RESUMO
New world cutaneous leishmaniasis (NWCL) is an anthropozoonosis caused by different species of the protozoan Leishmania. Colorimetric in situ hybridization (CISH) was shown to satisfactorily detect amastigote forms of Leishmania spp. in animal tissues, yet it was not tested for the diagnosis of human NWCL. The aim of this study was to compare CISH, histopathology (HP), and immunohistochemistry (IHC) techniques to diagnose NWCL in human cutaneous lesions. The sample comprised fifty formalin-fixed, paraffin-embedded skin biopsy specimens from patients with NWCL caused by L. (V.) braziliensis. These specimens were analyzed by CISH, using a generic probe for Leishmania, IHC, and HP to assess the sensitivity of these methods by using a parasitological culture as a standard reference. Additional specimens from three patients diagnosed with cutaneous mycoses were also included to evaluate cross-reactions between CISH and IHC. The sensitivities of IHC, CISH, and HP for detecting amastigotes was 66%, 54%, and 50%, respectively. IHC, unlike CISH, cross-reacted with different species of fungi. Together, these results demonstrate that CISH may be a complementary assay for the detection of amastigote in the laboratorial diagnosis routine of human NWCL caused by L. (V.) braziliensis.
RESUMO
BACKGROUND: Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. METHODOLOGY: A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10-20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. RESULTS: SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. CONCLUSIONS/SIGNIFICANCE: AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.
Assuntos
Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Adolescente , Adulto , Idoso , Brasil , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Injeções Intramusculares , Leishmania/efeitos dos fármacos , Leishmania/fisiologia , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The present study investigated the diagnostic value of polymerase chain reaction (PCR) performed in parallel to conventional methods at an American tegumentary leishmaniasis (ATL) referral centre for diagnosis. Accuracy parameters for PCR were calculated using 130 patients with confirmed ATL (ATL group), 15 patients established with other diseases and 23 patients with a lesion suggestive of ATL, but without parasitological confirmation (NDEF group). PCR showed 92.3% sensitivity, 93.3% specificity, a 99.2% positive predictive value and a 13.84 positive likelihood ratio. In the NDEF group, PCR confirmed ATL in 13 of the 23 patients, seven of whom responded to leishmaniasis treatment and six who presented spontaneous healing of the lesion. PCR should be included in the routine diagnostic procedures for ATL, especially for cases found to be negative by conventional methods.
Assuntos
DNA de Protozoário/análise , Leishmania/genética , Leishmaniose Cutânea/diagnóstico , Reação em Cadeia da Polimerase , Humanos , Leishmaniose Cutânea/parasitologia , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.
Assuntos
Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Idoso , Feminino , Humanos , Injeções Intralesionais , Masculino , Antimoniato de Meglumina , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. METHODS: A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. RESULTS: Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7-29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1-31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony. CONCLUSIONS: Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.
Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Brasil , Relação Dose-Resposta a Droga , Humanos , Meglumina/administração & dosagem , Antimoniato de Meglumina , Compostos Organometálicos/administração & dosagemRESUMO
BACKGROUND: Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (SL), which is clinically described as a primary ulcer combined with lymphangitis and nodules and/or ulcerated lesions along its pathway. AIMS: To assess the differences between patients with sporotrichoid leishmaniasis and typical cutaneous leishmaniasis (CL). METHODS: From January 2004 to December 2010, 23 cases of SL (4.7%) were detected among 494 CL patients diagnosed at a reference center for the disease in Rio de Janeiro State, Brazil. These 23 cases were compared with the remaining 471 patients presenting CL. RESULTS: SL predominated in female patients (60.9%, p = 0.024), with older age (p = 0.032) and with lesions in upper limbs (52.2%, p = 0.028). CL affected more men (64.5%), at younger age, and with a higher number of lesions exclusively in lower limbs (34.8%). CONCLUSIONS: Differences in clinical and epidemiological presentation were found between SL patients as compared to CL ones, in a region with a known predominance of Leishmania (Viannia) braziliensis. The results are similar to the features of most of the sporotrichosis patients as described in literature, making the differential diagnosis between ATL and sporotrichosis more important in overlapping areas for both diseases, like in Rio de Janeiro State.
Assuntos
Leishmania braziliensis , Leishmaniose Cutânea/diagnóstico , Adulto , Biópsia , Brasil/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/patologia , MasculinoRESUMO
INTRODUCTION:: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS: Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS: The technique is described in detail sufficient to enable replication. CONCLUSIONS:: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.
Assuntos
Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Humanos , Injeções Intralesionais/normas , Antimoniato de MegluminaRESUMO
A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb(5+)/kg/day of intramuscular meglumine antimoniate (Sb(5+)) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.
