Invasive fungal disease in immunocompromised hosts with focus on diagnostics

Abstract

Invasive fungal diseases (IFDs) are severe conditions affecting immunocompromised patients. The primary aim of this thesis was to explore different methods for diagnosis of IFD in different groups of immunocompromised patients. Papers I and II included patients with hematologic disorders. Paper I was a retrospective study evaluating two years of serial 1,3-β-d-glucan (betaglucan) testing. Paper II was a prospective study where samples were collected for the analysis of betaglucan, galactomannan, bm-gliotoxin (serum) and D-arabinitol/L-arabinitol (urine). The sensitivity of betaglucan and galactomannan was low early in the time course of IFD. The highest positive predictive value of betaglucan was obtained when using a cut-off level of at least 160 pg/ml and when testing patients upon clinical suspicion of IFD. Admission to ICU, previous administration of blood products and high serum triglyceride levels were associated with elevated betaglucan levels in patients without IFD. Betaglucan levels >800 pg/ml were highly indicative of IFD. Bm-gliotoxin could not be detected in patients with invasive aspergillosis. Paper III was a retrospective case-control study where frozen serum samples from HIV-infected patients and negative controls were analyzed for betaglucan and Pneumocystis PCR. Pneumocystis PCR in serum had a very high sensitivity and negative predictive value for the diagnosis of PCP. Paper IV was a prospective nationwide study on lung transplant recipients where serum and BAL-fluid samples were collected during the first post-transplant year for the analysis of betaglucan. Development of bronchiolitis obliterans syndrome (BOS) was assessed during a median 4.6 years of follow-up. Fungal colonization or tracheobronchitis had no impact on the development of BOS or on all-cause mortality. Betaglucan levels in serum were low while betaglucan levels in BAL fluid were elevated in patients with fungal tracheobronchitis. To conclude, betaglucan and Pneumocystis PCR in serum are useful diagnostic methods for different types of IFD although various issues need to be considered in order to determine their clinical applicability.