Skip to main content

Advertisement

Log in

Invasive Fungal Infections of the Central Nervous System in Immune-Competent Hosts

  • Clinical Pathology (S Challa, Section Editor)
  • Published:
Current Fungal Infection Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Fungal infections of the central nervous system (CNS) occur more commonly in immunosuppressed individuals. However, they are being recognized in apparently immune-competent hosts in recent times. Understanding the risk factors, characters of the fungus, and pathogenesis is important.

Recent Findings

Fungal infections of CNS in apparently immune-competent hosts are described following neurosurgical procedures, head trauma, patients exposed to contaminated devices/drugs, or natural disasters. Disruption of the meninges and blood-brain barrier and direct inoculation of the fungal spores into the subarachnoid space are implicated in the pathogenesis. Contamination of drugs used for epidural injections resulted in an epidemic of fungal meningitis by a dematiaceous fungus, which was never reported earlier to cause CNS disease. Certain fungi like Coccidioides, Paracoccidioides, Histoplasma, and Blastomyces are endemic and the high concentrations in the environment and exposure are risk factors for invasive infections. Heavy and constant exposure in hot and humid climate is responsible for Aspergillus flavus infections in tropical countries. Some fungi such as Cryptococcus spp. and dematiaceous fungi are neurotropic. Environmental, genetic, and socioeconomic factors are also implicated. The exact pathogenesis remains unclear. The intense inflammatory response elicited by immune-competent hosts is likely to result in host damage. Sub-optimal health care facilities in developing countries along with environmental and climatic changes likely result in invasive infections in immune-competent hosts.

Summary

Awareness of invasive fungal infections in immune-competent host with uncommon clinical presentation and uncommon etiological agents is important for early diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• McCarthy M, Rosengart A, Schuetz AN, Kontoyiannis DP, Walsh TJ. Mold infections of the central nervous system. New England J Med. 2014;371(2):150–60. A good and comprehensive review of the epidemiological and clinical manifestations of mold infections of the CNS.

    Google Scholar 

  2. Murthy JM, Sundaram C. Fungal infections of the central nervous system. In: Handbook of clinical neurology, vol. 121: Elsevier; 2014. p. 1383–401.

  3. Brumble LM, Reza MB, Dhakal LP, Cruz G, Abu Saleh OM, Heckman MG. Fungal infections of the central nervous system: clinical, radiographic and laboratory manifestations. J Microbiol Exp. 2017;5(6):00167.

    Google Scholar 

  4. Góralska K, Blaszkowska J, Dzikowiec M. Neuroinfections caused by fungi. Infection. 2018;46(4):443–59.

    PubMed  PubMed Central  Google Scholar 

  5. Chikley A, Ben-Ami R, Kontoyiannis DP. Mucormycosis of the central nervous system. Journal of Fungi. 2019;5(3):59.

    CAS  PubMed Central  Google Scholar 

  6. Kauffman CA. Central nervous system infection with other endemic mycoses: rare manifestation of Blastomycosis, Paracoccidioidomycosis, Talaromycosis, and Sporotrichosis. Journal of Fungi. 2019;5(3):64.

    CAS  PubMed Central  Google Scholar 

  7. •• Aspergillosis CS, Turgut M, Challa S, Akhaddar A. Editors. Fungal infections of the central nervous system: pathogens, diagnosis, and management: Springer; 2019. p. 91–106. A good review of pathogenesis and pathology of CNS aspergillosis.

  8. Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: a review of 101 cases. Clin Infect Dis. 2004;38(2):206–16.

    PubMed  Google Scholar 

  9. •• Velasco J, Revankar S. CNS Infections caused by brown-black fungi. J Fungi. 2019;5(3):60. A good account of etiological agents and pathogenesis of CNS infections due to melanized fungi.

    CAS  Google Scholar 

  10. • Antinori S, Corbellino M, Meroni L, Resta F, Sollima S, Tonolini M, et al. Aspergillus meningitis: a rare clinical manifestation of central nervous system aspergillosis. Case report and review of 92 cases. Journal of Infection. 2013;66(3):218–38. A good review of iotrogenic fungal meningitis.

    PubMed  Google Scholar 

  11. Perfect JR. Iatrogenic fungal meningitis: tragedy repeated. Ann Intern Med. 2012;157(11):825–6.

    PubMed  Google Scholar 

  12. •• Smith RM, Schaefer MK, Kainer MA, Wise M, Finks J, Duwve J, et al. Multistate fungal infection outbreak response team fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2013;369(17):1598–609. Report of multistate outbreak of fungal meningitis due to contaminated methylprednisolone injections. Exserohilum rostratum, a plant pathogen and dematiaceous fungus was isolated, which, prior to the outbreak was not reported to cause CNS disease.

