Fungal meningitis epidemiology and demographics: Difference between revisions

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==Overview==
==Overview==
While cryptococccus and candida infections occur worldwide, other [[fungal infections]] tend to cluster in specific geographical regions.<ref name="pmid17921648">{{cite journal| author=Shankar SK, Mahadevan A, Sundaram C, Sarkar C, Chacko G, Lanjewar DN et al.| title=Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario. | journal=Neurol India | year= 2007 | volume= 55 | issue= 3 | pages= 198-215 | pmid=17921648 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17921648  }} </ref><ref name="pmid11051295">{{cite journal| author=Gottfredsson M, Perfect JR| title=Fungal meningitis. | journal=Semin Neurol | year= 2000 | volume= 20 | issue= 3 | pages= 307-22 | pmid=11051295 | doi=10.1055/s-2000-9394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11051295  }} </ref> The most common cause of [[fungal meningitis]] is ''[[Cryptococcus neoformans]]''.<ref>Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.</ref><ref name="pmid27886201">{{cite journal| author=Williamson PR, Jarvis JN, Panackal AA, Fisher MC, Molloy SF, Loyse A et al.| title=Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. | journal=Nat Rev Neurol | year= 2017 | volume= 13 | issue= 1 | pages= 13-24 | pmid=27886201 | doi=10.1038/nrneurol.2016.167 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27886201  }} </ref><ref name="pmid11051295">{{cite journal| author=Gottfredsson M, Perfect JR| title=Fungal meningitis. | journal=Semin Neurol | year= 2000 | volume= 20 | issue= 3 | pages= 307-22 | pmid=11051295 | doi=10.1055/s-2000-9394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11051295  }} </ref>
While cryptococccus and candida infections occur worldwide, other [[fungal infections]] tend to cluster in specific geographical regions.<ref name="pmid17921648">{{cite journal| author=Shankar SK, Mahadevan A, Sundaram C, Sarkar C, Chacko G, Lanjewar DN et al.| title=Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario. | journal=Neurol India | year= 2007 | volume= 55 | issue= 3 | pages= 198-215 | pmid=17921648 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17921648  }} </ref><ref name="pmid11051295">{{cite journal| author=Gottfredsson M, Perfect JR| title=Fungal meningitis. | journal=Semin Neurol | year= 2000 | volume= 20 | issue= 3 | pages= 307-22 | pmid=11051295 | doi=10.1055/s-2000-9394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11051295  }} </ref> There is an increasing trend of fungal meningitis. This has been attributed  to enlarging population of high-risk immunosuppressed patients, more successful pharmacological immunosuppression and chemotherapies, increase in numbers of patients living with [[Human Immunodeficiency Virus (HIV)|human immunodeficiency virus]] (HIV) infection and the [[acquired immunodeficiency syndrome]] (AIDS), migration of susceptible persons into hyperendemic areas and aging of the population.<ref name="pmid11051295" /><ref name="pmid480580" /> Cryptococcal meningitis occurs worldwide but it is highly prevalent in southeast Asia and southern and east Africa where the prevalence of [[HIV]] is high.<ref name=":0" /> The incidence of cryptococcal meningitis is almost the same as in [[meningococcal meningitis]]<ref name="pmid8654513" /> with an incidence of one case per 100,000 persons.<ref name="pmid8654513" />
Prior to the introduction of [[AIDS antiretroviral drugs|highly active antiretroviral therapy]] (HAART) in the United States, yearly incidence rate of cryptococcal meningitis was on ascendancy with incidence of  6600 cases per 100,000 persons with AIDS<ref name="pmid12627365" />  The incidence has decreased with the advent of HAART <ref name="pmid11125898" /> although cases are still reported.<ref name="pmid10930155" /> The worldwide incidence of cryptococcal meningitis is pegged at 1,000,000 annually according to an estimate by Centers for Disease Control and Prevention CDC in 2009<ref name="pmid19182676" /> with approximately half of these resulting in death.<ref name="pmid19182676" /> The prevalence of fungal meningitis does not vary with gender.<ref name="pmid20375357" /> Non-Caucasian race have a higher prediclection to developing fungal meningitis especially coccidioidal meningitis<ref name="pmid7231152" /> The prevalence of fungal meningitis does not vary with age.<ref name="pmid20375357" /> The major factor accounting for age predilection has to do with the clinical state of the patient and the immune response. For example candida meningitis may occur in older children<ref name="pmid10066050" /><ref name="pmid10987704" /> and in adults with [[neutropenia]], often presenting with [[brain abscesses]] rather than [[meningitis]].<ref name="pmid9810800" /> Children with certain conditions have higher incidence of fungal meningitis example [[myeloperoxidase deficiency]],<ref name="pmid6834633" /><ref name="pmid8381226" /> [[chronic granulomatous disease]] of childhood<ref name="pmid7195647" /><ref name="pmid3706396" /> and [[chronic mucocutaneous candidiasis]].<ref name="pmid8160723" />


