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Clinical and Vaccine Immunology, October 2008, p. 1590-1597, Vol. 15, No. 10
1071-412X/08/$08.00+0 doi:10.1128/CVI.00168-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Selection of Antigens and Development of Prototype Tests for Point-of-Care Leprosy Diagnosis
,
Malcolm S. Duthie,1*
Greg C. Ireton,1
Ganga V. Kanaujia,2
Wakako Goto,1
Hong Liang,1
Ajay Bhatia,1
Jean Marie Busceti,2
Murdo Macdonald,3
Kapil Dev Neupane,3
Chaman Ranjit,3
Bishwa Raj Sapkota,3
Marivic Balagon,4
Javan Esfandiari,2
Darrick Carter,1,5 and
Steven G. Reed1
Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104,1 ChemBio Diagnostic Systems Inc., 3661 Horseblock Road, Medford, New York 11763,2 Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal,3 Leonard Wood Memorial Center for Leprosy Research, Cebu City, Philippines,4 Protein AI, 1102 Columbia St., Seattle, Washington 981045
Received 13 May 2008/ Returned for modification 12 June 2008/ Accepted 8 August 2008
Leprosy can be a devastating chronic infection that causes nerve function impairment and associated disfigurement. Despite the recent reduction in the number of registered worldwide leprosy cases as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains relatively stable. The diagnosis of leprosy is currently based on the appearance of clinical signs and requires expert clinical, as well as labor-intensive and time-consuming laboratory or histological, evaluation. For the purpose of developing an effective, simple, rapid, and low-cost diagnostic alternative, we have analyzed the serologic antibody response to identify Mycobacterium leprae proteins that are recognized by leprosy patients. More than 100 recombinant antigens were analyzed in a protein array format to select those with discriminatory properties for leprosy diagnosis. As expected, multibacillary leprosy patients recognized more antigens with stronger antibody responses than paucibacillary leprosy patients. Our data indicate, however, that multibacillary patients can be distinguished from paucibacillary patients, and both of these groups can be segregated from endemic control groups. We went on to confirm the diagnostic properties of antigens ML0405 and ML2331 and the LID-1 fusion construct of these two proteins by enzyme-linked immunosorbent assay. We then demonstrated the performance of these antigens in rapid test formats with a goal of developing a point-of-care diagnostic test. A serological diagnostic test capable of identifying and allowing treatment of leprosy could reduce transmission, prevent functional disabilities and stigmatizing deformities, and facilitate leprosy eradication.
* Corresponding author. Mailing address: Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104. Phone: (206) 330-2517. Fax: (206) 381-3678. E-mail: mduthie{at}idri.org
Published ahead of print on 20 August 2008.
Supplemental material for this article may be found at http://cvi.asm.org/.
Clinical and Vaccine Immunology, October 2008, p. 1590-1597, Vol. 15, No. 10
1071-412X/08/$08.00+0 doi:10.1128/CVI.00168-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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