Diagnostic Performance Characteristics of hTMK tool in discriminating against Infected from Uninfected MTB individuals

Abstract

Tuberculosis is one of the most contagious disease which can easily spread through air when an infected person coughs, sneezes or simply talks and another person breathes in the bacteria through air. It is caused by Mycobacterium tuberculosis (MTB). Tuberculosis is regarded into two categories; active Tuberculosis (ATB) and latent TB (LTBI). MTB currently has infected nearly 2 billion people worldwide with around 10.4 million new cases of TB each year. It is among the most infectious diseases after Human Immunodeficiency Virus (HIV). There has always been a challenge of differentiating the different MTB stages of infection and quick, accurate methods of diagnosing latent Tuberculosis still remain elusive. In this study, 40 archived samples of Ugandan adults were used to explore the performance characteristics of human Thymidylate Kinase 1 (hTMK) as a biomarker to discriminate against MTB infected from uninfected Ugandan adults. The samples included in this study were from participants who were either TST positive or Negative. The samples were tested using Interferon Gamma Release Assays (IGRA) to define individuals who were latently infected and uninfected ones. The diagnostic characteristics and cut-off for hTMK to differentiate uninfected from infected MTB individuals was obtained and compared with QFT-IGRA characteristics and cut-off. The two biomarkers (hTMK and Interferon-gamma (IFN-γ)) were analyzed to compare test accuracy, sensitivity and specificity.

Results show that the sensitivity and specificity of hTMK was 81.3% and 60% respectively compared to IFN-γ which had sensitivity and specificity of 65% and 45% respectively. The AUROC of IFN-γ and hTMK was determined to be 0.51 and 0.72 and corresponding p values were 0.914 and 0.120 respectively. in conclusion, hTMK is a potential biomarker in diagnosis of MTB infection due to its higher sensitivity. A combination of both IFN-γ and hTMK could serve as an option in improving the diagnostic performance in discriminating against latently infected from uninfected individuals. hTMK, therefore, presents a good diagnostic surrogate marker for discriminating the latently infected individuals from uninfected.