Volume 77, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Mucosal leishmaniasis (ML) is an important endemic disease and public-health problem in underdeveloped countries because of its significant morbidity and mortality. Increases in ecological tourism have extended this problem to developed countries. This form of leishmaniasis, caused by reactivation after primary cutaneous lesion, has a natural history of progressive destruction of the nasal septa and soft and hard palates, causing facial disfiguration and leading to respiratory disturbances. Treatment of ML, based on several therapies, depends on use of toxic compounds, and few drugs have emerged over the past 40 years. Drug resistance has increased, and the cure rate is no better than 70% in the largest studies. Despite these data, there has been no systematic review of therapies used to treat this important tropical disease. The aim of this study is to determine the best drug management for treatment of ML in Latin America based on the best studies offered by the medical literature. The MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to ML and therapy. The studies were independently selected by 2 authors. Articles with sufficient data for cure and treatment failures, internal and external validity information, and > 4 patients in each treatment were included. Validation of this systematic review was based on guidelines to guarantee quality; 22 articles met our inclusion criteria. Stibogluconate achieved a 51% cure rate (76/150 patients), and 88% of patients treated with meglumine were cured (121 patients). Pentamidine and amphotericin were as effective as meglumine. Use of itraconazole and other therapies (pentoxifylline, allopurinol, or interferon-γ) was controversial, and numbers of patients in some studies were insufficient for statistical analysis. Meglumine may be the drug of choice in the treatment of ML, as it offers similar cure rates when compared with amphotericin B and pentamidine. Cost, adverse effects, local experience, and availability of drugs to treat ML are strong points to be considered before determining the best management of this disease, especially in developing countries.


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  1. Silveira TG, Arraes SM, Bertolini DA, Teodoro U, Lonardoni MV, Roberto AC, Ramos M, Nerilo SA, Ishikawa E, Shaw J, 1999. The laboratory diagnosis and epidemiology of cutaneous leishmaniasis in Parana State, southern Brazil. Rev Soc Bras Med Trop 32 : 413–423. [Google Scholar]
  2. Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, Keystone JS, Pandey P, Cetron MS, 2006. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 354 : 119–130. [Google Scholar]
  3. Marsden PD, 1986. Mucosal leishmaniasis (“espundia” Escomel, 1911). Trans R Soc Trop Med Hyg 80 : 859–876. [Google Scholar]
  4. Jones TC, Johnson WD Jr, Barretto AC, Lago E, Badaro R, Cerf B, Reed SG, Netto EM, Tada MS, Franca TF, 1987. Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis. J Infect Dis 156 : 73–83. [Google Scholar]
  5. Amato VS, Boulos MI, Amato Neto V, Filomeno LT, 1995. [The use of a silicone T tube for the treatment of a case of American mucocutaneous leishmaniasis with tracheomalacia.]. Rev Soc Bras Med Trop 28 : 129–130 [article in Portugese]. [Google Scholar]
  6. Amato VS, Duarte MI, Nicodemo AC, de Carvalho LV, Pagliari C, da Matta VL, de Oliveira LS, de Castro SM, Uip DE, Amato JG, Amato Neto V, 1998. An evaluation of clinical, serologic, anatomopathologic and immunohistochemical findings for fifteen patients with mucosal leishmaniasis before and after treatment. Rev Inst Med Trop Sao Paulo 40 : 23–30. [Google Scholar]
  7. Grant A, Spraggs PD, Grant HR, Bryceson AD, 1994. Laryngeal leishmaniasis. J Laryngol Otol 108 : 1086–1088. [Google Scholar]
