Evaluation of mycobacterium tuberculosis thymidylate kinase as diagnostic biomarker for pulmonary tuberculosis among HIV positive individuals at mjap- iss clinic.

Abstract

Background Tuberculosis (TB) is the leading cause of morbidity & mortality among HIV positive individuals. Diagnosis of TB in context of HIV co-infection remains challenging. Mycobacterium tuberculosis (M.tb) thymidylate kinase (TMKmt) has been validated as a novel biomarker with high detection limit for TB in sputum. This study was carried out to evaluate TMKmt as a diagnostic biomarker for pulmonary tuberculosis among HIV positive individuals at Makerere University Joint AIDS Program (MJAP) ISS clinic. Methods A total of 120 participants with presumptive pulmonary tuberculosis were enrolled in a cross sectional study at the MJAP ISS clinic between May and August 2018. Venous blood and expectorated spot sputum were obtained from 116 consenting participants. M.tb culture was performed on sputum as the gold standard to confirm TB status while direct ELISAs were performed on sputum and serum to determine the level of TMKmt antigen. TMKmt levels were analyzed using t test set at a significant level (P<0.05). Sensitivity and specificity and receiver operator characteristic curves were used to assess the precision of TMKmt in diagnosing PTB. Results Of the 116 participants, only 22 (19%) were TB positive based on either LJ or MGIT culture. The mean sputum TMKmt levels were significantly higher in TB positive individuals (4.889 ± 0.135) ng/ml as compared to TB negative individuals (4.303 ± 0.07295) ng/ml (t-test, P<0.0005). At a cut off value of > 4.683 ng/ml, the test had a sensitivity of 73% (95% CI, 49.78% - 89.27%) and a specificity of 72% (95% CI, 62.15% - 81.07%). These results were supported by a receiver operator analysis which showed an area under the curve (AUC) of 0.75 (95% CI, 0.63 – O.86). There was no significant difference in the mean serum TMKmt levels between TB negative and TB positive individuals. Conclusion Sputum TMKmt is a very good diagnostic biomarker for active pulmonary tuberculosis. This forms an alternate test to replace smear microscopy and overcome the current TB diagnostic challenges.