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Education Materials > Publications > Self-Study Modules on TB > Module 1 > Reading Material

Self-Study Modules on Tuberculosis

This is an archived document. The links are no longer being updated.

 

Module 1: Transmission and Pathogenesis

Reading Material

History of TB

Tuberculosis a disease also known as consumption, wasting disease, and the white plague has affected humans for centuries. Until the mid-1800s, people thought that tuberculosis, or TB, was hereditary. They did not realize that it could be spread from person to person through the air. Also, until the 1940s and 1950s, there was no cure for TB. For many people, a diagnosis of TB was a slow death sentence.

In 1865 a French surgeon, Jean-Antoine Villemin, proved that TB was contagious, and in 1882 a German scientist named Robert Koch discovered the bacteria that causes TB. Yet half a century passed before drugs were discovered that could cure TB. Until then, many people with TB were sent to sanatoriums, special rest homes where they followed a prescribed routine every day. No one knows whether sanatoriums really helped people with TB; even so, many people with TB could not afford to go to a sanatorium, and they died at home.

A breakthrough came in 1943. An American scientist, Selman Waksman, discovered a drug that could kill TB bacteria. Between 1943 and 1952, two more drugs were found. After these discoveries, many people with TB were cured, and the death rate for TB in the United States dropped dramatically. Each year, fewer and fewer people got TB.

By the mid-1970s, most TB sanatoriums in the United States had closed. In the next two decades, people began to hope that TB could be eliminated from the United States, like polio and smallpox.

Since the mid-1980s, however, TB cases have started increasing again. This rise in cases is attributed to several factors, which are discussed further in Module 2, Epidemiology of Tuberculosis. Because of the increase in TB, health departments and other organizations are stepping up their efforts to prevent and control the disease. Even today, TB can be fatal if not treated. A timeline of major events in the history of TB is shown in Figure 1.1.

Figure 1.1.  Timeline of major events in the history of TB.
 

Study Question 1.1

1.1. In what year was each of the following discoveries made?

  1. TB was proven to be contagious
  2. The bacteria that causes TB was discovered
  3. The first drug that could kill TB bacteria was discovered

Answers 

Transmission

TB is caused by an organism called Mycobacterium tuberculosis. M. tuberculosis organisms are sometimes called tubercle bacilli.

M. tuberculosis is a type of mycobacteria. Mycobacteria can cause a variety of diseases. Some mycobacteria are called tuberculous mycobacteria because they cause TB or diseases similar to TB. These mycobacteria are M. tuberculosis, M. bovis, and M. africanum. Other mycobacteria are called nontuberculous mycobacteria because they do not cause TB. One common type of nontuberculous mycobacteria is M. avium complex. Nontuberculous mycobacteria are NOT usually spread from person to person.

TB is spread from person to person through the air. When a person with infectious TB disease (TB that can be spread) coughs or sneezes, tiny particles containing M. tuberculosis may be expelled into the air. These particles, called droplet nuclei, are about 1 to 5 microns in diameter less than 1/5000 of an inch. Droplet nuclei can remain suspended in the air for several hours, depending on the environment.

If another person inhales air that contains these droplet nuclei, transmission may occur. Transmission is the spread of an organism, such as M. tuberculosis, from one person to another (Figure 1.2).

Figure 1.2. Transmission of TB. TB is spread from person to person through the air. The dots in the air represent droplet nuclei containing tubercle bacilli. (This is a figure of transmission of TB. TB is spread from person to person through the air.)

Not everyone who is exposed to an infectious TB patient becomes infected with M. tuberculosis. The probability that TB will be transmitted depends on three factors:

  • How contagious is the TB patient?
  • In what kind of environment did the exposure occur?
  • How long did the exposure last?

The transmission of TB is discussed in more detail in Module 5, Infectiousness and Infection Control.
 

Study Questions 1.2-1.3

1.2. What organism causes TB? What are two other tuberculous mycobacteria?

1.3. How is TB spread?

Answers 

Pathogenesis

When a person inhales air that contains droplets, most of the larger droplets become lodged in the upper respiratory tract (the nose and throat), where infection is unlikely to develop. However, the droplet nuclei may reach the small air sacs of the lung (the alveoli), where infection begins (Figure 1.3). The following section describes the pathogenesis of TB (the way TB infection and disease develop in the body).

Figure 1.3 The lungs and the alveoli. (This is a figure of the lungs and the alveoli.)

At first, the tubercle bacilli multiply in the alveoli and a small number enter the bloodstream and spread throughout the body. Bacilli may reach any part of the body, including areas where TB disease is more likely to develop. These areas include the upper portions of the lungs, as well as the kidneys, the brain, and bone. Within 2 to 10 weeks, however, the body's immune system usually intervenes, halting multiplication and preventing further spread. The immune system is the system of cells and tissues in the body that protect the body from foreign substances.

