Infect Chemother.  2013 Mar;45(1):32-43.

Praziquantel Treatment in Trematode and Cestode Infections: An Update

• Chai JY

Abstract

Status and emerging issues in the use of praziquantel for treatment of human trematode and cestode infections are briefly reviewed. Since praziquantel was first introduced as a broadspectrum anthelmintic in 1975, innumerable articles describing its successful use in the treatment of the majority of human-infecting trematodes and cestodes have been published. The target trematode and cestode diseases include schistosomiasis, clonorchiasis and opisthorchiasis, paragonimiasis, heterophyidiasis, echinostomiasis, fasciolopsiasis, neodiplostomiasis, gymnophalloidiasis, taeniases, diphyllobothriasis, hymenolepiasis, and cysticercosis. However, Fasciola hepatica and Fasciola gigantica infections are refractory to praziquantel, for which triclabendazole, an alternative drug, is necessary. In addition, larval cestode infections, particularly hydatid disease and sparganosis, are not successfully treated by praziquantel. The precise mechanism of action of praziquantel is still poorly understood. There are also emerging problems with praziquantel treatment, which include the appearance of drug resistance in the treatment of Schistosoma mansoni and possibly Schistosoma japonicum, along with allergic or hypersensitivity reactions against praziquantel treatment. To cope with and overcome these problems, combined use of drugs, i.e., praziquantel and other newly introduced compounds such as triclabendazole, artemisinins, and tribendimidine, is being tried.

Keyword

Praziquantel; Trematode; Cestode; Chemotherapy; Adverse reaction; Combined therapy

MeSH Terms

Artemisinins
Benzimidazoles
Cestoda
Cestode Infections
Clonorchiasis
Cysticercosis
Diphyllobothriasis
Drug Resistance
Echinostomiasis
Fasciola
Fasciola hepatica
Humans
Hymenolepiasis
Hypersensitivity
Opisthorchiasis
Paragonimiasis
Phenylenediamines
Phosphatidylethanolamines
Praziquantel
Schistosoma japonicum
Schistosoma mansoni
Schistosomiasis
Sparganosis
Taenia
Taeniasis
Trematode Infections
Artemisinins
Benzimidazoles
Phenylenediamines
Phosphatidylethanolamines
Praziquantel

Reference

1. Andrews P, Thomas H, Pohlke R, Seubert J. Praziquantel. Med Res Rev. 1983. 3:147–200.

2. Lee SH, Chai JY. Praziquantel in the treatment of trematode and cestode infections. J Korean Soc Chemother. 1985. 3:95–118.

3. Keiser J, Utzinger J. Chemotherapy for major foodborne trematodes: a review. Expert Opin Pharmacother. 2004. 5:1711–1726.

4. Chan JD, Zarowiecki M, Marchant JS. Ca(2+) channels and Praziquantel: A view from the free world. Parasitol Int. 2012. pii: S1383-5769(12)00161-4.

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

6. Tinga N, De N, Vien HV, Chau L, Toan ND, Kager PA, Vries PJ. Little effect of praziquantel or artemisinin on clonorchiasis in Northern Vietnam. A pilot study. Trop Med Int Health. 1999. 4:814–818.

7. Kyung SY, Cho YK, Kim YJ, Park JW, Jeong SH, Lee JI, Sung YM, Lee SP. A paragonimiasis patient with allergic reaction to praziquantel and resistance to triclabendazole: successful treatment after desensitization to praziquantel. Korean J Parasitol. 2011. 49:73–77.

8. Lee JM, Lim HS, Hong ST. Hypersensitive reaction to praziquantel in a clonorchiasis patient. Korean J Parasitol. 2011. 49:273–275.

9. Pax R, Bennett JL, Fetterer R. A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Naunyn Schmiedebergs Arch Pharmacol. 1978. 304:309–315.

10. Becker B, Mehlhorn H, Andrews P, Thomas H, Eckert J. Light and electron microscopic studies on the effect of praziquantel on Schistosoma mansoni, Dicrocoelium dendriticum, and Fasciola hepatica (Trematoda) in vitro. Z Parasitenkd. 1980. 63:113–128.

11. Mehlhorn H, Becker B, Andrews P, Thomas H, Frenkel JK. In vivo and in vitro experiments on the effects of praziquantel on Schistosoma mansoni. Arzneimittelforschung. 1981. 31:544–554.

