2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Evaluation of environmental contamination by persistent organic pollutants utilizing simulation of leach processes

Environmental concern is growing in the current days and there is global agreement to banish production and use of persistent organic pollutants (POP). The synthetic insecticides chlordecone and mirex, classified as POPs, have similar structures and they are potentially toxic. This work uses properties and physicochemical constants related to the pesticides and computational simulation to evaluate the leach phenomenon and persistency in soil. The largest tendency of persistence of the compound is found to be in the surface of soil, but even low concentration in water represents a high risk due to bioaccumulation in adipose tissue.56556

Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial

Background: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. Method: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18–50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia. Patients were randomised with a computer-generated randomisation list, which was stratified by centre and used a block size of ten. Patients were randomly assigned (1:1:1:1:1) to five oral treatment groups: high-dose E1224 (duration 8 weeks, total dose 4000 mg), low-dose E1224 (8 weeks, 2000 mg), short-dose E1224 (4 weeks + 4 weeks placebo, 2400 mg), benznidazole (60 days, 5 mg/kg per day), or placebo (8 weeks, E1224-matched tablets). Double-blinding was limited to the E1224 and placebo arms, and assessors were masked to all treatment allocations. The primary efficacy endpoint was parasitological response to E1224 at the end of treatment, assessed by PCR. The secondary efficacy endpoints were parasitological response to benznidazole at end of treatment, assessed by PCR; sustainability of parasitological response until 12 months; parasite clearance and changes in parasite load; incidence of conversion to negative response in conventional and non-conventional (antigen trypomastigote chemiluminescent ELISA [AT CL-ELISA]) serological response; changes in levels of biomarkers; and complete response. The primary analysis population consisted of all randomised patients by their assigned treatment arms. This trial is registered with ClinicalTrials.gov, number NCT01489228. Findings: Between July 19, 2011, and July 26, 2012, we screened 560 participants with confirmed Chagas disease, of whom 231 were enrolled and assigned to high-dose E1224 (n=45), low-dose E1224 (n=48), short-dose E1224 (n=46), benznidazole (n=45), or placebo (n=47). Parasite clearance was observed with E1224 during the treatment phase, but no sustained response was seen with low-dose and short-dose regimens, whereas 13 patients (29%, 95% CI 16·4–44·3) had sustained response with the high-dose regimen compared with four (9%, 2·4–20·4) in the placebo group (p<0·0001). Benznidazole had a rapid and sustained effect on parasite clearance, with 37 patients (82%, 67·9–92·0) with sustained response at 12-month follow-up. After 1 week of treatment, mean quantitative PCR repeated measurements showed a significant reduction in parasite load in all treatment arms versus placebo. Parasite levels in the low-dose and short-dose E1224 groups gradually returned to placebo levels. Both treatments were well tolerated. Reversible, dose-dependent liver enzyme increases were seen with E1224 and benznidazole. 187 (81%) participants developed treatment-emergent adverse events and six (3%) developed treatment-emergent serious adverse events. Treatment-emergent adverse events were headaches, nausea, pruritus, peripheral neuropathy, and hypersensitivity. Interpretation: E1224 is the first new chemical entity developed for Chagas disease in decades. E1224 displayed a transient, suppressive effect on parasite clearance, whereas benznidazole showed early and sustained efficacy until 12 months of follow-up. Despite PCR limitations, our results support increased diagnosis and access to benznidazole standard regimen, and provide a development roadmap for novel benznidazole regimens in monotherapy and in combinations with E1224. Funding: Drugs for Neglected Diseases initiative.Fil: Torrico, Faustino. Universidad Mayor de San Simon Bolivia; Bolivia. Fundación Ceades; BoliviaFil: Gascon, Joaquim. Instituto de Salud Global de Barcelona; EspañaFil: Ortiz, Lourdes. Universidad Autónoma Juan Misael Saracho de Tarija; BoliviaFil: Alonso Vega, Cristina. Drugs For Neglected Diseases Initiative; SuizaFil: Pinazo, María-Jesús. Instituto de Salud Global de Barcelona; EspañaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Almeida, Igor C. University of Texas at El Paso; Estados UnidosFil: Alves, Fabiana. Drugs For Neglected Diseases Initiative; SuizaFil: Strub-Wourgaft, Nathalie. Drugs For Neglected Diseases Initiative; SuizaFil: Ribeiro, Isabela. Drugs For Neglected Diseases Initiative; SuizaFil: Santina, Glaucia. Drugs For Neglected Diseases Initiative; SuizaFil: Blum, Bethania. Drugs For Neglected Diseases Initiative; SuizaFil: Correia, Erika. Drugs For Neglected Diseases Initiative; SuizaFil: García Bournissen, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Vaillant, Michel. Competence Center in Methodology and Statistics; LuxemburgoFil: Ramos Morales, Jimena. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Pinto Rocha, Jimy Jose. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Rojas Delgadillo, Gimena. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Magne Anzoleaga, Helmut Ramon. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Mendoza, Nilce. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Quechover, Roxana Challapa. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Caballero, Maria Yurly Escobar. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Lozano Beltran, Daniel Franz. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Zalabar, Albert Mendoza. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Rojas Panozo, Lizeth. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Palacios Lopez, Alejandro. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Torrico Terceros, Dunia. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Fernandez Galvez, Violeta Alejandra. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Cardozo, Letty. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Cuellar, Gabriela. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Vasco Arenas, Rudy Nelson. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Gonzales, Isabel. Platform for Comprehensive Care of Patients with Chagas Disease; BoliviaFil: Hoyos Delfin, Carlos Florencio. Universidad Juan Misael Saracho; BoliviaFil: Garcia, Lineth. Universidad Mayor de San Simón; BoliviaFil: Parrado, Rudy. Universidad Mayor de San Simón; BoliviaFil: de la Barra, Anabelle. Universidad Mayor de San Simón; BoliviaFil: Montaño, Nair. Universidad Mayor de San Simón; BoliviaFil: Villarroel, Sandro. Universidad Mayor de San Simón; BoliviaFil: Duffy, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bisio, Margarita María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Duncanson, Fred. Eisai; JapónFil: Everson, Michael. Eisai; JapónFil: Daniels, Antonia. Eisai; JapónFil: Asada, Makoto. Eisai; JapónFil: Cox, Eugene. Quantitative Solutions; Países BajosFil: Wesche, David. Quantitative Solutions; Países BajosFil: Diderichsen, Paul Matthias. Quantitative Solutions; Países BajosFil: Marques, Alexandre F. Universidade Federal de Minas Gerais; BrasilFil: Izquierdo, Luis. ISGlobal; EspañaFil: Sender, Silvia Sanz. ISGlobal; EspañaFil: Reverter, Joan Carlos. Hospital Clinic Barcelona; EspañaFil: Morales, Manuel. Hospital Clinic Barcelona; EspañaFil: Jimenez, Wladimiro. Hospital Clinic Barcelona; Españ