Preventive effect of artemether in rabbits infected with Schistosoma japonicum cercariae.

AIM: To study the effect of artemether (Art) for prevention of schistosomal infection. METHODS: Rabbits with single infection or reinfection with Schistosoma japonicum cercariae were treated intramuscularly (i.m.) or intragastrically (i.g.) with Art 5 -20 mg.kg-1 on d 7-15 after the first infection, followed by various regimens. RESULTS: When rabbits were injected i.m. Art 7.5 mg.kg-1 (i.e., one half of the effective dose given i.g. on d 7) followed by once every week for twice, the female worm reduction rate was only 42%. In infected rabbits treated i.g. with Art 10-20 mg.kg-1 given in the same administration schedule, the female worm reduction rates were > 91%. When Art 15 mg.kg-1 was given to rabbits on d 7-14 and the following dose of the drug was given at intervals of 7-14 d, the female worm reduction rates were > 94%. In rabbits reinfected with cercariae, the female reduction rate of Art given i.g. once a week for 3 times since d 8 after the first infection was 96% which was similar to that given once a week twice since d 14 after the first infection. CONCLUSION: Art should be given i.g. on d 7-15 after infection, followed by repeated dosing once every 7-15 d for a total of 3 doses. Art given i.g. daily for 2 consecutive days or given at 1-wk intervals since 7-15 d after infection also showed preventive effect.

Microscopic observations on livers of rabbits and dogs infected with Schistosoma japonicum cercariae and early treatment with artemether or praziquantel.

UNLABELLED: To study the histopathological change of the liver of the hosts treated with artemether (Art) or praziquantel (Pra) in early stage after infection with Schistosoma japonicum cercariae. METHODS: Dogs infected once with schistosome cercariae were treated ig with Art 10 mg.kg-1 or Art capsule (ArtC) 15 mg.kg-1 on d 7, or praziquantel (Pra) 30-40 mg.kg-1 on d 21 after infection, followed by the repeated dosing once every 1 or 2 wk for 2-4 times. In rabbits, infected with 48-52 schistosome cercariae once every other day for 5 times, were treated ig with Art 10 mg.kg-1 or Pra 30 mg.kg-1 was started on d 7 or on d 21 after the first infection, followed by the repeated dosing every 1 or 2 wk for 2-3 times. RESULTS: After above mentioned dogs or rabbits were treated ig with Art, ArtC or Pra, the female worm reduction rates were 92.1%-100%. Histopathological examination showed that the reduction rates of total granuloma in the liver sections of the dogs and rabbits were 70.9%-97.3% and 76.5%-97.4%, respectively. Meantime, the structure of the hepatic lobules was normal with normal arrangement of the liver bundle. CONCLUSIONS: Early treatment with Art or Pra exhibited a promising effect of protection of the liver of the dogs and rabbits infected with schistosome cercariae. Early treatment of infection with schistosome cercariae kills the Female worms before oviposition. Thus, the host will be protected from the damage caused by schistosome eggs. Promising results were obtained when mice and rabbits received an early treatment with artemether (Art) or praziquantel (Pra). This work was to study the liver infected with cercariae and treated by intragastric gavage (ig) with Art, Art capsule (ArtC) or Pra in early stage after infection.

Experimental studies on early treatment of schistosomal infection with artemether.

An early treatment with artemether given in appropriate regimens was tested in mice, rabbits and dogs for prevention purposes. Artemether was administered intragastrically (ig) to the hosts on day 7 after infection with Schistosoma japonicum cercariae at a single dose, and the same dose of artemether was repeated every 1 or 2 weeks for 2-4 times. As a result, most of the female worms were killed before their oviposition with female worm reduction rates of 90-100%, resulting in protection of the host from damage induced by schistosome eggs. When rabbits were treated ig with artemether 10 mg kg-1 on day 7 after infection, followed by repeated dosing every week for 4 times, some parameters related to acute schistosomiasis, such as temperature, eosinophil count and eggs in the feces were negative, and low specific antigen and antibody levels in serum were seen. Further study showed that the appropriate regimens of Artemether were also effective in early treatment of reinfection with cercariae. When rabbits infected with 48-52 cercariae once every other day for 5 times were treated ig with artemether 15 mg kg-1, followed by repeated dosing every 1 or 2 week for 2- 3 times, the female worm reduction rates were 92.1-98.4%. Histopathological examination of the livers showed that the above-mentioned early treatment with Artemether exhibited a promising protective effect on dogs and rabbits. The major features included normal appearance of the liver resembling those of uninfected dogs and rabbits; few or no dispersed miliary egg tubercles appeared on the surface of the liver; the structure of the hepatic lobules was normal with normal arrangement of the liver bundles; few or no eggs appeared in the portal vein area and there was apparent diminution of total egg granuloma, comprising inflammatory, fibrous or scarred egg granuloma. On the basis of above-mentioned results, early treatment with Artemether could be recommended for field trial for controlling acute schistosomiasis, reducing infection rate and intensity of infection.

