New Drugs and Promising Drug Combinations in the Treatment of Chagas Disease in Brazil: A Systematic Review and Meta-Analysis

Elainne Silva Freire; Letícia Pinto da Silva; Aline do Carmo Silva; Pedro Alves Soares Vaz de Castro; Giovanna Rotondo de Araújo; Dayane Andriotti Otta; Danilo Cavalcante Braz; Juliana Maria Trindade Bezerra

doi:10.1016/j.arcmed.2024.103084

New Drugs and Promising Drug Combinations in the Treatment of Chagas Disease in Brazil: A Systematic Review and Meta-Analysis

Arch Med Res. 2024 Sep 26;56(1):103084. doi: 10.1016/j.arcmed.2024.103084. Online ahead of print.

Authors

Elainne Silva Freire¹, Letícia Pinto da Silva¹, Aline do Carmo Silva², Pedro Alves Soares Vaz de Castro³, Giovanna Rotondo de Araújo⁴, Dayane Andriotti Otta⁵, Danilo Cavalcante Braz⁶, Juliana Maria Trindade Bezerra⁷

Affiliations

¹ Curso de Licenciatura em Ciências Biológicas, Universidade Estadual do Maranhão, Campus de Lago da Pedra, Lago da Pedra, Maranhão, Brazil.
² Programa de Pós-Graduação em Ciência Animal, Centro de Ciências Agrárias, Universidade Estadual do Maranhão, São Luís, Maranhão, Brazil.
³ Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
⁴ Programa de Pós-Graduação em Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
⁵ Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
⁶ Instituto Federal do Amazonas, Departamento de Ensino Pesquisa e Extensão, Tefé, Amazonas, Brazil.
⁷ Curso de Licenciatura em Ciências Biológicas, Universidade Estadual do Maranhão, Campus de Lago da Pedra, Lago da Pedra, Maranhão, Brazil; Programa de Pós-Graduação em Ciência Animal, Centro de Ciências Agrárias, Universidade Estadual do Maranhão, São Luís, Maranhão, Brazil; Programa de Pós-Graduação em Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: julianabezerrauema@gmail.com.

PMID: 39332069
DOI: 10.1016/j.arcmed.2024.103084

Abstract

Chagas disease (CD) is a parasitic infection caused by the protozoan Trypanosoma cruzi (Kinetoplastida, Trypanosomatidae). Benznidazole (Bz) has a limited ability to interfere with the pathogenicity of the parasite, which manages to overcome host defenses. This study aimed to conduct a systematic literature review and meta-analysis to understand and describe the drugs and their combinations, as well as new promising compounds used in the treatment of CD in Brazil. This study was registered in the Open Science Framework (OSF) and the International Prospective Register of Systematic Reviews, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed in the electronic scientific databases PubMed, LILACS, SciELO, and BVS. Searches were conducted using descriptors cataloged in the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH), in Portuguese, English, and Spanish. Of the 26 articles included in this systematic review and meta-analysis, 16 were related to drug combinations, and nine described new inhibitors of parasitic molecules. Despite high heterogeneity (I² = 92%), studies that evaluated the combination of Bz with other treatments for CD had an overall grouped cure rate of 74% (95% CI 54-94%). Only one study presented drug repositioning by monotherapy. Thus, drug combinations offer quick and accessible solutions for CD treatment, acting against resistant strains of T. cruzi. Certainly, the introduction of these promising compounds into the pharmaceutical market is distant, and the adoption of prophylactic measures is recommended as a barrier to the increasing number of CD cases.

Keywords: Brazil; Chagas disease; Therapies under study; Trypanosoma cruzi.

Publication types

Review