title: Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation.
abstract: 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.
authors.affiliation: Tuberculosis Academic Program, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Pryscila
authors.initials: P
authors.lastname: Miranda
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil.|Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gil-Santana
authors.affiliation: Tuberculosis Academic Program, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marina G
authors.initials: MG
authors.lastname: Oliveira
authors.affiliation: Ary Parreira Institute, State Secretary of Health of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Eliene D D
authors.initials: ED
authors.lastname: Mesquita
authors.affiliation: Recognize the Biology Laboratory, Center of Bioscience and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil.|Rede Brasileira de Pesquisas em Tuberculose (Rede TB), Rio de Janeiro, Brazil.
authors.forename: Elisangela
authors.initials: E
authors.lastname: Silva
authors.affiliation: Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Anneloek
authors.initials: A
authors.lastname: Rauwerdink
authors.affiliation: Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Cobelens
authors.affiliation: Rede Brasileira de Pesquisas em Tuberculose (Rede TB), Rio de Janeiro, Brazil.|Development Center for Technology on Health (CDTS) Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Oliveira
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil.|Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil.|Rede Brasileira de Pesquisas em Tuberculose (Rede TB), Rio de Janeiro, Brazil.|Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil.|Universidade Salvador (UNIFACS), Laureate International Universities, Salvador, Brazil.
authors.forename: Bruno B
authors.identifier: http://orcid.org/0000-0001-6833-3811
authors.initials: BB
authors.lastname: Andrade
authors.affiliation: Tuberculosis Academic Program, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.|Rede Brasileira de Pesquisas em Tuberculose (Rede TB), Rio de Janeiro, Brazil.
authors.forename: Afrânio
authors.initials: A
authors.lastname: Kritski
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000995:Antitubercular Agents; D002097:C-Reactive Protein; D005293:Ferritins