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Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease
Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to addres...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153806/ https://www.ncbi.nlm.nih.gov/pubmed/30082291 http://dx.doi.org/10.1128/AAC.00832-18 |
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author | Francisco, Amanda Fortes Jayawardhana, Shiromani Taylor, Martin C. Lewis, Michael D. Kelly, John M. |
author_facet | Francisco, Amanda Fortes Jayawardhana, Shiromani Taylor, Martin C. Lewis, Michael D. Kelly, John M. |
author_sort | Francisco, Amanda Fortes |
collection | PubMed |
description | Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured in either the acute or chronic stage of infection with benznidazole. At the experimental endpoint (5 to 6 months postinfection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct T. cruzi lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine T. cruzi infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level. |
format | Online Article Text |
id | pubmed-6153806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-61538062018-09-28 Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease Francisco, Amanda Fortes Jayawardhana, Shiromani Taylor, Martin C. Lewis, Michael D. Kelly, John M. Antimicrob Agents Chemother Experimental Therapeutics Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured in either the acute or chronic stage of infection with benznidazole. At the experimental endpoint (5 to 6 months postinfection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct T. cruzi lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine T. cruzi infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level. American Society for Microbiology 2018-09-24 /pmc/articles/PMC6153806/ /pubmed/30082291 http://dx.doi.org/10.1128/AAC.00832-18 Text en Copyright © 2018 Francisco et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Experimental Therapeutics Francisco, Amanda Fortes Jayawardhana, Shiromani Taylor, Martin C. Lewis, Michael D. Kelly, John M. Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease |
title | Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease |
title_full | Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease |
title_fullStr | Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease |
title_full_unstemmed | Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease |
title_short | Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease |
title_sort | assessing the effectiveness of curative benznidazole treatment in preventing chronic cardiac pathology in experimental models of chagas disease |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153806/ https://www.ncbi.nlm.nih.gov/pubmed/30082291 http://dx.doi.org/10.1128/AAC.00832-18 |
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