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Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum?

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Abstract

Praziquantel is currently the only drug of choice for the treatment of human schistosomiases. However, it has been proved that Schistosoma japonicum subjected to drug pressure may develop resistance to praziquantel. To evaluate the efficacy of dihydroartemisinin against praziquantel-resistant S. japonicum, mice infected with a praziquantel-resistant isolate and a praziquantel-susceptible isolate of S. japonicum were treated with dihydroartemisinin at a single oral dose of 300 mg/kg given once on each of 35–36 post-infection days, while infected but untreated mice served as controls. All mice were sacrificed 50 days post-infection, and the worm burden reductions were estimated. Administration of dihydroartemisinin at a single oral dose of 300 mg/kg on each of 35–36 post-infection days reduced total worm burdens of 69.8 % and female worm burdens of 86 % in mice infected with the praziquantel-susceptible isolate, and total worm burdens of 66.1 % and female worm burdens of 85.1 % in mice infected with the praziquantel-resistant isolate (both P values > 0.05). It is concluded that the sensitivity of artemisinin derivative dihydroartemisinin does not reduce in praziquantel-resistant 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 

  • Caffrey CR (2007) Chemotherapy of schistosomiasis: present and future. Curr Opin Chem Biol 11:433–439

    Article  CAS  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 

  • Cioli D, Pica-Mattoccia L, Archer S (1993) Drug resistance in schistosomes. Parasitol Today 9:162–166

    Article  CAS  PubMed  Google Scholar 

  • Cioli D, Pica-Mattoccia L (2003) Praziquantel. Parasitol Res 90:S3–S9

    PubMed  Google Scholar 

  • da Silva SP, Noël F (1995) Time course of the effect of praziquantel on Schistosoma mansoni attachment in vitro: comparison with its effects on worm length and motility. Parasitol Res 81:543–548

    Article  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 

  • 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, McNeice C, Probert AJ, Doenhoff MJ (1994) Quantification of praziquantel-induced damage on the surface of adult Schistosoma mansoni worms: estimation of esterase and alkaline phosphatase activity. Parasitol Res 80:623–625

    Article  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 

  • Fenwick A, Webster JP (2006) Schistosomiasis: challenges for control, treatment and drug resistance. Curr Opin Infect Dis 19:577–582

    Article  PubMed  Google Scholar 

  • Gönnert R, Andrews P (1977) Praziquantel, a new board-spectrum antischistosomal agent. Parasitol Res 52:129–150

    Google Scholar 

  • Harder A, Andrews P, Thomas H (1987) Chlorpromazine, other amphiphilic cationic drugs and praziquantel: effects on carbohydrate metabolism of Schistosoma mansoni. Parasitol Res 73:245–249

    Article  CAS  PubMed  Google Scholar 

  • Harder A (2002) Chemotherapeutic approaches to schistosomes: current knowledge and outlook. Parasitol Res 88:395–397

    Article  CAS  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 

  • Huang YX, Xu YL, Yu CX, Li HJ, Yin XR, Wang TS, Wang W, Liang YS (2011) Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice. Parasitol Res 109:1453–1459

    Article  PubMed  Google Scholar 

  • Ismail MM, Taha SA, Farghaly AM, El-Azony AS (1994) Laboratory induced resistance to praziquantel in experimental schistosomiasis. J Egypt Soc Parasitol 24:685–695

    CAS  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 

  • Lawn SD, Lucas SB, Chiodini PL (2003) Schistosoma mansoni infection: failure of standard treatment with praziquantel in a returned traveller. Trans R Soc Trop Med Hyg 97:100–101

    Article  PubMed  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 (2011a) 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 (in Chinese)

    CAS  Google Scholar 

  • Li HJ, Wang W, Liang YS (2011b) Advances in research of dihydroartemisinin against parasitic diseases. Chin J Schisto Control 23:460–464

    CAS  Google Scholar 

  • Li HJ, Wang W, Li YZ, Qu GL, Xing YT, Tao YH, Wei JY, Dai JR, Liang YS (2011c) Effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum. Parasitol Res 109:515–519

    Article  PubMed  Google Scholar 

  • Li HJ, Wang W, Tao YH, Qu GL, Xing YT, Li YZ, Wei JY, Dai JR, Liang YS (2011d) Dihydroartemisinin-praziquantel combinations and multiple doses of dihydroartemisinin in the treatment of Schistosoma japonicum in experimentally infected mice. Ann Trop Med Parasitol 105:329–333

