Abstract. Decreased erythropoiesis and increased clearance of both parasitized and noninfected erythrocytes both contribute to the pathogenesis of anemia in falciparum malaria. Erythrocytes with reduced deformability are more likely to be cleared from the circulation by the spleen, a process that is augmented in acute malaria. Using a laser diffraction technique, we measured red blood cell (RBC) deformability over a range of shear stresses and related this to the severity of anemia in 36 adults with severe falciparum malaria. The RBC deformability at a high shear stress of 30 Pa, similar to that encountered in the splenic sinusoids, showed a significant positive correlation with the nadir in hemoglobin concentration during hospitalization (r ϭ 0.49, P Ͻ 0.002). Exclusion of five patients with microcytic anemia strengthened this relationship (r ϭ 0.64, P Ͻ 0.001). Reduction in RBC deformability resulted mainly from changes in unparasitized erythrocytes. Reduced deformability of uninfected erythrocytes at high shear stresses and subsequent splenic removal of these cells may be an important contributor to the anemia of severe malaria.Anemia is an important cause of morbidity and mortality in falciparum malaria. 1,2 The pathogenesis of anemia in malaria is multifactorial and incompletely understood. It is thought to result from a combination of parasitized erythrocyte destruction at schizont rupture, accelerated removal of both parasitized and unparasitized red blood cells, and ineffective erythropoiesis. [3][4][5][6] Of these factors, removal of unparasitized red blood cells is the most important, accounting for approximately 90% of the reduction in hematocrit in acute malaria (Price R and others, unpublished data). We have shown previously that the threshold for splenic removal of heat-damaged or antibody-coated erythrocytes in acute malaria is lowered, suggesting enhancement of both mechanical filtrative function and Fc receptor-mediated clearance. 7,8 Reduced red blood cell (RBC) deformability is thought to play an important role in the removal of senescent red blood cells from the circulation by the spleen. 9 Since reduced RBC deformability might also play a role in the clearance of both parasitized and unparasitized red blood cells in malaria, we have measured RBC deformability in relation to the development of anemia in severe falciparum malaria.
PATIENTS AND METHODSStudy site. The study was carried out during the rainy season months from May until July in both 1995 and 1996, in the provincial hospital of Mae Sot, Tak province, in western Thailand. Malaria transmission is low in this area with a seasonal peak during the rainy season that starts in late spring. 10 Severe disease occurs at all ages. Multiple drug resistance is an increasing problem in this area.Patients and clinical procedures. Consecutive adult patients admitted to Mae Sot Hospital with severe falciparum malaria were included, providing that written informed consent for blood sampling was obtained from the patients or their attendant relatives...
A randomized, open-label comparison of artesunate and quinine was conducted in 113 adults with clinically severe falciparum malaria in western Thailand. Mortality was 12% with artesunate and 22% with quinine treatment (relative risk, 0.53; 95% confidence interval, 0.23-1.26; P=.22). Multiple logistic regression analysis found admission plasma lactate level, Glasgow Coma Scale score, and total serum bilirubin level to be independent risk factors for death. Coma recovery and times to normalize plasma lactate levels were similar, but the parasite clearance time was much shorter among artesunate-treated patients (P=.019). Fewer patients became hypoglycemic during artesunate therapy (10%) than during quinine therapy (28%) (P=.03). Artesunate is at least as effective as quinine in the treatment of adults with severe malaria. Larger trials are required to determine whether mortality is reduced among patients treated with artesunate.
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