Assuntos
Antiprotozoários/uso terapêutico , Testes Intradérmicos/métodos , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Adolescente , Adulto , Antiprotozoários/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Meglumina/efeitos adversos , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Estudos Retrospectivos , Falha de Tratamento , Adulto JovemRESUMO
O antimoniato de meglumina (AM) intralesional (IL), por via subcutânea, é recomendado para o tratamento da leishmaniose cutânea (LC). A frequente falta de recursos nas unidades básicas de saúde costuma dificultar o monitoramento de efeitos adversos, o manuseio de comorbidades e o uso de medicamentos de segunda linha. São relatados seis casos de LC tratados com AM IL (devido a contraindicações ou efeitos adversos ao AM por via sistêmica) em uma unidade básica de saúde. As infiltrações com AM IL foram administradas quinzenalmente até a epitelização das lesões cutâneas, que ocorreu em todos os casos. Eczema local de intensidade moderada foi o único efeito adverso observado em um paciente. O AM IL se revelou um tratamento simples, eficiente e seguro para LC.
RESUMO
Abstract Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.
Assuntos
Humanos , Masculino , Feminino , Idoso , Compostos Organometálicos/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Antiprotozoários/administração & dosagem , Fatores de Tempo , Índice de Gravidade de Doença , Injeções Intralesionais , Resultado do Tratamento , Meglumina , Pessoa de Meia-IdadeRESUMO
We evaluated the effectiveness and safety of intralesional meglumine antimoniate (MA) in 24 not submitted to previous treatment patients with cutaneous leishmaniasis (CL) and with contraindication to systemic therapy. Each treatment consisted of one to four intralesional applications of MA at 15-day intervals. Patients' age ranged from 3 to 90 years; fourteen were females. Intralesional treatment in the absence of any relevant toxicity was successful in 20 (83.3%) patients. Three patients required additional treatment with amphotericin B and one required systemic MA. None of the patients developed mucosal lesions when followed up to 60 months. Intralesional MA is an effective and less toxic alternative treatment of patients with CL and contraindication to systemic therapy.
Assuntos
Antiprotozoários/administração & dosagem , Leishmania/crescimento & desenvolvimento , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intralesionais , Masculino , Antimoniato de Meglumina , Pessoa de Meia-Idade , Estatísticas não Paramétricas , População Urbana , Adulto JovemRESUMO
ABSTRACT Background Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (SL), which is clinically described as a primary ulcer combined with lymphangitis and nodules and/or ulcerated lesions along its pathway. Aims To assess the differences between patients with sporotrichoid leishmaniasis and typical cutaneous leishmaniasis (CL). Methods From January 2004 to December 2010, 23 cases of SL (4.7%) were detected among 494 CL patients diagnosed at a reference center for the disease in Rio de Janeiro State, Brazil. These 23 cases were compared with the remaining 471 patients presenting CL. Results SL predominated in female patients (60.9%, p = 0.024), with older age (p = 0.032) and with lesions in upper limbs (52.2%, p = 0.028). CL affected more men (64.5%), at younger age, and with a higher number of lesions exclusively in lower limbs (34.8%). Conclusions Differences in clinical and epidemiological presentation were found between SL patients as compared to CL ones, in a region with a known predominance of Leishmania (Viannia) braziliensis. The results are similar to the features of most of the sporotrichosis patients as described in literature, making the differential diagnosis between ATL and sporotrichosis more important in overlapping areas for both diseases, like in Rio de Janeiro State.
Assuntos
Humanos , Masculino , Feminino , Adulto , Leishmania braziliensis , Leishmaniose Cutânea/diagnóstico , Biópsia , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Estudos Transversais , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/epidemiologia , Técnica Indireta de Fluorescência para AnticorpoRESUMO
Acroangiodermatitis, often known as pseudo-Kaposi sarcoma, is an uncommon angioproliferative entity related to chronic venous insufficiency, arteriovenous fistulae, paralysed limbs, amputation stumps, vascular syndromes and conditions associated with thrombosis. It presents most frequently as purple macules, papules or plaques in the dorsal aspects of the feet, especially the toes, and the malleoli. We report a case of acroangiodermatitis in the plantar aspect of the foot, misdiagnosed for two years, in which haematoxylin-eosin hystopathological stain and immunolabeling with CD34 histochemistry examination were decisive for diagnosis. Patient had chronic venous insufficiency. The lesion responded well to the treatment with a combination of leg elevation and compression.
