Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL

Profile of pregnant women and children treated at a reference center for congenital toxoplasmosis in the northern state of Minas Gerais, Brazil

INTRODUCTION: To describe the clinical and epidemiological profile of pregnant women and children treated at a reference outpatient clinic for congenital toxoplasmosis. METHODS: Pregnant women potentially exposed to Toxoplasma gondii were observed. Diagnoses were made using serologic tests compatible with acute toxoplasmosis. Children presenting with: Toxoplasma-specific antibodies (IgM or IgA or ascending IgG titers higher than maternal titers in the first 3 months of life) coupled with toxoplasmosis symptoms; intracranial calcifications (by transfontanelar ultrasound or cephalic segment tomography); or retinochoroiditis (by fundoscopy examination) in the first 8 months of life were also included in the study. RESULTS: Fifty-eight mother-child pairs were observed (mean age of the mothers was 22.1 years). Most patients lived in urban areas (86.2%) and had attended less than 8 years of school (51.7%). Diagnosis was made after birth in 19 (32.8%) children. Thirty-four (58.6%) women received some type of treatment during pregnancy. Most (72.4%) of the children did not present with clinical alterations at birth. The main findings were ophthalmological: 20 (34.5%) children with retinochoroiditis, 17 (29.3%) with strabismus, and 7 (12.1%) with nystagmus. Of the children with retinochoroiditis, 9 presented with subnormal vision. Ten (32.3%) out of 31 children presented with intracranial calcifications by cephalic segment congenital toxoplasmosis, and 9 (42.9%) children presented with delayed psychomotor development. CONCLUSIONS: Our results highlight a critical situation. Protocols for follow-up of pregnant women and their children must be created to improve medical care and minimize sequelae

Achados oculares em crianças com toxoplasmose congênita

OBJETIVO: Conhecer as lesões oculares mais frequentes encontradas em crianças expostas à toxoplasmose congênita. MÉTODOS: Trata-se de um estudo retrospectivo, a partir de uma coorte histórica, de abordagem quantitativa. Foram avaliadas crianças encaminhadas de um serviço de infectologia pediátrica e inseridas apenas aquelas com diagnóstico confirmado de toxoplasmose congênita. A avaliação oftalmológica incluiu o mapeamento de retina sequencial, sob dilatação pupilar. RESULTADOS: Das 58 crianças presumivelmente expostas ao risco de doença durante a gestação, 20 apresentaram lesões oftalmológicas ao longo do primeiro ano de vida (34 olhos). Destas, 12 estavam assintomáticas ao nascimento. Estrabismo foi registrado em 14 crianças (70%). Em uma criança observou-se ptose palpebral e em outra diminuição da fenda palpebral (microftalmia). Retinocoroidite foi a complicação mais frequente, presente em todas as 20 crianças. Sete crianças apresentaram alterações unilaterais (35%) e 13 crianças apresentaram alterações bilaterais (65%), prevalecendo a localização no polo posterior e mácula. CONCLUSÃO: Retinocoroidite e estrabismo destacaram-se como importantes sequelas da toxoplasmose congênita

Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil.

Submitted by Nuzia Santos ([email protected]) on 2018-10-23T11:58:55Z No. of bitstreams: 1 Poor response to azithromycin.pdf: 5597435 bytes, checksum: 00c8da93ce9b22dca4a039cd3197e561 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2018-10-23T12:03:58Z (GMT) No. of bitstreams: 1 Poor response to azithromycin.pdf: 5597435 bytes, checksum: 00c8da93ce9b22dca4a039cd3197e561 (MD5)Made available in DSpace on 2018-10-23T12:03:58Z (GMT). No. of bitstreams: 1 Poor response to azithromycin.pdf: 5597435 bytes, checksum: 00c8da93ce9b22dca4a039cd3197e561 (MD5) Previous issue date: 2014Universidade José do Rosário Vellano. Serviço Multiprofissional de Infectologia. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Plataforma de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil/Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Pesquisa Clínica. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Plataforma de Pesquisa Clínica. Rio de Janeiro, RJ, BrasilUniversidade Estadual de Montes Claros. Hospital Universitário Clemente de Faria. Departamento de Doenças Infecciosas. Montes Claros, MG, BrasilUniversidade de Brasília. Núcleo de Medicina Tropical. Brasília, DF, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Pesquisa Clínica. Belo Horizonte, MG, BrasilIntroduction: Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods: This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results: Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions: Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL

Detection of Anti-Leishmania (Leishmania) chagasi Immunoglobulin G by Flow Cytometry for Cure Assessment following Chemotherapeutic Treatment of American Visceral Leishmaniasis

The residual serological reactivity observed in patients cured of visceral leishmaniasis (VL) represents the major factor underlying the low efficiency of most anti-Leishmania serological approaches to assess posttherapeutic cure in VL. Herein, we have described a detuned flow cytometry-based methodology to detect anti-live (FC-ALPA-immunoglobulin G [IgG]) and anti-fixed (FC-AFPA-IgG) L. chagasi promastigote IgG, along the titration curve (1:2,000 to 1:128,000), as a tool to assess late (12 months after treatment [12 mAT]) and early (2 and 6 mAT) posttherapeutic cure of pediatric American visceral leishmaniasis. Reactivities were reported as the percentage of positive fluorescent parasite (PPFP), using a PPFP of 50% as a cutoff to segregate positive and negative results. Our data demonstrated that both FC-ALPA-IgG at 1:4,000 and FC-ALPA-IgG at 1:32,000 are useful for late cure assessment in VL, with 100% specificity and outstanding likelihood ratio indices. Cure assessment at 6 mAT also showed promising performance indices, identifying 81% and 71.4% of the treated patients with negative results. However, new interpretation parameters were necessary to monitor cure at 2 mAT. We then introduced the differential PPFP (ΔPPFP) of 25% as a new cutoff for early cure assessment at specific serum dilutions to analyze IgG reactivity by FC-ALPA-IgG and FC-AFPA-IgG. Our data demonstrated that at 2 mAT, ΔPPFP was >25% in 60% and 57.1% of treated patients, whereas at 6 mAT, a ΔPPFP of >25% was observed in 100% and 95.2% of samples assayed by FC-ALPA-IgG and FC-AFPA-IgG, respectively. Together, our findings showed the potential of both FC-ALPA-IgG and FC-AFPA-IgG regarding their applicability to detect differential serological reactivity and further contribution to posttherapeutic cure assessment in VL

Perfil dos acidentes ofídicos no norte do Estado de Minas Gerais, Brasil Profile of snakebite accidents in the north of the State of Minas Gerais, Brazil

O objetivo deste estudo foi descrever o perfil epidemiológico dos acidentes ofídicos da macrorregião de saúde do Norte do Estado de Minas Gerais, Brasil. Foram analisadas informações sobre os acidentes ofídicos relativos ao período compreendido entre janeiro de 2002 a dezembro de 2006, por meio de bancos de dados. Os resultados demonstraram 10.553 casos notificados, com ênfase para a maior casuística em meses de tempo quente e chuvoso, em áreas urbanas (54,1%), faixa etária menor de 20 anos (39,7%), acometendo mais homens e estudantes (53,1% e 29,1%) respectivamente. Os membros inferiores (pé, dedo do pé, perna e coxa) foram os locais mais afetados (35,9%), as serpentes prevalentes foram do gênero Bothrops (82,9%) e a gravidade da maioria dos acidentes foi leve (66,2%). Observou-se nesse estudo um importante impacto da sazonalidade, urbanização, subnotificação das espécies envolvidas nesses acidentes e busca rápida pelo pronto atendimento. Espera-se que os dados inéditos da casuística obtida possam servir de substrato para o planejamento e execução de medidas voltadas para vigilância em saúde e atendimento.The aim of this study was to describe the epidemiological profile of snakebite accidents in the healthcare macroregion of the north of the State of Minas Gerais, Brazil. Database information on snakebite accidents covering the period from January 2002 to December 2006 was analyzed. It was found that 10,553 cases were notified, and that the samples were noticeably larger in the months of hot and rainy weather, in urban areas (54.1%), at ages less then 20 years (39.7%) and among men and students (53.1% and 29.1%) respectively. The lower limbs (feet, toes, legs and thighs) were the locations most affected (35.9%). The most prevalent snakes were in the genus Bothrops (82.9%) and most of the accidents were mild (66.2%). In this study, it was seen that the seasonality, urbanization and undernotification of the species involved in these accidents had a notable impact, along with seeking walk-in care. It is expected that the new data obtained from this sample may serve as the substrate for planning and implementing measures for healthcare surveillance