Comparación de la eficacia y toxicidad del estibogluconato de sodio y antimoniato de meglumina en el tratamiento de leishmaniasis cutánea en Perú / Efficacy and safety of sodium stibogluconate compared to meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru

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.

Respuesta al tratamiento con estibogluconato sódico para leishmaniasis cutánea en población indígena y mestiza, Amazonas 2014-2018 / Response to treatment with sodium stibogluconate for cutaneous leishmaniasis in indigenous and mestizo population, Amazonas, 2014-2018

Objetivo. Determinar la respuesta al tratamiento con Estibogluconato Sódico en población indígena y mestiza con diagnóstico de leishmaniasis cutánea según ciclo de tratamiento, sexo y etapa de vida, pertenecientes a las Microredes Nieva, Galilea, Tingo y Pedro Ruiz Gallo de la Región Amazonas del 2014 ­ 2018, en Perú. Material y métodos: Estudio descriptivo, retrospectivo, de corte longitudinal, teniendo como universo muestral 559 fichas de pacientes; el método fue inductivo, técnica análisis de datos y el instrumento fue la ficha de registro de datos. Resultados: En la población indígena el 98,1% respondió al tratamiento con primer ciclo de Estibogluconato Sódico y en la población mestiza fue el 94%, los demás pacientes respondieron con segundo ciclo de tratamiento; asimismo del total de pacientes mestizos, el 47,5% fue femenino y de la población indígena el 70,4% fue masculino (p=0,000); de las etapas de vida más afectadas con segundo ciclo de tratamiento fueron la adulta 50% (población indígena) y en la etapa niño 11,2% (población mestiza). Conclusión: El mayor porcentaje de los pacientes presentaron una respuesta adecuada (curaron con el primer ciclo de tratamiento) al Estibogluconato Sódico en ambas poblaciones asimismo las etapas de vida más afectadas fueron la adultez y la niñez

Objetive. To determine the response to treatment with Sodium Stibogluconate in indigenous and mestizo population with diagnosis of cutaneous leishmaniasis according to treatment cycle, sex and life stage, belonging to the Microredes Nieva, Galilea, Tingo and Pedro Ruiz Gallo of the Amazon Region of 2014 - 2018, in Pe r u . M a t e r i a l a n d m e t h o d s : D e s c r i p t i v e , retrospective, longitudinal-sectional study, having as sample universe 559 patient records; the method was inductive, technical data analysis and the instrument was the data record. Results: In the indigenous population, 98.1% responded to the treatment with the first cycle of Sodium Stibogluconate and in the mestizo population it was 94%, the other patients responded with the second treatment cycle; also of the total mestizo patients, 47.5% were female and 70.4% of the indigenous population were male (p=0,000); of the most affected life stages with the second cycle of treatment were the adult 50% (indigenous population) and in the child stage 11.2% (mestizo population). Conclusion: The highest percentage of the patients presented an adequate response (they cured with the first cycle of treatment) to Sodium Stibogluconate in both populations also the most affected life stages were adulthood and childhood

Leishmaniasis cutánea, a propósito de un caso / Cutaneous leishmaniasis, a purpose of a case

La Leishmaniasis es una enfermedad parasitaria catalogada como emer-gente y sin control debido al cambio en el perfil epidemiológico por el sur-gimiento de nuevos focos y urbanización del ciclo de transmisión. Se des-cribe el caso de un adolescente de la Comunidad Dos Ríos, del Cantón Taisha, quien presentó varias lesiones ulceradas, confirmándose diagnós-tico de Leishmaniasis Cutáneamediante estudio histológico, iniciándose tratamiento con sales de antimonio pentavalentes, logrando una resolución progresiva y paulatina de las lesiones. Destacándose la importancia del diagnóstico temprano, tratamiento supervisado, y seguimiento para preve-nir complicaciones.

Leishmaniasis is a parasitic, emergent and uncontrolled disease due to the change in the epidemiological profile for the appearance of new outbreaks and urbanization of the transmission cycle. A case of a 15-years-old ado-lescent, who is resident of the Community Dos Ríos located on the Taisha Canton, was described. The patient presented ulcerated lesions, confir-ming the diagnosis of Cutaneous Leishmaniasis through the histological study of the lesions, and starting intramuscular treatment with pentavalent antimony salts observing healing with a progressive and gradual resolution of the lesions and emphasizing the importance of early diagnosis, supervi-sed treatment, and monitoring to prevent complications.

