{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:36:49Z","timestamp":1787971009657,"version":"build-2784847793"},"reference-count":101,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,12,2]],"date-time":"2017-12-02T00:00:00Z","timestamp":1512172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal disease revealed a global incidence of 223,100 cases annually with 73% of these cases being diagnosed in sub-Saharan Africa. Furthermore, 75% of the estimated 181,100 deaths associated with cryptococcal disease occur in sub-Saharan Africa. Point-of-care diagnostic assays have revolutionised the diagnosis of this deadly opportunistic infection. The theory of asymptomatic cryptococcal antigenaemia as a forerunner to symptomatic meningitis and death has been conclusively proven. Thus, cryptococcal antigenaemia screening coupled with pre-emptive antifungal therapy has been demonstrated as a cost-effective strategy with survival benefits and has been incorporated into HIV national guidelines in several countries. However, this is yet to be implemented in a number of other high HIV burden countries. Flucytosine-based combination therapy during the induction phase is associated with improved survival, faster cerebrospinal fluid sterilisation and fewer relapses. Flucytosine, however, is unavailable in many parts of the world. Studies are ongoing on the efficacy of shorter regimens of amphotericin B. Early diagnosis, proactive antifungal therapy with concurrent management of raised intracranial pressure creates the potential to markedly reduce mortality associated with this disease.<\/jats:p>","DOI":"10.3390\/jof3040067","type":"journal-article","created":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T11:16:38Z","timestamp":1512386198000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["HIV-Associated Cryptococcal Disease in Resource-Limited Settings: A Case for \u201cPrevention Is Better Than Cure\u201d?"],"prefix":"10.3390","volume":"3","author":[{"given":"Rita","family":"Oladele","sequence":"first","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"},{"name":"Department of Microbiology and Parasitology, College of Medicine, University of Lagos, Lagos ,P.O.Box 132, Nigeria"},{"name":"Global Action Fund for Fungal Infections, 1211 Geneva 1, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-8517","authenticated-orcid":false,"given":"Felix","family":"Bongomin","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"},{"name":"Global Action Fund for Fungal Infections, 1211 Geneva 1, Switzerland"},{"name":"The National Aspergillosis Center, Education and Research Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-4598","authenticated-orcid":false,"given":"Sara","family":"Gago","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"},{"name":"Global Action Fund for Fungal Infections, 1211 Geneva 1, Switzerland"},{"name":"Manchester Fungal Infection Group, Core Technology Facility, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5626-2251","authenticated-orcid":false,"given":"David","family":"Denning","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"},{"name":"Global Action Fund for Fungal Infections, 1211 Geneva 1, Switzerland"},{"name":"The National Aspergillosis Center, Education and Research Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK"},{"name":"Manchester Fungal Infection Group, Core Technology Facility, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases\u2014Estimate Precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.fgb.2014.10.003","article-title":"Cryptococcosis diagnosis and treatment: What do we know now","volume":"78","author":"Perfect","year":"2015","journal-title":"Fungal Genet. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/clinids\/13.6.1163","article-title":"The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis","volume":"13","author":"Levitz","year":"1991","journal-title":"Rev. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.idc.2015.10.004","article-title":"The Global Burden of Fungal Diseases","volume":"30","author":"Vallabhaneni","year":"2016","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_5","first-page":"1","article-title":"New Insights into HIV\/AIDS-Associated Cryptococcosis","volume":"2013","author":"Antinori","year":"2013","journal-title":"Aids"},{"key":"ref_6","first-page":"1","article-title":"Global Burden of Disease of HIV-Associated Cryptococcal Meningitis: An Updated Analysis","volume":"3099","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ofv046","DOI":"10.1093\/ofid\/ofv046","article-title":"Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality","volume":"2","author":"Letang","year":"2015","journal-title":"Open Forum Infect. Dis."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/j.1399-3062.2010.00492.x","article-title":"Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients","volume":"12","author":"Neofytos","year":"2010","journal-title":"Transpl. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1086\/651262","article-title":"Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET)","volume":"50","author":"Pappas","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pyrgos, V., Seitz, A.E., Steiner, C.A., Prevots, D.R., and Williamson, P.R. (2013). Epidemiology of Cryptococcal Meningitis in the US: 1997\u20132009. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056269"},{"key":"ref_12","first-page":"585","article-title":"Prevalence and correlates of cryptococcal antigen positivity among AIDS patients\u2014United States, 1986\u20132012","volume":"63","author":"McKenney","year":"2014","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1056\/NEJM199201093260202","article-title":"Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis","volume":"326","author":"Saag","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1086\/515074","article-title":"Early mycological treatment failure in AIDS-associated cryptococcal meningitis","volume":"28","author":"Robinson","year":"1999","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1086\/587667","article-title":"Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy","volume":"46","author":"Kambugu","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"251","DOI":"10.7196\/SAMJ.4378","article-title":"Poor long-term outcomes for cryptococcal meningitis in rural South Africa","volume":"101","author":"Lessells","year":"2011","journal-title":"S. Afr. Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/j.1365-3156.2010.02565.x","article-title":"Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting","volume":"15","author":"Cohen","year":"2010","journal-title":"Trop. Med. Int. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s40475-015-0045-z","article-title":"Preventing Cryptococcosis\u2014Shifting the Paradigm in the Era of Highly Active Antiretroviral Therapy","volume":"2","author":"Meya","year":"2015","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1093\/cid\/ciu094","article-title":"Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America","volume":"58","author":"Masur","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","unstructured":"World Health Organization (2017, August 20). Rapid Advice: Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents and Children: December 2011. Available online: http:\/\/apps.who.int\/iris\/handle\/10665\/44786."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1086\/655143","article-title":"Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count <or =100 cells\/microL who start HIV therapy in resource-limited settings","volume":"51","author":"Meya","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1086\/657405","article-title":"Cryptococcal Antigen Screening for Patients Initiating Antiretroviral Therapy: Time for Action","volume":"51","author":"Jarvis","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/00002030-198902000-00004","article-title":"The value of cryptococcal serum antigen screening among HIV-positive\/AIDS patients in Kinshasa, Zaire","volume":"3","author":"Desmet","year":"1989","journal-title":"Aids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/QAI.0b013e31811ed32c","article-title":"Prevalence, determinants of positivity, and clinical utility of cryptococcal antigenemia in Cambodian HIV-infected patients","volume":"45","author":"Micol","year":"2007","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jinf.2010.03.015","article-title":"The role of serum cryptococcal antigen screening for the early diagnosis of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts","volume":"60","author":"Pongsai","year":"2010","journal-title":"J. Infect."},{"key":"ref_26","first-page":"344","article-title":"Cryptococcal antigenemia in anti-retroviral na\u00efve AIDS patients: Prevalence and its association with CD4 cell count","volume":"50","author":"Osazuwa","year":"2012","journal-title":"Acta Med. Iran."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"ofw055","DOI":"10.1093\/ofid\/ofw055","article-title":"Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence","volume":"3","author":"Oladele","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Alemu, A.S., Kempker, R.R., Tenna, A., Smitson, C., Berhe, N., Fekade, D., Blumberg, H.M., and Aseffa, A. (2013). High Prevalence of Cryptococcal Antigenemia among HIV-infected Patients Receiving Antiretroviral Therapy in Ethiopia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058377"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bongomin, F. (2017). A review of Odongo-Aginya stain: the other alternative to India ink. Trop. Dr.","DOI":"10.1177\/0049475517732661"},{"key":"ref_30","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":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1097\/00002030-200205030-00009","article-title":"Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults","volume":"16","author":"French","year":"2002","journal-title":"Aids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1128\/jcm.29.2.333-339.1991","article-title":"Performance of Cryptococcus antigen latex agglutination kits on serum and cerebrospinal fluid specimens of AIDS patients before and after pronase treatment","volume":"29","author":"Hamilton","year":"1991","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cassim, N., Schnippel, K., Coetzee, L.M., and Glencross, D.K. (2017). Establishing a cost-per-result of laboratorybased, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells\/\u03bcl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171675"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/cid\/cir613","article-title":"Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis","volume":"53","author":"Jarvis","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1517\/17530059.2012.681300","article-title":"CrAg lateral flow assay for cryptococcosis","volume":"6","author":"Kozel","year":"2012","journal-title":"Expert Opin. Med. Diagn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11904-010-0067-z","article-title":"Point-of-care testing","volume":"8","author":"Anderson","year":"2011","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/cid\/cir379","article-title":"Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis","volume":"53","author":"Lindsley","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"McMullan, B.J., Halliday, C., Sorrell, T.C., Judd, D., Sleiman, S., Marriott, D., Olma, T., and Chen, S.C.A. (2012). Clinical Utility of the Cryptococcal Antigen Lateral Flow Assay in a Diagnostic Mycology Laboratory. