Abstract
ObjectivesThe timely diagnosis of pulmonary tuberculosis (PTB) is challenging. Although pathogen-derived circulating cell-free DNA (cfDNA) has been detected in humans, the significance of Mycobacterium tuberculosis (MTB)-cfDNA detection in patients with PTB remains unclear.MethodsThis study enrolled patients with PTB and persons with latent tuberculosis infection (LTBI) as the study and control groups, respectively, from 2018 to 2020. We measured interferon-γ levels and calculated blood monocyte-to-lymphocyte ratio (MLR). We conducted plasma cfDNA extraction, quantitative polymerase chain reaction (qPCR), and droplet digital PCR targeting the IS6110 gene of MTB. We calculated the sensitivity and specificity of using MTB-cfDNA to identify PTB and analyzed the factors associated with PTB diagnosis and MTB-cfDNA positivity.ResultsWe enrolled 24 patients with PTB and 57 LTBI controls. The sensitivity of using MTB-cfDNA to identify PTB was 54.2%(13/24) in total and 46.2%(6/13) in smear-negative cases. Two LTBI controls (3.5%) tested positive for MTB-cfDNA, indicating a specificity of 96.5%(55/57). By using MTB-cfDNA positivity and an MLR ≥0.42 to identify PTB, sensitivity increased to 79.2%(19/24). Among patients with PTB, MTB-specific interferon-γ levels were higher in MTB-cfDNA positive participants than in those who tested negative (7.0 ±2.7 vs 2.7±3.0 IU/mL, p<0.001). MTB-cfDNA levels declined after 2 months of anti-tuberculosis therapy (p<0.001).ConclusionThe sensitivity of using MTB-cfDNA to identify PTB in participants was 54.2%, which increased to 79.2% after incorporating an MLR ≥0.42 into the analysis. MTB-cfDNA positivity was associated with MTB-specific immune response, and MTB-cfDNA levels declined after treatment. The clinical value of MTB-cfDNA in PTB management necessitates further investigation.
Highlights
Pulmonary tuberculosis (PTB) is caused by the Mycobacterium tuberculosis (MTB) complex, and bacteriological evidence is generally required to confirm diagnosis [1]
The sensitivity of using MTB-cell-free DNA (cfDNA) to identify PTB in participants was 54.2%, which increased to 79.2% after incorporating an monocyte-to-lymphocyte ratio (MLR) 0.42 into the analysis
MTB-cfDNA positivity was associated with MTB-specific immune response, and MTB-cfDNA levels declined after treatment
Summary
Pulmonary tuberculosis (PTB) is caused by the Mycobacterium tuberculosis (MTB) complex, and bacteriological evidence is generally required to confirm diagnosis [1]. Diagnosis and rapid treatment of PTB improves clinical outcomes and reduces the risk of transmission [2]. The time required to diagnose PTB (3–8 weeks) may be prolonged in patients with subclinical infection and those with a negative sputum-smear test for acid-fast bacilli [3, 4]. Some candidate biomarkers are used for rapid diagnosis; the interferon-γ release assays (IGRA) for the diagnosis of latent TB infection (LTBI) cannot distinguish between persons with LTBI and patients with PTB [5]. Developing noninvasive screening tests for the diagnosis of PTB remains worthwhile [1]
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