Mind the gap - Managing tuberculosis across the disease spectrum

Abstract

We currently have a binomial approach to managing tuberculosis. Those with active disease, ideally confirmed microbiologically, are treated with a standard 6-month, multi-drug regimen and those with latent infection and no evidence of disease with shorter, one or two drug regimens. Clinicians frequently encounter patients that fall between these two management pathways with some but not all features of disease and this will occur more often with the increasing emphasis on chest X-ray-based systematic screening. The view of tuberculosis as a spectrum of disease states is being increasingly recognised and is leading to new diagnostic approaches for early disease. However, the 6-month regimen for treating disease was driven by the duration required to treat the most extensive forms of pulmonary TB and shorter durations appear sufficient for less extensive disease. It is time undertake clinical trials to better define the optimal treatment for tuberculosis across the disease spectrum.

Keywords: Diagnosis; Disease spectrum; Subclinical disease; Treatment; Tuberculosis.

Figure 1

Shows an overview of the current management pathways for active and latent TB highlighting a group of patients that do not easily fit into either treatment algorithm and management is variable and practitioner dependent. In low income settings patients often get a trial of antibiotics leading to over use of antibiotics but ultimately the options are to provide empirical therapy with the standard 6-month regimen (over-treatment) or observation which can lead to loss to follow-up. Abn = abnormal, CXR = chest X-Ray, M.tb = Mycobacterium tuberculosis. R = Rifampicin, H = Isoniazid, Z = Pyrazinamide, E = Ethambutol, P = Rifapentine, TST = Tuberculin Skin Test, IGRA = Interferon Gamma Release Assay

Figure 2

Shows the spectrum of disease from latent infection (determined by immune sensitization to Mtb) where Mtb is thought to be contained within granuloma though early stages of disease following Mtb escape resulting in infiltrative pathology and later stages resulting in more extensive tissue damage and cavitation in the context of pulmonary disease. The table the current diagnostic and treatment approaches across the spectrum. In blue future treatment strategies are outlined. LTBI = Latent tuberculosis infection, CXR = chest X-Ray. R = Rifampicin, H = Isoniazid, Z = Pyrazinamide, E = Ethambutol, P = Rifapentine, TST = Tuberculin Skin Test, IGRA = Interferon Gamma Release Assay.