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.

Are opossums a relevant factor associated with asymptomatic Leishmania infection in the outskirts of the largest Brazilian cities?

Abstract A population survey was conducted to explore the prevalence and factors associated with Leishmania infection in the Fercal region of the Federal District. The Fercal region is a group of neighborhoods in Brasília in which the first cases of visceral leishmaniasis were described. Leishmania infection was established by a positive leishmanin test. Although other tests were performed in the study (an immunochromatographic assay (Kalazar detect®) and a molecular assay), only the leishmanin skin test provided sufficient results for the measurement of the disease prevalence. Data on the epidemiological, clinical and environmental characteristics of individuals were collected along with the diagnostic tests. After sampling and enrollment, seven hundred people from 2 to 14 years of age were included in the study. The prevalence of Leishmania infection was 33.28% (95% CI 29.87–36.84). The factors associated with Leishmania infection according to the multivariate analysis were age of more than seven years and the presence of opossums near the home. Age is a known factor associated with Leishmania infection; however, the presence of wild animals, as described, is an understudied factor. The presence of opossums, which are known reservoirs of Leishmania, in peri-urban areas could be the link between the rural and urban occurrence of visceral leishmaniasis in the outskirts of largest Brazilian cities, as suggested by previous studies.

Lyme disease in the state of Tocantins, Brazil: report of the first cases

Lyme disease is an underdiagnosed zoonosis in Brazil. There are no cases registered in the state of Tocantins, the newest Brazilian state. The cases of three patients in contact with rural areas in three Tocantins' districts are herein described, and the Brazilian literature is reviewed.

Autochthonous visceral leishmaniasis in Brasília, Federal District, Brazil / Leishmaniose visceral autóctone em Brasília, Distrito Federal, Brasil

INTRODUCTION: Visceral leishmaniasis is a public health threat in Brazil considering the high lethality rates and increasing geographical dispersion to large urban conglomerates over the past 25 years. This study aimed to confirm suspected autochthonous cases of visceral leishmaniasis reported from 2005 to 2009 among individuals living in Brasilia, Federal District. METHODS: A retrospective review of the surveillance data obtained on a regular basis and clinical records of the reported cases were performed in 2009. RESULTS: Data from entomological and canine surveys revealed the presence of both Lutzomyia longipalpis and positive serology for Leishmania in dogs within 19 of the 21 neighborhoods where human cases occurred since 2005. The review of surveillance data and medical records, together with the entomological and canine survey data, permitted confirmation of 21 autochthonous human cases in the Federal District. The disease predominantly affected children (12/21) and those from the Sobradinho region (16/21); the typical presentation of fever, hepatosplenomegaly and pancytopenia was observed in 67 percent of cases. Three deaths occurred during the study period. Leishmania (Leishmania) chagasi was successfully isolated from one human case and twelve canine cases. CONCLUSIONS: Visceral leishmaniasis should be considered endemic in Brasilia based on the documented epidemiological behavior herein described and the confirmed autochthony of human cases.

INTRODUÇÃO: A leishmaniose visceral é uma ameaça para a saúde pública no Brasil, considerando a elevada taxa de letalidade e a sua dispersão geográfica para grandes conglomerados urbanos durante os últimos 25 anos. Este trabalho teve como objetivo confirmar a suspeita de autoctonia de casos de leishmaniose visceral notificados de 2005 até 2009 em moradores de Brasília, Distrito Federal. MÉTODOS: Foi realizado em 2009 um estudo retrospectivo dos dados da vigilância obtidos na rotina e dos registros clínicos dos casos humanos notificados. RESULTADOS: Os dados dos inquéritos canino e entomológico revelaram a presença de Lutzomyia longipalpis e de cães com sorologia positiva para Leishmania na vizinhança onde ocorreram 19 dos 21 casos humanos desde 2005. A revisão das fichas de notificação e prontuários dos pacientes, em conjunto com os dados dos inquéritos canino e entomológico permitiram a comprovação da autoctonia de 21 casos humanos no Distrito Federal. A doença afetou predominantemente crianças (12/21), da região de Sobradinho (16/21), com quadro típico de febre, hepatoesplenomegalia e pancitopenia em 67 por cento dos casos. Houve três óbitos no período. Houve sucesso no isolamento de Leishmania (Leishmania) chagasi de um caso humano e de doze casos caninos. CONCLUSÕES: A leishmaniose visceral deve ser considerada endêmica em Brasília, considerando o comportamento epidemiológico aqui descrito e a confirmação da autoctonia dos casos humanos.

Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil

The positivities of two methods for the diagnosis of localised cutaneous leishmaniasis (CL) were estimated in 280 patients enrolled in a clinical trial. The trial was conducted in an endemic area of Leishmania (Viannia) braziliensis and trial participants were patients with skin ulcers and positive leishmanin skin tests. Patients underwent aspirative skin punctures of the ulcerated lesions and lymph nodes for in vitro cultures, which were processed under field conditions at the local health centre. Skin lesion biopsies were tested at a reference laboratory using kinetoplastid DNA (kDNA)-PCR to detect DNA. The median time required to obtain a positive culture from the skin samples was seven days and the contamination rate of the samples was 1.8 percent. The positivities of the cultures from skin lesions, kDNA-PCR and the combination of the two methods were 78.2 percent (95 percent CI: 73-82.6 percent), 89.3 percent (95 percent CI: 85.1-92.4 percent) and 97.1 percent (95 percent CI: 94.5-98.5 percent). We conclude that parasite culture is a feasible method for the detection of Leishmania in field conditions and that the combination of culture and PCR has a potential role for the diagnosis of CL in candidates for clinical trials.

Efeito de uma formulação hidrofílica de paromomicina tópica na leishmaniose cutânea em pacientes com contra-indicações de tratamento com antimonial pentavalente / Effect of a hydrophilic formulation of topical paromomycin on cutaneous leishmaniasis among patients with contraindications for treatment with pentavalent antimonials

Descrevem-se o efeito terapêutico e os eventos adversos associados com o uso tópico de paromomicina 10 por cento em gel na leishmaniose cutânea. Quinze pacientes com leishmaniose cutânea cumpriram os critérios de inclusão descritos a seguir: contra-indicação para o uso de antimoniato de meglumina, intradermorreação de Montenegro positiva e até quatro lesões ulceradas. A fórmula foi prescrita duas vezes ao dia por 20 dias. Quatorze pacientes estiveram disponíveis para a avaliação do desfecho terapêutico e a proporção de cura foi de 21,4 por cento (3/14), 50 por cento melhoraram até a epitelização completa e a proporção de falha foi de 28,6 por cento. Nove pacientes que não apresentaram cura inicialmente foram re-tratados. Oito receberam uma nova série de paromomicina tópica e um foi tratado com antimoniato de meglumina. Dois pacientes não receberam novo tratamento e tiveram melhora lenta e contínua. Cinco de oito pacientes retratados com paromomicina tópica alcançaram a cura clínica, e três apresentaram falha, incluindo um paciente que tinha apresentado melhora com o primeiro tratamento. Os eventos adversos foram leves e locais em 53,3 por cento dos pacientes e nunca levaram à suspensão do tratamento.

The therapeutic effect of and adverse events associated with topical use of 10 percent paromomycin gel on cutaneous leishmaniasis are described. Fifteen patients with cutaneous leishmaniasis fulfilled the following inclusion criteria: contraindication for the use of meglumine antimoniate, positive Montenegro skin test and up to four ulcerated lesions. The formula was prescribed twice a day for 20 days. Fourteen patients were available for the therapeutic outcome evaluation. The cure rate was 21.4 percent (3/14); 50 percent improved as far as complete epithelialization; and the failure rate was 28.6 percent. Nine patients who did not initially present cure were retreated. Eight received a new series of topical paromomycin and one was treated with meglumine antimoniate. Two patients did not receive any new treatment and had continuous slow improvement. Five out of the eight patients retreated with topical paromomycin achieved clinical cure, and three presented failure, including one patient who had shown any improvement with the first treatment. For 53.3 percent of the patients, the adverse events were mild and local and never led to treatment suspension.

Febre crônica associada a abscesso esplênico causado por Staphylococcus epidermidis / Chronic fever associated with splenic abscess due to Staphylococcus epidermidis

Abscessos ocultos são causa freqüente de febre crônica. Os abscessos esplênicos são entidades raras, usualmente associadas a quadros subjacentes de cirurgia abdominal, endocardite ou imunodepressão. Apresenta-se um caso de paciente com febre prolongada causada por um abscesso esplênico, cujo principal diagnóstico diferencial era leishmaniose visceral, que provavelmente esteve associado a traumatismo abdominal. O tratamento consistiu em antibioticoterapia seguida de esplenectomia.

Occult abscesses are frequent causes of chronic fever. Splenic abscesses are rare entities that are usually associated with underlying conditions such as abdominal surgery, endocarditis or immunodepression. We report on the case of a patient with prolonged fever caused by a splenic abscess, whose main differential diagnosis was visceral leishmaniasis. However, this condition was probably related to abdominal trauma. The treatment consisted of antibiotics followed by splenectomy.