Volume 80, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Cure rates for American cutaneous leishmaniasis (ACL) range between 60% and 90%. Early evidence suggests lower cure rates for early ACL before the development of the ulceration. We evaluated risk factors for treatment failure in patients with early and classic ulcerative ACL. Patients (n = 136) were 13–60 years of age and had lesions with a duration of 15–90-days. Patients were treated with antimony (20 mg/kg/day for 20 days). The primary outcome was lesion cure by 90 days without recurrence. Patients with early ACL (n = 16) had papules, nodules, plaques, or superficial ulcerations with less than 30 days of illness. Patients with classic ulcerative ACL (n = 120) had ulcerated classic lesions, longer duration, larger lesions, and higher levels of interferon-γ and tumor necrosis factor-α ( 0.01 for all comparisons). Ulcerated lesions were associated with a lower treatment failure rate compared with early ACL (25.8% versus 75.0%; < 0.001). Early treatment of ACL does not prevent lesion ulceration and is associated with higher rates of treatment failure.


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  1. Desjeux P, 2004. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27 : 305–318. [Google Scholar]
  2. Jones TC, Johnson WD Jr, Barretto AC, Lago E, Badaro R, Cerf B, Reed SG, Netto EM, Tada MS, Franca TF, Wiese K, Golightly L, Fikrig E, Costa JM, Cuba CC, Marsden PD, 1987. Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis. J Infect Dis 156 : 73–83. [Google Scholar]
  3. Barral-Netto M, Machado P, Bittencourt A, Barral A, 1997. Recent advances in the pathophysiology and treatment of human cutaneous leishmaniasis. Curr Opin Dermatol 4 : 51–58. [Google Scholar]
  4. Llanos Cuentas EA, Cuba CC, Barreto AC, Marsden PD, 1984. Clinical characteristics of human Leishmania braziliensis braziliensis infections. Trans R Soc Trop Med Hyg 78 : 845–846. [Google Scholar]
  5. Bittencourt AL, Costa JM, Carvalho EM, Barral A, 1993. Leishmaniasis recidiva cutis in American cutaneous leishmaniasis. Int J Dermatol 32 : 802–805. [Google Scholar]
  6. Carvalho EM, Barral A, Costa JM, Bittencourt A, Marsden P, 1994. Clinical and immunopathological aspects of disseminated cutaneous leishmaniasis. Acta Trop 56 : 315–325. [Google Scholar]
  7. Murray HW, Berman JD, Davies CR, Saravia NG, 2005. Advances in leishmaniasis. Lancet 366 : 1561–1577. [Google Scholar]
  8. Weina P, Neafie R, Wortmann G, Polheumus M, Aronson N, 2004. Old world leishmaniasis: an emerging infection among deployed US military and civilian workers. Clin Infect Dis 39 : 1674–1680. [Google Scholar]
  9. Almeida R, d’Oliveira A Jr, Machado P, Bacellar O, Ko A, de Jesus A, Mobashery N, Santos JB, Carvalho EM, 1999. Randomized, double-blind study of stibogluconate plus human granulocyte macrophage colony-stimulating factor versus stibogluconate alone in the treatment of cutaneous Leishmaniasis. J Infect Dis 180 : 1735–1737. [Google Scholar]
  10. Romero GA, Guerra MV, Paes MG, Macedo VO, 2001. Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate. Am J Trop Med Hyg 65 : 456–465. [Google Scholar]
  11. Carvalho EM, Johnson WD, Barreto E, Marsden PD, Costa JL, Reed S, Rocha H, 1985. Cell mediated immunity in American cutaneous and mucosal leishmaniasis. J Immunol 135 : 4144–4148. [Google Scholar]
  12. Ribeiro-de-Jesus A, Almeida RP, Lessa H, Bacellar O, Carvalho EM, 1998. Cytokine profile and pathology in human leishmaniasis. Braz J Med Biol Res 31 : 143–148. [Google Scholar]
