[Morphological changes in Pneumocystis carinii in the alveolar space due to treatment with co-trimoxazole--comparison of clinical cases and experimental rats].

In this study, transmission electron microscopy was employed to observe the morphological changes in Pneumocystis carinii (P. carinii) in the alveolar space of patients and experimental rats treated with co-trimoxazole. Experimentally, P. carinii pneumonia was induced in Wistar rats by peritoneal injection of prednisolone and then treated with co-trimoxazole. The animals were divided into an untreated group and groups treated with co-trimoxazole for 3-9 days. In the untreated group, various forms of P. carinii were seen to be filling up the alveolar space. There were few morphological changes (shape, size and intracellular substances) in the P. carinii in the alveolar space of the animals in the 3-day and 5-day treated groups. However, in the 7-day treated group, important intracellular components such as mitochondria were not seen, and after 7 or more days of treatment there were no crescent-shaped P. carinii, which are characteristically observed in the proliferative stage. In the 9-day treated group, the cell membranes of thick-walled cysts were ruptured, and there was intracellular vacuolization. In addition, untreated patients complicated with P. carinii pneumonia (2 cases), patients treated for 3-5 days (4 cases) and a patients treated for 1 month (1 case) were studied. The morphology of P. carinii in the alveoli of those clinical cases was similar to that seen in the rats, and the changes in shape, intracellular components and cell membranes after treatment were the same except in case 5. In case 5, lamellar-body-like substances such as seen in alveolar proteinosis filled up the alveoli, and the cell membranes of P. carinii were ruptured. Electron microscopic studies revealed no changes in the cell membranes during the early period of treatment. We surmise that co-trimoxazole is taken into P. carinii cells and then interferes with the cellular metabolism. On the basis of the results of this study, the critical period determining whether a patients with P. carinii pneumonia can be cured or not is around the 9th day of treatment with co-trimoxazole. Therefore, it is necessary to make an early diagnosis, begin treatment with co-trimoxazole as soon as possible and continue the treatment for 9 or more days.