Columbia - predictive value of CFP-10

A study into 2060 household contacts (HHCs) in Colombia using TST, IGRA and culture;

The main goal of our study was to establish the value of IFNy responses to CFP-10 as prognostic marker of tuberculosis disease development...

Herein we present evidence that levels of IFNy response to CFP-10 assessed shortly after exposure to an infectious source may be predictive of tuberculosis development in a population of HHCs at high risk of infection...


...Taken together our results clearly demonstrate that HHCs are a population at high risk of infection and disease development and show a marked difference in the risk of tuberculosis development depending on the levels of IFNy production in response to CFP-10 shortly after exposure to M. tuberculosis. Since the identification of close contacts at highest risk of disease development is a highly desirable tool for more efficient tuberculosis control, the results presented herein constitute a remarkable step forward in the search for a biomarker of disease prognosis and open up the possibility of providing targeted IPT administration to child contacts based on IFNc production in response to CFP-10 antigen.

The researchers opted to use their own "in house" whole blood 7 day culture method for production and measurement of IFNy

It has been argued that, in settings of high endemicity where a mixture of recent and old infections are commonly found, long term assays are more sensitive than those with shorter culture times

Regardless of the method used, the authors note that this could be the first study to uphold the model proposed by Andersen et al ie that different levels of IFNy production correspond with the various stages of disease development;

We hypothesize that, instead of using IGRAs only in a binary mode (infected and not infected) based on a cut-off value, the magnitude or conversion of an IGRA response might enable the identification of individuals who, although still asymptomatic, are in the process of developing active TB.

Reflecting on the stages described in Andersen's model the Colombian researchers found that

The more detailed assessment of the evolution of IFNy levels produced by incident cases and non-incident HHCs in response to CFP and CFP-10 is in agreement with the model proposed by Andersen et al

All in all the researchers found that measurement of IFNy was of critical importance to TB control

Since the identification of close contacts at highest risk of disease development is a highly desirable tool for more efficient tuberculosis control, the results presented herein constitute a remarkable step forward in the search for a biomarker of disease prognosis and open up the possibility of providing targeted IPT administration to child contacts based on IFNy production in response to CFP-10 antigen.

Whilst the study was undertaken in a high prevalence TB country the researchers felt that the results were significant enough to approach the government for a variation to existing guidelines with regards to treating children;

However, according to the Colombian TB Control Program IPT can only be provided to children under 5 years of age with a >10 mm induration in the TST test, no BCG vaccination, conditions that were not met by any of this cohort’s children

...We consider that this finding underscores the need to focus on this population subgroup and strengthen contact tracing activities. Since this message was delivered by members of our group to health authorities in several occasions, Colombian health authorities decided to change the national health regulations to allow the provision of tuberculosis IPT to all child contacts less than 5 years of age regardless of vaccination status (statement issued by the Public Health Director of the Colombian Ministry of Social Protection).