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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Clinical and laboratory profiles of patients with early spontaneous healing in cutaneous localized leishmaniasis: a historical cohort study

Authors: Carla Oliveira-Ribeiro, Maria Inês Fernandes Pimentel, Raquel de Vasconcellos Carvalhaes Oliveira, Aline Fagundes, Maria de Fatima Madeira, Cintia Xavier Mello, Eliame Mouta-Confort, Claudia Maria Valete-Rosalino, Erica de Camargo Ferreira Vasconcellos, Marcelo Rosandiski Lyra, Leonardo Pereira Quintella, Liliane de Fatima Antonio, Armando Schubach, Fatima Conceição-Silva

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

Skin ulcers in American cutaneous leishmaniasis (ACL) may heal spontaneously after months/years. However, few cases may present quick heal even during diagnosis procedure (early spontaneous healing- ESH). The main objective of this study was to compare ESH patients with cases requiring specific treatment [non-ESH (NESH)].

Methods

A historical cohort study of ACL patients (n = 445) were divided into 2 groups: ESH – spontaneously healed patients (n = 13; 2.90%), and NESH- treated patients (n = 432; 97.10%). We compared clinical and laboratorial findings at diagnosis, including the lesion healing process.

Results

ESH patients had a higher percentage of single lesions (p = 0.027), epithelialized lesion on initial examination (p = 0.001), lesions located in the dorsal trunk (p = 0.017), besides earlier healing (p < 0.001). NESH presents higher frequency of ulcerated lesions (p = 0.002), amastigotes identified in histopathology exams (p = 0.005), positive cultures (p = 0.001), and higher positivity in ≥3 parasitological exams (p = 0.030). All ESH cases were positive in only a single exam, especially in PCR.

