title: Associations between systemic inflammation, mycobacterial loads in sputum and radiological improvement after treatment initiation in pulmonary TB patients from Brazil: a prospective cohort study.
abstract: Mycobacterium tuberculosis infection is known to cause inflammation and lung tissue damage in high-risk populations. Nevertheless, direct associations between mycobacterial loads, systemic inflammation and pulmonary lesions upon treatment initiation have not been fully characterized. In the present exploratory study, we prospectively depict the immune profile, microbial clearance and evolution of radiographic lesions in a pulmonary tuberculosis (PTB) patient cohort before and 60 days after anti-tuberculous treatment (ATT) initiation.
  
  
  
  Circulating levels of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α) and C-reactive protein (CRP), as well as values of erythrocyte sedimentation rate (ESR) were measured in cryopreserved serum samples obtained from 73 PTB patients at pre-ATT and day 60 of treatment. Changes of the immune profile over time were compared with mycobacterial loads in sputum and culture conversion at day 60 of ATT. Additional analyses tested associations between improvement of chest radiographic lesions at day 60 and pre-treatment status of inflammation and mycobacterial loads.
  
  
  
  Within the inflammatory parameters evaluated, values of CRP, IL-2, IL-4, TNF-α and ESR significantly decreased upon treatment initiation. On the converse, IL-10 levels substantially increased at day 60 of ATT, whereas concentrations of IL-6 and IFN-γ remained unchanged. Multidimensional analyses revealed that ESR, IL-2, IL-4 and CRP were the parameters with the highest power to discriminate individuals before and after treatment initiation. We further demonstrated that higher bacterial loads in sputum at pre-ATT were associated with increased systemic inflammation and higher risk for positive M. tuberculosis sputum cultures at day 60 of treatment. Furthermore, we found that pre-ATT mycobacterial loads in sputum and systemic inflammation synergistically associated with the status of radiographic lesions during treatment (Relative risk for chest X-ray improvement: 10.0, 95 % confidence interval: 2.4-40.0, P = 0.002).
  
  
  
  M. tuberculosis loads in sputum are directly associated to the status of systemic inflammation and potentially impact the immune profile, culture conversion and evolution of lung lesions upon ATT initiation.
authors: Ary Parreira Institute, State Secretary of Health of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Eliene D D
authors: ED
authors: Mesquita
authors: Unidade de Medicina Investigativa, Laboratório Integrado de Microbiologia e Imunorregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil.|School of Medicine, Faculdade de Tecnologia e Ciências, Salvador, Brazil.
authors: Leonardo
authors: L
authors: Gil-Santana
authors: Tuberculosis Academic Program, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Daniela
authors: D
authors: Ramalho
authors: Radiology Department, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Elise
authors: E
authors: Tonomura
authors: Tuberculosis Academic Program, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.|Recognize the Biology Laboratory, Center of Bioscience and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil.
authors: Elisangela C
authors: EC
authors: Silva
authors: Development Center for Technology on Health, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Martha M
authors: MM
authors: Oliveira
authors: Unidade de Medicina Investigativa, Laboratório Integrado de Microbiologia e Imunorregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. bruno.andrade@bahia.fiocruz.br.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil. bruno.andrade@bahia.fiocruz.br.|School of Medicine, Faculdade de Tecnologia e Ciências, Salvador, Brazil. bruno.andrade@bahia.fiocruz.br.
authors: Bruno B
authors: BB
authors: Andrade
authors: Tuberculosis Academic Program, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. kritskia@gmail.com.
authors: Afrânio
authors: A
authors: Kritski
mesh_terms: D000328:Adult; D058491:Bacterial Load; D001938:Brazil; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000382:microbiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D013902:Radiography, Thoracic; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Acid-fast bacilli; Anti-tuberculous treatment; Biomarker; C-reactive protein; Erythrocyte sedimentation rate; Inflammation; Radiographic evaluation; Tuberculosis