RESUMO
Objetivos : Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos : Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados : Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones : La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectos adversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.
SUMMARY Objectives : To compare the efficacy and safety of sodium stibogluconate (SS) and meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in a general hospital. Methods: Case-series of 193 patients with CL treated in three clinical trials with MA (n=69) and SS (n=124) during 2001-2010. Both study drugs were administered intravenously at a slow speed at 20 mg Sb5+/kg/day for 20 consecutive days following WHO-PAHO recommendations. Clinical and safety data were gathered from clinical files. Results: Demographic characteristics were similar between the study groups, but the size and number of lesions were higher in the MA group. Efficacy was 76.0% in the MA vs. 68.4% in the SS group (p=0.340) and 55.1% vs. 50.8% (p=0.570) in the per protocol and intention to treat analysis. respectively. Side effects more frequently reported were dysgeusia (37.0%). dizziness (32.0%). headache (36.0%). arthralgia (31.0%) and lymphangitis (21.0%). These first three symptoms as well as elevation of transaminases, leukopenia, thrombocytopenia and prolonged QTc were numerically more frequent in the SS group but without reaching statistical significance. Treatment was stopped definitively for severe toxicity in the SS group due to refractory emesis (two patients) and prolonged QTc (one patient). Conclusions: The efficacy of MA and SS is comparable. The intravenous administration of these compounds did not produce immediate reactions, but it was associated with unusual clinical and laboratory abnormalities.
Assuntos
Humanos , Leishmaniose Cutânea , Gluconato de Antimônio e Sódio , Ensaios Clínicos Controlados como Assunto , Antimoniato de MegluminaRESUMO
La leishmaniasis es una enfermedad causada por pará- sitos protozoarios del género Leishmania. Se clasifica como: cutánea, mucocutánea y visceral. De las ante- riores, la Leishmaniasis cutánea (LC) es la forma más común a nivel mundial, transmitida a humanos por la picadura del mosquito hembra, el cual pertenece a la familia Phlebotominae y Lutzomyia. La cutánea gene- ralmente se manifiesta clínicamente por presentar una pápula ulcerada con exudado seroso, con fondo limpio de aspecto granular y bordes hiperémicos y engrosados. Presentamos el caso de un adolescente de 16 años de edad, procedente de Aldea Peña Blanca Norte, San Pe- dro Sula, con lesión eritemato-costrosa, tumefacta no dolorosa de 2 meses de evolución, en pabellón auri- cular derecho. El paciente fue visto en consulta exter- na de Dermatología Pediátrica del Instituto Hondure- ño de Seguridad Social Regional del Norte (I.H.S.S.), recibiendo tratamiento con antibióticos sistémicos y tópicos (trimetoprim sulfametoxazol, mupirocina un- güento), por 7 días. Previamente había recibido varios tratamientos sistémicos orales y parenterales (amoxici- lina/ ácido clavulánico, dicloxacilina, penicilina benza- tínica, y aplicación tópica de ácido fusídico) sin obtener mejoría clínica alguna; se le envió a realizar microsco- pía directa con tinción de Giemsa de frotis obtenido de la lesión en el Centro de Salud "Miguel Paz Barahona", demostrando la presencia de amastigotes. Se inició al antimoniato de meglumina según esquema estableci- do por la Organización Mundial de la Salud (OMS) a razón de 20 mg/kg/día intramuscular por 30 días. Debido a la falla de tratamiento se deci- de utilizar itraconazol durante 3 meses con buena respuesta y sin efectos adversos...(AU)
Assuntos
Humanos , Masculino , Adolescente , Leishmaniose Cutânea/diagnóstico , Antimoniato de Meglumina , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Pavilhão AuricularRESUMO
Abstract Introduction: Intralesional-pentavalent antimonials (IL-SbV) are recommended for simple cutaneous leishmaniasis (CL). Few treatment sessions (1-5) and drug volumes (1-5 ml each), relative to lesion size (LS), are recommended. There is not a validated IL-SbV protocol using doses calculated as mg/kg body weight and administered over a large number of IL-sessions, with small injection volumes. Objective: The study aim was to determine the efficacy of different concentrations of IL-SbV administered in 29 daily sessions of 100 μL each, on CL infected mice. Methods: Leishmania (Viannia) panamensis and L. (V.) braziliensis-infected mice (N = 6) were treated with 150, 50, and 16.6 mgSbV/kg/day x 29 days. Percentage of lesion area reduction, aesthetic and final (no lesions, no parasites) efficacy and effective dose (ED)50 were determined. In vitro-SbV activity against parasites was evaluated for both species. Results: The ED50 values were 72.2 and 66.3 (at the end of treatment), 54.3 and 37.7 (15-days pt.), and 145.3 and 148.6 (60-days pt.) for each species, respectively. Differences were observed between Leishmania species at 15-days pt., but not later. At 60-day pt., IL-SbV-150 mg showed final cure rates of 66.6 % for L. (V.) panamensis and 33.3 % for L. (V.) braziliensis-infected mice. After 15 days pt., lesion reactivation was observed in some "aesthetically cured" mice. Glucantime was not active in in vitro assays. Conclusions: The IL-SbV use with a dose calculated as mg/kg body weight and administered over a large number of IL-sessions, with small injection volumes each day could be effective against L. (V.) panamensis and L. (V.) braziliensis-CL infection. An appropriate SbV-dose (higher than 150 mg/kg/day x less than 29 days) must be evaluated.
Resumen Introducción: Los antimoniales pentavalentes aplicados intralesionalmente (IL-SbV) se recomiendan para el tratamiento de la leishmaniasis cutánea (LC) simple. Se recomiendan pocas sesiones (1-5) y volúmenes (1-5 ml cada uno) en relación con el tamaño de la lesión (LS). No existe un protocolo de IL-SbV validado que utilice dosis calculadas según el peso corporal (en mg/kg) y administradas durante varias sesiones en pocos volúmenes de inyección. Objetivo: El objetivo del estudio fue determinar la eficacia de diferentes concentraciones de IL-SbV administradas en 29 sesiones diarias de 100 μL cada una, en ratones con LC. Métodos: Ratones infectados con L. (V.) panamensis y L. (V.) braziliensis (N = 6) fueron tratados intralesionalmente con 150, 50 y 16,6 mg SbV/kg/día x 29 días. Se determinó el porcentaje de reducción del área de la lesión, la eficacia estética y final (sin lesiones, sin parásitos) y la dosis efectiva (DE)50. Adicionalmente de evaluó la actividad in vitro del SbV. Resultados: Los valores de DE50 fueron 72.2 y 66.3 (al final del tratamiento), 54.3 y 37.7 (15 días pt) y 145.3 y 148.6 (60 días pt) para cada especie. Se encontraron diferencias entre las especies sólo a los 15 días pt. La eficacia del tratamiento IL-SbV-150 mg, 60 días pt., fue de 66.6 y 33.3 % en ratones infectados con L. (V.) panamensis L. (V.) braziliensis respectivamente. Después de 15 días pt., se observó reactivación de la lesión en algunos ratones "estéticamente curados". Glucantime no fue activo in vitro. Conclusiones: El uso intralesional de SbV con una dosis calculada en mg/kg de peso corporal y administrada durante varias sesiones, con pequeños volúmenes de inyección cada día, podría ser eficaz en LC por L. (V.) panamensis y L. (V.) braziliensis. Dosis adecuadas de SbV (superiores a 150 mg/kg/día x 20) deben evaluarse.
Assuntos
Animais , Camundongos , Antimoniato de Meglumina , LeishmaniaRESUMO
Abstract Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.
Assuntos
Humanos , Leishmania mexicana , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Antiprotozoários/uso terapêutico , Brasil , Antimoniato de MegluminaRESUMO
Abstract Background: The treatment of cutaneous leishmaniasis is a challenge. A better understanding of the in situ mechanisms involved in the evolution and cure of the disease is essential for the development of new therapies. Objective: Correlate histopathological and immunological characteristics of cutaneous leishmaniasis lesions with clinical outcome after different treatment regimens. Methods: The authors analyzed cellular infiltration and immunohistochemistry staining for CD4, CD8 and IL-17 in biopsy samples from 33 patients with cutaneous leishmaniasis before treatment. All patients were recruited in a randomized clinical trial at Corte de Pedra (Bahia-Brazil) and assigned to receive Glucantime®, Glucantime® + Oral Tamoxifen or Glucantime® + Topical Tamoxifen. Patients were followed for 2 to 6 months to define disease outcome. Results: A similar expression of CD4, CD8 and IL-17 was observed in lesion samples regardless of clinical outcome. In general, a higher amount of CD8 cells were observed compared with CD4 cells. An important observation was that all patients whose cellular infiltrate did not contain plasma cells were cured after treatment. Study limitations: Isolated quantification of TCD8 and IL-17 using immunohistochemistry is insufficient to analyze the role of these molecules in the immunopathogenesis of cutaneous leishmaniasis. In addition, the expansion of the immunohistochemistry panel would allow a more complete analysis of the immune response in situ. Conclusions: The absence of plasma cells in cutaneous leishmaniasis lesions was related to a favorable therapeutic outcome.
Assuntos
Humanos , Leishmaniose Cutânea/tratamento farmacológico , Linfócitos T CD4-Positivos , Resultado do Tratamento , Linfócitos T CD8-Positivos , Antimoniato de MegluminaRESUMO
Abstract Cutaneous leishmaniasis is characterized by ulcers with raised edges and a granular bottom, mainly on the lower limbs. This is a case report of a male patient with an ulcer on the left plantar region. The diagnosis was confirmed by positive PCR for L. braziliensis and the presence of amastigotes of Leishmania sp. in the histopathological examination. After treatment with Glucantime, the patient showed full healing of the ulcer. The unusual location of the ulceration calls attention to atypical presentations of leishmaniasis, and the importance of histopathological examination and PCR, leading to the appropriate diagnosis and treatment.
Assuntos
Humanos , Masculino , Leishmania braziliensis , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Úlcera do Pé , Leishmania , Úlcera , Antimoniato de MegluminaRESUMO
Introdução: a Leishmaniose Tegumentar Americana (LTA) é uma infecção zoonótica cujo tratamento é realizado com a droga antimoniato de meglumina (AM). Objetivo: Relatar as alterações eletrocardiográficas decorrentes do uso de AM em pacientes com LTA. Metodologia: foi realizada uma revisão integrativa da literatura por meio das bases de dados BIREME, PUBMED, COCHRANE, SCIELO e literatura cinzenta, usando como estratégia de busca o cruzamento dos seguintes descritores, nos idiomas português e inglês: leishmaniose cutânea, eletrocardiografia, meglumina e toxicidade. Não foi estipulado um intervalo temporal para que um maior número de publicações fosse obtido. Resultados: foram encontrados 134 artigos, desses apenas 09 atenderam aos critérios de inclusão. As principais alterações eletrocardiográficas encontradas durante a terapêutica foram as alterações de repolarização ventricular, com destaque para o prolongamento do intervalo QT corrigido pela frequência cardíaca. Já entre as alterações mais graves em termos de morbimortalidade, destacam-se as arritmias ventriculares complexas, principalmente a Torsade de pointes. Discussão: em todos os artigos selecionados foram encontradas alterações ao eletrocardiograma (ECG) durante o tratamento com AM, sendo recomendado em todos os pacientes, o acompanhamento eletrocardiográfico. Apenas um estudo excluiu as alterações do ECG basal, presença de comorbidades e uso de drogas cardiotóxicas sendo esses possíveis vieses para avaliação da toxicidade cardíaca diretamente provocada pelo antimonial. Conclusão: considerando as alterações na repolarização ventricular e as possíveis arritmias ventriculares em pacientes em tratamento para LTA em uso de AM, o acompanhamento eletrocardiográfico é recomendado durante a terapêutica de todos esses pacientes, sendo útil para prevenção de complicações cardiovasculares importantes.
Introduction: American Tegumentary Leishmaniasis (ATL) is a zoonotic infection whose treatment is carried out with the meglumine antimoniate drug (AM). Objective: To report the electrocardiographic changes resulting from the use of AM in patients with ATL. Methodology: an integrative literature review was carried out using the BIREME, PUBMED, COCHRANE, SCIELO and gray literature databases, using as a search strategy the crossing of the following descriptors, in Portuguese and English: cutaneous leishmaniasis, electrocardiography, meglumine and toxicity. A time interval was not stipulated in order to obtain a greater number of publications. Results: we found 134 articles, of which only 9 met the inclusion criteria. The main electrocardiographic changes found during therapy were changes in ventricular repolarization, with emphasis on the prolongation of the QT interval corrected by heart rate. Already the most serious changes in terms of morbidity and mortality, complex ventricular arrhythmias, especially Torsade de pointes, stand out. Discussion: changes in the electrocardiogram (ECG) were found in all selected articles during treatment with AM, with electrocardiographic monitoring being recommended in all patients. Only one study excluded: changes in the baseline ECG, the presence of comorbidities and / or use of cardiotoxic drugs, these being possible biases to assess cardiac toxicity directly caused by the antimonial. Conclusion: considering the changes in ventricular repolarization and possible ventricular arrhythmias in patients undergoing treatment for ATL using AM, electrocardiographic monitoring is recommended during the therapy of all these patients, being useful for the prevention of important cardiovascular complications.
