Invasive fungal infections (IFI), mainly caused by Candida and Aspergillus spp., are associated with high morbidity and mortality in immunocompromised patients such as organ and stem cell transplant (SCT) recipients. The difficulties in establishing an early and specific diagnosis of IFI are among the recognized reasons for such high mortality rates. Recent progress has been made to find either antibodies against fungal molecules or fungal derived molecules (either polysaccharides or nucleic acids) whose presence in patient blood could indicate deep tissue invasion. The aim of this study was to assess the combination of pan-fungal PCR, Platelia Candida Antibody (Cab), Platelia Candida antigen (Cag),and Platelia Aspergillus (Aag) to detect IFI in Patients receiving allogeneic SCT and/or liver transplants. Fourteen patients (9 females, 5 males), with a median age of 33 years (range 4-53 years) were included. Invasive Candida infections (n=4 C. albicans, n=2 C. glabrata, n=3 Candida. spp.) or invasive Aspergillus infection (n=2), was proven by autopsy, biopsy, and blood cultures in 11 patients, 3 had no evidence of IFI. Eleven received SCT, 2 liver and 1 liver and SCT. Pan-fungal PCR was performed on blood according to a method previously described (Einsele et al., 1997; Loeffler et al., 1998). Cag, Aag and Cab were used to detect polysaccharide antigens and anti-Candida mannan antibodies in human sera (Sendid et al. 1999, Stynen et al. 1995). Some patients were prospectively followed with PCR and had sera collected continuously, others had samples taken only on suspicion or as a confirmation of a positive culture. All sera were retrospectively analysed by the Platelia tests. Ten of 11 patients with verified IFI were analysed by PCR; 7 of 10 were positive. Two of 9 patients with verified invasive Candida infection were only positive for Cag. Cab was positive in 6 of 9 patients with invasive Candida infection, two of these 6 patients were also positive in the Cag test, but not at the same time. Aag was positive for patients with verified invasive Aspergillus infection (2/2). For the remaining patients without evidence of IFI (3/14), PCR and Cag were constantly negative, only one of them was positive for Cab before transplantation but negative after. When the results of PCR and serology tests (either antigen and antibody tests) were related to the isolation of fungal species from blood or other normally sterile sites, 8 of 11 patients with IFI had positive results before cultures. PCR were positive in 4 of 6 patients in whom samples had been taken before first positive culture, and serology were positive for 5 of 8 patients before isolation of involved fungal species. In 3 patients PCR samples were taken when IFI already had been confirmed, all three were tested positive. A new series of patients with verified IFI was recently included, and the results will be presented. The data presented here suggest that combination of PCR and serology tests may contribute to an early and specific diagnosis of IFI in transplants recipients. However, prospective studies are necessary to determine whether this approach would be medically and economically beneficial to the control of current acute problems linked to the development of nosocomial invasive fungal infections.
Full conference title:
The 15 th Congress of the International Society for Human and Animal Mycology
- ISHAM 15th (2003)