American tegumentary leishmaniasis: severe side effects of pentavalent antimonial in a patient with chronic renal failure

Abstract: Pentavalent antimonials are the first-line drug treatment for American tegumentary leishmaniasis. We report on a patient with chronic renal failure on hemodialysis who presented with cutaneous lesions of leishmaniasis for four months. The patient was treated with intravenous meglumine under strict nephrological surveillance, but cardiotoxicity, acute pancreatitis, pancytopenia, and cardiogenic shock developed rapidly. Deficient renal clearance of meglumine antimoniate can result in severe toxicity, as observed in this case. These side effects are related to cumulative plasma levels of the drug. Therefore, second-line drugs like amphotericin B are a better choice for patients on dialysis.

Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary leishmaniasis acquired in different Brazilian regions

Abstract INTRODUCTION: Favorable responses in American tegumentary leishmaniasis (ATL) patients to treatment with 5 mg Sbv/kg/day meglumine antimoniate (MA) has been reported in Rio de Janeiro, but little is known regarding the therapeutic response to low doses in patients from other locations. METHODS: A retrospective review of medical records was conducted to compare the therapeutic response to 5 mg Sbv/kg/day MA treatment among 36 patients who acquired ATL in Brazilian states other than Rio de Janeiro (OS group) and 72 patients from Rio de Janeiro (RJ group). RESULTS: One course of 5 mg Sbv/kg/day MA cured 72.8% of 81 cutaneous (CL) and 66.6% of 27 mucosal (ML) leishmaniasis-infected patients: 70% in the CL/RJ group, 81% in the CL/OS group, 50% in the ML/RJ group, and 80% in the ML/OS group. After up to two additional treatment courses at the same dose, 88.9% and 85.2% of the CL and ML patients were cured, respectively. Adverse events were observed in 40% of patients in the CL/RJ group, 57% of the CL/OS group, 58% of the ML/RJ group, and 80% of the ML/OS group. No significant differences were observed in the cure rates or adverse effects between the RJ and OS groups. No patients required permanent discontinuation of treatment due to adverse events. CONCLUSIONS: Patients with ATL acquired in both RJ and OS may respond to low-dose MA. While high-dose MA should remain the standard treatment for ATL, low-dose MA might be preferred when toxicity is a primary concern.

Treatment of cutaneous leishmaniasis with thermotherapy in Brazil: an efficacy and safety study

Abstract: BACKGROUND: Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES: To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS: We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination. A single radiofrequency thermotherapy session at 50ºC for 30 seconds was applied to the lesion and its edges. In patients with more than one lesion, only the largest one was treated initially. If after 30 days there was no evidence of healing, the smaller lesion was also treated with thermotherapy. Clinical cure was defined as visible healing for three months after treatment. The patients were followed-up for six months and there was no follow-up loss. RESULTS: Of all 23 lesions, only two evolved to complete healing without the need of treatment. Of 21 lesions, 18 (85.7%) achieved full healing. The main observed side effects were itching, burning sensation, pain and blisters. STUDY LIMITATIONS: Sample with a small number of patients and short follow-up. CONCLUSION: Thermotherapy can be considered a therapeutic alternative in localized cutaneous leishmaniasis, especially in cases of single cutaneous lesions and with formal contraindications to conventional treatment with pentavalent antimonials.

Intralesional meglumine antimoniate for the treatment of localised cutaneous leishmaniasis: a retrospective review of a Brazilian referral centre

Although intralesional meglumine antimoniate (MA) infiltration is considered an option for cutaneous leishmaniasis (CL) therapy and is widely used in the Old World, there have been few studies supporting this therapeutic approach in the Americas. This study aims to describe outcomes and adverse events associated with intralesional therapy for CL. This retrospective study reviewed the experience of a Brazilian leishmaniasis reference centre using intralesional MA to treat 31 patients over five years (2008 and 2013). The median age was 63 years (22-86) and the median duration time of the lesions up to treatment was 16 weeks. In 22 patients (71%), intralesional therapy was indicated due to the presence of contraindications or previous serious adverse events with systemic MA. Other indications were failure of systemic therapy or ease of administration. Intralesional treatment consisted of one-six infiltrations (median three) for a period of up to 12 weeks. The initial (three months) and definitive (six months) cure rates were 70.9% and 67.7%, respectively. Most patients reported mild discomfort during infiltration and no serious adverse events were observed. In conclusion, these results show that the intralesional MA efficacy rate was very similar to that of systemic MA treatment, and reinforce the need for further studies with adequate design to establish the efficacy and safety of this therapeutic approach.

