Chapter 149 : Antiparasitic Agents

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Antiparasitic Agents, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817381/9781555817381.ch149-1.gif /docserver/preview/fulltext/10.1128/9781555817381/9781555817381.ch149-2.gif


This chapter discusses the mechanisms of action, pharmacology, clinical utility, and adverse effects of common first-line antiparasitic therapies and newer drug alternatives. Agents discussed in detail include albendazole, mebendazole, praziquantel, ivermectin, diethylcarbamazine, nitazoxanide, antimalarials, and those used to treat gastrointestinal protozoal infections, leishmaniasis, and trypanosomiasis.

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. The Medical Letter . 2013. Drugs for Parasitic Infections. The Medical Letter, Inc, New Rochelle, NY.
2. Mackenzie CD,, Geary TG. 2011. Flubendazole: a candidate macrofilaricide for lymphatic filariasis and onchocerciasis field programs. Expert Rev Anti Infect Ther 9: 497501.
3. Ceballos L,, Virkel G,, Elissondo C,, Canton C,, Canevari J,, Murno G,, Denegri G,, Lanusse C,, Alvarez L. 2013. A pharmacology-based comparison of the activity of albendazole and flubendazole against Echinococcus granulosus metacestode in sheep. Acta Trop 127: 216225.
4. van den Enden E. 2009. Pharmacotherapy of helminth infection. Expert Opin Pharmacother 10: 435451.
5. Calvopina M,, Guderian RH,, Paredes W,, Chico M,, Cooper PJ. 1998. Treatment of human pulmonary paragonimiasis with triclabendazole: clinical tolerance and drug efficacy. Trans R Soc Trop Med Hyg 92: 566569.
6. Villegas F,, Angles R,, Barrientos R,, Barrios G,, Valero MA,, Hamed K,, Grueninger H,, Ault SK,, Montresor A,, Engels D,, Mas-Coma S,, Gabrielli AF. 2012. Administration of triclabendazole is safe and effective in controlling fascioliasis in an endemic community of the Bolivian Altiplano. PLoS Negl Trop Dis 6: e1720. 10.1371/journal.pntd.0001720.
7. Cabada MM,, White AC, Jr. 2012. New developments in epidemiology, diagnosis, and treatment of fascioliasis. Curr Opin Infect Dis 25: 518522.
8. Winkelhagen AJ,, Mank T,, de Vries PJ,, Soetekouw R. 2012. Apparent triclabendazole-resistant human Fasciola hepatica infection, the Netherlands. Emerg Infect Dis 18: 10281029.
9. Fairweather I. 2009. Triclabendazole progress report, 2005–2009: an advancement of learning? J Helminthol 83: 139150.
10. Keiser J,, Engels D,, Buscher G,, Utzinger J. 2005. Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opin Investig Drugs 14: 15131526.
11. Lacey E. 1990. Mode of action of benzimidazoles. Parasitol Today 6: 112115.
12. Gilman A,, Rall TW,, Nies AS ( ed). 1990. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 8th ed. Pergamon Press, New York, NY.
13. Frayha GJ,, Smyth JD,, Gobert JG,, Savel J. 1997. The mechanisms of action of antiprotozoal and anthelmintic drugs in man. Gen Pharmacol 28: 273299.
14. de Silva N,, Guyatt H,, Bundy D. 1997. Anthelmintics. A comparative review of their clinical pharmacology. Drugs 53: 769788.
15. Edwards G,, Breckenridge AM. 1988. Clinical pharmacokinetics of anthelmintic drugs. Clin Pharmacokinet 15: 6793.
16. Marriner SE,, Morris DL,, Dickson B,, Bogan JA. 1986. Pharmacokinetics of albendazole in man. Eur J Clin Pharmacol 30: 705708.
17. Bogan JA,, Marriner S. 1980. Analysis of benzimidazoles in body fluids by high-performance liquid chromatography. J Pharm Sci 69: 422423.
18. Jung H,, Hurtado M,, Sanchez M,, Medina MT,, Sotelo J. 1992. Clinical pharmacokinetics of albendazole in patients with brain cysticercosis. J Clin Pharmacol 32: 2831.
19. Jung H,, Hurtado M,, Medina MT,, Sanchez M,, Sotelo J. 1990. Dexamethasone increases plasma levels of albendazole. J Neurol 237: 279280.
