Browsing by Autor "Alejandro G. Schijman"

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A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease
(Oxford University Press, 2022) Faustino Torrico; Joaquím Gascón; Lourdes Ortiz; Jimy Pinto; Gimena Rojas; Alejandro Palacios; Fabiana Barreira; Bethania Blum; Alejandro G. Schijman; Michel Vaillant
NCT02498782.
Chagas’ disease diagnosis: a multicentric evaluation of Chagas Stat-Pak, a rapid immunochromatographic assay with recombinant proteins of Trypanosoma cruzi
(Elsevier BV, 2003) Alejandro O. Luquetti; Carlos Ponce; Elisa Ponce; Javan Esfandiari; Alejandro G. Schijman; Susana Revollo; Néstor Áñez; Bianca Zingales; Rafael Ramgel-Aldao; Antonio G. González
Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region
(BioMed Central, 2007) Gonzalo Moratorio; Mariela Martínez; María Fernanda Gutiérrez; Katiuska González; Rodney Colina; Luis Fernando López Tort; Lilia López; Ricardo Recarey; Alejandro G. Schijman; Pilar Moreno
Phylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct type 1 sub-population. The coexistence of distinct type 1 HCV subpopulations is consistent with quasispecies dynamics, and suggests that multiple coexisting subpopulations may allow the virus to adapt to its human host populations.
Interest and limitations of Spliced Leader Intergenic Region sequences for analyzing Trypanosoma cruzi I phylogenetic diversity in the Argentinean Chaco
(Elsevier BV, 2010) Nicolás Tomasini; Juan José Lauthier; María M. Monje Rumi; Paula G. Ragone; A. ALBERTI D'AMATO; Cecilia Pérez Brandán; Carolina Cura; Alejandro G. Schijman; Christian Barnabé; Michel Tibayrenc
International Study to Evaluate PCR Methods for Detection of Trypanosoma cruzi DNA in Blood Samples from Chagas Disease Patients
(Public Library of Science, 2011) Alejandro G. Schijman; Margarita Bisio; Liliana Orellana; Mariela Sued; Tomás Duffy; Ana María Mejía‐Jaramillo; Carolina Cura; Frederic Auter; Vincent Véron; Yvonne Qvarnström
This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.
Molecular detection and parasite load of Trypanosoma cruzi in digestive tract tissue of Chagas disease patients affected by megacolon
(Elsevier BV, 2022) Lilian Pinto; Alejandro G. Schijman; Julio Alonso-Padilla; Daniel Lozano; Mary Cruz Torrico; Pietro Gamba; Margarita Torrez; Vania Lozada; Karina Cartagena; Jareth Sánchez
Quantifying anti-trypanosomal treatment effects in chronic indeterminate Chagas disease: an individual patient data meta-analysis of two proof of concept trials
(2024) James A Watson; Cintia Cruz; Fabiana Barreira; C. Forsyth; Alejandro G. Schijman; Rhys Peploe; Frauke Assmus; Caitlin Naylor; Jennifer Lee; Somya Mehra
Abstract Background The current antiparasitic treatment for chronic Chagas disease of 8 weeks daily benznidazole or nifurtimox is poorly tolerated and reaches only a small minority of those with chronic infections. Defining parasitological cure is compromised by the low blood trypomastigote densities, which fluctuate close to or below the limit of qPCR detection. Methods To address this limitation and improve the assessment of parasitological cure we developed a probabilistic model of therapeutic efficacy based on serial qPCR data. We pooled clinical and laboratory data from two prospective trials in Bolivian adults with chronic indeterminate Chagas disease. In both trials randomised arms included placebo or standard of care benznida-zole (300mg/day for 8 weeks). In the first trial, the experimental arms were fosravuconazole monotherapies (400mg/week for 4 or 8 weeks, or 200mg/week for 8 weeks); in the second trial the experimental arms were shorter or lower dose benznidazole regimens (300mg/day for 2 or 4, or 150mg/day for 4 weeks), or combinations of fosravuconazole 300mg weekly for 8 weeks with either benznidazole 150mg/day for 4 weeks or benznidazole 300mg/week for 8 weeks. Serial parasite densities were estimated from triplicate qPCRs targeting T. cruzi satellite DNA taken from one to three 5 or 10ml blood samples at 8-12 visits over one year. Treatment efficacies were estimated under a hierarchical Bayesian model, taking as input serial cycle threshold (Ct) data grouped by time point, blood draw and technical replicate. The primary analysis was done in a per-protocol population defined as patients randomised to placebo or patients who took an active treatment >80% of the allocated treatment duration. Results The two trials randomised 441 patients. 