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Efficacy of artemether and artesunate in mice infected with praziquantel non-susceptible isolate of Schistosoma japonicum

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Abstract

Praziquantel is currently the only drug of choice for the treatment of human Schistosoma japonicum infections, and praziquantel-based chemotherapy has been proved to be generally effective to control the morbidity and reduce the prevalence and intensity of S. japonicum infections. However, the potential emergence of praziquantel resistance in S. japonicum seriously threatens the elimination of this neglected tropical disease in China. The purpose of this study was designed, in mouse animals, to evaluate the in vivo efficacy of artemether and artesunate against praziquantel non-susceptible S. japonicum. Mice infected with a praziquantel non-susceptible isolate and a praziquantel-susceptible isolate of S. japonicum were treated with artemether and artesunate at a single oral dose of 300 mg/kg given once on each of days 7–8 and 35–36 post-infection to assess the efficacy against juvenile and adult worms. Administration with artemether and artesunate at a single oral dose of 300 mg/kg on each of days 7–8 post-infection resulted in total worm burden reductions of 72.8 and 73.5 % in mice infected with praziquantel-susceptible S. japonicum, and 77.9 and 74.1 % in mice infected with the non-susceptible isolate (both P values >0.05), while the same treatments given on days 35–36 post-infection reduced total worm burdens by 71.4 and 69.6 % in mice infected with the susceptible isolate, and 75.3 and 69.6 % in mice infected with the non-susceptible parasite (both P values >0.05). It is concluded that there is no evidence for reduced susceptibility of artemether and artesunate in praziquantel non-susceptible S. japonicum.

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References

  • Alonso D, Muñoz J, Gascón J, Valls ME, Corachan M (2006) Failure of standard treatment with praziquantel in two returned travelers with Schistosoma haematobium infection. Am J Trop Med Hyg 74:342–344

    PubMed  Google Scholar 

  • Aragon AD, Imani RA, Blackburn VR, Cupit PM, Melman SD, Goronga T, Webb T, Loker ES, Cunningham C (2009) Towards an understanding of the mechanism of action of praziquantel. Mol Biochem Parasitol 164:57–65

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen MG (2005) Use of praziquantel for clinical treatment and morbidity control of schistosomiasis japonica in China: a review of 30 years’ experience. Acta Trop 96:168–176

    Article  CAS  PubMed  Google Scholar 

  • Chen XY, Wang LY, Cai JM, Zhou XN, Zheng J, Guo JG, Wu XH, Engels D, Chen MG (2005) Schistosomiasis control in China: the impact of a 10-year World Bank Loan Project (1992–2001). Bull World Health Organ 83:43–48

    Google Scholar 

  • Doenhoff MJ, Kusel JR, Coles GC, Cioli D (2002) Resistance of Schistosoma mansoni to praziquantel: is there a problem? Trans R Soc Trop Med Hyg 96:465–469

    Article  CAS  PubMed  Google Scholar 

  • Doenhoff MJ, Cioli D, Utzinger J (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21:659–667

    Article  CAS  PubMed  Google Scholar 

  • Engels D, Wang LY, Palmer KL (2005) Control of schistosomiasis in China. Acta Trop 96:67–68

    Article  PubMed  Google Scholar 

  • Fallon PG, Doenhoff MJ (1994) Drug-resistant schistosomiasis: resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. Am J Trop Med Hyg 51:83–88

    CAS  PubMed  Google Scholar 

  • Fallon PG, Sturrock RF, Niang AC, Doenhoff MJ (1995) Diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni. Am J Trop Med Hyg 53:61–62

    CAS  PubMed  Google Scholar 

  • Fallon PG, Tao LF, Ismail MM, Bennett JL (1996) Schistosome resistance to praziquantel: fact or artifact? Parasitol Today 12:316–320

    Article  CAS  PubMed  Google Scholar 

  • Greenberg RM (2005) Are Ca2+ channels targets of praziquantel action? Int J Parasitol 35:1–9