20. Garcia HH,, Lescano AG,, Lanchote VL,, Pretell EJ,, Gonzales I,, Bustos JA,, Takayanagui OM,, Bonato PS,, Horton J,, Saavedra H,, Gonzalez AE,, Gilman RH, Cysticercosis Working Group in Peru. 2011. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis. Br J Clin Pharmacol 72: 7784.
21. Lima RM,, Ferreira MA,, de Jesus Ponte Carvalho TM,, Dumet Fernandes BJ,, Takayanagui OM,, Garcia HH,, Coelho EB,, Lanchote VL. 2011. Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity. Br J Clin Pharmacol 71: 528535.
22. Morris DL,, Chinnery JB,, Georgiou G,, Stamatakis G,, Golematis B. 1987. Penetration of albendazole sulphoxide into hydatid cysts. Gut 28: 7580.
23. Moskopp D,, Lotterer E. 1993. Concentrations of albendazole in serum, cerebrospinal fluid and hydatidous brain cyst. Neurosurg Rev 16: 3537.
24. Keiser J,, Utzinger J. 2008. Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA 299: 19371948.
25. Opatrny L,, Prichard R,, Snell L,, Maclean JD. 2005. Death related to albendazole-induced pancytopenia: case report and review. Am J Trop Med Hyg 72: 291294.
26. Lillie P,, McGann H. 2010. Empiric albendazole therapy and new onset seizures—a cautionary note. J Infect 60: 403404. (Author’s reply, 60: 404405.)
27. Ramos-Zuniga R,, Perez-Gomez HR,, Jauregui-Huerta F,, del Sol Lopez-Hernandez M,, Valera-Lizarraga JE,, Paz-Velez G,, Becerra-Valdivia A. 2013. Incidental consequences of antihelmintic treatment in the central nervous system. World Neurosurg 79: 149153.
28. Auer H,, Kollaritsch H,, Juptner J,, Aspock H. 1994. Albendazole and pregnancy. Appl Parasitol 35: 146147.
29. Abdel-tawab AM,, Bradley M,, Ghazaly EA,, Horton J,, el-Setouhy M. 2009. Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole. Br J Clin Pharmacol 68: 737742.
30. Brindley PJ,, Sher A. 1990. Immunological involvement in the efficacy of praziquantel. Exp Parasitol 71: 245248.
31. Doenhoff MJ,, Cioli D,, Utzinger J. 2008. Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21: 659667.
32. Sotelo J,, Jung H. 1998. Pharmacokinetic optimisation of the treatment of neurocysticercosis. Clin Pharmacokinet 34: 503515.
33. Kaojarern S,, Nathakarnkikool S,, Suvanakoot TU. 1989. Comparative bioavailability of praziquantel tablets. DICP 23: 2932.
34. Mohamed AE,, Yasawy MI,, Al Karawi MA. 1998. Combined albendazole and praziquantel versus albendazole alone in the treatment of hydatid disease. Hepatogastroenterology 45: 16901694.
35. Cobo F,, Yarnoz C,, Sesma B,, Fraile P,, Aizcorbe M,, Trujillo R,, Diaz-de-Liano A,, Ciga MA. 1998. Albendazole plus praziquantel versus albendazole alone as a pre-operative treatment in intra-abdominal hydatisosis caused by Echinococcus granulosus. Trop Med Int Health 3: 462466.
36. Bygott JM,, Chiodini PL. 2009. Praziquantel: neglected drug? Ineffective treatment? Or therapeutic choice in cystic hydatid disease? Acta Trop 111: 95101.
37. Lee JM,, Lim HS,, Hong ST. 2011. Hypersensitive reaction to praziquantel in a clonorchiasis patient. Korean J Parasitol 49: 273275.
38. Kyung SY,, Cho YK,, Kim YJ,, Park JW,, Jeong SH,, Lee JI,, Sung YM,, Lee SP. 2011. A paragonimiasis patient with allergic reaction to praziquantel and resistance to triclabendazole: successful treatment after desensitization to praziquantel. Korean J Parasitol 49: 7377.
39. Hewagama SS,, Darby JD,, Sheorey H,, Daffy JR. 2010. Seizures related to praziquantel therapy in neurocysticercosis. Med J Aust 193: 246247.
40. Olds GR. 2003. Administration of praziquantel to pregnant and lactating women. Acta Trop 86: 185195.
41. Adam I,, Elwasila el T,, Homeida M. 2004. Is praziquantel therapy safe during pregnancy? Trans R Soc Trop Med Hyg 98: 540543.
42. Allen HE,, Crompton DW,, de Silva N,, LoVerde PT,, Olds GR. 2002. New policies for using anthelmintics in high risk groups. Trends Parasitol 18: 381382.