TB Infection

TB infection means that tubercle bacilli are in the body but the body's immune system is keeping the bacilli under control. The immune system does this by producing special immune cells that surround the tubercle bacilli. The cells form a hard shell that keeps the bacilli contained and under control.

TB infection is detected by the tuberculin skin test. Most people with TB infection have a positive reaction to the tuberculin skin test. The tuberculin skin test is discussed in more detail in Module 3, Diagnosis of Tuberculosis Infection and Disease.

People who have TB infection but not TB disease are NOT infectious in other words, they cannot spread the infection to other people. These people usually have a normal chest x-ray. It is important to remember that TB infection is not considered a case of TB. Major similarities and differences between TB infection and TB disease are shown in Table 1.1.
 

Table 1.1
TB Infection vs. TB Disease
TB Infection TB Disease (in the lungs)
Tubercle bacilli in the body
Tuberculin skin test reaction usually positive
Chest x-ray usually normal Sputum smears and cultures usually positive
Sputum smears and cultures negative Chest x-ray usually abnormal
No symptoms Symptoms such as cough, fever, weight loss

Not infectious

Often infectious before treatment
Not a case of TB A case of TB

 
Study Questions 1.4-1.8

1.4. When a person inhales air that contains droplets, where do the droplet nuclei go?

1.5. After the tubercle bacilli reach the small air sacs of the lung (the alveoli), where do they go?

1.6. In people with TB infection (but not TB disease), how does the immune system keep the tubercle bacilli under control?

1.7. How is TB infection detected?

1.8. What are the major similarities and differences between TB infection and TB disease? List characteristics of each.

Answers 


 
Case Study 1.1
A 30-year-old man visits the health department for a tuberculin skin test because he is required to have one before starting his new job. He has a positive reaction to the tuberculin skin test. He has no symptoms of TB, and his chest x-ray findings are normal.
  • Should this be considered a case of TB?
  • Should this man be considered infectious?

Answers 

TB Disease

Some people with TB infection develop TB disease. TB disease develops when the immune system cannot keep the tubercle bacilli under control and the bacilli begin to multiply rapidly. The risk that TB disease will develop is higher for some people than for others. The pathogenesis of TB infection and disease is shown in Figure 1.4.

TB disease can develop very soon after infection or many years after infection. In the United States, about 5% of the people who have recently been infected with M. tuberculosis will develop TB disease in the first year or two after infection. Another 5% will develop disease later in their lives. In other words, about 10% of all people who have TB infection will develop disease at some point. The remaining 90% will stay infected, but free of disease, for the rest of their lives (Figure 1.5).

Figure 1.4. Pathogenesis of TB infection and disease. (This is a series of figures depicting the pathogenesis of TB infection and TB disease.)

Figure 1.5.  Progression of TB. People who are exposed to TB may or may not develop TB infection. People with TB infection may or may not develop TB disease. The risk of developing TB disease is highest in the first 2 years after infection. This is a flow chart of the progression of TB.

Because about half the risk of developing TB disease is concentrated in the first 2 years after infection, it is important to detect new infection early. People with TB infection can be given treatment to prevent them from getting TB disease. (This is discussed in Module 4, Treatment of Tuberculosis Infection and Disease.) Thus, detecting new infection early helps prevent new cases of TB.
 

Table 1.2
Risk Factors for the Development of TB Disease
Risk Factor How Many Times Higher Is the Risk of TB Disease?1
Acquired immunodeficiency syndrome (AIDS) 170
HIV infection 113
Recent TB infection (within past 2 years) 15
Certain medical conditions2 3-16
  1. Compared to the risk for people with no known risk factors
  2. For example, diabetes, certain types of cancer, or immunosuppressive therapy

Some conditions appear to increase the risk that TB infection will progress to disease (Table 1.2). The risk may be about 3 times higher (as with diabetes) to more than 100 times higher (as with HIV infection) for people who have these conditions than for those who do not. Some of these conditions are

  • Infection with HIV, the virus that causes AIDS
  • Injection of illicit drugs
  • Recent TB infection (within the past 2 years)
  • Chest x-ray findings suggestive of previous TB
  • Diabetes mellitus
  • Silicosis
  • Prolonged therapy with corticosteroids
  • Immunosuppressive therapy
  • Certain types of cancer (e.g., leukemia, Hodgkin's disease, or cancer of the head and neck)
  • Severe kidney disease
  • Certain intestinal conditions
  • Low body weight (10% or more below ideal)

For definitions of these terms, please see the glossary or the New Terms section at the beginning of this module.

