Tiêu đề Tuberculosis.pdf ✅

588 • RESPIRATORY MEDICINE (p. 594). If these reparative processes fail, primary progressive disease ensues (Fig. 17.36). The estimated lifetime risk of developing disease after primary infection is 10%, with roughly half of this risk occurring in the first 2 years after infection. Factors predisposing to TB are summarised in Box 17.45 and the natural history of infection with TB is summarised in Box 17.46. Clinical features: pulmonary disease Primary pulmonary TB Primary TB refers to the infection of a previously uninfected (tuberculin-negative) individual. A few patients develop a self- limiting febrile illness but clinical disease occurs only if there is a hypersensitivity reaction or progressive infection (Box 17.47). Progressive primary disease may appear during the course of the initial illness or after a latent period of weeks or months. Miliary TB Blood-borne dissemination gives rise to miliary TB, which may present acutely but more frequently is characterised by 2–3 weeks of fever, night sweats, anorexia, weight loss and a Fig. 17.34 Worldwide incidence of tuberculosis (2014). Estimated new cases (all forms) per 100 000 population. From World Health Organisation. Global tuberculosis report, 20th edn. Geneva: WHO; 2015. 0–9.9 10–19 20–49 50–124 125–299 300–499 ≥500 No data Not applicable Fig. 17.35 Tuberculous granuloma. Normal lung tissue is lost and replaced by a mass of fibrous tissue with granulomatous inflammation characterised by large numbers of macrophages and multinucleate giant cells (white arrow). The central area of this focus shows caseous degeneration (black arrow). Courtesy of Dr William Wallace, Department of Pathology, Royal Infirmary of Edinburgh. Tuberculosis Epidemiology Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis (MTB), which is part of a complex of organisms including M. bovis (reservoir cattle) and M. africanum (reservoir humans). The resurgence in TB in the UK observed over the latter part of the last century has finally halted and notification of TB has fallen by around 1.5% per year since 2000. None the less, its impact on world health remains significant. An estimated 9.6 million new cases were recorded in 2014, with the majority presenting in the world’s poorest nations, which struggle to cover the costs associated with management and control programmes (Fig. 17.34). In the same year, 1.5 million men, women and children died of TB, and TB continues to rank alongside HIV as a leading cause of death worldwide. Pathology and pathogenesis M. bovis infection arises mainly drinking non-sterilised milk from infected cows. M. tuberculosis is spread by the inhalation of aerosolised droplet nuclei from other infected patients. Once inhaled, the organisms lodge in the alveoli and initiate the recruitment of macrophages and lymphocytes. Macrophages undergo transformation into epithelioid and Langhans cells, which aggregate with the lymphocytes to form the classical tuberculous granuloma (Fig. 17.35). Numerous granulomas aggregate to form a primary lesion or ‘Ghon focus’ (a pale yellow, caseous nodule, usually a few millimetres to 1–2 cm in diameter), which is characteristically situated in the periphery of the lung. Spread of organisms to the hilar lymph nodes is followed by a similar pathological reaction, and the combination of the primary lesion and regional lymph nodes is referred to as the ‘primary complex of Ranke’. Reparative processes encase the primary complex in a fibrous capsule, limiting the spread of bacilli. If no further complications ensue, this lesion eventually calcifies and is clearly seen on a chest X-ray. Lymphatic or haematogenous spread may occur before immunity is established, however, seeding secondary foci in other organs, including lymph nodes, serous membranes, meninges, bones, liver, kidneys and lungs, which may lie dormant for years. The only clue that infection has occurred may be the appearance of a cell-mediated, delayed-type hypersensitivity reaction to tuberculin, demonstrated by tuberculin skin testing or an interferon gamma release assay (IGRA): so-called latent TB