    CAS  PubMed  Google Scholar 

  13. Kauffman CA, Pappas PG, Patterson TF. Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2013;368(26):2495–500.

    CAS  PubMed  Google Scholar 

  14. Benedict K, Park BJ. Invasive fungal infections after natural disasters. Emerg Infect Dis. 2014;20(3):349–55.

    PubMed  PubMed Central  Google Scholar 

  15. Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis: a study in 111 cases. Ann Intern Med. 1974;80(2):176–81.

    CAS  PubMed  Google Scholar 

  16. •• Shankar SK, Mahadevan A, Sundaram C, Sarkar C, Chacko G, Lanjewar DN, et al. Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario. Neurology India. 2007;55(3):198. An excellent review of pathology of CNS fungal infections, with particular reference to India.

    CAS  PubMed  Google Scholar 

  17. Li J, Vinh DC, Casanova JL, Puel A. Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals. Curr Opin Microbiol. 2017;40:46–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Drummond RA, Franco LM, Lionakis MS. Human CARD9: a critical molecule of fungal immune surveillance. Front Immunol. 2018;9:1836.

    PubMed  PubMed Central  Google Scholar 

  19. Kollath DR, Miller KJ, Barker BM. The mysterious desert dwellers: Coccidioides immitis and Coccidioides posadasii, causative fungal agents of coccidioidomycosis. Virulence. 2019;10(1):222–33.

    PubMed  PubMed Central  Google Scholar 

  20. Freedman M, Jackson BR, McCotter O, Benedict K. Coccidioidomycosis Outbreaks, United States and Worldwide, 1940-2015. Emerg Infect Dis 2018; 24 (3): 417–23

  21. Freedman M, Jackson BR, McCotter O, Benedict K. Coccidioidomycosis Outbreaks, United States and Worldwide, 1940–2015-Volume 24, Number 3—March 2018-Emerging Infectious Diseases journal-CDC.

  22. Wheat J, Myint T, Guo Y, Kemmer P, Hage C, Terry C, et al. Central nervous system histoplasmosis: multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine. 2018;97(13).

  23. Jamjoom A, Al-Hedaithy SS, Jamjoom ZA, Al-Sohaibani MO, Aziz SA. Cranial and intracranial aspergillosis of sino-nasal origin. Acta Neurochir. 1996;138(8):944–50.

    PubMed  Google Scholar 

  24. Murthy JM, Sundaram C, Prasad VS, Purohit AK, Rammurti S, Laxmi V. Aspergillosis of central nervous system: a study of 21 patients seen in a university hospital in South India. J Assoc Physicians India. 2000;48(7):677–81.

    CAS  PubMed  Google Scholar 

  25. Murthy JM, Sundaram C, Prasad VS, Purohit AK, Rammurti S, Laxmi V. Sinocranial aspergillosis: a form of central nervous system aspergillosis in South India. Mycoses. 2001;44(5):141–5.

    CAS  PubMed  Google Scholar 

  26. Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VS, Panigrahi M, et al. Pathology of fungal infections of the central nervous system: 17 years' experience from Southern India. Histopathology. 2006;49(4):396–405.

    CAS  PubMed  Google Scholar 

  27. Garcia-Solache MA, Casadevall A. Global warming will bring new fungal diseases for mammals. MBio. 2010;1(1):e00061–10.

    PubMed  PubMed Central  Google Scholar 

  28. Comrie AC. Climate factors influencing coccidioidomycosis seasonality and outbreaks. Environ Health Perspect. 2005;113(6):688–92.

    PubMed  PubMed Central  Google Scholar 

  29. Billmyre RB, Croll D, Li W, Mieczkowski P, Carter DA, Cuomo CA, et al. Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution. MBio. 2014;5(4):e01494–14.

    PubMed  PubMed Central  Google Scholar 

  30. McDonald R, Dufort E, Jackson BR, Tobin EH, Newman A, Benedict K, et al. Notes from the field: blastomycosis cases occurring outside of regions with known endemicity — New York, 2007–2017. MMWR / September 28. 2018;67(38):1077–8.

    Google Scholar 

  31. Permpalung N, Kaewpoowat Q, Prasidthrathsint K, Chongnarungsin D, Hyman CL. Pulmonary blastomycosis: a new endemic area in New York state. Mycoses. 2013;56:592–5.

    PubMed  Google Scholar 

  32. Nakamura Y, Utsumi Y, Suzuki N, Nakajima Y, Murata O, Sasaki N, et al. Multiple Scedosporium apiospermum abscesses in a woman survivor of a tsunami in northeastern Japan: a case report. J Med Case Rep. 2011;5(1):526.

    PubMed  PubMed Central  Google Scholar 

  33. Igusa R, Narumi S, Murakami K, Kitawaki Y, Tamii T, Kato M, et al. Escherichia coli pneumonia in combination with fungal sinusitis and meningitis in a tsunami survivor after the Great East Japan Earthquake. Tohoku J Exp Med. 2012;227(3):179–84.