  8. Barral A, Pedral-Sampaio D, Grimaldi G Jr, Momen H, McMahon-Pratt D, Ribeiro de Jesus A, Almeida R, Badaro R, Barral-Netto M, Carvalho EM, et al., 1991. Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. Am J Trop Med Hyg 44 : 536–546. [Google Scholar]
  9. Osorio LE, Castillo CM, Ochoa MT, 1998. Mucosal leishmaniasis due to Leishmania (Viannia) panamensis in Colombia: clinical characteristics. Am J Trop Med Hyg 59 : 49–52. [Google Scholar]
  10. Hunt DL, McKibbon KA, 1997. Locating and appraising systematic reviews. Ann Intern Med 126 : 532–538. [Google Scholar]
  11. Tuon FF, Litvoc MN, Lopes MI, 2006. Adenosine deaminase and tuberculous pericarditis—a systematic review with meta-analysis. Acta Trop 99 : 67–74. [Google Scholar]
  12. Soto-Mancipe J, Grogl M, Berman JD, 1993. Evaluation of pentamidine for the treatment of cutaneous leishmaniasis in Colombia. Clin Infect Dis 16 : 417–425. [Google Scholar]
  13. Martinez S, Gonzalez M, Vernaza ME, 1997. Treatment of cutaneous leishmaniasis with allopurinol and stibogluconate. Clin Infect Dis 24 : 165–169. [Google Scholar]
  14. 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 : E57–E61. [Google Scholar]
  15. 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. [Google Scholar]
  16. Miranda-Verastegui C, Llanos-Cuentas A, Arevalo I, Ward BJ, Matlashewski G, 2005. Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru. Clin Infect Dis 40 : 1395–1403. [Google Scholar]
  17. Llanos-Cuentas A, Echevarria J, Cruz M, La RA, Campos P, Campos M, Franke E, Berman J, Modabber F, Marr J, 1997. Efficacy of sodium stibogluconate alone and in combination with allopurinol for treatment of mucocutaneous leishmaniasis. Clin Infect Dis 25 : 677–684. [Google Scholar]
  18. Deville WL, Buntinx F, Bouter LM, Montori VM, de Vet HC, van der Windt DA, Bezemer PD, 2002. Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol 2 : 9. [Google Scholar]
  19. Jadad AR, McQuay HJ, 1996. Meta-analyses to evaluate analgesic interventions: a systematic qualitative review of their methodology. J Clin Epidemiol 49 : 235–243. [Google Scholar]
  20. Oxman AD, Guyatt GH, 1991. Validation of an index of the quality of review articles. J Clin Epidemiol 44 : 1271–1278. [Google Scholar]
  21. Machado-Coelho GL, Caiaffa WT, Genaro O, Magalhaes PA, Mayrink W, 2005. Risk factors for mucosal manifestation of American cutaneous leishmaniasis. Trans R Soc Trop Med Hyg 99 : 55–61. [Google Scholar]
  22. Larson EE, Marsden PD, 1987. The origin of espundia. Trans R Soc Trop Med Hyg 81 : 880. [Google Scholar]
  23. Lawn SD, Whetham J, Chiodini PL, Kanagalingam J, Watson J, Behrens RH, Lockwood DN, 2004. New World mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers. QJM 97 : 781–788. [Google Scholar]
  24. Scope A, Trau H, Anders G, Barzilai A, Confino Y, Schwartz E, 2003. Experience with New World cutaneous leishmaniasis in travelers. J Am Acad Dermatol 49 : 672–678. [Google Scholar]
  25. Chaudhry Z, Barrett AW, Corbett E, French PD, Zakrzewska JM, 1999. Oral mucosal leishmaniasis as a presenting feature of HIV infection and its management. J Oral Pathol Med 28 : 43–46. [Google Scholar]
  26. Iborra C, Caumes E, Carriere J, Cavelier-Balloy B, Danis M, Bricaire F, 1998. Mucosal leishmaniasis in a heart transplant recipient. Br J Dermatol 138 : 190–192. [Google Scholar]
  27. Motta AC, Arruda D, Souza CS, Foss NT, 2003. Disseminated mucocutaneous leishmaniasis resulting from chronic use of corticosteroid. Int J Dermatol 42 : 703–706. [Google Scholar]
  28. Alrajhi AA, Saleem M, Ibrahim EA, Gramiccia M, 1998. Leishmaniasis of the tongue in a renal transplant recipient. Clin Infect Dis 27 : 1332–1333. [Google Scholar]
