Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.

Evidências clínicas e imunológicas da eficácia do tratamento da leishmaniose cutânea com baixas doses de antimonial pentavalente na manutenção de cura por longo tempo / Evidence from clinical and immunological effectiveness of cutaneous leishmaniasis treatment with low doses of pentavalent antimony in curing maintained for a long time

O tratamento para leishmaniose cutânea (LC) utilizando antimoniais foi iniciado em 1912, no Brasil. O uso da forma pentavalente (Sb5+) se iniciou na década de 1940, e apesar de ainda ser eficaz para curar a LC efeitos adversos graves podem acontecer. Outras opções de tratamento, como pentamidina e anfotericina B também são de administração parenteral. Na tentativa de reduzir os efeitos adversos dos Sb5+, esquemas terapêuticos em doses baixas já evidenciaram ser seguros no tratamento da LC no Rio de Janeiro, sejam doses de apenas 5mg Sb5+/kg/dia por 30 dias (DB), aplicação intralesional (IL) ou em esquema de uso de uma ampola três vezes por semana (2ª/4ª/6ª) até a cura clínica...

Antimony therapy was first used to treat cutaneous leishmaniasis (CL) in 1912.Pentavalent antimonial (Sb5+) compounds were introduced as leishmaniasis therapy in the 1940s and are still efficient in curing CL, but they may cause serious adverse effects. Although there are other options for CL treatment, such as pentamidine and amphotericin B, similar to Sb5+, these drugs are also administered parenterally. To reduce the adverse effects of antimony, low-dose therapies were attempted and were proven safe in curing CL in patients in the state of Rio de Janeiro. Different schedules as 5mgSb5+/day/30 days (LowD), intralesional therapy (IL), or use of one ampoule three-times-a-week until clinical cure were proven to be efficient to cure CL...

The effect of age on the frequency of adverse reactions caused by antimony in the treatment of American tegumentary leishmaniasis in Governador Valadares, State of Minas Gerais, Brazil / Efeito da idade na frequência das reações adversas provocadas pelo antimônio no tratamento de pacientes com leishmaniose tegumentar americana, em Governador Valadares, Estado de Minas Gerais, Brasil

INTRODUCTION: Governador Valadares is an endemic area of American tegumentary leishmaniasis (ATL). The detection rate was 15.36 per 100,000 habitants from 2001 to 2006 (Miranda, 2008). This study aimed to analyze the effects of age on the frequency of adverse reactions caused by antimony in the treatment of ATL in the City of Governador Valadares, State of Minas Gerais, Brazil, during 2009. METHODS: Data were collected from the forms of the Information System for Notifiable Diseases, and from charts, questionnaires, and home visits to patients. RESULTS: The study included 40 patients, 26 (65%) of whom were males. Individuals over the age of 50 had a 66% higher rate of adverse effects than subjects who were 50 years old or less (CI 95%, 1.14-2.41). The average age of individuals who reported some type of adverse effect was 44.11 years (SD = 20.14), while the average age of the group that did not report any adverse effect was of 25.46 years (SD = 18.37; p < 0.01). Clinical healing was 67.5%, and 10% of patients discontinued the treatment. CONCLUSIONS: In the treatment of ATL, the age of patients should be considered, because most adverse reactions occur in individuals over 50 years of age. For this reason, the drug should be used with restriction in these cases.

INTRODUÇÃO: Governador Valadares constitui uma área endêmica de leshmaniose tegumentar americana (LTA) e o coeficiente de detecção foi de 15,36/100.000 habitantes no período de 2001 a 2006 (Miranda, 2008). Este estudo teve como objetivo analisar o efeito da idade na frequência das reações adversas provocadas pelo antimônio no tratamento de pacientes com LTA, em Governador Valadares, Estado de Minas Gerais, Brasil, no período de janeiro a dezembro de 2009. MÉTODOS: Para coleta de dados foram utilizados: ficha de notificação do Sistema de Informação de Agravos de Notificação (SINAN), prontuários, questionário e visitas domiciliares aos pacientes. RESULTADOS: Participaram do estudo 40 pacientes, sendo 26 (65%) do sexo masculino. Os indivíduos acima de 50 anos de idade tiveram prevalência 66% maior de reações adversas que as pessoas com idade de 50 ou menos (IC 95% -1,14-2,41). A média de idade dos indivíduos que relataram algum tipo de reação adversa foi de 44,11 anos (DP=20,14), enquanto no grupo que não relatou reação adversa, a média de idade foi de 25,46 anos (DP=18,37) e p < 0,01. A cura clínica foi de 67,5% e 10% dos pacientes abandonaram o tratamento. CONCLUSÕES: No tratamento da LTA, a idade do paciente deve ser considerada; pois ocorrem mais reações adversas em indivíduos acima de 50 anos de idade, que nesses casos o medicamento deve ser utilizado com restrição.

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.

Predictors of an unsatisfactory response to pentavalent antimony in the treatment of American visceral leishmaniasis

Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90 percent with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose / The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis

Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

Cardiac complications and electrocardiographic changes observed during treatment with pentavalant antimony in visceral leishmaniasis [KALA-AZAR]

A total of 41 adult parasitologically proved hospitalized visceral leishmaniasis[Kala-azar] cases of both sexes were studied to see the cardiac complications and the electrocardiographic alterations during pentavalant antimonial [sodium stibogluconate] therapy in standard dose. The mean [ +/- SD] age and duration of fever of the patients were 26.2 [ +/- 10.6] years and 18.7 [ +/- 12.5] weeks respectively. All had normal ECG prior to therapy. Various electrocardiographic alteration were noted in 12 [29.3%] of the cases after starting antimony therapy. Out of them, one case manifested as a heart failure and another Strokes- Adams attacks, but both improved with conservative treatment. Electrocardiographic alterations noted were in the form of diffuse "T" inversion [8], sinus tachycardia [3] and conduction defect with diffuse 'T" inversion [1]. These changes were observed during third week of therapy and disappeared within two weeks of stoppage of further antimony therapy. Alterations in ECG might be the prior evidences of cardiotixicity and might explain sudden deaths encountered during antimony in kala-azar. These ECG alterations are usually asymptomatic, developing during the latter part of therapy and reversible. Close clinical observations and ECG monitoring of the patients receiving antimony therapy for kal-azar is essential for early detection of cardiotixicity and therapy to prevent complications including sudden death

El caso de infecciosas: Leishmaniasis cutanea / The case of infectious: Leishmaniasis cutaneous

Se presenta el caso de un agricultor quien padecio lesion cutanea ulcerosa cronica producida por Leishmaniasis sp. la cual curo con tratamiento con Metilglucamina mas Cimetidina

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