43. Sutherland IH,, Campbell WC. 1990. Development, pharmacokinetics and mode of action of ivermectin. Acta Leiden 59: 161168.
44. Campbell WC. 1993. Ivermectin, an antiparasitic agent. Med Res Rev 13: 6179.
45. Fox LM. 2006. Ivermectin: uses and impact 20 years on. Curr Opin Infect Dis 19: 588593.
46. Geary TG,, Moreno Y. 2012. Macrocyclic lactone anthelmintics: spectrum of activity and mechanism of action. Curr Pharm Biotechnol 13: 866872.
47. Ottesen EA,, Campbell WC. 1994. Ivermectin in human medicine. J Antimicrob Chemother 34: 195203.
48. Fusco DN,, Downs JA,, Satlin MJ,, Pahuja M,, Ramos L,, Barie PS,, Fleckenstein L,, Murray HW. 2010. Non-oral treatment with ivermectin for disseminated strongyloidiasis. Am J Trop Med Hyg 83: 879883.
49. Grein JD,, Mathisen GE,, Donovan S,, Fleckenstein L. 2010. Serum ivermectin levels after enteral and subcutaneous administration for Strongyloides hyperinfection: a case report. Scand J Infect Dis 42: 234236.
50. Baraka OZ,, Mahmoud BM,, Marschke CK,, Geary TG,, Homeida MM,, Williams JF. 1996. Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus. Eur J Clin Pharmacol 50: 407410.
51. Naquira C,, Jimenez G,, Guerra JG,, Bernal R,, Nalin DR,, Neu D,, Aziz M. 1989. Ivermectin for human strongyloidiasis and other intestinal helminths. Am J Trop Med Hyg 40: 304309.
52. Wen LY,, Yan XL,, Sun FH,, Fang YY,, Yang MJ,, Lou LJ. 2008. A randomized, double-blind, multicenter clinical trial on the efficacy of ivermectin against intestinal nematode infections in China. Acta Trop 106: 190194.
53. Knopp S,, Mohammed KA,, Speich B,, Hattendorf J,, Khamis IS,, Khamis AN,, Stothard JR,, Rollinson D,, Marti H,, Utzinger J. 2010. Albendazole and mebendazole administered alone or in combination with ivermectin against Trichuris trichiura: a randomized controlled trial. Clin Infect Dis 51: 14201428.
54. Kraivichian K,, Nuchprayoon S,, Sitichalernchai P,, Chaicumpa W,, Yentakam S. 2004. Treatment of cutaneous gnathostomiasis with ivermectin. Am J Trop Med Hyg 71: 623628.
55. Gonzalez P,, Gonzalez FA,, Ueno K. 2012. Ivermectin in human medicine, an overview of the current status of its clinical applications. Curr Pharm Biotechnol 13: 11031109.
56. Njoo FL,, Beek WM,, Keukens HJ,, van Wilgenburg H,, Oosting J,, Stilma JS,, Kijlstra A. 1995. Ivermectin detection in serum of onchocerciasis patients: relationship to adverse reactions. Am J Trop Med Hyg 52: 9497.
57. Twum-Danso NA. 2003. Loa loa encephalopathy temporally related to ivermectin administration reported from onchocerciasis mass treatment programs from 1989 to 2001: implications for the future. Filaria J 2( Suppl 1) : S7. 10.1186/1475-2883-2-S1-S7.
58. Pacque M,, Munoz B,, Poetschke G,, Foose J,, Greene BM,, Taylor HR. 1990. Pregnancy outcome after inadvertent ivermectin treatment during community-based distribution. Lancet 336: 14861489.
59. Goa KL,, McTavish D,, Clissold SP. 1991. Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs 42: 640658.
60. Gyapong JO,, Chinbuah MA,, Gyapong M. 2003. Inadvertent exposure of pregnant women to ivermectin and albendazole during mass drug administration for lymphatic filariasis. Trop Med Int Health 8: 10931101.
61. Klion AD,, Ottesen EA,, Nutman TB. 1994. Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate visitors to endemic regions: long-term follow-up. J Infect Dis 169: 604610.
62. Edwards G,, Awadzi K,, Breckenridge AM,, Gilles HM,, Orme ML,, Ward SA. 1981. Diethylcarbamazine disposition in patients with onchocerciasis. Clin Pharmacol Ther 30: 551557.
63. Noroes J,, Dreyer G,, Santos A,, Mendes VG,, Medeiros Z,, Addiss D. 1997. Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg 91: 7881.
64. Ottesen EA. 1985. Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans. Rev Infect Dis 7: 341356.
