Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease.
Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challen...
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ftdoajarticles:oai:doaj.org/article:69d7b697f806433990c5f67edd7738ab 2023-05-15T15:06:02+02:00 Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. Pablo M De Salazar Sergio Sosa-Estani Fernando Salvador Elena Sulleiro Adrián Sánchez-Montalvá Isabela Ribeiro Israel Molina Caroline O Buckee 2022-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010828 https://doaj.org/article/69d7b697f806433990c5f67edd7738ab EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010828 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010828 https://doaj.org/article/69d7b697f806433990c5f67edd7738ab PLoS Neglected Tropical Diseases, Vol 16, Iss 11, p e0010828 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010828 2022-12-30T19:28:45Z Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accuracy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre- and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilistically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 11 e0010828 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Pablo M De Salazar Sergio Sosa-Estani Fernando Salvador Elena Sulleiro Adrián Sánchez-Montalvá Isabela Ribeiro Israel Molina Caroline O Buckee Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accuracy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre- and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilistically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228. |
format |
Article in Journal/Newspaper |
author |
Pablo M De Salazar Sergio Sosa-Estani Fernando Salvador Elena Sulleiro Adrián Sánchez-Montalvá Isabela Ribeiro Israel Molina Caroline O Buckee |
author_facet |
Pablo M De Salazar Sergio Sosa-Estani Fernando Salvador Elena Sulleiro Adrián Sánchez-Montalvá Isabela Ribeiro Israel Molina Caroline O Buckee |
author_sort |
Pablo M De Salazar |
title |
Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. |
title_short |
Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. |
title_full |
Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. |
title_fullStr |
Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. |
title_full_unstemmed |
Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. |
title_sort |
human trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: implications for drug-trial optimization in chagas disease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010828 https://doaj.org/article/69d7b697f806433990c5f67edd7738ab |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 11, p e0010828 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010828 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010828 https://doaj.org/article/69d7b697f806433990c5f67edd7738ab |
op_doi |
https://doi.org/10.1371/journal.pntd.0010828 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
16 |
container_issue |
11 |
container_start_page |
e0010828 |
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1766337699247030272 |