    PubMed  Google Scholar 

  34. Cortez KJ, Roilides E, Quiroz-Telles F, Meletiadis J, Antachopoulos C, Knudsen T, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev. 2008;21(1):157–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Warnock DW. Fungal diseases: an evolving public health challenge. Med Mycol. 2006 Jan 1;44(8):697–705.

    PubMed  Google Scholar 

  36. Radhakrishnan VV, Saraswathy A, Rout D, Mohan PK. Mycotic aneurysms of the intracranial vessels. Indian J Med Res. 1994;100:228–31.

    CAS  PubMed  Google Scholar 

  37. Gunaratne PS, Wijeyaratne CN, Chandrasiri P, Sivakumaran S, Sellahewa K, Perera P, et al. An outbreak of Aspergillus meningitis following spinal anaesthesia for caesarean section in Sri Lanka: a post-tsunami effect? Ceylon Med J. 2006;51(4):137–42.

    CAS  PubMed  Google Scholar 

  38. Sundaram C, Goel D, Uppin SG, Seethajayalakshmi S, Borgohain R. Intracranial mycotic aneurysm due to Aspergillus species. J Clin Neurosci. 2007;14(9):882–6.

    CAS  PubMed  Google Scholar 

  39. Elsawy A, Faidah H, Ahmed A, Mostafa A, Mohamed F. Aspergillus terreus meningitis in immunocompetent patient: a case report. Front Microbiol. 2015;6:1353.

    PubMed  PubMed Central  Google Scholar 

  40. Rodrigo N, Perera KN, Ranwala R, Jayasinghe S, Warnakulasuriya A, Hapuarachchi S. Aspergillus meningitis following spinal anaesthesia for caesarean section in Colombo, Sri Lanka. Int J Obstet Anesth. 2007;16(3):256–60.

    CAS  PubMed  Google Scholar 

  41. Lokuhetty MD, Wijesinghe HD, Weerasundera B, Dayapala A. Iatrogenic aspergillus infection of the central nervous system in a pregnant woman.

  42. Chakrabarti A, Chatterjee SS, Das A, Shivaprakash MR. Invasive aspergillosis in developing countries. Medical Mycol. 2011;49(Supplement_1):S35–47.

    Google Scholar 

  43. Adler A, Yaniv I, Samra Z, Yacobovich J, Fisher S, Avrahami G, et al. Exserohilum: an emerging human pathogen. Eur J Clin Microbiol Infect Dis. 2006;25(4):247–53.

    CAS  PubMed  Google Scholar 

  44. Abbas KM, Dorratoltaj N, O’Dell ML, Bordwine P, Kerkering TM, Redican KJ. Clinical response, outbreak investigation, and epidemiology of the fungal meningitis epidemic in the United States: systematic review. Disaster medicine and public health preparedness. 2016;10(1):145–51.

    PubMed  Google Scholar 

  45. Poon WS, Ng S, Wai S. CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomised study. In: InIntracranial pressure and neuromonitoring in brain injury. Vienna: Springer; 1998. p. 146–8.

    Google Scholar 

  46. •• O’Brien D, Stevens NT, Lim CH, O’Brien DF, Smyth E, Fitzpatrick F. Humphreys H. candida infection of the central nervous system following neurosurgery: a 12-year review. Acta neurochirurgica. 2011;153(6):1347–50 An extensive review of the candida infections of CNS following neurosurgery.

    PubMed  Google Scholar 

  47. Nguyen MH, Yu VL. Meningitis caused by Candida species: an emerging problem in neurosurgical patients. Clin Infect Dis. 1995;21(2):323–7.

    CAS  PubMed  Google Scholar 

  48. Geers TA, Gordon SM. Clinical significance of Candida species isolated from cerebrospinal fluid following neurosurgery. Clin Infect Dis. 1999;28(5):1139–47.

    CAS  PubMed  Google Scholar 

  49. Conen A, Fux CA, Vajkoczy P, Trampuz A. Management of infections associated with neurosurgical implanted devices. Expert Rev Anti-Infect Ther. 2017 Mar 4;15(3):241–55.

    CAS  PubMed  Google Scholar 

  50. Sharma RR, Gurusinghe NT, Lynch PG. Cerebral infarction due to Aspergillus arteritis following glioma surgery. Br J Neurosurg. 1992;6(5):485–90.

    CAS  PubMed  Google Scholar 

  51. Winterholler M, Coras R, Geißdörfer W, Rammensee R, Gölitz P, Bogdan C, et al. Fatal mycotic aneurysm of the basilar artery caused by Aspergillus fumigatus in a patient with pituitary adenoma and meningitis. Front Med. 2017;4:113.

    Google Scholar 

  52. Melsom SM, Khangure MS. Craniofacial mucormycosis following assault: an unusual presentation of an unusual disease. Australas Radiol. 2000;44(1):104–6.