Estudio de los conocimientos, actitudes y prácticas de la leishmaniasis: evidencias del olvido estatal en el Darién Colombiano / Study of knowledge, attitudes, and practices related to leishmaniasis: evidence of government neglect in the Colombian Darién / Estudo dos conhecimentos, atitudes e práticas da leishmaniose: evidências da negligência do Estado no Darién colombiano

La leishmaniasis cutánea americana (LCA) es considerada un problema de salud pública a nivel mundial, y su incidencia en Colombia es de 12 mil casos por año. Durante años se han implementado programas de control, que frecuentemente ignoran características sociales, económicas y demográficas de las regiones afectadas. Como parte de un estudio de tipo epidemiológico, en este artículo se presentarán los resultados de un estudio sobre los conocimientos, actitudes y prácticas (CAP) frente a la leishmaniasis, que tienen las poblaciones de las zonas rurales del municipio de Acandí, en el Darién Colombiano. Para el estudio se utilizaron herramientas cualitativas como la etnografía y cuantitativas, como las encuestas dirigidas. Los resultados ponen en manifiesto el desconocimiento de la población en aspectos fundamentales como el reconocimiento del vector. Además, existen diferencias en las CAP por género y por tipo de población, pero no por su distribución geográfica. Se evidenció el abandono estatal como factor determinante en la perpetuación de la enfermedad.

American cutaneous leishmaniasis (ACL) is considered a public health problem worldwide, and incidence in Colombia is 12,000 cases per year. Colombia has implemented control programs for years which have often overlooked the social, economic, and demographic characteristics of the regions where the disease occurs. As part of an epidemiological study, this article presents the results of a survey on knowledge, attitudes, and practices (KAP) related to leishmaniasis in rural populations in Acandí in the Colombian Darién. Qualitative and quantitative tools were used (ethnography and surveys, respectively). The results show scarce knowledge among the population on basic aspects such as recognition of the sand fly vector. There were also differences in KAP according to gender and type of population, rather than by geographic area. The study points to government neglect as a critical factor in the persistence of the disease.

A leishmaniose tegumentar americana (LTA) é considerada um problema de saúde pública em todo o mundo, e sua incidência na Colômbia é de 12 mil casos por ano. Os programas de controle implementados muitas vezes falham, provavelmente, por ignorarem as características sociais, econômicas e demográficas das regiões onde a doença ocorre. Como parte de um estudo de tipo ecoepidemiológico, neste artigo apresentamos os resultados de um estudo sobre os Conhecimentos, Atitudes e Práticas (CAP) sobre a leishmaniose em populações rurales do município de Acandí, na região do Darien colombiano. Para o estudo foram utilizados ferramentas qualitativas como a etnografia e quantitativas como levantamentos. Os resultados indicam que a população desconhece aspectos fundamentais da LTA, como por exemplo, o vetor. Além disso, existem diferenças nos CAP por sexo e tipo de população, mas não pela área geográfica. Desta forma, a nossa abordagem evidencia a negligência dos entes públicos de saúde, encabeçados pelo governo do estado. Esta negligencia é um fator determinante na perpetuação da doença.

Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

OX40+ T lymphocytes and IFN-γ are associated with American tegumentary leishmaniasis pathogenesis / Linfócitos T OX40+ e IFN-γ estão associados com a patogênese da leishmaniose tegumentar americana

