Fungal meningitis epidemiology and demographics

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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 cryptococcus 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]

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]

Gender

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

Race

Developed Vs developing countries

The geographical distribution of endemic fungi causing meningitis are shown below:[25]

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

Paracoccidioides brasiliensi Subtropical areas of Central and South America.
Hyalohyphomycoses There are numerous molds in this group, including AspergillusScedosporium, 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. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  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.

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