Artemether as Adjuvant Therapy to Praziquantel in Murine Egyptian Schistosomiasis Mansoni

Abstract

We investigated the activity of artemether (ART) against different developmental stages of schistosomes alone and in addition to praziquantel (PZQ). ART was administered orally (400 mg/kg) 4 and 6 wk postinfection (PI), 4 and 5 wk PI, or 4 or 6 wk PI alone and in addition to oral PZQ (500 x 2 mg/kg) 6 wk PI. Mice were killed in parallel to infected untreated controls 8 wk PI. Parasitological parameters and histological changes in the liver were studied. ART given 4 and 6 wk PI reduced worm burdens by 59 and 55% and tissue egg load by 96 and 90%, respectively. Moreover, eggs in different developmental stages were not found. The reduction in worm and egg burden (63 and 58%, and 96 and 99%, respectively) in mice treated with ART 4 and 5 wk or 4 and 6 wk PI was comparable with that in ART-treated mice at 4 or 6 wk PI. Compared with PZQ alone, combined treatment of PZQ and ART (4 and 5 wk or 4 and 6 wk PI) did not enhance worm eradication, but there was a complete absence of parasite eggs. Livers revealed no granulomata when ART was given 4 and 5 wk or 4 and 6 wk PI, with minimal central necrosis in those treated 4 and 6 wk PI. In conclusion, combined treatment of ART (4 and 6 wk PI) and PZQ resulted in >90% worm eradication and amelioration of Schistosoma mansoni eggs from the tissues, with minor histological changes in the liver.

Current chemotherapy arsenal for schistosomiasis mansoni: alternatives and challenges

“…In a subsequent study, it was found that, compared with praziquantel alone, combined treatment of praziquantel and artemether (4 and 5 weeks or 4 and 6 weeks post-infection) in mice infected with the Egyptian strain of S. mansoni did not enhance worm eradication, but there was a complete absence of parasite eggs (Mahmoud and Botros 2005). Therefore, an effect on the fecundity of female worms could be concluded.…”

“…Xiao and Catto (1989b) showed that artemether had also an effect on 35-to 56-day-old adult worms of S. mansoni with total worm reduction rates of 30-51%, although it was most effective against schistosomula. There is also some difference in the sex-related susceptibility of the adults where adult female worms have been found to be somewhat more susceptible to artemether than males (Mahmoud and Botros 2005).…”

“…Mahmoud and Botros (2005) investigated the activity of artemether against different developmental stages of schistosomes in mice, both alone and in combination with praziquantel. It was found that a single dose of 400 mg/kg artemether given 4 and 6 weeks post-infection reduced the total S. mansoni worm burden by 59% and 55% as well as tissue egg load by 96% and 90%, 4 and 5 weeks after treatment, respectively.…”

“…In contrast to the activity of artemether on other strains of S. mansoni, it has been proposed that the worms of the Egyptian strain of S. mansoni respond to artemether for an extended period of time (Mahmoud and Botros 2005), conferring at least some therapeutic efficacy.…”

Response to Letter

“…Artemisine has been proven to be partially active against juvenile forms of Schistosoma in murine models, 5 in which it has drastically reduced the egg burden when given between weeks 4 and 6 postinfection. Some human studies have also indirectly demonstrated a significant reduction in egg burden when artemisine was used in therapeutic doses, both in the acute and chronic phases of infection.…”