12. Mehlhorn H, Kojima S, Rim HJ, Ruenwongsa P, Andrews P, Thomas H, Bunnag B. Ultrastructural investigations on the effects of praziquantel on human trematodes from Asia: Clonorchis sinensis, Metagonimus yokogawai, Opisthorchis viverrini, Paragonimus westermani and Schistosoma japonicum. Arzneimittelforschung. 1983. 33:91–98.

13. Lee SH. In vitro effects of praziquantel on Fibricola seoulensis. Seoul J Med. 1985. 26:41–52.

14. Rim HJ, Park HY, Kim SJ, Lee SH. Morphological observations on Clonorchis sinensis obtained from rats treated with praziquantel. Korean J Parasitol. 1980. 18:192–198.

15. Seo BS, Cha IJ, Chai JY, Hong SJ, Lee SH. Studies on intestinal trematodes in Korea XIX. Light and scanning electron microscopy of Fibricola seoulensis collected from albino rats treated with praziquantel. Korean J Parasitol. 1985. 23:47–57.

16. Lee SH, Park HJ, Hong SJ, Chai JY, Hong ST. In vitro effect of praziquantel on Paragonimus westermani by light and scanning electron microscopic observation. Korean J Parasitol. 1987. 25:24–36.

17. Chiu HS, Kim SJ, Rim HJ. Electron-microscopic studies on the effect of praziquantel to Paragonimus westermani. Korea Univ Med J. 1982. 19:617–630.

18. Hörchner F, Langnes A, Oguz T. Die Wirkung von Mebendazole und Praziquantel auf larvale Taenienstadien bei Maus, Kaninchen und Schwein. Tropenmed Parasitol. 1977. 28:44–50.

19. Thomas H, Gönnert R. The efficay of praziquantel against cestodes in animals. Z Parasitenkd. 1977. 52:117–127.

20. Becker B, Mehlhorn H, Andrews P, Thomas H. Scanning and transmission electron microscope studies on the efficacy of praziquantel on Hymenolepis nana (Cestoda) in vitro. Z Parasitenkd. 1980. 61:121–133.

21. Becker B, Mehlhorn H, Andrews P, Thomas H. Ultrastructural investigations on the effect of praziquantel on the tegument of five species of cestodes. Z Parasitenkd. 1981. 64:257–269.

22. Bylund G, Bång B, Wikgren K. Tests with a new compound (Praziquantel) against Diphyllobothrium latum. J Helminthol. 1977. 51:115–119.

23. Thomas H, Gönnert R. The efficacy of praziquantel against experimental cysticercosis and hydatidosis (author's transl). Z Parasitenkd. 1978. 55:165–179.

24. Geary TG, Woo K, McCarthy JS, Mackenzie CD, Horton J, Prichard RK, de Silva NR, Olliaro PL, Lazdins-Helds JK, Engels DA, Bundy DA. Unresolved issues in anthelmintic pharmacology for helminthiases of humans. Int J Parasitol. 2010. 40:1–13.

25. Vokřál I, Jirásko R, Jedličková V, Bártíková H, Skálová L, Lamka J, Holčapek M, Szotáková B. The inability of tapeworm Hymenolepis diminuta and fluke Dicrocoelium dendriticum to metabolize praziquantel. Vet Parasitol. 2012. 185:168–174.

26. Jeziorski MC, Greenberg RM. Voltage-gated calcium channel subunits from platyhelminths: potential role in praziquantel action. Int J Parasitol. 2006. 36:625–632.

27. Angelucci F, Basso A, Bellelli A, Brunori M, Pica Mattoccia L, Valle C. The anti-schistosomal drug praziquantel is an adenosine antagonist. Parasitology. 2007. 134:1215–1221.

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

29. Coulibaly JT, N'gbesso YK, Knopp S, Keiser J, N'Goran EK, Utzinger J. Efficacy and safety of praziquantel in preschool-aged children in an area co-endemic for Schistosoma mansoni and S. haematobium. PLoS Negl Trop Dis. 2012. 6:e1917.

30. Lovis L, Mak TK, Phongluxa K, Ayé Soukhathammavong P, Vonghachack Y, Keiser J, Vounatsou P, Tanner M, Hatz C, Utzinger J, Odermatt P, Akkhavong K. Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial. PLoS Negl Trop Dis. 2012. 6:e1726.

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

32. Lee SH. Large scale treatment of Clonorchis sinensis infections with praziquantel under field conditions. Arzneimittelforschung. 1984. 34:1227–1230.

