Unusual manifestation of genital cutaneous leishmaniasis in an immunocompetent patient from São Paulo, Brazil: A case report

Abstract A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.

The direct costs of treating human visceral leishmaniasis in Brazil

Abstract INTRODUCTION: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

Periungual tegumentary leishmaniasis: a diagnostic challenge

Abstract: Periungual and paronychia-like skin lesions can mimic various diseases, setting up a diagnostic challenge that invariably requires correlation with complementary tests. We report a case of an ulcerated tumor of the nailfold diagnosed as leishmaniasis. Although paronychia-like cutaneous leishmaniasis is a rare variant, its epidemiological relevance in Brazil should prompt dermatologists to include it as a plausible diagnosis thus leading to correct work up and treatment.

Efficacy and safety of amphotericin B deoxycholate versus N-methylglucamine antimoniate in pediatric visceral leishmaniasis: an open-label, randomized, and controlled pilot trial in Brazil

ABSTRACT INTRODUCTION Despite their high toxicity, antimonials and amphotericin B deoxycholate are commonly used for treating visceral leishmaniasis (VL). Few studies showing conflictive data about their efficacy and adverse events in pediatric population are available. This study aimed to evaluate efficacy and safety of amphotericin B deoxycholate vs. that of N-methylglucamine antimoniate in treating pediatric VL in Brazil. METHODS This was a randomized, open-label, 2-arm and controlled pilot clinical trial. Treatment naïve children and adolescents with VL without signs of severe illness were treated with N-methylglucamine antimoniate (20mg/kg/day for 20 days) or amphotericin B deoxycholate (1 mg/kg/day for 14 days). All patients were diagnosed with positive direct examination and/or positive PCR for Leishmania spp. performed in bone marrow samples. The primary efficacy end-point was VL cure determined after 180 days of completion of treatment. The analysis was performed using intention-to-treat (ITT) and per protocol (PP) analyses. RESULTS In total, 101 volunteers were assessed. Efficacy was similar for both groups. The antimonial (n=51) and amphotericin B groups (n=50) had a cure rate of 94.1% and 100%, and 94% and 97.9% according to ITT and PP analyses, respectively. All patients reported adverse events (AE). Serious AE incidence was similar in both groups. Five individuals were excluded from the study because of severe adverse events. CONCLUSIONS N-methylglucamine antimoniate and amphotericin B deoxycholate have similar efficacy and adverse events rate in pediatric patients with VL.

Leishmaniasis cutáneo-mucosa: presentación de un caso con compromiso medio-facial / Mucocutaneous leishmaniasis: report of a case with midd lefacial commitment / Lehismaniasis mucocutânea: apresentação de um caso com o compromisso mid-facial

La leishmaniasis es una zoonosis parasitaria causada por protozoos. Puede afectar la piel y las mucosas o presentarse como una enfermedad visceral. La variedad mucocutánea conduce a la destrucción parcial o completa de las membranas mucosas de la nariz, las fauces y la faringe. Aproximadamente un 90% de los casos con afectación mucocutánea se producen en Brasil, Bolivia y Perú. En nuestro país afecta en forma endémica a las provincias del norte desde principios del siglo XX. Se relata el caso de un paciente de 53 años con odinodisfagia de aproximadamente 6 meses de evolución, asociado a formaciones granulomatosas medio- faciales, en el que se diagnosticó leishmaniasis cutaneomucosa mediante el rescate de amastigotes en muestras tomadas de lesiones de paladar blando para estudio anatomopatológico con tinción de Giemsa. Se realizó tratamiento con meglumina antimoniato con buena evolución clínica a partir de los quince días de instaurado el mismo.

Leishmaniasis is a parasitic zoonosis caused by protozoa. It can affect skin, mucous membranes or presented as visceral disease. Mucocutaneous variety leads to partial or complete destruction of the mucous membranes of the nose, mouth and pharynx. Approximately, 90% of cases with mucocutaneous involvement occurs in Brazil, Bolivia and Peru. In our country it affects endemic to the northern provinces since the beginning of the century. The case of a 53-year-old patient with odinodisphagia of approximately 6 months of evolution, associated with mid-facial granulomatous formations in which cutaneomucous leishmaniasis was diagnosed by rescue of amastigotes in samples taken from lesions of soft palate for anatomopathological study with Staining of Giemsa. Treatment with meglumina antimonia was carried out with good clinical evolution from the fifteen days of the same establishment.

A leishmaniose é uma zoonose parasitária causada por protozoários. Ele pode afectar a pele e membranas mucosas ou presente como doença visceral. variedade mucocutânea conduz à destruição parcial ou completa das membranas mucosas do nariz, boca e faringe. Aproximadamente 90% dos casos com envolvimento mucocutânea ocorrem no Brasil, Bolívia e Peru. Em nosso país que afeta endêmica para as províncias do norte, desde o início do século XX. O caso de um odinodisfagia 53 anos, aproximadamente, 6 meses evolução associada com formações granulomatosas mediofaciais em que a leishmaniose mucocutânea foi diagnosticada por resgatar amastigotas em amostras tomadas a partir de lesões do palato mole para estudo histopatológico contou Giemsa. O tratamento foi realizado com antimoniato de meglumina com boa evolução clínica a partir de quinze dias introduzidas ele.

Disseminated cutaneous leishmaniasis caused by Leishmania braziliensis in Southern Brazil

ABSTRACT The authors report a case of disseminated cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis, in a 55 years old patient with 1,119 lesions distributed throughout the body. The patient resides in Sabáudia municipality, North of Paraná State, Southern Brazil, where there was no previous report of this form of leishmaniasis. Treatment with meglumine antimoniate was successful, although the diagnosis was made only five months later.

Study of cutaneous leishmaniasis in the State of Campeche (Yucatan Peninsula), Mexico, over a period of two years / Estudio de la leishmaniasis cutánea en el estado de Campeche (Península de Yucatán), México, por un periodo de dos años

Objective. To study cutaneous leishmaniasis (CL), in the Calakmul municipality of the Campeche State, during two years. Materials and methods. Individuals with skin lesions were evaluated. Aspirates taken from the lesions were cultured, PCR was performed to diagnose the Leishmania species. Results. The culture detected 42% of the samples. PCR diagnosed CL in 76% of the samples; of those 38% were from children and 62% from adults. 89% of the patients were infected with L. mexicana; 14.4% with Mexican strains of L. mexicana; 7% with L. braziliensis; 3.6% with L. mexicana and L. braziliensis. The most affected villages with CL were Dos Lagunas Sur with 12.3%, La Mancolona with 6.5% and La Guadalupe with 2.2% of prevalence, respectively. After the treatment with Glucantime, 96% of the patients were healed. Conclusion. CL is an important public health concern in Calakmul, and the parasite causing it belongs to Leishmania mexicana and Leishmania braziliensis complexes.

Objetivo. Estudiar la leishmaniasis cutánea en Calakmul, Campeche, México, durante dos años. Material y métodos. Se estudiaron individuos con lesiones cutáneas, se tomaron aspirados y se inocularon medios de cultivo; se realizó la técnica de PCR para identificar la especie de Leishmania. Resultados. Los cultivos detectaron 42% de las muestras. Con la PCR se amplificaron 76% de las muestras, 38% fueron tomadas de niños y 62% de adultos. En 89% de las muestras positivas se identificó Leishmania mexicana, en 14.4% cepas mexicanas de L. mexicana, en 7% L. braziliensis y en 3.6% L. mexicana y L. braziliensis. En Dos Lagunas Sur se encontró una prevalencia de 12.3%, en La Mancolona 6.5% y en La Virgen 2.2%. Del total de los pacientes, 96% se curó con Glucantime. Conclusion. La leishmaniasis cutánea es un problema de salud pública en Calakmul y las especies causantes pertenecen a los complejos Leishmania mexicana y Leishmania braziliensis.

