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

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.

Spectrum of latent tuberculosis — existing tests cannot resolve the underlying phenotypes

“…If yes, a second cut-off, higher than the diagnostic cut-off, could be used to identify the subgroup that can benefit from preventive therapy. This hypothesis has been proposed 16 and is supported by limited evidence 6 , but again a single test showing an elevated IFNγ response does not provide information on when the response became elevated (whether this was recently or in the past) or whether it has stayed elevated for a long time (whether it has been persistently elevated or not). In summary, current latent TB tests cannot resolve the latent TB spectrum, especially with one-time testing.…”

“…This is borne out by the sobering fact that IGRAs have been shown to have only a modest predictive ability, and several studies show similar (and rather low) rates of progression among individuals with positive TST and IGRA results [2][3][4][5][6] . For example, the incidence rate of active disease in TB contacts with positive IGRA results was 9.2 per 1000 person-years (PY) in the Gambia 2 , 20.5 per 1000 PY in Turkey 4 and 7.7 per 1000 PY in Colombia 6 . These data suggest that even among IGRA-positive exposed individuals in TB-endemic settings, the rates of disease progression are low.…”

Rendimiento de la prueba Xpert MTB/RIF en muestras respiratorias en un escenario real de trabajo de un país en desarrollo

“…The aim of this study was to assess the performance of the Xpert MTB/RIF® test for the diagnosis of pulmonary tuberculosis in respiratory samples compared with culture and its correlation with phenotypic susceptibility testing in "real" working conditions in a developing country hospital with high prevalence of the disease and limited resources (9).…”

Gender Differences in the Interpretation of Experiences of Patients with Tuberculosis in Medellín, Colombia

“…9 The study is supported on the theoretical foundation of the symbolic interactionism with the grounded theory research method. To obtain information, 12 semi-structured interviews were applied to patients belonging to the cohort who had completed the antifimic treatment.…”

“…The interviews made may have been intimidating due to the stigma represented by TB in society, leading to their only mentioning "socially acceptable" aspects. The study only included TB index cases individuals who were part of a cohort study, 9 leaving out other subjects with the disease. The fact of having participated in the family follow up during the study may have modified the gender approach of the disease.…”