Association between bacterial homoplastic variants and radiological pathology in tuberculosis
- Autores
- Grandjean, Louis; Monteserin, Johana; Gilman, Robert; Pauschardt, Julia; Rokadiya, Sakib; Bonilla, Cesar; Ritacco, Gloria Viviana; Vidal, Julia Rios; Parkhill, Julian; Peacock, Sharon; Vidal, Julia Rios; Balloux, Francois
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: Understanding how pathogen genetic factors contribute to pathology in TB could enable tailored treatments to the most pathogenic and infectious strains. New strategies are needed to control drug-resistant TB, which requires longer and costlier treatment. We hypothesised that the severity of radiological pathology on the chest radiograph in TB disease was associated with variants arising independently, multiple times (homoplasies) in the Mycobacterium tuberculosis genome. Methods: We performed whole genome sequencing (Illumina HiSeq2000 platform) on M. tuberculosis isolates from 103 patients with drug-resistant TB in Lima between 2010 and 2013. Variables including age, sex, HIV status, previous TB disease and the percentage of lung involvement on the pretreatment chest radiograph were collected from health posts of the national TB programme. Genomic variants were identified using standard pipelines. Results: Two mutations were significantly associated with more widespread radiological pathology in a multivariable regression model controlling for confounding variables (Rv2828c.141, RR 1.3, 95% CI 1.21 to 1.39, p<0.01; rpoC.1040 95% CI 1.77 to 2.16, RR 1.9, p<0.01). The rpoB.450 mutation was associated with less extensive radiological pathology (RR 0.81, 95% CI 0.69 to 0.94, p=0.03), suggestive of a bacterial fitness cost for this mutation in vivo. Patients with a previous episode of TB disease and those between 10 and 30 years of age also had significantly increased radiological pathology. Conclusions: This study is the first to compare the M. tuberculosis genome to radiological pathology on the chest radiograph. We identified two variants significantly positively associated with more widespread radiological pathology and one with reduced pathology. Prospective studies are warranted to determine whether mutations associated with increased pathology also predict the spread of drug-resistant TB.
Fil: Grandjean, Louis. Imperial College London; Reino Unido
Fil: Monteserin, Johana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gilman, Robert. University Johns Hopkins; Estados Unidos
Fil: Pauschardt, Julia. Universidad Cayetano Heredia; Perú
Fil: Rokadiya, Sakib. Imperial College London; Reino Unido
Fil: Bonilla, Cesar. Ministerio de Salud; Perú
Fil: Ritacco, Gloria Viviana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vidal, Julia Rios. Ministerio de Salud; Perú
Fil: Parkhill, Julian. Wellcome Trust Sanger Institute; Reino Unido
Fil: Peacock, Sharon. University of Cambridge; Reino Unido
Fil: Vidal, Julia Rios. London School Of Hygiene And Tropical Medicine; Reino Unido
Fil: Balloux, Francois. University College London; Estados Unidos - Materia
-
CLINICAL EPIDEMIOLOGY
IMAGING/CT MRI ETC
TUBERCULOSIS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/169102
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/169102 |
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Association between bacterial homoplastic variants and radiological pathology in tuberculosisGrandjean, LouisMonteserin, JohanaGilman, RobertPauschardt, JuliaRokadiya, SakibBonilla, CesarRitacco, Gloria VivianaVidal, Julia RiosParkhill, JulianPeacock, SharonVidal, Julia RiosBalloux, FrancoisCLINICAL EPIDEMIOLOGYIMAGING/CT MRI ETCTUBERCULOSIShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Understanding how pathogen genetic factors contribute to pathology in TB could enable tailored treatments to the most pathogenic and infectious strains. New strategies are needed to control drug-resistant TB, which requires longer and costlier treatment. We hypothesised that the severity of radiological pathology on the chest radiograph in TB disease was associated with variants arising independently, multiple times (homoplasies) in the Mycobacterium tuberculosis genome. Methods: We performed whole genome sequencing (Illumina HiSeq2000 platform) on M. tuberculosis isolates from 103 patients with drug-resistant TB in Lima between 2010 and 2013. Variables including age, sex, HIV status, previous TB disease and the percentage of lung involvement on the pretreatment chest radiograph were collected from health posts of the national TB programme. Genomic variants were identified using standard pipelines. Results: Two mutations were significantly associated with more widespread radiological pathology in a multivariable regression model controlling for confounding variables (Rv2828c.141, RR 1.3, 95% CI 