Historical seriss of patients with visceral leihmaniasis treated with megluminne antimoniate in a hospital for tropical diseases, Maceió-AL, Brazil / Série histórica dos pacientes com leishmaniose visceral tratados com antimoniato de meglumina em hospital de Doenças Tropicais, Maceió-AL, Brasil

Introduction: Visceral leishmaniasis is an endemic protozoan found in Brazil. It is characterized by fever, pallor, hepatosplenomegaly, lymphadenopathy, and progressive weakness in the patient. It may lead to death if untreated. The drug of choice for treatment is meglumine antimoniate (Glucantime®). The aim of this study was to evaluate patients with visceral leishmaniasis according to criteria used for diagnosis, possible reactions to Glucantime® and blood pressure measured before and after treatment. Methods: 89 patients admitted to the Teaching Hospital Dr. Hélvio Auto (HEHA) in Maceió-AL, in the period from May 2006 to December 2009 were evaluated. Data were collected on age, sex, origin, method of diagnosis, adverse effects of drugs, duration of hospitalization, duration of treatment and dosage up to the onset of adverse effects. Results: There was a predominance of child male patients, aged between one and five years old, from the interior of the State of Alagoas. Parasitological diagnosis was made by bone marrow aspirate; three (3.37%) patients died, 12 (13.48%) had adverse reactions and treatment was changed to amphotericin B, and 74 (83.14%) were cured. Changes that led to replacing Glucantime® were persistent fever, jaundice, rash, bleeding and cyanosis. Conclusion: During the study, 89 patients hospitalized for VL were analyzed: 74 were healed, 12 were replaced by amphotericin B treatment and three died. Most of them were under five years old, male and came from the interior. The dosage and duration of treatment with Glucantime® were consistent with that advocated by the Ministry of Health. Persistence of fever, jaundice, rash, cyanosis and bleeding were the reactions that led the physician to modify treatment. No change was observed in blood pressure before and after treatment. This study demonstrated the work of a hospital, a reference in the treatment of leishmaniasis, which has many patients demanding its services in this area. It demonstrates that this disease is still important today, and needs to be addressed properly to prevent injury and death due to the disease.

A Leishmaniose visceral é doença infecciosa causada por protozoários das espécies chagasi e donovani sendo transmitida pela picada de insetos fêmea dos gêneros Lutzomyia e Phlebotomos. Constitui doença febril, determinando amplo aspecto de manifestações clínicas e prognóstico variável, que pode levar à morte se não for tratada. É doença endêmica encontrada no Brasil e nos últimos anos verificou-se intenso processo de urbanização da endemia e aumento da letalidade por leishmaniose visceral. O estudo teve como objetivo avaliar pacientes com leishmaniose visceral de acordo com os critérios utilizados para o diagnóstico, possíveis reações ao Glucantime® e pressão arterial, medidos antes e após o tratamento. Métodos: Foram avaliados 89 pacientes internados no Hospital Universitário Dr. Hélvio Auto (HEHA), em Maceió-AL, no período de maio de 2006 a dezembro de 2009. Foram coletados dados sobre idade, sexo, origem, método de diagnóstico, efeitos adversos da droga, duração da hospitalização, duração do tratamento e dose até o aparecimento de efeitos adversos. Resultados: Houve predomínio de crianças do sexo masculino, com idade entre um e cinco anos, a partir do interior do Estado de Alagoas. O diagnóstico parasitológico foi feito pelo aspirado de medula óssea, três (3,37%) pacientes morreram, 12 (13,48 %) apresentaram reações adversas e o tratamento foi alterado para anfotericina B, e 74 (83,14 %) foram curados. As alterações que levaram à substituição de Glucantime® foi febre persistente. A dosagem e duração do tratamento com Glucantime® foi seguido como preconizado pelo Ministério da Saúde. A persistência de febre, icterícia, prurido, cianose e sangramento foram as reações que levaram o médico a modificar o tratamento. Nenhuma mudança foi observada na pressão arterial antes e após o tratamento. O estudo realizado demonstrou o perfil de um Hospital, que recebe grande demanda de casos de leishmaniose visceral. Isso demonstra que essa doença continua sendo importante na atualidade, precisando ser abordada de maneira adequada, evitando assim agravos e mortes pela doença.

