Clinical laboratory analytes and platelet-associated parameters as surrogate markers of subclinical inflammation in latent tuberculosis infection

Sivaprakasam T Selvavinayagam¹Adukkadukkam Anusree²Yean Kong Yong³Sathish Sankar⁴Asha Frederick⁵Manivannan Rajeshkumar⁶Masilamani Senthil Kumar¹Palani Sampath¹Ganga Sankar⁶Chitrali Laha Roy²Karishma S Jith²Amudhan Murugesan⁷Pachamuthu Balakrishnan⁸Sakthivel Govindaraj⁹Siddappa N Byrareddy¹⁰Vijayakumar Velu⁹Esaki M. SHANKAR^11*Marie Larsson¹²Meganathan Kannan²Sivadoss Raju⁶

• ¹Directorate of Public Health and Preventive Medicine, Chennai, India
• ²Blood and Vascular Biology, Department of Biotechnology, Central University of Tamil Nadu, Thiruvarur, India
• ³Xiamen University - Malaysia, Sepang, Malaysia
• ⁴SIMATS Deemed University Saveetha Dental College, Chennai, India
• ⁵State TB Office, DMS Campus, Teynampet, Chennai, India
• ⁶State Public Health Laboratory, Directorate of Public Health and Preventive Medicine, DMS Campus, Teynampet, Chennai, India
• ⁷Government Theni Medical College, Theni, India
• ⁸Meenakshi Academy of Higher Education and Research, Chennai, India
• ⁹Emory University Emory National Primate Research Center, Atlanta, United States
• ¹⁰University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience, Omaha, United States
• ¹¹Infection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu, Thiruvarur, India
• ¹²Universitetssjukhuset i Linkoping, Linköping, Sweden

Background: The global burden of latent tuberculosis infection (LTBI), with one-third of the population, poses a significant challenge in the diagnosis and treatment of TB. Household contacts (HHCs) of active TB-infected individuals are one of the major high-risk groups for whom early screening and timely intervention are highly critical to interrupt TB transmission. The subclinical latent infection transitions into active TB disease due to multiple factors. Laboratory diagnostic markers inherent to interferon-gamma release assay (IGRA) positive and negative HHCs may help predict the risk of LTBI and subsequent reactivation. The study aims to identify biochemical and hematological diagnostic markers associated with HHCs and their IGRA status. Methods: A cross-sectional study was carried out on the HHCs of active TB-infected individuals and healthy controls to determine the association of biochemical and hematological markers with their IGRA status. Blood samples collected from the participants were tested for different laboratory parameters and analyzed by binary regression analysis to determine their efficacy in predicting the development of LTBI. Results: Erythrocyte sedimentation rate (ESR), mean platelet volume (MPV), D-dimer, platelet-large cell ratio (P-LCR), and platelet distribution width (PDW) were significantly high among LTBI-positive individuals. Among different markers, significant association with LTBI was observed with ESR, PDW, and P-LCR, with their AUC and p values reported as 0.6950 (p=0.0095**), 0.7333 (p=0.0469*), 0.7150 (p=0.0042**), respectively. Binary regression analysis revealed significantly higher odds of LTBI in individuals with elevated ESR (OR = 3.05), PDW (OR = 4.67), MPV (OR = 3.5), and P-LCR (OR = 7.67). Conclusion: Our study demonstrated clinical laboratory parameters as useful surrogate markers of subclinical inflammation associated with LTBI.