==Epidemiology==
==Epidemiology==
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*It is the most common cause of [[fungal meningitis]].<ref>Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.</ref><ref name="pmid27886201">{{cite journal| author=Williamson PR, Jarvis JN, Panackal AA, Fisher MC, Molloy SF, Loyse A et al.| title=Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. | journal=Nat Rev Neurol | year= 2017 | volume= 13 | issue= 1 | pages= 13-24 | pmid=27886201 | doi=10.1038/nrneurol.2016.167 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27886201  }} </ref><ref name="pmid11051295">{{cite journal| author=Gottfredsson M, Perfect JR| title=Fungal meningitis. | journal=Semin Neurol | year= 2000 | volume= 20 | issue= 3 | pages= 307-22 | pmid=11051295 | doi=10.1055/s-2000-9394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11051295  }} </ref>
*It is the most common cause of [[fungal meningitis]].<ref>Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.</ref><ref name="pmid27886201">{{cite journal| author=Williamson PR, Jarvis JN, Panackal AA, Fisher MC, Molloy SF, Loyse A et al.| title=Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. | journal=Nat Rev Neurol | year= 2017 | volume= 13 | issue= 1 | pages= 13-24 | pmid=27886201 | doi=10.1038/nrneurol.2016.167 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27886201  }} </ref><ref name="pmid11051295">{{cite journal| author=Gottfredsson M, Perfect JR| title=Fungal meningitis. | journal=Semin Neurol | year= 2000 | volume= 20 | issue= 3 | pages= 307-22 | pmid=11051295 | doi=10.1055/s-2000-9394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11051295  }} </ref>


*Cryptococcus meningitis occurs worldwide but it is highly prevalent in southeast Asia and southern and east Africa where the prevalence of [[HIV]] is high.<ref>Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg K (2003) Review of human immunodeficiency virus type 1-related opportunistic infections in Sub-Saharan Africa. Clin Infect Dis, 36, 652–662.</ref>
*Cryptococcus meningitis occurs worldwide but it is highly prevalent in southeast Asia and southern and east Africa where the prevalence of [[HIV]] is high.<ref name=":0">Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg K (2003) Review of human immunodeficiency virus type 1-related opportunistic infections in Sub-Saharan Africa. Clin Infect Dis, 36, 652–662.</ref>
*It is a common opportunistic infection in patients with [[HIV]] and it is considered as an [[AIDS]] defining lesion. <ref>Chariyalertsak S, Sirisanthana T, Saengwonloey O, Nelson K (2001) Clinical presentation and risk behaviors of patients with acquired immunodeficiency syndrome in Thailand, 1994–1998: Regional                                variation and temporal trends. Clin Infect Dis, 32, 955–962.</ref>
*It is a common opportunistic infection in patients with [[HIV]] and it is considered as an [[AIDS]] defining lesion. <ref>Chariyalertsak S, Sirisanthana T, Saengwonloey O, Nelson K (2001) Clinical presentation and risk behaviors of patients with acquired immunodeficiency syndrome in Thailand, 1994–1998: Regional                                variation and temporal trends. Clin Infect Dis, 32, 955–962.</ref>


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The worldwide incidence of cryptococcal meningitis is pegged at 1,000,000 annually according to an estimate by Centers for Disease Control and Prevention CDC in 2009<ref name="pmid19182676">{{cite journal| author=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 | year= 2009 | volume= 23 | issue= 4 | pages= 525-30 | pmid=19182676 | doi=10.1097/QAD.0b013e328322ffac | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182676  }} </ref> with approximately half of these resulting in death.<ref name="pmid19182676" />
The worldwide incidence of cryptococcal meningitis is pegged at 1,000,000 annually according to an estimate by Centers for Disease Control and Prevention CDC in 2009<ref name="pmid19182676">{{cite journal| author=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 | year= 2009 | volume= 23 | issue= 4 | pages= 525-30 | pmid=19182676 | doi=10.1097/QAD.0b013e328322ffac | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182676  }} </ref> with approximately half of these resulting in death.<ref name="pmid19182676" />


