Falla terapéutica y hepatotoxicidad de los esquemas de tratamiento endovenoso e intramuscular con estibogluconato de sodio en pacientes con leishmaniasis cutánea / Therapeutic failure and hepatotoxicity with schemes intravenous and intramuscular sodium stibogluconate treatment in patients with cutaneous leishmaniasis

OBJETIVO. Describir la falla terapéutica y hepatotoxicidad de los esquemas de tratamiento endovenoso e intramuscular con estibogluconato de sodio en pacientes con leishmaniasis cutánea. MATERIAL y MÉTODOS. Estudio de cohorte única retrospectivo. Los pacientes fueron tratados con estibogluconato de sodio con el esquema endovenoso continuo por 20 días en una sola dosis, los que presentaron falla terapéutica recibieron un segundo curso de estibogluconato de sodio con el esquema intramuscular dosis dividido en series de la días de tratamiento con intervalos de 7 días de descanso por 3 series. Se revisó las historias clínicas y se evaluó en ambos grupos la falla terapéutica y hepatotoxicidad. RESULTADOS. Cumplieron los criterios de inclusión/exclusión 64 pacientes, todos varones. Leishmania braziliensis fue la especie de leishmania infectante en 96,4 % de casos. La cura fue de 48,4 % en el esquema endovenoso, L. braziliensis fue la única especie identificada en los pacientes con falla terapéutica. La hepatotoxicidad fue de 28,1 % en el esquema endovenoso y 6,3 % en el esquema intramuscular. El grupo de pacientes que falló con el esquema endovenoso y repitió el tratamiento pero con el esquema intramuscular (32 pacientes) tuvo un porcentaje de cura de 100 %; solo 2 pacientes (6,3 %) que recibieron el esquema intramuscular desarrollaron hepatotoxicidad durante el tratamiento. CONCLUSIONES. Existe una alta frecuencia de falla terapéutica y hepatotoxicidad en pacientes con Leishmaniasis cutánea tratados con estibogluconato de sodio con el uso del esquema endovenoso. Los pacientes tratados con el esquema intramuscular no presentan falla terapéutica y tienen una baja frecuencia de hepatotoxicidad.

OBJECTIVE. Describe the therapeutic failure and hepatotoxicity schemes intravenous and intramuscular sodium stibogluconate treatment in patients with cutaneous leishmaniasis (CL). MATERIAL AND METHODS. Retrospective single cohort study. Patients were treated with sodium stibogluconate with continuous intravenous scheme for 20 days in a single dose; those with therapeutic failure received a second course of sodium stibogluconate with intramuscular scheme doses divided into sets of 10 days of treatment with intervals 7 days off per 3 series. The medical records were reviewed and evaluated in both groups treatment failure and hepatotoxicity. RESULTS. They met the inclusion/exclusion of 64 patients, all males. The specie of leishmania was present in 96,4 % of cases was the Leishmania braziliensis. Curing was 48,4 % for the intravenous scheme, L. braziliensis was the only species identified in patients with therapeutic failure. Hepatotoxicity was 28,1% in the scheme intravenous and intramuscular 6,3 % in the scheme. The group of patients who failed with the scheme and repeated intravenous treatment but with the intramuscular scheme (32 patients) had a cure rate of 100 %; only 2 patients (6,3 %) who received intramuscular scheme developed hepatotoxicity during treatment. CONCLUSIONS. There is a high rate of treatment failure and hepatotoxicity in patients treated with CL with sodium stibogluconate intravenous use scheme. Patients treated with intramuscular scheme have no therapeutic failure and have a low frequency of hepatotoxicity.

Acute erythroid toxicity in visceral leishmaniasis: a rare complication of antimonial therapy.

The spectrum of side-effects of sodium stibogluconate is well described, however, little is known regarding the acute erythroid toxicity caused by this drug. We hereby present a case with this unusual complication of antimonial therapy. A 6-year-old male with leishmaniasis was started on parenteral sodium stibogluconate. During the course of treatment, his hemoglobin (Hb) dropped from 7.2 g/dl to 3.5 g/dl. Bone-marrow aspirate showed karyorrhexis in many erythroid precursors with several Leishmania donovanii bodies. Sodium stibogluconate was stopped and amphotericin-B was started. Four days after the cessation of the antimonials, the patient's Hb improved to 5 gm/dl with a corrected reticulocyte count of 10% indicating bone-marrow erythroid regeneration. The exact mechanism of this acute erythroid toxicity of sodium stibogluconate remains unexplored.

Pharmacovigilance in kala-azar patients with severe thrombocytopenia caused by sodium antimony gluconate & miltefosine.

