Rat Model of Invasive Pulmonary Aspergillosis

Publisher Summary This chapter presents a rat model of invasive pulmonary aspergillosis. This model is based on the rat model of Klebsiella pneumoniae pneumonia, described by Bakker-Woudenberg et al. The main features of A. fumigatus pneumonia in this model are one-sided onset of infection of the lung, persistent granulocytopenia, and start of treatment at a time when hyphal growth is firmly established. The rats used are female R-strain albino rats, which receive a normal, pathogen-free diet, and water ad libitum and, during experiments are housed separately under filter caps. A clinical isolate of A. fumigatus from an immunocompromised patient with invasive pulmonary aspergillosis is used (strain number 1040403005) in this model. This strain is kept stored in oil on short agars during the study. To prevent bacterial superinfections, strict hygienic care is applied and the rats receive ciprofloxacin and polymyxin B in their drinking water throughout the experiment. Starting one day before inoculation, daily amoxicillin is added to this regime for the remainder of the experiment. Finally, gentamicin is administered shortly before and after inoculation. Leukopenia is induced and maintained by multiple doses of cyclophosphamide intraperitoneally. The rats first receive a dose of 0.1 ml Hypnorm i.m, after which they are sedated via an i.p. injection of 0.3 ml Nembutal. The parameters used in this model are mortality rate and time to death. During the infection process, the infection tends to spread from the inoculated left lung to the right lung and to other organs. Therefore, the dissemination of infection is also used as a parameter of efficacy of antifungal therapy.