The predominate specie involved is cryptococcus neoformans, although there have been recent reports of incidence with Cryptococcus gattii  Canada, Vancouver and the Pacific Northwestern United States<ref name="pmid15572442">{{cite journal| author=Kidd SE, Hagen F, Tscharke RL, Huynh M, Bartlett KH, Fyfe M et al.| title=A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). | journal=Proc Natl Acad Sci U S A | year= 2004 | volume= 101 | issue= 49 | pages= 17258-63 | pmid=15572442 | doi=10.1073/pnas.0402981101 | pmc=535360 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15572442  }} </ref><ref name="pmid17370514">{{cite journal| author=MacDougall L, Kidd SE, Galanis E, Mak S, Leslie MJ, Cieslak PR et al.| title=Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. | journal=Emerg Infect Dis | year= 2007 | volume= 13 | issue= 1 | pages= 42-50 | pmid=17370514 | doi=10.3201/eid1301.060827 | pmc=2725832 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17370514  }} </ref>
The predominate species involved is cryptococcus neoformans, although there have been recent reports of incidence with Cryptococcus gattii  Canada, Vancouver and the Pacific Northwestern United States<ref name="pmid15572442">{{cite journal| author=Kidd SE, Hagen F, Tscharke RL, Huynh M, Bartlett KH, Fyfe M et al.| title=A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). | journal=Proc Natl Acad Sci U S A | year= 2004 | volume= 101 | issue= 49 | pages= 17258-63 | pmid=15572442 | doi=10.1073/pnas.0402981101 | pmc=535360 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15572442  }} </ref><ref name="pmid17370514">{{cite journal| author=MacDougall L, Kidd SE, Galanis E, Mak S, Leslie MJ, Cieslak PR et al.| title=Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. | journal=Emerg Infect Dis | year= 2007 | volume= 13 | issue= 1 | pages= 42-50 | pmid=17370514 | doi=10.3201/eid1301.060827 | pmc=2725832 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17370514  }} </ref>


====  Histoplasma meningitis ====
====  Histoplasma meningitis ====
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The prevalence of fungal meningitis does not vary with age.<ref name="pmid20375357">{{cite journal| author=Saccente M, Woods GL| title=Clinical and laboratory update on blastomycosis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 2 | pages= 367-81 | pmid=20375357 | doi=10.1128/CMR.00056-09 | pmc=2863359 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375357  }} </ref> The major factor accounting for age predilection has to do with the clinical state of the patient and the immune response.
The prevalence of fungal meningitis does not vary with age.<ref name="pmid20375357">{{cite journal| author=Saccente M, Woods GL| title=Clinical and laboratory update on blastomycosis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 2 | pages= 367-81 | pmid=20375357 | doi=10.1128/CMR.00056-09 | pmc=2863359 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375357  }} </ref> The major factor accounting for age predilection has to do with the clinical state of the patient and the immune response.


For example candidda meningitis may occur in older children<ref name="pmid10066050">{{cite journal| author=Huttova M, Kralinsky K, Horn J, Marinova I, Iligova K, Fric J et al.| title=Prospective study of nosocomial fungal meningitis in children--report of 10 cases. | journal=Scand J Infect Dis | year= 1998 | volume= 30 | issue= 5 | pages= 485-7 | pmid=10066050 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10066050  }} </ref><ref name="pmid10987704">{{cite journal| author=McCullers JA, Vargas SL, Flynn PM, Razzouk BI, Shenep JL| title=Candidal meningitis in children with cancer. | journal=Clin Infect Dis | year= 2000 | volume= 31 | issue= 2 | pages= 451-7 | pmid=10987704 | doi=10.1086/313987 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10987704  }} </ref> and in adults with neutropenia, often presents with brain abscesses rather than meningitis.<ref name="pmid9810800">{{cite journal| author=del Pozo MM, Bermejo F, Molina JA, de la Fuente EC, Martínez-Martín P, Benito-León J| title=Chronic neutrophilic meningitis caused by Candida albicans. | journal=Neurologia | year= 1998 | volume= 13 | issue= 7 | pages= 362-6 | pmid=9810800 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9810800  }} </ref>
For example candida meningitis may occur in older children<ref name="pmid10066050">{{cite journal| author=Huttova M, Kralinsky K, Horn J, Marinova I, Iligova K, Fric J et al.| title=Prospective study of nosocomial fungal meningitis in children--report of 10 cases. | journal=Scand J Infect Dis | year= 1998 | volume= 30 | issue= 5 | pages= 485-7 | pmid=10066050 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10066050  }} </ref><ref name="pmid10987704">{{cite journal| author=McCullers JA, Vargas SL, Flynn PM, Razzouk BI, Shenep JL| title=Candidal meningitis in children with cancer. | journal=Clin Infect Dis | year= 2000 | volume= 31 | issue= 2 | pages= 451-7 | pmid=10987704 | doi=10.1086/313987 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10987704  }} </ref> and in adults with neutropenia, often presents with brain abscesses rather than meningitis.<ref name="pmid9810800">{{cite journal| author=del Pozo MM, Bermejo F, Molina JA, de la Fuente EC, Martínez-Martín P, Benito-León J| title=Chronic neutrophilic meningitis caused by Candida albicans. | journal=Neurologia | year= 1998 | volume= 13 | issue= 7 | pages= 362-6 | pmid=9810800 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9810800  }} </ref>


