Abstract
The aim of the study is to explore the effect of mefloquine against Clonorchis sinensis and Paragonimus westermani. For anti-C. sinensis study, a total of 71 rats were divided into four batches for oral infection of each rat with 50 C. sinensis metacercariae. Five to 7 weeks post-infection, groups of rats were treated orally with mefloquine at single doses or multiple daily doses while infected, but untreated rats served as control. All treated rats were euthanized 2 weeks post-treatment for assessment of efficacy. For anti-P. westermani study, two batches of eight and ten dogs were each infected intraperitoneally with 100 P. westermani metacercariae. Eighty-five to 96 days post-infection, groups of two or three dogs were treated orally with mefloquine and groups of two dogs were treated with praziquantel at a single dose or multiple doses. In each batch of test, three untreated but infected dogs served as control. All treated dogs were euthanized 26–30 days post-treatment for evaluation of efficacy. In rats infected with C. sinensis and treated orally with mefloquine at a single dose of 75 and 150 mg/kg, no effect against C. sinensis was observed. When the dose of mefloquine was increased to 250 mg/kg, one third (five out of 15) rats died 3–5 days post-treatment. Although the mean worm burden was lower than that of the control, the difference between the treated and control groups was not statistically significant (P > 0.05) with worm burden reduction of 22.4%. Whereas, the group of infected rats received mefloquine at a daily dose of 100 mg/kg for 3 days, one out of five rats died after the last administration. The mean worm burden was significantly lower than that of the control with worm burden reduction of 67.6% (P < 0.01). In the first test of mefloquine against P. westermani, three infected dogs received two oral doses of the drug, 50 mg/kg, given at a 4-h interval, the mean worm burden were similar to that of the control. While other two dogs were treated with praziquantel at the same dose schedule, the worm burden reduction of 78% was observed. In the second test, three and two dogs were treated with mefloquine 50 mg/kg daily for 5 days or 100 mg/kg daily for 2 days; the mean worm burdens of the two groups were lower than that of the control with worm burden reduction of 65.6% and 51.9%, respectively. However, only the difference of mean worm burdens between mefloquine 50 mg/kg given daily for 5 days and the control was statistically significant (P < 0.05). Other two dogs treated with praziquantel at a single dose of 100 mg/kg were cured. The results indicate that under the appropriate dose schedule mefloquine exhibits less effect against C. sinensis in rats and P. westermani in dogs.
Similar content being viewed by others
References
Canfield CJ (1980) Antimalarial aminoalcohol alteratives to mefloquine. Acta Trop 37:232–237
Gao JS, Liu YH, Wang XG, Yu DG, Shu J (1998) Experimental observation on treating the dogs infected with Clonorchis sinensis with praziquantel and triclabendazole. Chin J Parasitic Dis Cont 11:357
Keiser J, Utzinger J (2005) Emerging foodborne trematodiasis. Emerg Infect Dis 11:1507–1514
Keiser J, Xiao SH, Xue J, Chan ZS, Odermatt P, Tesana S, Tanner M, Utzinger J (2006a) Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis viverrini in rodent models. Int J Antimicrob Agents 28:370–373
Keiser J, Xiao SH, Utzinger J (2006b) Effect of tribendimidine on adult Echinostoma caproni harbored in mice, including scanning electron microscopic observations. J Parasitol 92:858–862
Keiser J, Brun R, Fried B, Utzinger J (2006c) Trematocidal activity of praziquantel and artemisinin derivatives: in vitro and in vivo investigations with adult Echinostoma caproni. Antimicrob Agents Chemother 50:803–805
Keiser J, Xiao SH, Tanner M, Utzinger J (2006d) Artesunate and artemether are effective fasciolicides in the rat model and in vitro. J Antimicrob Chemother 57:1139–1145
Keiser J and Utzinger J (2007a) Advances in discovery and development of novel trematocidel drugs, Expert Opin Drug Discov 2(Suppl 1:S9-S23
Keiser J, Xiao SH, Chollet J, Tanner M, Utzinger J (2007b) Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni, Fasciola hepatica Clonorchis sinensis, and Opisthorchis viverrini. Antimicrob Agents Chemother 51:1096–1098
Keiser J, Xiao SH, Dong Y, Utzinger J, Vennerstrom JL (2007c) Clonorchicidal properties of the synthetic trioxolane OZ78. J Parasitol 93:1208–13