    Article  PubMed  Google Scholar 

  • Li HJ, Wang W, Qu GL, Tao YH, Xing YT, Li YZ, Wei JY, Dai JR, Liang YS (2011e) In-vivo activity of dihydroartemisinin against Schistosoma japonicum. Ann Trop Med Parasitol 105:181–185

    Article  CAS  PubMed  Google Scholar 

  • Li HJ, Wang W, Qu GL, Li YZ, Tao YH, Xing YT, Wang XT, Dai Y, Wei JY, Dai JR, Coles GC, Liang YS (2012) Effect of the in vivo activity of dihydroartemisinin against Schistosoma mansoni infection in mice. Parasitol Res 110:1727–1732

    Article  PubMed  Google Scholar 

  • Li HJ, Wang W, Li YZ, Qu GL, Xing YT, Qian K, Jia Y, Yang ZK, Qian YL, Dai JR, Liang YS (2013) In vivo activity of dihydroartemisinin against Schistosoma mansoni schistosomula in mice. Southeast Asian J Trop Med Public Health 44:379–387

    PubMed  Google Scholar 

  • Liang YS, Li HJ, Dai JR, Wang W, Qu GL, Tao YH, Xing YT, Li YZ, Qian K, Wei JY (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 (in Chinese)

    CAS  Google Scholar 

  • Ma Y, Lu DM, Lu XJ, Liao L, Hu XS (2004) Activity of dihydroartemisinin against Leishmania donovani both in vitro and vivo. Chin Med J (Engl) 117:1271–1273

    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 

  • Ni X, Chen Y (2001) In vitro study of the anti-pneumocystis carinii effect of arteminsin derivatives. Chin J Tuberc Respir Dis 24:164–167

    CAS  Google Scholar 

  • Ribeiro-dos-Santos G, Verjovski-Almeida S, Leite LC (2006) Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res 99:505–521

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Sarciron ME, Saccharin C, Petavy AF, Peyron F (2000) Effects of artesunate, dihydroartemisinin, and an artesunate-dihydroartemisinin combination against Toxoplasma gondii. Am J Trop Med Hyg 62:73–6

    CAS  PubMed  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 

  • Seubert J, Pohlke R, Loebich F (1977) Synthesis and properties of praziquantel, a novel broad spectrum anthelmintic with excellent activity against schistosomes and cestodes. Experientia 33:1036–1037

    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 Oswald Cruz 100:445–449

    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 

  • Tang ZH, Zhou XO, Gao XZ (2007) Effect of dihydroartemisinin on the ultrastructure of Trichomonas vaginalis trophozoites in vitro. Chin J Parasitol Parasit Dis 25:41–44

    Google Scholar 

  • Tian XF, Shen HE, Li J, Chen Y, Yang ZH, Lu SQ (2010) The effects of dihydroartemisinin on Giardia lamblia morphology and cell cycle in vitro. Parasitol Res 107:369–375

    Article  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 Roy Soc Trop Med Hyg 2001(95):65–66

    Article  Google Scholar 

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

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • WHO (1993) The Control of Schistosomiasis: Second Report of WHO Expert Committee. WHO Technical Report Series No. 830. Geneva, Switzerland.

  • 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 

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

    Article  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

    PubMed  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 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Mrs. Jian-Ying Wei and Mr. Yong-Liang Xu for their kind help during animal experiments. Thanks are also addressed to the two anonymous referees for their comments on the manuscript. This study was funded by the National Science and Technology Pillar Program of China (2009BAI78B06), Jiangsu Department of Health (X200901, X200912 and X201111) and Jiangsu Provincial Scientific Foundation of Preventive Medicine (Y201031).

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The authors declare that they have no competing interests.

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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, Yun-Tian Xing, Zhen-Kun Yang, 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, Yun-Tian Xing, Zhen-Kun Yang, Jian-Rong Dai & You-Sheng Liang

  3. Jiangsu Provincial Key Laboratory of Molecular Biology of Parasites, 117 Yangxiang, Meiyuan, Wuxi City, Jiangsu Province, 214064, People’s Republic of China

    Wei Wang, Guo-Li Qu, Yun-Tian Xing, Zhen-Kun Yang, Jian-Rong Dai & You-Sheng Liang

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

    Hong-Jun Li

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  1. Wei Wang
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Correspondence to You-Sheng Liang.

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Wei Wang and Hong-Jun Li contributed equally to this work

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Wang, W., Li, HJ., Qu, GL. et al. Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum?. Parasitol Res 113, 223–228 (2014). https://doi.org/10.1007/s00436-013-3647-1

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