Title: Cryptococcosis

{{short description|Potentially fatal fungal disease}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{distinguish|Cryptosporidiosis}}
{{Infobox medical condition (new)
| name          = Cryptococcosis
| image         = Cryptococcus.jpg
| synonyms      = Busse-Buschke disease, cryptococcic meningitis, cryptococcosis lung, cryptococcosis skin, European Blastomycosis, torular meningitis, torulosis&lt;ref name=NORD&gt;{{cite web |title=Cryptococcosis |url=https://rarediseases.org/rare-diseases/cryptococcosis/ |website=NORD (National Organization for Rare Disorders) |access-date=5 June 2021}}&lt;/ref&gt;
| caption       = [[Micrograph]] of cryptococcosis showing the characteristically thick capsule of cryptococcus. [[Field stain]].
| field         = [[Infectious disease (medical specialty)|Infectious disease]]&lt;ref name=ICD-11/&gt;
| pronounce     = {{IPAc-en|ˌ|k|r|ɪ|p|t|ə|k|ə|ˈ|k|oʊ|s|ɪ|s|,_|-|t|oʊ|-|,_|-|k|ɒ|-}}{{refn|{{Cite encyclopedia |url=http://www.lexico.com/definition/Cryptococcosis |archive-url=https://web.archive.org/web/20210507044344/https://www.lexico.com/definition/cryptococcosis |archive-date=2021-05-07 |title=Cryptococcosis |dictionary=[[Lexico]] UK English Dictionary |publisher=[[Oxford University Press]]}} }}{{refn|{{MerriamWebsterDictionary|access-date=2016-01-21|Cryptococcosis}}}}|
| symptoms      = *Lung: [[Cough]], [[shortness of breath|difficulty breathing]], [[chest pain]] and [[fever]].&lt;ref name=CDCSymp/&gt;
* Brain: [[Headache]], fever, [[meningism|neck pain]], [[nausea]], [[vomiting]], [[Photophobia|light sensitivity]], [[cognitive impairment|confusion]], change in behaviour.&lt;ref name=CDCSymp/&gt;
* Skin: [[nodule (medicine)|Nodules]] with [[necrosis|dead tissue]].&lt;ref name=John2017/&gt;
| complications =
| onset         =
| duration      =
| types         =
| causes        = ''[[Cryptococcus neoformans]]'',&lt;ref name=CDC&gt;{{cite web |title=C. neoformans Infection |work=Fungal Diseases |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/index.html |publisher=Centers for Disease Control and Prevention |access-date=5 June 2021 |language=en-us |date=29 December 2020}}&lt;/ref&gt; ''[[Cryptococcus gattii]]''&lt;ref name=CDCGatti&gt;{{cite web |title=Where C. gattii Infection Comes From |work=Fungal Disease |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-gattii/causes.html |publisher=Centers for Disease Control and Prevention |access-date=5 June 2021 |language=en-us |date=29 January 2021}}&lt;/ref&gt;
| risks         = [[HIV/AIDS]],&lt;ref name=Maziarz2016/&gt; [[Aviculture]]
| diagnosis     = [[Biopsy]], [[microbiological culture|culture]]&lt;ref name=Maziarz2016/&gt;
| differential  =
| prevention    =
| treatment     = [[Antifungal drug|Antifungal medication]]
| medication    = *[[Fluconazole]]&lt;ref name=CDCTreat&gt;{{cite web |title=Treatment for C. neoformans Infection |work=Fungal Diseases |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/treatment.html |publisher=Centers for Disease Control and Prevention |access-date=6 June 2021 |language=en-us |date=14 January 2021}}&lt;/ref&gt;
* [[Amphotericin B]]&lt;ref name=Maziarz2016/&gt;
* [[Flucytosine]]&lt;ref name=&quot;Perfect 2010&quot; /&gt;
| prognosis     =
| frequency     =
| deaths        =
}}

'''Cryptococcosis''' is a potentially fatal [[mycosis|fungal infection]] of mainly the [[lungs]], presenting as a [[pneumonia]], and in the [[brain]], where it appears as a [[meningitis]].&lt;ref name=ICD-11&gt;{{cite web |title=ICD-11 — ICD-11 for Mortality and Morbidity Statistics |url=https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f390527954 |website=icd.who.int |access-date=5 June 2021}}&lt;/ref&gt;&lt;ref name=Maziarz2016&gt;{{cite journal | vauthors = Maziarz EK, Perfect JR | title = Cryptococcosis | journal = Infectious Disease Clinics of North America | volume = 30 | issue = 1 | pages = 179–206 | date = March 2016 | pmid = 26897067 | pmc = 5808417 | doi = 10.1016/j.idc.2015.10.006 }}&lt;/ref&gt;&lt;ref&gt;{{cite journal | vauthors = Rocha MF, Bain HD, Stone N, Meya D, Darie L, Toma AK, Lunn MP, Mehta AR, Coughlan C | title = Reframing the clinical phenotype and management of cryptococcal meningitis | journal = Practical Neurology | volume = 25 | issue = 1 | pages = 25–39 | date = January 2025 | pmid = 38997136 | doi = 10.1136/pn-2024-004133 | pmc = 11877062 }}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}&lt;/ref&gt; [[Coughing]], [[shortness of breath|difficulty breathing]], [[chest pain]] and [[fever]] are seen when the lungs are infected.&lt;ref name=CDCSymp&gt;{{cite web |title=Symptoms of C. neoformans Infection |work=Fungal Diseases |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/symptoms.html |publisher=Centers for Disease Control and Prevention |access-date=6 June 2021 |date=14 January 2021}}&lt;/ref&gt; When the brain is infected, symptoms include [[headache]], fever, [[meningism|neck pain]], [[nausea]] and [[vomiting]], [[Photophobia|light sensitivity]] and [[cognitive impairment|confusion]] or changes in behavior.&lt;ref name=CDCSymp/&gt; It can also affect other parts of the body including [[skin]], where it may appear as several fluid-filled [[nodule (medicine)|nodules]] with [[necrosis|dead tissue]].&lt;ref name=John2017&gt;{{cite book| vauthors = Johnstone RB |title=Weedon's Skin Pathology Essentials |url=https://books.google.com/books?id=NTE_DAAAQBAJ|year=2017|publisher=Elsevier |edition=2nd|isbn=978-0-7020-6830-0|page=446|chapter=25. Mycoses and Algal infections}}&lt;/ref&gt;

