Parasitemia, pitting rate, concentration of once-infected erythrocytes, and the risk of evolution toward PADH or other patterns of post-AS anemia in patients with severe malaria. (A) Individual values of parasitemia (as a percentage of infected erythrocytes) in patients with severe malaria treated with AS in whom posttreatment evolution of anemia could be categorized as rising (19 patients), persistent (10 patients), or PADH (13 patients). The dotted line corresponds to the threshold of 4% parasitemia, which provides the best discrimination between PADH and other patterns of post-AS anemia. Percentages at the top of the panel are the proportion of patients above this 4% threshold for each pattern of anemia. (B-C) Individual values of pitting rate (normalized against initial parasitemia [B]), and concentration of once-infected erythrocytes (g/L [C]) in 35 samples from 21 patients with severe malaria treated with AS in whom posttreatment evolution of anemia could be categorized as rising, persistent, or PADH. The dotted lines correspond to thresholds providing the best discrimination between PADH (9 patients) and other patterns of post-AS anemia (12 patients). Percentages at the top of the panel are the proportion of samples above this threshold of 45% pitting rate and above 0.18 billion once-infected erythrocytes per liter for each pattern of anemia. (D) Graphic representation of the relative influences of parasitemia on admission, peak pitting rate, and peak concentration of once-infected erythrocytes on the risk of evolution toward the different patterns of post-AS anemia. The concentration of circulating once-infected erythrocytes was computed by multiplying parasitemia by the pitting rate. Patients with high initial parasitemia and a high pitting rate harbor a high concentration of once-infected erythrocytes (upper right zone of the panel) and are at high risk of intense PADH in the following days or weeks. On the basis of these markers, the risk of subsequent PADH can be predicted before the end of the first week. The risk becomes significant when parasitemia on admission is above 4% and the peak pitting rate on days 2 through 8 is above 45%. On the basis of this data set (panels A-C), a concentration of circulating once-infected erythrocytes on days 2 to 8 greater than 0.18 g/L discriminates patients with PADH from patients with other patterns of anemia more effectively than do parasitemia or the peak pitting rate taken separately. This model also explains why delayed hemolysis has not been observed in severe malaria patients treated with quinine, a compound that induces low pitting rates.