Triggering of High-Level Resistance Against Schistosoma Mansoni Reinfection by Artemether in the Mouse Model

Abstract

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.

Current Status of Vaccines for Schistosomiasis

“…The attenuated larvae fail to mature into adult worms and do not produce eggs, so any results obtained are not confounded by egg-induced liver pathology. An even greater effect of triggering high-level resistance against schistosome reinfection has been shown for mice treated with artemether, a methyl ether derivative of dihydroartemesinin, followed by challenge (11). This model may provide an alternative approach to irradiated vaccines for dissecting different immune responses as putative effector mechanisms during schistosome infection and protective responses against reinfection.…”

Schistosomiasis—a century searching for chemotherapeutic drugs

“…As a schistosomicidal, it is not commercially available, but it is known to present strong activity against schistosomula during the first 21 days post infection. Furthermore, artemether was shown to have some prophylactic effect (Xiao et al 2000) and induce resistance against S. mansoni reinfection in mice (Bergquist et al 2004). Contrariwise, praziquantel does not kill 3-to 21-day-old schistosomula-the migrating larvae (Ross et al 2002).…”

Schistosomiasis vaccines

“…The list of antigens and associated prophylactic efficacy has been extensively reviewed in the last few years. 10,12,16,27,[42][43][44][45] From all of these antigens, only one S. hematobium antigen, Sh-28-GST, has advanced into clinical trials, though this occurred over a decade ago and detailed findings are not available. 46 Another important schistosome antigen, Sm-14, a fatty acid binding protein has also been developed for clinical trials.…”