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.

Highlights

  • A biomarker to discriminate active from latent Mycobacterium tuberculosis infection could help in exclusion of occult pulmonary and extrapulmonary tuberculosis

  • 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

  • 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

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Summary

Introduction

A biomarker to discriminate active from latent Mycobacterium tuberculosis infection could help in exclusion of occult pulmonary and extrapulmonary tuberculosis. There is no laboratory test available in clinical routine which can distinguish latent from active Mycobacterium (M.) tuberculosis infection. 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). 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

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