Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Schistosomiasis—a century searching for chemotherapeutic drugs


Schistosomiasis affects 200 million individuals in underdeveloped and developing regions and is a growing concern for travelers worldwide. There has been evidence of resistance to the praziquantel-based therapy and reports of acute-disease manifestation; therefore, other drugs affecting different stages of the schistosome parasites life cycle and alternative therapeutic regimens should be developed and become accessible. The present review results from a comprehensive search in the scientific literature for substances and compounds tested in the past centennial for schistosomiasis therapy. We gathered over 40 drugs providing information on therapeutic action in humans or animal model, toxicity, susceptible Schistosoma stages, species, etc. The drugs were grouped according to their known metabolic effects on the parasite, whether they are on membrane structure and function, carbohydrate metabolism, protein synthesis and function, or on nucleic acid metabolism. We discuss the current knowledge of drug–target interactions, their mechanism of action and possible therapy combinations. Furthermore, based in the literature and in our own experience with large-scale Schistosoma mansoni genome and transcriptome analyses, we put forward several recently described gene products that are promising target candidates for existing or new drugs.

This is a preview of subscription content, log in to check access.

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.


  1. Abo-Madyan AA, Morsy TA, Motawea SM, Morsy AT (2004) Clinical trial of Mirazid in treatment of human fascioliasis, Ezbet El-Bakly (Tamyia Center) Al-Fayoum Governorate. J Egypt Soc Parasitol 34:807–818

  2. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

  3. Ashton PD, Curwen RS, Wilson RA (2001) Linking proteome and genome: how to identify parasite proteins. Trends Parasitol 17:198–202

  4. Atalay G, Cardoso F, Awada A, Piccart MJ (2003) Novel therapeutic strategies targeting the epidermal growth factor receptor (EGFR) family and its downstream effectors in breast cancer. Ann Oncol 14:1346–1363

  5. Balde AM, Van Marck EA, Kestens L, Gigase PL, Vlietinck AJ (1989) Schistosomicidal effects of Pavetta owariensis and Harrisonia abyssinica in mice infected with Schistosoma mansoni. Planta Med 55:41–43

  6. Barth LR, Fernandes AP, Ribeiro-Paes JT, Rodrigues V (1997) Effects of goyazensolide during in vitro cultivation of Schistosoma mansoni. Mem Inst Oswaldo Cruz 92:427–429

  7. Basch PF, Clemens LE (1989) Schistosoma mansoni: reversible destruction of testes by procarbazine. Comp Biochem Physiol C 93:397–401

  8. Baselga J (2002) Combined anti-EGF receptor and anti-HER2 receptor therapy in breast cancer: a promising strategy ready for clinical testing. Ann Oncol 13:8–9

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

  10. Benson AB 3rd (1993) Oltipraz: a laboratory and clinical review. J Cell Biochem Suppl 17F:278–291

  11. Bergquist NR (1995) Schistosomiasis vaccine development: approaches and prospects. Mem Inst Oswaldo Cruz 90:221–227

  12. Bergquist NR (2002) Schistosomiasis: from risk assessment to control. Trends Parasitol 18:309–314

  13. Bergquist R, Utzinger J, Chollet J, Shu-Hua X, Weiss NA, Tanner M (2004) Triggering of high-level resistance against Schistosoma mansoni reinfection by artemether in the mouse model. Am J Trop Med Hyg 71:774–777

  14. Bhisutthibhan J, Meshnick SR (2001) Immunoprecipitation of [(3)H]dihydroartemisinin translationally controlled tumor protein (TCTP) adducts from Plasmodium falciparum-infected erythrocytes by using anti-TCTP antibodies. Antimicrob Agents Chemother 45:2397–2399

  15. Bhisutthibhan J, Pan XQ, Hossler PA, Walker DJ, Yowell CA, Carlton J, Dame JB, Meshnick SR (1998) The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin. J Biol Chem 273:16192–16198