    CAS  PubMed  Google Scholar 

  53. Chamdine O, Gaur AH, Broniscer A. Effective treatment of cerebral mucormycosis associated with brain surgery. Pediatr Infect Dis J. 2015;34(5):542–3.

    PubMed  PubMed Central  Google Scholar 

  54. Hussain FS, Hussain NS. A unique case of intracranial mucormycosis following an assault. Cureus. 2016;8(7).

  55. Kronen R, Liang SY, Bochicchio G, Bochicchio K, Powderly WG, Spec A. Invasive fungal infections secondary to traumatic injury. Int J Infect Dis. 2017;62:102–11.

    PubMed  Google Scholar 

  56. Lanternier F, Barbati E, Meinzer U, Liu L, Pedergnana V, Migaud M, et al. Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection. J Infect Dis. 2015;211(8):1241–50.

    CAS  PubMed  Google Scholar 

  57. McCarthy MW, Kalasauskas D, Petraitis V, Petraitiene R, Walsh TJ. Fungal infections of the central nervous system in children. J Pediatr Infect Dis Soc. 2017;6(3):e123–33.

    Google Scholar 

  58. Sharma BS, Khosla VK, Kak VK, Banerjee AK, Vasishtha RK, Prasad KM, et al. Intracranial fungal granuloma. Surg Neurol. 1997;47(5):489–97.

    CAS  PubMed  Google Scholar 

  59. Dubey A, Patwardhan RV, Sampth S, Santosh V, Kolluri S, Nanda A. Intracranial fungal granuloma: analysis of 40 patients and review of the literature. Surg Neurol. 2005;63(3):254–60.

    PubMed  Google Scholar 

  60. Sundaram C, Mahadevan A, Laxmi V, Yasha TC, Santosh V, Murthy JM, et al. Cerebral zygomycosis. Mycoses. 2005;48(6):396–407.

    CAS  PubMed  Google Scholar 

  61. •• Mishra A, Prabhuraj AR, Shukla DP, Nandeesh BN, Chandrashekar N, Ramalingaiah A, et al. Intracranial fungal granuloma: a single-institute study of 90 cases over 18 years. Neurosurgical Focus. 2019;47(2):E14 A report of 90 intracranial fungal granulomas of varied etiologies, from a single center in India, majority being in immunecompetent hosts.

    PubMed  Google Scholar 

  62. Suri P, Chhina DK, Kaushal V, Kaushal RK, Singh J. Cerebral phaeohyphomycosis due to Cladophialophora bantiana–a case report and review of literature from India. J Clin Diagn Res. 2014;8(4):DD01–5.

    PubMed  PubMed Central  Google Scholar 

  63. Koutsouras GW, Ramos RL, Martinez LR. Role of microglia in fungal infections of the central nervous system. Virulence. 2017;8(6):705–18.

    PubMed  Google Scholar 

  64. Speth C, Rambach G. Complement attack against Aspergillus and corresponding evasion mechanisms. Interdisciplinary perspectives on infectious diseases. 2012;2012.

  65. Klein RS, Hunter CA. Protective and pathological immunity during central nervous system infections. Immunity. 2017;46(6):891–909.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Casadevall A, Pirofski LA. The damage-response framework of microbial pathogenesis. Nat Rev Microbiol. 2003;1(1):17–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Bahr N, Boulware DR, Marais S, Scriven J, Wilkinson RJ, Meintjes G. Central nervous system immune reconstitution inflammatory syndrome. Curr Infect Dis Rep. 2013;15(6):583–93.

    PubMed  Google Scholar 

  68. •• Panackal AA, Williamson KC, van de Beek D, Boulware DR, Williamson PR. Fighting the monster: applying the host damage framework to human central nervous system infections. MBio. 2016;7(1):e01906–15 An excellent review of the pathogenesis of CNS infections with particular reference to the host damage framework in cryptococcal infection.

    PubMed  PubMed Central  Google Scholar 

  69. Santana-Ramírez A, Esparza-Gutiérrez SV, Avila-Rodríguez P, Jiménez-Gómez JE, Vélez-Gómez E, Bañuelos-Gallo D. Aspergillosis of the central nervous system in a previously healthy patient that simulated Creutzfeldt–Jakob disease. Surg Neurol Int. 2016;7(Suppl 39):S940–6.

    PubMed  PubMed Central  Google Scholar 

  70. Patterson TF, Thompson GR III, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–60.

    PubMed  PubMed Central  Google Scholar 

  71. Murthy JM. Fungal infections of the central nervous system: the clinical syndromes. Neurol India. 2007;55(3):221–5.

    CAS  PubMed  Google Scholar 

  72. Shamim MS, Siddiqui AA, Enam SA, Shah AA, Jooma R, Anwar S. Craniocerebral aspergillosis in immunocompetent hosts: surgical perspective. Neurol India. 2007;55(3):274–81.

