Colliding Epidemics and the Rise of Cryptococcosis

Abstract

Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in fermenting peach juice, and identified as a human pathogen in 1894 in a patient with bone lesions, this environmental pathogen has now found niches in soil, trees, birds, and domestic pets. Cryptococcosis is well recognized as an opportunistic infection and was first noted to be associated with reticuloendothelial cancers in the 1950s. Since then, advances in transplant immunology, medical science and surgical techniques have led to increasing numbers of solid organ transplantations (SOT) and hematological stem cell transplantations being performed, and the use of biological immunotherapeutics in increasingly high-risk and older individuals, have contributed to the further rise in cryptococcosis. Globally, however, the major driver for revivification of cryptococcosis is undoubtedly the HIV epidemic, particularly in Sub-Saharan Africa where access to care and antiretroviral therapy remains limited and advanced immunodeficiency, poverty and malnutrition remains the norm. As a zoonotic disease, environmental outbreaks of both human and animal cryptococcosis have been reported, possibly driven by climate change. This is best exemplified by the resurgence of C. gattii infection in Vancouver Island, Canada, and the Pacific Northwest of the United States since 1999. Here we describe how the colliding epidemics of HIV, transplantation and immunologics, climate change and migration have contributed to the rise of cryptococcosis.

Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection

“…Given the rise in lymphopenia due to HIV/AIDS, solid organ transplant, chemotherapy ( Li et al., 2019 ; Fierer, 2019 ; Pathakumari et al., 2020 ), and immunosuppressive therapies to control chronic diseases ( Grebenciucova et al., 2016 ; Ward et al., 2016 ; Bryan et al., 2020 ), opportunistic invasive fungal infections have emerged as a global health concern, killing ~1.5 million people per year. Among these opportunistic fungal infections, cryptococcosis is caused by Cryptococcus neoformans and Cryptococcus gattii ( Chang and Chen, 2015 ; Diaz, 2020 ; Montoya et al., 2021 ), resulting in ~220,000 new cases and ~180,000 deaths annually ( Rajasingham et al., 2017 ; Mayer and Kronstad, 2020 ).…”

Cryptococcal Meningitis Causing Refractory Hemichorea-Hemiballismus Treated With Pallidotomy

“…Approximately 20% of central nervous system infections are seen in HIV-negative patients, of which 10-40% have no apparent immune deficiency [ 5 , 6 ]. Risk factors for cryptococcal meningitis in HIV-negative patients include decompensated liver disease, sarcoidosis, systemic lupus erythematosus, solid organ transplantation, hematological malignancy, and cell-mediated immunosuppression by medications such as steroids [ 7 ].…”

Three models of vaccination strategies against cryptococcosis in immunocompromised hosts using heat-killedCryptococcus neoformansΔsgl1

“…One of these fungal pathogens is Cryptococcus neoformans , a basidiomycetous yeast ubiquitously found in environmental sources such as avian habitation, trees, and soil [3, 5, 26]. C. neoformans is a main etiological agent of cryptococcosis, a life-threatening invasive fungal infection that originates in the respiratory tract [27–29].…”

“…A.Experimental design schematic. B. CBA/J mice (n=9 mice/group) were administered either isotype or anti-CD4 antibody prior to vaccination with 5x105 Live Δsgl1 or PBS controls, and the depletion continued for the entirety of the experiment at noted intervals. After 30 days, vaccinated and unvaccinated mice were challenged with 5x10 5 C. neoformans WT on day 0 (WT challenge #1).…”