An improved rat model of Pneumocystis carinii pneumonia: induced infections in Pneumocystis-free animals.

An immunosuppressed rat model of Pneumocystis carinii pneumonia (PCP) is described that results in a predictable course of disease development which includes moderate P. carinii (Pc) infections in 2 to 3 weeks, heavy infections in 4 to 5 wk, and a high percentage of mortality due to PCP in 6 wk. The model also provides uninfected, immunosuppressed contemporary controls, an experimental compartment that is needed to correctly interpret results obtained from many different studies. Non-invasive intratracheal inoculation of cryopreserved parasites into Pc- and virus-free rats immunosuppressed by weekly injections of methylprednisolone are key features of the model that result in the development of consistent heavy Pc infections and very few secondary infections by bacteria and fungi. This model is useful for (1) maintaining isolates or strains of Pc over time, (2) producing large numbers of parasites for laboratory studies, and (3) evaluating the anti-Pc activity of experimental compounds and approved drugs.