Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation

PLoS One. 2017 Apr 6;12(4):e0175278. doi: 10.1371/journal.pone.0175278. eCollection 2017.

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.

MeSH terms

  • Adult
  • Antitubercular Agents / therapeutic use
  • C-Reactive Protein / metabolism*
  • Female
  • Ferritins / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / metabolism*

Substances

  • Antitubercular Agents
  • C-Reactive Protein
  • Ferritins

Grants and funding

This work was supported by CNPq /INCT 573548/2008-0; Faperj Process: Processo - E-26/110.974/2011. AK is the recipient of a career award from CNPq (produtividade em pesquisa) and FAPERJ (Cientistas do Nosso Estado). LG-S received scientific initiation fellowship from Fundação de Amparo à Pesquisa da Bahia (FAPESB) and Fundação Oswaldo Cruz (FIOCRUZ). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.