Diagnostic accuracy of anti-mycobacterial protein 51 antibodies as a biomarker for latent TB infection in asymptomatic HIV positive individuals

Abstract

Background: Tuberculosis (TB) continues to be a major global public health concern more so in sub-Saharan Africa and Uganda in particular due to inaccessibility to accurate, rapid and reliable diagnostic methods on top of the increased TB drug resistance. Tuberculin Skin Test (TST) and Interferon Gamma Release Assay (IGRA) the currently available diagnostic methods for latent TB still have challenges in regards to low sensitivities and poor predictive values for progression to active disease. The main goal of this investigation was to evaluate the diagnostic utility of anti-MPT51 antibodies as a biomarker for latent TB among asymptomatic HIV positive individuals. Methods: This was a cross-sectional study. Blood was collected from asymptomatic HIV positive individuals and plasma was obtained from these blood samples. ELISA was done to assess anti MPT51 antibody positivity. To determine diagnostic performance of the anti- MPT51 antibodies versus IGRA, QuantiFERON-TB Gold Plus was performed on the same participants’ blood. Data was recorded in an excel sheet, then exported to SPSS and tables. A 2 by 2 table was used to calculate sensitivity, specificity, positive and negative predictive values of anti -MPT51 antibodies against QuantiFERON-TB Gold Plus at 95% confidence interval. The univariate and multivariate logistic regression analysis was used to determine factors associated with antibody positivity. Results: Considering QuantiFERON-TB Gold Plus as the gold standard, antibody reactivity to MPT51 revealed sensitivity of 32.6% (95% CI 24.5-40.6), specificity of 56.1% (95% CI 47.6-64.6), positive predictive value of 61.7% (95% CI 53.4-70.1) and negative predictive value of 27.7% (95% CI 20-35.4). Among the factors tested, none was independently associated with an increased risk of antibody reactivity against MPT51. Conclusion: These results indicate that antibody reactivity against MPT51 could be a marker for M. tb infection in HIV positive individuals prior to the development of disease. If validated by larger studies with prospectively collected samples, these findings could lead to the development of screening tests identifying those M. tb-infected HIV positive individuals that are at risk for developing disease, which in turn could lead to early therapeutic interventions.