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Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection.

Eisenhut M, Hargreaves DS, Scott A, Housley D, Walters A, Mulla R - J Biomark (2016)

Bottom Line: Methods.Conclusions.Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

View Article: PubMed Central - PubMed

Affiliation: Luton & Dunstable University Hospital NHS Foundation Trust, London LU4 ODZ, UK.

ABSTRACT
Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p < 0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p < 0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

No MeSH data available.


Related in: MedlinePlus

Flow chart of patient selection.  ∗Patients with positive tuberculin skin test or positive interferon-gamma release assay and clinical, radiological, or culture evidence of tuberculosis.  ∗∗Positive tuberculin skin test and positive interferon-gamma release assay or only a positive interferon-gamma release assay with no clinical, radiological, or culture evidence of tuberculosis.  ∗∗∗Healthy relatives testing negative by interferon-gamma release assay and/or tuberculin skin test during contact screening.
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fig1: Flow chart of patient selection.  ∗Patients with positive tuberculin skin test or positive interferon-gamma release assay and clinical, radiological, or culture evidence of tuberculosis.  ∗∗Positive tuberculin skin test and positive interferon-gamma release assay or only a positive interferon-gamma release assay with no clinical, radiological, or culture evidence of tuberculosis.  ∗∗∗Healthy relatives testing negative by interferon-gamma release assay and/or tuberculin skin test during contact screening.

Mentions: We recruited 44 patients with M. tuberculosis infection out of which 12 had active tuberculosis. Amongst the patients with active tuberculosis, 9 patients had pulmonary and 3 patients had extrapulmonary tuberculosis (one each with tuberculous lymphadenitis, mandibular tuberculosis, and peritoneal tuberculosis). We also recruited nine healthy controls with negative interferon-gamma release assays on contact screening (for patient selection flow chart, see Figure 1). In 8/12 patients (66%), the tuberculosis was confirmed by culture. For patient characteristics and urinary neopterin/creatinine ratios, see Table 1. We included Supplementary Table 1 with the raw data for urinary neopterin levels, urinary creatinine levels, and urinary neopterin/creatinine ratios. None of the patients with active tuberculosis has been brought to our medical attention with a relapse at least two years after completion of the study and none of the patients with latent M. tuberculosis infection (LTBI) was diagnosed with active tuberculosis by our service at least two years after completion of treatment for latent infection. Age and gender were not significantly different between groups (p = 0.43 for age, female: active tuberculosis versus LTBI p = 0.77 and versus controls p = 1.0). Median urinary neopterin/creatinine ratio was significantly different between groups (p < 0.01) and significantly higher in patients with tuberculosis compared to latent M. tuberculosis infection and controls (p < 0.01) and not significantly different between patients with latent M. tuberculosis infection and controls (p = 0.66). Figure 2 depicts boxplots of urinary neopterin/creatinine ratios in patients with tuberculosis and latent M. tuberculosis infection and healthy controls. To illustrate distribution of ratios in the groups compared, we included a supplementary figure with a dot plot (Supplementary Figure 1). To determine test accuracy in detection of active tuberculosis in all patients with M. tuberculosis infection, a receiver operating characteristics curve was generated (see Figure 3).


Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection.

Eisenhut M, Hargreaves DS, Scott A, Housley D, Walters A, Mulla R - J Biomark (2016)

Flow chart of patient selection.  ∗Patients with positive tuberculin skin test or positive interferon-gamma release assay and clinical, radiological, or culture evidence of tuberculosis.  ∗∗Positive tuberculin skin test and positive interferon-gamma release assay or only a positive interferon-gamma release assay with no clinical, radiological, or culture evidence of tuberculosis.  ∗∗∗Healthy relatives testing negative by interferon-gamma release assay and/or tuberculin skin test during contact screening.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940561&req=5

fig1: Flow chart of patient selection.  ∗Patients with positive tuberculin skin test or positive interferon-gamma release assay and clinical, radiological, or culture evidence of tuberculosis.  ∗∗Positive tuberculin skin test and positive interferon-gamma release assay or only a positive interferon-gamma release assay with no clinical, radiological, or culture evidence of tuberculosis.  ∗∗∗Healthy relatives testing negative by interferon-gamma release assay and/or tuberculin skin test during contact screening.
Mentions: We recruited 44 patients with M. tuberculosis infection out of which 12 had active tuberculosis. Amongst the patients with active tuberculosis, 9 patients had pulmonary and 3 patients had extrapulmonary tuberculosis (one each with tuberculous lymphadenitis, mandibular tuberculosis, and peritoneal tuberculosis). We also recruited nine healthy controls with negative interferon-gamma release assays on contact screening (for patient selection flow chart, see Figure 1). In 8/12 patients (66%), the tuberculosis was confirmed by culture. For patient characteristics and urinary neopterin/creatinine ratios, see Table 1. We included Supplementary Table 1 with the raw data for urinary neopterin levels, urinary creatinine levels, and urinary neopterin/creatinine ratios. None of the patients with active tuberculosis has been brought to our medical attention with a relapse at least two years after completion of the study and none of the patients with latent M. tuberculosis infection (LTBI) was diagnosed with active tuberculosis by our service at least two years after completion of treatment for latent infection. Age and gender were not significantly different between groups (p = 0.43 for age, female: active tuberculosis versus LTBI p = 0.77 and versus controls p = 1.0). Median urinary neopterin/creatinine ratio was significantly different between groups (p < 0.01) and significantly higher in patients with tuberculosis compared to latent M. tuberculosis infection and controls (p < 0.01) and not significantly different between patients with latent M. tuberculosis infection and controls (p = 0.66). Figure 2 depicts boxplots of urinary neopterin/creatinine ratios in patients with tuberculosis and latent M. tuberculosis infection and healthy controls. To illustrate distribution of ratios in the groups compared, we included a supplementary figure with a dot plot (Supplementary Figure 1). To determine test accuracy in detection of active tuberculosis in all patients with M. tuberculosis infection, a receiver operating characteristics curve was generated (see Figure 3).

Bottom Line: Methods.Conclusions.Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

View Article: PubMed Central - PubMed

Affiliation: Luton & Dunstable University Hospital NHS Foundation Trust, London LU4 ODZ, UK.

ABSTRACT
Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p < 0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p < 0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

No MeSH data available.


Related in: MedlinePlus