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

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.

A 55-Year-Old Woman With Frequent Pulmonary Exacerbations and Endobronchial Lesions.

CASE PRESENTATION: A 55-year-old woman with COPD, heart failure with preserved ejection fraction (congestive heart failure), diabetes mellitus, and hypertension presented with baseline dyspnea at rest that had worsened over the last week. She reported associated runny nose, congestion, and cough productive of green sputum. She smoked six cigarettes per day and denied alcohol, drugs, or occupational exposure. She was admitted and initiated on treatment for acute exacerbation of COPD; however, her condition did not improve with steroid, ceftriaxone, and nebulized albuterol and budesonide treatments. She had been diagnosed with asthma and COPD without ever undergoing pulmonary function testing. She presented 11 times to the ED with six hospital admissions in the last 1.5 years for worsening dyspnea at rest, wheezing, and lower extremity edema deemed secondary to exacerbation of her COPD or congestive heart failure. She reported medication compliance, which included fluticasone-vilanterol, tiotropium bromide, and furosemide. She repeatedly demonstrated mild vascular congestion on imaging without hyperinflation, a normal to mildly elevated brain natriuretic peptide (<10 to 200 pg/mL), and dyspnea without hypoxia. She was treated normally for both COPD and congestive heart failure exacerbations simultaneously with methylprednisolone, albuterol, and furosemide with rapid improvement over the course of 1 to 2 days. No significant improvement was noted with steroid therapy, despite receiving them as an inpatient and outpatient. At the time of discharge, her symptoms would be at her baseline.

Trends in Strongyloides stercoralis Faecal Larvae Detections in the Northern Territory, Australia: 2002 to 2012.

Strongyloides stercoralis is a soil-transmitted helminth (STH) endemic to tropical and subtropical areas. We reviewed the temporal detection trends in patients with S. stercoralis larvae present in faecal samples, in Northern Territory (NT) Government Health facilities, between 2002 and 2012. This was a retrospective observational study of consecutive patients with microbiologically confirmed detection of S. stercoralis in faeces. The presence of anaemia, eosinophilia, polyparasitism, and geographic and demographic data, were included in the assessment. S. stercoralis larvae were present in 389 of 22,892 faecal samples (1.7%) collected across the NT over 11 years, examined by microscopy after formol ethyl acetate concentration. 97.7% of detections were in Indigenous patients. Detections, by number, occurred in a biphasic age distribution. Detections per number of faecal samples collected, were highest in the 0⁻5 year age group. Anaemia was present in 44.8%, and eosinophilia in 49.9% of patients. Eosinophilia was present in 65.5% of the ≤5 age group, compared to 40.8% of >5 year age (p < 0.0001). Polyparasitism was present in 31.4% of patients. There was an overall downward trend in larvae detections from 2.64% to 0.99% detections/number of faecal samples year between 2002 and 2012, consistent with the trends observed for other local STHs. S. stercoralis remains an important NT-wide pathogen.

Blood-borne viruses in the haemodialysis-dependent population attending Top End Northern Territory facilities 2000-2009.

AIM: To describe the incidence and prevalence of blood-borne viruses (BBV) including: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and human T-cell leukaemia virus type-1 (HTLV) in the haemodialysis-dependent population of the Top End of the Northern Territory (TENT). METHODS: We retrospectively reviewed the serology of BBV in a longitudinal fashion in the haemodialysis-dependent population treated in the TENT of Australia from 2000 to 2009 inclusive. HBV, HCV, HIV and HTLV serology on commencement of dialysis and at exit or January 2010, whichever was earlier, as well as demographic details were collected. Patients with a change in serological status had all serology reviewed. RESULTS: Four-hundred and forty patients were included in the analysis. Of these, 84.3% were Indigenous and 55.4% female, with a median age of 50 (IQR 43-59) years at the commencement of haemodialysis. Evidence of past HBV infection was documented in 42.7% and 8.9% were hepatitis B surface antigen-positive. Positive serology for HTLV was documented in 2.2%, 1.6% were hepatitis C antibody-positive and no individual was HIV-positive. Three patients had a definite change in their HBV serology over time; this equates to an absolute seroconversion risk of 0.1 per 100 person years or 0.0006 per dialysis episode. CONCLUSIONS: In this cohort, there was a high rate of past and current hepatitis B infection but low rates of seroconversion while on haemodialysis.