&lt;!-- Cause and mechanism --&gt;
It is caused by the [[pathogenic fungi|fungi]] ''[[Cryptococcus neoformans]]'' or less commonly ''[[Cryptococcus gattii]]'', and is acquired by [[inhalation|breathing in]] the [[propagule|spores]] from the air.&lt;ref name=ICD-11/&gt; These fungi are found globally in soil, decaying wood, pigeon droppings, and in the hollows of some species of trees.&lt;ref name=Maziarz2016/&gt;&lt;ref name=CDCWhere&gt;{{cite web |title=Where C. neoformans Infection Comes From |work=Fungal Diseases |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/causes.html |publisher=Centers for Disease Control and Prevention |access-date=5 June 2021 |language=en-us |date=2 February 2021}}&lt;/ref&gt; Whereas ''C.&amp;nbsp;neoformans'' generally infects people with HIV/AIDS and those on [[immunosuppressant drugs]] and does not usually affect fit and healthy people, ''C.&amp;nbsp;gattii'' (found in some parts of Canada and the US) does.&lt;ref name=Maziarz2016/&gt;&lt;ref name=CDCWhere/&gt; Once breathed in, the dried yeast cells colonize the lungs, where they are either cleared by [[phagocytes|immune cells]], lie dormant, or cause infection and spread.&lt;ref name=Sabiiti2012&gt;{{cite journal | vauthors = Sabiiti W, May RC | title = Mechanisms of infection by the human fungal pathogen Cryptococcus neoformans | journal = Future Microbiology | volume = 7 | issue = 11 | pages = 1297–1313 | date = November 2012 | pmid = 23075448 | doi = 10.2217/fmb.12.102 }}&lt;/ref&gt;

&lt;!-- Diagnosis and treatment --&gt;
Diagnosis is by isolating ''Cryptococcus'' from a sample of affected tissue or direct observation of the fungus by using staining of body fluids.&lt;ref name=Maziarz2016/&gt; It can be cultured from a [[cerebrospinal fluid]], sputum, and [[skin biopsy]].&lt;ref name=Maziarz2016/&gt;  Characteristic neuroimaging findings include dilated Virchow-Robin spaces, the 'dirty CSF sign',&lt;ref&gt;{{cite journal | vauthors = Coughlan CH, Hoskote C, Mehta AR | title = 'Dirty CSF': an MRI feature of CNS fungal infection | journal = BMJ Case Reports | volume = 16 | issue = 12 | article-number = e257720 | date = December 2023 | pmid = 38061848 | pmc = 10711893 | doi = 10.1136/bcr-2023-257720 }}&lt;/ref&gt; hydrocephalus, cryptococcomas and hazy brain base sign. Many of these findings are non-specific, but the presence of basal meningeal enhancement is significant as it is associated with the future development of cerebral infarct. Treatment is with [[fluconazole]] or [[amphotericin B|amphotericin''&amp;nbsp;''B]].&lt;ref name=Maziarz2016/&gt;&lt;ref name=CDCTreat/&gt;

&lt;!-- Epidemiology and history --&gt;
Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa, and 600,000 per year died.&lt;ref name=&quot;Vallab2016&quot;&gt;{{cite book | vauthors = Vallabhaneni S, Mody RK, Walker T, Chiller T  |title=Fungal Infections, An Issue of Infectious Disease Clinics of North America |date=2016 |publisher=Elsevier |isbn=978-0-323-41649-8 | veditors = Sobel J, Ostrosky-Zeichner L |location=Philadelphia |pages=3–4 |chapter=1. The global burden of fungal disease |chapter-url=https://books.google.com/books?id=uwndCwAAQBAJ&amp;pg=PA3}}&lt;/ref&gt; Cryptococcosis was rare before the 1970s, which saw an increase in at-risk groups such as people with [[organ transplant]] or on [[Immunosuppressive drug|immunosuppressant medications]].&lt;ref name=Maziarz2016/&gt; The number of cases escalated in the mid-1980s with over 80% occurring in people with [[HIV/AIDS]].&lt;ref name=Maziarz2016/&gt; Pigeon breeders (or otherwise people who spend significant time with pigeons) are known to have a high incidence of cryptococcal infections including primary cutaneous cryptococcus due to the fungi's association with pigeon droppings.&lt;ref&gt;{{cite journal | vauthors = Walter JE, Atchison RW | title = Epidemiological and immunological studies of Cryptococcus neoformans | journal = Journal of Bacteriology | volume = 92 | issue = 1 | pages = 82–87 | date = July 1966 | pmid = 5328755 | pmc = 276199 | doi = 10.1128/jb.92.1.82-87.1966 }}&lt;/ref&gt;{{Better source needed|date=October 2024}}

== Classification ==
Cryptococcus is generally classified according to how it is acquired and the site of infection.&lt;ref&gt;{{cite journal | vauthors = Alanazi AH, Adil MS, Lin X, Chastain DB, Henao-Martínez AF, Franco-Paredes C, Somanath PR | title = Elevated Intracranial Pressure in Cryptococcal Meningoencephalitis: Examining Old, New, and Promising Drug Therapies | journal = Pathogens | volume = 11 | issue = 7 | page = 783 | date = July 2022 | pmid = 35890028 | pmc = 9321092 | doi = 10.3390/pathogens11070783 | doi-access = free }}&lt;/ref&gt; It typically begins in the lungs before spreading to other parts of the body, particularly the brain and nervous system.&lt;ref name=NORD/&gt; Skin involvement is less common.&lt;ref name=NORD/&gt;

==Signs and symptoms==
Cough, shortness of breath, chest pain, and fever are seen when the lungs are infected, resembling pneumonia.&lt;ref name=CDCSymp/&gt; There may also be [[fatigue|feeling of tiredness]].&lt;ref name=ICD-11/&gt; When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity, confusion, or changes in behaviour.&lt;ref name=CDCSymp/&gt; It can also affect other parts of the body, including skin, eyes, bones, and prostate.&lt;ref name=Maziarz2016/&gt; In the skin, it may appear as several fluid-filled [[nodule (medicine)|nodules]] with [[necrosis|dead tissue]].&lt;ref name=John2017/&gt; Depending on the site of infection, other features may include [[Visual impairment|loss of vision]], [[diplopia|blurred vision]], inability to move an eye, and memory loss.&lt;ref name=Maziarz2016/&gt;

Symptom onset is often sudden when lungs are infected and gradual over several weeks when the central nervous system is affected.&lt;ref name=Maziarz2016/&gt;

Signs and symptoms of cryptococcal infection may be delayed in those with HIV or AIDS. A positive cryptococcal antigen test may precede symptoms by 3 weeks in those with HIV/AIDS. Others may have reactivation of latent cryptococcal disease years later. In those with HIV, approximately 50% of people have a fever, but fever is rare in previously healthy and immunocompetent people with cryptococcosis.&lt;ref name=&quot;Meya 2024&quot; /&gt;

