IFN gamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia

ABSTRACT: Objectives: Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. Methods: A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Results: Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). Discussion: CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.

• Autores: Rojas Arbeláez, Carlos Alberto; Paris Ángel, Sara Claudia; Marín Agudelo, Nancy Dora; Marín Pineda, Diana Marcela; López López, Lucelly; Henao Vanegas, Hanna Marisol; Martínez, Teresita; Villa, Liliana; Ortiz Reyes, Blanca Lucía; Ramírez Agudelo, María Elena; Montes, Carlos J.; Oquendo, María Cecilia; Arango, Lisandra M.; Riaño, Felipe; Aguirre Muñoz, Carlos Arturo; Bustamante Gallego, Libardo Alberto; Belisle, John; Dobos, Karen; Mejía, Gloria Isabel; Giraldo, Margarita Rosa; Brennan, Patrick; Arbeláez Montoya, María Patricia; Del Corral Londoño, Helena; Robledo Restrepo, Jaime A.; García, Luis Fernando; Ortiz Reyes, Blanca Lucía; Barrera Robledo, Luis Fernando
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2009
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/45447
• Acceso en línea: https://hdl.handle.net/10495/45447
• Palabra clave: Tuberculosis Resistente a Múltiples Medicamentos; Tuberculosis, Multidrug-Resistant; Mycobacterium tuberculosis; Colombia; Tuberculosis; Antígenos Bacterianos - immunología; Antigens, Bacterial - immunology; Demografía; Demography; Composición Familiar; Family Characteristics; Interferón gamma - biosíntesis; Interferon-gamma - biosynthesis; Incidencia; Incidence; Valor Predictivo de las Pruebas; Predictive Value of Tests; Factores de Riesgo; Risk Factors; Prueba de Tuberculina; Tuberculin Test; https://id.nlm.nih.gov/mesh/D018088; https://id.nlm.nih.gov/mesh/D009169; https://id.nlm.nih.gov/mesh/D003105; https://id.nlm.nih.gov/mesh/D014376; https://id.nlm.nih.gov/mesh/D000942; https://id.nlm.nih.gov/mesh/D003710; https://id.nlm.nih.gov/mesh/D005191; https://id.nlm.nih.gov/mesh/D007371; https://id.nlm.nih.gov/mesh/D015994; https://id.nlm.nih.gov/mesh/D011237; https://id.nlm.nih.gov/mesh/D012307; https://id.nlm.nih.gov/mesh/D014374
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/