Artemisone effective against murine cerebral malaria.
BACKGROUND
Artemisinins are the newest class of drug approved for malaria treatment. Due to their unique mechanism of action, rapid effect on Plasmodium, and high efficacy in vivo, artemisinins have become essential components of malaria treatment. Administration of artemisinin derivatives in combination with other anti-plasmodials has become the first-line treatment for uncomplicated falciparum malaria. However, their efficiency in cases of cerebral malaria (CM) remains to be determined.


METHODS
The efficacy of several artemisinin derivatives for treatment of experimental CM was evaluated in ICR or C57BL/6 mice infected by Plasmodium berghei ANKA. Both mouse strains serve as murine models for CM.


RESULTS
Artemisone was the most efficient drug tested, and could prevent death even when administered at relatively late stages of cerebral pathogenesis. No parasite resistance to artemisone was detected in recrudescence. Co-administration of artemisone together with chloroquine was more effective than monotherapy with either drug, and led to complete cure. Artemiside was even more effective than artemisone, but this substance has yet to be submitted to preclinical toxicological evaluation.


CONCLUSIONS
Altogether, the results support the use of artemisone for combined therapy of CM.
Waknine-Grinberg
Judith H
JH
Department of Microbiology and Molecular Genetics, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
Hunt
Nicholas
N
Bentura-Marciano
Annael
A
McQuillan
James A
JA
Chan
Ho-Wai
HW
Chan
Wing-Chi
WC
Barenholz
Yechezkel
Y
Haynes
Richard K
RK
Golenser
Jacob
J
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002738:Chloroquine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016779:Malaria, Cerebral / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei / Q000187:drug effects*
D000962:Antimalarials; D037621:Artemisinins; C514498:artemisone; D002738:Chloroquine