Current epidemiology and clinical features of Cryptococcus infection in patients without HIV infection: a multicentre study in 46 hospitals from Australia and New Zealand

Julien Coussement; Christopher H Heath; Matthew B Roberts; Rebekah J Lane; Tim Spelman; Olivia C Smibert; Anthony Longhitano; Orla Morrissey; Blake Nield; Monica Tripathy; Joshua S Davis; Karina J Kennedy; Sarah A Lynar; Lucy C Crawford; Simeon J Crawford; Benjamin J Smith; Andrew P Gador-Whyte; Rose Haywood; Andrew A Mahony; Julia C Howard; Genevieve B Walls; Gabrielle M O'Kane; Matthew T Broom; Caitlin L Keighley; Olivia Bupha-Intr; Louise Cooley; Jennifer A O'Hern; Justin D Jackson; Arthur J Morris; Caroline Bartolo; Adrian R Tramontana; Katherine C Grimwade; Victor Au Yeung; Roy Chean; Emily Woolnough; Benjamin W Teh; Sharon C-A Chen; Monica A Slavin; Australian and New Zealand study group for cryptococcosis in patients without HIV infection

doi:10.1093/cid/ciad321

Current epidemiology and clinical features of Cryptococcus infection in patients without HIV infection: a multicentre study in 46 hospitals from Australia and New Zealand

Clin Infect Dis. 2023 May 26;ciad321. doi: 10.1093/cid/ciad321. Online ahead of print.

Authors

Julien Coussement^{1

2}, Christopher H Heath^{3

4}, Matthew B Roberts^{5

6}, Rebekah J Lane⁷, Tim Spelman^{8

9

10

11}, Olivia C Smibert¹², Anthony Longhitano¹³, Orla Morrissey¹⁴, Blake Nield¹⁵, Monica Tripathy¹⁶, Joshua S Davis¹⁷, Karina J Kennedy¹⁸, Sarah A Lynar^{19

20}, Lucy C Crawford¹⁹, Simeon J Crawford²¹, Benjamin J Smith²², Andrew P Gador-Whyte²³, Rose Haywood²⁴, Andrew A Mahony²⁵, Julia C Howard²⁶, Genevieve B Walls²⁷, Gabrielle M O'Kane^{28

29}, Matthew T Broom^{30

31}, Caitlin L Keighley³², Olivia Bupha-Intr³³, Louise Cooley³⁴, Jennifer A O'Hern^{19

35}, Justin D Jackson³⁶, Arthur J Morris⁷, Caroline Bartolo³⁷, Adrian R Tramontana^{38

39}, Katherine C Grimwade^{40

41}, Victor Au Yeung⁴², Roy Chean⁴³, Emily Woolnough⁴⁴, Benjamin W Teh^{1

2}, Sharon C-A Chen⁴⁵, Monica A Slavin^{1

2

46}; Australian and New Zealand study group for cryptococcosis in patients without HIV infection

Collaborators

Australian and New Zealand study group for cryptococcosis in patients without HIV infection:
Kylie Alcorn, Justin Beardsley, Aaron Bloch, Amy Crowe, Wendy Doyle, Michelle England, David Griffin, Kate Hamilton, Tony M Korman, Victoria Madigan, Hugh McGann, William Pratt, Sebastiaan Van Hal, Prue Waters, Eloise Williams

Affiliations

¹ Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
² Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
³ Department of Microbiology, PathWest Laboratory Medicine, and Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, WA, Australia.
⁴ Department of Infectious Diseases, Royal Perth Hospital, Perth, WA, Australia.
⁵ Royal Adelaide Hospital, Adelaide, SA, Australia.
⁶ Flinders Medical Centre, Bedford Park, SA, Australia.
⁷ Te Toka Tumai, Auckland, New Zealand.
⁸ Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
⁹ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁰ Burnet Institute, Melbourne, VIC, Australia.
¹¹ The University of Melbourne Department of Surgery, St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
¹² Austin Health, Heidelberg, VIC, Australia.
¹³ Monash Health, Clayton, VIC, Australia.
¹⁴ Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia.
¹⁵ Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹⁶ Gold Coast Hospital and Health Service, Southport, QLD, Australia.
¹⁷ John Hunter Hospital, Newcastle, NSW, Australia.
¹⁸ ACT Pathology, Canberra Health Services, Canberra, ACT, Australia.
¹⁹ Royal Darwin and Palmerston Hospitals, Darwin, NT, Australia.
²⁰ Menzies School of Health Research, Darwin, NT, Australia.
²¹ Wollongong Hospital, Wollongong, NSW, Australia.
²² Eastern Health, Box Hill, VIC, Australia.
²³ St Vincent's Hospital Melbourne, Melbourne, VIC, Australia.
²⁴ The Prince of Wales Hospital, Sydney, NSW, Australia.
²⁵ Bendigo Health, Bendigo, VIC, Australia.
²⁶ Te Whatu Ora Waikato, Hamilton, New Zealand.
²⁷ Middlemore Hospital, Te Whatu Ora Counties Manukau, Auckland, New Zealand.
²⁸ Gosford Hospital, Gosford, NSW, Australia.
²⁹ Wyong Hospital, Hamlyn Terrace, NSW, Australia.
³⁰ North Shore Hospital, Auckland, New Zealand.
³¹ Waitakere Hospital, Auckland, New Zealand.
³² Southern IML Pathology, Wollongong, NSW, Australia.
³³ Capital, Coast and Hutt Valley District, Wellington, New Zealand.
³⁴ Royal Hobart Hospital, Hobart, TAS, Australia.
³⁵ Launceston General Hospital, Launceston, TAS, Australia.
³⁶ Albury Wodonga Health, Albury, VIC, Australia.
³⁷ Barwon Health, Geelong, VIC, Australia.
³⁸ Western Health, Footscray, VIC, Australia.
³⁹ Western Clinical School, Melbourne Medical School, the University of Melbourne, St Albans, VIC, Australia.
⁴⁰ Tauranga Hospital, Hauora a Toi Bay of Plenty, Tauranga, New Zealand.
⁴¹ Whakatane Hospital, Hauora a Toi Bay of Plenty, Whakatane, New Zealand.
⁴² Ballarat Health Services, Ballarat, VIC, Australia.
⁴³ Latrobe Regional Hospital, Traralgon, VIC, Australia.
⁴⁴ St John of God Midland Public and Private Hospital, Midland, WA, Australia.
⁴⁵ Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, The University of Sydney, Sydney, NSW, Australia.
⁴⁶ Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, VIC, Australia.

PMID: 37235212
DOI: 10.1093/cid/ciad321

Abstract

Introduction: Patients without HIV infection are increasingly recognised to be at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete.

Methods: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV, and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included.

Results: Of 475 patients with cryptococcosis, 90% were HIV-negative (426/475) with the marked predominance of HIV-negative cases evident in both Cryptococcus neoformans (88.7%) and C. gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n=91), organ transplantation (n=81), other immunocompromising condition (n=97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70/426). The serum cryptococcal antigen test was positive in 85.1 % of tested patients (319/375); high titres independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titre and/or fungaemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (p=0.89).

Conclusion: The present study revealed 90% of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii cases, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Keywords: Cryptococcus gattii; Cryptococcus neoformans; cancer; cryptococcosis; transplantation.