Volume 84, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



We used a species-specific approach to treat 10 patients with cutaneous leishmaniasis diagnosed using polymerase chain reaction. Non-antimony treatments (oral miltefosine, ketoconazole, and liposomal amphotericin B) were chosen as an alternative to pentavalent antimony drugs based on likely or proven drug efficacy against the infecting species. was diagnosed in three patients and treated successfully with oral ketoconazole. Miltefosine treatment cured two patients with . A wide variety of responded to liposomal amphotericin B administered for 5–7 days. Three patients with , one patient with , and two patients with were treated successfully. One person with healed slowly because of a resistant bacterial superinfection, and a second patient with relapsed and was retreated with miltefosine. These drugs were reasonably well-tolerated. In this limited case series, alternative non-antimony–based regimens were convenient, safe, and effective.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. David CV, Craft N, , 2009. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther 22: 491502.[Crossref] [Google Scholar]
  2. Herwaldt BL, Berman JD, , 1992. Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies. Am J Trop Med Hyg 46: 296306. [Google Scholar]
  3. Herwaldt BL, , 1999. Leishmaniasis. Lancet 354: 11911199.[Crossref] [Google Scholar]
  4. Murray HW, Berman JD, Davies CR, Saravia NG, , 2005. Advances in leishmaniasis. Lancet 366: 15611577.[Crossref] [Google Scholar]
  5. Wortmann G, Miller RS, Oster C, Jackson J, Aronson N, , 2002. A randomized, double-blind study of the efficacy of a 10- or 20-day course of sodium stibogluconate for treatment of cutaneous leishmaniasis in United States military personnel. Clin Infect Dis 35: 261267.[Crossref] [Google Scholar]
  6. Tuon FF, Amato VS, Graf ME, Siqueira AM, Nicodemo AC, Amano Neto V, , 2008. Treatment of New World cutaneous leishmaniasis—a systematic review with a meta-analysis. Int J Dermatol 47: 109124.[Crossref] [Google Scholar]
  7. Arevalo J, Ramirez L, Adaui V, Zimic M, Tulliano G, Miranda-Verástegui C, Lazo M, Loayza-Muro R, De Doncker S, Maurer A, Chappuis F, Dujardin JC, Llanos-Cuentas A, , 2007. Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. J Infect Dis 95: 18461851.[Crossref] [Google Scholar]
  8. Schwartz E, Hatz C, Blum J, , 2006. New World cutaneous leishmaniasis in travelers. Lancet Infect Dis 6: 342349.[Crossref] [Google Scholar]
  9. Kreutzer RD, Christensen HA, , 1980. Characterization of Leishmania spp. by isozyme electrophoresis. Am J Trop Med Hyg 29: 199208. [Google Scholar]
  10. Karamian M, Motazedian MH, Fakhar M, Pakshir K, Jowkar F, Rezanezhad H, , 2008. Atypical presentation of Old-World cutaneous leishmaniasis, diagnosis and species identification by PCR. J Eur Acad Dermatol Venereol 22: 958962.[Crossref] [Google Scholar]
  11. Wortmann G, Hochberg L, Houng H, Sweeney C, Zapor M, Aronson N, Weina P, Ockenhouse C, , 2005. Rapid identification of Leishmania complexes by a real-time PCR assay. Am J Trop Med Hyg 73: 9991004. [Google Scholar]
  12. Stevenson LG, Fedorko DP, Zelazny AM, , 2010. An enhanced method for the identification of Leishmania spp. using real-time polymerase chain reaction and sequence analysis of the 7SL RNA gene region. Diagn Microbiol Infect Dis 66: 432435.[Crossref] [Google Scholar]
  13. Zelazny A, Fedorko DP, Li L, Neva F, Fischer SH, , 2005. Evaluation of 7SL RNA gene sequences for the identification of Leishmania spp. Am J Trop Med Hyg 72: 415420. [Google Scholar]
  14. el Tai NO, Osman OF, el Fari M, Presber W, Schonian G, , 2000. Genetic heterogeneity of ribosomal internal transcribed spacer in clinical samples of Leishmania donovani spotted on filter paper as revealed by single-strand conformation polymorphisms and sequencing. Trans R Soc Trop Med Hyg 94: 575579.[Crossref] [Google Scholar]
  15. Kreutzer RD, Semko ME, Hendricks LD, Wright N, , 1983. Identification of Leishmania spp. by multiple isozyme analysis. Am J Trop Med Hyg 32: 703715. [Google Scholar]
  16. Sindermann H, Engel K, Fischer C, Bommer W, , 2004. Oral miltefosine for leishmaniasis in immunocompromised patients: compassionate use in 39 patients with HIV infection. Clin Infect Dis 39: 15201523.[Crossref] [Google Scholar]
  17. Ritmeijer K, Dejenie A, Assefa Y, Hundie TB, Mesure J, Boots G, den Boer M, Davidson RN, , 2006. A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis 43: 357364.[Crossref] [Google Scholar]
  18. Saenz RE, Paz H, Berman JD, , 1990. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med 89: 147155.[Crossref] [Google Scholar]
  19. Solomon M, Baum S, Barzilai A, Scope A, Trau H, Schwartz E, , 2007. Liposomal amphotericin B in comparison to sodium stibogluconate for cutaneous infection due to Leishmania braziliensis . J Am Acad Dermatol 56: 612661.[Crossref] [Google Scholar]
  20. Keynan Y, Larios OE, Wiseman MC, Plourde M, Ouellette M, Rubinstein E, , 2008. Use of oral miltefosine for cutaneous leishmaniasis in Canadian soldiers returning from Afghanistan. Can J Infect Dis Med Microbiol 19: 394396. [Google Scholar]
  21. Killingley B, Lamb LE, Davidson RN, , 2009. Miltefosine to treat cutaneous leishmaniasis caused by Leishmania tropica . Ann Trop Med Parasitol 103: 171175.[Crossref] [Google Scholar]
  22. Alborzi A, Pouladfar GR, Fakhar M, Motazedian MH, Hatam GR, Kadivar MR, , 2008. Isolation of Leishmania tropica from a patient with visceral leishmaniasis and disseminated cutaneous leishmaniasis, southern Iran. Am J Trop Med Hyg 79: 435437. [Google Scholar]
  23. Tappe D, Müller A, Stich A, , 2010. Resolution of cutaneous old world and new world leishmaniasis after oral miltefosine treatment. Am J Trop Med Hyg 82: 13.[Crossref] [Google Scholar]
  24. del Rosal T, Artigao FB, Miguel MJ, de Lucas R, del Castillo F, , 2010. Successful treatment of childhood cutaneous leishmaniasis with liposomal amphotericin B: report of two cases. J Trop Pediatr 56: 122124.[Crossref] [Google Scholar]
  25. Brown M, Noursadeghi M, Boyle J, Davidson RN, , 2005. Successful liposomal amphotericin B treatment of Leishmania braziliensis cutaneous leishmaniasis. Br J Dermatol 153: 203205.[Crossref] [Google Scholar]
  26. Campos-Muñoz L, Quesada-Cortés A, Martín-Díaz MA, Rubio-Flores C, de Lucas-Laguna R, , 2007. Leishmania braziliensis: report of a pediatric imported case with response to liposomal amphotericin B. Actas Dermosifiliogr 98: 4244.[Crossref] [Google Scholar]