Conclusions

ESH group apparently presented a lower parasitic load evidenced by the difficulty of parasitological confirmation and its positivity only by PCR method. The absence or deficiency of specific treatment is commonly identified as predisposing factors for recurrence and metastasis in ACL. However, due to the drugs toxicity, the treatment of cases which progress to early spontaneous healing is controversial. ESH patients were followed for up to 5 years after cure, with no evidence of recrudescence, therefore suggesting that not treating these patients is justifiable, but periodic dermatological and otorhinolaryngological examinations are advisable to detect a possible relapse.
Literature
1.
go back to reference Silveira FT, Lainson R, Corbett C. Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review. Mem Inst Oswaldo Cruz. 2004;99:239–51.CrossRefPubMed Silveira FT, Lainson R, Corbett C. Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review. Mem Inst Oswaldo Cruz. 2004;99:239–51.CrossRefPubMed
2.
go back to reference Hepburn N, Tidman M, Hunter J. Aminosidine (paromomycin) versus sodium stibogluconate for the treatment of American cutaneous leishmaniasis. Trans R Soc Trop Med Hyg. 1994;88:700–3.CrossRefPubMed Hepburn N, Tidman M, Hunter J. Aminosidine (paromomycin) versus sodium stibogluconate for the treatment of American cutaneous leishmaniasis. Trans R Soc Trop Med Hyg. 1994;88:700–3.CrossRefPubMed
3.
go back to reference Deps PD, Viana MC, Falqueto A, Dietze R. Avaliação comparativa da eficácia e toxicidade do antimoniato de N-metil-glucamina e do estibogluconato de Sódio BP88© no tratamento da leishmaniose cutânea localizada. Rev Soc Bras Med Trop. 2000;33:535–43.CrossRefPubMed Deps PD, Viana MC, Falqueto A, Dietze R. Avaliação comparativa da eficácia e toxicidade do antimoniato de N-metil-glucamina e do estibogluconato de Sódio BP88© no tratamento da leishmaniose cutânea localizada. Rev Soc Bras Med Trop. 2000;33:535–43.CrossRefPubMed
4.
go back to reference Lima MVN, Oliveira RZ, Lima AP, et al. Leishmaniose cutânea com desfecho fatal durante tratamento com antimonial pentavalente. An Bras Dermatol. 2007;82:269–71.CrossRef Lima MVN, Oliveira RZ, Lima AP, et al. Leishmaniose cutânea com desfecho fatal durante tratamento com antimonial pentavalente. An Bras Dermatol. 2007;82:269–71.CrossRef
5.
go back to reference Palacios R, Osorio LE, Grajalew LF, Ochoa MT. Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonite for cutaneous leishmaniasis due to Leishmania viannia species. Am J Trop Med Hyg. 2001;64:187–93.CrossRefPubMed Palacios R, Osorio LE, Grajalew LF, Ochoa MT. Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonite for cutaneous leishmaniasis due to Leishmania viannia species. Am J Trop Med Hyg. 2001;64:187–93.CrossRefPubMed
6.
go back to reference Andersen EMC-SM, Llanos-Cuentos A, Luz-Cjuno M, et al. Comparison of meglumine antimoniate and pentamidine for perureian cutaneous leishmaniasis. J Trop Med Hyg. 2005;72:133–7. Andersen EMC-SM, Llanos-Cuentos A, Luz-Cjuno M, et al. Comparison of meglumine antimoniate and pentamidine for perureian cutaneous leishmaniasis. J Trop Med Hyg. 2005;72:133–7.
7.
go back to reference Bermudez H, Rojas E, Garcia L, et al. Generic sodium stibogluconate is as safe and effective as branded meglumine antimoniate, for the treatment of tegumentary leishmaniasis in Isiboro Secure Park. Bolivia Ann Trop Med Parasitol. 2006;100:591–600.CrossRefPubMed Bermudez H, Rojas E, Garcia L, et al. Generic sodium stibogluconate is as safe and effective as branded meglumine antimoniate, for the treatment of tegumentary leishmaniasis in Isiboro Secure Park. Bolivia Ann Trop Med Parasitol. 2006;100:591–600.CrossRefPubMed
8.
go back to reference Llanos-Cuentas A, Tulliano G, Araujo-Castillo R, et al. Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru. Clin Infect Dis. 2008;46:223–31.CrossRefPubMed Llanos-Cuentas A, Tulliano G, Araujo-Castillo R, et al. Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru. Clin Infect Dis. 2008;46:223–31.CrossRefPubMed
9.
go back to reference World Health Organization. Technical Report Series 949. Control of the leishmaniasis. Genebra, 2010, 186 p. World Health Organization. Technical Report Series 949. Control of the leishmaniasis. Genebra, 2010, 186 p.
10.