  16. Bickle QD, Andrews BJ (1985) Resistance following drug attenuation (Ro 11-3128 or oxamniquine) of early Schistosoma mansoni infections in mice. Parasitology 90(Pt 2):325–338

  17. Bickle QD, Sacko M, Vignali DA (1990) Induction of immunity against Schistosoma mansoni by drug (Ro11-3128)-terminated infections: analysis of surface antigen recognition. Parasite Immunol 12:569–586

  18. Bonn D (2004) Schistosomiasis: a new target for calcium-channel blockers? Lancet Infect Dis 4:190

  19. Boros DL (1989) Immunopathology of Schistosoma mansoni infection. Clin Microbiol Rev 2:250–269

  20. Botros S, William S, Hammam O, Zidek Z, Holy A (2003) Activity of 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine against Schistosomiasis mansoni in mice. Antimicrob Agents Chemother 47:3853–3858

  21. Botros S, Sayed H, El-Dusoki H, Sabry H, Rabie I, El-Ghannam M, Hassanein M, El-Wahab YA, Engels D (2005) Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma mansoni-infected school children and households. Am J Trop Med Hyg 72:119–123

  22. Bout D, Deslee D, Capron A (1986) Antischistosomal effect of cyclosporin A: cure and prevention of mouse and rat schistosomiasis mansoni. Infect Immun 52:823–827

  23. Bueding E, Batzinger R, Petterson G (1976) Antischistosomal and some toxicological properties of a nitrodiphenylaminoisothiocyanate (C 9333-Go/CGP 4540). Experientia 32:604–606

  24. Bueding E, Hawkins J, Cha YN (1981) Antischistosomal effects of cyclosporin A. Agents Actions 11:380–383

  25. Burtrum D, Zhu Z, Lu D, Anderson DM, Prewett M, Pereira DS, Bassi R, Abdullah R, Hooper AT, Koo H, Jimenez X, Johnson D, Apblett R, Kussie P, Bohlen P, Witte L, Hicklin DJ, Ludwig DL (2003) A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Res 63:8912–8921

  26. Chen GZ, Foster L, Bennett JL (1990) Antischistosomal action of mevinolin: evidence that 3-hydroxy-methylglutaryl-coenzyme a reductase activity in Schistosoma mansoni is vital for parasite survival. Naunyn Schmiedebergs Arch Pharmacol 342:477–482

  27. Cioli D (2000) Praziquantel: is there real resistance and are there alternatives? Curr Opin Infect Dis 13:659–663

  28. Cioli D, Pica-Mattoccia L, Archer S (1995) Antischistosomal drugs: past, present ... and future? Pharmacol Ther 68:35–85

  29. Costa G, Aguiar BG, Coelho PM, Cunha-Melo JR (2003) On the increase of portal pressure during the acute and chronic phases of murine schistosomiasis mansoni and its reversibility after treatment with oxamniquine. Acta Trop 89:13–16

  30. Dillon GP, Feltwell T, Skelton JP, Ashton PD, Coulson PS, Quail MA, Nikolaidou-Katsaridou N, Wilson RA, Ivens AC (2006) Microarray analysis identifies genes preferentially expressed in the lung schistosomulum of Schistosoma mansoni. Int J Parasitol 36:1–8

  31. Dunsford HA, Keysser CH, Dolan PM, Seed JL, Bueding E (1984) Carcinogenicity of the antischistosomal nitrofuran trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole. J Natl Cancer Inst 73:151–160

  32. Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG, Kimura M, O’Neill PM, Bray PG, Ward SA, Krishna S (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature 424:957–961

  33. El Baz MA, Morsy TA, El Bandary MM, Motawea SM (2003) Clinical and parasitological studies on the efficacy of Mirazid in treatment of schistosomiasis haematobium in Tatoon, Etsa Center, El Fayoum Governorate. J Egypt Soc Parasitol 33:761–776

  34. el Kouni MH, Diop D, O’Shea P, Carlisle R, Sommadossi JP (1989). Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5′-monophosphate for the treatment of schistosomiasis. Antimicrob Agents Chemother 33:824–827

