Tuberculosis

Specialists

• Barer
• Carr
• Garton
• Haldar
• Mukamolova
• O’Hare
• Woltmann

Leicester has a large number of tuberculosis patients and so both the diagnosis, management and pathogenesis of TB are important priorities for the theme.

Highlights

Most UK tuberculosis (TB) cases occur in immigrants from high TB incidence areas, implicating reactivation of imported latent TB infection (LTBI). Strategies to identify and treat immigrant LTBI in primary care at the time of first registration (coded Flag-4) may be effective. We concluded that LTBI screening at primary care registration offers an effective strategy for potentially identifying immigrants at high risk of developing TB.

The effectiveness of primary care based risk stratification for targeted latent tuberculosis infection screening in recent immigrants to the UK: a retrospective cohort study. Panchal RK, Browne I, Monk P, Woltmann G, Haldar P. Thorax. 2014 Apr;69(4):354-62. doi: 10.1136/thoraxjnl-2013-203805.

The effectiveness of tuberculosis (TB) contact screening programmes using interferon γ release assays remains uncertain as prospective contact TB risk is not well characterised. Our objective was to quantify 2-year TB risk and evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT) in adult contacts. To compare TB risk between QFT tested subgroups stratified by exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB) and age (younger (16-35 years) versus older (≥36 years)). We concluded that QFT based single-step contact screening is effective in young adults.

Single-step QuantiFERON screening of adult contacts: a prospective cohort study of tuberculosis risk. Haldar P, Thuraisingam H, Patel H, Pereira N, Free RC, Entwisle J, Wiselka M, Hoskyns EW, Monk P, Barer MR, Woltmann G. Thorax. 2013 Mar;68(3):240-6. doi: 10.1136/thoraxjnl-2011-200956.

We are fortunate in having both a strong clinical group and a strong pathogenesis group. A collaboration between these two led to an important paper showing that smear-positive sputum samples are dominated by a population of Mtb cells that can be grown only in the presence of resuscitation promotion factors (Rpfs) which are therefore relevant to human infection. The Rpf-dependent population is invisible to conventional culture and is progressively enhanced in relative terms during chemotherapy, indicating a form of phenotypic resistance that may be significant for both chemotherapy and transmission.

Resuscitation-promoting factors reveal an occult population of tubercle Bacilli in Sputum. Mukamolova GV, Turapov O, Malkin J, Woltmann G, Barer MR.  Am J Respir Crit Care Med. 2010;181:174-180

We previously demonstrated that TB from sputum contains large numbers of lipid bodies which are associated with non-replicating and therefore antibiotic resistant bacteria. Identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis.

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. Garton NJ, Waddell SJ, Sherratt AL, Lee SM, Smith RJ, Senner C, Hinds J, Rajakumar K, Adegbola RA, Besra GS, Butcher PD, Barer MR. PLoS Med. 2008;5:e75. (IF 13.05)