Síndrome hemofagocítico secundario a leishmaniasis visceral en un lactante mayor: reporte de caso / Hemophagocytic síndrome secondary to visceral leishmaniasis in a toddler: report of a case

El síndrome hemofagocítico está caracterizado por la activación anómala del sistema inmune. De etiología primaria o secundaria a enfermedades infecciosas, metabólicas, inmunitarias o neoplásicas. Con incidencia de 0,12 a 1 casos por cada 100 000 niños y una sobrevida de dos meses de no recibir tratamiento. Se diagnostica con 5 de 8 criterios propuestos por la Asociación Internacional de Histocitosis, y tratamiento según etiología. . Se presenta el caso de un paciente masculino de 15 meses de edad, procedente una zona endémica de leishmaniasis (Choluteca, Honduras), que ingresó al Hospital Escuela Universitario con cuadro clínico de fiebre prolongada y hepatoesplenomegalia. En los exámenes auxiliares de detectó: pancitopenia, serología positiva para leishmania, hipertrigliceridemia y valor de ferritina aumentada. Se hizo el diagnóstico de leishmaniasis visceral y síndrome hemofagocítico. Se trató con antimoniato de meglumina por 28 días, metilprednisolona y prednisona; con evolución favorable. El síndrome hem ofagocítico podría ocurrir secundario a leishmaniasis visceral por lo que su diagnóstico debería sospecharse tempranamente para un tratamiento oportuno y mejor pronóstico

The hemophagocytic syndrome is characterized by an abnormal activation of the immune system. This condition may be primary or secondary to infectious, metabolic, immunological, or malignant conditions. Its incidence is 0.12 to 1 case per 100,000 children, and the survival time is around two months with no therapy. The condition is diagnosed with the occurrence of 5 of 8 criteria proposed by the International Histiocytosis Association, and its therapy is according the original etiology. We present the case of a 15-month old male patient, who was brought from Choluteca (an endemic area for leishmaniasis), who was admitted to the University Hospital with prolonged fever and hepatosplenomegaly. Laboratory tests showed pancytopenia, positive serology for Leishmania, hypertriglyceridemia, and increased ferritin levels. Visceral leishmaniasis and hemophagocytic syndrome were diagnosed. The patient received meglumine antimoniate for 28 days, and also methylprednisolone and prednisone; and he had a favorable outcome. The hemophagocytic syndrome may be secondary to visceral leishmaniasis, and its diagnosis should be promptly suspected in order to have timely therapy and a better prognosis

Manifestaciones oftalmológicas de la leishmaniasis: reporte de un caso / Ophthalmologic manifestations of leishmaniasis: a case report

Fundamento: la leishmaniasis es una enfermedad producida por un protozoo del género leishmanias, que se transmite por la picadura del mosquito del género phlebotomus y una mosca del tipo lutzomyia (mosca de arena o sandfly, en inglés) y puede causar enfermedad de la piel y enfermedad sistémica. Se pueden distinguir tres formas: leishmaniasis visceral, leishmaniasis cutánea y leishmaniasis mucocutánea. La forma sistémica puede ser mortal, pero el tratamiento compuestos que contengan antimonio logra una tasa de curación alta. Objetivo: presentar un caso típico de leishmaniasis que desarrolló alteraciones oftalmológicas no comunes en el mismo. Caso clínico: se recogió el antecedente de haber estado en zona endémica de leishmaniasis antes de la presentación clínica. El cuadro clínico, los antecedentes, los exámenes de laboratorio y los cultivos de piel, confirmaron la presencia de una leishmaniasis. Conclusiones: las leishmaniasis son un conjunto de enfermedades de manifestaciones diversas, pero todas ellas tienen efectos devastadores, por ello siempre se debe tener presente esta enfermedad en el diagnóstico diferencial sobre todo en zonas endémicas.

