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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/169102
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/169102
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T12:15:04Zoai: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:34982025-10-22 12:15:04.551CONICET 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)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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score 12.982451

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