Tuberculosis (TB) is the world's second deadliest infectious disease, overshadowed only byHIV/AIDS. A prompt, accurate diagnosis is required for effective control of TB, but in endemicregions, patient management is initially based upon clinical suspicion and low-sensitivity sputummicroscopy. Confirmatory culture testing is slow, costly, and not routinely available. There iscurrently a lack of early diagnostic tests, which, when combined with marginal clinical laboratoryinfrastructure, can result in the under- or over-diagnosis of TB. The former impacts successfulpatient outcomes and efforts to block secondary transmission, while the latter promotesunnecessary treatment and poor utilization of healthcare resources. The number of new TBcases diagnosed in the U.S. remains sizable, with a significant proportion of infections occurringin individuals who have limited access to health care, are foreign-born, and/or are HIV-infected.We have assembled a team of clinicians, TB experts, immunologists, and chemists to develop anew test for TB. Using surface-enhanced Raman spectroscopy (SERS) to significantly lower thelimit of detection, we propose the development of an inexpensive, rapid, and accurate point-of-care immunodiagnostic assay utilizing multiplexed monoclonal antibodies to concurrentlyidentify a panel of Mycobacterium tuberculosis target antigens that have been identified in bodyfluids during active infection. It is anticipated that a paired test to detect M. tuberculosis antigensin both serum and urine will significantly improve the overall sensitivity of antigen detection,redefining the way TB is managed. This approach is expected to provide the qualitative andquantitative data necessary for rapid, reliable diagnosis in a variety of settings, allowing theprompt accurate treatment of TB, as well as immediate infection control measures designed toavert transmission to others. The impact of the approach is amplified as the SERS platform canbe adapted to the diagnosis of other infectious diseases by changing the array of detectionantibodies.
Every year tuberculosis (TB) kills millions worldwide. Although early differential diagnosis is essential to arrest and reverse the onslaught of this deadly disease, it is lacking in many TB endemic areas due, in part, to poor diagnostic tests or inadequate infrastructure. Using surface- enhanced Raman spectroscopy to significantly lower the limit of detection, we propose the development of an inexpensive, rapid, and accurate point-of-care immunodiagnostic assay utilizing multiplexed monoclonal antibodies to identify a panel of Mycobacterium tuberculosis target antigens that have been identified in body fluids during active infection.
|Crawford, Alexis C; Skuratovsky, Aleksander; Porter, Marc D (2016) Sampling Error: Impact on the Quantitative Analysis of Nanoparticle-Based Surface-Enhanced Raman Scattering Immunoassays. Anal Chem 88:6515-22|