IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.

<h4>Objectives</h4>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-g...

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Main Authors: Helena del Corral, Sara C París, Nancy D Marín, Diana M Marín, Lucelly López, Hanna M Henao, Teresita Martínez, Liliana Villa, Luis F Barrera, Blanca L Ortiz, María E Ramírez, Carlos J Montes, María C Oquendo, Lisandra M Arango, Felipe Riaño, Carlos Aguirre, Alberto Bustamante, John T Belisle, Karen Dobos, Gloria I Mejía, Margarita R Giraldo, Patrick J Brennan, Jaime Robledo, María P Arbeláez, Carlos A Rojas, Luis F García
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-12-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008257&type=printable
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author Helena del Corral
Sara C París
Nancy D Marín
Diana M Marín
Lucelly López
Hanna M Henao
Teresita Martínez
Liliana Villa
Luis F Barrera
Blanca L Ortiz
María E Ramírez
Carlos J Montes
María C Oquendo
Lisandra M Arango
Felipe Riaño
Carlos Aguirre
Alberto Bustamante
John T Belisle
Karen Dobos
Gloria I Mejía
Margarita R Giraldo
Patrick J Brennan
Jaime Robledo
María P Arbeláez
Carlos A Rojas
Luis F García
author_facet Helena del Corral
Sara C París
Nancy D Marín
Diana M Marín
Lucelly López
Hanna M Henao
Teresita Martínez
Liliana Villa
Luis F Barrera
Blanca L Ortiz
María E Ramírez
Carlos J Montes
María C Oquendo
Lisandra M Arango
Felipe Riaño
Carlos Aguirre
Alberto Bustamante
John T Belisle
Karen Dobos
Gloria I Mejía
Margarita R Giraldo
Patrick J Brennan
Jaime Robledo
María P Arbeláez
Carlos A Rojas
Luis F García
author_sort Helena del Corral
collection DOAJ
description <h4>Objectives</h4>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 IFNgamma 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 IFNgamma levels in HHCs correlate with tuberculosis development.<h4>Methods</h4>A cohort of 2060 HHCs was followed for 2-3 years after exposure to a tuberculosis case. Besides TST, IFNgamma 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.<h4>Results</h4>Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNgamma 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 IFNgamma 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 IFNgamma producers was observed (trend Log rank p = 0.007).<h4>Discussion</h4>CFP-10-induced IFNgamma 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 chemoprophylaxis to child contacts regardless of BCG vaccination.
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publisher Public Library of Science (PLoS)
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spelling doaj-art-abaeb41dcb5045198904a0e591de07322025-08-20T02:01:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e825710.1371/journal.pone.0008257IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.Helena del CorralSara C ParísNancy D MarínDiana M MarínLucelly LópezHanna M HenaoTeresita MartínezLiliana VillaLuis F BarreraBlanca L OrtizMaría E RamírezCarlos J MontesMaría C OquendoLisandra M ArangoFelipe RiañoCarlos AguirreAlberto BustamanteJohn T BelisleKaren DobosGloria I MejíaMargarita R GiraldoPatrick J BrennanJaime RobledoMaría P ArbeláezCarlos A RojasLuis F García<h4>Objectives</h4>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 IFNgamma 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 IFNgamma levels in HHCs correlate with tuberculosis development.<h4>Methods</h4>A cohort of 2060 HHCs was followed for 2-3 years after exposure to a tuberculosis case. Besides TST, IFNgamma 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.<h4>Results</h4>Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNgamma 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 IFNgamma 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 IFNgamma producers was observed (trend Log rank p = 0.007).<h4>Discussion</h4>CFP-10-induced IFNgamma 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 chemoprophylaxis to child contacts regardless of BCG vaccination.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008257&type=printable
spellingShingle Helena del Corral
Sara C París
Nancy D Marín
Diana M Marín
Lucelly López
Hanna M Henao
Teresita Martínez
Liliana Villa
Luis F Barrera
Blanca L Ortiz
María E Ramírez
Carlos J Montes
María C Oquendo
Lisandra M Arango
Felipe Riaño
Carlos Aguirre
Alberto Bustamante
John T Belisle
Karen Dobos
Gloria I Mejía
Margarita R Giraldo
Patrick J Brennan
Jaime Robledo
María P Arbeláez
Carlos A Rojas
Luis F García
IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.
PLoS ONE
title IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.
title_full IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.
title_fullStr IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.
title_full_unstemmed IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.
title_short IFNgamma response to Mycobacterium tuberculosis, risk of infection and disease in household contacts of tuberculosis patients in Colombia.
title_sort ifngamma response to mycobacterium tuberculosis risk of infection and disease in household contacts of tuberculosis patients in colombia
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008257&type=printable
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