65. Nicolas L,, Plichart C,, Nguyen LN,, Moulia-Pelat JP. 1997. Reduction of Wuchereria bancrofti adult worm circulating antigen after annual treatments of diethylcarbamazine combined with ivermectin in French Polynesia. J Infect Dis 175: 489492.
66. Joseph CA,, Dixon PA. 1984. Possible prostaglandin-mediated effect of diethylcarbamazine on rat uterine contractility. J Pharm Pharmacol 36: 281282.
67. Ferrara P,, Bersani I,, Bottaro G,, Vitelli O,, Liberatore P,, Gatto A,, del Bufalo F,, Romano V,, Stabile A. 2011. Massive proteinuria: a possible side effect of pyrantel pamoate? Ren Fail 33: 534536.
68. Tietze PE,, Jones JE. 1991. Parasites during pregnancy. Prim Care 18: 7599.
69. Fox LM,, Saravolatz LD. 2005. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis 40: 11731180.
70. Anonymous. 2003. Nitazoxanide (Alinia)—a new anti-protozoal agent. Med Lett Drugs Ther 45: 2931.
71. Gilles HM,, Hoffman PS. 2002. Treatment of intestinal parasitic infections: a review of nitazoxanide. Trends Parasitol 18: 9597.
72. Stockis A,, Allemon AM,, De Bruyn S,, Gengler C. 2002. Nitazoxanide pharmacokinetics and tolerability in man using single ascending oral doses. Int J Clin Pharmacol Ther 40: 213220.
73. Broekhuysen J,, Stockis A,, Lins RL,, De Graeve J,, Rossignol JF. 2000. Nitazoxanide: pharmacokinetics and metabolism in man. Int J Clin Pharmacol Ther 38: 387394.
74. Ortiz JJ,, Ayoub A,, Gargala G,, Chegne NL,, Favennec L. 2001. Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern Peru. Aliment Pharmacol Ther 15: 14091415.
75. Adagu IS,, Nolder D,, Warhurst DC,, Rossignol JF. 2002. In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. J Antimicrob Chemother 49: 103111.
76. Stockis A,, Deroubaix X,, Lins R,, Jeanbaptiste B,, Calderon P,, Rossignol JF. 1996. Pharmacokinetics of nitazoxanide after single oral dose administration in 6 healthy volunteers. Int J Clin Pharmacol Ther 34: 349351.
77. Diaz E,, Mondragon J,, Ramirez E,, Bernal R. 2003. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg 68: 384385.
78. Olliaro P,, Seiler J,, Kuesel A,, Horton J,, Clark JN,, Don R,, Keiser J. 2011. Potential drug development candidates for human soil-transmitted helminthiases. PLoS Negl Trop Dis 5: e1138. 10.1371/journal.pntd.0001138.
79. Slater AF,, Cerami A. 1992. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature 355: 167169.
80. Krogstad DJ,, Schlesinger PH,, Gluzman IY. 1989. Chloroquine and acid vesicle function. Prog Clin Biol Res 313: 5359.
81. Pussard E,, Verdier F. 1994. Antimalarial 4-aminoquinolines: mode of action and pharmacokinetics. Fundam Clin Pharmacol 8: 117.
82. Krishna S,, White NJ. 1996. Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications. Clin Pharmacokinet 30: 263299.
83. Rombo L,, Bjorkman A,, Sego E,, Ericsson O. 1986. Whole blood concentrations of chloroquine and desethylchloroquine during and after treatment of adult patients infected with Plasmodium vivax, P. ovale or P. malariae. Trans R Soc Trop Med Hyg 80: 763766.
84. Daneshvar C,, Davis TM,, Cox-Singh J,, Rafa’ee MZ,, Zakaria SK,, Divis PC,, Singh B. 2010. Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections. Malar J 9: 238. doi:10.1186/1475-2875-9-238.
85. Levy M,, Buskila D,, Gladman DD,, Urowitz MB,, Koren G. 1991. Pregnancy outcome following first trimester exposure to chloroquine. Am J Perinatol 8: 174178.
86. Olliaro P,, Nevill C,, LeBras J,, Ringwald P,, Mussano P,, Garner P,, Brasseur P. 1996. Systematic review of amodiaquine treatment in uncomplicated malaria. Lancet 348: 11961201.
87. Foley M,, Tilley L. 1997. Quinoline antimalarials: mechanisms of action and resistance. Int J Parasitol 27: 231240.
88. White NJ. 1985. Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet 10: 187215.
89. Looareesuwan S,, Phillips RE,, White NJ,, Kietinun S,, Karbwang J,, Rackow C,, Turner RC,, Warrell DA. 1985. Quinine and severe falciparum malaria in late pregnancy. Lancet 2: 48.