Children with the following conditions have higher incidence of fungal meningitis:
Children with the following conditions have higher incidence of fungal meningitis:


*Myeloperoxidase deficiency<ref name="pmid6834633">{{cite journal| author=Oleske J, Minnefor A, Cooper R, Thomas K, dela Cruz A, Ahdieh H et al.| title=Immune deficiency syndrome in children. | journal=JAMA | year= 1983 | volume= 249 | issue= 17 | pages= 2345-9 | pmid=6834633 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6834633  }} </ref><ref name="pmid8381226">{{cite journal| author=Ludviksson BR, Thorarensen O, Gudnason T, Halldorsson S| title=Candida albicans meningitis in a child with myeloperoxidase deficiency. | journal=Pediatr Infect Dis J | year= 1993 | volume= 12 | issue= 2 | pages= 162-4 | pmid=8381226 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8381226  }} </ref>
*[[Myeloperoxidase deficiency]]<ref name="pmid6834633">{{cite journal| author=Oleske J, Minnefor A, Cooper R, Thomas K, dela Cruz A, Ahdieh H et al.| title=Immune deficiency syndrome in children. | journal=JAMA | year= 1983 | volume= 249 | issue= 17 | pages= 2345-9 | pmid=6834633 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6834633  }} </ref><ref name="pmid8381226">{{cite journal| author=Ludviksson BR, Thorarensen O, Gudnason T, Halldorsson S| title=Candida albicans meningitis in a child with myeloperoxidase deficiency. | journal=Pediatr Infect Dis J | year= 1993 | volume= 12 | issue= 2 | pages= 162-4 | pmid=8381226 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8381226  }} </ref>


*Chronic granulomatous disease of childhood<ref name="pmid7195647">{{cite journal| author=Cohen MS, Isturiz RE, Malech HL, Root RK, Wilfert CM, Gutman L et al.| title=Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi. | journal=Am J Med | year= 1981 | volume= 71 | issue= 1 | pages= 59-66 | pmid=7195647 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7195647  }} </ref><ref name="pmid3706396">{{cite journal| author=Fleischmann J, Church JA, Lehrer RI| title=Primary Candida meningitis and chronic granulomatous disease. | journal=Am J Med Sci | year= 1986 | volume= 291 | issue= 5 | pages= 334-41 | pmid=3706396 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3706396  }} </ref>
*[[Chronic granulomatous disease]] of childhood<ref name="pmid7195647">{{cite journal| author=Cohen MS, Isturiz RE, Malech HL, Root RK, Wilfert CM, Gutman L et al.| title=Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi. | journal=Am J Med | year= 1981 | volume= 71 | issue= 1 | pages= 59-66 | pmid=7195647 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7195647  }} </ref><ref name="pmid3706396">{{cite journal| author=Fleischmann J, Church JA, Lehrer RI| title=Primary Candida meningitis and chronic granulomatous disease. | journal=Am J Med Sci | year= 1986 | volume= 291 | issue= 5 | pages= 334-41 | pmid=3706396 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3706396  }} </ref>


*Chronic mucocutaneous candidiasis<ref name="pmid8160723">{{cite journal| author=Germain M, Gourdeau M, Hébert J| title=Case report: familial chronic mucocutaneous candidiasis complicated by deep candida infection. | journal=Am J Med Sci | year= 1994 | volume= 307 | issue= 4 | pages= 282-3 | pmid=8160723 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8160723  }} </ref>
*[[Chronic mucocutaneous candidiasis]]<ref name="pmid8160723">{{cite journal| author=Germain M, Gourdeau M, Hébert J| title=Case report: familial chronic mucocutaneous candidiasis complicated by deep candida infection. | journal=Am J Med Sci | year= 1994 | volume= 307 | issue= 4 | pages= 282-3 | pmid=8160723 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8160723  }} </ref>


