Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease
IntroductionChagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays...
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| Format: | Article |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1340755/full |
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| author | Fernanda Fortes de Araujo Rana Nagarkatti Ana Lia Mazzeti Karolina Ribeiro Gonçalves Lívia de Figueiredo Diniz Isabela Campos do Vale Olindo Assis Martins-Filho Alain Debrabant Maria Terezinha Bahia Andréa Teixeira-Carvalho |
| author_facet | Fernanda Fortes de Araujo Rana Nagarkatti Ana Lia Mazzeti Karolina Ribeiro Gonçalves Lívia de Figueiredo Diniz Isabela Campos do Vale Olindo Assis Martins-Filho Alain Debrabant Maria Terezinha Bahia Andréa Teixeira-Carvalho |
| author_sort | Fernanda Fortes de Araujo |
| collection | DOAJ |
| description | IntroductionChagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays for drug discovery are required to accelerate the development of new drugs with reduced side effects, which are much needed for human treatment.MethodsWe used a cure model of infected mice treated with Fexinidazole (FZ) to further validate a novel Enzyme Linked Aptamer (ELA) assay that detects parasite biomarkers circulating in the blood of infected animals.ResultsThe ELA assay showed cure by FZ in ~71% and ~77% of mice infected with the VL-10 and Colombiana strains of T. cruzi, respectively. The ELA assay also revealed superior treatment efficacy of FZ compared to Benznidazole prior to immunosuppression treatment.DiscussionOur study supports the use of ELA assay as an alternative to traditional serology or blood PCR to assess the efficacy of antichagasic drugs during their preclinical phase of development. Further, the combination of high sensitivity and ease of use make this parasite antigen detection assay an attractive new tool to facilitate the development of much needed new therapies for CD. |
| first_indexed | 2024-03-08T14:30:59Z |
| format | Article |
| id | doaj.art-60fe01f1e4f84f4b87ea28d4a4c2b88a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T14:30:59Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-60fe01f1e4f84f4b87ea28d4a4c2b88a2024-01-12T11:06:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13407551340755Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas diseaseFernanda Fortes de Araujo0Rana Nagarkatti1Ana Lia Mazzeti2Karolina Ribeiro Gonçalves3Lívia de Figueiredo Diniz4Isabela Campos do Vale5Olindo Assis Martins-Filho6Alain Debrabant7Maria Terezinha Bahia8Andréa Teixeira-Carvalho9Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United StatesLaboratório de Doenças Parasitárias, Escola de Medicina, Departamento de Ciências Biológicas & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, BrazilLaboratório de Doenças Parasitárias, Escola de Medicina, Departamento de Ciências Biológicas & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, BrazilLaboratório de Parasitologia Básica, Programa de Pós-Graduação em Ciências Biológicas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United StatesLaboratório de Doenças Parasitárias, Escola de Medicina, Departamento de Ciências Biológicas & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilIntroductionChagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays for drug discovery are required to accelerate the development of new drugs with reduced side effects, which are much needed for human treatment.MethodsWe used a cure model of infected mice treated with Fexinidazole (FZ) to further validate a novel Enzyme Linked Aptamer (ELA) assay that detects parasite biomarkers circulating in the blood of infected animals.ResultsThe ELA assay showed cure by FZ in ~71% and ~77% of mice infected with the VL-10 and Colombiana strains of T. cruzi, respectively. The ELA assay also revealed superior treatment efficacy of FZ compared to Benznidazole prior to immunosuppression treatment.DiscussionOur study supports the use of ELA assay as an alternative to traditional serology or blood PCR to assess the efficacy of antichagasic drugs during their preclinical phase of development. Further, the combination of high sensitivity and ease of use make this parasite antigen detection assay an attractive new tool to facilitate the development of much needed new therapies for CD.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1340755/fullChagas diseaseTrypanosoma cruziaptamertreatmentefficacy |
| spellingShingle | Fernanda Fortes de Araujo Rana Nagarkatti Ana Lia Mazzeti Karolina Ribeiro Gonçalves Lívia de Figueiredo Diniz Isabela Campos do Vale Olindo Assis Martins-Filho Alain Debrabant Maria Terezinha Bahia Andréa Teixeira-Carvalho Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease Frontiers in Immunology Chagas disease Trypanosoma cruzi aptamer treatment efficacy |
| title | Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease |
| title_full | Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease |
| title_fullStr | Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease |
| title_full_unstemmed | Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease |
| title_short | Trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of Chagas disease |
| title_sort | trypanosoma cruzi antigen detection in blood to assess treatment efficacy and cure in mice models of chagas disease |
| topic | Chagas disease Trypanosoma cruzi aptamer treatment efficacy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1340755/full |
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