    PubMed  Google Scholar 

  73. Challa S, Uppin SG, Hanumanthu S, Panigrahi MK, Purohit AK, Sattaluri S, et al. Fungal rhinosinusitis: a clinicopathological study from South India. Eur Arch Otorhinolaryngol. 2010;267(8):1239–45.

    PubMed  Google Scholar 

  74. Sundaram C, Murthy JM. Intracranial aspergillus granuloma. Pathol Res Int. 2011;2011.

  75. Al-Doory Y, Wagner GE. editors. Aspergillosis: Charles C Thomas Pub Limited; 1985.

  76. Hedayati MT, Pasqualotto AC, Warn PA, Bowyer P, Denning DW. Aspergillus flavus: human pathogen, allergen and mycotoxin producer. Microbiology. 2007;153(6):1677–92.

    CAS  PubMed  Google Scholar 

  77. Chimelli L, Mahler-Araújo MB. Fungal infections. Brain Pathol. 1997 Jan;7(1):613–27.

    CAS  PubMed  Google Scholar 

  78. Krishnan S, Manavathu EK, Chandrasekar PH. Aspergillus flavus: an emerging non-fumigatus Aspergillus species of significance. Mycoses. 2009;52(3):206–22.

    CAS  PubMed  Google Scholar 

  79. Raksha GS, Urhekar AD. Virulence factors detection in Aspergillus isolates from clinical and environmental samples. J Clin Diagn Res. 2017;11(7):DC13.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Challa S, Uppin SG, Purohit AK. Isolated cerebral Aspergillus granuloma with no obvious source of infection. Neurol India. 2007;55(3):289–91.

    PubMed  Google Scholar 

  81. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000;13(2):236–301.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53.

    PubMed  Google Scholar 

  83. Chakrabarti A, Singh R. Mucormycosis in India: unique features. Mycoses. 2014;57:85–90.

    PubMed  Google Scholar 

  84. Prakash H, Ghosh AK, Rudramurthy SM, Paul RA, Gupta S, Negi V, et al. The environmental source of emerging Apophysomyces variabilis infection in India. Sabouraudia. 2016;54(6):567–75.

    CAS  Google Scholar 

  85. Wolkow N, Jakobiec FA, Stagner AM, Cunnane ME, Piantadosi AL, Basgoz N, et al. Chronic orbital and calvarial fungal infection with Apophysomyces variabilis in an immunocompetent patient. Surv Ophthalmol. 2017;62(1):70–82.

    PubMed  Google Scholar 

  86. Kerezoudis P, Watts CR, Bydon M, Dababneh AS, Deyo CN, Frye JM, et al. Diagnosis and treatment of isolated cerebral mucormycosis: patient-level data meta-analysis and Mayo Clinic Experience. World neurosurgery. 2019;123:425–34.

    PubMed  Google Scholar 

  87. Mackenzie DW, Soothill JF, Millar JH. Meningitis caused by Absidia corymbifera. J Infect. 1988;17(3):241–8.

    CAS  PubMed  Google Scholar 

  88. Radner AB, Witt MD, Edwards JE Jr. Acute invasive rhinocerebral zygomycosis in an otherwise healthy patient: case report and review. Clin Infect Dis. 1995;20(1):163–6.

    CAS  PubMed  Google Scholar 

  89. Garcia-Covarrubias L, Bartlett R, Barratt DM, Wassermann RJ. Rhino-orbitocerebral mucormycosis attributable to Apophysomyces elegans in an immunocompetent individual: case report and review of the literature. J Trauma Acute Care Surg. 2001;50(2):353–7.

    CAS  Google Scholar 

  90. Lelievre L, Garcia-Hermoso D, Abdoul H, Hivelin M, Chouaki T, Toubas D, et al. Posttraumatic mucormycosis: a nationwide study in France and review of the literature. Medicine. 2014;93(24).

  91. Rangel-Guerra RA, Martínez HR, Sáenz C, Bosques-Padilla F, Estrada-Bellmann I. Rhinocerebral and systemic mucormycosis. Clinical experience with 36 cases. J Neurol Sci. 1996;143(1–2):19–30.

    CAS  PubMed  Google Scholar 

  92. El Benaye J, Zoobo T, Chahdi H, Baba N, Oukabli M, Ghfir M, et al. Erysipelas of the face revealing a mucormycosis. Journal de mycologie médicale. 2011;21(3):202.

    PubMed  Google Scholar 

  93. Higo T, Kobayashi T, Yamazaki S, Ando S, Gonoi W, Ishida M, et al. Cerebral embolism through hematogenous dissemination of pulmonary mucormycosis complicating relapsed leukemia. Int J Clin Exp Pathol. 2015;8(10):13639–42.

    PubMed  PubMed Central  Google Scholar 

  94. Economides MP, Ballester LY, Kumar VA, Jiang Y, Tarrand J, Prieto V, et al. Invasive mold infections of the central nervous system in patients with hematologic cancer or stem cell transplantation (2000–2016): uncommon, with improved survival but still deadly often. J Infect. 2017;75(6):572–80.