== Cause ==
Cryptococcosis is a common opportunistic infection for [[AIDS]] and is particularly common among people living with AIDS in [[Africa]]. Other conditions that pose an increased risk include certain [[malignancy|malignancies]] (such as [[lymphoma]]), liver [[cirrhosis]], [[organ transplant]]s, and long-term [[corticosteroid]] therapy.&lt;ref name=Setianingrum19&gt;{{cite journal | vauthors = Setianingrum F, Rautemaa-Richardson R, Denning DW | title = Pulmonary cryptococcosis: A review of pathobiology and clinical aspects | journal = Medical Mycology | volume = 57 | issue = 2 | pages = 133–150 | date = February 2019 | pmid = 30329097 | doi = 10.1093/mmy/myy086 | doi-access = free }}&lt;/ref&gt;

Distribution is worldwide in soil.&lt;ref&gt;{{cite encyclopedia |title=Meningitis: cryptococcal: Overview |date=September 2010 |encyclopedia=Medical Reference: Encyclopedia |publisher=University of Maryland Medical Center |url=http://www.umm.edu/ency/article/000642.htm |access-date=2011-04-26 |archive-date=2013-05-23 |archive-url=https://web.archive.org/web/20130523235445/http://www.umm.edu/ency/article/000642.htm }}&lt;/ref&gt; The prevalence of cryptococcosis has been increasing over the past 50 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.&lt;ref name=&quot;gushiken-2021&quot;&gt;{{cite journal | vauthors = Gushiken AC, Saharia KK, Baddley JW | title = Cryptococcosis | journal = Infectious Disease Clinics of North America | volume = 35 | issue = 2 | pages = 493–514 | date = June 2021 | pmid = 34016288 | doi = 10.1016/j.idc.2021.03.012 | s2cid = 235074157 }}&lt;/ref&gt;

In humans, ''C.&amp;nbsp;neoformans'' chiefly infects the skin, lungs, and central nervous system (causing [[meningitis]]).&lt;ref name=&quot;gushiken-2021&quot;/&gt; Less commonly, it may affect other organs such as the eye or prostate.&lt;ref name=&quot;gushiken-2021&quot;/&gt;

== Primary cutaneous cryptococcosis ==
Primary cutaneous cryptococcosis (PCC) is a distinct clinical diagnosis separate from the secondary cutaneous cryptococcosis that is spread by systemic infection. Males are more likely to develop the infection and a 2020 study showed that the sex bias may be due to a growth hormone, produced by ''C.&amp;nbsp;neoformans'' called gibberellic acid (GA) that is upregulated by testosterone.&lt;ref&gt;{{cite journal | vauthors = Tucker JS, Guess TE, McClelland EE | title = The Role of Testosterone and Gibberellic Acid in the Melanization of &lt;i&gt;Cryptococcus neoformans&lt;/i&gt; | journal = Frontiers in Microbiology | volume = 11 | issue =  | article-number = 1921 | date = 2020 | pmid = 32922377 | pmc = 7456850 | doi = 10.3389/fmicb.2020.01921 | doi-access = free }}&lt;/ref&gt;  The upper limbs account for a majority of infections. Isolates found in PCC include ''[[Cryptococcus neoformans]]'' (most common), ''[[Cryptococcus gattii]]'', and ''[[Cryptococcus laurentii]]''. The prognosis for PCC is generally good outside of disseminated infection.&lt;ref&gt;{{cite journal | vauthors = Du L, Yang Y, Gu J, Chen J, Liao W, Zhu Y | title = Systemic Review of Published Reports on Primary Cutaneous Cryptococcosis in Immunocompetent Patients | journal = Mycopathologia | volume = 180 | issue = 1–2 | pages = 19–25 | date = August 2015 | pmid = 25736173 | doi = 10.1007/s11046-015-9880-7 }}&lt;/ref&gt;

Morphologic description of the lesions shows umbilicated papules, nodules, and violaceous plaques that can mimic other cutaneous diseases like [[molluscum contagiosum]] and [[Kaposi's sarcoma]]. These lesions may be present months before other signs of systemic infection in patients with AIDS.&lt;ref&gt;{{cite journal | vauthors = Murakawa GJ, Kerschmann R, Berger T | title = Cutaneous Cryptococcus infection and AIDS. Report of 12 cases and review of the literature | journal = Archives of Dermatology | volume = 132 | issue = 5 | pages = 545–548 | date = May 1996 | pmid = 8624151 | doi = 10.1001/archderm.1996.03890290079010 }}&lt;/ref&gt;

== Pulmonary cryptococcosis ==
''Cryptococcus'' (both ''C.&amp;nbsp;neoformans'' and ''C.&amp;nbsp;gattii'') plays a common role in pulmonary invasive mycosis seen in adults with HIV and other immunocompromised conditions.&lt;ref name=Setianingrum19/&gt; It also affects healthy adults at a much lower frequency and severity, as healthy hosts may have no or mild symptoms.&lt;ref&gt;{{cite journal | vauthors = Choi KH, Park SJ, Min KH, Kim SR, Lee MH, Chung CR, Han HJ, Lee YC | title = Treatment of asymptomatic pulmonary cryptococcosis in immunocompetent hosts with oral fluconazole | journal = Scandinavian Journal of Infectious Diseases | volume = 43 | issue = 5 | pages = 380–385 | date = May 2011 | pmid = 21271944 | doi = 10.3109/00365548.2011.552521 }}&lt;/ref&gt; Immune-competent hosts may not seek or require treatment, but careful observation may be important.&lt;ref&gt;{{cite journal | vauthors = Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, Sobel JD, Dismukes WE | title = Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America | journal = Clinical Infectious Diseases | volume = 30 | issue = 4 | pages = 710–718 | date = April 2000 | pmid = 10770733 | doi = 10.1086/313757 }}&lt;/ref&gt;  Cryptococcal pneumonia has the potential to disseminate to the central nervous system (CNS), especially in immunocompromised individuals.&lt;ref&gt;{{cite journal | vauthors = Brizendine KD, Baddley JW, Pappas PG | title = Pulmonary cryptococcosis | journal = Seminars in Respiratory and Critical Care Medicine | volume = 32 | issue = 6 | pages = 727–734 | date = December 2011 | pmid = 22167400 | doi = 10.1055/s-0031-1295720 }}&lt;/ref&gt;

Pulmonary cryptococcosis has a worldwide distribution and is commonly underdiagnosed due to limitations in diagnostic capabilities. Since pulmonary nodules are its most common radiological feature, they can clinically and radiologically mimic lung cancer, TB, and other pulmonary mycoses. The sensitivity of cultures and the Cryptococcal (CrAg) antigen with a lateral flow device on serum is rarely positive in the absence of disseminated disease.&lt;ref name=Setianingrum19 /&gt; Moreover, pulmonary cryptococcosis worsens the prognosis of cryptococcal meningitis.&lt;ref name=Setianingrum19 /&gt;