  35. Feldmeier H, Chitsulo L (1999) Therapeutic and operational profiles of metrifonate and praziquantel in Schistosoma haematobium infection. Arzneimittelforschung 49:557–565

  36. Fenwick A, Savioli L, Engels D, Robert Bergquist N, Todd MH (2003) Drugs for the control of parasitic diseases: current status and development in schistosomiasis. Trends Parasitol 19:509–515

  37. Ferrari ML, Coelho PM, Antunes CM, Tavares CA, da Cunha AS (2003) Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial. Bull World Health Organ 81:190–196

  38. Fetterer RH, Pax RA, Bennett JL (1980) Praziquantel, potassium and 2,4-dinitrophenol: analysis of their action on the musculature of Schistosoma mansoni. Eur J Pharmacol 64:31–38

  39. Fitzpatrick JM, Johnston DA, Williams GW, Williams DJ, Freeman TC, Dunne DW, Hoffmann KF (2005) An oligonucleotide microarray for transcriptome analysis of Schistosoma mansoni and its application/use to investigate gender-associated gene expression. Mol Biochem Parasitol 141:1–13

  40. Gönnert R, Andrews P (1977) Praziquantel, a new broad-spectrum antischistosomal agent. Z Parasitenkd 52:129–150

  41. Graves PR, Kwiek JJ, Fadden P, Ray R, Hardeman K, Coley AM, Foley M, Haystead TA (2002) Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol Pharmacol 62:1364–1372

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

  43. Gunasekera AM, Patankar S, Schug J, Eisen G, Wirth DF (2003) Drug-induced alterations in gene expression of the asexual blood forms of Plasmodium falciparum. Mol Microbiol 50:1229–1239

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

  45. Harder A (2002b) Milestones of helmintic research at Bayer. Parasitol Res 88:477–480

  46. Hardjawidjaja L, Clark RT, Sorensen K, Putrali J (1976) Drug trial of Schistosoma japonicum enfection in Indonesia. Southeast Asian J Trop Med Public Health 7:314–318

  47. Harnett W, Kusel JR (1986) Increased exposure of parasite antigens at the surface of adult male Schistosoma mansoni exposed to praziquantel in vitro. Parasitology 93(Pt 2):401–405

  48. Hassan M, El-Motaiem M, Afify H, Abaza B, El-Shafei M, Massoud AM (2003) In vitro effect of Mirazid on Schistosoma mansoni worms. J Egypt Soc Parasitol 33:999–1008

  49. Haynes RK, Monti D, Taramelli D, Basilico N, Parapini S, Olliaro P (2003) Artemisinin antimalarials do not inhibit hemozoin formation. Antimicrob Agents Chemother 47:1175

  50. Hoffmann KF, Dunne DW (2003) Characterization of the Schistosoma transcriptome opens up the world of helminth genomics. Genome Biol 5:203

  51. Holy A, Votruba I, Merta A, Cerny J, Vesely J, Vlach J, Sediva K, Rosenberg I, Otmar M, Hrebabecky H et al (1990) Acyclic nucleotide analogues: synthesis, antiviral activity and inhibitory effects on some cellular and virus-encoded enzymes in vitro. Antiviral Res 13:295–311

  52. Hu W, Yan Q, Shen DK, Liu F, Zhu ZD, Song HD, Xu XR, Wang ZJ, Rong YP, Zeng LC, Wu J, Zhang X, Wang JJ, Xu XN, Wang SY, Fu G, Zhang XL, Wang ZQ, Brindley PJ, McManus DP, Xue CL, Feng Z, Chen Z, Han ZG (2003) Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource. Nat Genet 35:139–147

  53. Huffman MA (2001) Self-medicative behavior in the African great apes: an evolutionary perspective into the origins of human traditional medicine. BioScience 51:651–661

