Abstract. The effect of artesunate and its metabolite dihydroartemisinin against the cerebral cysts of Toxoplasma gondii was studied. In vitro experiments were performed with the THP-1 cell line and showed an inhibition of parasite growth of approximately 70% with 0.1-0.5 g/ml of dihydroartemisinin for 96 hr. However, with artesunate, dihydroartemisinin, or a combination (50:50) of them, the number of tachyzoites decreased approximately 40-50% and they appeared motionless. Fifty-eight to 72 hr after washing of the tachyzoites and THP-1 cells in culture, parasitized cells reappeared. In vivo, the 50:50 artesunate-dihydroartemisinin combination produced a decrease in cerebral cysts of approximately 40% after only 5 days of treatment. However, transplantations into naïve mice using brains of treated mice gave positive results.Artemisinin, a peroxide-containing sesquiterpene lactone isolated from the herb Artemisia annua, has been found to possess potent antimalarial activity and low toxicity both in animals and humans. 1,2 Artesunate (a water soluble half-ester succinate derivative) and artemether (a methyl ether derivative) are the only 2 derivatives of artemisinin that have been licensed in Thailand for treatment of Plasmodium falciparum malaria since 1990.Because of their low solubility in either water or oil 1 and the short plasma half-life of artemisinin, artesunate and artemether have been studied, in particular, sodium artesunate. 3 All artemisinin derivatives are metabolized to an active metabolite, dihydroartemisinin, whose half-life is 2 hr compared with the 45 min half-life of artesunate. 4 Artesunate and dihydroartemisinin are active against severe or complicated P. falciparum malaria. 5 Artesunate contains an endo-peroxide bridge. The peroxide moiety has been demonstrated to be responsible for the antimalarial activity of these compounds 6,7 and presumably for antitoxoplasmal activity. 8 Since these drugs cross the blood-brain barrier, they have been tested as a treatment for toxoplasmosis. To our knowledge, these qinghaosu derivatives have been only tested on the RH strain, a highly virulent strain of Toxoplasma gondii. [8][9][10] The purpose of the present study was to evaluate the in vitro and in vivo effects of artesunate, dihydroartemisinin, and their combination on the cyst-forming strain of T. gondii. MATERIALS AND METHODSParasite. Toxoplasma gondii strain DUR was isolated from the amniotic fluid of a pregnant woman. This isolate is considered to be of low virulence because it causes a chronic infection in mice and grows slowly in culture. This avirulent strain was maintained in our laboratory by oral passage of cysts from the brain of an infected mouse.Cell culture. The human myelomonocytic cell line THP-1 (European Collection of Animal Cell Cultures number 88081201; Sophia-Antipolis, France) was used for T. gondii culture. These non-adherent cells were suspended in RPMI 1640 medium (DAP, Vogelgrun, France) supplemented with 100 U/ml of penicillin, 100 g/ml of streptomycin (SigmaAldrich, L'Isle...

The activity against Toxoplasma gondii of 2',3' dideoxyinosine (ddI), an anti-human immunodeficiency virus drug, was examined in an in vitro and in vivo study. Cell cultures infected with a strain known to cause chronic infections were used to show the dose-dependent effect of this drug compared with spiramycin and sulfadiazine. When a dose of 4 microg/ml was used, no infected THP-1 cells or parasites were found after 60 h of incubation. An electron-microscopic study confirmed that after 12 h at 1 microg/ml, the few parasites observed were severely altered. The treatment of chronically infected mice 3 months postinfection showed that a 30-day treatment with 2 mg of ddI/ml induced a significant reduction in the number of T. gondii cysts in the cerebral tissue. These cysts were not viable, as confirmed by immunofluorescence and reinfection experiments. These experiments suggest a possible role for ddI in the treatment of toxoplasmosis, and this possibility deserves further investigation.