== Cryptococcal meningitis ==
[[Image:Meningitis criptocócica diseminada.png|thumb|250px|Disseminated cryptococcal meningitis]]
{{See also|Chronic meningitis}}
Cryptococcal meningitis (infection of the [[meninges]], the tissue covering the brain) is believed to result from the dissemination of the fungus from either an observed or undetected pulmonary infection. Often, there is also silent dissemination throughout the brain when meningitis is present. People with defects in their [[cell-mediated immunity]], for example, people with [[AIDS]], are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, even if treated.  It is estimated that the three-month [[case-fatality rate]] is 9% in high-income regions, 55% in low/middle-income regions, and 70% in sub-Saharan Africa.  As of 2009 there were globally approximately 958,000 annual cases and 625,000 deaths within three months after infection.&lt;ref&gt;{{cite journal | vauthors = Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM | title = Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS | journal = AIDS | volume = 23 | issue = 4 | pages = 525–530 | date = February 2009 | pmid = 19182676 | doi = 10.1097/QAD.0b013e328322ffac | s2cid = 5735550 | doi-access = free }}&lt;/ref&gt;

Although ''C.&amp;nbsp;neoformans'' infection most commonly occurs as an opportunistic infection in immunocompromised people (such as those living with AIDS), ''C.&amp;nbsp;gattii'' often infects immunocompetent people as well.&lt;ref&gt;{{cite journal | vauthors = D'Souza CA, Kronstad JW, Taylor G, Warren R, Yuen M, Hu G, Jung WH, Sham A, Kidd SE, Tangen K, Lee N, Zeilmaker T, Sawkins J, McVicker G, Shah S, Gnerre S, Griggs A, Zeng Q, Bartlett K, Li W, Wang X, Heitman J, Stajich JE, Fraser JA, Meyer W, Carter D, Schein J, Krzywinski M, Kwon-Chung KJ, Varma A, Wang J, Brunham R, Fyfe M, Ouellette BF, Siddiqui A, Marra M, Jones S, Holt R, Birren BW, Galagan JE, Cuomo CA | title = Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts | journal = mBio | volume = 2 | issue = 1 | pages = e00342–e00310 | date = 2011-02-08 | article-number = e00342-10 | pmid = 21304167 | pmc = 3037005 | doi = 10.1128/mBio.00342-10 | publisher = American Society for Microbiology }}&lt;/ref&gt;

''[[Cryptococcus]]'' species (both ''[[Cryptococcus neoformans|C.&amp;nbsp;neoformans]]'' and ''[[Cryptococcus gattii|C.&amp;nbsp;gattii]]'') are responsible for 68% of meningitis cases in those with HIV.&lt;ref name=&quot;Meya 2024&quot;&gt;{{cite journal | vauthors = Meya DB, Williamson PR | title = Cryptococcal Disease in Diverse Hosts | journal = The New England Journal of Medicine | volume = 390 | issue = 17 | pages = 1597–1610 | date = May 2024 | pmid = 38692293 | doi = 10.1056/NEJMra2311057 }}&lt;/ref&gt; Cryptococcus is considered an &quot;emerging&quot; disease in healthy adults.&lt;ref&gt;{{cite journal | vauthors = Pasquier E, Kunda J, De Beaudrap P, Loyse A, Temfack E, Molloy SF, Harrison TS, Lortholary O | title = Long-term Mortality and Disability in Cryptococcal Meningitis: A Systematic Literature Review | journal = Clinical Infectious Diseases | volume = 66 | issue = 7 | pages = 1122–1132 | date = March 2018 | pmid = 29028957 | doi = 10.1093/cid/cix870 }}&lt;/ref&gt; Though the rate of infection is clearly higher with immunocompromised individuals, some studies suggest a higher mortality rate in patients with non-HIV cryptococcal meningitis secondary to the role of T-cell mediated reaction and injury.&lt;ref&gt;{{cite journal | vauthors = Anjum S, Williamson PR | title = Clinical Aspects of Immune Damage in Cryptococcosis | journal = Current Fungal Infection Reports | volume = 13 | issue = 3 | pages = 99–108 | date = September 2019 | pmid = 33101578 | pmc = 7580832 | doi = 10.1007/s12281-019-00345-7 }}&lt;/ref&gt; CD4+ T cells have proven roles in the defense against ''Cryptococcus'', but it can also contribute to clinical deterioration due its inflammatory response.&lt;ref&gt;{{cite journal | vauthors = Neal LM, Xing E, Xu J, Kolbe JL, Osterholzer JJ, Segal BM, Williamson PR, Olszewski MA | title = CD4&lt;sup&gt;+&lt;/sup&gt; T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during &lt;i&gt;Cryptococcus neoformans&lt;/i&gt; Meningoencephalitis | journal = mBio | volume = 8 | issue = 6 | pages = e01415–17 | date = November 2017 | article-number = e01415-17 | pmid = 29162707 | pmc = 5698549 | doi = 10.1128/mBio.01415-17 }}&lt;/ref&gt;

== Diagnosis ==
Symptom onset is often subacute, progressively worsens over several weeks, and delays in diagnosis are associated with increased mortality.&lt;ref name=&quot;gushiken-2021&quot;/&gt;&lt;ref name=&quot;Meya 2024&quot; /&gt;

