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TRIGGERING OF HIGH-LEVEL RESISTANCE AGAINST SCHISTOSOMA MANSONI REINFECTION BY ARTEMETHER IN THE MOUSE MODEL

Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1–3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

Received April 12, 2004. Accepted for publication July 12, 2004.

Acknowledgments: We thank Professors Frank Cox, Jacques Louis, and Don McManus for useful comments on earlier drafts of this manuscript, Prof. Thomas A. Smith for help with the statistical analysis, and two external referees for a series of excellent comments.

Financial support: Jürg Utzinger is currently supported by a grant from the Swiss National Science Foundation (project no. PPOOB-102883).

Authors’ addresses: Robert Bergquist, Ingerod 407, S-454 94 Brastad, Sweden. Jürg Utzinger, Jacques Chollet, Niklaus A. Weiss, and Marcel Tanner, Swiss Tropical Institute, PO Box, CH-4002 Basel, Switzerland. Xiao Shu-Hua, National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention, Shanghai 200025, People’s Republic of China.

Reprint requests: Marcel Tanner, Swiss Tropical Institute, PO Box, CH-4002 Basel, Switzerland, Telephone: 41-61-284-8283, Fax: 41-61-271-5179, E-mail: marcel.tanner{at}unibas.ch.

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