    Article  CAS  PubMed  Google Scholar 

  • Greenberg RM (2013) New approaches for understanding mechanisms of drug resistance in schistosomes. Parasitology 140:1534–1546

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Harnett W (1988) The anthelmintic action of praziquantel. Parasitol Today 4:144–146

    Article  CAS  PubMed  Google Scholar 

  • Hommel M (2008) The future of artemisinins: natural, synthetic or recombinant? J Biol 7:38

    Article  PubMed Central  PubMed  Google Scholar 

  • Hua HY, Liang YS, Zhang Y, Wei JF, Guo HX (2010) The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China. Parasitol Res 107:873–878

    Article  PubMed  Google Scholar 

  • Ismail M, Metwally A, Farghaly A, Bruce J, Tao LF, Bennett JL (1996) Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel. Am J Trop Med Hyg 55:214–218

    CAS  PubMed  Google Scholar 

  • Ismail M, Botros S, Metwally A, William S, Farghally A, Tao LF, Day TA, Bennett JL (1999) Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers. Am J Trop Med Hyg 60:932–935

    CAS  PubMed  Google Scholar 

  • Keiser J, Utzinger J (2012) Antimalarials in the treatment of schistosomiasis. Curr Pharm Des 18:3531–3538

    CAS  PubMed  Google Scholar 

  • Köhler P (2001) The biochemical basis of anthelmintic action and resistance. Int J Parasitol 31:336–345

    Article  PubMed  Google Scholar 

  • Li S, Wu L, Liu Z, Hu L, Xu P, Xuan Y, Liu Y, Liu X, Fan J (1996) Studies on prophylactic effect of artesunate on schistosomiasis japonica. Chin Med J (Engl) 109:848–853

    CAS  Google Scholar 

  • Li YS, Chen HG, He HB, Hou XY, Ellis M, McManus DP (2005) A double-blind field trial on the effects of artemether on Schistosoma japonicum infection in a highly endemic focus in southern China. Acta Trop 96:184–190

    Article  CAS  PubMed  Google Scholar 

  • Li SZ, Luz A, Wang XH, Xu LL, Wang Q, Qian YJ, Wu XH, Guo JG, Xia G, Wang LY, Zhou XN (2009) Schistosomiasis in China: acute infections during 2005-2008. Chin Med J (Engl) 122:1009–1014

    Google Scholar 

  • Li HJ, Liang YS, Dai JR, Wang W, Qu GL, Li YZ, Xing YT, Tao YH, Qian K, Jia Y, Yang ZK, Wei JY (2011) Studies on resistance of Schistosoma to praziquantel XIV experimental comparison of susceptibility to praziquantel between PZQ-resistant isolates and PZQ-susceptible isolates of Schistosoma japonicum in stages of adult worms, miracidia and cercariae. Chin J Schisto Control 23:611–619

    CAS  Google Scholar 

  • Liang YS, Dai JR, Ning A, Yu DB, Xu XJ, Zhu YC, Coles GC (2001) Susceptibility of Schistosoma japonicum to praziquantel in China. Trop Med Int Health 6:707–714

    Article  CAS  PubMed  Google Scholar 

  • Liang YS, Li HJ, Dai JR et al (2011) Studies on resistance of Schistosoma to praziquantel XIII resistance of Schistosoma japonicum to praziquantel is experimentally induced in laboratory. Chin J Schisto Control 23:605–610

    CAS  Google Scholar 

  • Liu R, Dong HF, Guo Y, Zhao QP, Jiang MS (2011) Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis. Parasitol Vectors 4:201

    Article  CAS  Google Scholar 

  • Melman SD, Steinauer ML, Cunningham C, Kubatko LS, Mwangi IN, Wynn NB, Mutuku MW, Karanja DM, Colley DG, Black CL, Secor WE, Mkoji GM, Loker ES (2009) Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Negl Trop Dis 3:e504

    Article  PubMed Central  PubMed  Google Scholar 

  • Meshnick SR (2002) Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol 32:1655–1660

    Article  CAS  PubMed  Google Scholar 

  • Pérez del Villar L, Burguillo FJ, López-Abán J, Muro A (2012) Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PLoS One 7:e45867