Avaliação não-clínica da segurança do antimoniato de meglumina em roedores: toxicocinética, toxicidade para o desenvolvimento e efeitos sobre citocromos P450 hepáticos / Non-clinical safety of meglumine antimoniate evaluation in rodents: toxicokinetics, developmental toxicity and effects on liver cytochromes P450

Antimoniais pentavalentes são considerados medicamentos de primeira linha no tratamento das diferentes formas de leishmaniose. O perfil de segurança dos medicamentos à base de antimônio (Sb), entretanto, ainda não foi completamente elucidado. O objetivo deste conjunto de estudos que constam desta tese foi fornecer informações adicionais sobre a segurança de um curso de tratamento com o antimoniato de meglumina (AM). O primeiro estudo investigou o acúmulo e eliminação do Sb do sangue e órgãos de ratos machos adultos tratados com uma dose diária de AM, por um período de 21 dias consecutivos. Foi observado que o antimônio é lentamente eliminado. O segundo estudo avaliou o desenvolvimento pós-natal da prole nascida e amamentada por ratas tratadas na gestação e lactação até o desmame com AM. A transferência de Sb através da placenta e via leite materno para a prole foi determinada. Os resultados mostraram, em geral, que o desenvolvimento pós-natal e a fertilidade dos ratos expostos não foram alterados. Os dados também sugerem que o Sb passa facilmente para o leite e está presente nesta matriz biológica em uma forma química que o torna bem absorvido pelos lactentes. Além disso, nós também investigamos se as atividades das enzimas citocromo P450 hepáticas (CYP), que participam do metabolismo de endo- e xenobióticos, foram alteradas pelo tratamento. Os resultados mostraram que um curso de tratamento de 24 dias com AM causou um consistente declínio das atividades de CYP1A no fígado de camundongos SW e DBA-2, e uma diminuição nas atividades de CYP2B9/10 nas fêmeas de SW, mas não em DBA-2 de ambos os sexos...

Pentavalent antimony compounds are considered as first choice drugs to treat different clinical manifestations of leishmaniasis. The safety profile of antimony-based anti-leishmanial drugs, however, has not been entirely elucidated so far. The objective of the set of experimental studies presented in this thesis was to provide additional information on the safety of a course of treatment with meglumine antimoniate (MA). The first study was an investigation of the accumulation and clearance of antimony (Sb) in the blood and organs of adult male rats treated with a 21-day course of MA. It was observed that residual Sb is slowly eliminated from rat’s organs and blood. The second study evaluated the postnatal development of the offspring born to and nursed by rats treated during gestation and lactation until weaning with MA. The transfer of Sb via placenta and mothers’ milk to the offspring was determined as well. Results showed that offspring postnatal development and fertility remained virtually unaltered after treatment with MA. Data suggested that Sb is transferred into breast milk and is present there in a chemical form that makes this metalloid bioavailable to suckling pups. Furthermore, we investigated whether activities of liver cytochrome P450 enzymes that take part in the metabolism of endogenous and exogenous substances were altered after a course of treatment with MA. It was found that a 24-d course of treatment with MA caused a consistent decline in CYP1A activity in the mouse liver. A decrease of CYP2B9/10 activity was noted in SW females but not in SW males and in DBA-2 of either sex...

Miltefosina versus antimoniato de meglumina en el tratamiento de la leishmaniasis mucosa

El tratamiento convencional para la leishmaniasis tegumentaria es el antimoniato de meglumina, el cual presenta falla terapéutica creciente, producción de efectos adversos graves, y necesidad de administración parenteral, justificando la búsqueda de alternativas terapéuticas. Presentamos aquí los resultados preliminares de un ensayo clínico de fase II en pacientes con leishmaniasis mucosa, en el que se comparó la eficacia de miltefosina por vía oral con respecto a la del compuesto antimonial. La evaluación de la respuesta a los tratamientos se realizó mediante un seguimiento con videofibroscopia nasofaríngea, utilizándose un score de gravedad de lesiones mucosas para aplicar en cada momento del seguimiento de los pacientes. No se encontraron hasta ahora diferencias significativas entre el número de pacientes curados con miltefosina o con la quimioterapia convencional. Los resultados favorables de este trabajo sugieren que miltefosina podría constituir una alternativa terapéutica efectiva y segura en la región.

The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.

Zosteriform cutaneous leishmaniasis due to Leishmania ( Viannia ) panamensis and Leishmania ( Viannia ) braziliensis: Report of three cases / Leishmaniasis cutánea zosteriforme causada por Leishmania ( Viannia) panamensis y Leishmania ( Viannia ) braziliensis: reporte de tres casos

In Colombia, zosteriform leishmaniasis is a little-known and infrequent clinical variant of cutaneous leishmaniasis. Its clinical features include one or more plaques made up of papules and pseudo-vesicles, which conform to a lineal pattern, as well as satellite lesions that affect one or more dermatomes, without crossing the median line. We present three zosteriform cutaneous leishmaniasis cases in which Leishmania panamensis and Leishmania braziliensis were identified as the infective species. In light of the fact that the disease occurs infrequently, diagnosis was reached by taking into account epidemiological and clinical suspicion.

La leishmaniasis zosteriforme es una variante clínica de la leishmaniasis cutánea, infrecuente y poco conocida en Colombia. Clínicamente se caracteriza por una o varias placas conformadas por pápulas y pseudovesículas que siguen un patrón lineal, y por lesiones satelitales que comprometen uno o varios dermatomas sin sobrepasar la línea media. Se presentan tres casos de leishmaniasis cutánea zosteriforme en los que se identificaron Leishmania panamensis y Leishmania braziliensis como especies infectantes. La sospecha epidemiológica derivada de la procedencia de los pacientes, así como la sospecha clínica a partir del reconocimiento de una presentación infrecuente de la enfermedad, permitieron hacer el diagnóstico.

Montenegro skinttest and age of skin lesion as redictors of treatment failure in cutaneous leishmaniasis / Intensidade da intradermorreação de Montenegro e tempo de evolução da lesão como preditores de falha na resposta terapêutica da leishmaniose cutânea

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.

Visceral Leishmaniasis without Fever in an 11-Month-Old Infant: a Rare Clinical Feature of Kala-azar

Visceral leishmaniasis or kala-azar is an endemic parasitic disease in some parts of the world which is characterized by fever, splenomegaly, and pancytopenia in most of the cases. Herein we report an 11 month-old male infant with diagnosis of kala-azar who presented with pallor, hepatosplenomegaly, failure to gain weight, and no history of fever. Surprisingly, fever started after beginning of meglumine antimoniate treatment in this patient. As far as we are aware of, this is a rare presentation of visceral leishmaniasis. Therefore, clinicians especially in endemic areas are highly recommended to include kala-azar among differential diagnosis of unexplained anemia without fever to prevent misdiagnosis of this potentially fatal, but treatable condition.

Histopathological and immunohistochemical aspects of American cutaneous leishmaniasis before and after different treatments* / Aspectos histopatológicos e imuno-histoquímicos da leishmaniose tegumentar americana antes e depois de diferentes tratamentos

The histopathology and immune responses of the healing process of leishmaniasis are still poorly studied. This study aimed to examine the histopathological and immunological aspects of lesions of patients with cutaneous leishmaniasis before and after different therapeutic methods. We studied 23 individuals grouped according to the treatments: Glucantime, Glucantime + Leishvacin and Glucantime + Leishvacin associated with Bacillus Calmette-Guerin. For analysis of the histopathological changes present in the dermis and epidermis, histological sections were stained with hematoxylin and eosin. The samples were immunostained before and after treatment to analyze the expression of interferon (IFN)-γ, interleukin (IL) 12, IL-10 and IL-4. Before treatment the presence of intense infiltrates of mononuclear cells was noticed and after treatment, even with a diagnosis of clinical cure, the subjects still showed a moderate inflammatory process. In the immunohistochemical analyses, we noticed a difference between the cytokines, with increased expression of cytokines IFN-γ and IL-12 compared to IL 10 and IL-4, both before and after treatment and, comparatively, the difference in this expression was more intense before treatment. However, the cytokine expression analyzed by treatment group showed no statistically significant difference. We conclude that a clinical cure does not always coincide with the histopathological ...

A histopatologia e as respostas imunológicas do processo de cura da leishmaniose são ainda pouco estudadas. Este estudo teve como objetivo avaliar os aspectos histopatológicos e imunológicos das lesões de pacientes com leishmaniose tegumentar, antes e após diferentes métodos terapêuticos. Foram estudados 23 indivíduos agrupados de acordo com os tratamentos: Glucantime, Glucantime + Leishvacin e Glucantime + Leishvacin associado com Bacilo Calmette-Guerin. Para a análise das alterações histopatológicas presentes na derme e epiderme, cortes histológicos foram corados com hematoxilina e eosina. Para avaliar a expressão de interferon (IFN)-γ, interleucina (IL) 12, IL-10 e IL-4 foi utilizada a técnica de imuno-histoquímica antes e após o tratamento. Antes do tratamento houve um intenso infiltrado de células mononucleares, após o tratamento, mesmo com um diagnóstico de cura clínica, apresentou-se ainda um moderado processo inflamatório. Na análise imuno-histoquímica, notamos uma diferença entre as citocinas, com expressão aumentada de citocinas IFN-γ e IL-12 em comparação com IL-10 e IL-4 tanto antes quanto depois do tratamento, e comparativamente, a diferença nesta expressão mostrou-se mais intensa antes do tratamento. No entanto, a expressão das citocinas analisadas por grupo de tratamento não mostraram diferenças ...

Ensaio clínico fase III para leishmaniose tegumentar americana forma cutânea. Equivalência entre esquemas de alta e baixa dose de antimoniato de meglumina / Phase III clinical trial for american cutaneous leishmaniasis. Equivalence between high and low dose schemes of meglumine antimoniate

Neste estudo comparamos esquemas de alta e baixa dose de antimoniato demeglumina (AM) para o tratamento da forma cutânea de leishmaniose tegumentar americana, em pacientes oriundos do estado do Rio de Janeiro. OBJETIVO:Comparar a eficácia representada pela cura imediata (epitelização em 120 dias),tardia (cicatrização em 360 dias) e definitiva (ausência de reativação ou lesão mucosa em 720 dias) e toxicidade (clínica, laboratorial e eletrocardiográfica) com duas diferentes doses de tratamento com AM para leishmaniose cutânea (LC) e comparar os critérios de cura clínica aqui adotados com aqueles estabelecidos pelo Ministério da Saúde. MÉTODO: Ensaio clínico de não inferioridade, controlado,randomizado, cego e de fase III, com 60 pacientes com LC alocados em dois grupos de tratamento: (A) 20mg Sb5+/kg/dia por 20 dias e (B) 5mg Sb5+/kg/dia por 30 dias administrados por via intramuscular. RESULTADOS: Pacientes dos grupos A e B apresentaram, respectivamente: Cura imediata 90,0% e 86,7%, com tempo médio de epitelização de 58,7 e 54,9 dias; cura tardia por intenção de tratar 76,7% e73,3%; e cura tardia por análise de protocolo 84,6% e 75,9%. Dos 53 pacientes que apresentaram epitelização em até 120 dias, 44 (83,4%)evoluíram para cura tardia...