  54. Kannan R, Kumar K, Sahal D, Kukreti S, Chauhan VS (2005) Reaction of artemisinin with haemoglobin: implications for antimalarial activity. Biochem J 385:409–418

  55. Kayser O, Olbrich C, Croft SL, Kiderlen AF (2003a) Formulation and biopharmaceutical issues in the development of drug delivery systems for antiparasitic drugs. Parasitol Res 90(Suppl 2):S63–S670

  56. Kayser O, Kiderlen AF, Croft SL (2003b) Natural products as antiparasitic drugs. Parasitol Res 90(Suppl 2):S55–S62

  57. Khattab A, Pica-Mattoccia L, Klinkert MQ, Wenger R, Cioli D (1998) Cyclosporins: lack of correlation between antischistosomal properties and inhibition of cyclophilin isomerase activity. Exp Parasitol 90:103–109

  58. Kikuth W, Goennert R (1948) Experimental studies on the therapy of schistosomiasis. Ann Trop Med Parasitol 42:256–267

  59. Kloos H, David R (2002) The paleoepidemiology of schistosomiasis in ancient Egypt. Hum Ecol Rev 9:14–25

  60. Kohn AB, Anderson PA, Roberts-Misterly JM, Greenberg RM (2001) Schistosome calcium channel beta subunits. Unusual modulatory effects and potential role in the action of the antischistosomal drug praziquantel. J Biol Chem 276:36873–36876

  61. Kohn A, Roberts-Misterly J, Anderson P, Khan N, Greenberg R (2003) Specific sites in the beta interaction domain of a schistosome Ca2+ channel beta subunit are key to its role in sensitivity to the anti-schistosomal drug praziquantel. Parasitology 127:349–356

  62. Kramata P, Votruba I, Otova B, Holy A (1996) Different inhibitory potencies of acyclic phosphonomethoxyalkyl nucleotide analogs toward DNA polymerases alpha, delta and epsilon. Mol Pharmacol 49:1005–1011

  63. Magnussen P (2003) Treatment and re-treatment strategies for schistosomiasis control in different epidemiological settings: a review of 10 years’ experiences. Acta Trop 86:243–254

  64. Massoud AM, El Ebiary FH, Abd El Salam NF (2004) Effect of myrrh extract on the liver of normal and bilharzially infected mice. An ultrastructural study. J Egypt Soc Parasitol 34:1–21

  65. Matsuyama H, Takahashi H, Watanabe K, Fujimaki Y, Aoki Y (2004) The involvement of cyclic adenosine monophosphate in the control of schistosome miracidium cilia. J Parasitol 90:8–14

  66. McManus DP, Hu W, Brindley PJ, Feng Z, Han ZG (2004) Schistosome transcriptome analysis at the cutting edge. Trends Parasitol 20:301–304

  67. Mehlhorn H, Becker B, Andrews P, Thomas H, Frenkel JK (1981) In vivo and in vitro experiments on the effects of praziquantel on Schistosoma mansoni. A light and electron microscopic study. Arzneimittelforschung 31:544–554

  68. Melo AL, Silva-Barcellos NM, Demicheli C, Frezard F (2003) Enhanced schistosomicidal efficacy of tartar emetic encapsulated in pegylated liposomes. Int J Pharm 255:227–230

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

  70. Meshnick SR, Taylor TE, Kamchonwongpaisan S (1996) Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev 60:301–315

  71. Moczon T, Swiderski Z (1992) Schistosoma haematobium: histochemistry of glycogen, glycogen phosphorylase a and glycogen branching enzyme in niridazole-treated females. Int J Parasitol 22:55–63

  72. N’Goran EK, Utzinger J, Gnaka HN, Yapi A, N’Guessan NA, Kigbafori SD, Lengeler C, Chollet J, Shuhua X, Tanner M (2003) Randomized, double-blind, placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections. Am J Trop Med Hyg 68:24–32

  73. Nontprasert A, Pukrittayakamee S, Dondorp AM, Clemens R, Looareesuwan S, White NJ (2002a) Neuropathologic toxicity of artemisinin derivatives in a mouse model. Am J Trop Med Hyg 67:423–429