Cerebrospinal fluid (CSF) or blood antigen testing by [[lateral flow assay]] for cryptococcal antigens has a sensitivity and specificity greater than 99% for cryptococcosis.&lt;ref name=&quot;Meya 2024&quot; /&gt; A CSF [[Microbiological culture|fungal culture]] can tell if there is a microbiological failure (failure of the fungal infections to treat the infection). CSF fungal culture has a 90% sensitivity and 100% specificity for the diagnosis of cryptococcal meningitis. CSF cell analysis is characterized by increased lymphocytes, reduced protein, and reduced glucose.&lt;ref name=&quot;Meya 2024&quot; /&gt; For any person who has cryptococcosis at a site outside of the central nervous system (e.g., pulmonary cryptococcosis), a [[lumbar puncture]] is indicated to evaluate the [[cerebrospinal fluid]] (CSF) for evidence of cryptococcal meningitis, even if they do not have signs or symptoms of CNS disease. Detection of cryptococcal [[antigen]] (capsular material) by [[Microbiological culture|culture]] of CSF, [[sputum]], and [[urine]] provides a definitive diagnosis.&lt;ref name=Rhein /&gt; Blood cultures may be positive in heavy infections. [[India ink]] of the CSF is a traditional microscopic method of diagnosis,&lt;ref name=&quot;pmid8862601&quot;&gt;{{cite journal | vauthors = Zerpa R, Huicho L, Guillén A | title = Modified India ink preparation for Cryptococcus neoformans in cerebrospinal fluid specimens | journal = Journal of Clinical Microbiology | volume = 34 | issue = 9 | pages = 2290–2291 | date = September 1996 | pmid = 8862601 | pmc = 229234 | doi = 10.1128/JCM.34.9.2290-2291.1996 }}&lt;/ref&gt; although the sensitivity is poor in early infection, and may miss 15–20% of patients with culture-positive cryptococcal meningitis.&lt;ref name=&quot;Boulware 45–53&quot;&gt;{{cite journal | vauthors = Boulware DR, Rolfes MA, Rajasingham R, von Hohenberg M, Qin Z, Taseera K, Schutz C, Kwizera R, Butler EK, Meintjes G, Muzoora C, Bischof JC, Meya DB | title = Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast | journal = Emerging Infectious Diseases | volume = 20 | issue = 1 | pages = 45–53 | date = January 2014 | pmid = 24378231 | pmc = 3884728 | doi = 10.3201/eid2001.130906 }}&lt;/ref&gt; Rapid diagnostic methods to detect cryptococcal antigen include latex agglutination testing, lateral flow [[immunochromatographic]] assay (LFA), or enzyme immunoassay (EIA). Polymerase chain reaction (PCR) has been used on tissue specimens, with PCR having a sensitivity of 82% and a specificity of 98% for cryptococcal infection.&lt;ref name=&quot;Meya 2024&quot; /&gt;

&lt;gallery&gt;
Image:Cryptococcosis of lung in patient with AIDS. Mucicarmine stain 962 lores.jpg
Image:Pulmonary cryptococcosis (1) histiocytic penumonia.jpg
Image:Pulmonary cryptococcosis (3) Alcian blue-PAS.jpg
Image:Cryptococcus smear MGG 2010-01-26.JPG
Image:Cryptococcus smear MGG 2010-01-27.JPG
Image:Cryptococcus smear PAS 2010-01-26.JPG
&lt;/gallery&gt;

== Prevention ==
Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rate of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.&lt;ref&gt;{{cite web|title=FIGURE 1. Prevalence of asymptomatic antigenemia with corresponding cost per life saved based on LFA cost of $2.50 per test.|url=http://journals.lww.com/jaids/_layouts/oaks.journals/ImageView.aspx?k=jaids:2012:04150:00011&amp;i=FF1&amp;year=2012&amp;issue=04150&amp;article=00011}}&lt;/ref&gt;&lt;ref name=&quot;pmid20597693&quot;&gt;{{cite journal | vauthors = Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR | title = Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count &lt; or = 100 cells/microL who start HIV therapy in resource-limited settings | journal = Clinical Infectious Diseases | volume = 51 | issue = 4 | pages = 448–455 | date = August 2010 | pmid = 20597693 | pmc = 2946373 | doi = 10.1086/655143 }}&lt;/ref&gt;
Cryptococcal antigen screen and preemptive treatment with fluconazole are cost-saving to the healthcare system by avoiding cryptococcal meningitis.&lt;ref&gt;{{cite journal | vauthors = Rajasingham R, Meya DB, Boulware DR | title = Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care | journal = Journal of Acquired Immune Deficiency Syndromes | volume = 59 | issue = 5 | pages = e85–e91 | date = April 2012 | pmid = 22410867 | pmc = 3311156 | doi = 10.1097/QAI.0b013e31824c837e }}&lt;/ref&gt;  The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4&lt;100 cells/μL.&lt;ref name=&quot;WHO Recs&quot; /&gt; This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy.&lt;ref name=&quot;pmid20597693&quot;/&gt;&lt;ref&gt;{{cite journal | vauthors = Jarvis JN, Harrison TS, Govender N, Lawn SD, Longley N, Bicanic T, Maartens G, Venter F, Bekker LG, Wood R, Meintjes G | title = Routine cryptococcal antigen screening for HIV-infected patients with low CD4+ T-lymphocyte counts--time to implement in South Africa? | journal = South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde | volume = 101 | issue = 4 | pages = 232–234 | date = April 2011 | pmid = 21786721 | doi = 10.7196/samj.4752 | doi-broken-date = 11 July 2025 | doi-access = free }}&lt;/ref&gt;  Cryptococcosis accounts for 20–25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4&lt;100 cells/μL.&lt;ref&gt;{{cite journal | vauthors = Rajasingham R, Boulware DR | title = Reconsidering cryptococcal antigen screening in the U.S. among persons with CD4 &lt;100 cells/mcL | journal = Clinical Infectious Diseases | volume = 55 | issue = 12 | pages = 1742–1744 | date = December 2012 | pmid = 22918997 | pmc = 3501329 | doi = 10.1093/cid/cis725 }}&lt;/ref&gt;&lt;ref name=&quot;pmid25006824&quot;&gt;{{cite journal | vauthors = McKenney J, Smith RM, Chiller TM, Detels R, French A, Margolick J, Klausner JD | title = Prevalence and correlates of cryptococcal antigen positivity among AIDS patients--United States, 1986-2012 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 63 | issue = 27 | pages = 585–587 | date = July 2014 | pmid = 25006824 | pmc = 4584711 }}&lt;/ref&gt;

Antifungal prophylaxis such as fluconazole and itraconazole reduces the risk of contracting cryptococcosis in those with low CD4 cell count and high risk of developing such disease in a setting of cryptococcal antigen screening tests are not available.&lt;ref&gt;{{cite journal | vauthors = Awotiwon AA, Johnson S, Rutherford GW, Meintjes G, Eshun-Wilson I | title = Primary antifungal prophylaxis for cryptococcal disease in HIV-positive people | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 8 | article-number = CD004773 | date = August 2018 | pmid = 30156270 | pmc = 6513489 | doi = 10.1002/14651858.CD004773.pub3 | collaboration = Cochrane Infectious Diseases Group }}&lt;/ref&gt;

== Treatment ==
Treatment options for persons without HIV infection have not been well studied. [[Intravenous]] [[amphotericin B|amphotericin&amp;nbsp;B]] combined with [[flucytosine]] by mouth is recommended for initial treatment (induction therapy).&lt;ref&gt;{{cite web |title=Practice Guidelines for the Management of Cryptococcal Disease |publisher=Infectious Disease Society of America |year=2010 |url=http://www.idsociety.org/Organism/#CryptococcalDisease |access-date=2013-09-14 |archive-date=2018-07-25 |archive-url=https://web.archive.org/web/20180725230335/http://www.idsociety.org/organism/#CryptococcalDisease }}&lt;/ref&gt;