In this study, we compare schemes of high and low dose of meglumine antimoniate(MA) for the treatment of cutaneous form of American tegumentary leishmaniasis in patients from Rio de Janeiro. OBJECTIVE: To compare the efficacy represented by immediate healing ( epithelialization in 120 days) , late healing (scarring within 360days ) and final healing (no reactivation or mucosal lesion in 720 days) and clinical ,laboratory and electrocardiographic toxicity with two different schemes of treatment with MA for cutaneous leishmaniasis (CL ) and compare the clinical cure criteria adopted here with those established by the Ministry of Health. METHOD :Randomized, controlled, blind, phase III clinical trial, of non-inferiority with 60patients presenting CL divided into two treatment groups: (A) 20 mg Sb5+ / kg / day for 20 days and (B) 5 mg Sb5+ / kg / day for 30 days administered intramuscularly.RESULTS : Patients in groups A and B presented, respectively : immediate healingof 86.7 % and 90.0 % , with a mean time of epithelialization of 58.7 and 54.9 days;late healing by intention to treat of 76.7 % and 73.3%; and late healing by protocol analysis of 84.6 % and 75.9 % .From 53 patients who presented epithelialization within 120 days , 44 (83.4 %) had late healing...

Estudo clínico randomizado comparando antimoniato de meglumina, pentamidina e anfotericina B para o tratamento da leishmaniose cutânea ocasionada por Leishmania guyanensis / A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by Leishmania guyanensis

FUNDAMENTOS: O tratamento da leishmaniose tegumentar americana (LTA) ainda constitui desafio, pois a maioria dos medicamentos é injetável e têm-se poucos ensaios clínicos randomizados comparando a eficácia das drogas. Além disso, é provável que as espécies de Leishmania tenham influência nas respostas terapêuticas. OBJETIVOS: Avaliar e comparar a eficácia e a segurança dos esquemas de tratamento na LTA, ocasionada por Leishmania (Viannia) guyanensis. MÉTODOS: 185 pacientes foram selecionados, conforme critérios de elegibilidade, e distribuídos, aleatoriamente, em 3 grupos - 2 com 74 enfermos e outro com 37 - que receberam, respectivamente, antimoniato de meglumina, isotionato de pentamidina e anfotericina B em doses, períodos e vias de administração padronizados. Os enfermos foram reexaminados um, dois e seis meses após o final dos tratamentos. RESULTADOS: Não houve diferença entre os grupos terapêuticos em relação ao sexo, idade, número ou local das lesões. A análise por intenção de tratar (ITT) mostrou eficácias de 58,1 por cento para a pentamidina e 55,5 por cento para o antimoniato (p=0,857). O grupo da anfotericina B foi analisado separadamente, pois 28 (75,7 por cento) pacientes negaram-se a continuar no estudo após a randomização. Eventos adversos leves ou moderados foram relatados por 74 (40 por cento) pacientes, principalmente artralgia (20,3 por cento), para o grupo do antimoniato, e dor (35,1 por cento) ou enduração (10,8 por cento) no local das injeções para a pentamidina. CONCLUSÕES: A pentamidina tem eficácia similar ao antimonial pentavalente para o tratamento da LTA ocasionada por L. guyanensis. Face aos baixos resultados de eficácia apresentados por ambas as drogas, necessita-se, com urgência, investigar novas opções terapêuticas para esta enfermidade.

FUNDAMENTALS: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. METHODS: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1 percent for pentamidine and 55.5 percent for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7 percent) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40 percent) patients, especially arthralgia (20.3 percent) in the meglumine group, and pain (35.1 percent) or induration (10.8 percent) at the site of injection in the pentamidine group. CONCLUSION: Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.

Avanços no tratamento da leishmaniose tegumentar do novo mundo nos últimos dez anos: uma revisão sistemática da literatura / Advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years: a systematic literature review

INTRODUÇÃO: O arsenal terapêutico contra a leishmaniose tegumentar é muito restrito. Os antimoniais pentavalentes permanecem como as drogas de escolha para seu tratamento há mais de 50 anos. Apesar da sua eficácia, necessita de injeções diárias, apresenta muitos efeitos colaterais e tempo de cura prolongado.

INTRODUCTION: The therapeutic arsenal against cutaneous leishmaniasis is very limited. Pentavalent antimonial compounds have been the drugs of choice for treatment of this disease for over 50 years. Despite their effectiveness, these drugs require daily injections, have many side effects and present prolonged healing time.