  74. Nontprasert A, Pukrittayakamee S, Prakongpan S, Supanaranond W, Looareesuwan S, White NJ (2002b) Assessment of the neurotoxicity of oral dihydroartemisinin in mice. Trans R Soc Trop Med Hyg 96:99–101

  75. Ogboli A (2000) Medicinal application of Vernonia amygdalina del leaf extracts in the treatment of schistosomiasis in mice. Niger J Nat Prod Med 4:73–75

  76. Olds GR, Dasarathy S (2000) Schistosomiasis. Curr Treat Options Infect Dis 2:88–99

  77. Oliveira MF, Silva JR, Dansa-Petretski M, de Souza W, Braga CM, Masuda H, Oliveira PL (2000) Haemozoin formation in the midgut of the blood-sucking insect Rhodnius prolixus. FEBS Lett 477:95–98

  78. Oliveira MF, d’Avila JC, Tempone AJ, Soares JB, Rumjanek FD, Ferreira-Pereira A, Ferreira ST, Oliveira PL (2004) Inhibition of heme aggregation by chloroquine reduces Schistosoma mansoni infection. J Infect Dis 190:843–852

  79. Oliveira MF, Kycia SW, Gomez A, Kosar AJ, Bohle DS, Hempelmann E, Menezes D, Vannier-Santos MA, Oliveira PL, Ferreira ST (2005) Structural and morphological characterization of hemozoin produced by Schistosoma mansoni and Rhodnius prolixus. FEBS Lett 579:6010–6016

  80. O’Neill PM, Bray PG, Hawley SR, Ward SA, Park BK (1998) 4-Aminoquinolines—past, present, and future: a chemical perspective. Pharmacol Ther 77:29–58

  81. Pandey AV, Tekwani BL, Singh RL, Chauhan VS (1999) Artemisinin, an endoperoxide antimalarial, disrupts the hemoglobin catabolism and heme detoxification systems in malarial parasite. J Biol Chem 274:19383–19388

  82. Penido ML, Nelson DL, Vieira LQ, Coelho PM (1994) Schistosomicidal activity of alkylaminooctanethiosulfuric acids. Mem Inst Oswaldo Cruz 89:595–602

  83. Penido ML, Coelho PM, Nelson DL (1999) Efficacy of a new schistosomicidal agent 2-[(methylpropyl)amino]-1-octanethiosulfuric acid against an oxamniquine resistant Schistosoma mansoni isolate. Mem Inst Oswaldo Cruz 94:811–813

  84. Pereira LH, Coelho PM, Costa JO, de Mello RT (1995) Activity of 9-acridanone-hydrazone drugs detected at the pre-postural phase, in the experimental schistosomiasis mansoni. Mem Inst Oswaldo Cruz 90:425–428

  85. Pica-Mattoccia L, Cioli D (1985) Studies on the mode of action of oxamniquine and related schistosomicidal drugs. Am J Trop Med Hyg 34:112–118

  86. Rao KV, Chen L, Gnanasekar M, Ramaswamy K (2002) Cloning and characterization of a calcium-binding, histamine-releasing protein from Schistosoma mansoni. J Biol Chem 277:31207–31213

  87. Rege AA, Wang W, Dresden MH (1992) Cysteine proteinases from Schistosoma haematobium adult worms. J Parasitol 78:16–23

  88. Roca C, Balanzo X, Gascon J, Fernandez-Roure JL, Vinuesa T, Valls ME, Sauca G, Corachan M (2002) Comparative, clinico-epidemiologic study of Schistosoma mansoni infections in travellers and immigrants in Spain. Eur J Clin Microbiol Infect Dis 21:219–223

  89. Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, McManus DP (2002) Schistosomiasis. N Engl J Med 346:1212–1220

  90. Sabah AA, Fletcher C, Webbe G, Doenhoff MJ (1986) Schistosoma mansoni: chemotherapy of infections of different ages. Exp Parasitol 61:294–303