  13. Bittencourt A, Barral A, de Jesus A, de Almeida R, Grimaldi Junior G, 1989. In situ identification of Leishmania amazonensis associated with diffuse cutaneous leishmaniasis in Bahia, Brazil. Mem Inst Oswaldo Cruz 84 : 585–586. [Google Scholar]
  14. Barral A, Costa JM, Bittencourt AL, Barral-Netto M, Carvalho EM, 1995. Polar and subpolar diffuse cutaneous leishmaniasis in Brazil: clinical and immunopathologic aspects. Int J Dermatol 34 : 474–479. [Google Scholar]
  15. Bomfim G, Nascimento C, Costa J, Carvalho EM, Barral-Netto M, Barral A, 1996. Variation of cytokine patterns related to therapeutic response in diffuse cutaneous leishmaniasis. Exp Parasitol 84 : 188–194. [Google Scholar]
  16. Follador I, Araujo C, Bacellar O, Araujo CB, Carvalho LP, Almeida RP, Carvalho EM, 2002. Epidemiologic and immunologic findings for the subclinical form of Leishmania braziliensis infection. Clin Infect Dis 34 : E54–E58. [Google Scholar]
  17. Castes M, Trujillo D, Rojas M, Fernandez CT, Araya L, Cabrera M, Blackwell J, Convit J, 1993. Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis. Biol Res 26 : 233–238. [Google Scholar]
  18. Bacellar O, Lessa H, Schriefer A, Machado P, Ribeiro de Jesus A, Dutra WO, Gollob KJ, Carvalho EM, 2002. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infect Immun 70 : 6734–6740. [Google Scholar]
  19. Machado P, Kanitakis J, Almeida R, Chalou A, Araujo C, Carvalho E, 2002. Evidence of in situ cytotoxicity in American cutaneous leishmaniasis. Eur J Dermatol 12 : 449–451. [Google Scholar]
  20. Faria D, Gollob K, Barbosa JJ, Schriefer A, Machado PR, Lessa H, Carvalho LP, Romano-Silva MA, de Jesus AR, Carvalho EM, Dutra WO, 2005. Decreased in situ expression of interleukin-10 receptor is correlated with the exacerbated inflammatory and ctyotoxic responses observed in mucosal leishmaniasis. Infect Immun 73 : 7853–7859. [Google Scholar]
  21. Machado PR, Lessa H, Lessa M, Guimarães LH, Bang H, Ho JL, Carvalho EM, 2007. Oral pentoxifylline combined with pen-tavalent antimony: a randomized trial for mucosal leishmaniasis. Clin Infect Dis 44 : 788–793. [Google Scholar]
  22. Lessa HA, Machado P, Lima F, Cruz AA, Bacellar O, Guerreiro J, Carvalho EM, 2001. Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony. Am J Trop Med Hyg 65 : 87–89. [Google Scholar]
  23. Sadeghian G, Nilforoushzadeh M, 2006. Effect of combination therapy with systemic glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis. Int J Dermatol 45 : 819–821. [Google Scholar]
  24. Báfica A, Oliveira F, Freitas L, Nascimento E, Barral A, 2003. American cutaneous leishmaniasis unresponsive to antimonial drugs: successful treatment using combination of N-methylglucamine antimoniate plus pentoxifylline. Int J Dermatol 42 : 203–207. [Google Scholar]
  25. Barral A, Barral-Netto M, Almeida R, de Jesus AR, Grimaldi Jr G, Netto EM, Santos I, Bacellar O, Carvalho EM, 1992. Lymphadenopathy associated with Leishmania braziliensis cutaneous infection. Am J Trop Med Hyg 47 : 587–592. [Google Scholar]
  26. Barral A, Guerreiro J, Bomfim G, Correia D, Barral-Netto M, Carvalho EM, 1995. Lymphadenopathy as the first sign of human cutaneous infection by Leishmania braziliensis. Am J Trop Med Hyg 53 : 256–259. [Google Scholar]
  27. Machado P, Araujo C, Da Silva AT, Almeida RP, d’Oliveira A Jr, Bittencourt A, Carvalho EM, 2002. Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer. Clin Infect Dis 34 : E69–E73. [Google Scholar]
  28. O’Neal SE, Guimaraes LH, Machado PR, Alcântara L, Morgan DJ, Passos S, Glesby MJ, Carvalho EM, 2007. Influence of helminth infections on the clinical course of and immune response to Leishmania braziliensis cutaneous leishmaniasis. J Infect Dis 195 : 142–148. [Google Scholar]