33. Bunnag D, Harinasuta T. Studies on the chemotherapy of human opisthorchiasis: III. Minimum effective dose of praziquantel. Southeast Asian J Trop Med Public Health. 1981. 12:413–417.

34. Zavoĭkin VD, Zelia OP, Bronshteĭn AM, Sokerina OA, Iarotskiĭ LS, Firsova RA, Mikhaĭlov MM, Gerasimov IV. The procedure for the wide use of praziquantel in a complex of measures to control opisthorchiasis. 1. The tolerance and efficacy of different doses of biltricide during outpatient use in foci. Med Parazitol (Mosk). 1994. (3):24–27.

35. Rim HJ, Yoo KS. Chemotherapeutc effect of praziquantel (Embay 8440) in the treatment of clonorchiasis sinensis. Korea Univ Med J. 1979. 16:459–470.

36. Wegner DH. The profile of the trematodicidal compound praziquantel. Arzneimittelforschung. 1984. 34:1132–1136.

37. Farag HF, Ragab M, Salem A, Saden K. A short note on praziquantel in human fascioliasis. J Trop Med Hyg. 1986. 89:79–80.

38. Farid Z, Kamal M, Mansour N. Praziquantel and Fasciola hepatica infection. Trans R Soc Trop Med Hyg. 1989. 83:813.

39. Keiser J, Engels D, Büscher G, Utzinger J. Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opin Investig Drugs. 2005. 14:1513–1526.

40. Rim HJ, Chang YS. Chemotherapeutic effect of niclofolan and praziquantel in the treatment of paragonimiasis. Korea Univ Med J. 1980. 17:113–128.

41. Udonsi JK. Clinical field trials of praziquantel in pulmonary paragonimiasis due to Paragonimus uterobilateralis in endemic populations of the Igwun Basin, Nigeria. Trop Med Parasitol. 1989. 40:65–68.

42. Bunnag D, Radomyos P, Harinasuta T. Field trial on the treatment of fasciolopsiasis with praziquantel. Southeast Asian J Trop Med Public Health. 1983. 14:216–219.

43. Hong ST, Cho TK, Hong SJ, Chai JY, Lee SH, Seo BS. Fifteen human cases of Fibricola seoulensis infection in Korea. Korean J Parasitol. 1984. 22:61–65.

44. Lee SK, Chung NS, Ko IH, Sohn WM, Hong ST, Chai JY, Lee SH. An epidemiological survey of Echinostoma hortense infection in Chongsong-gun, Kyongbuk Province. Korean J Parasitol. 1988. 26:199–206.

45. Lee SH, Chai JY, Lee HJ, Hong ST, Yu JR, Sohn WM, Kho WG, Choi MH, Lim YJ. High prevalence of Gymnophalloides seoi infection in a village on a southwestern island of the Republic of Korea. Am J Trop Med Hyg. 1994. 51:281–285.

46. Chai JY, Nam HK, Kook J, Lee SH. The first discovery of an endemic focus of Heterophyes nocens (Heterophyidae) infection in Korea. Korean J Parasitol. 1994. 32:157–161.

47. Chai JY, Han ET, Park YK, Guk SM, Lee SH. Acanthoparyphium tyosenense: the discovery of human infection and identification of its source. J Parasitol. 2001. 87:794–800.

48. Rim HJ, Park SB, Lee JS, Joo KH. Therapeutic effects of praziquantel (Embay 8440) against Taenia solium infection. Korean J Parasitol. 1979. 17:67–72.

49. Chai JY, Sohn WM, Hong SJ, Lee SH, Seo BS. Anthelmintic effect of praziquantel (Cestocide@) in the treatment of Taenia saginata and Diphyllobothrium latum infection. J Korean Soc Chemother. 1985. 3:181–184.

50. Schenone H, Galdames M, Rivadeneira A, Morales E, Hoffmann MT, Asalgado N, Meneses G, Mora MV, Cabrera G. Treatment of Hymenolepis nana infection in children by a single oral dose of praziquantel (Embay 8440). Bol Chil Parasitol. 1977. 32:11–13.

51. Rim HJ, Park CY, Lee JS, Joo KH, Lyu KS. Therapeutic effects of praziquantel (Embay 8440) against Hymenolepis nana infection. Korean J Parasitol. 1978. 16:82–87.

52. Schenone H. Praziquantel in the treatment of Hymenolepis nana infection in children. Am J Trop Med Hyg. 1980. 29:320–321.

