In the highy acclaimed journal
Nature C E Barry et al
write that infection by MtB can
result in the formation of physiologically distinct granulomatous lesions that provide microenvironments with differential ability to support or suppress the persistence of viable bacteria.
This prompted a
response from Madhukar Pai
Barry and colleagues argue that Mycobacterium tuberculosis infection may be better viewed as a continuous spectrum, extending from sterilizing immunity to active infection and clinical disease1.
They suggest that treatment of M. tuberculosis infection might be most effective when targeted towards the part of the spectrum that corresponds to those individuals who are at the highest risk of progression to disease. These suggestions are reasonable, and literature on interferon-γ (IFNγ) release assays (IGRAs) adds some support to these arguments.
Pai noted that by studying levels of IFNγ four groups emerge;
- Persistently positive pattern is seen in individuals who are repeatedly interferon-γ release assay (IGRA)-positive for a long time.
- Unstable conversion refers to individuals who convert their IGRA result from negative to positive and then revert again to negativity.
- Stable conversion refers to individuals who convert their IGRA result and stay converted, at least in the short term.
- Persistently negative refers to individuals who stay repeatedly IGRA-negative for a long time.
Dr Pai suggests serial testing with IGRAs would help provide the data necessary to define those at greatest risk of progression and the most appropriate medical intervention.
Without serial testing, the underlying phenotypes are not separable, and this will undermine the predictive value of a single test result.
Barry et al
responded by saying
The strategy of serial IGRA testing as proposed by Pai is likely to be one element in progressing towards this goal, although broadening the range of cytokines beyond a reliance solely on interferon-γ may well be important.
Importantly, as Pai noted, TST is not a suitable alternative for such studies
Repeated tuberculin tests are rarely carried out because of the belief that, once positive, a TST is likely to remain positive and, therefore, not clinically useful; even when tests are repeated, the results are hard to interpret. Serial IGRA testing shows that IGRAs are highly dynamic, with high rates of conversions and reversions