Background: leishmaniasis is a disease caused by protozoan of the genus leishmanias, transmitted by the bite of the sand fly of the genus phlebotomus and a sand fly of genus Lutzomyia(mosca de arena en español). It can cause skin disease and systemic disease. Three forms can be distinguished clinically: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. Systemic form can be deadly, but treatments that contain antimony achieve a high percent of recovery. Objective: to present a typical case of leishmaniasis that developed uncommon ophthalmic alterations in the disease. Clinical case: it was found out that the person had been in an endemic area of leishmaniasis before having the clinical symptoms. Clinical manifestation, backgrounds, laboratory tests and skin culture confirmed the presence of leishmaniasis. Conclusions: leishmaniasis are a group of diseases of diverse manifestations, however all of them have potentially devastating effects. Consequently, this disease should be always taken into account in differential diagnosis, mainly in endemic areas.

Efeito do Antimoniato de Meglumina durante o período fetal sobre o desenvolvimento físico da prole em camundongos / Effect of the Meglumine Antimoniate during fetal period on physical development of pups in mice

A exposição a agentes químicos durante a prenhez podealterar o desenvolvimento animal e a maturação dos sistemasfisiológicos. O Antimoniato de Meglumina (AM) é a primeiraescolha no tratamento das leishmanioses, mesmoapresentando toxicidade e suposta impregnação neural.Objetivo: O objetivo desde estudo foi verificar odesenvolvimento físico da prole de camundongos Swiss,expostos ao AM durante o período fetal. Material e método:Fêmeas prenhes foram tratadas com AM (100mg/kg/dia)durante o 13° ao 18° dia de gestação – ddg e o grupo controlefoi tratado com o veículo. No dia zero pós-natal - dpn foiregistrado o número e peso da prole de cada ninhada eavaliou-se o desenvolvimento físico (nascimento de pêlos,abertura de olhos e orelhas, dente inciso, abertura da vaginae descida dos testículos) do 0 ao 31º dpn. Os filhotes forampesados no 3°, 5°, 7°, 14° e 21° dpn. Resultados: Não houvediferenças significativas no número e peso da prole no 0 dpnentre os grupos experimental e controle. O desenvolvimentoponderal da prole de ambos os grupos foi semelhante, assimcomo o aparecimento dos indicadores de desenvolvimentofísico. Conclusão: A exposição ao AM durante o períodofetal em camundongos não interferiu no desenvolvimentofísico das crias...

The exposition to the quimical agents during the pregnantcan alter the animal development and the maturation of thephysiological systems. The Meglumine antimoniate (MA) isthe first-choice of treatment of of leishmaniosis samepresented toxicity and suppond neural impregnation.Objective: The aim this work was verify the physicaldevelopmental of the pups of Swiss mice exposed to MAduring the fetal period. Material and methods: Pregnant damsreceived MA (100mg/kg/day) during day 13° to 18° of gestation– ddg. Control group received deionized water. At birth day(0 postnatal – dpn) the number and corporal weight of thepups of each litter was registered. The corporal weight ofthe pups was realized on day 3°, 5°, 7°, 14° and 21° postnatal.Physical development was assessed by monitoring daily onthe 0 to 31º dpn the following parameters in 16 litters: birt ofpilus, eye opening, ear unfolding, incisor eruption, vaginaopening and descent of the testis. Results: No statisticdifference was observed in the number and corporal weightbetween the experimental and control pups at 0 dpn.Conclusion: The ponderal development of the pups of boththe groups was similar, as well the appearance of indicatorsof the physical development. The maternal exposition in miceto MA throughout the fetal period did not interfere in thephysical development of the pups...

