Mechanism

Transmission

How is TB transmitted? 

TB is spread when TB-infected people with the active form of the illness cough, sneeze, laugh, shout etc. The bacteria are carried in the air in tiny droplets of liquid that are 1–5 microns in diameter. These tiny droplet nuclei remain suspended in the air for up to several hours.  

Transmission occurs when people who are uninfected inhale the droplets. Tuberculosis bacteria (Mycobacterium tuberculosis) however are transmitted through the air, not by surface contact, which means touching cannot spread the infection unless it is breathed in.

The form of TB caused by M. bovis also occurs in cattle and is spread to humans in meat and milk. It is estimated that there were about 800,000 deaths in the UK between 1850 and 1950 as a result of TB transmitted from cattle. However, very few now acquire TB in this way in developed countries. 

 

What determines the probability of transmission of Tuberculosis?

The factors that determine the probability of transmission of tuberculosis bacteria include:-

• If the person it is transmitted to is susceptible to the tuberculosis infection.
• If the person transmitting the infection is at the infectious stage of the disease.
• If the environment is suitable for transmission. Suitable environment means presence of more droplet nuclei, exposure to the infection in a small, closed and cramped space with poor ventilation and positive air pressure etc. Improper handling of laboratory specimen containing the bacteria is another reason for transmission.
• The length of exposure of the susceptible person to the person transmitting the infection. The longer the duration of exposure, proximity or closeness to the infected person, and frequency of exposure, the higher the risk of getting the infection.

Who is most likely to transmit Tuberculosis?

Patients with high loads of the bacteria in their expelled sputum are more likely to transmit the infection than those with low numbers of bacteria.

An individual who is infectious will have certain features. This includes presence of cough lasting three weeks or more, those with involvement of the larynx, those who fail to cover their mouth and nose while coughing or sneezing and those on inappropriate and inadequate treatment of the infection.

Young children with pulmonary and laryngeal tuberculosis are less likely than adults to be infectious because children generally do not produce sputum when they cough.

Persons who show presence of cavities in the lungs on X rays, have a positive culture for tuberculosis from their sputum and have a positive presence of the bacteria under the microscope after Ziehl-Neelsen stain are also infectious.

Pathogenesis

Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs, and travel to the alveoli.

Tubercle bacillus multiply in the alveoli.

A small number of tubercle bacilli enter the bloodstream and spread throughout the body. The tubercle bacilli may reach any part of the body, including areas where TB disease is more likely to develop (such as the brain, larynx, lymph node, lung, spine, bone, or kidney).

Within 2 to 8 weeks, special immune cells called macrophages ingest and surround the tubercle bacilli. The cells form a barrier shell, called a granuloma, that keeps the bacilli contained and under control (LTBI).

If the immune system cannot keep the tubercle bacilli under control, the bacilli begin to multiply rapidly (TB disease). This process can occur in different areas in the body, such as the lungs, kidneys, brain, or bone (see diagram in box 3).




   



Latent Tuberculosis Infection (LTBI)
People with LTBI have M. tuberculosis in their bodies, but do not have TB disease and cannot spread the infection to other people. A person with LTBI is not regarded as having a case of TB. The process of LTBI begins when extracellular bacilli are ingested by macrophages and presented to other white blood cells. This triggers the immune response in which white blood cells kill or encapsulate most of the bacilli, leading to the formation of a granuloma. At this point, LTBI has been established. 

TB Disease

In some people, the tubercle bacilli overcome the immune system and multiply, resulting in progression from LTBI to TB disease. People who have TB disease are usually infectious and may spread the bacteria to other people. The progression from LTBI to TB disease may occur at any time, from soon to many years later. 

Progression of TB

 
Without treatment, approximately 5% of persons who have been infected with M. tuberculosis will develop disease in the first year or 2 after infection, and another 5% will develop disease sometime later in life. Thus, without treatment, approximately 10% of persons with normal immune systems who are infected with M. tuberculosis will develop TB disease at some point in their lives.

Sites of TB Disease

TB disease can occur in pulmonary and extrapulmonary sites.

Pulmonary

TB disease most commonly affects the lungs; this is referred to as pulmonary TB. In 2011, 67% of TB cases in the United States were exclusively pulmonary. Patients with pulmonary TB usually have a cough and an abnormal chest radiograph, and may be infectious. Although the majority of TB cases are pulmonary, TB can occur in almost any anatomical site or as disseminated disease.

Extrapulmonary

Extrapulmonary TB disease occurs in places other than the lungs, including the larynx, the lymph nodes, the pleura, the brain, the kidneys, or the bones and joints. In HIV-infected persons, extrapulmonary TB disease is often accompanied by pulmonary TB. 
People with extrapulmonary TB disease usually are not infectious unless they have 

1. pulmonary disease in addition to extrapulmonary disease; 
2. extrapulmonary disease located in the oral cavity or the larynx; or 
3. extrapulmonary disease that includes an open abscess or lesion in which the concentration of organisms is high, especially if drainage from the abscess or lesion is extensive, or if drainage fluid is aerosolised. 

Those with TB pleural effusions may have underlying pulmonary TB that is masked on chest radiograph because the effusion fluid compresses the lung. These patients should be considered infectious until pulmonary TB disease is excluded.

Miliary TB

Miliary TB occurs when tubercle bacilli enter the bloodstream and disseminate to all parts of
the body, where they grow and cause disease in multiple sites. This condition is rare but serious. “Miliary” refers to the radiograph appearance of millet seeds scattered throughout the lung. It is most common in infants and children younger than 5 years of age, and in severely immunocompromised persons. Miliary TB may be detected in an individual organ, including the brain; in several organs; or throughout the whole body. The condition is characterized by a large amount of TB bacilli, although it may easily be missed, and is fatal if untreated. Up to 25% of patients with miliary TB may have meningeal involvement.

Central Nervous System

When TB occurs in the tissue surrounding the brain or spinal cord, it is called tuberculous meningitis. Tuberculous meningitis is often seen at the base of the brain on imaging studies. Symptoms include headache, decreased level of consciousness, and neck stiffness. The duration of illness before diagnosis is variable and relates in part to the presence or absence of other sites of involvement. In many cases, patients with meningitis have abnormalities on a chest radiograph consistent with old or current TB, and often have miliary TB.








Reference: 
1. http://www.news-medical.net/health/Tuberculosis-Transmission.aspx 
2. http://en.wikipedia.org/wiki/Tuberculosis#Transmission

3. (2013). Tuberculosis. In R. F. Mary Jones, Cambridge International AS and A level Biology Coursebook Third Edition (pp. 208-211). United Kingdom: Cambridge University Press.
4. http://www.cdc.gov/tb/education/corecurr/pdf/chapter2.pdf