  29. Saenz RE, de Rodriguez CG, Johnson CM, Berman JD, 1991. Efficacy and toxicity of pentostam against Panamanian mucosal leishmaniasis. Am J Trop Med Hyg 44 : 394–398. [Google Scholar]
  30. Berman JD, 1988. Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy, and future strategies. Rev Infect Dis 10 : 560–586. [Google Scholar]
  31. Rojas R, Valderrama L, Valderrama M, Varona MX, Ouellette M, Saravia NG, 2006. Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. J Infect Dis 193 : 1375–1383. [Google Scholar]
  32. Rodrigues AM, Hueb M, Santos TA, Fontes CJ, 2006. Factors associated with treatment failure of cutaneous leishmaniasis with meglumine antimoniate. Rev Soc Bras Med Trop 39 : 139–145. [Google Scholar]
  33. Rey JA, Travi BL, Valencia AZ, Saravia NG, 1990. Infectivity of the subspecies of the Leishmania braziliensis complex in vivo and in vitro. Am J Trop Med Hyg 43 : 623–631. [Google Scholar]
  34. Saravia NG, Weigle K, Segura I, Giannini SH, Pacheco R, Labrada LA, Goncalves A, 1990. Recurrent lesions in human Leishmania braziliensis infection—reactivation or reinfection? Lancet 336 : 398–402. [Google Scholar]
  35. Mebrahtu YB, Lawyer PG, Pamba H, Koech D, Perkins PV, Roberts CR, Were JB, Hendricks LD, 1992. Biochemical characterization and zymodeme classification of Leishmania isolates from patients, vectors, and reservoir hosts in Kenya. Am J Trop Med Hyg 47 : 852–892. [Google Scholar]
  36. Deps PD, Viana MC, Falqueto A, Dietze R, 2000. Comparative assessment of the efficacy and toxicity of N-methylglucamine and BP88 sodium stibogluconate in the treatment of localized cutaneous leishmaniasis. Rev Soc Bras Med Trop 33 : 535–543. [Google Scholar]
  37. Saldanha AC, Romero GA, Merchan-Hamann E, Magalhaes AV, Macedo VO, 1999. A comparative study between sodium stibogluconate BP 88R and meglumine antimoniate in the treatment of cutaneous leishmaniasis. I. The efficacy and safety. Rev Soc Bras Med Trop 32 : 383–387. [Google Scholar]
  38. Oliveira-Neto MP, Mattos M, Pirmez C, Fernandes O, Goncalves-Costa SC, Souza CF, Grimaldi G Jr, 2000. Mucosal leishmaniasis (“espundia”) responsive to low dose of N-methylglucamine (Glucantime) in Rio de Janeiro, Brazil. Rev Inst Med Trop Sao Paulo 42 : 321–325. [Google Scholar]
  39. Roberts WL, McMurray WJ, Rainey PM, 1998. Characterization of the antimonial antileishmanial agent meglumine antimonate (glucantime). Antimicrob Agents Chemother 42 : 1076–1082. [Google Scholar]
  40. Berman JD, Grogl M, 1988. Leishmania mexicana: chemistry and biochemistry of sodium stibogluconate (Pentostam). Exp Parasitol 67 : 96–103. [Google Scholar]
  41. Dedet JP, Melogno R, Cardenas F, Valda L, David C, Fernandez V, Torrez ME, Demier-David L, Lyevre P, Villareal ME, 1995. Rural campaign to diagnose and treat mucocutaneous leishmaniasis in Bolivia. Bull World Health Organ 73 : 339–345. [Google Scholar]
  42. Adler-Moore J, Proffitt RT, 2002. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience. J Antimicrob Chemother 49 (Suppl 1): 21–30. [Google Scholar]
  43. Nonata R, Sampaio R, Marsden PD, 1997. Mucosal leishmaniasis unresponsive to glucantime therapy successfully treated with AmBisome. Trans R Soc Trop Med Hyg 91 : 77. [Google Scholar]
  44. Sampaio RN, Marsden PD, 1997. Treatment of the mucosal form of leishmaniasis without response to glucantime, with liposomal amphotericin B. Rev Soc Bras Med Trop 30 : 125–128. [Google Scholar]
  45. Amato VS, Tuon FF, Campos A, Bacha HA, Nicodemo AC, Neto VA, Shikanai-Yasuda MA, 2007. Treatment of mucosal leishmaniasis with a lipid formulation of amphotericin B. Clin Infect Dis 44 : 311–312. [Google Scholar]
  46. Sampaio RN, Marsden PD, 1997. Treatment of the mucosal form of leishmaniasis without response to glucantime, with liposomal amphotericin B. Rev Soc Bras Med Trop 30 : 125–128. [Google Scholar]
