title: Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study.
abstract: Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ≥14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ≥14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, 95% CI 1.74-41.22; p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB.
authors.affiliation: Unité des Mycobactéries, Institut Pasteur de Madagascar, Antananarivo, Madagascar niaina@pasteur.mg.
authors.forename: Niaina
authors.identifier: http://orcid.org/0000-0002-2352-9797
authors.initials: N
authors.lastname: Rakotosamimanana
authors.affiliation: Unité d'Epidémiologie, Institut Pasteur de Madagascar, Antananarivo, Madagascar Unité d'Epidémiologie, Institut Pasteur de Dakar, Dakar, Sénégal.
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.affiliation: Unité d'Epidémiologie, Institut Pasteur de Dakar, Dakar, Sénégal.
authors.forename: Vaomalala
authors.initials: V
authors.lastname: Raharimanga
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur Paris, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.affiliation: Staten Serum Institut, Copenhagen, Denmark GlaxoSmithKline, Copenhagen, Denmark.
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.affiliation: Division of Infection and Immunity, University College London (UCL) and National Institute for Health Research Biomedical Research Centre, UCL Hospital, London, UK The University of Zambia-University College London Medical School (UNZA-UCLMS) Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.affiliation: Unité des Mycobactéries, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Voahangy
authors.initials: V
authors.lastname: Rasolofo Razanamparany
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001772:Blood Cell Count; D002648:Child; D002675:Child, Preschool; D016358:Contact Tracing; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes / Q000166:cytology; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009169:Mycobacterium tuberculosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012882:Skin Tests; D014373:Tuberculin / Q000737:chemistry; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000635:transmission*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014373:Tuberculin