Self-Study Modules on Tuberculosis
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Module 1: Transmission and Pathogenesis
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
|Study Question 1.1
1.1. In what year
was each of the following discoveries made?
- TB was proven to be contagious
- The bacteria that causes TB was discovered
- The first drug that could kill TB bacteria was discovered
TB is caused by an organism called Mycobacterium tuberculosis.
M. tuberculosis organisms are sometimes called tubercle
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?
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 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.
|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
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.
|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?
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.
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
- 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?
|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?
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.)
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.
|Study Questions 1.13-1.14
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?