosis today: It is not all about HIV infection","volume":"4","author":"Powderly","year":"2017","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1086\/322597","article-title":"Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy","volume":"33","author":"Pappas","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","first-page":"61","article-title":"Cryptococcal infections in non-HIV-infected patients","volume":"124","author":"Pappas","year":"2013","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s42770-020-00383-1","article-title":"Cryptococcal meningitis in non-HIV patients in the State of Amazonas, Northern Brazil","volume":"52","author":"Pinheiro","year":"2021","journal-title":"Braz. J. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bratton, E.W., El Husseini, N., Chastain, C.A., Lee, M.S., Poole, C., Sturmer, T., Juliano, J.J., Weber, D.J., and Perfect, J.R. (2012). Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative\/non-transplant. PLoS ONE, 7.","DOI":"10.1371\/annotation\/a94bc542-6682-4579-a315-57019cef7e0e"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.7883\/yoken.JJID.2015.340","article-title":"Cryptococcosis in Anti-Interferon-Gamma Autoantibody-Positive Patients: A Different Clinical Manifestation from HIV-Infected Patients","volume":"70","author":"Chetchotisakd","year":"2017","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rujirachun, P., Sangwongwanich, J., and Chayakulkeeree, M. (2020). Triple infection with Cryptococcus, varicella-zoster virus, and Mycobacterium abscessus in a patient with anti-interferon-gamma autoantibodies: A case report. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4949-4"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/S0140-6736(98)03201-2","article-title":"Changing patterns of mortality across Europe in patients infected with HIV-1","volume":"352","author":"Mocroft","year":"1998","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1056\/NEJM199803263381301","article-title":"Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection","volume":"338","author":"Palella","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1097\/00002030-200012010-00019","article-title":"Declining number of patients with cryptococcosis in the Netherlands in the era of highly active antiretroviral therapy","volume":"14","author":"Walenkamp","year":"2000","journal-title":"AIDS"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Beardsley, J., Sorrell, T.C., and Chen, S.C. (2019). Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients. J. Fungi, 5.","DOI":"10.3390\/jof5030071"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1053\/jhin.1998.0610","article-title":"The prognostic factors of cryptococcal meningitis in HIV-negative patients","volume":"42","author":"Lu","year":"1999","journal-title":"J. Hosp. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/qjmed\/hcl014","article-title":"Cryptococcosis in apparently immunocompetent patients","volume":"99","author":"Lui","year":"2006","journal-title":"QJM"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/qjmed\/93.4.245","article-title":"Cryptococcal meningitis in non-HIV-infected patients","volume":"93","author":"Shih","year":"2000","journal-title":"QJM"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3109\/13693780903437876","article-title":"Cryptococcal meningitis in non-HIV-infected patients in a Chinese tertiary care hospital, 1997\u20132007","volume":"48","author":"Zhu","year":"2010","journal-title":"Med. Mycol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ebiom.2018.10.045","article-title":"Genetic influence of Toll-like receptors on non-HIV cryptococcal meningitis: An observational cohort study","volume":"37","author":"Jiang","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s11046-020-00491-4","article-title":"Cryptococcus neoformans Meningitis Cases Among China\u2019s HIV-Infected Population may have been Severely Under-Reported","volume":"185","author":"Chen","year":"2020","journal-title":"Mycopathologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.fgb.2014.10.017","article-title":"Epidemiology of Cryptococcus and cryptococcosis in China","volume":"78","author":"Fang","year":"2015","journal-title":"Fungal Genet. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1093\/infdis\/jir152","article-title":"Genotypes coding for mannose-binding lectin deficiency correlated with cryptococcal meningitis in HIV-uninfected Chinese patients","volume":"203","author":"Ou","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1136\/jnnp.48.9.853","article-title":"Cryptococcal meningitis","volume":"48","author":"Tjia","year":"1985","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/13693780410001731628","article-title":"Management of cryptococcosis in non-HIV-related patients","volume":"43","author":"Yao","year":"2005","journal-title":"Med. Mycol."},{"key":"ref_26","first-page":"227","article-title":"Saprophytic sources of Cryptococcus neoformans associated with the pigeon (Columba livia)","volume":"62","author":"Emmons","year":"1955","journal-title":"Am. J. Hyg."},{"key":"ref_27","unstructured":"Diem, P.K., Pimple, U., Sitthi, A., Varnakovida, P., Kaewthongrach, R., and Chidthaisong, A. (2017, January 23\u201325). Responses of Tropical Deciduous Forest Phenology to Climate Variation in Northern Thailand. Proceedings of the International Conference on Environmental Research and Technology (ICERT 2017), Georgetown, Penang, Malaysia."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1038\/s41396-018-0084-2","article-title":"Decomposer food web in a deciduous forest shows high share of generalist microorganisms and importance of microbial biomass recycling","volume":"12","author":"Brabcova","year":"2018","journal-title":"ISME J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Byrnes, E.J., Li, W., Ren, P., Lewit, Y., Voelz, K., Fraser, J.A., Dietrich, F.S., May, R.C., Chaturvedi, S., and Chaturvedi, V. (2011). A diverse population of Cryptococcus gattii molecular type VGIII in southern Californian HIV\/AIDS patients. PLoS Pathog., 7.","DOI":"10.1371\/annotation\/a23709b0-8d67-4b57-aa05-d5d70d830724"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1128\/CMR.00126-13","article-title":"Cryptococcus gattii infections","volume":"27","author":"Chen","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.2217\/fmb-2020-0086","article-title":"Cerebrospinal fluid microscopy as an index for predicting the prognosis of cryptococcal meningitis patients with and without HIV","volume":"15","author":"Zhang","year":"2020","journal-title":"Future Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"450","DOI":"10.5811\/cpcem.2021.8.53368","article-title":"An Uncommon Presentation of Cryptococcal Meningitis in an Immunocompetent Patient: A Case Report","volume":"5","author":"Correa","year":"2021","journal-title":"Clin. Pract. Cases Emerg. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2324709619834578","DOI":"10.1177\/2324709619834578","article-title":"Cryptococcal Meningitis in an Apparent Immunocompetent Patient","volume":"7","author":"Poley","year":"2019","journal-title":"J. Investig. Med. High Impact. Case Rep."},{"key":"ref_34","first-page":"756","article-title":"Hematologic derangements in HIV\/AIDS patients and their relationship with the CD4 counts: A cross-sectional study","volume":"13","author":"Bhardwaj","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fcimb.2020.00170","article-title":"Underlying Cryptococcal Diseases and the Correlation With Serum Cryptococcal Antigen Titers in Hospitalized HIV-Infected Patients Screened Positive for Cryptococcal Antigenemia","volume":"10","author":"Xu","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.jiph.2019.10.011","article-title":"Cryptococcus neoformans seropositivity and some haematological parameters in HIV seropositive subjects","volume":"13","author":"Chukwuanukwu","year":"2020","journal-title":"J. Infect. Public Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111","DOI":"10.7883\/yoken.JJID.2008.111","article-title":"Comparison of clinical features and survival between cryptococcosis in human immunodeficiency virus (HIV)-positive and HIV-negative patients","volume":"61","author":"Jongwutiwes","year":"2008","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_38","first-page":"33","article-title":"Cryptococcal meningitis in human immunodeficiency virus (HIV)-positive and HIV-negative patients","volume":"35","author":"Viriyavejakul","year":"2004","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/cid\/cis529","article-title":"Clinical manifestations of Cryptococcus gattii infection: Determinants of neurological sequelae and death","volume":"55","author":"Chen","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1155\/2009\/719659","article-title":"Clinical presentation, diagnosis and management of Cryptococcus gattii cases: Lessons learned from British Columbia","volume":"20","author":"Galanis","year":"2009","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1093\/cid\/cir723","article-title":"Cryptococcus gattii in the United States: Clinical aspects of infection with an emerging pathogen","volume":"53","author":"Harris","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jns.2016.06.069","article-title":"Spectrum of neuroimaging findings in cryptococcal meningitis in immunocompetent patients in China\u2014A series of 18 cases","volume":"368","author":"Tan","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s10096-017-2941-8","article-title":"Magnetic resonance imaging study of cryptococcal neuroradiological lesions in HIV-negative cryptococcal meningitis","volume":"36","author":"Zhong","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s40475-015-0046-y","article-title":"Cryptococcal Meningitis: Diagnosis and Management Update","volume":"2","author":"Abassi","year":"2015","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_45","first-page":"636","article-title":"Cryptococcal meningitis in HIV-infected patients at Chiang Mai University Hospital: A retrospective study","volume":"45","author":"Chaiwarith","year":"2014","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/COH.0000000000000488","article-title":"Post-treatment and spontaneous HIV control","volume":"13","author":"Martin","year":"2018","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_47","unstructured":"Sadiq, U., Shrestha, U., and Guzman, N. (2022). StatPearls, StatPearls."},{"key":"ref_48","first-page":"1122","article-title":"Long-term Mortality and Disability in Cryptococcal Meningitis: A Systematic Literature Review","volume":"66","author":"Pasquier","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/cid\/ciab268","article-title":"MSG07: An International Cohort Study Comparing Epidemiology and Outcomes of Patients With Cryptococcus neoformans or Cryptococcus gattii Infections","volume":"73","author":"Baddley","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_50","first-page":"1368","article-title":"Longitudinal clinical findings and outcome among patients with Cryptococcus gattii infection in British Columbia","volume":"60","author":"Phillips","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sim, B.Z., Conway, L., Smith, L.K., Fairhead, L., Der, Y.S., Payne, L., Binotto, E., Smith, S., and Hanson, J. (2022). The aetiology and clinical characteristics of cryptococcal infections in Far North Queensland, tropical Australia. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0265739"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Smith, R.M., Mba-Jonas, A., Tourdjman, M., Schimek, T., DeBess, E., Marsden-Haug, N., and Harris, J.R. (2014). Treatment and outcomes among patients with Cryptococcus gattii infections in the United States Pacific Northwest. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088875"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/cid\/cit341","article-title":"Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii","volume":"57","author":"Chen","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"779435","DOI":"10.3389\/fneur.2022.779435","article-title":"Clinical Characteristics and Risk Factors for Mortality in Cryptococcal Meningitis: Evidence From a Cohort Study","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1053\/jinf.2001.0916","article-title":"A prospective study of AIDS-associated cryptococcal meningitis in Thailand treated with high-dose amphotericin B","volume":"43","author":"Pitisuttithum","year":"2001","journal-title":"J. Infect."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/3\/427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:00Z","timestamp":1760122260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/3\/427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["pathogens12030427"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12030427","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]}}}