Selection of antigens and development of prototype tests for point-of-care leprosy diagnosis.
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.
Duthie
Malcolm S
MS
Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104, USA. mduthie@idri.org
Ireton
Greg C
GC
Kanaujia
Ganga V
GV
Goto
Wakako
W
Liang
Hong
H
Bhatia
Ajay
A
Busceti
Jean Marie
JM
Macdonald
Murdo
M
Neupane
Kapil Dev
KD
Ranjit
Chaman
C
Sapkota
Bishwa Raj
BR
Balagon
Marivic
M
Esfandiari
Javan
J
Carter
Darrick
D
Reed
Steven G
SG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial; D005260:Female; D006801:Humans; D007918:Leprosy / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000302:isolation & purification*; D019095:Point-of-Care Systems; D011994:Recombinant Proteins
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D011994:Recombinant Proteins