go back to reference Marsden PD, Tada MS, Barreto AC, Cuba CC. Spontaneous healing of Leishmania braziliensis braziliensis skin ulcers. Trans R Soc Trop Med Hyg. 1984;78:561–2.CrossRefPubMed Marsden PD, Tada MS, Barreto AC, Cuba CC. Spontaneous healing of Leishmania braziliensis braziliensis skin ulcers. Trans R Soc Trop Med Hyg. 1984;78:561–2.CrossRefPubMed
11.
go back to reference Costa JML, Vale KC, França F, et al. Cura espontânea da leishmaniose causada por Leishmania viannia braziliensis em lesões cutâneas. Rev Soc Bras Med Trop. 1990;23:205–8.CrossRefPubMed Costa JML, Vale KC, França F, et al. Cura espontânea da leishmaniose causada por Leishmania viannia braziliensis em lesões cutâneas. Rev Soc Bras Med Trop. 1990;23:205–8.CrossRefPubMed
12.
go back to reference Olliaro P, Vaillant M, Arana B, et al. Methodology of clinical trials aimed at assessing interventions for cutaneous Leishmaniasis. PLoS Negl Trop Dis. 2013;7(3):1–19.CrossRef Olliaro P, Vaillant M, Arana B, et al. Methodology of clinical trials aimed at assessing interventions for cutaneous Leishmaniasis. PLoS Negl Trop Dis. 2013;7(3):1–19.CrossRef
13.
go back to reference Fagundes A, Schubach A, De Paula CC, et al. Evaluation of polymerase chain reaction in the routine diagnosis for tegumentary leishmaniasis in a referral centre. Mem Inst Oswaldo Cruz. 2010;105:109–12.CrossRefPubMed Fagundes A, Schubach A, De Paula CC, et al. Evaluation of polymerase chain reaction in the routine diagnosis for tegumentary leishmaniasis in a referral centre. Mem Inst Oswaldo Cruz. 2010;105:109–12.CrossRefPubMed
14.
go back to reference Cota GF, Sousa MR, Fereguetti TO, Saleme OS, Alvarisa TK, Rabello A. The cure rate after placebo or no therapy in American cutaneous leishmaniasis: a systematic review and meta-analysis. PLoS One. 2016;11(2):1–15.CrossRef Cota GF, Sousa MR, Fereguetti TO, Saleme OS, Alvarisa TK, Rabello A. The cure rate after placebo or no therapy in American cutaneous leishmaniasis: a systematic review and meta-analysis. PLoS One. 2016;11(2):1–15.CrossRef
15.
go back to reference Furtado T. Critérios para o diagnóstico da leishmaniose tegumentar americana. An Bras Dermatol. 1980;55:81–6. Furtado T. Critérios para o diagnóstico da leishmaniose tegumentar americana. An Bras Dermatol. 1980;55:81–6.
16.
go back to reference Romero GA, Guerra MV, Paes MG, Macedo VO. 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. 2001;65:456–65.CrossRefPubMed Romero GA, Guerra MV, Paes MG, Macedo VO. 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. 2001;65:456–65.CrossRefPubMed
17.
go back to reference Amato VS, de Andrade HF, Duarte M. Mucosal leishmaniasis: in situ characterization of the host inflamatory response, before and after treatment. Acta Trop. 2003;85:39–49.CrossRefPubMed Amato VS, de Andrade HF, Duarte M. Mucosal leishmaniasis: in situ characterization of the host inflamatory response, before and after treatment. Acta Trop. 2003;85:39–49.CrossRefPubMed
18.
go back to reference Belkaid Y, Stebut EV, Mendez S, et al. CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J Immunol. 2002;168:3992–4000.CrossRefPubMed Belkaid Y, Stebut EV, Mendez S, et al. CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J Immunol. 2002;168:3992–4000.CrossRefPubMed
19.
go back to reference Gomes-Silva A, de Cássia BR, Dos Santos NR, et al. Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection? Clin Exp Immunol. 2007;149:440–4.CrossRefPubMedPubMedCentral Gomes-Silva A, de Cássia BR, Dos Santos NR, et al. Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection? Clin Exp Immunol. 2007;149:440–4.CrossRefPubMedPubMedCentral
20.
go back to reference Awasthi A, Mathur RK, Saha B. Immune response to Leishmania infection. Indian J Med Res. 2004;119:238–58.PubMed Awasthi A, Mathur RK, Saha B. Immune response to Leishmania infection. Indian J Med Res. 2004;119:238–58.PubMed
21.
go back to reference Gollob KJ, Antonelli LRV, Faria DR, et al. Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology. Int Immunopharmacol. 2008;8:1338–43.CrossRefPubMedPubMedCentral Gollob KJ, Antonelli LRV, Faria DR, et al. Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology. Int Immunopharmacol. 2008;8:1338–43.CrossRefPubMedPubMedCentral
22.
