Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation
Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (...
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| Published in: | PloS one Vol. 12; no. 4; p. e0175278 |
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06.04.2017
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| Abstract | Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT).
Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested.
Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point.
CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. |
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| AbstractList | Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT).BACKGROUNDClinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT).Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested.METHODSProspective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested.Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point.RESULTSCirculating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point.CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT.CONCLUSIONSCRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Methods Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Results Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. Conclusions CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Methods Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Results Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. Conclusions CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT).Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested.Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point.CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. |
| Audience | Academic |
| Author | Gil-Santana, Leonardo Oliveira, Marina G. Andrade, Bruno B. Rauwerdink, Anneloek Cobelens, Frank Miranda, Pryscila Mesquita, Eliene D. D. Kritski, Afrânio Silva, Elisangela Oliveira, Martha M. |
| AuthorAffiliation | 1 Tuberculosis Academic Program, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 2 Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil 9 Development Center for Technology on Health (CDTS) Fundação Oswaldo Cruz, Rio de Janeiro, Brazil 8 Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands Institut de Pharmacologie et de Biologie Structurale, FRANCE 4 Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil 3 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil 6 Recognize the Biology Laboratory, Center of Bioscience and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil 11 Universidade Salvador (UNIFACS), Laureate International Universities, Salvador, Brazil 5 Ary Parreira Institute, State Secretary of Health of Rio de Janeiro, Rio de Janeiro, B |
| AuthorAffiliation_xml | – name: 2 Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil – name: 11 Universidade Salvador (UNIFACS), Laureate International Universities, Salvador, Brazil – name: 3 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil – name: 5 Ary Parreira Institute, State Secretary of Health of Rio de Janeiro, Rio de Janeiro, Brazil – name: 9 Development Center for Technology on Health (CDTS) Fundação Oswaldo Cruz, Rio de Janeiro, Brazil – name: 10 Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil – name: 6 Recognize the Biology Laboratory, Center of Bioscience and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil – name: 8 Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands – name: 1 Tuberculosis Academic Program, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil – name: Institut de Pharmacologie et de Biologie Structurale, FRANCE – name: 7 Rede Brasileira de Pesquisas em Tuberculose (Rede TB), Rio de Janeiro, Brazil – name: 4 Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil |
| Author_xml | – sequence: 1 givenname: Pryscila surname: Miranda fullname: Miranda, Pryscila – sequence: 2 givenname: Leonardo surname: Gil-Santana fullname: Gil-Santana, Leonardo – sequence: 3 givenname: Marina G. surname: Oliveira fullname: Oliveira, Marina G. – sequence: 4 givenname: Eliene D. D. surname: Mesquita fullname: Mesquita, Eliene D. D. – sequence: 5 givenname: Elisangela surname: Silva fullname: Silva, Elisangela – sequence: 6 givenname: Anneloek surname: Rauwerdink fullname: Rauwerdink, Anneloek – sequence: 7 givenname: Frank surname: Cobelens fullname: Cobelens, Frank – sequence: 8 givenname: Martha M. surname: Oliveira fullname: Oliveira, Martha M. – sequence: 9 givenname: Bruno B. orcidid: 0000-0001-6833-3811 surname: Andrade fullname: Andrade, Bruno B. – sequence: 10 givenname: Afrânio surname: Kritski fullname: Kritski, Afrânio |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28384354$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2017 Public Library of Science 2017 Miranda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2017 Miranda et al 2017 Miranda et al |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceptualization: LG-S BBA AK.Data curation: PM LG-S MGO EDDM ES AR.Formal analysis: LG-S BBA.Funding acquisition: AK FC MMO.Investigation: PM MGO EDDM ES AR FC MMO AK.Methodology: LG-S BBA.Project administration: MMO AK.Resources: PM LG-S MGO EDDM FC MMO AK BBA.Software: LG-S BBA.Supervision: AK BBA.Validation: BBA.Visualization: LG-S BBA.Writing – original draft: LG-S BBA.Writing – review & editing: PM LG-S ES FC BBA AK. These authors also contributed equally to this work |
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| References_xml | – volume: 7 start-page: e37350 year: 2012 ident: ref19 article-title: Iron status predicts treatment failure and mortality in tuberculosis patients: a prospective cohort study from Dar es Salaam, Tanzania publication-title: PLoS One doi: 10.1371/journal.pone.0037350 – ident: ref1 – volume: 81 start-page: 50 year: 2016 ident: ref7 article-title: Host biomarkers detected in saliva show promise as markers for the diagnosis of pulmonary tuberculosis disease and monitoring of the response to tuberculosis treatment publication-title: Cytokine doi: 10.1016/j.cyto.2016.02.004 – volume: 60 start-page: 764 year: 2015 ident: ref9 article-title: Complex anemia in tuberculosis: the need to consider causes and timing when designing interventions publication-title: Clin Infect Dis doi: 10.1093/cid/ciu945 – volume: 2015 year: 2015 ident: ref18 article-title: Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis publication-title: J 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| Snippet | Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis... Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium... Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium... |
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| Title | Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation |
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