Can treatment outcomes of latent TB infection and TB in silicosis be improved?

Occupational exposure to silica dust (respirable crystalline silica) leading to the development of silicosis still occurs in many parts of the world, including countries such as South Africa, Turkey, China and Sri Lanka. Immune dysfunction (or dysregulation), through involvement of host macrophages and lymphocytes alongside their elaborated cytokines, resulting in exaggerated humoral response and suppression of cell-mediated immunity, is believed to be important mechanisms of pathogenesis in this form of pneumoconiosis (1). Inflammation and fibrosis are well known pathological changes in the lungs of patients inflicted with silicosis, resulting in compromised respiratory function. Furthermore, these unfortunate patients are also at an increased risk of developing active pulmonary tuberculosis (TB), largely through endogenous reactivation of latent infection due to Mycobacterium tuberculosis (2), which is prevalent in many countries and geographical areas worldwide. Thus, TB in silicotic subjects poses an important challenge to global lung health. Preventive therapy for TB in patients with silicosis is beneficial. In a double-blind placebo-controlled clinical trial of 3 anti-TB regimens, namely isoniazid monotherapy, rifampicin monotherapy and combined therapy with isoniazid and rifampicin, the estimated proportions of patients with active pulmonary TB were about half of those who received placebo, 5% versus 9% at 2 years, 8% versus 15% at 3 years, 10% versus 20% at 4 years and 13% versus 27% at 5 years of study (3). However such results still appear somewhat inferior to the generally recognised efficacy of treatment of latent TB infection of about 60–90% (2). A short-course (3-month) chemoprophylaxis regimen comprising rifampicin, isoniazid and pyrazinamide in combination also has not been shown to effectively prevent the development of active TB in miners with silicosis, as revealed by the results of a randomised double-blind placebo controlled trial (4), although the study findings might have been confounded by a high risk of TB reinfection among gold mine workers that could have offset treatment protective effect, as also alluded to in another isoniazid preventive therapy trial (5). Several years ago, the use of 12 doses of weekly rifapentine and isoniazid has been shown to be as effective as 9 months of daily isoniazid for treating latent TB infection in a clinical trial (6). However, as the study did not clearly provide the number of included subjects with silicosis, it is not possible to firmly extrapolate that this short-course regimen comprising