  29. Reed SG, Badaro R, Masur H, Carvalho EM, Lorenco R, Lisboa A, Teixeira R, Johnson WD Jr, Jones TC, 1986. Selection of a skin test antigen for American visceral leishmaniasis. Am J Trop Med Hyg 35 : 79–85. [Google Scholar]
  30. Herwaldt B, Arana B, Navin T, 1992. The natural history of cutaneous leishmaniasis in Guatemala. J Infect Dis 165 : 518–527. [Google Scholar]
  31. Weigle K, Saravia N, 1996. Natural history, clinical evolution, and the host-parasite interaction in New World cutaneous leishmaniasis. Clin Dermatol 14 : 433–450. [Google Scholar]
  32. Hernandez C, 2006. Natural history of cutaneous and mucocutaneous leishmaniasis. Biomedica (Bogota) 26 : 10–12. [Google Scholar]
  33. Llanos-Cuentas EA, Marsden PD, Cuba CC, Barreto AC, Campos M, 1984. Possible risk factors in development of mucosal lesions in leishmaniasis. Lancet 2 : 295. [Google Scholar]
  34. Machado-Coelho G, Caiatta W, Genaro O, Magalhaes P, Mayrink W, 2005. Risk factors for mucosal manifestations of ACL. Trans R Soc Trop Med Hyg 99 : 59–61. [Google Scholar]
  35. Llanos-Cuentas A, Tulliano G, Araujo-Castillo R, Miranda-Verastegui C, Santamaria-Castrellon G, Ramirez L, Lazo M, De Doncker S, Boelaert M, Robays J, Dujardin JC, Arevalo J, Chappuis F, 2008. Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru. Clin Infect Dis 46 : 223–231. [Google Scholar]
  36. 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 195 : 1846–1851. [Google Scholar]
  37. Rodrigues M, Hueb M, Santos T, Fontes CJ, 2006. Factors associated with treatment failure of cutaneous leishmaniasis with meglumine antimoniate. Rev Soc Bras Med Trop 39 : 139–145. [Google Scholar]
  38. Palacios R, Osorio L, Grajalew L, Ochoa M, 2001. Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species. Am J Trop Med Hyg 64 : 187–193. [Google Scholar]
  39. Antonelli L, Dutra W, Almeida R, Bacellar O, Carvalho E, Gollob K, 2005. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis. Immunol Lett 101 : 226–230. [Google Scholar]
  40. Da-Cruz A, Bittar R, Mattos M, Oliveira-Neto MP, Nogueira R, Pinho-Ribeiro V, Azeredo-Coutinho RB, Coutinho SG, 2002. T-cell mediated immune responses in patients with cutaneous or mucosal leishmaniasis: long-term evaluation after therapy. Clin Diagn Lab Immunol 9 : 251–256. [Google Scholar]
  41. Salhi A, Rodrigues V Jr, Santoro F, Dessein H, Romano A, Castellano LR, Sertorio M, Rafati S, Chevillard C, Prata A, Alcaïs A, Argiro L, Dessein A, 2008. Immunological and genetic evidence for a crucial role of IL-10 in cutaneous lesions in humans infected with Leishmania braziliensis. J Immunol 180 : 6139–6148. [Google Scholar]
  42. Rocha PN, Almeida RP, Bacellar O, Ribeiro de Jesus A, Correia Filho D, Cruz Filho A, Barral A, Coffman RL, Carvalho EM, 1999. Down-regulation of Th1 type of response in early human American cutaneous leishmaniasis. J Infect Dis 180 : 1731–1734. [Google Scholar]
  43. de Oliveira Guerra JA, Talhari S, Paes MG, Garrido M, Talhari JM, 2003. Clinical and diagnostic aspects of American tegumentary leishmaniasis in soldiers simultaneously exposed to the infection in the Amazon region. Rev Soc Bras Med Trop 36 : 587–590. [Google Scholar]
  44. Correia D, Macedo VO, Carvalho EM, Barral A, Magalhães AV, Abreu MVA, Orge Orge MG, Marsden P, 1996. Estudo com-parativo entre antimoniato de meglumina, isotianato de pent-amidina e sulfato de aminosidine, no tratamento de lesões cutâneas primárias causadas por Leishmania (viannia) braziliensis. Rev Soc Bras Med Trop 29 : 447–453. [Google Scholar]

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  • Received : 05 Aug 2008
  • Accepted : 20 Dec 2008

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