1.21 to 1.39, p<0.01; rpoC.1040 95% CI 1.77 to 2.16, RR 1.9, p<0.01). The rpoB.450 mutation was associated with less extensive radiological pathology (RR 0.81, 95% CI 0.69 to 0.94, p=0.03), suggestive of a bacterial fitness cost for this mutation in vivo. Patients with a previous episode of TB disease and those between 10 and 30 years of age also had significantly increased radiological pathology. Conclusions: This study is the first to compare the M. tuberculosis genome to radiological pathology on the chest radiograph. We identified two variants significantly positively associated with more widespread radiological pathology and one with reduced pathology. Prospective studies are warranted to determine whether mutations associated with increased pathology also predict the spread of drug-resistant TB.Fil: Grandjean, Louis. Imperial College London; Reino UnidoFil: Monteserin, Johana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gilman, Robert. University Johns Hopkins; Estados UnidosFil: Pauschardt, Julia. Universidad Cayetano Heredia; PerúFil: Rokadiya, Sakib. Imperial College London; Reino UnidoFil: Bonilla, Cesar. Ministerio de Salud; PerúFil: Ritacco, Gloria Viviana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vidal, Julia Rios. Ministerio de Salud; PerúFil: Parkhill, Julian. Wellcome Trust Sanger Institute; Reino UnidoFil: Peacock, Sharon. University of Cambridge; Reino UnidoFil: Vidal, Julia Rios. London School Of Hygiene And Tropical Medicine; Reino UnidoFil: Balloux, Francois. University College London; Estados UnidosB M J Publishing Group2020-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/169102Grandjean, Louis; Monteserin, Johana; Gilman, Robert; Pauschardt, Julia; Rokadiya, Sakib; et al.; Association between bacterial homoplastic variants and radiological pathology in tuberculosis; B M J Publishing Group; Thorax.; 75; 7; 7-2020; 584-5910040-6376CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://thorax.bmj.com/lookup/doi/10.1136/thoraxjnl-2019-213281info:eu-repo/semantics/altIdentifier/doi/10.1136/thoraxjnl-2019-213281info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:23Zoai:ri.conicet.gov.ar:11336/169102instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:42:23.888CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
title |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
spellingShingle |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis Grandjean, Louis CLINICAL EPIDEMIOLOGY IMAGING/CT MRI ETC TUBERCULOSIS |
title_short |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
title_full |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
title_fullStr |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
title_full_unstemmed |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
title_sort |
Association between bacterial homoplastic variants and radiological pathology in tuberculosis |
dc.creator.none.fl_str_mv |
Grandjean, Louis Monteserin, Johana Gilman, Robert Pauschardt, Julia Rokadiya, Sakib Bonilla, Cesar Ritacco, Gloria Viviana Vidal, Julia Rios Parkhill, Julian Peacock, Sharon Vidal, Julia Rios Balloux, Francois |
author |
Grandjean, Louis |
author_facet |
Grandjean, Louis Monteserin, Johana Gilman, Robert Pauschardt, Julia Rokadiya, Sakib Bonilla, Cesar Ritacco, Gloria Viviana Vidal, Julia Rios Parkhill, Julian Peacock, Sharon Balloux, Francois |
author_role |
author |
author2 |
Monteserin, Johana Gilman, Robert Pauschardt, Julia Rokadiya, Sakib Bonilla, Cesar Ritacco, Gloria Viviana Vidal, Julia Rios Parkhill, Julian Peacock, Sharon Balloux, Francois |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
CLINICAL EPIDEMIOLOGY IMAGING/CT MRI ETC TUBERCULOSIS |
topic |
CLINICAL EPIDEMIOLOGY IMAGING/CT MRI ETC TUBERCULOSIS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Background: Understanding how pathogen genetic factors contribute to pathology in TB could enable tailored treatments to the most pathogenic and infectious strains. New strategies are needed to control drug-resistant TB, which requires longer and costlier treatment. We hypothesised that the severity of radiological pathology on the chest radiograph in TB disease was associated with variants arising independently, multiple times (homoplasies) in the Mycobacterium tuberculosis genome. Methods: We performed whole genome sequencing (Illumina HiSeq2000 platform) on M. tuberculosis isolates from 103 patients with drug-resistant TB in Lima between 2010 and 2013. Variables including age, sex, HIV status, previous TB disease and the percentage of lung involvement on the pretreatment chest radiograph were collected from health posts of the national TB programme. Genomic variants were identified using standard pipelines. Results: Two mutations were significantly associated with more widespread