* White blood cell defects<ref name="pmid7195647">{{cite journal| author=Cohen MS, Isturiz RE, Malech HL, Root RK, Wilfert CM, Gutman L et al.| title=Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi. | journal=Am J Med | year= 1981 | volume= 71 | issue= 1 | pages= 59-66 | pmid=7195647 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7195647  }} </ref><ref name="pmid3706396">{{cite journal| author=Fleischmann J, Church JA, Lehrer RI| title=Primary Candida meningitis and chronic granulomatous disease. | journal=Am J Med Sci | year= 1986 | volume= 291 | issue= 5 | pages= 334-41 | pmid=3706396 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3706396  }} </ref>
* White blood cell defects<ref name="pmid7195647">{{cite journal| author=Cohen MS, Isturiz RE, Malech HL, Root RK, Wilfert CM, Gutman L et al.| title=Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi. | journal=Am J Med | year= 1981 | volume= 71 | issue= 1 | pages= 59-66 | pmid=7195647 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7195647  }} </ref><ref name="pmid3706396">{{cite journal| author=Fleischmann J, Church JA, Lehrer RI| title=Primary Candida meningitis and chronic granulomatous disease. | journal=Am J Med Sci | year= 1986 | volume= 291 | issue= 5 | pages= 334-41 | pmid=3706396 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3706396  }} </ref>


*Severe combined immunodeficiency SCID<ref name="pmid6726524">{{cite journal| author=Smego RA, Devoe PW, Sampson HA, Perfect JR, Wilfert CM, Buckley RH| title=Candida meningitis in two children with severe combined immunodeficiency. | journal=J Pediatr | year= 1984 | volume= 104 | issue= 6 | pages= 902-4 | pmid=6726524 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6726524  }} </ref>
*[[Severe combined immunodeficiency]] [[Severe combined immunodeficiency|SCID]]<ref name="pmid6726524">{{cite journal| author=Smego RA, Devoe PW, Sampson HA, Perfect JR, Wilfert CM, Buckley RH| title=Candida meningitis in two children with severe combined immunodeficiency. | journal=J Pediatr | year= 1984 | volume= 104 | issue= 6 | pages= 902-4 | pmid=6726524 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6726524  }} </ref>
   
   
*Advanced HIV<ref name="pmid9314460">{{cite journal| author=Casado JL, Quereda C, Oliva J, Navas E, Moreno A, Pintado V et al.| title=Candidal meningitis in HIV-infected patients: analysis of 14 cases. | journal=Clin Infect Dis | year= 1997 | volume= 25 | issue= 3 | pages= 673-6 | pmid=9314460 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9314460  }} </ref>
*Advanced HIV<ref name="pmid9314460">{{cite journal| author=Casado JL, Quereda C, Oliva J, Navas E, Moreno A, Pintado V et al.| title=Candidal meningitis in HIV-infected patients: analysis of 14 cases. | journal=Clin Infect Dis | year= 1997 | volume= 25 | issue= 3 | pages= 673-6 | pmid=9314460 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9314460  }} </ref>

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby; Prince Tano Djan, BSc, MBChB [2]

Overview

While cryptococccus and candida infections occur worldwide, other fungal infections tend to cluster in specific geographical regions.[1][2] There is an increasing trend of fungal meningitis. This has been attributed to enlarging population of high-risk immunosuppressed patients, more successful pharmacological immunosuppression and chemotherapies, increase in numbers of patients living with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS), migration of susceptible persons into hyperendemic areas and aging of the population.[2][3] Cryptococcal meningitis occurs worldwide but it is highly prevalent in southeast Asia and southern and east Africa where the prevalence of HIV is high.[4] The incidence of cryptococcal meningitis is almost the same as in meningococcal meningitis[5] with an incidence of one case per 100,000 persons.[5] Prior to the introduction of highly active antiretroviral therapy (HAART) in the United States, yearly incidence rate of cryptococcal meningitis was on ascendancy with incidence of 6600 cases per 100,000 persons with AIDS[6] The incidence has decreased with the advent of HAART [7] although cases are still reported.[8] The worldwide incidence of cryptococcal meningitis is pegged at 1,000,000 annually according to an estimate by Centers for Disease Control and Prevention CDC in 2009[9] with approximately half of these resulting in death.[9] The prevalence of fungal meningitis does not vary with gender.[10] Non-Caucasian race have a higher prediclection to developing fungal meningitis especially coccidioidal meningitis[11] The prevalence of fungal meningitis does not vary with age.[10] The major factor accounting for age predilection has to do with the clinical state of the patient and the immune response. For example candida meningitis may occur in older children[12][13] and in adults with neutropenia, often presenting with brain abscesses rather than meningitis.[14] Children with certain conditions have higher incidence of fungal meningitis example myeloperoxidase deficiency,[15][16] chronic granulomatous disease of childhood[17][18] and chronic mucocutaneous candidiasis.[19]

Epidemiology

Incidence and prevalence

There is an increasing trend of fungal meningitis. This has been attributed to the following: [2][3]

  • Enlarging population of high-risk immunosuppressed patients
  • More successful pharmacological immunosuppression and chemotherapies
  • Increase in numbers of patients living with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS)
  • Migration of susceptible persons into hyperendemic areas
  • Aging of the population

Cryptococcus Meningitis

  • Cryptococcus meningitis occurs worldwide but it is highly prevalent in southeast Asia and southern and east Africa where the prevalence of HIV is high.[4]
  • It is a common opportunistic infection in patients with HIV and it is considered as an AIDS defining lesion. [22]

The incidence of cryptococcal meningitis in is almost the same as in meningococcal meningitis[5] with an incidence of one case per 100,000 persons.[5] Prior to the introduction of highly active antiretroviral therapy (HAART) in the United States, yearly incidence rate of cryptococcal meningitis was on ascendancy with incidence of 6600 cases per 100,000 persons with AIDS[6] The incidence has decreased with the advent of HAART [7] although cases are still reported.[8]

The worldwide incidence of cryptococcal meningitis is pegged at 1,000,000 annually according to an estimate by Centers for Disease Control and Prevention CDC in 2009[9] with approximately half of these resulting in death.[9]

The predominate species involved is cryptococcus neoformans, although there have been recent reports of incidence with Cryptococcus gattii Canada, Vancouver and the Pacific Northwestern United States[23][24]

Histoplasma meningitis

The incidence of Histoplasma meningitis is estimated to be 2.3 per 100,000 persons.[3]

Blastomyces meningitis

The incidence of Blastomyces meningitis is estimated to be 0.2 per 100,000 persons.[3]

Coccidioido meningitis

  • Coccidioidomycosis is only prevalent in the Western Hemisphere, especially in the southwestern United States and northwestern Mexico.
  • The annual incidence of the disease is not known.

Age

The prevalence of fungal meningitis does not vary with age.[10] The major factor accounting for age predilection has to do with the clinical state of the patient and the immune response.

For example candida meningitis may occur in older children[12][13] and in adults with neutropenia, often presents with brain abscesses rather than meningitis.[14]

Children with the following conditions have higher incidence of fungal meningitis:

  • Direct extension via trauma [27]
  • Post ventriculostomy placement, or ventricular shunts, especially after antibacterial therapy[28][29]
  • Use of bischloroethylnitrosourea polymer wafers implanted for local therapy of CNS malignancies[30][31]
  • CNS drains and catheters represent disease[32]
  • In premature infants and neonates[33]

Gender

The prevalence of fungal meningitis does not vary with gender.[10]

Race

  • Non-Caucasian race have a higher prediclection to developing fungal meningitis especially coccidioidal meningitis[11]

Developed Vs developing countries

The geographical distribution of endemic fungi causing meningitis are shown below:[34]

Fungus Demography
Blastomyces dermatiditis Midwest and southeast of USA, lower Mississippi Valley up to the north central states and into the mid-Atlantic states.
Coccidiodes immitis Mostly in dry, slightly acidic soil making it common in Southwest of USA, parts of Mexico and Central and South America.
Histoplasma Capsulatum: Ohio, central Mississippi River Valley and Appalachian Mountains,
Cryptococcus spp Cryptococcus neoformans is distributed worldwide with the following specifics:
  • Serotype A is the most common. Found in people with or without HIV worldwide
  • Serotypes B and C are mostly found in Australia, Southeast Asia, Central Africa and

recently in Vancouver, Canada and the Pacific Northwestern United States

  • Serotype D polysaccharide capsule and are primarily found in Europe and the United States.
Paracoccidioides brasiliensi Subtropical areas of Central and South America.
Hyalohyphomycoses There are numerous molds in this group, including Aspergillus, Scedosporium, and Fusarium species.  It has a worldwide distribution.
Candida Species Worldwide distribution
Sporothrix schenckii Worldwide distribution

