Cryptococcosis-a systematic review to inform the World Health Organization Fungal Priority Pathogens List.

Jan-Willem Alffenaar, Tania C Sorrell, Sharon C-A Chen, Ana Alastruey-Izquierdo, Aiken Dao, Hannah Yejin Kim, Katherine Garnham, Sarah Kidd, Hatim Sati, John Perfect, Thomas Harrison, Volker Rickerts, Valeria Gigante, C Orla Morrissey, Justin Beardsley

Journal: Medical mycology 2024;62(6):

PMID: 38935902

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Abstract

Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%-61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16-32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%-33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%-23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%-27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25-0.5 mg/l), 5-flucytosine (MIC range: 0.5-2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06-0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.

Address: Sydney Infectious Diseases Institute, The University of Sydney, Sydney, Australia.; Westmead Institute for Medical Research, Westmead, Sydney, Australia.; Westmead Clinical School, Westmead Hospital, Sydney, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Sydney, Australia.; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.; Department of Pharmacy, Westmead Hospital, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Sydney, Australia.; Sunshine Coast University Hospital, Birtinya, Qld 4575, Australia.; National Mycology Reference Centre, Microbiology and Infectious Diseases, SA Pathology, Adelaide, Australia.; AMR Division, World Health Organization, Geneva, Switzerland.; Duke University Medical Center, Durham, NC, USA.; Institute of Infection and Immunity, St George's University London, London, UK.; Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, UK.; Robert Koch Institute, Berlin, Germany.; Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.; Sydney Infectious Diseases Institute, The University of Sydney, Sydney, Australia.; Westmead Clinical School, Westmead Hospital, Sydney, Australia.; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.; Department of Infectious Diseases, Alfred Health, Melbourne, Australia.; Monash University, Department of Infectious Diseases, Melbourne, Victoria, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, Westmead, Sydney, Australia.

DOI: 10.1093/mmy/myae043

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MeSH Terms: Humans, Cryptococcosis, Antifungal Agents, Cryptococcus gattii, Cryptococcus neoformans, Drug Resistance, Fungal, World Health Organization, Microbial Sensitivity Tests