Telomere length and outcome of treatment for pulmonary tuberculosis in a gold mining community
Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and n...
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| Published in | Scientific reports Vol. 11; no. 1; pp. 4031 - 10 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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Nature Publishing Group UK
17.02.2021
Nature Publishing Group Nature Portfolio |
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| Abstract | Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. |
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| AbstractList | Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Abstract Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by - 0.85% (- 0.19 to - 0.52) (p ≤ 0.0001) and - 14% (- 28.22 to - 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome.Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by - 0.85% (- 0.19 to - 0.52) (p ≤ 0.0001) and - 14% (- 28.22 to - 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by - 0.85% (- 0.19 to - 0.52) (p ≤ 0.0001) and - 14% (- 28.22 to - 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. |
| ArticleNumber | 4031 |
| Author | Nawrot, Tim S. Martens, Dries S. Nachega, Jean B. Nemery, Benoit Pollitt, Krystal J. Godri Katoto, Patrick D. M. C. Kayembe-Kitenge, Tony Ghosh, Manosij |
| Author_xml | – sequence: 1 givenname: Patrick D. M. C. surname: Katoto fullname: Katoto, Patrick D. M. C. email: katotopatrick@gmail.com organization: Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Department of Internal Medicine, Division of Respiratory Medicine, CEGEMI and Prof. Lurhuma Biomedical Research Laboratory, Mycobacterium Unit, Catholic University of Bukavu, Department of Medicine and Center for Infectious Diseases, Faculty of Medicine and Health Sciences, Stellenbosch University – sequence: 2 givenname: Tony surname: Kayembe-Kitenge fullname: Kayembe-Kitenge, Tony organization: Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Department of Public Health, Unit of Toxicology, University of Lubumbashi – sequence: 3 givenname: Krystal J. Godri surname: Pollitt fullname: Pollitt, Krystal J. Godri organization: Department of Environmental Health Sciences, School of Public Health, Yale University – sequence: 4 givenname: Dries S. surname: Martens fullname: Martens, Dries S. organization: Centre of Environmental Health, University of Hasselt – sequence: 5 givenname: Manosij surname: Ghosh fullname: Ghosh, Manosij organization: Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven – sequence: 6 givenname: Jean B. surname: Nachega fullname: Nachega, Jean B. organization: Department of Medicine and Center for Infectious Diseases, Faculty of Medicine and Health Sciences, Stellenbosch University, Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Departments of Epidemiology, Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health – sequence: 7 givenname: Benoit surname: Nemery fullname: Nemery, Benoit organization: Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven – sequence: 8 givenname: Tim S. surname: Nawrot fullname: Nawrot, Tim S. email: tim.nawrot@uhasselt.be organization: Department of Public Health and Primary Care, Centre for Environment and Health, KU Leuven, Centre of Environmental Health, University of Hasselt |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33597559$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_tube_2021_102144 crossref_primary_10_3390_genes14081596 crossref_primary_10_1016_j_envint_2021_106866 |
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| Snippet | Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and... Abstract Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined... |
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| SubjectTerms | 692/1537 692/53 692/699 692/699/255 692/699/255/1856 Adolescent Adult Aged Aging Biomarkers, Pharmacological - blood Child Child, Preschool Clinical outcomes Democratic Republic of the Congo - epidemiology DNA, Mitochondrial - analysis DNA, Mitochondrial - drug effects DNA, Mitochondrial - genetics Female Gold HIV Human immunodeficiency virus Humanities and Social Sciences Humans Leukocytes Male Middle Aged Miners Mining Mitochondrial DNA multidisciplinary Occupational Diseases - etiology Oxidative stress Peripheral blood Proportional Hazards Models Prospective Studies Science Science (multidisciplinary) Telomere - genetics Telomere - metabolism Telomere Homeostasis - drug effects Telomere Homeostasis - genetics Telomere Homeostasis - physiology Telomeres Tuberculosis Tuberculosis, Pulmonary - genetics Tuberculosis, Pulmonary - therapy |
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| Title | Telomere length and outcome of treatment for pulmonary tuberculosis in a gold mining community |
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