BACKGROUND: Leishmaniases are zoonoses considered a public health problem, representing a complex group of diseases with a broad clinical spectrum and epidemiological diversity. Leishmaniasis is caused by several species of protozoa of the genus Leishmania. The evolution of the pathology and the resolution of the leishmaniasis are dependent mainly on the Leishmania species involved, although the cytokine profile plays an important role in the development of the immune response. OBJECTIVES: The purpose of our study was to evaluate the immune response of patients affected by lesions of cutaneous leishmaniasis by immunostaining of the OX40, CD20, IFN-γ and IL-4 proteins. METHODS: The tissue samples were collected from indolent skin ulcers confirmed as cutaneous leishmaniasis of 41 patients aged between six and 90 years. The lesions were submitted to OX40, CD20, INF-γ and IL-4 immunolabeling. RESULTS: We observed a statistically significant higher expression of IFN-γ compared with IL-4 (p=0.009). Besides, OX40 had higher expression when compared with CD20 (p<0.001). CONCLUSION: The present study indicates that the immune response in lesions of cutaneous leishmaniasis is associated with a healing process, which can be explained by the higher expression of IFN-γ when compared with IL4 protein levels.

FUNDAMENTOS: As leishmanioses são zoonoses consideradas um problema de saúde pública, representando um grupo de doenças complexas, com uma diversidade de amplo espectro clínico e epidemiológico. A leishmaniose é uma doença causada por várias espécies de protozoários do gênero Leishmania spp. A evolução da patologia e a resolução da leishmaniose são dependentes principalmente da espécie de Leishmania envolvida; embora o perfil das citocinas tenha um importante papel no desenvolvimento da resposta imune. OBJETIVOS: Proporcionar mais conhecimentos sobre os eventos inflamatórios na leishmaniose tegumentar através da avaliação da imunoexpressão de OX40, CD20, IFN-γ e IL-4. MÉTODOS: Foram coletadas amostras de tecido de 41 pacientes, com idade variando entre 6 a 90 anos, com úlceras indolentes na pele confirmados através de exames de diagnóstico como leishmaniose tegumentar. As lesões foram submetidas a imunomarcação das proteínas OX40, CD20, IFN-γ e IL-4. RESULTADOS: Observamos uma maior expressão de IFN-γ em comparação com IL-4, com diferenças estatisticamente significativa (p = 0,009). Além disso, OX40 tinha maior expressão quando comparada com IL-4 (p <0,001). CONCLUSÃO: O presente estudo indica que a resposta imune nas lesões de LTA está associada a um processo de cura, que pode ser explicado pela maior expressão de IFN-γ quando comparadas com os níveis de IL-4.

Leishmaniose tegumentar americana: imunopatologia diagnóstica e contribuiçäo à patogenia / American tegumentary leishmaniasis: diagnostic immunopathology and contribution to the pathogenesis

O quadro histopatológico da Leishmaniose Tegumentar Americana (LTA) é representaod por inflamaçäo crônica inespecífica por vezes com formaçäo de granulomas epitelióides. A plasmocitose, as alteraçöes do colágeno e vasculares associadas completam o quadro sugestivo, porém näo característico da doença . A sua especificidade depende da demonstraç1 o dos parasitas, os quais geralmente säo muito escassos. Com o propósito de desenvolver metodologia diagnóstica em material de biópsias de pele e mucosas na LTA foram estudados espécimes provenientes de quarenta doentes da Divisäo de Dermatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de Säo Paulo. A caracterizaçäo da doença foi firmada pelo exame clínico, reaçäo intradêrmica de MONTENEGRO e pesquisa de anticorpos séricos antileishmânia. Dezenove biópsias apresentaram resposta inflamatória inespecífica e vinte e uma inflamaçäo com formaçäo de granulomas epitelióides. A positividade do encontro de parasitas no exame histopatológico foi de 20%. A positividade alcançada com a metodologia desenvolvida foi de 88,46% pela técnica de imunofluorescência indireta em amterial congelado, 89,28% em material parafinado e 64,51% pela técnica de peroxidase-antiperoxidase (PAP). Nä houve diferenças, estatisticamente significativas, na positividade de antígeno entre as três técnicas utilizadas ou segundo o tipo de resposta tecidual. A metodologia realizada possibilitou determinar os caminhos e as diferentes morfologias de expressäo do antígeno parasitário. Este apresentou-se com 4 padröes: formas amastigotas (AM), padräo celular (PC), fluorescêncioa em zona de membrana basal (ZMB) e padräo vascular (PV). Näo houve diferenças na fdorma de apresentaçäo do antígeno em relaçäo ao tipo de resposta tecidual...