Latent Tuberculosis Diagnostics: A Systematic Review What is the past, present, and future in the diagnosis of latent tuberculosis?

ABSTRACT Background Tuberculosis (TB) is the second leading infectious killer after COVID-19 and the 13 th leading cause of death worldwide. Latent tuberculosis (LTBI) has become a major pool of potential active tuberculosis cases and is propelling the TB global health burden further. Objective The creation and application of a diagnostic to effectively identify LTBI is vital. This systematic review aims to examine and analyze the present and proposed future diagnostics in the identification of latent tuberculosis. Design Systematic Review Methods PubMed and Scopus were scanned as primary databases during May 2022. Exclusion criteria for the papers scanned included patients with immunosuppression (due to HIV or treatment), pediatric TB, cancer and dialysis patients, pregnancy, IV drug users, animal models, papers published before 2005, co-infected patients, IBD and transplant patients, and finally secondary literature. Such criteria were incorporated due to the differences in TB immunology in these circumstances. 18 papers were included in this review and their risk of bias assessed using the QUADAS-2 guidelines. For analysis the papers’ sensitivities and specificities were examined. There was also a deeper look into the surrounding variables such as population differentiation, diagnostic technologies, clinical translation, and bias. Findings With thorough analysis of the data, it was determined that there are promising diagnostics for the precise identification of LTBI. Specifically, 2 studies one which used ELISA measuring the IgG response of LTBI and ATB patients when exposed to a combination of antigens and this resulted in a sensitivity and specificity of 93.33% and 93.10% respectively. The second study utilizes ESAT-6 SFC MSS (mean spot size) and the modified TBAg/PHA ratio diagnostic model to establish LTBI or ATB and using ROC curve analysis found a sensitivity of 90.12% and specificity of 91.02%. Interpretation To conclude, specific diagnostics still being examined in the preliminary phase could in the future be used as adjuncts to already present diagnostics for the diagnosis of LTBI based on their strong sensitivities and specificities. No funding. SUMMARY BOX What is already known on this topic? The WHO guidelines for diagnosing LTBI include TST and IGRA, but neither can distinguish LTBI from ATB therefore a new diagnostic must be proposed for the specific detection of LTBI What this study adds Our review reveals new two specific new diagnostic tools for the diagnosis of LTBI How this study might affect research, practice, or policy Our study can impact the future specific diagnosis of LTBI through proposing new ways of differentiating between ATB and LTBI and their possible further progression into clinical practice