Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort

Abstract

Background Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia’s Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. Methods A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996–2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. Results 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166–715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. Conclusion C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.

Criptococoma pulmonar gigante en paciente inmunocompetente

“…The invasive infections by Cryptococcus neoformans or Cryptococcus gattii more frequently involve the lungs and the central nervous system (CNS) with a high mortality rate; besides, the muscles, skeletal, skin and soft tissues, abdominal viscera, eyes, and prostate of both previous healthy and immunosuppressed individuals may be affected. [1][2][3][4][5] More often, C. gattii causes mass lesions in CNS, while C. neoformans does it in lungs. 2 Risk factors include HIV/AIDS, solid organ transplant, immunomodulatory agents, liver cirrhosis, chronic renal disease, diabetes mellitus, malignancy, and autoimmune disease.…”

“…O'Hern JA et al reviewed data of 45 patients with infections by C. gattii (35 confirmed and 10 probable), with median age of 41 (5-60) years and median follow-up of five years. 4 They were treated by 166-715 days; 44% had both pulmonary and CNS lesions, 20% died up to one year after diagnosis, while 11% of survivors evolved with major sequels. Cryptococcomas measuring 6 (2.2-10) cm underwent surgery and 90% were cured; four cases of brain lesions developed immune reconstitution inflammatory syndrome (IRIS), characterized by intracranial hypertension and a cryptococcal antigen over than 1:512 and a schedule of corticosteroids from 63 days to over six months was utilized with success.…”

“…Cryptococcomas measuring 6 (2.2-10) cm underwent surgery and 90% were cured; four cases of brain lesions developed immune reconstitution inflammatory syndrome (IRIS), characterized by intracranial hypertension and a cryptococcal antigen over than 1:512 and a schedule of corticosteroids from 63 days to over six months was utilized with success. 4 The authors highlighted that morbidity associated with C. gattii infection remains high, although early diagnosis and combined surgical and medical management can eradicate the disease, differing from the outcomes following therapy of C. neoformans infection. 4 Tucker M et al also reported the development of IRIS in an immunocompetent male patient with rapidly enlarging cryptococcoma by C. neoformans that compressed vascular structures in spite of the four weeks of amphotericin B plus eight weeks of fluconazole.…”

“…4 The authors highlighted that morbidity associated with C. gattii infection remains high, although early diagnosis and combined surgical and medical management can eradicate the disease, differing from the outcomes following therapy of C. neoformans infection. 4 Tucker M et al also reported the development of IRIS in an immunocompetent male patient with rapidly enlarging cryptococcoma by C. neoformans that compressed vascular structures in spite of the four weeks of amphotericin B plus eight weeks of fluconazole. 5 The critical consequences of vascular encroachment were responsive to prednisone, and authors stressed that this was the first cryptococcal-IRIS in an immunocompetent host.…”