  91. Santos AJ (1976) Prevalence and distribution of schistosomiasis in the Philippines: a review. Southeast Asian J Trop Med Public Health 7:133–136

  92. Shaw MK (1990) Schistosoma mansoni: stage-dependent damage after in vivo treatment with praziquantel. Parasitology 100(Pt 1):65–72

  93. Sheir Z, Nasr AA, Massoud A, Salama O, Badra GA, El-Shennawy H, Hassan N, Hammad SM (2001) A safe, effective, herbal antischistosomal therapy derived from myrrh. Am J Trop Med Hyg 65:124–700

  94. Shekhar KC (1991) Schistosomiasis drug therapy and treatment considerations. Drugs 42:379–405

  95. Silva IM, Thiengo R, Conceicao 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

  96. Smeijsters LJ, Nieuwenhuijs H, Hermsen RC, Dorrestein GM, Franssen FF, Overdulve JP (1996) Antimalarial and toxic effects of the acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine in Plasmodium berghei-infected mice. Antimicrob Agents Chemother 40:1584–1588

  97. Smith DA, Bickle QD, Kaye PM (1994) Resistance induced by drug abbreviated Schistosoma mansoni infections: treatment with the drug Ro11-3128 leads to enhanced antigen presentation. Immunology 82:419–426

  98. Soliman MF, Ibrahim MM (2005) Antischistosomal action of atorvastatin alone and concurrently with medroxyprogesterone acetate on Schistosoma haematobium harboured in hamster: surface ultrastructure and parasitological study. Acta Trop 93:1–9

  99. Striebel HP (1976) 4-Isothiocyanato-4′-nitrodiphenylamine (C 9333-Go/CGP 4540), an anthelminthic with an unusual spectrum of activity against intestinal nematodes, filariae and schistosomes. Experientia 32:457–458

  100. Sulaiman SM, Ali HM, Homeida MM, Bennett JL (1989) Efficacy of a new Hoffmann-La Roche compound (Ro 15-5458) against Schistosoma mansoni (Gezira strain, Sudan) in vervet monkeys (Cercopithecus aethiops). Trop Med Parasitol 40:335–336

  101. Sullivan DJ (2002) Theories on malarial pigment formation and quinoline action. Int J Parasitol 32:1645–1653

  102. Sullivan DJ Jr, Gluzman IY, Russell DG, Goldberg DE (1996) On the molecular mechanism of chloroquine’s antimalarial action. Proc Natl Acad Sci U S A 93:11865–11870

  103. Talla E, de Mendonca RL, Degand I, Goffeau A, Ghislain M (1998) Schistosoma mansoni Ca2+-ATPase SMA2 restores viability to yeast Ca2+-ATPase-deficient strains and functions in calcineurin-mediated Ca2+ tolerance. J Biol Chem 273:27831–27840

  104. Thomas SM, Grandis JR (2004) Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigation. Cancer Treat Rev 30:255–268

  105. Utzinger J, Xiao S, Keiser J, Chen M, Zheng J, Tanner M (2001) Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites. Curr Med Chem 8:1841–1860

  106. Utzinger J, Keiser J, Shuhua X, Tanner M, Singer BH (2003) Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials. Antimicrob Agents Chemother 47:1487–1495

  107. Verjovski-Almeida S, DeMarco R, Martins EA, Guimaraes PE, Ojopi EP, Paquola AC, Piazza JP, Nishiyama MY Jr, Kitajima JP, Adamson RE, Ashton PD, Bonaldo MF, Coulson PS, Dillon GP, Farias LP, Gregorio SP, Ho PL, Leite RA, Malaquias LC, Marques RC, Miyasato PA, Nascimento AL, Ohlweiler FP, Reis EM, Ribeiro MA, Sa RG, Stukart GC, Soares MB, Gargioni C, Kawano T, Rodrigues V, Madeira AM, Wilson RA, Menck CF, Setubal JC, Leite LC, Dias-Neto E (2003) Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni. Nat Genet 35:148–157

