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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

Circulating levels of ferritin, but not CRP, substantially decrease in pulmonary TB patients undergoing anti-tuberculous therapy (ATT).(A) Serum concentrations of ferritin and CRP were prospectively measured in a cohort of 165 treatment-naïve patients with culture confirmed pulmonary TB. Lines and whiskers represent median and interquartile values. Data were analyzed using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted. *P<0.05; **P<0.01. (B) Serum levels of Ferritin and CRP were tested for correlations at different study time points. Data were analyzed using the Spearman’s rank test. Non-linear curve fit analysis was used to illustrate the trends in data distribution in the correlation plots. (C) Concentrations of ferritin and CRP were examined prospectively in patients stratified by HIV infection status.
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pone.0175278.g001: Circulating levels of ferritin, but not CRP, substantially decrease in pulmonary TB patients undergoing anti-tuberculous therapy (ATT).(A) Serum concentrations of ferritin and CRP were prospectively measured in a cohort of 165 treatment-naïve patients with culture confirmed pulmonary TB. Lines and whiskers represent median and interquartile values. Data were analyzed using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted. *P<0.05; **P<0.01. (B) Serum levels of Ferritin and CRP were tested for correlations at different study time points. Data were analyzed using the Spearman’s rank test. Non-linear curve fit analysis was used to illustrate the trends in data distribution in the correlation plots. (C) Concentrations of ferritin and CRP were examined prospectively in patients stratified by HIV infection status.

Mentions: Circulating levels of both CRP and ferritin at initiation of ATT were negatively correlated with BMI (CRP: r = -0.66, p<0.0001; ferritin: r = -0.29, p<0.0001) and positively correlated with age (CRP: r = 0.54, p<0.0001; ferritin: r = 0.53, p<0.0001). Out of all patients recruited, 37 patients did not return to the follow up visit at day 30 and 32 individuals missed the visit at day 60 of ATT. Twenty-six patients missed both follow up visits and we had only baseline assessment from those. Prospective analyses demonstrated that CRP levels consistently decreased between day 0 and day 30 of treatment, with a trend to further decrease by day 60 (Fig 1A). At day 30 of ATT, ferritin levels presented a trend to decrease compared to pre-treatment values. Furthermore, serum levels of ferritin substantially decreased at day 60 of ATT compared with previous study time points (Fig 1A). Of note, we observed that ferritin and CRP levels were positively correlated not only at pre-treatment (r = 0.55, p<0.0001) but also at day 30 (r = 0.32, p = 0.001) and day 60 (r = 0.43, p<0.0001) of therapy (Fig 1B). Interestingly, levels of both CRP and ferritin gradually decreased in HIV-uninfected patients undergoing anti-TB treatment whereas there were non-statistically significant trends to decrease in in HIV-infected persons (Fig 1C). These findings indicate that although both CRP and ferritin levels substantially decrease upon ATT initiation, patients who remained with high concentrations of CRP simultaneously displayed elevated levels of ferritin. The above results also indicate that some individuals exhibit a residual systemic inflammation at the end of the intensive phase of TB treatment.


Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation
Circulating levels of ferritin, but not CRP, substantially decrease in pulmonary TB patients undergoing anti-tuberculous therapy (ATT).(A) Serum concentrations of ferritin and CRP were prospectively measured in a cohort of 165 treatment-naïve patients with culture confirmed pulmonary TB. Lines and whiskers represent median and interquartile values. Data were analyzed using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted. *P<0.05; **P<0.01. (B) Serum levels of Ferritin and CRP were tested for correlations at different study time points. Data were analyzed using the Spearman’s rank test. Non-linear curve fit analysis was used to illustrate the trends in data distribution in the correlation plots. (C) Concentrations of ferritin and CRP were examined prospectively in patients stratified by HIV infection status.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0175278.g001: Circulating levels of ferritin, but not CRP, substantially decrease in pulmonary TB patients undergoing anti-tuberculous therapy (ATT).(A) Serum concentrations of ferritin and CRP were prospectively measured in a cohort of 165 treatment-naïve patients with culture confirmed pulmonary TB. Lines and whiskers represent median and interquartile values. Data were analyzed using Kruskal Wallis test with Dunn’s multiple comparisons. Statistically significant differences are highlighted. *P<0.05; **P<0.01. (B) Serum levels of Ferritin and CRP were tested for correlations at different study time points. Data were analyzed using the Spearman’s rank test. Non-linear curve fit analysis was used to illustrate the trends in data distribution in the correlation plots. (C) Concentrations of ferritin and CRP were examined prospectively in patients stratified by HIV infection status.
Mentions: Circulating levels of both CRP and ferritin at initiation of ATT were negatively correlated with BMI (CRP: r = -0.66, p<0.0001; ferritin: r = -0.29, p<0.0001) and positively correlated with age (CRP: r = 0.54, p<0.0001; ferritin: r = 0.53, p<0.0001). Out of all patients recruited, 37 patients did not return to the follow up visit at day 30 and 32 individuals missed the visit at day 60 of ATT. Twenty-six patients missed both follow up visits and we had only baseline assessment from those. Prospective analyses demonstrated that CRP levels consistently decreased between day 0 and day 30 of treatment, with a trend to further decrease by day 60 (Fig 1A). At day 30 of ATT, ferritin levels presented a trend to decrease compared to pre-treatment values. Furthermore, serum levels of ferritin substantially decreased at day 60 of ATT compared with previous study time points (Fig 1A). Of note, we observed that ferritin and CRP levels were positively correlated not only at pre-treatment (r = 0.55, p<0.0001) but also at day 30 (r = 0.32, p = 0.001) and day 60 (r = 0.43, p<0.0001) of therapy (Fig 1B). Interestingly, levels of both CRP and ferritin gradually decreased in HIV-uninfected patients undergoing anti-TB treatment whereas there were non-statistically significant trends to decrease in in HIV-infected persons (Fig 1C). These findings indicate that although both CRP and ferritin levels substantially decrease upon ATT initiation, patients who remained with high concentrations of CRP simultaneously displayed elevated levels of ferritin. The above results also indicate that some individuals exhibit a residual systemic inflammation at the end of the intensive phase of TB treatment.

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