Assuntos
Humanos , Masculino , Feminino , Eletrocardiografia Ambulatorial , Leishmaniose Cutânea , Toxicidade , Antimoniato de Meglumina , RevisãoRESUMO
Abstract INTRODUCTION: The objective of this study was to estimate the direct medical costs of the treatment for mucosal leishmaniasis (ML) using three therapeutic approaches in the Brazilian context. METHODS: We performed this economic assessment from the perspective of the Brazilian public healthcare system. The following therapeutic approaches were evaluated: meglumine antimoniate, liposomal amphotericin B, and miltefosine. Direct medical costs were estimated considering four treatment components: a) drug, b) combined medical products, c) procedures, and d) complementary tests. RESULTS: Treatment with meglumine antimoniate had the lowest average cost per patient (US$ 167.66), followed by miltefosine (US$ 259.92) in the outpatient treatment regimen. The average cost of treatment with liposomal amphotericin B was US$ 715.35 both in inpatient regimen. In all estimates, the drugs accounted for more than 60% of the total cost for each treatment approach. CONCLUSIONS: These results demonstrate the marked differences in costs between the therapeutic alternatives for ML. In addition to efficacy rates and costs related to adverse events, our data have the potential to support a complete cost-effectiveness study in the future. Complete analyses comparing costs and benefits for interventions will assist health managers in choosing drugs for ML treatment in Brazil as well as in establishing effective public health policies.
Assuntos
Humanos , Leishmaniose Mucocutânea/tratamento farmacológico , Antiprotozoários/uso terapêutico , Brasil , Análise Custo-Benefício , Antimoniato de Meglumina/uso terapêuticoRESUMO
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.
Assuntos
Humanos , Masculino , Adulto , Compostos Organometálicos/uso terapêutico , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Antiprotozoários/uso terapêutico , Brasil , Reação em Cadeia da Polimerase , Antimoniato de Meglumina/uso terapêutico , Genitália , Meglumina/uso terapêuticoRESUMO
Abstract Mucocutaneous leishmaniasis (MCL) is a chronic infection that can affect the skin and mucous membranes. We report a case of oral, nasopharyngeal, and penile lesions in a 35-year-old cocaine user. The patient presented with ulcerated lesions in 2014. Histopathologic analysis revealed amastigotes, and serological test results were positive for leishmaniasis. Systemic therapy with meglumine antimoniate was administered; however, the patient failed to present for follow-up. In 2018, he returned with nasal collapse, and another histopathologic test confirmed MCL. This case illustrates the importance of careful differential diagnosis of skin and mucous ulcers to identify the particular pathology.
Assuntos
Humanos , Masculino , Adulto , Leishmaniose Mucocutânea/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/complicações , Antimoniato de Meglumina/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Mucocutânea/complicações , Leishmaniose Mucocutânea/tratamento farmacológicoRESUMO
En Bolivia, los medicamentos utilizados para el tratamiento de la leishmaniasis cutánea son los antimoniales, de aplicación sistémica en dosis/kg peso, los cuales provocan efectos adversos por la aplicación en largos periodos y grandes volúmenes. La aplicación perilesional de antimonio tiene similar eficacia terapéutica que la sistémica. Sin embargo, no se cuenta con información documentada respecto a la eficacia del tratamiento perilesional en pacientes con falla terapéutica, posterior al tratamiento sistémico. El objetivo de esta serie de casos fue evaluar el tratamiento perilesional con glucantime, en pacientes con leishmaniasis cutánea y falla terapéutica, posterior a un primer ciclo de tratamiento sistémico con antimoniales. El estudio se realizó con once pacientes con leishmaniasis cutánea con falla terapéutica, posterior a la administración de un primer ciclo de tratamiento sistémico con glucantime procedentes de la zona tropical de Bolivia. Se consideró como falla terapéutica la persistencia de la lesión y presencia de parásitos obtenidos de los bordes de la lesión. La intervención perilesional consistió en la aplicación día por medio de glucantime en cinco sesiones. La inoculación se realizó sobre el borde de la lesión y la dosificación del medicamento se calculó multiplicando el área de la lesión por el factor 0.008. Todos los pacientes presentaron dolor local durante el momento de inoculación del medicamento, así como también presentaron un ligero agrandamiento del área de la lesión después de la primera aplicación del medicamento En las siguientes inoculaciones se observó la reducción progresiva del área de la lesión hasta su completa cicatrización.