    Article  PubMed Central  PubMed  Google Scholar 

  • Prociv P (1997) A case of refractory schistosomiasis. Med J Aust 166:568

    CAS  PubMed  Google Scholar 

  • Ru WW, Liang YS, Dai JR, Li HJ, Xu YL, Zhu YC, Xu M (2006) Studies on effect of artesunate against Schistosoma japonicum. I Susceptibility of different developmental stages of worms in mice to artesunate. Chin J Schisto Control 18:161–164

    Google Scholar 

  • Seto EY, Wong BK, Lu D, Zhong B (2011) Human schistosomiasis resistance to praziquantel in China: should we be worried? Am J Trop Med Hyg 85:74–82

    Article  CAS  PubMed  Google Scholar 

  • Silva IM, Thiengo R, Conceição MJ, Rey L, Lenzi HL, Pereira Filho E, Ribeiro PC (2005) Therapeutic failure of praziquantel in the treatment of Schistosoma haematobium infection in Brazilians returning from Africa. Mem Inst Oswaldo Cruz 100:445–449

    PubMed  Google Scholar 

  • Spear RC, Seto EY, Carlton EJ, Liang S, Remais JV, Zhong B, Qiu D (2011) The challenge of effective surveillance in moving from low transmission to elimination of schistosomiasis in China. Int J Parasitol 41:1243–1247

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6:411–425

    Article  PubMed  Google Scholar 

  • Stelma FF, Talla I, Sow S, Kongs A, Niang M, Polman K, Deelder AM, Gryseels B (1995) Efficacy and side effects of praziquantel in an epidemic focus of Schistosoma mansoni. Am J Trop Med Hyg 53:167–170

    CAS  PubMed  Google Scholar 

  • Stelma FF, Sall S, Daff B, Sow S, Niang M, Gryseels B (1997) Oxamniquine cures Schistosoma mansoni infection in a focus in which cure rates with praziquantel are unusually low. J Infect Dis 176:304–307

    Article  CAS  PubMed  Google Scholar 

  • Tchuem-Tchuenté LA, Southgate VR, Mbaye A, Engels D, Gryseels B (2001) The efficacy of praziquantel against Schistosoma mansoni infection in Ndombo, northern Senegal. Trans R Soc Trop Med Hyg 95:65–66

    Article  PubMed  Google Scholar 

  • Tu YY (2011) The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med 2011(17):1217–1220

    Article  Google Scholar 

  • Utzinger J, Xiao S, N’Goran EK, Bergquist R, Tanner M (2001) The potential of artemether for the control of schistosomiasis. Int J Parasitol 31:1549–1562

    Article  CAS  PubMed  Google Scholar 

  • Utzinger J, Zhou XN, Chen MG, Bergquist R (2005) Conquering schistosomiasis in China: the long march. Acta Trop 96:69–96

    Article  PubMed  Google Scholar 

  • Utzinger J, Bergquist R, Olveda R, Zhou XN (2010) Important helminth infections in Southeast Asia diversity, potential for control and prospects for elimination. Adv Parasitol 72:1–30

    Article  PubMed  Google Scholar 

  • Wang LD, Utzinger J, Zhou XN (2008) Schistosomiasis control: experiences and lessons from China. Lancet 372:1793–1795

    Article  PubMed  Google Scholar 

  • Wang LD, Chen HG, Guo JG, Zeng XJ, Hong XL, Xiong JJ, Wu XH, Wang XH, Wang LY, Xia G, Hao Y, Chin DP, Zhou XN (2009a) A strategy to control transmission of Schistosoma japonicum in China. N Engl J Med 360:121–128

    Article  CAS  PubMed  Google Scholar 

  • Wang LD, Guo JG, Wu XH, Chen HG, Wang TP, Zhu SP, Zhang ZH, Steinmann P, Yang GJ, Wang SP, Wu ZD, Wang LY, Hao Y, Bergquist R, Utzinger J, Zhou XN (2009b) China’s new strategy to block Schistosoma japonicum transmission: experiences and impact beyond schistosomiasis. Trop Med Int Health 14:1475–1483