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049541"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1128\/CVI.00446-12","article-title":"Comparison of four assays for the detection of cryptococcal antigen","volume":"19","author":"Binnicker","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3109\/13693786.2013.781692","article-title":"Evaluation of a rapid lateral flow immunoassay for the detection of cryptococcal antigen for the early diagnosis of cryptococcosis in HIV patients in Colombia","volume":"51","author":"Lizarazo","year":"2013","journal-title":"Med. Mycol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1111\/tmi.12157","article-title":"Cryptococcal antigen prevalence in HIV-infected Tanzanians: A cross-sectional study and evaluation of a point-of-care lateral flow assay","volume":"18","author":"Rugemalila","year":"2013","journal-title":"Trop. Med. Int. Health"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/cid\/civ263","article-title":"Evaluation of Fingerstick Cryptococcal Antigen Lateral Flow Assay in HIV-Infected Persons: A Diagnostic Accuracy Study","volume":"61","author":"Williams","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_44","first-page":"16","article-title":"Sensitivity and specificity of a new cryptococcal antigen lateral flow assay in serum and cerebrospinal fluid","volume":"45","author":"Klausner","year":"2013","journal-title":"MLO Med. Lab. Obs."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"19040","DOI":"10.7448\/IAS.17.1.19040","article-title":"Utility of urine and serum lateral flow assays to determine the prevalence and predictors of cryptococcal antigenemia in HIV-positive outpatients beginning antiretroviral therapy in Mwanza, Tanzania","volume":"17","author":"Magambo","year":"2014","journal-title":"J. Int. Aids Soc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/cid\/cit641","article-title":"Point-of-Care Diagnosis and Prognostication of Cryptococcal Meningitis With the Cryptococcal Antigen Lateral Flow Assay on Cerebrospinal Fluid","volume":"58","author":"Kabanda","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.1128\/JCM.43.11.5828-5829.2005","article-title":"The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis","volume":"43","author":"Antinori","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1097\/QCO.0b013e32832fa214","article-title":"Treatment of cryptococcal meningitis in resource limited settings","volume":"22","author":"Sloan","year":"2009","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1086\/649858","article-title":"Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america","volume":"50","author":"Perfect","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1056\/NEJMoa1110404","article-title":"Combination Antifungal Therapy for Cryptococcal Meningitis","volume":"368","author":"Day","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S1473-3099(13)70078-1","article-title":"Cryptococcal meningitis: Improving access to essential antifungal medicines in resource-poor countries","volume":"13","author":"Loyse","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4102\/sajhivmed.v14i2.82","article-title":"Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update","volume":"14","author":"Govender","year":"2013","journal-title":"S. Afr. J. HIV Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1086\/588792","article-title":"High-dose Amphotericin B with Flucytosine for the Treatment of Cryptococcal Meningitis in HIV-Infected Patients: A Randomized Trial","volume":"47","author":"Bicanic","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1086\/593194","article-title":"Dose response effect of high-dose fluconazole for HIV-associated cryptococcal meningitis in southwestern Uganda","volume":"47","author":"Longley","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1093\/infdis\/173.5.1216","article-title":"Treatment of experimental cryptococcal meningitis with fluconazole: Impact of dose and addition of flucytosine on mycologic and pathophysiologic outcome","volume":"173","author":"Kartalija","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1086\/649861","article-title":"Combination Flucytosine and High-Dose Fluconazole Compared with Fluconazole Monotherapy for the Treatment of Cryptococcal Meningitis: A Randomized Trial in Malawi","volume":"50","author":"Nussbaum","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Rajasingham, R., Rolfes, M.A., Birkenkamp, K.E., Meya, D.B., and Boulware, D.R. (2012). Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis. PLoS Med., 9.","DOI":"10.1371\/journal.pmed.1001316"},{"key":"ref_59","unstructured":"Jarvis, J.N., Leeme, B.T., and Chofle, A.A. (2017, January 13\u201316). Ambition-CM: High-dose liposomal amphotericin for HIV-related cryptococcal meningitis. Proceedings of the Conference on Retroviruses and Opportunistic Infections, Seattle, WA, USA."