Blood Loss and Replacement in Plasmodial Infections I. Plasmodium Berghei in Untreated Rats of Varying Age and in Adult Rats with Erythropoietic Mechanisms Manipulated before Inoculation

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Abstract
A new method for describing changing erythrocyte populations employs the basophilic index, which gives increasing weight to more immature reticulocytes. For computing this index reticulocytes were classified as to content of retuculum on a scale from + through +++++. Particularly during erythropoietic stress, as after hemolytic crisis, the basophilic index gives more complete information than percent of reticulocytes. The chief reticulocyte observed in normal rat blood is the ++ cell. Following infection with P. berghei, blood loss differs in young and mature rats. In young rats all the observed loss can be attributed to direct rupture of red cells by parasites emerging from them. In mature rats observed loss is far in excess of that attributable to direct rupture, and anemia is at its height when parasitemia is receding. Red cells in mature rats are therefore destroyed not only by direct rupture, but also by some other agency as well, possibly a lytic antibody. Reticulocytic replacement after infection begins in rats of all ages about a week after inoculation, and reaches a peak 4 or 5 days later. Normal reticulocyte levels are restored in surviving rats a few days after peak. Correlations between this stable rhythm and the development of acquired immunity (which occurs earlier in mature than in young rats), the preference of P. berghei merozoites for reticulocytes, and the fact that reticulocytes are numerous in young and rare in mature rats before crisis, are all factors in the age immunity of rats to this parasite. The onset of reticulocytic repair before crisis (as in the young rat) endangers the life of the host by providing an ideal medium for development of the parasite when host defenses are still inadequate; when occurring after crisis (as in the mature rat) it does not endanger the host, since emerging merozoites are then destroyed by adequate host defenses before or soon after they invade clean cells. In untreated rats of all ages and in mature rats repeatedly bled before inoculation, P. berghei selectively invades +++ and ++++ reticulocytes and normoblasts with similarly reticulated cytoplasm; and it avoids or invades as if by chance definitive erythrocytes and cells with +, ++, and +++++ reticulation. Mature rats repeatedly bled before inoculation to induce reticulocytosis react like young rats in certain fundamental respects (1) parasitemia before crisis is intensified; about 30% die with fulminating infection; and (2) observed blood loss is all attributable to direct rupture by parasites. Prebleeding does not disturb the stable rhythm of reticulocytic repair described above.