    PubMed  Google Scholar 

  95. Bannykh SI, Hunt B, Moser F. Intra-arterial spread of Mucormycetes mediates early ischemic necrosis of brain and suggests new venues for prophylactic therapy. Neuropathology. 2018;38(5):539–41.

    PubMed  Google Scholar 

  96. Hopkins RJ, Rothman M, Fiore A, Goldblum SE. Cerebral mucormycosis associated with intravenous drug use: three case reports and review. Clin Infect Dis. 1994;19(6):1133–7.

    CAS  PubMed  Google Scholar 

  97. Huston SM, Mody CH. Cryptococcosis: an emerging respiratory mycosis. Clin Chest Med. 2009;30(2):253–64.

    PubMed  Google Scholar 

  98. Mitchell DH, Sorrell TC, Allworth AM, Heath CH, McGregor AR, Papanaoum K, et al. Cryptococcal disease of the CNS in immunocompetent hosts: influence of cryptococcal variety on clinical manifestations and outcome. Clin Infect Dis. 1995;20(3):611–6.

    CAS  PubMed  Google Scholar 

  99. Chrétien F, Lortholary O, Kansau I, Neuville S, Gray F, Dromer F. Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia. J Infect Dis. 2002;186(4):522–30.

    PubMed  Google Scholar 

  100. Santangelo R, Zoellner H, Sorrell T, Wilson C, Donald C, Djordjevic J, et al. Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model. Infect Immun. 2004;72(4):2229–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Charlier C, Chrétien F, Baudrimont M, Mordelet E, Lortholary O, Dromer F. Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier. Am J Pathol. 2005;166(2):421–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Jain N, Guerrero A, Fries BC. Phenotypic switching and its implications for the pathogenesis of Cryptococcus neoformans. FEMS Yeast Res. 2006;6(4):480–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. •• Saijo T, Chen J, Chen SC, Rosen LB, Yi J, Sorrell TC, et al. Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. MBio. 2014;5(2):e00912–14 Highlights the importance of screening for Anti GM-CSF autoantibodies to CNS cryptococcosis due to C gatti infection in immune competent hosts.

    PubMed  PubMed Central  Google Scholar 

  104. Schoffelen T, Illnait-Zaragozi MT, Joosten LA, Netea MG, Boekhout T, Meis JF, et al. Cryptococcus gattii induces a cytokine pattern that is distinct from other cryptococcal species. PloS one. 2013;8(1).

  105. Panackal AA, Wuest SC, Lin YC, Wu T, Zhang N, Kosa P, et al. Paradoxical immune responses in non-HIV cryptococcal meningitis. PLoS Pathogens. 2015;11(5).

  106. Komori M, Blake A, Greenwood M, Lin YC, Kosa P, Ghazali D, et al. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis. Ann Neurol. 2015;78(1):3–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Petzold A, Michel P, Stock M, Schluep M. Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome. J Stroke Cerebrovasc Dis. 2008;17(4):196–203.

    PubMed  Google Scholar 

  108. Li Q, You C, Liu Q, Liu Y. Central nervous system cryptococcoma in immunocompetent patients: a short review illustrated by a new case. Acta Neurochir. 2010;152(1):129–36.

    PubMed  Google Scholar 

  109. Sing Y, Ramdial PK. Cryptococcal inflammatory pseudotumors. Am J Surg Pathol. 2007;31(10):1521–7.

    PubMed  Google Scholar 

  110. Mahadevan A, Susarla SK. Cryptococcosis. In: Fungal Infections of the Central Nervous System. Cham: Springer; 2019. p. 167–85.

    Google Scholar 

  111. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18:19–37.

    CAS  PubMed  Google Scholar 

  112. McCullers JA, Vargas SL, Flynn PM, Razzouk BI, Shenep JL. Candidal meningitis in children with cancer. Clin Infect Dis. 2000;31:451–7.

    CAS  PubMed  Google Scholar 

  113. Benjamin DK Jr, Poole C, Steinbach WJ, Rowen JL, Walsh TJ. Neonatal candidemia and end-organ damage: a critical appraisal of the literature using meta-analytic techniques. Pediatrics. 2003;112(3 Pt 1):634–40.

    PubMed  Google Scholar 

  114. Walsh TJ, Katragkou A, Chen T, Salvatore CM, Roilides E. Invasive candidiasis in infants and children: recent advances in epidemiology, diagnosis, and treatment. J Fungi (Basel). 2019;5(1):11.

