Neuroinfections Caused by Fungi

Of an estimated 1.5 million fungal species in the world, about 300 can cause infection and about 45 of these can infect the nervous system (1, 2)  Fungal infections of the nervous system and the rest of the body have been growing rapidly over the past 30 years due to many factors including an aging population, and increased numbers of patients with immunocompromised states such as HIV+, leukemia, lymphoma, and immunosuppressive drugs for bone marrow/ organ transplants (1).

Cryptococcus fungi (especially Cryptococcus neoformans and gatti) commonly causes both cryptococcal meningitis of the brain and disseminated infection(2). It is especially common in HIV+ patients. In 2014, there were an estimated 214,000 cases and 181,1000 fatalities due to cryptococcal meningitis worldwide in 2014 (1). The blastospores of Cryptococcus can survive as phagocytised cells in macrophages. From the lungs Cryptococcus can spread to other parts of the body and can enter the brain via macrophages. Cryptococcal meningitis can cause severe head and neck pain, altered mental status, convulsions, strokes, and paralysis of the lower limbs.

Candida fungi (yeasts) frequently cause disseminated infections in humans, especially if they are immunocompromised. Meningoencephalitis is a common manifestations of disseminated Candida infections and has a mortality rate of up to 90% (1).

Aspergillus infections most commonly involve the lung but can spread to other body areas including the CNS (central nervous system) in 10 to 20% of cases (1).  CNS Aspergillus infections have a mortality rate of 90-100%, however treatment with voriconazole can increase survival by 35-47% (1).

Other fungi which can cause neuroinfections include Coccidioides, Exserohilum, Histoplasma, Mucor, Rhizopus, Absidia, Blastomyces, and Syncephalastrum (1).

Diagnoses of fungal neuroinfections are often missed in hospitalized patients.  Diagnosis of fungal neuroinfections often involves a number of factors including examination of risk factors, clinical symptoms (such as fever and altered mental states), neuroimaging, serological testing of body fluids.  Fungal neuroinfections are commonly treated with amphotericin and various azole antifungal drugs such as fluconazole, itraconazole, voriconazole, posanconazole, and isavucanazole (1).

Fungal infections/ exposure may also possibly play a role in the development of dementia. Autopsy studies have reported significant levels of fungi (including Candida species, Cladosporium, Malassezia species, Neosartorya hiratsuka, Phoma, Sacharomyces cerevisae, andSclerotinia borealis) in the brains of Alzheimer’s and amyotrophic lateral sclerosis patients, suggesting that fungal exposure may play a role in these neurodegenerative diseases  (3, 4).

Resources

1. Goralska K, Blaszkowska J, Dzikowiec M. Neuroinfections caused by fungi. Infection. 2018;46(4):443-59.
2. Chakrabarti A. Epidemiology of central nervous system mycoses. Neurology India. 2007;55(3):191-7.
3. Alonso R, Pisa D, Marina AI, Morato E, Rabano A, Rodal I, et al. Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis. International journal of biological sciences. 2015;11(5):546-58.
4. Pisa D, Alonso R, Rabano A, Rodal I, Carrasco L. Different Brain Regions are Infected with Fungi in Alzheimer’s Disease. Sci Rep. 2015;5:15015.