34,804 qPCR Ct values were recorded over 5,402 unique visits, comprising 449 participant years follow-up. In a per-protocol population ( n =424), an estimated 81% (95% Credible Interval [CrI] 70 to 89%, n =69) had parasitological cure following benznidazole 300mg/day for 8 weeks. All other benznidazole regimens had similar estimated cure proportions (95% CrIs >63%) except the 2-week regimen (63% cured [95%CrI 43-81%], n =27, probability of inferiority relative 8-week: 0.95). Recurrent parasitaemias following benznidazole were at substantially lower densities than at baseline. In comparison, only 3.9% of patients allocated to placebo were cured (95%CrI 1 to 9%, n =77). Fosravuconazole was relatively ineffective: 23% cured following 400mg for 8 weeks (95%CrI, 10 to 40%, n =45); 9% following 400mg for 4 weeks (95%CrI 3 to 21%, n =46); and 2% following 200mg for 8 weeks (95%CrI 0 to 11%, n =48). Recurrent parasitaemias one year after fosravuconazole treatment were only slightly lower than at baseline. Fosravuconazole caused dose-dependent increases in liver transaminases. Conclusions Therapeutic assessments in Chagas disease must account probabilistically for qPCR test performance and low density post treatment parasitaemias. In Bolivian chronic Chagas disease, weekly dosing for eight weeks or daily dosing over four weeks both appear as effective as the current eight weeks daily regimen. The total dose of benznidazole in the current standard of care regimen is excessive.
The burden of congenital Chagas disease and implementation of molecular diagnostic tools in Latin America
(BMJ, 2018) Albert Picado; Israel Cruz; Maël Redard-Jacot; Alejandro G. Schijman; Faustino Torrico; Sergio Sosa‐Estáni; Zachary Katz; Joseph Mathu Ndung’u
It is estimated that between 8000 and 15 000 <i>Trypanosoma cruzi</i> infected babies are born every year to infected mothers in Chagas disease endemic countries. Currently, poor access to and performance of the current diagnostic algorithm, based on microscopy at birth and serology at 8-12 months after delivery, is one of the barriers to congenital Chagas disease (CCD) control. Detection of parasite DNA using molecular diagnostic tools could be an alternative or complement to current diagnostic methods, but its implementation in endemic regions remains limited. Prompt diagnosis and treatment of CCD cases would have a positive clinical and epidemiological impact. In this paper, we analysed the burden of CCD in Latin America, and the potential use of molecular tests to improve access to early diagnosis and treatment of <i>T. cruzi</i> infected newborns.
Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease
(American Society for Microbiology, 2013) Rodolfo Viotti; Belkisyolé Alarcón de Noya; Tânia Cremonini de Araújo-Jorge; Mario J. Grijalva; Felipe Guhl; Manuel Carlos López; Janine M. Ramsey; Isabela Ribeiro; Alejandro G. Schijman; Sergio Sosa‐Estáni
Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.
Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial
(Elsevier BV, 2018) Faustino Torrico; Joaquím Gascón; Lourdes Ortiz; Cristina Alonso‐Vega; María‐Jesús Pinazo; Alejandro G. Schijman; Igor C. Almeida; Fabiana Alves; Nathalie Strub‐Wourgaft; Isabela Ribeiro
Ultra-Rapid DNA Extraction Coupled with Loop-Mediated Isothermal Amplification for Point-of-Care Detection of Trypanosoma cruzi Infection in Heparinized Blood and Dried Blood Spots
(Springer Science+Business Media, 2025) Silvia A. Longhi; Lady J García-Casares; Arturo Muñoz-Calderón; Julio Alonso-Padilla; Alejandro G. Schijman