    CAS  Google Scholar 

  115. Petraitiene R, Petraitis V, Hope WW, Mickiene D, Kelaher AM, Murray HA, et al. Cerebrospinal fluid and plasma (1–>3)-beta-D-glucan as surrogate markers for detection and monitoring of therapeutic response in experimental hematogenous Candida meningoencephalitis. Antimicrob Agents Chemother. 2008;52:4121–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Bagheri F, Cervellione KL, Maruf M, Marino W, Santucci T Jr. Candida parapsilosis meningitis associated with shunt infection in an adult male. Clin Neurol Neurosurg. 2010;112(3):248–51.

    PubMed  Google Scholar 

  117. Bhalla GS, Malik M, Sarao MS, Bandyopadhyay K, Singh P, Tadepalli S, et al. Device-associated central nervous system infection caused by Candida parapsilosis. Cureus. 2018;10(8).

  118. Singhal T, Kumar A, Borade P, Shah S, Soman R. Successful treatment of C. auris shunt infection with intraventricular caspofungin. Med Mycol Case Rep. 2018;22:35–7.

    PubMed  PubMed Central  Google Scholar 

  119. Fennelly AM, Slenker AK, Murphy LC, Moussouttas M, Desimone JA. Candida cerebral abscesses: a case report and review of the literature. Med Mycol. 2013;51(7):779–84.

    PubMed  Google Scholar 

  120. Merwick Á, Minhas Z, Curtis C, Thom M, Choi D, Mummery C. Intradural extramedullary spinal candida infection. Pract Neurol. 2015;15(5):400–4.

    CAS  PubMed  Google Scholar 

  121. Zimmermann J, Güresir Á, Nelles M, Güresir E. Rapid development and rupture of a cerebral mycotic aneurysm in Candida infective endocarditis. Intensive Care Med. 2016;42(2):275–6.

    PubMed  Google Scholar 

  122. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–50.

    PubMed  Google Scholar 

  123. Lionakis MS, Holland SM. Human invasive mycoses: immunogenetics on the rise. J Infect Dis. 2015;211:1205–7.

    CAS  PubMed  Google Scholar 

  124. Pilmis B, Puel A, Lortholary O, Lanternier F. New clinical phenotypes of fungal infections in special hosts. Clin Microbiol Infect. 2016;22(8):681–7.

    CAS  PubMed  Google Scholar 

  125. Biggs PJ, Allen RL, Powers JM, Holley HP. Phaeohyphomycosis complicating compound skull fracture. Surg Neurol. 1986;25(4):393–6.

    CAS  PubMed  Google Scholar 

  126. Carter E, Boudreaux C. Fatal cerebral phaeohyphomycosis due to Curvularia lunata in an immunocompetent patient. J Clin Microbiol. 2004;42(11):5419–23.

    PubMed  PubMed Central  Google Scholar 

  127. Gadgil N, Kupferman M, Smitherman S, Fuller GN, Rao G. Curvularia brain abscess. J Clin Neurosci. 2013;20(1):173–5.

    PubMed  Google Scholar 

  128. Al-Tawfiq JA, Boukhamseen A. Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei (formerly Ramichloridium mackenziei): case presentation and literature review. J Infect Public Health. 2011;4(2):96–102.

    PubMed  Google Scholar 

  129. Jacobson ES. Pathogenic roles for fungal melanins. Clin Microbiol Rev. 2000;13(4):708–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Hamilton AJ, Gomez BL. Melanins in fungal pathogens. J Med Microbiol. 2002;51(3):189.

    Google Scholar 

  131. Kuan CS, Cham CY, Singh G, Yew SM, Tan YC, Chong PS, et al. Genomic analyses of Cladophialophora bantiana, a major cause of cerebral phaeohyphomycosis provides insight into its lifestyle, virulence and adaption in host. PloS one. 2016;11(8).

  132. Jayakeerthi SR, Dias M, Nagarathna S, Anandh B, Mahadevan A, Chandramuki A. Brain abscess due to Cladophialophora bantiana. Indian J Med Microbiol. 2004;22(3):193–5.

    CAS  PubMed  Google Scholar 

  133. Garg N, Devi IB, Vajramani GV, Nagarathna S, Sampath S, Chandramouli BA, et al. Central nervous system cladosporiosis: an account of ten culture-proven cases. Neurol India. 2007;55(3):282–8.

    PubMed  Google Scholar 

  134. Borkar SA, Sharma MS, Rajpal G, Jain M, Xess I, Sharma BS. Brain abscess caused by Cladophialophora bantiana in an immunocompetent host: need for a novel cost-effective antifungal agent. Indian J Med Microbiol. 2008;26(3):271.

    CAS  PubMed  Google Scholar 

  135. Revankar SG. Cladophialophora bantiana brain abscess in an immunocompetent patient. Can J Infect Dis Med Microbiol. 2011;22(4):149–50.

    PubMed  PubMed Central  Google Scholar 

  136. Fisher FS, Bultman MW, Johnson SM, Pappagianis D, Zaborsky E. Coccidioides niches and habitat parameters in the southwestern United States. Ann N Y Acad Sci 2007;1111(1):47–72.