  108. Verjovski-Almeida S, Leite LC, Dias-Neto E, Menck CF, Wilson RA (2004) Schistosome transcriptome: insights and perspectives for functional genomics. Trends Parasitol 20:304–308

  109. Vicogne J, Dissous C (2003) Schistosoma mansoni receptor tyrosine kinases: towards new therapeutic targets. J Soc Biol 197:367–373

  110. Vicogne J, Pin JP, Lardans V, Capron M, Noel C, Dissous C (2003) An unusual receptor tyrosine kinase of Schistosoma mansoni contains a Venus Flytrap module. Mol Biochem Parasitol 126:51–62

  111. Votruba I, Bernaerts R, Sakuma T, De Clercq E, Merta A, Rosenberg I, Holy A (1987) Intracellular phosphorylation of broad-spectrum anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and inhibition of viral DNA synthesis. Mol Pharmacol 32:524–529

  112. Walter RD, Albiez EJ (1984) Interaction of amoscanate with the cyclic AMP-phosphodiesterases from Schistosoma mansoni, Onchocerca volvulus and bovine heart. Tropenmed Parasitol 35:78–80

  113. Wasilewski MM, Lim KC, Phillips J, McKerrow JH (1996) Cysteine protease inhibitors block schistosome hemoglobin degradation in vitro and decrease worm burden and egg production in vivo. Mol Biochem Parasitol 81:179–189

  114. WHO (2002) TDR Strategic direction for research. Disease TDR Strategic direction for research. Disease burden and epidemiological trends.

  115. WHO–Geneva (2002) WHO technical report series 912: prevention and control of schistosomiasis and soil-transmitted helminthiasis. WHO, Geneva

  116. Wu GY, Halim MH (2000) Schistosomiasis: progress and problems. World J Gastroenterol 6:12–19

  117. Xiao S, Utzinger J, Chollet J, Endriss Y, N’Goran EK, Tanner M (2000) Effect of artemether against Schistosoma haematobium in experimentally infected hamsters. Int J Parasitol 30:1001–1006

  118. Xiao SH, Yue WJ, Yang YQ, You JQ (1987) Susceptibility of Schistosoma japonicum to different developmental stages to praziquantel. Chin Med J (Engl) 100:759–768

  119. Xiao S, Shen B, Chollet J, Utzinger J, Tanner M (2001) Tegumental alterations in juvenile Schistosoma haematobium harboured in hamsters following artemether treatment. Parasitol Int 50:175–183

  120. Xiao SH, Wu YL, Tanner M, Wu WM, Utzinger J, Mei JY, Scorneaux B, Chollet J, Zhai Z (2003) Schistosoma japonicum: in vitro effects of artemether combined with haemin depend on cultivation media and appraisal of artemether products appearing in the media. Parasitol Res 89:459–466

  121. Xiao SH, Guo J, Chollet J, Wu JT, Tanner M, Utzinger J (2004) Effect of artemether on Schistosoma mansoni: dose–efficacy relationship, and changes in worm morphology and histopathology. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 22:148–153

  122. Zerda KS, Dresden MH, Chappell CL (1988) Schistosoma mansoni: expression and role of cysteine proteinases in developing schistosomula. Exp Parasitol 67:238–246

Download references


This research was mainly supported by Hebron S/A. Indústrias Químicas e Farmacêuticas, Recife-PE, Brazil. The work in the laboratories of the authors is supported by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo, Brasil, and Conselho Nacional do Desenvolvimento Científico e Tecnológico, Brasil, the State and Federal research funding agencies, respectively.

Author information

Correspondence to Gabriela Ribeiro-dos-Santos.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ribeiro-dos-Santos, G., Verjovski-Almeida, S. & Leite, L.C.C. Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res 99, 505 (2006).

Download citation


  • Malaria
  • Artemisinin
  • Schistosomiasis
  • Schistosoma
  • Praziquantel