Background: Few reports have described the clinical and microbiological features of cryptococcosis in immunocompetent patients. Aim: To compare clinical presentations and outcomes of cryptococcosis in immunocompetent vs. immunocompromised patients. Design: Retrospective case series. Methods: All culture- or histology-confirmed cases ( n = 46) of cryptococcosis in two acute hospitals in Hong Kong (1995–2005) were included. Clinical presentations, rates of fungaemia, cerebrospinal fluid (CSF) parameters and clinical outcomes were recorded. Results : Twenty patients (43.5%) were apparently immunocompetent, 17 (37.0%) had predisposing factors other than HIV infection, and 9 (19.6%) were HIV-positive. Thirty-one (67.4%) presented with meningitis, four (8.7%) with pulmonary cryptococcosis, and 11 (23.9%) with extraneural, extrapulmonary cryptococcosis. Of the immunocompetent patients with retrievable isolates ( n = 8), three (37.5%) were Cryptococcus gattii ; all isolates ( n = 6) from immunocompromised patients were Cryptococcus neoformans var. grubii . Immunocompetent patients more commonly presented with meningitis (80.0% vs. 47.1%, p = 0.03), and tended toward lower rates of fungaemia (10.0% vs. 35.3%, p = 0.06) and mortality (25.0% vs. 52.9%, p = 0.06). Death was associated with fungaemia ( p = 0.01) and underlying malignancy ( p < 0.01). In cryptococcal meningitis, immunocompetent patients had longer mean time from illness onset to presentation (34.4 vs. 12.6 days, p = 0.02), more intense inflammatory responses (CSF: white blood cells 108 vs. 35×10 9 /l, p = 0.03; protein 1.61 g/l vs. 0.79 g/l, p = 0.07), less fungaemia (0% vs. 26.7%, p = 0.04) and more satisfactory clinical outcomes (81.3% vs. 46.7%, p = 0.04). Discussion: A substantial proportion of patients with cryptococcosis are apparently immunocompetent. C. neoformans var. grubii and C. gattii are the common causes. Immunocompetent patients tend to present with localized, indolent neurological disease, with more intense inflammatory responses but better clinical outcomes.
Background: Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. Aim: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. Methods: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. Results: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). Conclusion: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.
Background: Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment. Methods: In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses. Results: A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13–28%) and higher viral concentration despite late-presentation (multiple linear regression, β=0.94, 95% confidence interval 0.15–1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0–8.0], TA 11.0 days [7.8–14.3] versus milder illness group NPFS of 2.0 days [1.0–3.0] days; P<0.01). High viral load in lower respiratory tract despite upper-tract RNA negativity and viral rebound after stopping treatment were noted in some patients. H275Y mutation was absent. High plasma levels of interleukin (IL)-6, CXCL-8 (IL-8), CCL2 (monocyte chemoattractant protein-1) and soluble tumour necrosis factor receptor-1 were observed, which correlated with the extent and progression of pneumonia in hospital. Conclusions: In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.