Student Presentation on:

Mycobacterium tuberculosis
by Maleana Ozimek

Introduction
Mycobacterium tuberculosis has been present in the human population for thousands of years; fragments of the spinal column from Egyptian mummies from 2400 BCE show definite pathological signs of tubercular decay. Called "consumption," tuberculosis was recognized as the leading cause of mortality by 1650. Using a new staining technique, Robert Koch identified the bacterium responsible for causing consumption in 1882. While scientists finally had a target for fighting the disease, they did not have the means to treat patients; the spread of infection was controlled only by attempting to isolate patients. At the turn of the twentieth century, more than 80% of the population in the United States was infected before age 20, and tuberculosis was still the leading cause of death. The production of antibiotics in the 1940’s allowed physicians to begin effectively treating patients, leading to huge drops in the death rate of the disease. Tuberculosis is still a major cause of mortality in young adults worldwide, but is less of a problem in developed countries.

Microbiological characteristics
Mycobacterium tuberculosis is a nonmotile, acid-fast, obligate aerobe. The bacilli are 2-4 um in length and have a very slow generation time of between 15 and 20 hours. The cell wall of the mycobacterium is unique in that it is composed mainly of acidic waxes, specifically mycolic acids. M. tuberculosis is unusually resistant to drying and chemicals, contributing to the ease with which it is transmitted.

Encounter/Entry
Tuberculosis is transmitted by inhalation of aerosols containing the tubercle bacilli. The required inoculum size for infection is usually high, but easily occurs with exposure to a patient who is currently infected. The products of dried aerosols, droplet nuclei, are particularly infectious because they remain in the air for an extended time, and upon inhalation easily move to the alveoli. The severe damage related to infection is caused by the reaction of the host. The tuberculosis infection has two phases, primary and secondary.
Primary infection
Primary tuberculosis is the initial infection of the host, usually being mild and asymptomatic. A healthy person recently infected with the mycobacterium may exhibit flu-like symptoms and has no reason to suspect tuberculosis. Left untreated, the bacilli infect and multiply within pulmonary alveolar macrophages, migrating to the hilar lymph nodes. An immune response is exhibited by the T-helper cells, and inflammation develops at multiple sites. A person may test positive in the tuberculin skin test at this point, and a chest x-ray may shows opacities in the lungs. Tuberculosis gets its name from the small granulomas called tubercles, consisting of epitheliod cells, giant cells, and lymphocytes, where the bacteria are contained. In normal patients, the lesions in the lung tissue become fibrotic and heal, but are visible in x-rays for the patient's lifetime. During latency, a person cannot transmit tuberculosis to others.
Secondary disease
Those with weakened immune systems rapidly progress to secondary tuberculosis, while in a healthy, untreated patient, the disease usually remains latent for many years. In some people, the infection may never develop into tuberculosis disease. A frequent cough is the most prevalent sign of advancement to pulmonary tuberculosis disease. While the cough may initially be unproductive, increased inflammation and necrosis of lung tissue results in the production of a bloody sputum. While disease is usually limited to the lungs, M. tuberculosis can colonize most parts of the body. Infection of the spine may cause its collapse, leading to lifelong disability.


Diagnosis/Treatment
An initial diagnosis of tuberculosis is made by the tuberculin skin test (Mantoux test), where purified protein derivative (PPD) used as the antigen is injected intracutaneously into the forearm. The test is read within 48-72 hours, and is determined to be positive if a large, round, hardened bump develops at the injection site. False negatives may occur in persons with a severely compromised immune system, particularly AIDS. Following a positive test, more conclusive results are obtained through a chest x-ray, direct serum inspection, and growth in culture. Serum examination may not show the presence of bacteria, so colony growth is used as a definitive test. The problem with culturing the organism is its slow growth, and colonies may not be read as positive for 3-8 weeks. Drugs available to treat tuberculosis include isoniazid (INH), rifampin, streptomycin, and others. The course of treatment usually involves a combination of drugs, as the bacterium is increasingly antibiotic resistant. Treatment is prescribed for at least 6 months due to the slow growth and death rates of the bacterium. Following 2-3 weeks of therapy, a person is usually unable to transmit tuberculosis to others. Antibiotic resistance has become more prevalent as patients do not complete the entire course of treatment. A person is determined to be cured following three rounds of serum examination tests.

Prevention
Improving the standards of living, basic sanitary measures, and diagnostic techniques has proven to control the spread of tuberculosis. The key to reducing the spread of tuberculosis is early detection and proper treatment of infected individuals so that they will transmit it further. Simple measures such as restricting contact during the initial treatment stages can prevent transmission. Health care workers and emergency services personnel are provided with fitted HEPA filter masks if they are to come in contact with a patient suspected of having tuberculosis. In developing countries, controlling the spread of the disease is more difficult. Proper education on tuberculosis and how to prevent its spread are not as common, and once people are infected, they may not be able to afford the high cost of combined drug treatment. The Bacille Calmette-Guerin (BCG) vaccine is a vaccine made from a weakened mycobacterium that infects cattle. BCG does not necessarily prevent a tuberculosis infection, but reduces the severity of the pulmonary disease. The vaccine is used only in countries where tuberculosis is endemic, and is not used in the United States. When a person has been vaccinated with BCG, he/she will test positive using the tuberculin skin test. The positive result is a requirement for being determined successfully vaccinated.


Current News/Data
United States
The Center for Disease Control has data for the number of reported cases in the United States since 1981. While the number of cases reported dropped in the early 1980’s, it increased 20% between 1985 and 1992. The cause for the increase is attributed to a reduced awareness by the population and the explosion of HIV/AIDS cases. Among patients with AIDS, the incidence of tuberculosis is 500 times greater than in the general population. Tuberculosis progresses much more rapidly to the secondary stage, and death from severe systemic disease can occur within 4 weeks of a tuberculosis diagnosis. Responsible for the death of 1/3 of persons with HIV/AIDS, tuberculosis is listed as the leading cause of death for AIDS patients by the CDC. During 2002, 15,078 tuberculosis cases were reported to the CDC, a 5.7% decrease from 2001, with California having the highest number and rate of reported cases. The percentage of tuberculosis cases is much higher for foreign-born persons than US-born persons living in the United States. It is estimated that 10 to 15 million people in the U.S. are currently infected with latent tuberculosis. Without proper intervention, 10% of those infected will develop disease.

Worldwide
The World Health Organization declared tuberculosis to be a Global Emergency in 1993. Approximately 8 million new cases are reported each year, with 3 million people dying of the disease. Of the 1.7 billion people estimated to be infected with Mycobacterium tuberculosis, 1.3 billion live in developing countries. The global incidence rate of infection is growing by 0.4% a year, but is much higher in sub-Saharan Africa and countries of the former Soviet Union. The WHO has developed a program called DOTS (directly observed treatment short-course) in an attempt to increase adherence to the required treatment. People involved in the DOTS program meet with a health care worker several time a week to ensure they are taking their medication properly.

 

References
Todar’s Online Texbook of Bacteriology, http://www.textbookofbacteriology.net/tuberculosis.html
Mechanisms of Microbial Disease, 3rd Ed. Schaechter, M. 1999, Lippincott Williams & Wilkins.
http://www.umdnj.edu/~ntbcweb/history.htm

© 2003, J.Graf. Site made by Maleana Ozimek, for comments please contact Joerg.Graf@uconn.edu