  27. Sampaio SAP, Castro RM, Dillon NL, Martins JEC, , 1971. Treatment of mucocutaneous (American) leishmaniasis with amphotericin B: report of 70 cases. Int J Dermatol 10: 179181.[Crossref] [Google Scholar]
  28. Crofts MAJ, , 1976. Use of amphotericin B in mucocutaneous leishmaniasis. J Trop Med 79: 111113. [Google Scholar]
  29. Di Lella F, Vincenti V, Zennaro D, Afeltra A, Baldi A, Giordano D, Pasanisi E, Bacciu A, Bacciu S, Di Lella G, , 2006. Mucocutaneous leishmaniasis: report of a case with massive involvement of nasal, pharyngeal and laryngeal mucosa. Int J Oral Maxillofac Surg 35: 870872.[Crossref] [Google Scholar]
  30. Soto J, Rea J, Balderrama M, Toledo J, Soto P, Valda L, Berman JD, , 2008. Efficacy of miltefosine for Bolivian cutaneous leishmaniasis. Am J Trop Med Hyg 78: 210211. [Google Scholar]
  31. Wöhrl S, Schnedl J, Auer H, Walochnik J, Stingl G, Geusau A, , 2008. Successful treatment of a married couple for American leishmaniasis with miltefosine. J Eur Acad Dermatol Venereol 22: 258259. [Google Scholar]
  32. Urcuyo FG, Zaias N, , 1982. Oral ketoconazole in the treatment of leishmaniasis. Int J Dermatol 21: 414416.[Crossref] [Google Scholar]
  33. Weinrauch L, Livshin R, El-On J, , 1983. Cutaneous leishmaniasis: treatment with ketoconazole. Cutis 32: 288294. [Google Scholar]
  34. Weinrauch L, Livshin R, El-On J, , 1987. Ketoconazole in cutaneous leishmaniasis. Br J Dermatol 117: 666667.[Crossref] [Google Scholar]
  35. Bellazoug S, Ammar-Khodja A, Belkaid M, Tabett-Derraz O, , 1985. La leishmanisose cutanee du nord de L'Algeria. Bull Soc Pathol Exot 78: 615622. [Google Scholar]
  36. Viallet J, MacLean JD, Robson H, , 1986. Response to ketoconazole in two cases of longstanding cutaneous leishmaniasis. Am J Trop Med Hyg 35: 491495. [Google Scholar]
  37. Leitner V, Weingast J, Harmankaya K, Walochnik J, Pehamberger H, Petzelbauer P, Auer H, Binder M, , 2010. Leishmaniasis in the tongue of an immunocompetent man. Am J Trop Med Hyg 82: 597599.[Crossref] [Google Scholar]
  38. Rongioletti F, Cannata GE, Parodi A, , 2009. Leishmaniasis due to L. infantum presenting as macrocheilitis and responding to liposomal amphotericin B. Eur J Dermatol 19: 281282. [Google Scholar]
  39. Paradisi A, Capizzi R, Zampetti A, Proietti I, De Simone C, Feliciani C, Amerio PL, , 2005. Atypical multifocal cutaneous leishmaniasis in an immunocompetent patient treated by liposomal amphotericin B. J Infect 51: e261e264.[Crossref] [Google Scholar]
  40. Davidson RN, Di Martino L, Gradoni L, Giacchino R, Russo R, Gaeta GB, Pempinello R, Scott S, Raimondi F, Cascio A, Prestileo T, Caldiera L, Wilkinson RJ, Bryceson ADM, , 1994. Liposomal amphotericin B (AmBisome) in Mediterranean visceral leishmaniasis: a multi-centre trial. Q J Med 87: 7581. [Google Scholar]
  41. Davidson RN, di Martino L, Gradoni L, Giacchino R, Gaeta GB, Pempinello R, Scotti S, Cascio A, Castagnola E, Maisto A, Gramiccia M, di Caprio D, Wilkinson RJ, Bryceson AD, , 1996. Short-course treatment of visceral leishmaniasis with liposomal amphotericin B (AmBisome). Clin Infect Dis 22: 938943.[Crossref] [Google Scholar]
  42. Seaman J, Boer C, Wilkinson R, de Jong J, de Wilde E, Sondorp E, Davidson R, , 1995. Liposomal amphotericin B (AmBisome) in the treatment of complicated kala-azar under field conditions. Clin Infect Dis 21: 188193.[Crossref] [Google Scholar]
