David CV, Craft N, 2009. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther 22: 491–502.
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: 296–306.
Herwaldt BL, 1999. Leishmaniasis. Lancet 354: 1191–1199.
Murray HW, Berman JD, Davies CR, Saravia NG, 2005. Advances in leishmaniasis. Lancet 366: 1561–1577.
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: 261–267.
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: 109–124.
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: 1846–1851.
Schwartz E, Hatz C, Blum J, 2006. New World cutaneous leishmaniasis in travelers. Lancet Infect Dis 6: 342–349.
Kreutzer RD, Christensen HA, 1980. Characterization of Leishmania spp. by isozyme electrophoresis. Am J Trop Med Hyg 29: 199–208.
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: 958–962.
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: 999–1004.
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: 432–435.
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: 415–420.
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: 575–579.
Kreutzer RD, Semko ME, Hendricks LD, Wright N, 1983. Identification of Leishmania spp. by multiple isozyme analysis. Am J Trop Med Hyg 32: 703–715.
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: 1520–1523.
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: 357–364.
Saenz RE, Paz H, Berman JD, 1990. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med 89: 147–155.
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: 612–661.
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: 394–396.
Killingley B, Lamb LE, Davidson RN, 2009. Miltefosine to treat cutaneous leishmaniasis caused by Leishmania tropica. Ann Trop Med Parasitol 103: 171–175.
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: 435–437.
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: 1–3.
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: 122–124.
Brown M, Noursadeghi M, Boyle J, Davidson RN, 2005. Successful liposomal amphotericin B treatment of Leishmania braziliensis cutaneous leishmaniasis. Br J Dermatol 153: 203–205.
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: 42–44.
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: 179–181.
Crofts MAJ, 1976. Use of amphotericin B in mucocutaneous leishmaniasis. J Trop Med 79: 111–113.
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: 870–872.
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: 210–211.
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: 258–259.
Urcuyo FG, Zaias N, 1982. Oral ketoconazole in the treatment of leishmaniasis. Int J Dermatol 21: 414–416.
Weinrauch L, Livshin R, El-On J, 1983. Cutaneous leishmaniasis: treatment with ketoconazole. Cutis 32: 288–294.
Weinrauch L, Livshin R, El-On J, 1987. Ketoconazole in cutaneous leishmaniasis. Br J Dermatol 117: 666–667.
Bellazoug S, Ammar-Khodja A, Belkaid M, Tabett-Derraz O, 1985. La leishmanisose cutanee du nord de L'Algeria. Bull Soc Pathol Exot 78: 615–622.
Viallet J, MacLean JD, Robson H, 1986. Response to ketoconazole in two cases of longstanding cutaneous leishmaniasis. Am J Trop Med Hyg 35: 491–495.
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: 597–599.
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: 281–282.
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: e261–e264.
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: 75–81.
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: 938–943.
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: 188–193.
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: 133–137.
Meyerhoff A, 1999. U.S. Food and Drug Administration approval of liposomal amphotericin B for treatment of visceral leishmaniasis. Clin Infect Dis 28: 42–48.
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: 1061–1064.
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: 695–696.
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: 1739–1746.
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: 357–364.
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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. Leishmania Viannia panamensis was diagnosed in three patients and treated successfully with oral ketoconazole. Miltefosine treatment cured two patients with L. infantum chagasi. A wide variety of Leishmania responded to liposomal amphotericin B administered for 5–7 days. Three patients with L. V. braziliensis, one patient with L. tropica, and two patients with L. infantum chagasi were treated successfully. One person with L. V. braziliensis healed slowly because of a resistant bacterial superinfection, and a second patient with L. infantum chagasi 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.
Authors' addresses: Roshan Ramanathan, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: ramanathanr@niaid.nih.gov. Kawsar R. Talaat, International Health Center for Immunization Research, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: ktalaat@jhsph.edu. Daniel P. Fedorko, Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, E-mail: dfedorko@mail.nih.gov. Siddhartha Mahanty, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: smahanty@niaid.nih.gov. Theodore E. Nash, Gastrointestinal Parasites Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: tnash@niaid.nih.gov.
Reprint requests: Roshan Ramanathan, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Center Drive, Room 4/B1-05, Bethesda, MD 20892, E-mail: ramanathanr@niaid.nih.gov.
David CV, Craft N, 2009. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther 22: 491–502.
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: 296–306.
Herwaldt BL, 1999. Leishmaniasis. Lancet 354: 1191–1199.
Murray HW, Berman JD, Davies CR, Saravia NG, 2005. Advances in leishmaniasis. Lancet 366: 1561–1577.
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: 261–267.
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: 109–124.
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: 1846–1851.
Schwartz E, Hatz C, Blum J, 2006. New World cutaneous leishmaniasis in travelers. Lancet Infect Dis 6: 342–349.
Kreutzer RD, Christensen HA, 1980. Characterization of Leishmania spp. by isozyme electrophoresis. Am J Trop Med Hyg 29: 199–208.
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: 958–962.
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: 999–1004.
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: 432–435.
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: 415–420.
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: 575–579.
Kreutzer RD, Semko ME, Hendricks LD, Wright N, 1983. Identification of Leishmania spp. by multiple isozyme analysis. Am J Trop Med Hyg 32: 703–715.
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: 1520–1523.
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: 357–364.
Saenz RE, Paz H, Berman JD, 1990. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med 89: 147–155.
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: 612–661.
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: 394–396.
Killingley B, Lamb LE, Davidson RN, 2009. Miltefosine to treat cutaneous leishmaniasis caused by Leishmania tropica. Ann Trop Med Parasitol 103: 171–175.
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: 435–437.
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: 1–3.
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: 122–124.
Brown M, Noursadeghi M, Boyle J, Davidson RN, 2005. Successful liposomal amphotericin B treatment of Leishmania braziliensis cutaneous leishmaniasis. Br J Dermatol 153: 203–205.
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: 42–44.
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: 179–181.
Crofts MAJ, 1976. Use of amphotericin B in mucocutaneous leishmaniasis. J Trop Med 79: 111–113.
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: 870–872.
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: 210–211.
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: 258–259.
Urcuyo FG, Zaias N, 1982. Oral ketoconazole in the treatment of leishmaniasis. Int J Dermatol 21: 414–416.
Weinrauch L, Livshin R, El-On J, 1983. Cutaneous leishmaniasis: treatment with ketoconazole. Cutis 32: 288–294.
Weinrauch L, Livshin R, El-On J, 1987. Ketoconazole in cutaneous leishmaniasis. Br J Dermatol 117: 666–667.
Bellazoug S, Ammar-Khodja A, Belkaid M, Tabett-Derraz O, 1985. La leishmanisose cutanee du nord de L'Algeria. Bull Soc Pathol Exot 78: 615–622.
Viallet J, MacLean JD, Robson H, 1986. Response to ketoconazole in two cases of longstanding cutaneous leishmaniasis. Am J Trop Med Hyg 35: 491–495.
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: 597–599.
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: 281–282.
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: e261–e264.
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: 75–81.
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: 938–943.
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: 188–193.
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: 133–137.
Meyerhoff A, 1999. U.S. Food and Drug Administration approval of liposomal amphotericin B for treatment of visceral leishmaniasis. Clin Infect Dis 28: 42–48.
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: 1061–1064.
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: 695–696.
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