A nonhuman primate model for human cerebral malaria: effects of artesunate (qinghaosu derivative) on rhesus monkeys experimentally infected with Plasmodium coatneyi
Maeno, Y.; Brown, A.E.; Smith, C.D.; Tegoshi, T.; Toyoshima, T.; Ockenhouse, C.F.; Corcoran, K.D.; Ngampochjana, M.; Kyle, D.E.; Webster, H.K.
American Journal of Tropical Medicine and Hygiene 49(6): 726-734
1993
ISSN/ISBN: 0002-9637 PMID: 7506497 Document Number: 413531
The effects of artesunate were studied in rhesus monkeys infected with Plasmodium coatneyi. Sixteen rhesus monkeys were divided into 4 groups. Group I consisted of 3 monkeys that were splenectomized and were treated with 3 doses (loading dose: 3.3 mg/kg, maintenance doses: 1.7 mg/kg) of artesunate, group II consisted of 3 monkeys that were treated with 3 doses of artesunate (same as group I), group III consisted of 2 monkeys that were treated with one dose (3.3 mg/kg) of artesunate, and group IV consisted of 5 untreated monkeys. Parasitaemias of these groups ranged from 13.3% to 19.5% before treatment. Twenty-four h after administration, the parasitaemia was reduced to 2.2% in group I and to <0.1% in group II; parasitaemia was lowered to 10.6% in group III only 3 h 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 h after treatment), and 2.0% in group III (3 h after treatment). It is concluded that artesunate not only reduced parasitaemia, but also reduced the rate of parasitized red blood cell (PRBC) sequestration in cerebral microvessels. In an immunohistological 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.From AS The effects of artesunate were studied in rhesus monkeys infected with Plasmodium coatneyi. Sixteen rhesus monkeys were divided into 4 groups. Group I consisted of 3 monkeys that were splenectomized and were treated with 3 doses (loading dose: 3.3 mg/kg, maintenance doses: 1.7 mg/kg) of artesunate, group II consisted of 3 monkeys that were treated with 3 doses of artesunate (same as group I), group III consisted of 2 monkeys that were treated with one dose (3.3 mg/kg) of artesunate, and group IV consisted of 5 untreated monkeys. Parasitaemias of these groups ranged from 13.3% to 19.5% before treatment. Twenty-four h after administration, the parasitaemia was reduced to 2.2% in group I and to <0.1% in group II; parasitaemia was lowered to 10.6% in group III only 3 h 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 h after treatment), and 2.0% in group III (3 h after treatment). It is concluded that artesunate not only reduced parasitaemia, but also reduced the rate of parasitized red blood cell (PRBC) sequestration in cerebral microvessels. In an immunohistological 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.