Alteração na função renal e pancreatite: efeitos adversos do tratamento da leishmaniose visceral / Change in renal function and pancreatitis: adverse effects of the treatment of visceral leishmaniasis

Introdução: Estudos têm demonstrado que a Leishmania sp. causa glomerulonefrites mesangial, membranoproliferativa focal e difusa, e nefrite intersticial. Estas alterações podem levar à ocorrência de proteinúria, alterações do sedimento urinário e perda da função renal. Como medicação de primeira escolha para o tratamento de LVA é recomendado o antimonial pentavalente, que possui boa eficácia, mas apresenta riscos de cardiotoxicidade, nefrotoxicidade e hepatotoxicidade. A Anfotecina B é utilizada como segunda escolha, mas esta droga também é nefrotóxica. O objetivo do presente trabalho é relatar o comprometimento da função renal em um paciente com diagnóstico de LVA, e que desenvolveu pancreatite após o tratamento com glucantime e apresentou melhoras nesse quadro após uso de anfotericina B, apresentando, porém, um quadro de nefrotoxicidade devido ao uso da segunda droga. Materiais e metodologia: Estudo retrospectivo de prontuário do caso de um paciente do sexo masculino, 64 anos, com diagnóstico de leishmaniose visceral. Na admissão apresentava creatinina sérica de 1,2mg/dL, uréia de 30 mg/dL, potássio de 4,6 mEq/L, proteinúria de 3+ e hematúria com 10 hemácias/campo. Após o tratamento com glucantime houve redução dos níveis de creatinina e desaparecimento da proteinúria. Porém, houve o aparecimento de pancreatite, com amilase 351mg/dL e lipase 1421 mg/dL. Devido a este efeito adverso, desencadeado pelo antimonial, foi utilizada a anfotericina B, que provocou uma piora da função renal, com creatinina 1,8 mg/dL. Após ajuste do intervalo entre as doses de anfotericina B houve normalização da função renal. Este caso ilustra os efeitos adversos relacionados ao tratamento da LVA. Conclusão: É necessário instituir um monitoramento laboratorial sistematizado da função renal e dos níveis séricos da amilase/lipase em pacientes que estejam sob tratamento de leishmaniose com antimonial pentavalente ou anfotericina B.

Introdution: Studies have shown that Leishmania sp causes glomurelonephritis characterized by mesangialcell proliferation, focal and diffuse membranoproliferative glomerulonephrittis and interstitial nephritis. These alterations may lead to the occurrence of proteinurea, alterations in urinary sedimentation and loss of renalfunction. Pentavalent antimoniate is recommended as a first choice in the treatment of AVL; this drug isefficient, but it presents the risk of cardiotoxicity, nephrotoxicity and hepatotoxicity. Amphotericin B is used as a second choice drug, but it is also nephrotoxic and may cause reactions. The objective of the present report is to demonstrate the impairment of renal function in a patient with visceral leishmaniasis who developed pancreatitis after treatment with glucantime and improved after treatment with amphotericin B, presenting, however, a case of nephrotoxicity due to the use of this second drug. Materials and methods: We report acase of a 64 year-old male patient, diagnosed with visceral leishmaniasis. On admission the patient presented creatinine 1.2mg/dL, urea 30 mg/dL, potassium 4.6 mEq/L, proteinurea 3+ and hematuria 10/field. After treatment with antimoniate a decrease in creatinine levels and the disappearance of proteinurea were observed; however, the patient developed pancreatitis, and an increase in the levels of amylase 351 mg/dL and lipase 1421 mg/dLwas verified. Due to this adverse effect triggered by the antimonial, amphotericin B was used, which provokeda worsening of the renal function, with creatinine 1.8mg/dL. After adjusting the interval between doses of amphotericin B, renal function returned to normality. This case illustrates the adverse effects related to the treatment of AVL. Conclusion: There must be a laboratorial follow up of the renal function and sera levels of amylase and lipase in patients under treatment with pentavalente antimoniate or anfotericin B.

Leishmaniose cutânea com desfecho fatal durante tratamento com antimonial pentavalente / American cutaneous leishmaniasis with fatal outcome during pentavalent antimoniate treatment

Os autores relatam o caso de paciente de 58 anos, hipertensa e diabética, com diagnóstico de leishmaniose tegumentar americana, tratada com antimoniato de N-metil-glucamina (15mg SbV/kg/dia), acompanhada pelo serviço de atenção básica em saúde e que evoluiu para óbito no 18° dia de tratamento.

The authors report a case of a 58 years-old, hypertensive, diabetic female patient, with the diagnosis of American cutaneous leishmaniasis, undergoing treatment with Nmethyl glucamine antimoniate (15mg SbV/Kg/day). She was followed up by the basic health care service, but has died on the 18th treatment day.