    Article  PubMed  Google Scholar 

  • Wang W, Dai JR, Li HJ, Shen XH, Liang YS (2010) Is there reduced susceptibility to praziquantel in Schistosoma japonicum? Evidence from China. Parasitology 137:1905–1912

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Dai JR, Li HJ, Shen XH, Liang YS (2012a) The sensitivity of Schistosoma japonicum to praziquantel: a field evaluation in areas with low endemicity of China. Am J Trop Med Hyg 86:834–836

    Article  PubMed  Google Scholar 

  • Wang W, Wang L, Liang YS (2012b) Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol Res 111:1871–1877

    Article  PubMed  Google Scholar 

  • Wang W, Li HJ, Qu GL, Xing YT, Yang ZK, Dai JR, Liang YS (2013) Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum? Parasitol Res, in press

  • Webster HK, Lehnert EK (1994) Chemistry of artemisinin: an overview. Trans R Soc Trop Med Hyg 88:S27–S29

    Article  PubMed  Google Scholar 

  • Wu W, Huang Y (2013) Application of praziquantel in schistosomiasis japonica control strategies in China. Parasitol Res 112:909–915

    Article  PubMed  Google Scholar 

  • Wu W, Wang W, Huang YX (2011) New insight into praziquantel against various developmental stages of schistosomes. Parasitol Res 109:1501–1507

    Article  PubMed  Google Scholar 

  • Xiao SH (2005) Development of antischistosomal drugs in China, with particular consideration to praziquantel and the artemisinins. Acta Trop 96:153–167

    Article  CAS  PubMed  Google Scholar 

  • Xiao SH, Shi Z, Zhuo S, Wang C, Zhang Z, Chu B, Zheng J, Chen M (1995) Field studies on preventive effect of artemether against infection with Schistosoma japonicum. Chin J Parasitol Parasitol Dis 13:170–173

    CAS  Google Scholar 

  • Xiao SH, Booth M, Tanner M (2000) The prophylactic effects of artemether against Schistosoma japonicum infections. Parasitol Today 16:122–126

    Article  CAS  PubMed  Google Scholar 

  • Xiao SH, Tanner M, N’Goran EK, Utzinger J, Chollet J, Bergquist R, Chen M, Zheng J (2002) Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia. Acta Trop 82:175–181

    Article  CAS  PubMed  Google Scholar 

  • Xiao SH, Keiser J, Chen MG, Tanner M, Utzinger J (2010) Research and development of antischistosomal drugs in the People’s Republic of China: a 60-year review. Adv Parasitol 73:231–295

    Article  PubMed  Google Scholar 

  • Xu M, Zhang S, Li S, Wang T, Chen J, Ou N, Fang G, Wang Q, Li J, Zhang X (1999) Field application of oral artesunate for preventing Schistosoma japonicum infection. Chin J Parasitol Parasitol Dis 17:241–243

    CAS  Google Scholar 

  • Yu DB, Li Y, Sleigh AC, Yu XL, Li YS, Wei WY, Liang YS, McManus DP (2001) Efficacy of praziquantel against Schistosoma japonicum: field evaluation in an area with repeated chemotherapy compared with a newly identified endemic focus in Hunan, China. Trans R Soc Trop Med Hyg 95:537–541

    Article  CAS  PubMed  Google Scholar 

  • Yuan H, Jiang Q, Zhao G, He N (2002) Achievements of schistosomiasis control in China. Mem Inst Oswaldo Cruz 97:187–189

    Article  PubMed  Google Scholar 

  • Zhang Z, Jiang Q (2011) Schistosomiasis elimination. Lancet Infect Dis 11:345

    Article  PubMed  Google Scholar 

  • Zhao GM, Zhao Q, Jiang QW, Chen XY, Wang LY, Yuan HC (2005) Surveillance for schistosomiasis japonica in China from 2000 to 2003. Acta Trop 96:288–295

    Article  PubMed  Google Scholar 

  • Zhou XN, Wang LY, Chen MG, Wu XH, Jiang QW, Chen XY, Zheng J, Utzinger J (2005) The public health significance and control of schistosomiasis in China—then and now. Acta Trop 96:97–105

    Article  PubMed  Google Scholar 

  • Zhou XN, Guo JG, Wu XH, Jiang QW, Zheng J, Dang H, Wang XH, Xu J, Zhu HQ, Wu GL, Li YS, Xu XJ, Chen HG, Wang TP, Zhu YC, Qiu DC, Dong XQ, Zhao GM, Zhang SJ, Zhao NQ, Xia G, Wang LY, Zhang SQ, Lin DD, Chen MG, Hao Y (2007a) Epidemiology of schistosomiasis in the People’s Republic of China, 2004. Emerg Infect Dis 13:1470–1476

    Article  PubMed  Google Scholar 

  • Zhou YB, Zhao GM, Jiang QW (2007b) Effects of the praziquantel-based control of schistosomiasis japonica in China. Ann Trop Med Parasitol 101:695–703

    Article  CAS  PubMed  Google Scholar 

  • Zhou XN, Bergquist R, Leonardo L, Yang GJ, Yang K, Sudomo M, Olveda R (2010) Schistosomiasis japonica control and research needs. Adv Parasitol 72:145–178

    Article  PubMed  Google Scholar 

  • Zhou YB, Zheng HM, Jiang QW (2011) A diagnostic challenge for schistosomiasis japonica in China: consequences on praziquantel-based morbidity control. Parasitol Vectors 4:194

    Article  Google Scholar 

  • Zhou YB, Liang S, Jiang QW (2012) Factors impacting on progress towards elimination of transmission of schistosomiasis japonica in China. Parasitol Vectors 5:275

    Article  Google Scholar 

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Acknowledgments

We would like to thank Drs. Zhen-Kun Yang, Ke Qian, and Yong-Liang Xu for their kind help during animal experiments. Thanks are also addressed to the anonymous referees for their comments on the manuscript. This study was funded by the National Science and Technology Pillar Program of China (2009BAI78B06), the Program of Scientific and Technological Development of Nanjing Medical University (2011njmu204), the Major Collaborating Program of Wuxi Hospital Management Center (YGZX1115) and the Jiangsu Provincial Government Overseas Scholarship.

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Authors and Affiliations

  1. Jiangsu Institute of Parasitic Diseases, 117 Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, 214064, People’s Republic of China

    Wei Wang, Guo-Li Qu, Yi-Li Qian, Jian-Rong Dai & You-Sheng Liang

  2. Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, 117 Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, 214064, People’s Republic of China

    Wei Wang, Guo-Li Qu, Yi-Li Qian, Jian-Rong Dai & You-Sheng Liang

  3. Wuxi Children’s Hospital, 299 Qingyang Road, Wuxi City, Jiangsu Province, 214194, People’s Republic of China

    Tian-Yu Li

  4. Department of Hepatobiliary Surgery, Wuxi No. 2 Hospital Affiliated to Nanjing Medical University, 68 Zhongshan Road, Wuxi City, Jiangsu Province, 214002, People’s Republic of China

    Yuan Ji

  5. Department of Laboratory Medicine, The Affiliated Hospital of Weifang Medical University, 465 Yuhe Road, Kuiwen District, Weifang City, Shandong Province, 261031, People’s Republic of China

    Hong-Jun Li

  6. Jiangsu Institute of Parasitic Diseases and Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, 117 Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, 214064, People’s Republic of China

    You-Sheng Liang

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  1. Wei Wang
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  2. Tian-Yu Li
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Correspondence to You-Sheng Liang.

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Wei Wang, Tian-Yu Li, and Yuan Ji contributed equally to this work.

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Wang, W., Li, TY., Ji, Y. et al. Efficacy of artemether and artesunate in mice infected with praziquantel non-susceptible isolate of Schistosoma japonicum . Parasitol Res 113, 925–931 (2014). https://doi.org/10.1007/s00436-013-3724-5

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