Keiser J, Chollet J, Xiao SH, Mei JY, Jiao PY, Utzinger J, Tanner M (2009) Mefloquine—an aminoalcohol with promising antischistosomal properties in mice. PLoS Negl Trop Dis 3:e350
Liu Q, Wei F, Liu W, Yang S, Zhang X (2008) Paragonimiasis: an important food-borne zoonosis in China. Trends Parasitol 24:318–323
Lun ZR, Gasser RB, Cai DH, Zhu XQ, Yu XB, Fang YY (2005) Clonorchiasis: a key foodborne zoonosis in China. Lancet Infect Dis 5:31–41
Ohnmacht CJ, Patel AR, Lutz RE (1971) Antimalarials. 7. Bis (trifluoromethyl)- (2-piperidyl)-4-quinolinemethanols. J Med Chem 14:926–928
Schwartz DE, Weber W, Richard-Lenoble D, Gentilini M (1980) Kinetic studies of mefloquine and of one of its metabolites Ro 21-5104, in the dog and in man. Acta Trop 37:238–242
Shen YP, Cai SC (1982) Experimental study on treatment of paragonimiasis in dogs with praziquantel. National Med J Chin 62:109 (in Chinese)
Tinga N, De N, Vien HV, Chau L, Toan ND, Kager PA, Vries PJ (1999) Little effect of praziquantel or artemisinin on clonorchiasis in noethern Vietnam. A pilot study. Trop Med Int Health 4:814–818
Toovey S (2009) Mefloquine neurotoxicity: a literature review. Travel Med Infect Dis 7:2–6
UNDP/World Bank/WHO (1983) Development of mefloquine as an antimalarial drug. Bull WHO 61:169–178
Utzinger J, Xiao SH, Tanner M, Keiser J (2007) Artemisinins for schistosomiasis and beyond. Curr Opin Investig Drugs 8:105–116
Van Nassauw L, Toovey S, Op V, den Bosch J, Timmermans JP, Vercruysse J (2008) Schistosomicidal activity of the antimalarial drug, mefloquine, in Schistosoma mansoni-infected mice. Travel Med Infect Dis 6:253–258
White NJ (1985) Clinical pharmacolinetics of antimalarial drugs. Clin Pharmacokinet 10:187–215
Xiao SH (2005) Study on prevention and cure of artemether against schistosomiasis. Chin J Schistosomiasis Cont 17:310–320
Xiao SH, Booth M, Tanner M (2000) The prophylactic effects of artemether against Schistosoma japonicum infections. Parasitol Today 16:122–126
Xiao SH, Keiser J, Chollet J, Utzinger J, Dong Y, Endriss Y, Vennerstrom JL, Tanner M (2007) In vitro and in vivo activities of synthetic trioxolanes against major human schistosome species. Antimicrob Agents Chemother 51:1440–1445
Xiao SH, Xue J, Tanner M, Zhang YN, Keiser J Utzinger, Qiang HQ (2008) Artemether, artesunate, praziquantel and tribendimidine administered singly at different dosages against Clonorchis sinensis–a comparative in vivo study. Acta Trop 106:54–59
Xiao SH, Chollet J, Utzinger J, Mei JY, Jiao PY, Keiser J, Tanner M (2009a) Effect of single-dose oral mefloquine on the morphology of adult Schistosoma japonicum in mice. Parasitol Res 105:853–861
Xiao SH, Mei JY, Jian PY (2009b) Further study on mefloquine concerning several aspects in experimental treatment of mice and hamsters infected with Schistosoma japonicum. Parasitol Res 106:131–138
Xiao SH, Xue J, Shen BG (2010a) Tegumental alterations of adult Schuistosoma japonicum harbored in mice treated with a single oral dose of mefloquine. Chin J Parasitol Parasitic Dis 28:1–7
Xiao SH, Xue J, Shen BG (2010b) Transmission electron microscopic observation on ultrastructural alterations in Schistosoma japonicum caused by mefloquine. Parasitol Res 106:1179–1187
Xu SE, Lu XJ, Jin LQ (2000) Killing effect of triclabendazole on Paragonimus westermani in vitro and in vivo and the measurements on the contents of protein, glycogen and DNA in the worm. Chin J Zoonoses 16:18–21
Xue J, Utzinger J, Zhang YN, Tanner M, Keiser J, Xiao SH (2008) Artemether and tribendimidine lack activity in experimental treatment of Paragonmus westermani in the dogs. Parasitol Res 102:537–540
Xue J, Xu LL, Qiang HQ, Zhang YN, Xiao SH (2009) Therapeutic effect of tribendimidine, artesunate and praziquantel administered to hamsters infected with Clonorchis sinensis. Chin J Parasitol Parasitic Dis 27:215–218
Zhang CW, Xiao SH, Utzinger J, Chollet J, Keiser J, Tanner M (2009) Histo- pathological changes in adult Schistosoma japonicum harbored in mice treated with a single dose of mefloquine. Parasitol Res 104:1407–1416
Acknowledgment
This investigation received financial support from the National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Shanghai, China).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Xiao, Sh., Xue, J., Li-li, X. et al. Effectiveness of mefloquine against Clonorchis sinensis in rats and Paragonimus westermani in dogs. Parasitol Res 107, 1391–1397 (2010). https://doi.org/10.1007/s00436-010-2007-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-010-2007-7