Tuberculosis

by Alexa Anderson

Etiological Agent

Mycobacterium tuberculosis. (6)

Discovery

The bacterium was isolated in 1882 by Robert Koch. (1)

General Characteristics

M. tuberculosis is a Gram resistant, non-motile bacillus coated in mycolic acid. It is an obligate aerobe and facultative intracellular pathogen of macrophages. It has a relatively long generation time of 12 – 18 hours. (6, 7)

Means of Transportation

The bacteria are carried by human hosts and transmitted through aerosol droplets. (2)

Usual Reservoirs

The bacteria multiply within its host and are found in the human body. (1)

Microbial Virulence Factors

Coat of mycolic acid inhibits phagocytosis. Pathogen-host interaction is still largely unknown, though it is hypothesized that tiny pili allow the bacteria to invade epithelial cells and macrophages.

The infection can be latent within the human host for many years before symptoms arise. (7)

Disease name

Tuberculosis. It gets its name because of the formation of tuber shaped damaged tissue in the lungs of its victims. It was also commonly called Consumption, a reference to the physical wasting away of its victims. (2)

Historical Information

Tuberculosis is one of the oldest human diseases. Egyptian mummies have been discovered that show tubercular decay; records indicate it was also common during the Greek and Roman empires. It is hypothesized that the cause of Tuberculosis, M. tuberculosis, mutated from M. bovis and began to infect humans when human began to settle into hunter-gatherer societies and drank the milk of domesticated bovines. Tuberculosis was the leading cause of death in the United States and Europe through the nineteenth century. With the introduction of antibiotics and improved living conditions, the disease rate dropped. With the outbreak of HIV in the 1980s, Tuberculosis disease began to rise again, and in 1993, the WHO declared it a global health emergency. Tuberculosis remains a leading cause of death in less developed countries. (5, 6)

Disease Mechanism

M. tuberculosis is taken up by alveolar macrophages where it is then taken to the lymph nodes and can spread through the bloodstream. Most infections are in the lungs. The inflammatory response causes the tuber-shaped tissue damage. (1)

Signs and Symptoms

·         Cough lasting three weeks or longer

·         Pain when breathing

·         Blood in sputum

·         Weakness and fatigue

·         Unexpected weight loss

·         Lack of appetite

·         Fever

Less commonly, the bacteria will infiltrate other organs and cause tissue damage resulting in the following signs and symptoms:

·         Back pain indicates (spinal infection)

·         Blood in urine (kidney infection)

·         Joint pain (bone infection)

·         Meningitis of the brain (brain infection)

·         Cardiac tamponade (heart infection) (3, 4)

Key Tests

Screening for tuberculosis is done by a Tuberculin skin test and/or tuberculosis blood tests. The Tuberculin skin test is done by delivering a dose of tuberculosis antigens into the skin and reading the immune response 48-72 hours later. A positive result is one where there is inflammation.  The blood test, interferon-gamma release assays (IGRA), measures the body’s response to M. tuberculosis.

Although it has the cell wall structure of a Gram positive bacterium, because of its coat of mycolic acid, M. tuberculosis will not Gram stain. The bacterium is identified using the acid-fast Ziehl-Neelson staining procedure. (1, 7)

Control and Treatment

The latent form of the infection is treated with an array of antibiotics that suppress the infection and inhibit growth of the bacteria. Once the infection has progress to a disease state, it is treated with a longer use of the same antibiotics. The treatment lasts six to nine months.

Failure to complete the intensive treatment fosters multi-drug resistant tuberculosis (MDR-TB) which requires two years of treatment. In 2006, an even rarer extensively drug resistant tuberculosis (XDR-TB) was discovered. (4, 6)

Incidence Figures

IT is estimated that one third of the world’s population is infected with M. tuberculosis, and 16.2 million have the disease. There are approximately 9 million new infections each year. There are approximately 3 million deaths each year, mostly consisting of children under five years and in underdeveloped countries. 3-4% of infections are MDR-TB. It is estimated that .006% of infections are XDR-TB. In the United States, the incidence rate has fallen from 16,000 in 2000 to 10,000 in 2011. (5)

Prevention

The only commonly used vaccine for tuberculosis is the Bacille Camette Geurin (BCG,) a live attenuated vaccine of M. bovis. It is used in countries where tuberculosis is rampant, and is primary protective of severe adolescent tuberculosis, not the adult pulmonary variety. BCG is not used in the United States. In recent years, this vaccine has lost is ability to prevent a global resurgence of tuberculosis.

Research is being conducted to better understand bacteria-host relationship to develop a more effective vaccine. Dr. Jacobs of the NIAID is currently running trials testing a severely attenuated live vaccine that initiates a fuller immune response. This vaccine has proven to protect against both adolescent and adult pulmonary tuberculosis at a higher rate than BCG. (1, 2)

References

1. Smith, Issar. “Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence” July 2003. http://cmr.asm.org/content/16/3/463.full#sec-4. May 3.

2. National Institute of Allergy and Infectious Diseases. “Tuberculosis” March 2013. http://www.niaid.nih.gov/topics/tuberculosis/Pages/Default.aspx. May 3.

3. National Institute of Health. “Tuberculosis” April 2013. http://www.nlm.nih.gov/medlineplus/tuberculosis.html#cat22. May 3.

4. Centers for Disease Control. “Tuberculosis” April 2013. www.cdc.com/tb/. May 3.

5. National Institute of Health. “Tuberculosis Fact Sheet” March 2013. http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=31. May 3.

6. MicrobiologyBytes. “Mycobacterium tuberculosis”. http://www.microbiologybytes.com/video/Mtuberculosis.html. May 3.

7. MicrobeWiki. “Mycobacterium tuberculosis” December 2012. http://microbewiki.kenyon.edu/index.php/Mycobacterium_tuberculosis. May 3