Fungal meningitis natural history, complications and prognosis

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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

Fungal meningitis usually presents with progressive symptoms of headache, low grade fever and fatigue. If left untreated, neurological complications might occur.

Natural History, Complications and Prognosis

Natural History

Fungal meningitis is rarely found in immunocompetent patients. It usually occurs in patients with immunosuppression like patients with HIV and transplant patients on immunosuppression and long term steroid therapy. The onset of symptoms is progressive and the course of the infection is protracted. The patients tend to present with symptoms like headache, low grade fever, fatigue and even weight loss[1]. This obscure presentation might cause delay in the diagnosis and in the initiation of the appropriate treatment.

Complications

The following are some complications that may follow fungal meningitis:[2][3][4][5]

  • Abscesses
  • Bone invasion
  • Fluid collections
  • Neurological deficits
  • Ocular invasion
  • Papilledema
  • Seizures[1]
  • Neurodevelopmental delays in children

Complications from therapy

Treatment of fungal meningitis in HIV-infected patients receiving HAART, organ transplantation, and pregnancy may result in immune reconstitution syndrome.[6][7][8][9]

This may result in worsening of the pre-existing condition. Despite this, the duration of starting antifungal therapy when HAART has been initiated still remains unclear.[10]

Prognosis

The mortality associated with fungal meningitis is high. Better prognosis is associated with early diagnosis, early initiation of the treatment and compliance of patients with medications.

Prognosis of cryptococcal meningitis

Prior to the introduction of amphotericin B therapy, cryptococcal meningitis was almost always fatal. Now, although most of these patients can be cured with course of intravenous amphotericin B, the optimum duration of therapy is often unclear, and there is still a significant percentage of early deaths and late treatment failure.[11][12][13]

Increasing levels of the following worsens the prognosis of HIV-negative cryptococcal meningitis patients with acute/subacute onset

  • Ratio of CSF glucose/blood glucose
  • Impaired consciousness and
  • Hospitalization length

Factors associated with a bad prognosis of coccidioidal meningitis are:[14]

hydrocephalus, non-Caucasian race, or presence of an underlying disease.

The mortality of cryptococcal meningitis is high (10-30%).[15]

Prognosis of coccidioidal meningitis

Prognosis is worst in patients with sevral sites of extrapulmonary dissemination compared to patients who have only meningeal involment.[16] Prior to the introduction of antifungal therapy coccidioidal meningitis wa almost always fatal.[16]

References

  1. 1.0 1.1 John Marx. Chapter 107. Central Nervous System Infections. Marx: Rosen's Emergency Medicine, 7th ed. Mosby: Elsevier; 2009.
  2. Farrugia MK, Fogha EP, Miah AR, Yednock J, Palmer HC, Guilfoose J (2016). "Candida meningitis in an immunocompetent patient detected through (1→3)-beta-d-glucan". Int J Infect Dis. 51: 25–26. doi:10.1016/j.ijid.2016.08.020. PMID 27590564.
  3. Nyazika TK, Hagen F, Machiridza T, Kutepa M, Masanganise F, Hendrickx M; et al. (2016). "Cryptococcus neoformans population diversity and clinical outcomes of HIV-associated cryptococcal meningitis patients in Zimbabwe". J Med Microbiol. 65 (11): 1281–1288. doi:10.1099/jmm.0.000354. PMID 27638836.
  4. Leonhard SE, Fritz D, van de Beek D, Brouwer MC (2016). "Cryptococcal meningitis complicating sarcoidosis". Medicine (Baltimore). 95 (35): e4587. doi:10.1097/MD.0000000000004587. PMC 5008555. PMID 27583871.
  5. Neo WL, Durisala N, Ho EC (2016). "Reversible hearing loss following cryptococcal meningitis: case study". J Laryngol Otol. 130 (7): 691–5. doi:10.1017/S002221511600801X. PMID 27210482.
  6. Singh N, Perfect JR (2007). "Immune reconstitution syndrome associated with opportunistic mycoses". Lancet Infect Dis. 7 (6): 395–401. doi:10.1016/S1473-3099(07)70085-3. PMID 17521592.
  7. Jenny-Avital ER, Abadi M (2002). "Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy". Clin Infect Dis. 35 (12): e128–33. doi:10.1086/344467. PMID 12471589.
  8. Blanche P, Gombert B, Ginsburg C, Passeron A, Stubei I, Rigolet A; et al. (1998). "HIV combination therapy: immune restitution causing cryptococcal lymphadenitis dramatically improved by anti-inflammatory therapy". Scand J Infect Dis. 30 (6): 615–6. PMID 10225395.
  9. Woods ML, MacGinley R, Eisen DP, Allworth AM (1998). "HIV combination therapy: partial immune restitution unmasking latent cryptococcal infection". AIDS. 12 (12): 1491–4. PMID 9727570.
  10. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ; et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clin Infect Dis. 50 (3): 291–322. doi:10.1086/649858. PMID 20047480.
  11. Diamond RD, Bennett JE (1974). "Prognostic factors in cryptococcal meningitis. A study in 111 cases". Ann Intern Med. 80 (2): 176–81. PMID 4811791.
  12. Lewis JL, Rabinovich S (1972). "The wide spectrum of cryptococcal infections". Am J Med. 53 (3): 315–22. PMID 5054723.
  13. NEWCOMER VD, STERNBERG TH, WRIGHT ET, REISNER RM, McNALL EG, SORENSEN LJ (1960). "The treatment of systemic fungus infections with amphotericin B." Ann N Y Acad Sci. 89: 221–39. PMID 13728643.
  14. 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.
  15. Van der Horst CM, Saag MS, Cloud GA et al. (1997) Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med, 337, 15–21.
  16. 16.0 16.1 Vincent T, Galgiani JN, Huppert M, Salkin D (1993). "The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955-1958". Clin Infect Dis. 16 (2): 247–54. PMID 8443303.

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