Sodium antimony gluconate (SAG) and miltefosine used in the treatment of kala-azar are known to cause several side effects but severe thrombocytopenia has not been reported. Four cases of severe thrombocytopenia, two caused by SAG and two by miltefosine were promptly detected and treated by immediate withdrawal of the offending drugs, platelet and blood transfusions and dexamethasone. After improvement Leishman-Donovan (LD) bodies were demonstrated in splenic aspirates of both patients of SAG group and one of miltefosine and they were treated with 1 mg/kg body wt of amphotericin B for 20 days and cured. One patient of miltefosine group treated outside only on the basis of rK-39 positivity did not show LD bodies in splenic aspirates and improved without any antikala- azar drug. None of the patients relapsed within 6 months of follow up. Prompt detection of side effects under the concept of pharmacovigilance can save life of such patients.

Alteration of serum copper in Kala-azar patients during SAG therapy.

We conducted an analytic case-control study in Kala-azar patients during Sodium Antimony Gluconate (SAG) therapy to assess the changes in serum copper. A total of 89 subjects were included in the study. Diagnosed patients of Kala-azar with parasitological evidence of Leishmania Donovani (LD) bodies in bone marrow, were selected as cases (n=54). They were selected from Medicine and Paediatric wards of Mymensingh Medical College Hospital, Mymensingh and nearby Fulbaria upazila of Mymensingh district. Physically healthy volunteers of similar age, sex and body mass index (BMI) as cases, were included in control group (n=35). The study period was from July 2003 to June 2004. SAG was given intramuscularly (20 mg/kg/day) to Kala-azar patients for 30 days. Blood samples were collected from controls, Kala-azar cases before therapy and same cases during 15-20 days of SAG therapy. Serum copper was higher in cases before therapy than those of controls (p<0.001). However, serum copper reduced significantly (p<0.001) during SAG therapy. So biochemical monitoring may be considered in the management of the disease.

Antimony-induced cerebellar ataxia

Visceral leishmaniasis VL, caused by Leishmania donovani is endemic over several parts of Sudan. The disease is fatal if not treated. Although sodium stibogluconate Pentostam, a pentavalent antimonial is not free from toxicity, it has been in use for treatment of VL for the last 50 years. Like other infectious diseases, neurological manifestations of VL and sodium stibogluconate have been documented. In this report, we present 2 cases of cerebellar ataxia most likely induced by Pentostam, and explain the probable cause

Sodium stibogluconate and polymorphic ventricular tachycardia.

Numerous antimicrobials including pentavalent antimonials are implicated in causing prolong QT-interval and ventricular tachycardia. Torsades de pointes is rarely documented with use of sodium stibogluconate. Here is described a 12-yr-old girl with visceral leishmaniasis, who developed syncopal attacks, prolong QT-interval, polymorphic ventricular tachycardia and torsades de pointes after completing a course of Stibogluconate (20 mg/kg/day for 30 days). Prolong lidocaine infusion and cardioversion were life saving.

Obito durante tratamento da leishmaniose tegumentar americana com stibogluconato de sódio bp 88® (shandong xinhua) / Fatal case during treatment of american tegumentary leishmaniasis with sodium stibogluconate bp 88® (shandong xinhua)

Os autores relatam a ocorrência de óbito em paciente portador da forma cutânea da LTA no município de Caxias-MA. Trata-se de paciente do sexo masculino, 22 anos, gari, portador de lesäo ulcerada no membro inferior (perna esquerda), diagnosticado, após encontro do parasita (Leishmania) na lesäo, tratado com stibogluconato de sódio BP88® (Shandong Xinhua) na dose de 10mg/Sb+5/kg/dia/20 dias. Após a 3ª dose apresentou dores articulares, naúseas, mal estar geral. Com a continuaçäo da medicaçäo houve agravamento do quadro com dor epigástrica e no hipocôndrio direito irradiando-se para o hemitórax homolateral. Após a 7ª dose apresentou dispnéia associado à dor torácica de leve intensidade. Na 9ª dose houve piora do quadro, mesmo assim continuou a usar o medicamento até a 11ª dose quando seu estado agravou-se. Foi internado, necessitando de tratamento intensivo. Nos exames realizados apresentou: 4,4 milhöes de eritócitos, 10,6 por cento de hemoglobina, 35 por cento de hematócrito, 26.400 de leucócitos, basófilos e mielócitos (0), 59 por cento de segmentados, 30 por cento de linfócitos, 2 por cento de monócitos, plaquetas (normais), glicose 42mg por cento, uréia 73mg por cento, creatinina (2,4mg por cento), eletrocardiograma (bloqueio de ramo direito). Veio a falecer tendo como causa do óbito, insuficiência cárdio respiratória. O relato atual mostra a necessidade de esclarecimento das equipes de saúde quanto ao uso dos Sb+5 e também lembrar o Ministério da Saúde quando da aquisiçäo de novos produtos, preocupar-se com a qualidade e procedência do mesmo