  43. Russo R, Nigro LC, Minniti S, Montineri A, Gradoni L, Caldeira L, Davidson RN, , 1996. Visceral leishmaniasis in HIV infected patients: treatment with high dose liposomal amphotericin B (AmBisome). J Infect 32: 133137.[Crossref] [Google Scholar]
  44. Meyerhoff A, , 1999. U.S. Food and Drug Administration approval of liposomal amphotericin B for treatment of visceral leishmaniasis. Clin Infect Dis 28: 4248.[Crossref] [Google Scholar]
  45. Neub A, Krahl D, Stich A, Amon U, , 2008. Cutaneous infection with Leishmania infantum in an infant successfully treated with miltefosine. J Dtsch Dermatol Ges 6: 10611064.[Crossref] [Google Scholar]
  46. Ruiz-Villaverde R, Sanchez-Cano D, Villaverde-Gutierrez C, , 2007. Chronic cutaneous leishmaniasis in an immunocompetent patient: response to miltefosine. J Eur Acad Dermatol Venereol 21: 695696. [Google Scholar]
  47. 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.[Crossref] [Google Scholar]
  48. Ritmeijer JK, Dejenie A, Assefa Y, Hundie T, Mesure J, Boots G, den Boer M, Davidson R, , 2006. A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis 43: 357364.[Crossref] [Google Scholar]
  49. Safaei A, Motazedian MH, Vasei M, , 2002. Polymerase chain reaction for diagnosis of cutaneous leishmaniasis in histologically positive, suspicious and negative skin biopsies. Dermatology 205: 1824.[Crossref] [Google Scholar]
  50. Bensoussan E, Nasereddin A, Jonas F, Schnur LF, Jaffe CL, , 2006. Comparison of PCR assays for diagnosis of cutaneous leishmaniasis. J Clin Microbiol 44: 14351439.[Crossref] [Google Scholar]
  51. Shahbazi F, Shahabi S, Kazemi B, Mohebali M, Abadi AR, Zare Z, , 2008. Evaluation of PCR assay in diagnosis and identification of cutaneous leishmaniasis: a comparison with the parasitological methods. Parasitol Res 103: 11591162.[Crossref] [Google Scholar]
  52. Singh S, Sivakumar R, , 2004. Challenges and new discoveries in the treatment of leishmaniasis. J Infect Chemother 10: 307315.[Crossref] [Google Scholar]
  53. Jolliffe DS, , 1986. Cutaneous leishmaniasis from Belize—treatment with ketoconazole. Clin Exp Dermatol 11: 6268.[Crossref] [Google Scholar]
  54. Navin TR, Arana BA, Arana FE, Berman JD, Chajón JF, , 1992. Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala. J Infect Dis 165: 528534.[Crossref] [Google Scholar]
  55. Dan M, Verner E, el-On J, Zuckerman F, Michaeli D, , 1986. Failure of oral ketoconazole to cure cutaneous ulcers caused by Leishmania braziliensis . Cutis 38: 198199. [Google Scholar]
  56. Dedet JP, Jamet P, Esterre P, Ghipponi PM, Genin C, Lalande G, , 1986. Failure to cure Leishmania braziliensis guyanensis cutaneous leishmaniasis with oral ketoconazole. Trans R Soc Trop Med Hyg 80: 176.[Crossref] [Google Scholar]
  57. Ziaei H, Sadeghian G, Hejazi SH, , 2008. Distribution frequency of pathogenic bacteria isolated from cutaneous leishmaniasis lesions. Korean J Parasitol 46: 191193.[Crossref] [Google Scholar]
  58. el-On J, Sneier R, Elias E, , 1992. Leishmania major: bacterial contamination of cutaneous lesions in experimental animals. Isr J Med Sci 28: 847851. [Google Scholar]
  59. Amato VS, Rabello A, Rotondo-Silva A, Kono A, Maldonado TP, Alves IC, Floeter-Winter LM, Neto VA, Shakanai-Yasuda MA, , 2004. Successful treatment of cutaneous leishmaniasis with lipid formulations of amphotericin B in two immunocompromised patients. Acta Trop 92: 127132.[Crossref] [Google Scholar]