References

  1. ↑ Shankar SK, Mahadevan A, Sundaram C, Sarkar C, Chacko G, Lanjewar DN; et al. (2007). "Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario". Neurol India. 55 (3): 198–215. PMID 17921648.
  2. ↑ 2.0 2.1 2.2 2.3 Gottfredsson M, Perfect JR (2000). "Fungal meningitis". Semin Neurol. 20 (3): 307–22. doi:10.1055/s-2000-9394. PMID 11051295.
  3. ↑ 3.0 3.1 3.2 3.3 Fraser DW, Ward JI, Ajello L, Plikaytis BD (1979). "Aspergillosis and other systemic mycoses. The growing problem". JAMA. 242 (15): 1631–5. PMID 480580.
  4. ↑ 4.0 4.1 Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg K (2003) Review of human immunodeficiency virus type 1-related opportunistic infections in Sub-Saharan Africa. Clin Infect Dis, 36, 652–662.
  5. ↑ 5.0 5.1 5.2 5.3 Hajjeh RA, Brandt ME, Pinner RW (1995). "Emergence of cryptococcal disease: epidemiologic perspectives 100 years after its discovery". Epidemiol Rev. 17 (2): 303–20. PMID 8654513.
  6. ↑ 6.0 6.1 Mirza SA, Phelan M, Rimland D, Graviss E, Hamill R, Brandt ME; et al. (2003). "The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992-2000". Clin Infect Dis. 36 (6): 789–94. doi:10.1086/368091. PMID 12627365.
  7. ↑ 7.0 7.1 van Elden LJ, Walenkamp AM, Lipovsky MM, Reiss P, Meis JF, de Marie S; et al. (2000). "Declining number of patients with cryptococcosis in the Netherlands in the era of highly active antiretroviral therapy". AIDS. 14 (17): 2787–8. PMID 11125898.
  8. ↑ 8.0 8.1 Hakim JG, Gangaidzo IT, Heyderman RS, Mielke J, Mushangi E, Taziwa A; et al. (2000). "Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients". AIDS. 14 (10): 1401–7. PMID 10930155.
  9. ↑ 9.0 9.1 9.2 9.3 Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM (2009). "Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS". AIDS. 23 (4): 525–30. doi:10.1097/QAD.0b013e328322ffac. PMID 19182676.
  10. ↑ 10.0 10.1 10.2 10.3 Saccente M, Woods GL (2010). "Clinical and laboratory update on blastomycosis". Clin Microbiol Rev. 23 (2): 367–81. doi:10.1128/CMR.00056-09. PMC 2863359. PMID 20375357.
  11. ↑ 11.0 11.1 Bouza E, Dreyer JS, Hewitt WL, Meyer RD (1981). "Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature". Medicine (Baltimore). 60 (3): 139–72. PMID 7231152.
  12. ↑ 12.0 12.1 Huttova M, Kralinsky K, Horn J, Marinova I, Iligova K, Fric J; et al. (1998). "Prospective study of nosocomial fungal meningitis in children--report of 10 cases". Scand J Infect Dis. 30 (5): 485–7. PMID 10066050.
  13. ↑ 13.0 13.1 McCullers JA, Vargas SL, Flynn PM, Razzouk BI, Shenep JL (2000). "Candidal meningitis in children with cancer". Clin Infect Dis. 31 (2): 451–7. doi:10.1086/313987. PMID 10987704.
  14. ↑ 14.0 14.1 del Pozo MM, Bermejo F, Molina JA, de la Fuente EC, Martínez-Martín P, Benito-León J (1998). "Chronic neutrophilic meningitis caused by Candida albicans". Neurologia. 13 (7): 362–6. PMID 9810800.
  15. ↑ 15.0 15.1 Oleske J, Minnefor A, Cooper R, Thomas K, dela Cruz A, Ahdieh H; et al. (1983). "Immune deficiency syndrome in children". JAMA. 249 (17): 2345–9. PMID 6834633.
  16. ↑ 16.0 16.1 Ludviksson BR, Thorarensen O, Gudnason T, Halldorsson S (1993). "Candida albicans meningitis in a child with myeloperoxidase deficiency". Pediatr Infect Dis J. 12 (2): 162–4. PMID 8381226.
  17. ↑ 17.0 17.1 17.2 Cohen MS, Isturiz RE, Malech HL, Root RK, Wilfert CM, Gutman L; et al. (1981). "Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi". Am J Med. 71 (1): 59–66. PMID 7195647.
