The overall objective of this application is to develop a specific and simple diagnostic test to identify individuals infected with Mycobacterium leprae and therefore sources of continuing new case detection, enabling rational chemoprophylaxis of leprosy leading not only to decrease in infectious burden but in reductions in nerve damage and disabilities. We hypothesize that such a diagnostic test can be achieved by measuring the immunologic response patterns to specific M. leprae antigens in peripheral blood samples from patients and contacts.
The specific aims of this proposal are to: 1) develop a specific and simple first generation diagnostic test using advanced bioinformatics to identify M. leprae-specific peptides predicted to bind to 11 major HLA-DR alleles and to activate T-cell release of IFN-, to be incorporated into the QuantiFERON(R) platform;2) To identify novel M. leprae antigens, including glycoproteins and lipoglycoproteins, that trigger innate and acquired immune responses during infection;and, 3) to develop an advanced integrated microfluidics-based portable diagnostic test to simultaneously measure multiple immunologic parameters providing enhanced specificity, sensitivity, and, perhaps, predictions of disease. The proposed experimental strategy will ensure development of a portable, state-of-the-art diagnostic test to detect M. leprae infection, identify sources of continuing new cases but also a new technology platform that can be readily adapted to implementation in leprosy endemic areas and to other neglected tropical infectious diseases. H Leprosy continues as a major health and economic burden in developing countries. We propose to develop a microfluidics-based portable diagnostic test to allow diagnosis of infection and sources of continuing transmission, allowing informed chemoprophylaxis and thereby further reduction in the global leprosy burden including disease complications including permanent damage to the skin, nerves, limbs and eyes.

Public Health Relevance

TO PUBLIC HEALTH Leprosy continues as a major health and economic burden in developing countries. We propose to develop a microfluidics-based portable diagnostic test to allow diagnosis of infection and sources of continuing transmission, allowing informed chemoprophylaxis and thereby further reduction in the global leprosy burden including disease complications including permanent damage to the skin, nerves, limbs and eyes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI082575-04
Application #
8316325
Study Section
Special Emphasis Panel (ZAI1-GSM-M (J2))
Program Officer
Jacobs, Gail G
Project Start
2009-09-28
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$336,175
Indirect Cost
$60,987
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kim, Hee Jin; Prithiviraj, Kalyani; Groathouse, Nathan et al. (2013) Gene expression profile and immunological evaluation of unique hypothetical unknown proteins of Mycobacterium leprae by using quantitative real-time PCR. Clin Vaccine Immunol 20:181-90
Geluk, Annemieke; Bobosha, Kidist; van der Ploeg-van Schip, Jolien J et al. (2012) New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy. J Immunol 188:4782-91