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

Pryscila Miranda,Frank Cobelens,Anneloek Rauwerdink,Marina G Oliveira,Eliene D D Mesquita,Martha M Oliveira,Elisangela Silva,Bruno B Andrade,Leonardo Gil-Santana,Afrânio Kritski,Olivier Neyrolles

doi:10.1371/journal.pone.0175278

Pryscila Miranda, Frank Cobelens + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0175278

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Journal: PloS one	Publication Date: Apr 6, 2017
Citations: 27	License type: CC BY 4.0

Affiliation: Universidade Federal do Rio de Janeiro

Abstract

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).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.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.ConclusionsCRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT.

Highlights

Despite intense investment from both governmental and private sectors, tuberculosis (TB) continues to cause substantial morbidity and mortality in several countries worldwide
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)
Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of anti-tubercular treatment (ATT) were tested. Circulating levels of both ferritin and CRP gradually decreased over time on ATT

Summary

Introduction

Despite intense investment from both governmental and private sectors, tuberculosis (TB) continues to cause substantial morbidity and mortality in several countries worldwide. In places where there is emergence of drug resistance, TB eradication becomes difficult and the mortality rates documented at 24 and 60 months from diagnosis in these regions are 46% and 73% of patients, respectively [3]. A better understanding of the utility of immune and inflammatory markers as readouts of treatment outcomes can potentially lead to development of innovative prediction tools as well as to establishing targets for host-directed therapies to optimize treatment efficacy. 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. 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)

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