  18. ↑ 18.0 18.1 18.2 Fleischmann J, Church JA, Lehrer RI (1986). "Primary Candida meningitis and chronic granulomatous disease". Am J Med Sci. 291 (5): 334–41. PMID 3706396.
  19. ↑ 19.0 19.1 Germain M, Gourdeau M, Hébert J (1994). "Case report: familial chronic mucocutaneous candidiasis complicated by deep candida infection". Am J Med Sci. 307 (4): 282–3. PMID 8160723.
  20. ↑ Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  21. ↑ Williamson PR, Jarvis JN, Panackal AA, Fisher MC, Molloy SF, Loyse A; et al. (2017). "Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy". Nat Rev Neurol. 13 (1): 13–24. doi:10.1038/nrneurol.2016.167. PMID 27886201.
  22. ↑ Chariyalertsak S, Sirisanthana T, Saengwonloey O, Nelson K (2001) Clinical presentation and risk behaviors of patients with acquired immunodeficiency syndrome in Thailand, 1994–1998: Regional variation and temporal trends. Clin Infect Dis, 32, 955–962.
  23. ↑ Kidd SE, Hagen F, Tscharke RL, Huynh M, Bartlett KH, Fyfe M; et al. (2004). "A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada)". Proc Natl Acad Sci U S A. 101 (49): 17258–63. doi:10.1073/pnas.0402981101. PMC 535360. PMID 15572442.
  24. ↑ MacDougall L, Kidd SE, Galanis E, Mak S, Leslie MJ, Cieslak PR; et al. (2007). "Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA". Emerg Infect Dis. 13 (1): 42–50. doi:10.3201/eid1301.060827. PMC 2725832. PMID 17370514.
  25. ↑ Smego RA, Devoe PW, Sampson HA, Perfect JR, Wilfert CM, Buckley RH (1984). "Candida meningitis in two children with severe combined immunodeficiency". J Pediatr. 104 (6): 902–4. PMID 6726524.
  26. ↑ Casado JL, Quereda C, Oliva J, Navas E, Moreno A, Pintado V; et al. (1997). "Candidal meningitis in HIV-infected patients: analysis of 14 cases". Clin Infect Dis. 25 (3): 673–6. PMID 9314460.
  27. ↑ Brenier-Pinchart MP, Leclercq P, Mallié M, Bettega G (1999). "Candida meningitis possibly resulting from a harpoon injury". Eur J Clin Microbiol Infect Dis. 18 (6): 454–5. PMID 10442428.
  28. ↑ O'Brien D, Stevens NT, Lim CH, O'Brien DF, Smyth E, Fitzpatrick F; et al. (2011). "Candida infection of the central nervous system following neurosurgery: a 12-year review". Acta Neurochir (Wien). 153 (6): 1347–50. doi:10.1007/s00701-011-0990-9. PMID 21431456.
  29. ↑ Nguyen MH, Yu VL (1995). "Meningitis caused by Candida species: an emerging problem in neurosurgical patients". Clin Infect Dis. 21 (2): 323–7. PMID 8562739.
  30. ↑ O'Brien D, Cotter M, Lim CH, Sattar MT, Smyth E, Fitzpatrick F (2011). "Candida parapsilosis meningitis associated with Gliadel (BCNU) wafer implants". Br J Neurosurg. 25 (2): 289–91. doi:10.3109/02688697.2010.534202. PMID 21158511.
  31. ↑ Glick JA, Graham RS, Voils SA (2010). "Candida meningitis post Gliadel wafer placement successfully treated with intrathecal and intravenous amphotericin B." Ann Pharmacother. 44 (1): 215–8. doi:10.1345/aph.1M453. PMID 20028954.
  32. ↑ Geers TA, Gordon SM (1999). "Clinical significance of Candida species isolated from cerebrospinal fluid following neurosurgery". Clin Infect Dis. 28 (5): 1139–47. doi:10.1086/514755. PMID 10452649.
  33. ↑ Fernandez M, Moylett EH, Noyola DE, Baker CJ (2000). "Candidal meningitis in neonates: a 10-year review". Clin Infect Dis. 31 (2): 458–63. doi:10.1086/313973. PMID 10987705.
  34. ↑ Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.

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