PROTOCOL TO DEVELOP MODEL OF PNEUMOCYSTIS CARINII PNEUMONIA IN RHESUS MONKEY

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This study is a continuation of previously reported work to develop a rhesus monkey model of Pneumocystis carinii pneumonia (PCP). This model will be important to study the pathogenesis and novel drug compounds that may be used to treat PCP. Four rhesus monkeys were chosen for this pilot study. Three animals received alternate day dosing of prednisone and cyclophosphamide to induce immunosuppression. The fourth animal was used as a non-immunosuppressed control. Bronchoalveolar lavage (BAL) was performed one week prior to immunosuppression and weekly thereafter. All four animals were inoculated via a bronchoscope with a homogenate from P. carinii frozen lung tissue derived from three SIV infected animals. Viability was assessed prior to the time of inoculation. Five ml of homogenate (2.8 x 106 organisms/ml) was inoculated in the right caudal lung lobe of each animal. Followup included BAL, silver stain, PCR, bacterial culture, complete blood counts, serum chemistries, chest radiographs, and physical examinations performed at weekly intervals. Total lymphocyte counts in peripheral blood as well as CD4+ And CD8+ subsets decreased to a nadir by day 21. The lung homogenate was positive by DNA PCR for SIV at the time of inoculation. All four animals became positive by DNA PCR for SIV by 14 days post inoculation. BAL samples were negtive for P. carinii by PCR and by Giemsa stain evaluation at all time points. Silver stains of cytospin samples from BAL were also negative. Thoracic radiographs were normal throughout the study period. Future experiments will involve timing of inoculation at the nadir of the CD4+ lymphocyte count and inoculation of SIV-negative lung homogenate. FUNDING Base Grant PUBLICATIONS None