2.3 Development of tuberculosis disease

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Tuberculosis affects the human body in two main stages.

The first stage occurs when an individual is exposed to micro-organisms from a person with an infectious type of tuberculosis and becomes infected (tuberculous infection). Entry and establishment of bacilli in human body constitutes infection. It usually takes 6-8 weeks for the establishment and manifestation of infection. Infection is indicated by detection of release of interferon gamma by a positive reaction to a tuberculin skin test (Mantoux test) or Direct IGRA. Primary infection is an infection occurring for the first time in susceptible individuals who are exposed to tubercle bacilli. Droplet nuclei that are inhaled into the lungs, are so small (< 5μm) that they evade the muco-ciliary defenses of the bronchi and lodge in the terminal bronchiole or alveoli of the lungs. Subsequently, the bacilli multiply and invade the hilar lymph nodes through the lymphatics. The subpleural lung lesion, lymphangitis and hilar adenopathy together constitute a “primary complex”. In most cases, the host’s immune defenses overcome the primary infection, which generally passes unnoticed.

In the second stage, the person with tuberculous infection falls ill and manifests various symptoms and signs that indicates that s/he has developed the disease (tuberculosis disease). TB disease may occur after a latent period of many months or even years after the primary infection. Disease may occur either due to endogenous reactivation of dormant tubercle bacilli acquired from a primary infection or by exogenous re-infection. Post-primary TB disease usually affects the lungs but can involve any part of the body except nails and hair.

All those who get infected do not necessarily develop TB disease. If the body immune mechanism is not seriously compromised, approximately 90% of the infected cases will not develop tuberculosis disease; in this case the bacilli usually remain dormant within the body. The remaining 10% of infected individuals will subsequently develop disease, half of them within 1-2 years after infection, the other half later in their life.

As explained above, Tuberculosis usually affects the lungs (Pulmonary TB ) but can affect other sites as well (extra-pulmonary TB). When the tubercle bacilli enter the body of an individual but remain dormant without causing disease it is called a latent TB infection (LTBI). The life time risk of breaking down to disease among those infected with TB is 5–15%, which gets increased to 10% per year amongst those co-infected with HIV. Other determinants such as diabetes mellitus, smoking tobacco products, alcohol abuse and malnutrition also increase the risk of progression from infection to TB disease. A person is said to have tuberculous disease when s/he starts manifesting symptoms and signs. The disease is spread via air when people who are sick with pulmonary TB expel bacteria while coughing and sneezing.