radiological pathology in a multivariable regression model controlling for confounding variables (Rv2828c.141, RR 1.3, 95% CI 1.21 to 1.39, p<0.01; rpoC.1040 95% CI 1.77 to 2.16, RR 1.9, p<0.01). The rpoB.450 mutation was associated with less extensive radiological pathology (RR 0.81, 95% CI 0.69 to 0.94, p=0.03), suggestive of a bacterial fitness cost for this mutation in vivo. Patients with a previous episode of TB disease and those between 10 and 30 years of age also had significantly increased radiological pathology. Conclusions: This study is the first to compare the M. tuberculosis genome to radiological pathology on the chest radiograph. We identified two variants significantly positively associated with more widespread radiological pathology and one with reduced pathology. Prospective studies are warranted to determine whether mutations associated with increased pathology also predict the spread of drug-resistant TB. Fil: Grandjean, Louis. Imperial College London; Reino Unido Fil: Monteserin, Johana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gilman, Robert. University Johns Hopkins; Estados Unidos Fil: Pauschardt, Julia. Universidad Cayetano Heredia; Perú Fil: Rokadiya, Sakib. Imperial College London; Reino Unido Fil: Bonilla, Cesar. Ministerio de Salud; Perú Fil: Ritacco, Gloria Viviana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vidal, Julia Rios. Ministerio de Salud; Perú Fil: Parkhill, Julian. Wellcome Trust Sanger Institute; Reino Unido Fil: Peacock, Sharon. University of Cambridge; Reino Unido Fil: Vidal, Julia Rios. London School Of Hygiene And Tropical Medicine; Reino Unido Fil: Balloux, Francois. University College London; Estados Unidos |
description |
Background: Understanding how pathogen genetic factors contribute to pathology in TB could enable tailored treatments to the most pathogenic and infectious strains. New strategies are needed to control drug-resistant TB, which requires longer and costlier treatment. We hypothesised that the severity of radiological pathology on the chest radiograph in TB disease was associated with variants arising independently, multiple times (homoplasies) in the Mycobacterium tuberculosis genome. Methods: We performed whole genome sequencing (Illumina HiSeq2000 platform) on M. tuberculosis isolates from 103 patients with drug-resistant TB in Lima between 2010 and 2013. Variables including age, sex, HIV status, previous TB disease and the percentage of lung involvement on the pretreatment chest radiograph were collected from health posts of the national TB programme. Genomic variants were identified using standard pipelines. Results: Two mutations were significantly associated with more widespread radiological pathology in a multivariable regression model controlling for confounding variables (Rv2828c.141, RR 1.3, 95% CI 1.21 to 1.39, p<0.01; rpoC.1040 95% CI 1.77 to 2.16, RR 1.9, p<0.01). The rpoB.450 mutation was associated with less extensive radiological pathology (RR 0.81, 95% CI 0.69 to 0.94, p=0.03), suggestive of a bacterial fitness cost for this mutation in vivo. Patients with a previous episode of TB disease and those between 10 and 30 years of age also had significantly increased radiological pathology. Conclusions: This study is the first to compare the M. tuberculosis genome to radiological pathology on the chest radiograph. We identified two variants significantly positively associated with more widespread radiological pathology and one with reduced pathology. Prospective studies are warranted to determine whether mutations associated with increased pathology also predict the spread of drug-resistant TB. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-07 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/169102 Grandjean, Louis; Monteserin, Johana; Gilman, Robert; Pauschardt, Julia; Rokadiya, Sakib; et al.; Association between bacterial homoplastic variants and radiological pathology in tuberculosis; B M J Publishing Group; Thorax.; 75; 7; 7-2020; 584-591 0040-6376 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/169102 |
identifier_str_mv |
Grandjean, Louis; Monteserin, Johana; Gilman, Robert; Pauschardt, Julia; Rokadiya, Sakib; et al.; Association between bacterial homoplastic variants and radiological pathology in tuberculosis; B M J Publishing Group; Thorax.; 75; 7; 7-2020; 584-591 0040-6376 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://thorax.bmj.com/lookup/doi/10.1136/thoraxjnl-2019-213281 info:eu-repo/semantics/altIdentifier/doi/10.1136/thoraxjnl-2019-213281 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
B M J Publishing Group |
publisher.none.fl_str_mv |
B M J Publishing Group |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614456440520704 |
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13.070432 |