People living with AIDS often have a greater burden of disease and higher mortality (30–70% at 10 weeks). Recommended therapy is with amphotericin&amp;nbsp;B and flucytosine. Adding flucytosine to amphotericin''&amp;nbsp;''B is associated with earlier fungal clearance and increased survival; however, it is not readily available in many lower-income regions.&lt;ref name=&quot;Meya 2024&quot; /&gt; Where flucytosine is not available, [[fluconazole]] should be used with amphotericin.&lt;ref name=&quot;WHO Recs&quot;&gt;{{cite web|last=World Health Organization|title=Rapid advice: Diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents, and children|url=https://www.who.int/hiv/pub/cryptococcal_disease2011/en/|archive-url=https://web.archive.org/web/20140221174558/http://www.who.int/hiv/pub/cryptococcal_disease2011/en/|archive-date=February 21, 2014|access-date=1 August 2012}}&lt;/ref&gt; [[Amphotericin]]-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10 weeks.&lt;ref name=&quot;Rhein&quot;&gt;{{cite journal| vauthors = Rhein J, Boulware DR|title=Prognosis and management of cryptococcal meningitis in patients with HIV infection|journal=Neurobehavioral HIV Medicine |year=2012 |volume=4 |page=45 |doi=10.2147/NBHIV.S24748 |doi-access=free}}&lt;/ref&gt;&lt;ref name=Rajasingham&gt;{{cite journal | vauthors = Rajasingham R, Rolfes MA, Birkenkamp KE, Meya DB, Boulware DR | title = Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis | journal = PLOS Medicine | volume = 9 | issue = 9 | article-number = e1001316 | year = 2012 | pmid = 23055838 | pmc = 3463510 | doi = 10.1371/journal.pmed.1001316 | veditors = Farrar J | doi-access = free }}&lt;/ref&gt;  Based on a systematic review, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin''&amp;nbsp;''B coupled with high-dose fluconazole.&lt;ref name=Rajasingham /&gt;  After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks, used with secondary prophylaxis with fluconazole thereafter.&lt;ref name=&quot;WHO Recs&quot; /&gt;

The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis.&lt;ref&gt;{{cite journal | vauthors = Boulware DR, Meya DB, Muzoora C, Rolfes MA, Huppler Hullsiek K, Musubire A, Taseera K, Nabeta HW, Schutz C, Williams DA, Rajasingham R, Rhein J, Thienemann F, Lo MW, Nielsen K, Bergemann TL, Kambugu A, Manabe YC, Janoff EN, Bohjanen PR, Meintjes G | title = Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis | journal = The New England Journal of Medicine | volume = 370 | issue = 26 | pages = 2487–2498 | date = June 2014 | pmid = 24963568 | pmc = 4127879 | doi = 10.1056/NEJMoa1312884 }}&lt;/ref&gt; A 2018 Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment.&lt;ref&gt;{{cite journal | vauthors = Eshun-Wilson I, Okwen MP, Richardson M, Bicanic T | title = Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningitis | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 7 | article-number = CD009012 | date = July 2018 | pmid = 30039850 | pmc = 6513637 | doi = 10.1002/14651858.CD009012.pub3 }}&lt;/ref&gt;

Increased [[intracranial pressure]] is seen in about 50% of those with HIV-associated cryptococcal meningitis and is usually associated with a high fungal burden. Regular (often daily) [[lumbar puncture]]s to lower the intracranial pressure by draining CSF is associated with reduced mortality in those with cryptococcal meningitis (with or without HIV).&lt;ref name=&quot;Meya 2024&quot; /&gt;&lt;ref name=&quot;Rolfes 2014&quot;&gt;{{cite journal | vauthors = Rolfes MA, Hullsiek KH, Rhein J, Nabeta HW, Taseera K, Schutz C, Musubire A, Rajasingham R, Williams DA, Thienemann F, Muzoora C, Meintjes G, Meya DB, Boulware DR | title = The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis | journal = Clinical Infectious Diseases | volume = 59 | issue = 11 | pages = 1607–1614 | date = December 2014 | pmid = 25057102 | doi = 10.1093/cid/ciu596 | pmc = 4441057 }}&lt;/ref&gt;&lt;ref name=&quot;Perfect 2010&quot;&gt;{{cite journal | vauthors = Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC | title = Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america | journal = Clinical Infectious Diseases | volume = 50 | issue = 3 | pages = 291–322 | date = February 2010 | pmid = 20047480 | pmc = 5826644 | doi = 10.1086/649858 }}&lt;/ref&gt; But in those with suspicion of non-communicating [[hydrocephalus]] (which may present as focal neurologic symptoms or impaired mentation), a CT or MRI of the brain is required before lumbar puncture to rule out hydrocephalus, due to the risk of [[brain herniation]] with lumbar puncture. Non-communicating hydrocephalus is rare in those with HIV-associated cryptococcal meningitis.&lt;ref name=&quot;Meya 2024&quot; /&gt;
=== IRIS ===
[[Immune reconstitution inflammatory syndrome]] is possible in those with cryptococcal infection, especially those with concurrent HIV starting [[Management of HIV/AIDS|anti-retroviral therapy]]. With anti-retroviral therapies for HIV, the CD4+ T-cell counts recover, and the restored immune system mounts an exaggerated, hyperinflammatory response against cryptococcal infection in the body.&lt;ref name=&quot;Meya 2024&quot; /&gt;

IRIS has a 5% incidence in those with HIV and cryptococcosis starting anti-retroviral therapy. It usually occurs within 4 weeks of starting antiretroviral therapy.&lt;ref name=&quot;Meya 2024&quot; /&gt; The risk of IRIS is increased in those with a high fungal burden, lower CD4+ T-cell count, and lower inflammatory marker levels.&lt;ref name=&quot;Meya 2024&quot; /&gt;

