Characterization of adverse reactions to benznidazole in patients with Chagas disease in the Federal District, Brazil

Abstract INTRODUCTION: Benznidazole is used for treating Chagas disease (CD). This cross-sectional study aimed to characterize the adverse drug reactions (ADRs) of benznidazole at a public hospital in Brazil's Federal District. METHODS: Medical records were analyzed and ADRs were categorized by type, intensity, seriousness, and causality. RESULTS: Of the 62 patients who started benznidazole treatment for CD, 41 (66%) presented with 105 ADRs; 23 (37%) discontinued the treatment. Most reactions were classified as probable (81%), severe (63%), serious (67%), and dose-dependent (56%). CONCLUSIONS: The high incidence of ADRs because of treatment withdrawal revealed the need for safer alternatives for CD treatment.

Epidemiological features, echocardiographic findings, and parasite load in patients with Chagas disease

Abstract INTRODUCTION Chagas disease is a major public health problem that is endemic in Brazil and Latin America. This study aimed to determine the socioeconomic, demographic, and clinical characteristics of 171 patients (mean age, 45 years; female, 65%) with Chagas disease at Hospital Universitário de Brasília, Federal District, Brazil. METHODS We implemented this cross-sectional study using a clinical epidemiological questionnaire, electrocardiography, echocardiography, and quantitative detection of Trypanosoma cruzi DNA in blood using qRT-PCR. RESULTS Among the patients, 26.3% had a full elementary education, and 13.2% were illiterate. Most (63.6%) were economically classified as class C, and 51.5% were born in Bahia state. A total of 62.0% participants reported previous contact with the triatomine bug. The clinical forms of the disease were indeterminate (69.51%), cardiac (15.24%), digestive (10.37%), and mixed (4.88%). The most common electrocardiographic abnormality was complete right bundle branch block in association with a divisional anterosuperior block. Only 14.6% of the patients complied with benznidazole medication for at least 60 days, and 164 of them were assessed by echocardiography. The parasite load was positive in 56% of the patients. CONCLUSIONS: Chagas disease affected mostly women, with the indeterminate chronic form of the disease.

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.

Adverse drug reactions among patients admitted with infectious diseases at a Brazilian hospital

Abstract INTRODUCTION: Despite the therapeutic benefits of drugs, adverse drug reactions (ADRs) occur. Method: We assessed a series of suspected ADRs identified from notifications and intensive monitoring of inpatients from March 2013 to March 2014. RESULTS: Skin reactions predominated (31%). Systemic anti-infective agents were implicated in 16 (72%) reactions. Fifteen (68%) ADRs were classified as possible. The implicated drug was not correctly identified by the healthcare team in 12 cases. CONCLUSIONS: Some reactions were not correctly attributed to the causative drug(s), suggesting that the use of a validated evaluation method can promote successful identification of causal links between ADRs and drugs.

Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection

In Brazil, human and canine visceral leishmaniasis (CVL) caused byLeishmania infantum has undergone urbanisation since 1980, constituting a public health problem, and serological tests are tools of choice for identifying infected dogs. Until recently, the Brazilian zoonoses control program recommended enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescence assays (IFA) as the screening and confirmatory methods, respectively, for the detection of canine infection. The purpose of this study was to estimate the accuracy of ELISA and IFA in parallel or serial combinations. The reference standard comprised the results of direct visualisation of parasites in histological sections, immunohistochemical test, or isolation of the parasite in culture. Samples from 98 cases and 1,327 noncases were included. Individually, both tests presented sensitivity of 91.8% and 90.8%, and specificity of 83.4 and 53.4%, for the ELISA and IFA, respectively. When tests were used in parallel combination, sensitivity attained 99.2%, while specificity dropped to 44.8%. When used in serial combination (ELISA followed by IFA), decreased sensitivity (83.3%) and increased specificity (92.5%) were observed. Serial testing approach improved specificity with moderate loss in sensitivity. This strategy could partially fulfill the needs of public health and dog owners for a more accurate diagnosis of CVL.

