Further study on mefloquine concerning several aspects in experimental treatment of mice and hamsters infected with Schistosoma japonicum

Abstract

Antischistosomal properties of mefloquine against Schistosoma japonicum have been further studied. A total of 260 mice were divided into four batches, and three batches of them were infected percutaneously with 40 S. japonicum cercariae. In the remaining batch, mice were infected with 20, 40, or 80 S. japonicum cercariae. Other 45 hamster, divided into two batches, were each infected two or three times with 50 S. japonicum cercariae at days 0 and 7 or 0, 14, and 21. The infected mice and hamsters were treated orally with single doses of mefloquine or praziquantel at various intervals post-infection, while infected but untreated mice and hamsters served as control. All treated animals were killed 4 weeks post-treatment for assessment of effect. In hamsters concurrently infected with 14- and 21-day-old or 14-, 21-, and 35-day-old schistosomes and treated orally with mefloquine at a single dose of 100 and 200 mg/kg, the total worm burdens were significantly lower than that of control (P < 0.05 or P < 0.01) with worm burden reductions of 45.4% and 89.9% as well as 82.5% and 90.6%, respectively. In the first batch of mice treated with mefloquine and four structurally related amino alcohol antimalarials 5 weeks post-infection at a single dose of 400 mg/kg, mefloquine, quinine, and quinidine possessed similar potential effect with total worm burden reductions of 80.9-90.3%, while halofantrine and lumefantrine showed moderate and poor effect with total worm burden reductions of 67.5% and 38.4%, respectively. In the second batch of mice infected with 20, 40, and 80 S. japonicum cercariae and treated orally with mefloquine at a single dose of 200 and 400 mg/kg 5 weeks post-infection, similar effects were seen in groups of mice with various infection intensity, the total worm burden reductions were 59.9-73.0% (200 mg/kg) and 85.0-89.1% (400 mg/kg). In the other two batches of mice infected with various stages of schistosomes and treated orally with mefloquine and praziquantel at a single dose of 200 or 400 mg/kg, potential and moderate effects of praziquantel against d0 worms (3-h-old) and adult worms (28- and 35-day-old) with total worm burden reductions of 83.6-95.6% and 42.4-69.3% were observed, but no effect against various stages of juvenile schistosome was seen. Under the two single doses used, mefloquine exhibited no effect against d0 worms, but showed moderate or potential effect against various stages of juvenile and adult schistosomes with total worm burden reductions of 56.3-89.1% (200 mg/kg) and 81.1-100% (400 mg/kg). The results indicate that mefloquine shows potential effect on hamsters concurrently infected with various stages of juvenile and adult S. japonicum; among the four structurally related amino alcohol antimalarials tested, quinine and its isomer quinidine exhibit potential effect against adult S. japonicum similar to that of mefloquine, while halofantrine and lumefantrine posses moderate and poor effect; no impact of infection intensity on the effect of mefloquine against schistosomes was observed in mice; under the same dose level, the effect of mefloquine against development stages of juvenile and adult S. japonicum is superior to that of praziquantel.