1.3 Evolution of TB infection and disease in humans

When a person inhales infectious droplets containing M. tuberculosis, most of the larger droplets become lodged in the upper respiratory tract (nose and throat), where infection is unlikely to develop. However, smaller droplet nuclei may reach the small air sacs of the lung (the alveoli), where infection may begin.

1.3.1 Primary infection

After transmission, M. tuberculosis multiplies slowly, in most cases in the terminal alveoli of the lungs (primary focus) and in the lymph nodes of corresponding drainage areas: this represents the primary infection. The primary focus and related hilar lymphadenopathy form the primary complex.

In one to two months, due to the action of lymphocytes and macrophages (cellular immunity), the primary focus will be contained and encapsulated with a central zone of parenchymal necrosis (caseous necrosis). It is at this moment that specific TB immunity appears, and a positive skin reaction to tuberculin is observed4,5. This stage is usually asymptomatic; however, in some rare cases, hypersensitivity reactions may occur.

Note: a small area of granulomatous inflammation will occur in the alveoli, which is not usually detectable on chest X-ray unless it calcifies or grows substantially. It is called a primary focus.

In the majority of cases (90 to 95% of non-HIV infected patients), the pulmonary lesions gradually heal. In 5 to 10% of the cases, the pulmonary lesion will progress to active disease either by gradual progression and/or spread via lymphatics or blood or by reactivation (often many years later) of primary or secondary lesions.

1.3.2 Active TB

Before immunity is established, bacilli from the primary infectious focus or from a near-by lymph node can be transported and disseminated throughout the body via the lymph system or the bloodstream. Secondary foci containing bacilli can be born this way, particularly in the lungs, lymph nodes, serous membranes, meninges, bones and kidneys. As soon as an immune response is mounted, most of these foci spontaneously resolve. Yet, a number of bacilli may remain latent in the secondary foci for months or even years6.

Different factors can reduce immunity (e.g. HIV infection) and lead to reactivation of the bacilli and their multiplication in one or more of these foci. This reactivation or progression of the primary or secondary foci results in “active TB disease”5.

While active TB may occur after months or years without clinical signs following primary infection, it is estimated that half of the cases of active TB appear in the year following infection.

1.3.3 Risk factors for developing active TB

The risk depends on a number of factors including those that lead to a weakened immune system, damaged lungs, or the intensity and duration of exposure:

Host immune defences:
– HIV infection (risk multiplied by 20-40);
– Diabetes mellitus (risk multiplied by 3-5);
– Malnutrition;
– Prolonged therapy with corticosteroids (such as prednisolone) and other immuno - suppressive therapies;
– Certain types of cancer (e.g., leukaemia, Hodgkin's lymphoma, or cancer of the head and neck);
– Severe kidney disease;
– Alcoholism;
– Substance abuse;
– Age:
• Young children (children under 5 have twice the risk and higher risks are observed for those under 6 months);
• Persons over sixty years have 5 times the risk;
– Pregnancy.

Conditions that damage the lung:
– Tobacco smoking;
– Silicosis.

Intensity of exposure (number of inhaled bacilli):
– Contagiousness of the source;
– Environment and proximity in which the exposure took place;
– Duration of exposure;
– Residents and employees of high-risk congregate setting.