53. Rim HH. Treatment of Hymenolepis nana infection. Postgrad Dr Asia. 1981. 67–72.

54. Park CY, Joo KH, Rim HJ. Clinical observation on the chemotherapy of cerebral cysticercosis. Korea Univ Med J. 1982. 19:595–616.

55. Sotelo J, Escobedo F, Rodriguez-Carbajal J, Torres B, Rubio-Donnadieu F. Therapy of parenchymal brain cysticercosis with praziquantel. New Eng J Med. 1984. 310:1001–1007.

56. del Brutto OH, Sotelo J. Albendazole therapy for subarachnoid and ventricular cysticercosis. Case report. J Neurosurg. 1990. 72:816–817.

57. Takayanagui OM, Odashima NS, Bonato PS, Lima JE, Lanchote VL. Medical management of neurocysticercosis. Expert Opin Pharmacother. 2011. 12:2845–2856.

58. Santos R, Chavarria M, Aguirre AE. Failure of medical treatment in two cases of intraocular cysticerscosis. Am J Ophthalmol. 1984. 97:249–250.

59. Chai JY, Yu JR, Lee SH, Kim SI, Cho SY. Ineffectiveness of praziquantel treatment for human sparganosis: a case report. Seoul J Med. 1988. 29:397–399.

60. Sohn WM, Hong ST, Chai JY, Lee SH. Infectivity of the sparganum treated by praziquantel, gamma-irradiation and mechanical cutting. Korean J Parasitol. 1993. 31:135–139.

61. Tanaka S, Maruyama H, Ishiwata K, Nawa Y. A case of pleural sparganosis. Parasitol Int. 1997. 46:73–75.

62. Ishii H, Mukae H, Inoue Y, Kadota JI, Kohno S, Uchiyama F, Nawa Y. A rare case of eosinophilic pleuritis due to sparganosis. Intern Med. 2001. 40:783–785.

63. Lee JH, Kim GH, Kim SM, Lee SY, Lee WY, Bae JW, Shin KS, Hwang KK, Kim DW, Cho MC. A case of sparganosis that presented as a recurrent pericardial effusion. Korean Circ J. 2011. 41:38–42.

64. Haralabidis S, Diakou A, Frydas S, Papadopoulos E, Mylonas A, Patsias A, Roilides E, Giannoulis E. Long-term evaluation of patients with hydatidosis treated with albendazole and praziquantel. Int J Immunopathol Pharmacol. 2008. 21:429–435.

65. Tekin R, Kara AF, Tekin RC, Cimen D. Cardiac hydatid cyst case recovered with medical treatment. Anadolu Kardiyol Derg. 2011. 11:650–651.

66. Shaw JG, Aggarwal N, Acosta LP, Jiz MA, Wu HW, Leenstra T, Coutinho HM, Olveda RM, Kurtis JD, McGarvey ST, Friedman JF. Reduction in hookworm infection after praziquantel treatment among children and young adults in Leyte, the Philippines. Am J Trop Med Hyg. 2010. 83:416–421.

67. Mehlhorn H, Frenkel JK, Andrews P, Thomas H. Light and electron microscopic studies on Schistosoma mansoni granulomas of mouse livers following treatment with praziquantel. Tropenmed Parasitol. 1982. 33:229–239.

68. Cheever AW, Deb S. Persistence of hepatic fibrosis and tissue eggs following treatment of Schistosoma japonicum infected mice. Am J Trop Med Hyg. 1989. 40:620–628.

69. Cheever AW, Macedonia JG, Deb S, Cheever EA, Mosimann JE. Persistence of eggs and hepatic fibrosis after treatment of Schistosoma mansoni-infected mice. Am J Trop Med Hyg. 1992. 46:752–758.

70. Lee SH, Chai JY, Yang EC, Yun CK, Hong ST, Lee JB. Observation of liver pathology after praziquantel treatment in experimental Clonorchis sinensis infection in guinea pigs. Seoul J Med. 1988. 29:253–262.

71. Lee SH, Hong ST, Kim CS, Sohn WM, Chai JY, Lee YS. Histopathological changes of the liver after praziquantel treatment in Clonorchis sinensis infected rabbits. Korean J Parasitol. 1987. 25:110–122.

72. Lee SH, Kim SY, Han YC, Lee YS, Hong ST, Sohn WM, Chai JY. Effect of praziquantel treatment on pulmonary lesions of rats infected with Paragonimus iloktsuenensis. Korean J Parasitol. 1989. 27:119–130.