Specificity of the rapid rK39 antigen-based immunochromatographic test Kalazar Detect(r) in patients with cutaneous leishmaniasis in Brazil

The aim of this study was to evaluate the specificity of a rapid immunochromatographic test that was developed to detect antibodies against the rK39 antigen for the diagnosis of visceral leishmaniasis (VL). This evaluation was performed using sera from patients with a confirmed diagnosis of active cutaneous leishmaniasis. The sera from 272 patients with a confirmed diagnosis of localised cutaneous leishmaniasis (CL) who resided in an area endemic for Leishmania braziliensis in Brazil were obtained before the initiation of antileishmanial treatment. Kalazar Detect(r)(InBios, Seattle, WA) recombinant K39 antigen-based immunochromatographic strips were used according to the manufacturer's instructions. The test results were evaluated independently by two examiners in sequential order. The positive controls for the test included five serum samples from five patients with parasitologically confirmed diagnosis of VL caused by Leishmania infantum in Brazil. Overall, 100% of the samples obtained from patients with CL were negative, confirming the absence of a serological cross-reaction for individuals with cutaneous disease when these patients were evaluated using the rapid test. The lack of a cross-reaction in patients who were infected by parasites of the same genus highlights the specificity of the rK39 antigen for the diagnosis of VL in areas with the sympatric circulation of L. braziliensis and L. infantum.

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.

Incidência de tuberculose e taxa de cura, Brasil, 2000 a 2004 / Tuberculosis incidence and cure rates, Brazil, 2000-2004

OBJETIVO: Descrever a distribuição geográfica da incidência de tuberculose, a partir de um conjunto de indicadores epidemiológicos e operacionais de dados de notificação oficial. MÉTODOS: Dados sobre incidência de tuberculose foram coletados no Sistema de Informação de Agravos de Notificação, após processo de pareamento e depuração de registros repetidos. As taxas de incidência de tuberculose foram calculadas segundo unidade geográfica, grupo etário, sexo, forma clínica e regime de tratamento, e padronizadas para a distribuição etária da população com base no Censo de 2000. RESULTADOS: Em 2004, o Brasil apresentou taxa de incidência de 41/100.000 habitantes, com 74.540 casos novos notificados. Desses, 52,8 por cento eram casos pulmonares com baciloscopia positiva, 24,1 por cento estavam em tratamento supervisionado, 63,5 por cento eram provenientes de capitais ou das regiões metropolitanas e 54,9 por cento eram casos curados. Excluindo-se os registros sem preenchimento da variável de desfecho, a proporção de cura alcançou 72,4 por cento para casos novos, 47 por cento para casos novos HIV positivos, 64,9 por cento para recidivas, 64,5 por cento transferências e 40 por cento para reingressos após abandono. A taxa de cura para os casos novos em tratamento supervisionado foi de 77,1 por cento. A proporção de registros sem informação sobre desfecho foi maior em anos mais recentes. CONCLUSÕES: Houve extensas diferenças estaduais em relação à incidência e às categorias de desfecho. Para alcançar a meta de 85 por cento de cura para casos novos e aumentar a cura dos casos HIV positivos e reingressos são necessários esforços adicionais por parte do Programa Nacional de Controle da Tuberculose, incluindo a expansão da estratégia de tratamento diretamente supervisionado.

OBJECTIVE: To describe the geographical distribution of tuberculosis incidence rates based on a set of epidemiological and operational indicators from information system database. METHODS: Data from the Sistema de Informação de Agravos de Notificação (Brazilian Information System for Tuberculosis Notification) were collected after removal of improper repeat records and record linkage. Tuberculosis incidence rates were estimated according to geographical unit, age group, sex, clinical manifestation and treatment schedule and standardized for population age group distribution based on 2000 Population Census. RESULTS: In 2004, in Brazil, tuberculosis incidence rate was 41 per 100,000 inhabitants and 74,540 new cases were notified. Of these, 52.8 percent were pulmonary tuberculosis with positive bacilloscopy, 24.1 percent were under supervised treatment, 63.5 percent were from state capitals or metropolitan areas, and 54.9 percent were cured cases (complete treatment). After records with missing outcome data were excluded, cure rates were 72.4 percent for new cases, 47 percent for new HIV-positive cases, 64.9 percent for relapses, 64.5 percent for transfers in/out, and 40 percent for returns after default. Cure rate for new cases under supervised treatment was 77.1 percent. A higher proportion of records with missing outcome information was seen in recent years. CONCLUSIONS: Different incidence rates and treatment outcomes were found in different Brazilian states. To reach the 85 percent cure goal for new cases and to increase cure in HIV-positive and defaults cases additional efforts are needed by the Brazilian National Tuberculosis Program, including scaling up the Directly Observed Therapy Strategy.