90. Silver H. 1997. Malarial infection during pregnancy. Infect Dis Clin North Am 11: 99107.
91. Karbwang J,, White NJ. 1990. Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet 19: 264279.
92. Hennequin C,, Bouree P,, Bazin N,, Bisaro F,, Feline A. 1994. Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine. Arch Intern Med 154: 23602362.
93. van Riemsdijk MM,, van der Klauw MM,, van Heest JA,, Reedeker FR,, Ligthelm RJ,, Herings RM,, Stricker BH. 1997. Neuro-psychiatric effects of antimalarials. Eur J Clin Pharmacol 52: 16.
94. Vanhauwere B,, Maradit H,, Kerr L. 1998. Post-marketing surveillance of prophylactic mefloquine (Lariam) use in pregnancy. Am J Trop Med Hyg 58: 1721.
95. Nosten F,, Vincenti M,, Simpson J,, Yei P,, Thwai KL,, de Vries A,, Chongsuphajaisiddhi T,, White NJ. 1999. The effects of mefloquine treatment in pregnancy. Clin Infect Dis 28: 808815.
96. Veenendaal JR,, Parkinson AD,, Kere N,, Rieckmann KH,, Edstein MD. 1991. Pharmacokinetics of halofantrine and N-desbutylhalofantrine in patients with falciparum malaria following a multiple dose regimen of halofantrine. Eur J Clin Pharmacol 41: 161164.
97. Bryson HM,, Goa KL. 1992. Halofantrine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic potential. Drugs 43: 236258.
98. Bouchaud O,, Imbert P,, Touze JE,, Dodoo AN,, Danis M,, Legros F. 2009. Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base. Malar J 8: 289. doi:10.1186/1475-2875-8-289.
99. Ezzet F,, van Vugt M,, Nosten F,, Looareesuwan S,, White NJ. 2000. Pharmacokinetics and pharmacodynamics of lumefantrine (benflumetol) in acute falciparum malaria. Antimicrob Agents Chemother 44: 697704.
100. Warhurst DC. 1984. Why are primaquine and other 8-aminoquinolines particularly effective against the mature gametocytes and the hypnozoites of malaria? Ann Trop Med Parasitol 78: 165.
101. Mihaly GW,, Ward SA,, Edwards G,, Orme ML,, Breckenridge AM. 1984. Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. Br J Clin Pharmacol 17: 441446.
102. Nasveld PE,, Edstein MD,, Reid M,, Brennan L,, Harris IE,, Kitchener SJ,, Leggat PA,, Pickford P,, Kerr C,, Ohrt C,, Prescott W, Tafenoquine Study Team . 2010. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Agents Chemother 54: 792798.
103. Walsh DS,, Wilairatana P,, Tang DB,, Heppner DG, Jr,, Brewer TG,, Krudsood S,, Silachamroon U,, Phumratanaprapin W,, Siriyanonda D,, Looareesuwan S. 2004. Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse. Clin Infect Dis 39: 10951103.
104. Brueckner RP,, Coster T,, Wesche DL,, Shmuklarsky M,, Schuster BG. 1998. Prophylaxis of Plasmodium falciparum infection in a human challenge model with WR 238605, a new 8-aminoquinoline antimalarial. Antimicrob Agents Chemother 42: 12931294.
105. Gu HM,, Warhurst DC,, Peters W. 1984. Uptake of [3H] dihydroartemisinine by erythrocytes infected with Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 78: 265270.
106. Na-Bangchang K,, Krudsood S,, Silachamroon U,, Molunto P,, Tasanor O,, Chalermrut K,, Tangpukdee N,, Matangkasombut O,, Kano S,, Looareesuwan S. 2004. The pharmacokinetics of oral dihydroartemisinin and artesunate in healthy Thai volunteers. Southeast Asian J Trop Med Public Health 35: 575582.
107. Morris CA,, Duparc S,, Borghini-Fuhrer I,, Jung D,, Shin CS,, Fleckenstein L. 2011. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration. Malar J 10: 263. 10.1186/1475-2875-10-263.
108. Price RN,, Nosten F,, Luxemburger C,, ter Kuile FO,, Paiphun L,, Chongsuphajaisiddhi T,, White NJ. 1996. Effects of artemisinin derivatives on malaria transmissibility. Lancet 347: 16541658.
109. Chen PQ,, Li GQ,, Guo XB,, He KR,, Fu YX,, Fu LC,, Song YZ. 1994. The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin. Chin Med J (Engl) 107: 709711.
110. Dondorp A,, Nosten F,, Stepniewska K,, Day N,, White N. 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717725.
111. Sinclair D,, Donegan S,, Isba R,, Lalloo DG. 2012. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev ( 6): CD005967. 10.1002/14651858. CD005967.pub4.
112. Dondorp AM,, Fanello CI,, Hendriksen IC,, Gomes E,, Seni A,, Chhaganlal KD,, Bojang K,, Olaosebikan R,, Anunobi N,, Maitland K,, Kivaya E,, Agbenyega T,, Nguah SB,, Evans J,, Gesase S,, Kahabuka C,, Mtove G,, Nadjm B,, Deen J,, Mwanga-Amumpaire J,, Nansumba M,, Karema C,, Umulisa N,, Uwimana A,, Mokuolu OA,, Adedoyin OT,, Johnson WB,, Tshefu AK,, Onyamboko MA,, Sakulthaew T,, Ngum WP,, Silamut K,, Stepniewska K,, Woodrow CJ,, Bethell D,, Wills B,, Oneko M,, Peto TE,, von Seidlein L,, Day NP,, White NJ,, AQUAMAT group. 2010. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 376: 16471657.
113. Talisuna AO,, Karema C,, Ogutu B,, Juma E,, Logedi J,, Nyandigisi A,, Mulenga M,, Mbacham WF,, Roper C,, Guerin PJ,, D’Alessandro U,, Snow RW. 2012. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infect Dis 12: 888896.
114. Antinori S,, Galimberti L,, Milazzo L,, Corbellino M. 2013. Plasmodium knowlesi: the emerging zoonotic malaria parasite. Acta Trop 125: 191201.
115. Utzinger J,, Xiao SH,, Tanner M,, Keiser J. 2007. Artemisinins for schistosomiasis and beyond. Curr Opin Investig Drugs 8: 105116.
116. Wikman-Jorgensen PE,, Henriquez-Camacho CA,, Serrano-Villar S,, Perez-Molina JA. 2012. The role of artesunate for the treatment of urinary schistosomiasis in schoolchildren: a systematic review and meta-analysis. Pathog Glob Health 106: 397404.
117. Perez del Villar L,, Burguillo FJ,, Lopez-Aban J,, Muro A. 2012. Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PLoS One 7: e45867. 10.1371/journal.pone.0045867.
118. Nosten F,, White NJ. 2007. Artemisinin-based combination treatment of falciparum malaria. Am J Trop Med Hyg 77: 181192.
119. Li Q,, Si Y,, Xie L,, Zhang J,, Weina P. 2009. Severe embryolethality of artesunate related to pharmacokinetics following intravenous and intramuscular doses in pregnant rats. Birth Defects Res B Dev Reprod Toxicol 86: 385393.
120. Looareesuwan S,, Chulay JD,, Canfield CJ,, Hutchinson DB, Malarone Clinical Trials Study Group . 1999. Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Am J Trop Med Hyg 60: 533541.
121. Srivastava IK,, Vaidya AB. 1999. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother 43: 13341339.
122. Edstein MD,, Looareesuwan S,, Viravan C,, Kyle DE. 1996. Pharmacokinetics of proguanil in malaria patients treated with proguanil plus atovaquone. Southeast Asian J Trop Med Public Health 27: 216220.
123. Radloff PD,, Philipps J,, Hutchinson D,, Kremsner PG. 1996. Atovaquone plus proguanil is an effective treatment for Plasmodium ovale and P. malariae malaria. Trans R Soc Trop Med Hyg 90: 682.
124. McAuley JB,, Herwaldt BL,, Stokes SL,, Becher JA,, Roberts JM,, Michelson MK,, Juranek DD. 1992. Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years’ experience in the United States. Clin Infect Dis 15: 464468.
125. Markell EK,, Udkow MP. 1986. Blastocystis hominis: pathogen or fellow traveler? Am J Trop Med Hyg 35: 10231026.
126. Chulay JD,, Fleckenstein L,, Smith DH. 1988. Pharmacokinetics of antimony during treatment of visceral leishmaniasis with sodium stibogluconate or meglumine antimoniate. Trans R Soc Trop Med Hyg 82: 6972.
127. Oliveira LF,, Schubach AO,, Martins MM,, Passos SL,, Oliveira RV,, Marzochi MC,, Andrade CA. 2011. Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Trop 118: 8796.
128. Murray HW. 2012. Leishmaniasis in the United States: treatment in 2012. Am J Trop Med Hyg 86: 434440.
