IFNγ Response to Mycobacterium tuberculosis, Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

Helena Del Corral,Jaime Robledo,Luis F García,Luis F Barrera,John T Belisle,Nancy D Marín,Patrick J Brennan,María C Oquendo,Lucelly López,Lisandra M Arango,Teresita Martínez,Felipe Riaño,Alberto Bustamante,Carlos Aguirre,Blanca L Ortíz ,Liliana Villa Vélez ,Hanna Marisol Henao ,Margarita Rosa Giraldo ,María Patricia Arbeláez ,Carlos Montes ,Sara París ,Carlos Rojas ,Karen M Dobos ,Martha E Ramírez ,Gloria Isabel Mejía ,Diana Marín

doi:10.1371/journal.pone.0008257

Abstract

ObjectivesHousehold 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.MethodsA 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.ResultsUsing 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).DiscussionCFP-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.

Highlights

IntroductionIn 2006, there were an estimated 9.2 million new cases of the disease and more than two billion people were expected to be infected with Mycobacterium tuberculosis [1]
Tuberculosis (TB) is still a major cause of illness and death worldwide
We present evidence that levels of IFNc response to culture filtrate protein (CFP)-10 assessed shortly after exposure to an infectious source may be predictive of tuberculosis development in a population of household contacts (HHCs) at high risk of infection

Summary

Introduction

In 2006, there were an estimated 9.2 million new cases of the disease and more than two billion people were expected to be infected with Mycobacterium tuberculosis [1]. In addition to providing supervised therapy to cases, new tools to prevent infection and reduce transmission are required to accelerate progress in TB control [3]. In countries with medium to high TB prevalence, where a large percentage of cases are due to recent transmission, household contacts (HHCs) of pulmonary TB cases are at high risk [4] and constitute an important target for early preventive alternatives in TB control [5]. There is a need of information coming from population based studies in disease endemic settings to revise such estimates under current epidemiological conditions

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