We studied the effects of
artesunate on rhesus monkeys infected with Plasmodium coatneyi. Sixteen rhesus monkeys were divided in four groups. Group I consisted of three monkeys that were splenectomized and were treated with three doses (loading dose: 3.3 mg/kg, maintenance doses: 1.7 mg/kg) of
artesunate, group II consisted of three monkeys that were treated with three doses of
artesunate (same as group I), group III consisted of two monkeys that were treated with one dose (3.3 mg/kg) of
artesunate, and group IV consisted of five untreated monkeys.
Parasitemias of these groups ranged from 13.3% to 19.5% before treatment. Twenty-four hours after administration, the
parasitemia was reduced to 2.2% in group I and to < 0.1% in group II;
parasitemia was lowered to 10.6% in group III only 3 hr after
drug administration. The rate of sequestration in the cerebral microvessels, which was 29.4% in untreated animals, was < 0.1% in groups I and II (24 hr
after treatment), and 2.0% in group III (3 hr
after treatment). These data clearly indicate that
artesunate not only reduced
parasitemia, but also reduced the rate of parasitized red blood cell (PRBC) sequestration in cerebral microvessels. In an immunohistologic study,
endothelial-leukocyte adhesion molecule-1 (ELAM-1) was not detected in group I
after treatment with
artesunate, although the presence of CD36,
thrombospondin,
intercellular adhesion molecule-1,
IgG, and C3 in the cerebral microvessels was not altered. This is the first in vivo study to show that
artesunate interferes with continued PRBC sequestration in the cerebral microvessels in
cerebral malaria.(ABSTRACT TRUNCATED AT 250 WORDS)