Tuberculosis and Other Mycobacterial Infections

Mycobacterium tuberculosis (MTB) is a thin, aerobic, non-spore forming, slow-growing (doubling time twelve hours) non-motile rod-shaped bacteria, belonging to the family Mycobacteriaceae. Mycobacterium tuberculosis complex is made up of several species, including M. tuberculosis, M. bovis, Bacillus Calmette-Guerin (BCG), M. africanum, M. canetii, M.caprae, M. microti, and others. Transmission is via inhalation of aerosolized respiratory secretions. After inhalation, majority of bacilli are captured in the upper respiratory tract by mucus and removed through a process called clearance, although bacteria in small droplets can reach the alveoli where the bacilli are ingested by macrophages. If clearance is not effective infection may result. With the involvement of CD4 lymphocytes, interferon-γ and tumour necrosis factor-α, a granuloma is formed, and bacilli may be destroyed. In many cases, the bacilli are not destroyed and can spread into lymphatics or via blood to other sites (any organs) where it can lie dormant for years. This asymptomatic situation is called latent TB infection (LTBI). It may reactivate in 10% of people throughout their lifetime; this increases with immunosuppression and HIV infection. The course of illness is chronic and indolent. However, rapid progression to fulminant disease may result if the host is immunocompromised. Pulmonary TB is the most common and important form of TB because it is the infectious form of the disease. In areas where reactivation predominates (like the UK), there is a higher proportion of extrapulmonary TB. Tuberculosis bacilli resist destaining with acid alcohol treatment hence the term. This retention is due to complexing of the carbolfuschin Ziehl-Neelsen stain with mycolic acids present in the waxy cell wall, including lipoarabinomannan (which facilitates survival in macrophages). Microscopy will diagnose TB in 80% of smear-positive patients with a first sputum sample, a further 15% with the second, and 5% with a third. In endemic areas finding acid-fast bacilli in sputum has a 98% specificity, but this is not the case in the UK, a low-prevalence setting, where atypical mycobacteria can have a similar prevalence. In the best settings only 60% of culture-positive patients are also sputum smear-positive as liquid culture, the gold standard, and most sensitive test.