Avaliaçäo comparativa da eficácia e toxicidade do antimoniato de N-metil-glucamina e do Estibogluconato de Sódio BP88© no tratamento da leishimaniose cutânea localizada / Evaluation of the eficacy and toxicity of N-methyl-glucamine vs BP88© Sodium Stibogluconate in the treatment of localized cutaneous leishmaniasis

Foi realizado ensaio clínico randomizado simples cego para comparar a eficácia e a toxicidade do estibogluconato de Na+ (ES) e o antimoniato de N-metil glucamina, o Glucantime®(GL). Sessenta e três pacientes foram distribuídos em um dos dois grupos: 32 pacientes foram tratados com GL e 31 pacientes com o ES. Ambos os grupos receberam 15mg Sb+5/kg/dia durante 20 dias. A toxicidade foi avaliada através do ECG, dosagens de uréia, creatinina, TGO, TGP, fosfatase alcalina, amilase, e lipase, avaliados antes do tratamento, nos dias 10 e 20 do tratamento, e 90 dias após o término do mesmo. No grupo tratado com GL 81 por cento (26/32) dos pacientes curaram, comparados com 77 por cento (24/31) no grupo do ES. Um paciente em cada grupo näo respondeu ao tratamento. TGO, TGP, amilase, e lipase foram mais elevadas no grupo que usou o ES (p < 0,05). Concluiu-se que, a eficácia de ambos os tratamentos foram similares, apesar da maior toxicidade observada no grupo tratado com ES

Estudo comparativo entre estibogluconato de sódio BP 88© e antimoniato de meglumina no tratamento da leishmaniose cutânea: Toxidade bioquímica e cardíaca / Comparative study between sodium stibogluconate BP 88© and meglumine antimoniate in cutaneous leishmaniasis treatment: Biochemical and cardiac toxicity

Foi avaliada a toxicidade de dois antimoniais pentavalentes em 111 pacientes com leishmaniose cutânea. Quarenta e sete pacientes receberam antimoniato de meglumina (Grupo I) B 64 pacientes, estibogluconato de sódio BP 88© (Grupo II), 20mg Sbv/kg/dia por 20 dias. Realizou-se a avaliaçäo de aminotransferases, fosfatase alcalina, amilase, creatinina, uréia, exame de urina e eletrocardiograma, antes do tratamento e no décimo e vigésimo dias. Observou-se maior freqüência de valores anormais de aminotransferases no décimo e vigésimo dias de tratamento no grupo II (p < 0,001) e maior proporçäo de valores anormais de amilase no décimo dia no mesmo grupo (p < 0, 00 1). Houve maior variaçäo dos níveis de aminotransferases, fosfatase alcalina e amilase nos primeiros dez dias no grupo II (p < 0,01). No vigésimo dia observou-se maior variaçäo nos níveis de aminotransferases no grupo II (p = 0,02 e p = 0,03, respectivamente). Quarenta e três porcento dos pacientes do grupo I e 54 por cento dos pacientes do grupo II apresentaram alteraçöes eletrocardiográficas (p = 0,30)

Nuevos aportes clínico-patológicos y terapéuticos en leishmaniasis / New development on the clinical, pathological and therapeutics aspects of leishmaniasis

La leshmaniasis es producida por un protozoo, trasmitida por muchos mosquitos hematófagos (Lutzomia brasiliensis), artrópodos (Rhipicephalus turanicus) y probablemente triatomideos (Triatoma infestans, Pansterongilus infestans). En Bolivia existen tres formas de leishmaniasis: cutánea, mucocutánea y visceral, producidas por el mismo agente etiológico, con tres diferentes fases evolutivas relacionadas con mecanismos inmunológicos dependientes de muchos factores. Las tres responden a diversas drogas, a veces inespecíficas, que son empleadas para otras enfermedades (plasmodios, trichomonas, giardias, hongos y bacilos de Koch). Las sales antimoniales pentavalentes son las más comúnmente usadas, con resultados variables, a veces adversos, por su toxicidad, ineficacia ineficiencia y, sobre todo, resistencia y difícil manejo. Se ha demostrado que la L. cutánea tratada con glucantime, anfotericina B y otros presenta posteriormente lesiones mucocutáneas. Por otro lado, leishmaniosos que curaron espontáneamente han mostrado lesiones secundarias en forma ocasional. Lo que demuestra que en esta enfermedad existe una falla inmunológica, razón por la que usamos un inmunomodulador (DECARIS-clorhidrato de levamisol-, que es un antiparasitario), con buenos resultados (95 por ciento de éxito), sobre todo por su bajo costo, uso cómodo y efectos colaterales mínimos. Finalmente concluimos que en el momento actual no existe un leishmanicida eficaz para el tratamiento de esta enfermedad. El tratamiento inmunológico parece ser muy prometedor

Combination therapy in Kala-azar.