In Bolivia, the drugs used for the treatment of cutaneous leishmaniasis are the antimonials by systemic application in doses/kg/weight, which cause adverse effects due to the applications in long periods and large volumes. The perilesional application of antimony has similar therapeutic efficacy than the systemic one. However, there is no documented information regarding the efficacy of perilesional treatment in patients with therapeutic failure after systemic treatment. The aim of this series of cases was to evaluate the perilesional treatment with Glucantime, in patients with cutaneous leishmaniasis and therapeutic failure, after a first cycle of systemic treatment with antimonials. The study was conducted with eleven patients with cutaneous leishmaniasis and therapeutic failure, after the administration of a first cycle of systemic treatment with Glucantime. From the tropical zone of Bolivia. The persistence of the lesion and the presence of parasites at the edge of the lesion were considered as therapeutic failure. The perilesional intervention consisted in the application past one day of glucantime in five sessions. The inoculation was performed on the edge of the lesion and the dosage of the medication was calculated by multiplying the area of the lesion by the factor 0.008. All the cases presented local pain during the time of inoculation of the drug, as well as a slight enlargement of the area of the lesion after the first inoculation of the drug. In the following inoculations the progressive reduction of the area of the lesion was observed until its complete healing.
Assuntos
Humanos , Leishmaniose Cutânea/diagnóstico por imagem , Úlcera , Antimoniato de Meglumina/administração & dosagem , LinfangiteRESUMO
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.
Assuntos
Humanos , Masculino , Adulto , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Antimoniato de Meglumina/efeitos adversos , Antiprotozoários/efeitos adversos , Brasil , Anfotericina B/uso terapêutico , Diálise Renal , Leishmaniose Cutânea/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antiprotozoários/uso terapêuticoRESUMO
Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.
Assuntos
Humanos , Masculino , Feminino , Fosforilcolina/análogos & derivados , Leishmaniose Mucocutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Antiprotozoários/administração & dosagem , Fosforilcolina/administração & dosagem , Fatores de Tempo , Projetos Piloto , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.(AU)
Assuntos
Animais , Camundongos , Farmacocinética , Leishmaniose Cutânea , Antimoniato de Meglumina , Infecções , Leishmania , Antimônio , NêutronsRESUMO
Abstract Cutaneous leishmaniasis (CL) is a high-morbidity, vector-borne disease endemic to Colombia. Unlike conventional systemic antileishmanial therapy, intralesional meglumine antimoniate administration has fewer adverse effects and can be as effective and safe. We describe 12 patients treated with intralesional meglumine antimoniate: seven with primary and five with recurrent lesions. The majority (11/12) met all cure criteria after 1-7 sessions of meglumine antimoniate administration (1-5 mL). Adverse effects comprised mainly of local pain and edema. Intralesional meglumine antimoniate administration could be an excellent alternative treatment for uncomplicated CL; however, controlled clinical trials are needed to test the efficacy and safety thereof.
Assuntos
Humanos , Masculino , Feminino , Lactente , Adulto , Adulto Jovem , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Antiprotozoários/administração & dosagem , Injeções Intralesionais , Resultado do TratamentoRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico , Antiprotozoários/uso terapêutico , Brasil , Estudos Retrospectivos , Resultado do Tratamento , Leishmaniose Cutânea/patologia , Geografia , Pessoa de Meia-IdadeRESUMO
Abstract Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.
Assuntos
Humanos , Masculino , Lactente , Compostos Organometálicos/administração & dosagem , Pentamidina/administração & dosagem , Anfotericina B/administração & dosagem , Leishmaniose Visceral/tratamento farmacológico , Meglumina/administração & dosagem , Antiprotozoários/administração & dosagem , Quimioterapia Combinada , Antimoniato de MegluminaRESUMO
Resumen La leishmaniasis es una enfermedad parasitaria crónica endémica en muchas partes del mundo. La variabilidad de cepas, su clínica y respuesta a tratamiento ha hecho que se clasifique en dos grandes grupos: la leishmaniasis del Nuevo Mundo y la del Viejo Mundo. Según esto, varían las recomendaciones respecto a manejo y seguimiento. En esta revisión se hace énfasis a la leishmaniasis de nuestro medio, revisando opciones terapéuticas y posibilidades principalmente en la población pediátrica.
Abstract Leishmaniasis is a chronic parasitic disease endemic in many parts of the world. The variability of strains, their clinic and response to treatment has led to their classification into two major groups: New World leishmaniasis and Old World leishmaniasis. According to this, the recommendations regarding management and follow-up vary. In this review, emphasis is placed on leishmaniasis in our environment, reviewing therapeutic options and possibilities mainly in the pediatric population.
Assuntos
Humanos , Doenças Parasitárias , Pediatria , Pentamidina/uso terapêutico , Paromomicina/uso terapêutico , Leishmaniose/classificação , Leishmaniose Mucocutânea , Anfotericina B/uso terapêutico , Leishmaniose Cutânea , Costa Rica , Antimoniato de Meglumina/uso terapêuticoRESUMO
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.