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Chagas disease

  • Open Access
    Drug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male Volunteers
    Clinical Therapeutics
    Drug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male Volunteers

    E1224 is a prodrug of ravuconazole (RVZ), an antifungal drug with promising anti-Trypanosoma cruzi activity, the causative organism of Chagas disease (CD). This study was designed to assess the pharmacokinetics (PK) and safety interactions of benznidazole (BNZ), the drug of choice for treatment of CD, and E1224 in healthy volunteers.

    Isabela Ribeiro, Bethania Blum, Jayme Fernandes, Glaucia Santina, Makoto Asada, Michael Everson, Edgar Schuck, Ethel Feleder, Eric Evene, Virginie Gualano
  • Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients
    Clinical Therapeutics
    Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients

    Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS).

    Marisa L. Fernández, María E. Marson, Guido E. Mastrantonio, Marcelo A. Corti, Ulises Fleitas, Susana C. Lloveras, Nicolas Lista, Maria M. Priarone, Cecilia Domínguez, Facundo Garcia-Bournissen
  • Screening and Identification of Metacaspase Inhibitors: Evaluation of Inhibition Mechanism and Trypanocidal Activity
    Mechanisms of Action: Physiological Effects
    Screening and Identification of Metacaspase Inhibitors: Evaluation of Inhibition Mechanism and Trypanocidal Activity

    A common strategy to identify new antiparasitic agents is the targeting of proteases, due to their essential contributions to parasite growth and development. Metacaspases (MCAs) are cysteine proteases present in fungi, protozoa, and plants.

    Brian Pérez, León A. Bouvier, Juan José Cazzulo, Fernán Agüero, Emir Salas-Sarduy, Vanina E. Alvarez
  • Pharmacokinetics of Benznidazole in Experimental Chronic Chagas Disease Using the Swiss Mouse–Berenice-78 <span class="named-content genus-species" id="named-content-1">Trypanosoma cruzi</span> Strain Model
    Experimental Therapeutics
    Pharmacokinetics of Benznidazole in Experimental Chronic Chagas Disease Using the Swiss Mouse–Berenice-78 Trypanosoma cruzi Strain Model

    Chronic Chagas disease might have an impact on benznidazole pharmacokinetics with potential alterations in the therapeutic dosing regimen. This study aims to investigate the influence of chronic Trypanosoma cruzi infection on the pharmacokinetics and biodistribution of benznidazole in mice.

    Suzana Marques de Jesus, Leonardo Pinto, Fernanda de Lima Moreira, Glauco Henrique Balthazar Nardotto, Rodrigo Cristofoletti, Luísa Perin, Kátia da Silva Fonseca, Pauliana Barbêdo, Lorena Cera Bandeira, Paula Melo de Abreu Vieira, Claudia Martins Carneiro
  • New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with <span class="named-content genus-species" id="named-content-1">Trypanosoma cruzi</span>: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-Up
    Clinical Therapeutics
    New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-Up

    In a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two...

    María Gabriela Álvarez, Juan Carlos Ramírez, Graciela Bertocchi, Marisa Fernández, Yolanda Hernández, Bruno Lococo, Constanza Lopez-Albizu, Alejandro Schijman, Carolina Cura, Marcelo Abril, Susana Laucella, Rick L. Tarleton, María Ailen Natale, Melisa Castro Eiro, Sergio Sosa-Estani, Rodolfo Viotti
  • Efficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of <span class="named-content genus-species" id="named-content-1">Trypanosoma cruzi</span>
    Experimental Therapeutics
    Efficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of Trypanosoma cruzi

    Pyrazolones are heterocyclic compounds with interesting biological properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cyclic AMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease (CD), a...

    Julianna Siciliano de Araújo, Cristiane França da Silva, Denise da Gama Jaén Batista, Aline Nefertiti, Ludmila Ferreira de Almeida Fiuza, Cristina Rosa Fonseca-Berzal, Patrícia Bernardino da Silva, Marcos Meuser Batista, Maarten Sijm, Titilola D. Kalejaiye, Harry P. de Koning, Louis Maes, Geert Jan Sterk, Rob Leurs, Maria de Nazaré Correia Soeiro
  • Amlodipine Increases the Therapeutic Potential of Ravuconazole upon <span class="named-content genus-species" id="named-content-1">Trypanosoma cruzi</span> Infection
    Experimental Therapeutics
    Amlodipine Increases the Therapeutic Potential of Ravuconazole upon Trypanosoma cruzi Infection

    Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon Trypanosoma cruzi experimental infection. In vitro assays confirmed...

    Yara Almeida Machado, Maria Terezinha Bahia, Ivo Santana Caldas, Ana Lia Mazzeti, Rômulo Dias Novaes, Breno Raimundo Vilas Boas, Lorena Júnia de Souza Santos, Olindo Assis Martins-Filho, Marcos José Marques, Lívia de Figueiredo Diniz
  • Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase
    Clinical Therapeutics
    Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are...

    Rito Santo Pereira, Aparecida Donizette Malvezi, Maria Isabel Lovo-Martins, Bruno Fernando Cruz Lucchetti, Jussevania Pereira Santos, Eliandro Reis Tavares, Waldiceu Aparecido Verri, Eduardo José de Almeida Araújo, Lucy Megumi Yamauchi, Sueli Fumie Yamada-Ogatta, Marli Cardoso Martins-Pinge, Phileno Pinge-Filho
  • A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic <span class="named-content genus-species" id="named-content-1">Trypanosoma cruzi</span> Infection
    Clinical Therapeutics
    A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection

    One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and...

    Adriana Egui, M. Carmen Thomas, Ana Fernández-Villegas, Elena Pérez-Antón, Inmaculada Gómez, Bartolomé Carrilero, Ángel del Pozo, Maialen Ceballos, Eduardo Andrés-León, Miguel Ángel López-Ruz, Eusebio Gainza, Enrique Oquiñena, Manuel Segovia, Manuel Carlos López
  • Open Access
    Synergic Effect of Allopurinol in Combination with Nitroheterocyclic Compounds against <span class="named-content genus-species" id="named-content-1">Trypanosoma cruzi</span>
    Experimental Therapeutics
    Synergic Effect of Allopurinol in Combination with Nitroheterocyclic Compounds against Trypanosoma cruzi

    Combination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitroheterocyclic compounds on infection with the Y strain of Trypanosoma cruzi.

    Ana Lia Mazzeti, Lívia de F. Diniz, Karolina R. Gonçalves, Ruan Schott WonDollinger, Tassiane Assíria, Isabela Ribeiro, Maria T. Bahia

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