go back to reference Arana BA, Navin TR, Arana FE, et al. Efficacy of a short course (10 days) of high-dose meglumine antimonate with or without interferon-gamma in treating cutaneous leishmaniasis in Guatemala. Clin Infect Dis. 1994;18:381–4.CrossRefPubMed Arana BA, Navin TR, Arana FE, et al. Efficacy of a short course (10 days) of high-dose meglumine antimonate with or without interferon-gamma in treating cutaneous leishmaniasis in Guatemala. Clin Infect Dis. 1994;18:381–4.CrossRefPubMed
23.
go back to reference Armijos RX, Weigel MM, Calvopina M, et al. Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for new world cutaneous leishmaniasis. Acta Trop. 2004;91:153–60.CrossRefPubMed Armijos RX, Weigel MM, Calvopina M, et al. Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for new world cutaneous leishmaniasis. Acta Trop. 2004;91:153–60.CrossRefPubMed
24.
go back to reference Oliveira-Neto MP, Mattos MS. An alternative antimonial schedule to be used in cutaneous leishmaniasis when high doses of antimony are undesirable. Rev Soc Bras Med Trop. 2006;39:323–6.CrossRefPubMed Oliveira-Neto MP, Mattos MS. An alternative antimonial schedule to be used in cutaneous leishmaniasis when high doses of antimony are undesirable. Rev Soc Bras Med Trop. 2006;39:323–6.CrossRefPubMed
25.
go back to reference Machado P, Araujo C, Da Silva AT, et al. Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer. Clin Infect Dis. 2002;34:69–73.CrossRef Machado P, Araujo C, Da Silva AT, et al. Failure of early treatment of cutaneous leishmaniasis in preventing the development of an ulcer. Clin Infect Dis. 2002;34:69–73.CrossRef
26.
go back to reference Unger A, O’Neal S, Machado PRL, et al. Association of Treatment of American cutaneous Leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil. Am J Trop Med Hyg. 2009;80:574–9.PubMedPubMedCentral Unger A, O’Neal S, Machado PRL, et al. Association of Treatment of American cutaneous Leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil. Am J Trop Med Hyg. 2009;80:574–9.PubMedPubMedCentral
27.
go back to reference Antonio LF, Fagundes A, Oliveira RV, et al. Montenegro skin test and age of skin lesion as predictors of treatment failure in cutaneous leishmaniasis. Rev Inst Med Trop Sao Paulo. 2014;56:375–80.CrossRefPubMedCentral Antonio LF, Fagundes A, Oliveira RV, et al. Montenegro skin test and age of skin lesion as predictors of treatment failure in cutaneous leishmaniasis. Rev Inst Med Trop Sao Paulo. 2014;56:375–80.CrossRefPubMedCentral
28.
go back to reference Berman JD, Chulay JD, Hendricks LD, Oster CN. Susceptibility of clinically sensitive and resistant Leishmania to pentavalent antimony in vitro. Am J Trop Med Hyg. 1982;31:459–65.CrossRefPubMed Berman JD, Chulay JD, Hendricks LD, Oster CN. Susceptibility of clinically sensitive and resistant Leishmania to pentavalent antimony in vitro. Am J Trop Med Hyg. 1982;31:459–65.CrossRefPubMed
29.
go back to reference Arevalo I, Ward B, Miller R, et al. Successful treatment of drug resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis. 2001;33:1847–51.CrossRefPubMed Arevalo I, Ward B, Miller R, et al. Successful treatment of drug resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis. 2001;33:1847–51.CrossRefPubMed
30.
go back to reference Brochu C, Wang J, Roy G, et al. Antimony uptake systems in the protozoan parasite Leishmania and accumulation differences in antimony-resistant parasites. Antimicrob Agents Chemother. 2003;47:3073–9.CrossRefPubMedPubMedCentral Brochu C, Wang J, Roy G, et al. Antimony uptake systems in the protozoan parasite Leishmania and accumulation differences in antimony-resistant parasites. Antimicrob Agents Chemother. 2003;47:3073–9.CrossRefPubMedPubMedCentral
31.
go back to reference Croft SL, Coombs GH. Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol. 2003;19:502–8.CrossRefPubMed Croft SL, Coombs GH. Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol. 2003;19:502–8.CrossRefPubMed
32.
go back to reference Croft SL, Sundar S, Fairlamb AH. Drug resistance in Leishmaniasis. Clin Micobiol Rev. 2006;19:111–26.CrossRef Croft SL, Sundar S, Fairlamb AH. Drug resistance in Leishmaniasis. Clin Micobiol Rev. 2006;19:111–26.CrossRef
33.
go back to reference Rodrigues M, Hueb M, Santos T, Fontes CJ. Factors associated with treatment failure of cutaneous leishmaniasis with meglumine antimoniate. Rev Soc Bras Med Trop. 2006;39:139–45.CrossRefPubMed Rodrigues M, Hueb M, Santos T, Fontes CJ. Factors associated with treatment failure of cutaneous leishmaniasis with meglumine antimoniate. Rev Soc Bras Med Trop. 2006;39:139–45.CrossRefPubMed
