Tuberculosis (TB) is the world's second deadliest infectious disease, overshadowed only by HIV/AIDS. A prompt, accurate diagnosis is required for effective control of TB, but in endemic regions, patient management is initially based upon clinical suspicion and low-sensitivity sputum microscopy. Confirmatory culture testing is slow, costly, and not routinely available. There is currently a lack of early diagnostic tests, which, when combined with marginal clinical laboratory infrastructure, can result in the under- or over-diagnosis of TB. The former impacts successful patient outcomes and efforts to block secondary transmission, while the latter promotes unnecessary treatment and poor utilization of healthcare resources. The number of new TB cases diagnosed in the U.S. remains sizable, with a significant proportion of infections occurring in 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 a new test for TB. Using surface-enhanced Raman spectroscopy (SERS) 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 concurrently identify a panel of Mycobacterium tuberculosis target antigens that have been identified in body fluids during active infection. It is anticipated that a paired test to detect M. tuberculosis antigens in 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 and quantitative data necessary for rapid, reliable diagnosis in a variety of settings, allowing the prompt accurate treatment of TB, as well as immediate infection control measures designed to avert transmission to others. The impact of the approach is amplified as the SERS platform can be adapted to the diagnosis of other infectious diseases by changing the array of detection antibodies.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Demonstration--Cooperative Agreements (U18)
Project #
5U18FD004034-03
Application #
8535547
Study Section
Special Emphasis Panel (ZFD1-SRC (99))
Project Start
2010-09-17
Project End
2013-09-16
Budget Start
2012-09-17
Budget End
2013-09-16
Support Year
3
Fiscal Year
2012
Total Cost
Indirect Cost
Name
University of Utah
Department
Pathology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112