  60. Gregoriadis G, , 1991. Overview of liposomes. J Antimicrob Chemother 28 (Suppl B): 3948.[Crossref] [Google Scholar]
  61. Yardley V, Croft S, , 1997. Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis. Antimicrob Agents Chemother 41: 752756. [Google Scholar]
  62. Wortmann GW, Fraser SL, Aronson NE, Davis C, Miller RS, Jackson JD, Oster CN, , 1998. Failure of amphotericin B lipid complex in the treatment of cutaneous leishmaniasis. Clin Infect Dis 26: 10061007.[Crossref] [Google Scholar]
  63. Yardley V, Croft SL, , 2000. A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis. Int J Antimicrob Agents 13: 243248.[Crossref] [Google Scholar]
  64. Shani-Adir A, Kamil S, Rozenman D, Schwartz E, Ramon M, Zalman L, Nasereddin A, Jaffe CL, Ephros M, , 2005. Leishmania tropica in northern Israel: a clinical overview of an emerging focus. J Am Acad Dermatol 53: 810815.[Crossref] [Google Scholar]
  65. Escobar P, Yardley V, Croft SL, , 2001. Activities of hexadecylophosphocholine (miltefosine), liposomal amphotericin B, and sodium stibogluconate (Pentostam) against Leishmania donovani in immunodeficient scid mice. Antimicrob Agents Chemother 45: 18721875.[Crossref] [Google Scholar]
  66. 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.[Crossref] [Google Scholar]
  67. Lewis JH, Zimmerman HJ, Benson GD, Ishak KG, , 1984. Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. Gastroenterology 86: 503513. [Google Scholar]
  68. Heiberg JK, Svejgaard E, , 1981. Toxic hepatitis during ketoconazole treatment. Br Med J (Clin Res Ed) 283: 825826.[Crossref] [Google Scholar]
  69. Duarte PA, Chow CC, Simmons F, Ruskin J, , 1984. Fatal hepatitis associated with ketoconazole therapy. Arch Intern Med 144: 10691070.[Crossref] [Google Scholar]
  70. Knight TE, Shikuma CY, Knight J, , 1991. Ketoconazole-induced fulminant hepatitis necessitating liver transplantation. J Am Acad Dermatol 25: 398400.[Crossref] [Google Scholar]
  71. Lake-Bakaar G, Scheuer PJ, Sherlock S, , 1987. Hepatic reactions associated with ketoconazole in the United Kingdom. Br Med J (Clin Res Ed) 294: 419422.[Crossref] [Google Scholar]
  72. Moen MD, Lyseng-Williamson KA, Scott LJ, , 2009. Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs 69: 361392.[Crossref] [Google Scholar]
  73. Johnson MD, Drew RH, Perfect JR, , 1998. Chest discomfort associated with liposomal amphotericin B: report of three cases and review of the literature. Pharmacotherapy 18: 10531061. [Google Scholar]
  74. Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, Pappas P, Seibel N, Greenberg RN, Dummer S, Schuster M, Holcenberg JS, , 1999. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 340: 764771.[Crossref] [Google Scholar]
  75. Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW, , 2010. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med 362: 504512.[Crossref] [Google Scholar]
  76. Soto J, Berman J, , 2006. Treatment of New World cutaneous leishmaniasis with miltefosine. Trans R Soc Trop Med Hyg 100 (Suppl 1): S34S40.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 04 Aug 2010
  • Accepted : 27 Oct 2010
  • Published online : 05 Jan 2011

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error