==Epidemiology==
Cryptococcosis is usually associated with immunosuppressed people, such as those with [[HIV/AIDS|AIDS]], [[corticosteroid]] use, [[diabetes]], and [[Organ transplantation|organ transplant]].&lt;ref name = &quot;Mada_2023&quot;&gt;{{cite book | vauthors = Mada PK, Jamil RT, Alam MU  | chapter = ''Cryptococcus'' |date=2023 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK431060/ | title = StatPearls |access-date=2023-11-15 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28613714 }}&lt;/ref&gt; ''Cryptococcus'' comprizes two clinically relevant species, ''Cryptococcus neoformans'' and ''Cryptococcus gattii''.&lt;ref&gt;{{cite journal | vauthors = Choi YH, Ngamskulrungroj P, Varma A, Sionov E, Hwang SM, Carriconde F, Meyer W, Litvintseva AP, Lee WG, Shin JH, Kim EC, Lee KW, Choi TY, Lee YS, Kwon-Chung KJ | title = Prevalence of the VNIc genotype of Cryptococcus neoformans in non-HIV-associated cryptococcosis in the Republic of Korea | journal = FEMS Yeast Research | volume = 10 | issue = 6 | pages = 769–778 | date = September 2010 | pmid = 20561059 | pmc = 2920376 | doi = 10.1111/j.1567-1364.2010.00648.x }}&lt;/ref&gt; ''C.&amp;nbsp;gattii'' was previously thought to only be found in tropical climates and in immunocompetent persons, but recent findings of ''C.&amp;nbsp;gattii'' in regions such as Canada and Western regions of North America have challenged this initial presumption of the geographic patterns.&lt;ref&gt;{{cite journal | vauthors = Harris J, Lockhart S, Chiller T | title = Cryptococcus gattii: where do we go from here? | journal = Medical Mycology | volume = 50 | issue = 2 | pages = 113–129 | date = February 2012 | pmid = 21939343 | doi = 10.3109/13693786.2011.607854 | s2cid = 21577621 }}&lt;/ref&gt;

Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa and 600,000 per year died.&lt;ref name=&quot;Vallab2016&quot; /&gt; In 2014, amongst people who had a low [[T helper cell|CD4+ cell]] count, the annual incidence rate was estimated to be 278,000 cases. Of those, 223,100 resulted in cryptococcal meningitis.&lt;ref name=&quot;Rajasingham-2017&quot;&gt;{{cite journal | vauthors = Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, Denning DW, Loyse A, Boulware DR | title = Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 8 | pages = 873–881 | date = August 2017 | pmid = 28483415 | pmc = 5818156 | doi = 10.1016/S1473-3099(17)30243-8 | bibcode = 2017LanID..17..873R }}&lt;/ref&gt; About 73% of cryptococcal meningitis cases occurred in Sub-Saharan Africa. More than 180,000 fatalities are attributed to cryptococcal meningitis, 135,000 of which occur in sub-Saharan Africa. Case fatality of cryptococcal meningitis varies widely depending on the country where the infection occurs. In low-income countries, the case fatality from cryptococcal meningitis is 70%. This differs from middle-income countries, where the case fatality rate is 40%. In wealthy countries, the case fatality is 20%.&lt;ref name=&quot;Rajasingham-2017&quot; /&gt; 19% of all AIDS-related deaths are due to cryptococcal disease.&lt;ref name=&quot;Rajasingham 2022&quot;&gt;{{cite journal | vauthors = Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, Meya DB, Chiller TM, Boulware DR | title = The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis | journal = The Lancet. Infectious Diseases | volume = 22 | issue = 12 | pages = 1748–1755 | date = December 2022 | pmid = 36049486 | pmc = 9701154 | doi = 10.1016/S1473-3099(22)00499-6 }}&lt;/ref&gt; Cryptococcal disease is the second leading cause of death in those with HIV/AIDS, second only to tuberculosis, which is responsible for 40% of deaths.&lt;ref name=&quot;Meintjes 2024&quot;&gt;{{cite journal | vauthors = Meintjes G, Maartens G | title = HIV-Associated Tuberculosis | journal = The New England Journal of Medicine | volume = 391 | issue = 4 | pages = 343–355 | date = July 2024 | pmid = 39047241 | doi = 10.1056/NEJMra2308181 }}&lt;/ref&gt; In sub-Saharan Africa, approximately a third of HIV patients will develop cryptococcosis.&lt;ref name=&quot;Alemayehu-2020&quot;/&gt;

=== In the United States ===
In the United States, the incidence of cryptococcosis is estimated to be about 0.4–1.3 cases per 100,000 population and 2–7 cases per 100,000 in people affected with AIDS, with a case fatality ratio of about 12%. Since 1990, the incidence of AIDS-associated cryptococcosis has fallen by 90% due to the proliferation of [[Management of HIV/AIDS|antiretroviral therapy]].&lt;ref&gt;{{Cite web |date=2022-11-02 |title=C. neoformans Infection Statistics |work=Fungal Diseases |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html |access-date=2023-11-15 |publisher=Centers for Disease Control and Prevention |language=en-us}}&lt;/ref&gt;&lt;ref name=&quot;Mada_2023&quot; /&gt; The estimated prevalence of cryptococcosis cases amongst HIV patients in the U.S. is 2.8%.&lt;ref&gt;{{cite journal | vauthors = Alemayehu T, Ayalew S, Buzayehu T, Daka D | title = Magnitude of &lt;i&gt;Cryptococcosis&lt;/i&gt; among HIV patients in sub-Saharan Africa countries: a systematic review and meta-analysis | journal = African Health Sciences | volume = 20 | issue = 1 | pages = 114–121 | date = March 2020 | pmid = 33402899 | pmc = 7750036 | doi = 10.4314/ahs.v20i1.16 }}&lt;/ref&gt; In immunocompetent patients, cryptococcus typically presents itself as ''[[Cryptococcus gattii]]''.&lt;ref name=&quot;Mada_2023&quot; /&gt; Despite its rarity, cryptococcus has been more commonly seen, with upwards of 20% of cases in immunocompetent people.&lt;ref&gt;{{cite journal | vauthors = Stack M, Hiles J, Valinetz E, Gupta SK, Butt S, Schneider JG | title = Cryptococcal Meningitis in Young, Immunocompetent Patients: A Single-Center Retrospective Case Series and Review of the Literature | journal = Open Forum Infectious Diseases | volume = 10 | issue = 8 | article-number = ofad420 | date = August 2023 | pmid = 37636518 | pmc = 10456216 | doi = 10.1093/ofid/ofad420 }}&lt;/ref&gt; Over 50% of cryptococcosis infections in North America are caused by ''C.&amp;nbsp;gattii.'' Though ''C.&amp;nbsp;gattii'' was originally thought to be restricted to subtropical and tropical regions it has become more prevalent worldwide.&lt;ref&gt;{{cite journal | vauthors = Howard-Jones AR, Sparks R, Pham D, Halliday C, Beardsley J, Chen SC | title = Pulmonary Cryptococcosis | journal = Journal of Fungi | volume = 8 | issue = 11 | page = 1156 | date = October 2022 | pmid = 36354923 | pmc = 9696922 | doi = 10.3390/jof8111156 | doi-access = free }}&lt;/ref&gt; ''C.&amp;nbsp;gattii'' has been found in over 90 people in the United States, most of these cases originating in Washington or Oregon.&lt;ref&gt;{{cite journal | vauthors = Harris J, Lockhart S, Chiller T | title = Cryptococcus gattii: where do we go from here? | journal = Medical Mycology | volume = 50 | issue = 2 | pages = 113–129 | date = February 2012 | pmid = 21939343 | doi = 10.3109/13693786.2011.607854 | s2cid = 21577621 }}&lt;/ref&gt;