34.
go back to reference Ministério da Saúde. Secretaria de Vigilância em Saúde. Manual de Vigilância da Leismaniose Tegumentar Americana. 2 ed atualizada: Ministério da Saúde. 2010:180p. Ministério da Saúde. Secretaria de Vigilância em Saúde. Manual de Vigilância da Leismaniose Tegumentar Americana. 2 ed atualizada: Ministério da Saúde. 2010:180p.
35.
go back to reference Oliveira-Neto MP, Schubach A, Mattos M, et al. A low-dose antimony treatment in 159 patients with American cutaneous leishmaniasis: extensive follow-up studies (up to 10 years). Am J Trop Med Hyg. 1997;57:651–5.CrossRefPubMed Oliveira-Neto MP, Schubach A, Mattos M, et al. A low-dose antimony treatment in 159 patients with American cutaneous leishmaniasis: extensive follow-up studies (up to 10 years). Am J Trop Med Hyg. 1997;57:651–5.CrossRefPubMed
36.
go back to reference Berman JD. Treatment of new world cutaneous and mucosal leishmaniasis. Clin Dermatol. 1996;14:519–22.CrossRefPubMed Berman JD. Treatment of new world cutaneous and mucosal leishmaniasis. Clin Dermatol. 1996;14:519–22.CrossRefPubMed
37.
go back to reference Lainson R. The American leishmaniasis: some observations on their ecology and epidemiology. Trans R Soc Trop Med Hyg. 1983;77:569–96.CrossRefPubMed Lainson R. The American leishmaniasis: some observations on their ecology and epidemiology. Trans R Soc Trop Med Hyg. 1983;77:569–96.CrossRefPubMed
38.
go back to reference Llanos-Cuentas EA, Arana M, Cuba CAC, et al. Leishmaniasis cutanea diseminada asociada a metastasis en mucosas, causada por Leishmania braziliensis braziliensis: fracaso en el hallazgo de parasitos circulantes. Rev Soc Bras Med Trop. 1985;18:271–2.CrossRef Llanos-Cuentas EA, Arana M, Cuba CAC, et al. Leishmaniasis cutanea diseminada asociada a metastasis en mucosas, causada por Leishmania braziliensis braziliensis: fracaso en el hallazgo de parasitos circulantes. Rev Soc Bras Med Trop. 1985;18:271–2.CrossRef
39.
go back to reference Marsden PD, Llanos-Cuentas EA, Lago EL, et al. Human mucocutaneous leishmaniasis in Três Braços, Bahia - Brazil. An area of Leishmania braziliensis braziliensis transmission. III: mucosal disease presentation and initial evolution. Rev Soc Bras Med Trop. 1984;17:179–86.CrossRef Marsden PD, Llanos-Cuentas EA, Lago EL, et al. Human mucocutaneous leishmaniasis in Três Braços, Bahia - Brazil. An area of Leishmania braziliensis braziliensis transmission. III: mucosal disease presentation and initial evolution. Rev Soc Bras Med Trop. 1984;17:179–86.CrossRef
40.
go back to reference Schubach AO, Marzochi KBF, Moreira JS, et al. Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate. Rev Soc Bras Med Trop. 2005;38:213–7.CrossRefPubMed Schubach AO, Marzochi KBF, Moreira JS, et al. Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate. Rev Soc Bras Med Trop. 2005;38:213–7.CrossRefPubMed
41.
go back to reference Azeredo-Coutinho RB, Mendonça SC, Callahan H, et al. Sensitivity of Leishmania braziliensis promastigotes to meglumine antimoniate (glucantime) is higher than that of other Leishmania species and correlates with response to therapy in American tegumentary leishmaniasis. J Parasitol. 2007;93:688–93.CrossRefPubMed Azeredo-Coutinho RB, Mendonça SC, Callahan H, et al. Sensitivity of Leishmania braziliensis promastigotes to meglumine antimoniate (glucantime) is higher than that of other Leishmania species and correlates with response to therapy in American tegumentary leishmaniasis. J Parasitol. 2007;93:688–93.CrossRefPubMed
Metadata
Title
Clinical and laboratory profiles of patients with early spontaneous healing in cutaneous localized leishmaniasis: a historical cohort study
Authors
Carla Oliveira-Ribeiro
Maria Inês Fernandes Pimentel
Raquel de Vasconcellos Carvalhaes Oliveira
Aline Fagundes
Maria de Fatima Madeira
Cintia Xavier Mello
Eliame Mouta-Confort
Claudia Maria Valete-Rosalino
Erica de Camargo Ferreira Vasconcellos
Marcelo Rosandiski Lyra
Leonardo Pereira Quintella
Liliane de Fatima Antonio
Armando Schubach
Fatima Conceição-Silva
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2658-4

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