Tuberculosis

1. Tuberculosis

2. Definition • Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Characteristic features include: • patient-to-patient airborne transmission, • a prolonged latency period between the initial infection and overt disease, • a granulomatous response associated with intense tissue inflammation and damage, • and prominent pulmonary disease, although many other organs can be involved as well.

3. The Pathogen • Mycobacteria are small, rod-shaped, aerobic bacilli. • The genus Mycobacterium contains a group of organisms so closely related that they are referred to as the “tuberculosis complex”: M. tuberculosis, M. bovis, M. canetti, M. africanum, and M. microti. • The term tuberculosis should be reserved exclusively for infection or disease caused by M. tuberculosis. Disease caused by other organisms of this genus should be referred to as “mycobacteriosis due to M. x” and not as “atypical tuberculosis”. • M. tuberculosis has become so adapted to the human body that it has no natural reservoirs in nature other than infected/diseased persons.

4. Mycobacterial cell walls contain high concentrations of lipids or waxes, which makes them resistant to standard staining techniques. They can be induced to take up a dye by imposing alkalinity or by heating. After dye absorption, they are resistant to the potent decolorizing agent acid-alcohol, a trait that provides the basis of the reference to acid-fast bacilli (AFB). M. tuberculosis and most of the other mycobacteria grow quite slowly; colonies typically do not appear on solid media for 2.5 to 5 week, so there has been great interest in rapid techniques

5. Epidemiology • The impact of TB on world health is significant; in 2006, there were an estimated 9.2 million new cases and 1.5 million deaths attributable to TB. • Furthermore, it is estimated that around one-third of the world's population has latent TB. • The majority of cases occur in the world's poorest nations, who struggle to cover the costs associated with management and control programmes. • The resurgence of TB has been largely driven in Africa by HIV disease. World-wide incidence of tuberculosis. Estimated new cases (all forms) per 100 000 population (WHO).

6. World TB incidence. Cases per 100.000; Red > 300orange = 300-200, yellow = 200-100, green100-50, blue < 50andgrey = n/a. Data from WHO, 2006

8. Transmission • Infection is spread almost exclusively by aerosolization of contaminated respiratory secretions. • Patients with cavitary lung disease are particularly infectious more than non cavitary lesions like miliary TB, because their sputum contains relatively greater numbers of bacilli and they cough frequently. • droplet are generated by high-velocity exhalational maneuvers like cough .These droplet nuclei are calculated to be 0.5 to 3 μm in diameter, may remain suspended in room air for many hours, and when inhaled, can traverse the airways to reach the alveoli. • For infection to occur, bacilli must be delivered to the distal air spaces of the lung (the alveoli), where they are not subject to mucociliary clearance

9. Droplets and lung involvement

10. Factors increasing the risk of TB Patient-related • Age (children > young adults < elderly) • First-generation immigrants from high-prevalence countries • Close contacts of patients with smear-positive pulmonary TB • Overcrowding (prisons, collective dormitories); homelessness • Chest radiographic evidence of self-healed TB • Primary infection < 1 year previously • Smoking: cigarettes and bidis Associated diseases • Immunosuppression: HIV, anti-TNF therapy, high-dose corticosteroids, cytotoxics • Malignancy (especially lymphoma and leukaemia) • Type 1 diabetes mellitus • Chronic renal failure • Silicosis • Gastrointestinal disease associated with malnutrition (gastrectomy, jejuno-ileal bypass, cancer of the pancreas, malabsorption) • Deficiency of vitamin D or A • Recent measles: increases risk of child contracting TB

11. Pathobiology • To initiate infection, the tubercle bacillus must be taken up by phagocytic cells within the alveoli. • When an alveolar macrophage engulfs a tubercle bacillus, it initially provides a nurturing environment within its phagosome in which the bacilli survive and replicate. • Indeed, part of the pathogenic strategy of the tubercle bacillus is the ability to prevent fusion of the phagosome with the lysosome. • However, the infected phagocytic cells release substances that attract a variety of immune effector cells, including peripheral blood monocyte-derived dendritic cells and T lymphocytes.

12. Through complex interactions involving mononuclear phagocytes and various T-cell subsets, host defenses are enhanced. This cell-mediated immunity is related to but not identical with delayed-type hypersensitivity. • Delayed-type hypersensitivity is associated with development of the tuberculin reaction, an indurated response 48 to 96 hours after the intradermal injection of tuberculosis protein antigens (e.g., purified protein derivative [PPD]). • Skin test reactivity typically appears 4 to 6 weeks after infection,

13. The recruited macrophages undergo transformation into epithelioid and Langhans cells which aggregate with the lymphocytes to form the classical tuberculousgranuloma. • Numerous granulomas aggregate to form a primary lesion or 'Ghon focus' (a pale yellow, caseous nodule, usually a few mm 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; the combination of a 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: so-called latent TB. If no further complications ensue, this lesion eventually calcifies and is clearly seen on a chest X-ray.

14. 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. • If these reparative processes fail, primary progressive disease ensues. • However, lymphatic or haematogenous spread may occur before immunity is established, seeding secondary foci in other organs including lymph nodes, serous membranes, meninges, bones, and lungs, which may lie dormant for years. • 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. Primary pulmonary TB. (1) Spread from the primary focus to hilar and mediastinal lymph glands to form the 'primary complex', which in most cases heals spontaneously. (2) Direct extension of the primary focus-'progressive pulmonary tuberculosis'. (3) Spread to the pleura-tuberculous pleurisy and pleural effusion. (4) Blood-borne spread: few bacilli-pulmonary, skeletal, renal, genitourinary infection often months or years later; massive spread-miliary tuberculosis and meningitis.