Consensus guidelines for the diagnosis and management of cryptococcosis and rare yeast infections in the haematology/oncology setting, 2021

Abstract

Cryptococcosis caused by the Cryptococcus neoformans-Cryptococcus gattii complex is an important opportunistic infection in people with immunodeficiency, including in the haematology/oncology setting. This may manifest clinically as cryptococcal meningitis or pulmonary cryptococcosis, or be detected incidentally by cryptococcal antigenemia, a positive sputum culture or radiological imaging. Non-Candida, non-Cryptococcus spp. rare yeast fungaemia are increasingly common in this population. These consensus guidelines aim to provide clinicians working in the Australian and New Zealand haematology/oncology setting with clear guiding principles and practical recommendations for the management of cryptococcosis, while also highlighting important and emerging rare yeast infections and their recommended management.

Development of a Real-Time PCR Assay to Identify and Distinguish between Cryptococcus neoformans and Cryptococcus gattii Species Complexes

“…The identification of C. neoformans and C. gattii to the species level is important to guide treatment regimens and inform clinical progression and outcomes [ 1 , 3 , 4 ]. Although the differentiation of the two species from culture-positive clinical specimens can be performed reliably by matrix-assisted laser desorption ionization-time of flight mass spectrometry, inoculation onto canavanine-glycine-bromothymol (CGB) agar [ 24 , 25 ], or a variety of molecular methods, including multi-locus sequence typing, PCR fingerprinting and amplified fragment length polymorphism analysis [ 7 , 8 ], these approaches are either slow (up to several days) and/or require access to laboratories performing genotyping methods.…”

“…A global study of the molecular epidemiology of Cryptococcus found that in Australia the prevalent genotypes are VNI (131/164) and VNII (25/164) for C. neoformans and VGI (179/300) and VGII (121/300) for C. gattii [ 26 ]. Whilst the relevance of detecting known genotypes remains uncertain in clinical practice [ 4 ], global travel and immigration from regions where other genotypes are more frequent make it important to have an all-encompassing approach for a diagnostic assay. Of note, we designed the assay to directly detect and distinguish between C. neoformans and C. gattii in clinical specimens, because this addresses the major clinical need.…”

“…Both species are species complexes and can each be further divided into two serotypes and four molecular types ( C. neoformans , serotypes A and D and VNI-IV, and C. gattii , serotypes B and C and VGI-IV) [ 2 ]. Differences in ecology, epidemiology, clinical manifestations and treatment approaches emphasize the importance of distinguishing between the two species complexes [ 3 , 4 ].…”

“…Laboratory diagnoses of cryptococcosis are based on a combination of histopathology, direct microscopy, fungal culture and/or a positive cryptococcal antigen (CRAG) test [ 4 , 5 ]. While culture is generally sensitive and simple to perform, culture-negative infections can occur.…”

Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics

“…Traditionally, cryptococcosis management guidelines did not consider it necessary to establish the species of Cryptococcus in clinical practice [ 48 , 52 , 53 ]. The most recent guidelines recommend doing this speciation in the clinical laboratory due to the differences in the morphology, biology, and phylogenetics of the two species [ 54 , 55 ]. Mortality and sequelae of CNS cryptococcosis due to C. gattii remain high (20.2%) [ 56 ].…”