Assuntos
Acrodermatite/etiologia , Dermatoses do Pé/etiologia , Insuficiência Venosa/complicações , Acrodermatite/patologia , Idoso , Doença Crônica , Feminino , Dermatoses do Pé/patologia , HumanosRESUMO
Abstract INTRODUCTION: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS The technique is described in detail sufficient to enable replication. CONCLUSIONS: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.
Assuntos
Humanos , Compostos Organometálicos/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Antiprotozoários/administração & dosagem , Injeções Intralesionais/normas , Antimoniato de MegluminaRESUMO
This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed following two systemic treatments with meglumine antimoniate. The patient was treated with amphotericin B, which was interrupted due to poor tolerance. Following isolation of Leishmania sp., six intralesional infiltrations of meglumine antimoniate resulted in no response. Leishmania sp promastigotes were again isolated. The patient was submitted to intramuscular 4 mg/kg pentamidine. Parasites from the first and second biopsies were identified as Leishmania (Viannia) braziliensis; those isolated from the first biopsy were more sensitive to meglumine antimoniate in vitro than those isolated from the second biopsy. No relapse was observed.
Assuntos
Antiprotozoários/uso terapêutico , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Pentamidina/uso terapêutico , Adulto , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Antimoniato de Meglumina , Testes de Sensibilidade Parasitária , Resultado do TratamentoRESUMO
Relatamos caso de paciente de 42 anos atendida em centro de referência em leishmanioses no Rio de Janeiro, Brasil, apresentando lesão de leishmaniose cutânea no antebraço direito. Iniciado tratamento com baixa dose de antimoniato de meglumina (AM) intramuscular (5 mg Sb5+/kg/dia), houve melhora após 28 dias, porém com desenvolvimento de eczema generalizado. Após 87 dias, notou-se piora da lesão. A paciente recusou o tratamento com anfotericina B. Infiltrou-se AM na lesão em duas sessões, resultando em eczema local com bolhas. Entretanto, 20 dias depois, tanto a úlcera quanto o eczema regrediram. A administração intralesional do AM deve ser utilizada com cautela em pacientes com hipersensibilidade cutânea a este fármaco.
Assuntos
Leishmaniose/terapia , Leishmaniose Cutânea , Meglumina , EczemaRESUMO
We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.
Relatamos caso de paciente de 42 anos atendida em centro de referência em leishmanioses no Rio de Janeiro, Brasil, apresentando lesão de leishmaniose cutânea no antebraço direito. Iniciado tratamento com baixa dose de antimoniato de meglumina (AM) intramuscular (5 mg Sb5+/kg/dia), houve melhora após 28 dias, porém com desenvolvimento de eczema generalizado. Após 87 dias, notou-se piora da lesão. A paciente recusou o tratamento com anfotericina B. Infiltrou-se AM na lesão em duas sessões, resultando em eczema local com bolhas. Entretanto, 20 dias depois, tanto a úlcera quanto o eczema regrediram. A administração intralesional do AM deve ser utilizada com cautela em pacientes com hipersensibilidade cutânea a este fármaco.
Assuntos
Adulto , Feminino , Humanos , Antiprotozoários/efeitos adversos , Toxidermias/tratamento farmacológico , Eczema/induzido quimicamente , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/efeitos adversos , Compostos Organometálicos/efeitos adversos , Antiprotozoários/administração & dosagem , Eczema/tratamento farmacológico , Injeções Intralesionais , Injeções Intramusculares , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagemRESUMO
A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.
Conduzimos estudo caso-controle que verificou a associação entre a intradermorreação de Montenegro (IDRM), o tempo de evolução da lesão e a resposta terapêutica em pacientes com leishmaniose cutânea (LC) atendidos no Instituto de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brasil. Para cada caso com má resposta à terapêutica foram selecionados aleatoriamente dois controles que evoluíram com cicatrização das lesões após o tratamento, pareados por sexo e idade. Todos os pacientes realizaram tratamento com antimoniato de meglumina (Sb5+) IM, na dose de 5 mg Sb5+/kg/dia, continuamente, por 30 dias. Pacientes com LC apresentaram aproximadamente cinco vezes mais chance de falhar quando as lesões apresentavam menos de dois meses de evolução no primeiro dia de atendimento. Pacientes com falha terapêutica apresentaram reações de IDRM menos intensas que pacientes que evoluíram para a cura clínica. A cada 10 milímetros de aumento na resposta à IDRM, houve uma redução de 26% na chance de ocorrência de falha. O tratamento precoce, traduzido pelo tempo de evolução da lesão menor que dois meses no primeiro dia de atendimento, e resposta de imunidade celular deficiente, traduzida por IDRM menos intensa, demonstraram contribuir para a ocorrência de falha terapêutica na leishmaniose cutânea.