http://repub.eur.nl/res/aut/6498/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/19730/ 1999-02-03T00:00:00Z Fungal infections in man usually are divided into three categories based upon their major pathophysiological characteristics: superficial and cutaneous, subcutaneous and, systemic infections. The last category consists of two separate entities. First there are the so called "endemic mycoses" caused by dimorphic fungi including Coccidioides immiiis, Paracoccidioides brasiliensis, Histoplasma capsula tum and Blastomyces dermatitidis which occur in patients who live in, or have travelled through geographical regions in which these pathogenic fungi have their habitat. Although the consequences of endemic mycoses are sometimes very severe, these infections were not viewed as a very major subject in the field of infectious diseases, probably due to their relatively rare and geographically restricted occurrence. The second entity consists of opportunistic infections caused by fungi that are ubiquitously present around the globe. The number of these infections has increased dramatically during the last three decades. For example, in 1966 invasive aspergillosis was called a disease of medical progress, and world literature on this subject was reviewed in a paper only six pages in length. In contrast in 1990, Denning et al. used 55 pages only to review the literature on the treatment of such infections. Several factors have been recognized to be responsible for this rapid increase, all of which are the consequence of advances in medicine. The use of antibacterial agents, the use of cytotoxic chemotherapy, organ transplantation combined with the use of immunosuppressive therapy, the use of indwelling catheters all one way or the other, compromise the defence mechanisms of the human host (Table 1 ) Some of these factors disrupt more than one line of defence; for example, longterm use of steroids, influences cellular immunity, macrophage function and neutrophil function, whereas the integrity of the skin and mucous membranes is little affected. http://repub.eur.nl/res/pub/9093/ 1999-01-01T00:00:00Z After five patients were diagnosed with nosocomial invasive aspergillosis caused by Aspergillus fumigatus and A. flavus, a 14-month surveillance program for pathogenic and nonpathogenic fungal conidia in the air within and outside the University Hospital in Rotterdam (The Netherlands) was begun. A. fumigatus isolates obtained from the Department of Hematology were studied for genetic relatedness by randomly amplified polymorphic DNA (RAPD) analysis. This was repeated with A. fumigatus isolates contaminating culture media in the microbiology laboratory. The density of the conidia of nonpathogenic fungi in the outside air showed a seasonal variation: higher densities were measured during the summer, while lower densities were determined during the fall and winter. Hardly any variation was found in the numbers of Aspergillus conidia. We found decreasing numbers of conidia when comparing air from outside the hospital to that inside the hospital and when comparing open areas within the hospital to the closed department of hematology. The increase in the number of patients with invasive aspergillosis could not be explained by an increase in the number of Aspergillus conidia in the outside air. The short-term presence of A. flavus can only be explained by the presence of a point source, which was probably patient related. Genotyping A. fumigatus isolates from the department of hematology showed that clonally related isolates were persistently present for more than 1 year. Clinical isolates of A. fumigatus obtained during the outbreak period were different from these persistent clones. A. fumigatus isolates contaminating culture media were all genotypically identical, indicating a causative point source. Knowledge of the epidemiology of Aspergillus species is necessary for the development of strategies to prevent invasive aspergillosis. RAPD fingerprinting of Aspergillus isolates can help to determine the cause of an outbreak of invasive aspergillosis. http://repub.eur.nl/res/pub/8631/ 1996-01-01T00:00:00Z The efficacy of AmBisome, a liposomal formulation of amphotericin B, was compared with that of Fungizone (amphotericin B desoxycholate), in a rat model of unilateral, pulmonary aspergillosis. Repeated administration of cyclophosphamide resulted in persistent, severe granulocytopenia. The left lung was inoculated with a conidial suspension of Aspergillus fumigatus, thus establishing an unilateral infection. Antifungal treatment was started 40 h after fungal inoculation, at which time mycelial disease was confirmed by histological examination. Both Fungizone 1 mg/kg and AmBisome 10 mg/kg resulted in increased survival in terms of delayed as well as reduced mortality. Quantitative cultures of lung tissue showed that only AmBisome 10 mg/kg resulted in reduction of the number of fungal cfus in the inoculated left lung. Compared with Fungizone, both AmBisome 1 mg/kg/day and AmBisome 10 mg/kg/day significantly prevented dissemination from the infected left lung to the right lung. In addition, both AmBisome regimens reduced hepatosplenic dissemination, and the 10 m/kg dosage fully prevented this complication. In conclusion, when compared with Fungizone, in this model AmBisome is more effective in reducing dissemination of unilateral, pulmonary aspergillosis, even when given in relatively low dosage. Such low dosages may have a place in prophylactic settings. http://repub.eur.nl/res/pub/8633/ 1996-01-01T00:00:00Z During a 2-month period, five patients suffering from invasive infections caused by Aspergillus flavus or Aspergillus fumigatus were identified in the Hematology Department of the University Hospital Dijkzigt (Rotterdam, The Netherlands). To study the epidemiological aspects of invasive aspergillosis, strains from these patients and from the hospital environment, isolated during extensive microbiological screening, were subjected to genotyping. A novel DNA extraction technique, involving freezing, grinding, and direct lysis in guanidium isothiocyanate-containing buffers of mycelial material, was applied. DNA isolation was followed by typing by random amplification of polymorphic DNA (RAPD) analysis. This showed that strains isolated from all patients infected with the same fungal species were genotypically distinct, thus providing evidence against the possibility of an ongoing, single-source nosocomial outbreak. Strains could also be differentiated from strains of geographically diverse origins. However, an A. flavus strain from one of the patients was also frequently encountered in the hospital environment. As all environmental strains were collected after this patient had been diagnosed with invasive disease, the epidemiological value of this observation could not be ascertained. Intensive investigations showed no single source of A. flavus or other aspergilli. RAPD genotyping proved that the outbreak of invasive aspergillosis in the hematology ward