Early treatment of schistosomal infection with artemether and praziquantel in rabbits.

Artemether (Art, beta-methyl ether of artemisinin) first synthesized by Shanghai Institute of Materia Medica, Chinese Academy of Sciences, is effective against not only malaria but also schistosomiasis. When rabbits infected with Schistosoma japonicum cercariae for 7 d were treated ig with Art 10 mg.kg-1, the total worm reduction rates were 74.6-76.7%. If Art (10 mg.kg-1) was given once weekly after the first treatment for 3-4 times, the total worm reduction rate was > 98%, and most of the rabbits were free from female worms. When praziquantel (Pra) was given ig 40 mg.kg-1 to rabbits on d 21 after infection, and repeated once every week for 3 wk, most rabbits showed a total worm reduction rate > 98% with their livers showing normal or mild changes, and their parameters relevant to acute schistosomiasis were negative as compared to the controls. Hence Art and Pra are suggested to be used in field trial for control of acute schistosomiasis or reduction of the intensity of schistosomal infection.

Effect of early treatment of artemether against schistosomiasis in mice.

When artemether (Art) was given ig to mice on the day of infection with Schistosoma japonicum cercariae at a single dose of 300 mg.kg-1 and followed by the repeated dosing at 2-3 wk intervals, the total and female worm reduction rates as compared with the control were evident. In mice treated ig with Art on d7 at the same dosage and repeated once every wk for 4 times, the female worm reduction rates were about or over 90%, and part of the animals was free from female worm. Nevertheless, the liver appearance of some treated animals was similar to that of the normal mouse. The results indicated that if Art was given in the early stage after infection, it could be expected to protect the host from schistosomal infection or reduce the intensity of infection.

Early treatment of schistosomal infection with praziquantel in mice.

The first single dose of praziquantel (Pra) was given ig to mice on the day of infection with Schistosoma japonicum cercariae, or 7 d, 14 d, and 21 d after infection. Afterwards, the same dose of Pra was given once at 1-3 wk intervals for 2-3 times. The prophylactic effect was estimated by the reduction of average number of total and female worms, the number of mice without female worm, and the gross change of the liver. When mice were treated with Pra 300-500 mg.kg-1 initially on d 21 after infection and repeated once every 1-2 wk for 2-3 times, almost all the female worms lodged in the host were killed, showing that either the host was protected from the infection of schistosomes or a great decrease in the intensity of the infection resulted.

[Effect of artemether against Schistosoma japonicum].

Artemether (beta-methyl ether of artemisinin) first synthesized by Shanghai Institute of Materia Medica, Chinese Academy of Sciences(1), appears in colorless crystal and is more lipid-soluble than artemisinin. When artemether was given ig or im to mice infected with Schistosoma japonicum for 32-35 d at the dosage of 1/10-1/2 LD50. Its effects in the two administration routes were similar. After artemether 200 mg.kg.d-1 ig or 100 mg.kg-1.d-1 im for 1-2 d was given to mice infected with S japonicum cercariae at different intervals, d 7 schistosomules were more susceptible to the drug with worm reduction rates of 73.9-92.0%. The d 35 adult worms also exhibited susceptibility to the drug and the worm reduction rates were 47.0-70.1%, but less susceptibility to the drug in other developmental stages of schistosomes. The major morphological alteration of adult worms induced by artemether was sustained shrinkage accompanied by atrophy and degeneration of the worm's reproductive glands, eg, the testis in males and ovary as well as vitelline gland in females. The in vitro tests indicated that artemether showed apparent effects on different stages of schistosomes only when a higher concentration of 40 micrograms.ml-1 was used.