129. Jha TK,, Sundar S,, Thakur CP,, Bachmann P,, Karbwang J,, Fischer C,, Voss A,, Berman J. 1999. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N Engl J Med 341: 17951800.
130. More B,, Bhatt H,, Kukreja V,, Ainapure SS. 2003. Miltefosine: great expectations against visceral leishmaniasis. J Postgrad Med 49: 101103.
131. Prasad R,, Kumar R,, Jaiswal BP,, Singh UK. 2004. Miltefosine: an oral drug for visceral leishmaniasis. Indian J Pediatr 71: 143144.
132. Soto J,, Soto P. 2006. Miltefosine: oral treatment of leishmaniasis. Expert Rev Anti Infect Ther 4: 177185.
133. Sindermann H,, Croft SL,, Engel KR,, Bommer W,, Eibl HJ,, Unger C,, Engel J. 2004. Miltefosine (Impavido): the first oral treatment against leishmaniasis. Med Microbiol Immunol 193: 173180.
134. Croft SL,, Seifert K,, Duchene M. 2003. Antiprotozoal activities of phospholipid analogues. Mol Biochem Parasitol 126: 165172.
135. Bhattacharya SK,, Jha TK,, Sundar S,, Thakur CP,, Engel J,, Sindermann H,, Junge K,, Karbwang J,, Bryceson AD,, Berman JD. 2004. Efficacy and tolerability of miltefosine for childhood visceral leishmaniasis in India. Clin Infect Dis 38: 217221.
136. Sundar S,, Jha TK,, Thakur CP,, Engel J,, Sindermann H,, Fischer C,, Junge K,, Bryceson A,, Berman J. 2002. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 347: 17391746.
137. Sundar S,, Sinha P,, Jha TK,, Chakravarty J,, Rai M,, Kumar N,, Pandey K,, Narain MK,, Verma N,, Das VN,, Das P,, Berman J,, Arana B. 2013. Oral miltefosine for Indian post-kala-azar dermal leishmaniasis: a randomised trial. Trop Med Int Health 18: 96100.
138. Webster D,, Umar I,, Kolyvas G,, Bilbao J,, Guiot MC,, Duplisea K,, Qvarnstrom Y,, Visvesvara GS. 2012. Treatment of granulomatous amoebic encephalitis with voriconazole and miltefosine in an immunocompetent soldier. Am J Trop Med Hyg 87: 715718.
139. Martinez DY,, Seas C,, Bravo F,, Legua P,, Ramos C,, Cabello AM,, Gotuzzo E. 2010. Successful treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement. Clin Infect Dis 51: e7e11.
140. Soto J,, Toledo J,, Gutierrez P,, Nicholls RS,, Padilla J,, Engel J,, Fischer C,, Voss A,, Berman J. 2001. Treatment of American cutaneous leishmaniasis with miltefosine, an oral agent. Clin Infect Dis 33: E57E61.
141. Sands M,, Kron MA,, Brown RB. 1985. Pentamidine: a review. Rev Infect Dis 7: 625634.
142. Waalkes TP,, DeVita VT. 1970. The determination of pentamidine (4,4′-diamidinophenoxypentane) in plasma, urine, and tissues. J Lab Clin Med 75: 871878.
143. Davidson RN,, den Boer M,, Ritmeijer K. 2009. Paromomycin. Trans R Soc Trop Med Hyg 103: 653660.
144. Harris J,, Plummer S,, Lloyd D. 2001. Antigiardial drugs. Appl Microbiol Biotechnol 57: 614619.
145. Botero D. 1970. Paromomycin as effective treatment of Taenia infections. Am J Trop Med Hyg 19: 234237.
146. Katz M. 1977. Anthelmintics. Drugs 13: 124136.
147. Pepin J,, Milord F. 1994. The treatment of human African trypanosomiasis. Adv Parasitol 33: 147.
148. Dumas M,, Bouteille B. 2000. Treatment of human African trypanosomiasis. Bull World Health Organ 78: 1474.
149. Taylor HR. 1984. Recent developments in the treatment of onchocerciasis. Bull World Health Organ 62: 509515.
150. Voogd TE,, Vansterkenburg EL,, Wilting J,, Janssen LH. 1993. Recent research on the biological activity of suramin. Pharmacol Rev 45: 177203.
151. Burri C,, Baltz T,, Giroud C,, Doua F,, Welker HA,, Brun R. 1993. Pharmacokinetic properties of the trypanocidal drug melarsoprol. Chemotherapy 39: 225234.
152. Lutje V,, Seixas J,, Kennedy A. 2010. Chemotherapy for second-stage human African trypanosomiasis. Cochrane Database Syst Rev ( 8): CD006201. doi:10.1002/14651858. CD006201.pub2.
153. Kingsnorth AN. 1986. The chemotherapeutic potential of polyamine antimetabolites. Ann R Coll Surg Engl 68: 7681.
