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 i...

Further observation on histopathological alterations of adult Schistosoma japonicum harbored in mice following treatment with mefloquine at a smaller single dose

“…But up to 28 days posttreatment with mefloquine at a smaller dose of 200 mg/kg, more then 40% of male worms shifted to the liver were classified as degenerated, and they might recover to normal gradually. All these indicate that under a lower dose level of mefloquine, the speed and intensity of activity against male schistosomes are decreased, while its potential activity against female worms is still remained, which is consistent with the therapeutic efficacy observed in experimental studies Xiao et al 2009a). …”

“…(Yue et al 1985;Sabah et al 1986;Xiao et al 1987). On the contrary, mefloquine exhibits similarly potential effect against both juvenile and adult schistosomes harbored in the same infected host, indicating the possibility to develop this category of compound as a prophylactictherapeutic agent used for treatment and prevention of schistosomiasis (Xiao et al 2009a). In addition, histopathological observation showed that a curative dose of mefloquine (400 mg/kg) exhibited strong lethal action on both juvenile and adult schistosomes Xiao and Zhang 2009).…”

“…Morphological and ultrastructural observation demonstrated that administration of mefloquine to mice, infected with adult S. japonicum, at a single dose of 400 mg/kg, induced extensive and severe damage to the worm tegument, musculatures, parenchymal tissues, digestive system, and reproductive system (Xiao et al 2009b(Xiao et al , 2010a(Xiao et al , 2010b. Since promising therapeutic efficacy was also seen, when infected, mice were treated with mefloquine at a half dose of 200 mg/kg Xiao et al 2009a). Therefore, it is interesting to observe on the process of histopathological alterations of schistosomes harbored in mice and treated with mefloquine at a smaller dose.…”

The in vitro effect of mefloquine and praziquantel against juvenile and adult Schistosoma japonicum

“…The result is consistent to the previous observation that 7-and 14-day-old juvenile schistosomes are unsusceptible to praziquantel (You et al 1986). Interestingly, although mefloquine exhibits potential in vitro effect against 3-h-old schistosomula (skin stage), no or poor efficacy is seen in mice infected with schistosome cercariae for 3 h and treated with mefloquine Xiao et al 2009b). Therefore, it is suggested that no drug could be excreted and secreted from the mouse skin after oral administration of mefloquine which might be the major cause.…”

Effectiveness of mefloquine against Clonorchis sinensis in rats and Paragonimus westermani in dogs

“…In 2008 and 2009, another antimalarial agent mefloquine (Ohnmacht et al 1971), an aminoalcohol compound, was reported to be effective in the significant reduction of egg production in Schistosoma mansoni-infected mice (Van Nassauw et al 2008) and also exhibited a similar potential effect against juvenile stages and adult S. mansoni and Schistosoma japonicum ). The distinctively anti-schistosomal properties of mefloquine against juvenile and adult schistosomes had been identified by morphological, histopathological, and ultrastructural observations Xiao et al 2009aXiao et al , 2009bXiao et al , 2010aXiao et al , 2010b. Since mefloquine and artemisinins are anti-malarial agents, further understanding the effect of mefloquine against C. sinensis and P. westermani is very interesting and necessary.…”