Efeito da remoção de notificações repetidas sobre a incidência da tuberculose no Brasil / Impact on tuberculosis incidence rates of removal of repeat notification records

OBJETIVO: Avaliar o impacto nas taxas de incidência de tuberculose com a exclusão de registros indevidamente repetidos no sistema de notificação. MÉTODOS: Foram analisados dados do Sistema de Informação de Agravos de Notificação do Ministério da Saúde, referentes ao período de 2000 a 2004. Os registros repetidos foram identificados por pareamento probabilístico e classificados em seis categorias excludentes que determinaram suas remoções, vinculações ou permanências na base. RESULTADOS: Verificou-se que 73,7 por cento das notificações eram únicas, 18,9 por cento formavam duplas, 4,7 por cento triplas e 2,7 por cento grupos de quatro ou mais registros. Dentre os registros repetidos, 47,3 por cento foram classificados como transferência entre unidades de saúde, 23,6 por cento reingresso, 16,4 por cento duplicidade verdadeira, 10 por cento recidiva, 2,5 por cento foram inconclusivos e 0,2 por cento tinham dados incompletos. Essas percentagens variaram entre estados. A exclusão de registros indevidamente repetidos resultou em redução na taxa de incidência por 100.000 habitantes de 6,1 por cento em 2000 (de 44 para 41,3), 8,3 por cento em 2001 (de 44,5 para 40,8), 9,4 por cento em 2002 (de 45,8 para 41,5), 9,2 por cento em 2003 (de 46,9 para 42,6) e 8,4 por cento em 2004 (de 45,4 para 41,6). CONCLUSÕES: Os resultados sugerem que as taxas observadas de incidência de tuberculose representem estimativas mais próximas do que seriam os valores reais do que as obtidas com a base em seu estado bruto, tanto em nível nacional como estadual. A prática de pareamento de registros de notificação de tuberculose deve ser estimulada e mantida para melhoria da qualidade dos dados de notificação.

OBJECTIVE: To evaluate the impact on tuberculosis (TB) incidence rates of removal of improper duplicate records from the notification system. METHODS: Data from the Sistema de Informação de Agravos de Notificação (Brazilian Information System for Tuberculosis Notification) from 2000 to 2004 were analyzed. Repeat records were identified through probabilistic record linkage and classified into six mutually exclusive categories and then kept, combined or removed from database. RESULTS: Of all TB records, 73.7 percent had no duplicate, 18.9 percent were duplicate, 4.7 percent were triplicate, and 2.7 percent were quadruplicate or more. Of all repeat records, 47.3 percent were classified as transfer in/out; 23.6 percent return after default, 16.4 percent true duplicates, 10 percent relapse, 2.5 percent inconclusive and 0.2 percent had missing data. These proportions were different in Brazilian states. Removal of improper duplicate records reduced TB incidence rate per 100.000 inhabitants by 6.1 percent in the year 2000 (from 44 to 41.3), 8.3 percent in 2001 (from 44.5 to 40.8), 9.4 percent in 2002 (from 45.8 to 41.5), 9.2 percent in 2003 (from 46.9 to 42.6) and 8.4 percent in 2004 (from 45.4 to 41.6). CONCLUSIONS: The study results indicate that the observed tuberculosis incidence rates represent estimates that would be closer to the actual rates than those obtained from the raw database at state and country level. The use of record linkage approach should be promoted for better quality of notification system data.

High frequency of skin reactions in patients with leishmaniasis treated with meglumine antimoniate contaminated with heavy metals. A comparative approach using historical controls

We analyzed data from historical controls treated with meglumine antimoniate to compare the frequency of adverse events observed in patients with cutaneous leishmaniasis treated with the same dose of meglumine antimoniate contaminated with heavy metals in an endemic area of the State of Bahia, Brazil. Group A patients were treated in 2000 with the drug produced by Eurofarma Laboratórios Ltda., São Paulo, Brazil (lot A) and group B patients were treated in 1996 with the reference drug produced by Rhodia Farma Ltda., São Paulo, Brazil (lot B). We observed an unusual higher frequency of skin reactions in group A patients. However, all type of adverse events observed in group A were also observed in group B. The physico-chemical analysis of these lots revealed that lot A had lower pH and higher concentration of total and trivalent antimony, lead, cadmium, and arsenic. Our findings suggest that the skin reactions could be attributed to heavy metal contamination of lot A