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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

CRP and Ferritin concentrations in serum of treatment-naïve pulmonary TB patients are not significantly influenced by mycobacterial loads in sputum.(A) CRP and ferritin levels were compared between pulmonary TB patients with negative or positive identification of acid-fast bacilli (AFB) in sputum smears using the Mann-Whitney test (CRP: p = 0.094, Ferritin: p = 0.830). (B) These markers were further compared between groups of TB patients presenting with different sputum smear grades (**p<0.01, AFB ≥3+ vs. 0) or (C) those exhibiting different culture grades using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted.
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pone.0175278.g002: CRP and Ferritin concentrations in serum of treatment-naïve pulmonary TB patients are not significantly influenced by mycobacterial loads in sputum.(A) CRP and ferritin levels were compared between pulmonary TB patients with negative or positive identification of acid-fast bacilli (AFB) in sputum smears using the Mann-Whitney test (CRP: p = 0.094, Ferritin: p = 0.830). (B) These markers were further compared between groups of TB patients presenting with different sputum smear grades (**p<0.01, AFB ≥3+ vs. 0) or (C) those exhibiting different culture grades using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted.

Mentions: We next examined whether the circulating concentrations of these two markers are associated with mycobacterial loads in sputum in PTB patients before ATT initiation. CRP and ferritin levels were undistinguishable between individuals presenting with positive or negative AFB identification in sputum smears (Fig 2A). Furthermore, we analyzed the variation of this marker according to AFB smear grade and observed that CRP levels were gradually increased following AFB smear grades (linear trend analysis p<0.0001), with the highest values observed in individuals with AFB of ≥3+ (p = 0.0094, compared to AFB = 0; Fig 2B). In this setting, ferritin concentrations presented considerable variability within the different groups and median values did not significantly change following increases in AFB smear grade. In addition, neither CRP or ferritin values could distinguish patients with different bacterial loads in sputum cultures (Fig 2C). These results indicated that CRP, but not ferritin, levels reflect pre-treatment bacterial loads as observed in AFB smear grades in sputum samples in the study population.


Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation
CRP and Ferritin concentrations in serum of treatment-naïve pulmonary TB patients are not significantly influenced by mycobacterial loads in sputum.(A) CRP and ferritin levels were compared between pulmonary TB patients with negative or positive identification of acid-fast bacilli (AFB) in sputum smears using the Mann-Whitney test (CRP: p = 0.094, Ferritin: p = 0.830). (B) These markers were further compared between groups of TB patients presenting with different sputum smear grades (**p<0.01, AFB ≥3+ vs. 0) or (C) those exhibiting different culture grades using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5383283&req=5

pone.0175278.g002: CRP and Ferritin concentrations in serum of treatment-naïve pulmonary TB patients are not significantly influenced by mycobacterial loads in sputum.(A) CRP and ferritin levels were compared between pulmonary TB patients with negative or positive identification of acid-fast bacilli (AFB) in sputum smears using the Mann-Whitney test (CRP: p = 0.094, Ferritin: p = 0.830). (B) These markers were further compared between groups of TB patients presenting with different sputum smear grades (**p<0.01, AFB ≥3+ vs. 0) or (C) those exhibiting different culture grades using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted.
Mentions: We next examined whether the circulating concentrations of these two markers are associated with mycobacterial loads in sputum in PTB patients before ATT initiation. CRP and ferritin levels were undistinguishable between individuals presenting with positive or negative AFB identification in sputum smears (Fig 2A). Furthermore, we analyzed the variation of this marker according to AFB smear grade and observed that CRP levels were gradually increased following AFB smear grades (linear trend analysis p<0.0001), with the highest values observed in individuals with AFB of ≥3+ (p = 0.0094, compared to AFB = 0; Fig 2B). In this setting, ferritin concentrations presented considerable variability within the different groups and median values did not significantly change following increases in AFB smear grade. In addition, neither CRP or ferritin values could distinguish patients with different bacterial loads in sputum cultures (Fig 2C). These results indicated that CRP, but not ferritin, levels reflect pre-treatment bacterial loads as observed in AFB smear grades in sputum samples in the study population.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus