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PATHOGEN-SPECIFIC EPITOPES AS EPIDEMIOLOGICAL TOOLS FOR DEFINING THE MAGNITUDE OF MYCOBACTERIUM LEPRAE TRANSMISSION IN AREAS ENDEMIC FOR LEPROSY
Author
Martins, Marcia V. S. B.
Guimarães, Marjorie M. da S.
Spencer, John S.
Hacker, Mariana A.V. B.
Costa, Luciana S.
Carvalho, Fernanda M.
Geluk, Annemieke
van der Ploeg-van Schip, Jolien J.
Pontes, Maria A. A.
Gonçalves, Heitor S.
Morais, Janvier P. de
Bandeira, Tereza J. P. G.
Pessolani, Maria C .V.
Brennan, Patrick J.
Pereira, Geraldo M. B.
Guimarães, Marjorie M. da S.
Spencer, John S.
Hacker, Mariana A.V. B.
Costa, Luciana S.
Carvalho, Fernanda M.
Geluk, Annemieke
van der Ploeg-van Schip, Jolien J.
Pontes, Maria A. A.
Gonçalves, Heitor S.
Morais, Janvier P. de
Bandeira, Tereza J. P. G.
Pessolani, Maria C .V.
Brennan, Patrick J.
Pereira, Geraldo M. B.
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, Colorado, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Curz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Laboratório de Informática Médica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, The Netherlands.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, The Netherlands.
Centro de Referência Dona Libania. Fortaleza, CE, Brasil.
Centro de Referência Dona Libania. Fortaleza, CE, Brasil.
SER V. Programa de Controle de Hanseníase. Fortaleza, CE, Brasil
LabPasteur Diagnostic Medicine / Diagnostics of America (DASA), Fortaleza, Brazil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, Colorado, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, Colorado, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Curz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Laboratório de Informática Médica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, The Netherlands.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, The Netherlands.
Centro de Referência Dona Libania. Fortaleza, CE, Brasil.
Centro de Referência Dona Libania. Fortaleza, CE, Brasil.
SER V. Programa de Controle de Hanseníase. Fortaleza, CE, Brasil
LabPasteur Diagnostic Medicine / Diagnostics of America (DASA), Fortaleza, Brazil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, Colorado, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil.
Abstract
During recent years, comparative genomic analysis has allowed the identification of Mycobacterium leprae-specific genes with potential application for the diagnosis of leprosy. In a previous study, 58 synthetic peptides derived from these sequences were tested for their ability to induce production of IFN-γ in PBMC from endemic controls (EC) with unknown exposure to M. leprae, household contacts of leprosy patients and patients, indicating the potential of these synthetic peptides for the diagnosis of sub- or preclinical forms of leprosy. In the present study, the patterns of IFN-γ release of the individuals exposed or non-exposed to M. leprae were compared using an Artificial Neural Network algorithm, and the most promising M. leprae peptides for the identification of exposed people were selected. This subset of M. leprae-specific peptides allowed the differentiation of groups of individuals from sites hyperendemic for leprosy versus those from areas with lower level detection rates. A progressive reduction in the IFN-γ levels in response to the peptides was seen when contacts of multibacillary (MB) patients were compared to other less exposed groups, suggesting a down modulation of IFN-γ production with an increase in bacillary load or exposure to M. leprae. The data generated indicate that an IFN-γ assay based on these peptides applied individually or as a pool can be used as a new tool for predicting the magnitude of M. leprae transmission in a given population.
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