128 untreated cases of Kala-azar were divided in 4 equal groups of 32, Group A was treated with Sodium Stibogluconate (SSG) in the dose of 20 mg/kg/body wt. for 30 days. Group B was treated SSG plus allopurinol in the dose of 20 mg/kg/body wt. orally in divided dosage for 30 days. Group C received SSG plus Ketoconazole 600 mg orally in divided dosage for 30 days. Group D in addition to SSG also received levamisole in single oral daily dose of 13 mg/kg/body wt. for 30 days. Response of Group B, C and D was compared to Group A. Results from this study revealed combination of allopurinol with SSG to be statistically not superior to SSG alone.

Renal dysfunction in patients of kala azar treated with sodium antimony gluconate.

We studied 27 patients presenting with renal dysfunction after Stibamate therapy. Eighteen patients were proved cases of Kala Azar, others of PUO. Out of 10 cases in whom Kidney biopsy was done, 6 had tubular necrosis, one had mild mesangial proliferation and 3 had normal picture.

Efficacy of prolonged therapy with stibogluconate in post kala-azar dermal leishmaniasis.

Fifty three (30 male and 23 female), previously untreated, patients with post kala-azar dermal leishmaniasis (PKDL) were treated with sodium stibogluconate, at the dose of 20 mg/kg/bw/d/im/(with a maximum of 8.5 ml) for 120 days (or more, if necessary). All the patients were followed up for 12 months. The patients were assessed after 40 days and thereafter at an interval of 20 days. The mean age of onset was 24 yr, maximum number of patients developed the disease within 3 yr of apparent cure of kala-azar. Maximum number of patients sought treatment within 5 yr of the onset of PKDL. The disease affected the face (98%), trunk (83%), upper limb (72%), lower limb (40%), genetalia (6%), and mucus membrane of the tongue 40%. The lesions observed were nodules (19%), papules (30%), and hypopigmented (45%) and reddish macules (7%). The parasites could be demonstrated in the nodules (100%), papules (69%) and macules (59%). The response to treatment started in 72 per cent of patients in the first 20 days and in 40 days in all patients. All the nodules and papules disappeared in 120 days, and the macules within 200 days. The side effects of treatment noted were changes in S T and T in electrocardiogram (7%), arthralgia (11%), allergic rash (7%), swelling at the site of injection (5%), neuralgia (4%) and metalic taste (6%). The S T and T changes reverted to normal when the drug was discontinued for 20 days. Arthralgia improved with indomethacin. The higher dosages and longer course of treatment were well tolerated and resulted in a cure in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluación de la efectividad y toxicidad del pentostam y del glucantime en el tratamiento de la Leishmaniasis cutánea / Evaluation of effectiveness and toxicity of pentostam and glucantime in the treatment of cutaneous leishmaniasis

El propósito de este estudio fue determinar la efectividad y la toxicidad del estibogluconato sódico y del antimoniato de glucantime, en las dosis recomendadas por la Organización Mundial de la Salud (OMS), en el tratamiento de la leishmaniasis cutánea. Con tal objeto tratamos un grupo de 59 pacientes, que tenían leishmaniasis cutánea causada por L. braziliensis panamensis y fueron seleccionados al azar. Estos pacientes recibieron glucantime o pentostam durante 20 días, en dosis diaria de 20 mg de Sb por Kg de peso, por vía intramuscular (hasta un máximo de 850 mg, diariamente). Las dos drogas antimoniales fueron igualmente efectivas. Un total de 35 pacientes (70%) se hizo negativo parasitológicamente al finalizar el tratamiento y todos permanecieron cicatrizados después de 6 a 12 meses de seguimiento; en un grupo de 13 (26%) casos cicatrizó la lesión, pero se reactivó de 1 a 6 meses después del tratamiento; y en otros dos (4%) pacientes se observó una cicatrización incompleta y la persistencia de los parásitos hasta por 2 meses. En 58% de los casos notamos efectos levemente adversos, tales como mialgias, artralgias, cefalea y fiebre. En ningún caso observamos toxicidad hepática, hematológica, cardíaca o renal. Un descenso progresivo en los títulos y la seronegativización se observó, por inmunofluorescencia indirecta, en los pacientes curados