73. Lee SH, Kim BI, Hong ST, Sohn WM, Chai JY. Observation of mucosal pathology after praziquantel treatment in experimental Fibricola seoulensis infection in rats. Korean J Parasitol. 1989. 27:35–40.

74. Gustowska L, Pawlowski Z. Histopathological and histoenzymatic studies on experimental Taenia saginata cysticercosis. Vet Parasitol. 1981. 8:211–218.

75. Hong ST, Lee SH, Lee SJ, Kho WG, Lee M, Chung BS, Seo M, Choi MH. Sustained-release praziquantel tablet: pharmacokinetics and the treatment of clonorchiasis in beagle dogs. Parasitol Res. 2003. 91:316–320.

76. Lei L, Cheng L, Hou J, Guo S, Zhu C, Shi Y, Jiang Y, Lin J. Prevention of Schistosoma japonicum infection in mice with long-acting praziquantel implants. Exp Parasitol. 2012. 131:442–447.

77. Rim HJ. The current pathobiology and chemotherapy of clonorchiasis. Korean J Parasitol. 1986. 24:Suppl. 1–141.

78. Huang SW. A clinical approach to a patient with praziquantel hypersensitivity. J Allergy Clin Immunol. 1992. 90:867.

79. Shen C, Choi MH, Bae YM, Yu G, Wang S, Hong ST. A case of anaphylactic reaction to praziquantel treatment. Am J Trop Med Hyg. 2007. 76:603–605.

80. Adam I, Elwasila ET, Homeida M. Is praziquantel therapy safe during pregnancy? Trans R Soc Trop Med Hyg. 2004. 98:540–543.

81. Adam I, Elwasila E, Homeida M. Praziquantel for the treatment of schistosomiasis mansoni during pregnancy? Ann Trop Med Parasitol. 2005. 99:37–40.

82. Liang YS, Coles GC, Dai JR, Zhu YC, Doenhoff MJ. Adult worm tegumental damage and egg-granulomas in praziquantel-resistant and -susceptible Schistosoma mansoni treated in vivo. J Helminthol. 2002. 76:327–333.

83. Liang YS, Wang W, Dai JR, Li HJ, Tao YH, Zhang JF, Li W, Zhu YC, Coles GC, Doenhoff MJ. Susceptibility to praziquantel of male and female cercariae of praziquantel-resistant and susceptible isolates of Schistosoma mansoni. J Helminthol. 2010. 84:202–207.

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

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

86. Couto FF, Coelho PM, Araújo N, Kusel JR, Katz N, Jannotti-Passos LK, Mattos AC. Schistosoma mansoni: a method for inducing resistance to praziquantel using infected Biomphalaria glabrata snails. Mem Inst Oswaldo Cruz. 2011. 106:153–157.

87. Fallon PG, Sturrock RF, Niang CM, Doenhoff MJ. Short report: diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni. Am J Trop Med Hyg. 1995. 53:61–62.

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

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

90. Keiser J, Utzinger J. The drugs we have and the drugs we need against major helminth infections. Adv Parasitol. 2010. 73:197–230.

91. Lateef M, Zargar SA, Khan AR, Nazir M, Shoukat A. Successful treatment of niclosamide- and praziquantel-resistant beef tapeworm infections with nitazoxanide. Int J Infect Dis. 2008. 12:80–82.

92. Rim HJ, Chu DS, Lee JS, Joo KH, Won CY. Anthelmintic effects of various drugs against metagonimiasis. Korean J Parasitol. 1978. 16:117–122.

93. Lee SH, Chai JY, Hong SJ, Jun YS, Seo BS. Anthelminti effect of praziquantel (Distocide®) against Metagonimus yokogawai infection. J Korean Soc Chemother. 1984. 2:167–171.

94. el-Hawy AM, Safwat M, el-Nasr SS, Abdel Rahman MM. The cure rates of patients infected with heterophyiasis and treated with praziquantel versus niclosamide. J Egypt Soc Parasitol. 1988. 18:437–442.

95. Ata AA, el-Khashab MN, Mourad AA, Soliman HM. The effect of praziquantel on Heterophyes heterophyes, Hymenolepis nana and Fasciola sp. infections. J Egypt Soc Parasitol. 1988. 18:243–246.

96. Pungpak S, Radomyos P, Radomyos B, Schelp FP, Jongsulsuntigul P, Bunnag D. Treatment of Opisthorchis viverrini and intestinal fluke infections with Praziquantel. Southeast Asian J Trop Med Public Health. 1998. 29:246–249.