When the immune system is weakened, the body may not be able to control the multiplication and spread of tubercle bacilli. For this reason, people who are infected with both M. tuberculosis and HIV are much more likely to develop TB disease than people who are infected only with M. tuberculosis. Studies suggest that the risk of developing TB disease is 7% to 10% each year for people who are infected with both M. tuberculosis and HIV, whereas it is 10% over a lifetime for people infected only with M. tuberculosis.

Figure 1.6.  Risk of developing TB disease. 

Figure 1.6 shows the risk of developing TB disease for three different groups of people. For people with TB infection and no risk factors, the risk is about 10% over a lifetime. For people with TB infection and diabetes, the risk is 3 times as high, or about 30% over a lifetime. For people with TB infection and HIV infection, the risk is about 7% to 10% PER YEAR, a very high risk over a lifetime.

In an HIV-infected person, TB disease can develop in either of two ways. First, a person who has TB infection can become infected with HIV and then develop TB disease as the immune system is weakened. Second, a person who has HIV infection can become infected with M. tuberculosis and then rapidly develop TB disease.
 

Study Questions 1.9-1.12

1.9. What happens if the immune system cannot keep the tubercle bacilli under control and the bacilli begin to multiply rapidly?

1.10. What percentage of people who have TB infection (but not HIV infection) develop TB disease?

1.11. What conditions appear to increase the risk that TB infection will progress to disease?

1.12. How does being infected with both M. tuberculosis and HIV affect the risk for TB disease?

Answers 


 
Case Study 1.2

A 45-year-old woman is referred to the health department by her private physician because she was found to have TB infection. She is an obese woman who has high blood pressure and heart problems. Upon further questioning, she reports that she has injected illicit drugs in the past but has never been tested for HIV infection.

  • What conditions does this woman have that increase the risk that she will develop TB disease?

Answer 

Sites of TB Disease

TB disease can occur in different places in the body (Figure 1.7). Pulmonary TB is TB that occurs in the lungs. About 85% of TB cases are pulmonary. Most patients with pulmonary TB have a cough and an abnormal chest x-ray, and they should be considered infectious until they meet certain criteria (see Module 5, Infectiousness and Infection Control).

Extrapulmonary TB occurs in places other than the lungs, such as the larynx, the lymph nodes, the pleura (the membrane surrounding each lung), the brain, the kidneys, or the bones and joints. Extrapulmonary TB occurs more often in people who are infected with HIV than in people who are not infected with HIV. In HIV-infected people, extrapulmonary TB is often accompanied by pulmonary TB. Most types of extrapulmonary TB are not considered infectious (this will be discussed in Module 5, Infectiousness and Infection Control).

Miliary TB occurs when tubercle bacilli enter the bloodstream and are carried to all parts of the body, where they grow and cause disease in multiple sites. This condition, which is rare but serious, is called miliary TB because the chest x-ray has the appearance of millet seeds scattered throughout the lung.

Figure 1.7. Common sites of TB disease. (This is a graphic of the common sites of TB disease.)

Classification System

Many systems have been used to classify people who have TB. The current classification system (Table 1.3) is based on the pathogenesis of TB. Many health departments and private health care providers use this system when describing patients. Thus, it is important for public health workers to be familiar with this system. In particular, public health workers should be aware that any patient with a classification of 3 or 5 should be receiving treatment for TB, and the case or suspected case should be reported.
 

Table 1.3
Classification System for TB
Class Type Description
0 No exposure to TB

Not infected

No history of exposure, negative reaction to the tuberculin skin test
1 Exposure to TB

No evidence of infection

History of exposure, negative reaction to a tuberculin skin test given at least 10 weeks after exposure
2

TB infection

No TB disease

Positive reaction to the tuberculin skin test, negative smears and cultures (if done), no clinical or x-ray evidence of TB disease

3

Current TB disease

Positive culture for M. tuberculosis (if done), or

A positive reaction to the tuberculin skin test and clinical or x-ray evidence of current TB disease

4 Previous TB disease
(not current)
Medical history of TB disease, or

Abnormal but stable x-ray findings for a person who has a positive reaction to the tuberculin skin test, negative smears and cultures (if done), and no clinical or x-ray evidence of current TB disease

5 TB suspected Signs and symptoms of TB disease, but evaluation not complete

 
Study Questions 1.13-1.14

1.13. What site of the body is the most common site for TB disease? What are some other common sites?

1.14. What is the classification system for TB based on? What is it used for?

Answers

 


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination - http://www.cdc.gov/tb

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