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1056\/NEJM199102283240902","article-title":"A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group","volume":"324","author":"Bozzette","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_61","unstructured":"Katende, A., Mbwanji, G., and Faini, D. (2017, January 13\u201316). Sertraline and high-dose fluconazole treatment of cryptococcal meningitis in Tanzania. Proceedings of the Conference on Retroviruses and Opportunistic Infections, Seattle, WA, USA."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1056\/NEJMoa1312884","article-title":"Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis","volume":"370","author":"Boulware","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/infdis\/jiv067","article-title":"Early ART after cryptococcal meningitis is associated with cerebrospinal fluid pleocytosis and macrophage activation in a multisite randomized trial","volume":"212","author":"Scriven","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1056\/NEJM199707033370103","article-title":"Treatment of Cryptococcal Meningitis Associated with the Acquired Immunodeficiency Syndrome","volume":"337","author":"Saag","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1086\/597262","article-title":"Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa","volume":"48","author":"Jarvis","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0002-9343(91)90126-I","article-title":"Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome","volume":"91","author":"Denning","year":"1991","journal-title":"Am. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/cid\/ciu596","article-title":"The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis","volume":"59","author":"Rolfes","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"567","DOI":"10.2217\/hiv.10.46","article-title":"HIV-related cryptococcal meningitis in resource-limited settings","volume":"4","author":"Chirianni","year":"2010","journal-title":"HIV Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0163-4453(92)92954-H","article-title":"Raised intracranial pressure and visual complications in AIDS patients with cryptococcal meningitis","volume":"24","author":"Johnston","year":"1992","journal-title":"J. Infect."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1056\/NEJMoa1509024","article-title":"Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis","volume":"374","author":"Beardsley","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1097\/QAD.0b013e32830007cd","article-title":"Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa","volume":"22","author":"Lawn","year":"2008","journal-title":"Aids"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1086\/516372","article-title":"Combination therapy with fluconazole and flucytosine for cryptococcal meningitis in Ugandan patients with AIDS","volume":"26","author":"Oishi","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1097\/01.aids.0000287549.79368.33","article-title":"AIDS-associated central nervous system cryptococcosis: A Brazilian case study","volume":"21","author":"Pappalardo","year":"2007","journal-title":"Aids"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1136\/pgmj.77.914.769","article-title":"Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions","volume":"77","author":"Mwaba","year":"2001","journal-title":"Postgrad. Med. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s40588-016-0035-5","article-title":"HIV-Associated Cryptococcal Meningitis: Bridging the Gap Between Developed and Resource-Limited Settings","volume":"3","author":"Tenforde","year":"2016","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_76","unstructured":"Leeme, T.B., Patel, R.K., and Azzo, C. (2017, January 13\u201316). Mortality due to HIV-associated cryptococcal meningitis in Botswana in the art era. Proceedings of the Conference on Retroviruses and Opportunistic Infections, Seattle, WA, USA."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1128\/AAC.37.6.1383","article-title":"Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole","volume":"37","author":"Casadevall","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_78","first-page":"213","article-title":"A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. [Spanish] Comparacion de itraconazol vs fluconazol como tratamiento de mantenimiento para la meningitis criptococica relacionada con el SID","volume":"19","author":"Saag","year":"1999","journal-title":"Enfermedades Infecc y Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1097\/01.aids.0000252060.80704.68","article-title":"Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy","volume":"20","author":"Lortholary","year":"2006","journal-title":"Aids"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4314\/ahs.v12i2.23","article-title":"Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings","volume":"12","author":"Musubire","year":"2012","journal-title":"Afr. Health Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S1473-3099(10)70170-5","article-title":"Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: Proposed clinical case definitions","volume":"10","author":"Haddow","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s12281-011-0064-8","article-title":"Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome(IRIS): Pathogenesis and Its Clinical Implications","volume":"5","author":"Wiesner","year":"2011","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/S0161-6420(89)32794-1","article-title":"Ocular manifestations of acquired immune deficiency syndrome","volume":"96","author":"Jabs","year":"1989","journal-title":"Ophthalmology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1097\/QAD.0b013e32832605fe","article-title":"Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures","volume":"23","author":"Bicanic","year":"2009","journal-title":"Aids"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.1468-1293.2004.00201.x","article-title":"A multicentre, randomized, double-blind, placebo-controlled trial of primary cryptococcal meningitis prophylaxis in HIV-infected patients with severe immune deficiency","volume":"5","author":"Chetchotisakd","year":"2004","journal-title":"HIV Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S1473-3099(11)70245-6","article-title":"Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: A double-blind, randomised, placebo-controlled trial","volume":"11","author":"Wakeham","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/cid\/cix036","article-title":"Primary Prophylaxis for Cryptococcosis With Fluconazole in Human Immunodeficiency Virus\u2013Infected Patients With CD4 T-Cell Counts <100 Cells\/\u03bcL and Receiving Antiretroviral Therapy","volume":"64","author":"Sungkanuparph","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jinf.2012.09.014","article-title":"The prevalence of cryptococcal antigenemia in newly diagnosed HIV patients in a Southwest London cohort","volume":"66","author":"Patel","year":"2013","journal-title":"J. Infect."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1128\/AAC.01299-15","article-title":"Cryptococcus neoformans in Uganda","volume":"59","author":"Smith","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"378","DOI":"10.7196\/SAMJ.3515","article-title":"Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: The role of inadequate secondary prophylaxis","volume":"100","author":"Jarvis","year":"2010","journal-title":"S. Afr. Med. J."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Montgomery, M.P., Nakasujja, N., Morawski, B.M., Rajasingham, R., Rhein, J., Nalintya, E., Williams, D.A., Huppler Hullsiek, K., Kiragga, A., and Rolfes, M.A. (2017). Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: A comparison of three prospective cohorts. BMC Neurol., 17.","DOI":"10.1186\/s12883-017-0878-2"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1177\/1545109712459077","article-title":"Cryptococcal antigen screening and preemptive therapy in patients initiating antiretroviral therapy in resource-limited settings: A proposed algorithm for clinical implementation","volume":"11","author":"Jarvis","year":"2012","journal-title":"J. Int. Assoc. Physicians AIDS Care"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1086\/604716","article-title":"Independent association between rate of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: Analysis of a combined cohort of 262 patients","volume":"49","author":"Bicanic","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Wake, R.M., Britz, E., Sriruttan, C., Rukasha, I., Omar, T., Spencer, D.C., Nel, J.S., Mashamaite, S., Adelekan, A., and Chiller, T.M. (2017). High Cryptococcal Antigen Titers in Blood are Predictive of Subclinical Cryptococcal Meningitis among HIV-Infected Patients. Clin. Infect. Dis.","DOI":"10.1093\/cid\/cix872"},{"key":"ref_95","unstructured":"Morawski, B., Boulware, D., and Nalintya, E. (2016, January 22\u201325). Pre-ART cryptococcal antigen titer associated with preemptive fluconazole failure. Proceedings of the Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0158986","article-title":"Screening HIV-Infected patients with low cd4 counts for cryptococcal antigenemia prior to initiation of antiretroviral therapy: Cost effectiveness of alternative screening strategies in South Africa","volume":"11","author":"Larson","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/hiv.12245","article-title":"Evaluation of screening and treatment of cryptococcal antigenaemia among HIV-infected persons in Soweto, South Africa","volume":"16","author":"Govender","year":"2015","journal-title":"HIV Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1097\/QAI.0b013e31828e1e56","article-title":"Cost-effective diagnostic checklists for meningitis in resource-limited settings","volume":"63","author":"Durski","year":"2013","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Micol, R., Tajahmady, A., Lortholary, O., Balkan, S., Quillet, C., Dousset, J.-P., Chanroeun, H., Madec, Y., Fontanet, A., and Yazdanpanah, Y. (2010). Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in Cambodia. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013856"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Jarvis, J.N., Harrison, T.S., Lawn, S.D., Meintjes, G., Wood, R., and Cleary, S. (2013). Cost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South Africa. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069288"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Smith, R.M., Nguyen, T.A., Ha, H.T.T., Thang, P.H., Thuy, C., Lien, T.X., Bui, H.T., Le, T.H., Struminger, B., and McConnell, M.S. (2013). Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program\u2014Vietnam. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062213"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/3\/4\/67\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:52:23Z","timestamp":1760208743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/3\/4\/67"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,2]]},"references-count":101,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["jof3040067"],"URL":"https:\/\/doi.org\/10.3390\/jof3040067","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,2]]}}}