  137. Das R, McNary J, Fitzsimmons K, Dobraca D, Cummings K, Mohle-Boetani J, et al. Occupational coccidioidomycosis in California: outbreak investigation, respirator recommendations, and surveillance findings. J Occup Environ Med. 2012;54(5):564–71.

    PubMed  Google Scholar 

  138. Laws RL, Cooksey GS, Jain S, Wilken J, McNary J, Moreno E, et al. Coccidioidomycosis outbreak among workers constructing a solar power farm—Monterey County, California, 2016–2017. Morb Mortal Wkly Rep. 2018;67(33):931.

    Google Scholar 

  139. De Almeida SM, Queiroz-Telles F, Teive HA, Ribeiro CE, Werneck LC. Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings. J Infect. 2004;48(2):193–8.

    PubMed  Google Scholar 

  140. Challa S. Aspergillosis In Fungal infections of the central nervous system: pathogens, diagnosis and management Eds: Turgut M, Challa S, Akhaddar A. Springer; 2019. P 91–106

  141. Bahr NC, Antinori S, Wheat LJ, Sarosi GA. Histoplasmosis infections worldwide: thinking outside of the Ohio River valley. Current Tropical Med Rep. 2015;2(2):70–80.

    Google Scholar 

  142. Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine. 1990;69(4):244–60.

    CAS  PubMed  Google Scholar 

  143. Pappas PG, Threlkeld MG, Bedsole GD, Cleveland KO, Gelfand MS, Dismukes WE. Blastomycosis in immunocompromised patients. Medicine. 1993;72(5):311–25.

    CAS  PubMed  Google Scholar 

  144. Bariola JR, Perry P, Pappas PG, Proia L, Shealey W, Wright PW, et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010;50(6):797–804.

    PubMed  Google Scholar 

  145. Bush JW, Wuerz T, Embil JM, Del Bigio MR, McDonald PJ, Krawitz S. Outcomes of persons with blastomycosis involving the central nervous system. Diagn Microbiol Infect Dis. 2013;76(2):175–81.

    PubMed  Google Scholar 

  146. Hessler C, Kauffman CA, Chow FC. The upside of bias: a case of chronic meningitis due to Sporothrix schenckii in an immunocompetent host. The Neurohospitalist. 2017;7(1):30–4.

    PubMed  Google Scholar 

  147. Kawila R, Chaiwarith R, Supparatpinyo K. Clinical and laboratory characteristics of penicilliosis marneffei among patients with and without HIV infection in Northern Thailand: a retrospective study. BMC Infect Dis. 2013;13(1):464.

    PubMed  PubMed Central  Google Scholar 

  148. Chan JF, Lau SK, Yuen KY, Woo PC. Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients. Emerging microbes & infections. 2016;5(1):1–9.

    Google Scholar 

  149. Natarajan M, Balakrishnan D, Muthu AK, Arumugham K. Maduromycosis of the brain: case report. J Neurosurg. 1975;42(2):229–31.

    CAS  PubMed  Google Scholar 

  150. Beeram V, Challa S, Vannemreddy P. Cerebral mycetoma with cranial osteomyelitis: case report. J Neurosurg Pediatr. 2008;1(6):493–5.

    PubMed  Google Scholar 

  151. Maheshwari S, Figueiredo A, Narurkar S, Goel A. Madurella mycetoma—a rare case with cranial extension. World neurosurgery. 2010;73(1):69–71.

    PubMed  Google Scholar 

  152. Rao KV, Praveen A, Megha S, Sundaram C, Purohith AK. Atypical craniocerebral eumycetoma: a case report and review of literature. Asian J Neurosurg. 2015;10(1):56.

    PubMed  PubMed Central  Google Scholar 

  153. Behera BR, Mishra S, Dhir MK, Panda RN, Samantaray S. “Madura head”—a rare case of Craniocerebral Maduromycosis. Indian J Neurosurg. 2018;7(02):159–63.

    Google Scholar 

  154. Goel RS, Kataria R, Sinha VD, Gupta A, Singh S, Jain A. Craniocerebral maduromycosis: case report. J Neurosurg Pediatr. 2012;10(1):67–70.

    PubMed  Google Scholar 

  155. Queiroz-Telles F, Nucci M, Colombo AL, Tobón A, Restrepo A. Mycoses of implantation in Latin America: an overview of epidemiology, clinical manifestations, diagnosis and treatment. Med Mycol. 2011;49(3):225–36.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sundaram Challa.

Ethics declarations

Conflict of Interest

Sundaram Challa declares no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Clinical Pathology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Challa, S. Invasive Fungal Infections of the Central Nervous System in Immune-Competent Hosts. Curr Fungal Infect Rep 14, 174–185 (2020). https://doi.org/10.1007/s12281-020-00384-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12281-020-00384-5

Keywords

Navigation