  47. de Paula CD, Sampaio JH, Cardoso DR, Sampaio RN, 2003. [A comparative study between the efficacy of pentamidine isothionate given in three doses for one week and N-methil-glucamine in a dose of 20mgSbV/day for 20 days to treat cutaneous leishmaniasis.] Rev Soc Bras Med Trop 36 : 365–371 [article in Portugese]. [Google Scholar]
  48. Amato V, Amato J, Nicodemo A, Uip D, Amato-Neto V, Duarte M, 1998. [Treatment of mucocutaneous leishmaniasis with pentamidine isothionate.] Ann Dermatol Venereol 125 : 492–495 [article in French]. [Google Scholar]
  49. Amato VS, de Paula JG, Imamura R, Amato Neto V, Duarte MI, Boulos MI, Boulos M, Nicodemo AC, de Mendonca JS, 1996. [Treatment of American cutaneous leishmaniasis, with lesions in the mucosa, using pentamidine isethionate.] Rev Soc Bras Med Trop 29 : 477–481 [article in Portugese]. [Google Scholar]
  50. Borelli D, 1987. A clinical trial of itraconazole in the treatment of deep mycoses and leishmaniasis. Rev Infect Dis 9 (Suppl 1): S57–S63. [Google Scholar]
  51. Albanese G, Giorgetti P, Santagostino L, Crippa D, Sala G, 1989. Cutaneous leishmaniasis. Treatment with itraconazole. Arch Dermatol 125 : 1540–1542. [Google Scholar]
  52. Akuffo H, Dietz M, Teklemariam S, Tadesse T, Amare G, Berhan TY, 1990. The use of itraconazole in the treatment of leishmaniasis caused by Leishmania aethiopica. Trans R Soc Trop Med Hyg 84 : 532–534. [Google Scholar]
  53. Pialoux G, Hennequin C, Dupont B, Ravisse P, 1990. Cutaneous leishmaniasis in an AIDS patient: cure with itraconazole. J Infect Dis 162 : 1221–1222. [Google Scholar]
  54. Van den Enden E, Van Gompel A, Stevens A, Vandeghinste N, Le Ray D, Gigase P, De Beule K, Van den Ende J, 1994. Treatment of cutaneous leishmaniasis with oral itraconazole. Int J Dermatol 33 : 285–286. [Google Scholar]
  55. Gangneux JP, Dullin M, Sulahian A, Garin YJ, Derouin F, 1999. Experimental evaluation of second-line oral treatments of visceral leishmaniasis caused by Leishmania infantum. Antimicrob Agents Chemother 43 : 172–174. [Google Scholar]
  56. Rodriguez LV, Dedet JP, Paredes V, Mendoza C, Cardenas F, 1995. A randomized trial of amphotericin B alone or in combination with itraconazole in the treatment of mucocutaneous leishmaniasis. Mem Inst Oswaldo Cruz 90 : 525–528. [Google Scholar]
  57. Viegas AC, Furtado TA, 1968. Therapeutic tests with leishmaniasis Americana. VII. Pyrimethamine. An Bras Dermatol 43 : 162–175. [Google Scholar]
  58. Avila JL, Casanova MA, 1982. Comparative effects of 4-aminopyrazolopyrimidine, its 2′-deoxyriboside derivative, and allopurinol on in vitro growth of American Leishmania species. Antimicrob Agents Chemother 22 : 380–385. [Google Scholar]
  59. Martinez S, Marr JJ, 1992. Allopurinol in the treatment of American cutaneous leishmaniasis. N Engl J Med 326 : 741–744. [Google Scholar]
  60. Marsden PD, Cuba CC, Barreto AC, 1984. Allopurinol treatment in human Leishmania braziliensis braziliensis infections. Trans R Soc Trop Med Hyg 78 : 701. [Google Scholar]
  61. Guerra MF, Marsden PD, Cuba CC, Barretto AC, 1981. Further trials of nifurtimox in mucocutaneous leishmaniasis. Trans R Soc Trop Med Hyg 75 : 335–337. [Google Scholar]
  62. Marsden PD, Cuba CC, Barreto AC, Sampaio RN, Rocha RA, 1979. Nifurtimox in the treatment of South American leishmaniasis. Trans R Soc Trop Med Hyg 73 : 391–394. [Google Scholar]
  63. Romero GA, Lessa HA, Macedo VO, Carvalho EM, Barral A, Magalhaes AV, Orge MG, Abreu MV, Marsden PD, 1996. [Open therapeutic study with aminosidine sulfate in mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis.] Rev Soc Bras Med Trop 29 : 557–565 [article in Portugese]. [Google Scholar]

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  • Received : 31 Jan 2007
  • Accepted : 04 Apr 2007

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