Using QFT to monitor TB treatment

There has been some speculation that monitoring IFN-y levels during TB treatment can determine the efficacy of that treatment; whilst Markova et al found that

QFT Gold In tube assay could be used in routine clinical practice for monitoring anti-tuberculosis therapy

as did Katiyar et al

Our results suggest that QFT-G can potentially be used as a tool to monitor the efficacy of anti-tuberculosis treatment

Pollock et al disagreed;

To evaluate the utility of the QuantiFERON-TB Gold assay for monitoring latent tuberculosis treatment efficacy, the assay was performed serially for healthcare workers receiving isoniazid therapy. After 9 months of isoniazid therapy, all of these healthcare workers remained QuantiFERON-TB Gold positive, and cellular proliferation assays revealed persistently strong purified protein derivative responses. These results do not support the use of the QuantiFERON-TB Gold assay to monitor therapy.

It appears that Pollock accepts that the 9 months of isoniazid therapy is sufficient and the failure of changes to IFN-y levels was a failure of the diagnosis not the treatment. When monitoring treatment of QFT-G positive contacts with isoiazid Harada et al recording "waning" in all subjects

however a majority of contacts still showed positive responses in the QFT-G test even after chemotherapy

Recent studies into the growth patterns of TB mention that

slowly growing bacteria are non-responsive to treatment with isoniazid, one of the main antibiotics used to treat TB.

This is an important issue considering that improper treatment of TB can result in the development of drug resistant forms. Whilst INH therapy is accepted as proper treatment for LTBI there is no real way to test the efficacy of the INH and it is quite possible that those in the Pollock study remained infected with TB despite the medication. This issue has been considered by Cardona who asks

Why can a 9-month treatment with isoniazid eliminate dormant bacilli? As isoniazid is active only against growing bacilli, and thus is only able to destroy them after reactivation of latent bacilli, this treatment should have to be provided for life if the traditionally accepted postulate is correct.

It is important to note that both Markova and Katiyar were monitoring treatment of active TB whilst Harada and Pollock were monitoring treatment of latent TB. However it remains that Pollock may well be at fault in dismissing the results of QFT-G in monitoring treatment given that he had accepted the primary diagnosis by QFT-G. Current treatment guidelines often refer to the IUAT trial on the efficacy of isonaizid but it is important to note that the subjects for the study were selected as those with fibrotic pulmonary lesions compatible with tuberculosis (X ray), +6mm Mantoux induration (TST), no previous TB treatment, no history of positive diagnosis and whose sputum did not grow a culture.

In other words, current treatment regimes are based on studies of people who have already had active TB which had not been diagnosed and medically treated, not on healthy latent TB carriers.

It is feasible that QFT-G has a role in monitoring treatment for active TB and it is feasible that for some the current treatment of latent TB is inappropriate. Better treatment of TB is now a public health priority;

Considering the continued rise of multidrug-resistant TB,47 our results suggest that QFT-G may be useful in the early detection of likely non-responders, with broader implications for designing individualised treatment. (Katiyar)