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Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection

The trypanosome Trypanosoma brucei gambiense (Tbg) is a cause of human African trypanosomiasis (HAT) endemic to many parts of sub‐Saharan Africa. The disease is almost invariably fatal if untreated and there is no vaccine, which makes monitoring and managing drug resistance highly relevant. A recent...

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Autores principales: Richardson, Joshua B., Evans, Benjamin, Pyana, Patient P., Van Reet, Nick, Sistrom, Mark, Büscher, Philippe, Aksoy, Serap, Caccone, Adalgisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721075/
https://www.ncbi.nlm.nih.gov/pubmed/26834831
http://dx.doi.org/10.1111/eva.12338
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author Richardson, Joshua B.
Evans, Benjamin
Pyana, Patient P.
Van Reet, Nick
Sistrom, Mark
Büscher, Philippe
Aksoy, Serap
Caccone, Adalgisa
author_facet Richardson, Joshua B.
Evans, Benjamin
Pyana, Patient P.
Van Reet, Nick
Sistrom, Mark
Büscher, Philippe
Aksoy, Serap
Caccone, Adalgisa
author_sort Richardson, Joshua B.
collection PubMed
description The trypanosome Trypanosoma brucei gambiense (Tbg) is a cause of human African trypanosomiasis (HAT) endemic to many parts of sub‐Saharan Africa. The disease is almost invariably fatal if untreated and there is no vaccine, which makes monitoring and managing drug resistance highly relevant. A recent study of HAT cases from the Democratic Republic of the Congo reported a high incidence of relapses in patients treated with melarsoprol. Of the 19 Tbg strains isolated from patients enrolled in this study, four pairs were obtained from the same patient before treatment and after relapse. We used whole genome sequencing to investigate whether these patients were infected with a new strain, or if the original strain had regrown to pathogenic levels. Clustering analysis of 5938 single nucleotide polymorphisms supports the hypothesis of regrowth of the original strain, as we found that strains isolated before and after treatment from the same patient were more similar to each other than to other isolates. We also identified 23 novel genes that could affect melarsoprol sensitivity, representing a promising new set of targets for future functional studies. This work exemplifies the utility of using evolutionary approaches to provide novel insights and tools for disease control.
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spelling pubmed-47210752016-01-31 Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection Richardson, Joshua B. Evans, Benjamin Pyana, Patient P. Van Reet, Nick Sistrom, Mark Büscher, Philippe Aksoy, Serap Caccone, Adalgisa Evol Appl Original Articles The trypanosome Trypanosoma brucei gambiense (Tbg) is a cause of human African trypanosomiasis (HAT) endemic to many parts of sub‐Saharan Africa. The disease is almost invariably fatal if untreated and there is no vaccine, which makes monitoring and managing drug resistance highly relevant. A recent study of HAT cases from the Democratic Republic of the Congo reported a high incidence of relapses in patients treated with melarsoprol. Of the 19 Tbg strains isolated from patients enrolled in this study, four pairs were obtained from the same patient before treatment and after relapse. We used whole genome sequencing to investigate whether these patients were infected with a new strain, or if the original strain had regrown to pathogenic levels. Clustering analysis of 5938 single nucleotide polymorphisms supports the hypothesis of regrowth of the original strain, as we found that strains isolated before and after treatment from the same patient were more similar to each other than to other isolates. We also identified 23 novel genes that could affect melarsoprol sensitivity, representing a promising new set of targets for future functional studies. This work exemplifies the utility of using evolutionary approaches to provide novel insights and tools for disease control. John Wiley and Sons Inc. 2016-01-09 /pmc/articles/PMC4721075/ /pubmed/26834831 http://dx.doi.org/10.1111/eva.12338 Text en © 2015 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Richardson, Joshua B.
Evans, Benjamin
Pyana, Patient P.
Van Reet, Nick
Sistrom, Mark
Büscher, Philippe
Aksoy, Serap
Caccone, Adalgisa
Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
title Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
title_full Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
title_fullStr Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
title_full_unstemmed Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
title_short Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
title_sort whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721075/
https://www.ncbi.nlm.nih.gov/pubmed/26834831
http://dx.doi.org/10.1111/eva.12338
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