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

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.

Elevated circulating levels of monocyte activation markers among tuberculosis patients with diabetes co‐morbidity

“…Previously published data also indicate that circulating CRP levels were significantly increased in active TB disease compared with controls . During M. tuberculosis infection, CRP levels are increased in TB patients starting ATT and decreased during the first 2 months of treatment, and these elevated CRP levels reflected higher AFB smear grades and correlated with disease severity . Similar to earlier findings, our data recapitulate those results and show that CRP levels are present at significantly enhanced levels in TB‐DM and TB compared with the other groups.…”

“…We previously reported that pulmonary TB displayed heightened serum CRP levels compared with latent TB and extrapulmonary TB . Previously published data also indicate that circulating CRP levels were significantly increased in active TB disease compared with controls . During M. tuberculosis infection, CRP levels are increased in TB patients starting ATT and decreased during the first 2 months of treatment, and these elevated CRP levels reflected higher AFB smear grades and correlated with disease severity .…”

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT – A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

“…Second, ferritin levels are very high during severe graft-versus-host disease and during macrophage activation syndromes after alloSCT (12). Third, ferritin is an acute phase protein that is regularly elevated during acute and chronic infections (24,25). Ferritin has been implicated in fungal growth and high ferritin levels have previously been suggested to be a risk factor for infections after alloSCT (26)(27)(28).…”

Can we predict tuberculosis cure? What tools are available?

“…Although promising, further research is needed to establish the efficacy of this new assay as marker for treatment monitoring and/or outcome. 166,195,196] [158] [172,173,197] [ 162,175] Markers of lung tissue repair (platelet activity VEGF, TGF-β, MMPs) [195,196] [135].…”

“…Circulating levels of C-reactive protein (CRP), an established biomarker of systemic inflammation, has been described to reflect TB disease severity and radiographic improvement after 2 months of treatment [162,163]. In an African study, CRP decreased significantly after 2 months of treatment, whereas levels of β 2 -microglobulin, a component of class I MHC found in a free state in various body fluids in different disease pathologies [164], and neopterin, a clinical marker of immune activation during inflammation [165] showed little change by 2 months, but a significant decrease after 6 months of treatment [166].…”