title: Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis.
abstract: Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Torres
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico garcigarml@gmail.com.
authors.forename: Lourdes
authors.initials: L
authors.lastname: García-García
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cruz-Hervert
authors.affiliation: Dept of Medicine, Imperial College, London, UK.
authors.forename: Heinner
authors.initials: H
authors.lastname: Guio
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carranza
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Ferreyra-Reyes
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Canizales
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Susana
authors.initials: S
authors.lastname: Molina
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ferreira-Guerrero
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: Téllez
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Montero-Campos
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Delgado-Sánchez
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: Mongua-Rodriguez
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.
authors.forename: Jose
authors.initials: J
authors.lastname: Sifuentes-Osornio
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ponce-de Leon
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sada
authors.affiliation: Dept of Medicine, Imperial College, London, UK MRC National Institute for Medical Research, London, UK.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.affiliation: Dept of Medicine, Imperial College, London, UK MRC National Institute for Medical Research, London, UK Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D000860:Hypoxia; D007371:Interferon-gamma / Q000378:metabolism*; D007538:Isoniazid / Q000627:therapeutic use*; D055985:Latent Tuberculosis / Q000097:blood* / Q000382:microbiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010455:Peptides; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007538:Isoniazid