Evaluation of novel diagnostic tests and strategies for the detection of tuberculosis.

摘要

Background: Tuberculosis (TB) remains a leading cause of death worldwide. A key obstacle for TB control is the lack of adequate tools for TB diagnosis. Evaluation of novel TB diagnostic strategies is a global priority. Promising approaches for rapid active TB diagnosis are the urinary liporabinommanan (LAM) assays and Xpert MTB/Rif, an automated molecular beacon platform. Interferon-gamma-release assays (IGRA) such as QuantiFERON-Gold-in-Tube (QFT-GIT) are an emerging alternative to tuberculin skin testing (TST) for detection of M. tuberculosis infection.;Methods: Prospective studies were conducted in South Africa and Uganda to evaluate diagnostic accuracy and dynamics of the urinary LAM assays, and to compare performance with Xpert MTB/Rif and conventional diagnostics. A cost-analysis was performed. Two studies evaluated optimal strategies for detection of M. tuberculosis infection. A prospective study compared TST to IGRAs among pediatric contacts of adult TB cases in SA; we analyzed the impact of IGRA implementation on latent TB diagnosis in Baltimore City and performed an economic evaluation.;Results: For detection of active TB: Urine LAM-ELISA and LF-LAM have improved sensitivity (50-61%) compared to sputum microscopy (42%). Combining urine LAM testing and sputum microscopy identifies 75% of active TB cases and was no different than Xpert MTB/Rif alone (77%). Performing Xpert MTB/Rif with urine LAM detection had improved sensitivity (87%) compared to either test alone and demonstrated additive yield (p<0.001). For detection of latent TB (LTBI): Usage of QFT-GIT led to higher estimates of M. tuberculosis infection in pediatric contacts than TST in South Africa. In Baltimore City, a low prevalence setting, usage of QFT-GIT reduced LTBI diagnosis by 30% and was highly cost-effective compared to reliance on TST.;Conclusions: Detection of TB remains challenging, but new tests may allow rapid diagnosis. Usage of IGRAs for LTBI detection may be helpful in specific target populations.