=== In sub-Saharan Africa ===
Sub-Saharan Africa is the main hub for HIV/AIDS worldwide. HIV/AIDS accounts for about 0.5% of the world's population.&lt;ref&gt;{{Cite web |title=HIV and AIDS Epidemic Global Statistics |url=https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics |access-date=2023-12-12 |website=HIV.gov |language=en}}&lt;/ref&gt; Remarkably, sub-Saharan Africa holds 71% of HIV/AIDs cases.&lt;ref&gt;{{cite journal | vauthors = Kharsany AB, Karim QA | title = HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities | journal = The Open AIDS Journal | volume = 10 | pages = 34–48 | date = 2016-04-08 | pmid = 27347270 | pmc = 4893541 | doi = 10.2174/1874613601610010034 }}&lt;/ref&gt; Cryptococcal meningitis is a primary contributor to mortality among individuals with HIV/AIDS in sub-Saharan Africa.&lt;ref&gt;{{Cite web |date=2022-11-02 |title=C. neoformans Infection Statistics |work=Fungal Diseases |url=https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html |access-date=2023-11-26 |publisher=Centers for Disease Control and Prevention |language=en-us}}&lt;/ref&gt;  Approximately 160,000 cases of cryptococcal meningitis are reported in West Africa, resulting in 130,000 deaths in sub-Saharan Africa.&lt;ref&gt;{{cite journal | vauthors = Akaihe CL, Nweze EI | title = Epidemiology of Cryptococcus and cryptococcosis in Western Africa | journal = Mycoses | volume = 64 | issue = 1 | pages = 4–17 | date = January 2021 | pmid = 32969547 | doi = 10.1111/myc.13188 | s2cid = 221884476 }}&lt;/ref&gt; Uganda is reported to have the highest occurrence of cryptococcus meningitis.&lt;ref name=&quot;Alemayehu-2020&quot;&gt;{{cite journal | vauthors = Alemayehu T, Ayalew S, Buzayehu T, Daka D | title = Magnitude of &lt;i&gt;Cryptococcosis&lt;/i&gt; among HIV patients in sub-Saharan Africa countries: a systematic review and meta-analysis | journal = African Health Sciences | volume = 20 | issue = 1 | pages = 114–121 | date = March 2020 | pmid = 33402899 | pmc = 7750036 | doi = 10.4314/ahs.v20i1.16 }}&lt;/ref&gt; Reflecting that, Ethiopia has the least occurrence.&lt;ref name=&quot;Alemayehu-2020&quot; /&gt; Presently, treatment options involve either a 7 or 14-day regimen of amphotericin-B, coupled with oral antifungal tablets or oral fluconazole. It is important to note that amphotericin B is not considered a treatment, as it showed no significant reduction in the mortality rate.&lt;ref&gt;{{cite journal | vauthors = Patel RK, Leeme T, Azzo C, Tlhako N, Tsholo K, Tawanana EO, Molefi M, Mosepele M, Lawrence DS, Mokomane M, Tenforde MW, Jarvis JN | title = High Mortality in HIV-Associated Cryptococcal Meningitis Patients Treated With Amphotericin B-Based Therapy Under Routine Care Conditions in Africa | journal = Open Forum Infectious Diseases | volume = 5 | issue = 11 | article-number = ofy267 | date = November 2018 | pmid = 30488038 | pmc = 6251350 | doi = 10.1093/ofid/ofy267 }}&lt;/ref&gt;

== Other animals ==
Cryptococcosis is also seen in cats and occasionally in dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with [[FeLV]] infection in cats. Cryptococcosis is most common in dogs and cats, but cattle, sheep, goats, horses, wild animals, and birds can also be infected. Soil, fowl manure, and [[pigeon]] droppings are among the sources of infection.&lt;ref&gt;{{cite web|url=http://www.cathealth.com/FungalINFXdeep.htm|title=Deep Fungal Infections|archive-url=https://web.archive.org/web/20100413225853/http://www.cathealth.com/FungalINFXdeep.htm|archive-date=2010-04-13}}&lt;/ref&gt;&lt;ref&gt;{{cite journal|url=http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&amp;PID=6653&amp;O=Generic|title=Feline Cryptococcosis – WSAVA 2003 Congress – VIN|website=Vin.com|date=July 2014| vauthors = Takeuchi A }}&lt;/ref&gt;

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC | title = Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america | journal = Clinical Infectious Diseases | volume = 50 | issue = 3 | pages = 291–322 | date = February 2010 | pmid = 20047480 | pmc = 5826644 | doi = 10.1086/649858 }}
* {{cite journal | vauthors = Gullo FP, Rossi SA, Sardi J, Teodoro VL, Mendes-Giannini MJ, Fusco-Almeida AM | title = Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment | journal = European Journal of Clinical Microbiology &amp; Infectious Diseases | volume = 32 | issue = 11 | pages = 1377–1391 | date = November 2013 | pmid = 24141976 | doi = 10.1007/s10096-013-1915-8 | s2cid = 11317427 }}
* {{cite journal | vauthors = Perfect JR | title = Cryptococcus neoformans: a sugar-coated killer with designer genes | journal = FEMS Immunology and Medical Microbiology | volume = 45 | issue = 3 | pages = 395–404 | date = September 2005 | pmid = 16055314 | doi = 10.1016/j.femsim.2005.06.005 | doi-access = free }} (Review)
{{refend}}

== External links ==
* [http://emedicine.medscape.com/article/215354-overview Medscape entry on cryptococcosis]

{{Mycoses}}
{{Diseases of meninges}}
{{Medical resources
| ICD10           = {{ICD10|B|45||b|35}}
| ICD9            = {{ICD9|117.5}}
| ICDO            =
| OMIM            =
| DiseasesDB      = 3213
| MedlinePlus     = 001328
| eMedicineSubj   = med
| eMedicineTopic  = 482
| MeshID          = D003453
| Orphanet        = 1546
}}
{{Authority control}}

[[Category:Animal fungal diseases]]
[[Category:Bird diseases]]
[[Category:Bovine diseases]]
[[Category:Cat diseases]]
[[Category:Dog diseases]]
[[Category:Fungi and humans]]
[[Category:HIV/AIDS]]
[[Category:Horse diseases]]
[[Category:Mycosis-related cutaneous conditions]]
[[Category:Sheep and goat diseases]]
[[Category:Tremellomycetes]]
[[Category:Zoonoses]]
[[Category:Fungal diseases]]