154. Huebert ND,, Schwartz JJ,, Haegele KD. 1997. Analysis of 2-difluoromethyl-DL-ornithine in human plasma, cerebrospinal fluid and urine by cation-exchange high-performance liquid chromatography. J Chromatogr A 762: 293298.
155. Milord F,, Loko L,, Ethier L,, Mpia B,, Pepin J. 1993. Eflornithine concentrations in serum and cerebrospinal fluid of 63 patients treated for Trypanosoma brucei gambiense sleeping sickness. Trans R Soc Trop Med Hyg 87: 473477.
156. Kennedy PG. 2013. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol 12: 186194.
157. Croft SL. 1997. The current status of antiparasite chemotherapy. Parasitology 114: S3S15.
158. Fozard JR,, Part ML,, Prakash NJ,, Grove J. 1980. Inhibition of murine embryonic development by alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase. Eur J Pharmacol 65: 379391.
159. Polak A,, Richle R. 1978. Mode of action of the 2-nitroimidazole derivative benznidazole. Ann Trop Med Parasitol 72: 4554.
160. Murta SM,, Ropert C,, Alves RO,, Gazzinelli RT,, Romanha AJ. 1999. In-vivo treatment with benznidazole enhances phagocytosis, parasite destruction and cytokine release by macrophages during infection with a drug-susceptible but not with a derived drug-resistant Trypansoma cruzi population. Parasite Immunol 21: 535544.
161. Docampo R,, Moreno SN. 1984. Free radical metabolites in the mode of action of chemotherapeutic agents and phagocytic cells on Trypanosoma cruzi. Rev Infect Dis 6: 223238.
162. Gutteridge WE. 1985. Existing chemotherapy and its limitations. Br Med Bull 41: 162168.
163. Workman P,, White RA,, Walton MI,, Owen LN,, Twentyman PR. 1984. Preclinical pharmacokinetics of benznidazole. Br J Cancer 50: 291303.
164. Matta Guedes PM,, Gutierrez FR,, Nascimento MS,, Do-Valle-Matta MA,, Silva JS. 2012. Antiparasitical chemotherapy in Chagas’ disease cardiomyopathy: current evidence. Trop Med Int Health 17: 10571065.
165. Bern C. 2011. Antitrypanosomal therapy for chronic Chagas’ disease. N Engl J Med 364: 25272534.
166. Rassi A, Jr,, Rassi A,, Marin-Neto JA. 2010. Chagas disease. Lancet 375: 13881402.
167. Jackson Y,, Chatelain E,, Mauris A,, Holst M,, Miao Q,, Chappuis F,, Ndao M. 2013. Serological and parasitological response in chronic Chagas patients 3 years after nifurtimox treatment. BMC Infect Dis 13: 85. 10.1186/1471-2334-13-85.
168. de Toranzo EG,, Masana M,, Castro JA. 1984. Administration of benznidazole, a chemotherapeutic agent against Chagas disease, to pregnant rats. Covalent binding of reactive metabolites to fetal and maternal proteins. Arch Int Pharmacodyn Ther 272: 1723.
169. Garcia-Bournissen F,, Altcheh J,, Panchaud A,, Ito S. 2010. Is use of nifurtimox for the treatment of Chagas disease compatible with breast feeding? A population pharmacokinetics analysis. Arch Dis Child 95: 224228.


Generic image for table

Treatment of intestinal, blood/tissue (nonplasmodial), and urogenital protozoal infections

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Treatment of major helminthic infections

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Major indications for albendazole

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Major indications for mebendazole

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Major indications for praziquantel

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Major indications for ivermectin

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Major indications for DEC

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Major indications for nitazoxanide

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149
Generic image for table

Treatment regimens for malaria

Citation: Leder K, Weller P. 2015. Antiparasitic Agents, p 2529-2549. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch149

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error