What is tuberculosis?

Tuberculosis (TB) is an infectious disease caused by bacteria whose scientific name is

Mycobacterium tuberculosis. It was first isolated in 1882 by a German physician named Robert
Koch who received the Nobel Prize for this discovery. TB most commonly affects the lungs but
also can involve almost any organ of the body. Many years ago, this disease was referred to as
"consumption" because without effective treatment, these patients often would waste away.
Today, of course, tuberculosis usually can be treated successfully with antibiotics.

How does a person get TB?

A person can become infected with tuberculosis bacteria when he or she inhales minute particles
of infected sputum from the air. The bacteria get into the air when someone who has a
tuberculosis lung infection coughs, sneezes, shouts, or spits. People who are nearby can then
possibly breathe the bacteria into their lungs. You don't get TB by just touching the clothes or
shaking the hands of someone who is infected. Tuberculosis is spread (transmitted) primarily
from person to person by breathing infected air during close contact.

What happens to the body when a person gets TB?

When the inhaled tuberculosis bacteria enter the lungs, they can multiply and cause a local lung
infection (pneumonia). The local lymph nodes associated with the lungs may also become
involved with the infection and usually become enlarged. The hilar lymph nodes (the lymph
nodes adjacent to the heart in the central part of the chest) are often involved.

In addition, TB can spread to other parts of the body. The body's immune (defense) system,
however, can fight off the infection and stop the bacteria from spreading. The immune system
does so ultimately by forming scar tissue around the TB bacteria and isolating it from the rest of
the body. Tuberculosis that occurs after initial exposure to the bacteria is often referred to as
primary TB. If the body is able to form scar tissue (fibrosis) around the TB bacteria, then the
infection is contained in an inactive state. Such an individual typically has no symptoms and
cannot spread TB to other people. The scar tissue and lymph nodes may eventually harden, like
stone, due to the process of calcification of the scars (deposition of calcium from the bloodstream
in the scar tissue). These scars often appear on X-rays and imaging studies like round marbles
and are referred to as a granuloma. If these scars do not show any evidence of calcium on X-ray,
they can be difficult to distinguish from cancer.

Sometimes, however, the body's immune system becomes weakened, and the TB bacteria break
through the scar tissue and can cause active disease, referred to as reactivation tuberculosis or
secondary TB. For example, the immune system can be weakened by old age, the development
of another infection or a cancer, or certain medications such as cortisone, anticancer drugs, or
certain medications used to treat arthritis or inflammatory bowel disease. The breakthrough of
bacteria can result in a recurrence of the pneumonia and a spread of TB to other locations in the
body. The kidneys, bone, and lining of the brain and spinal cord (meninges) are the most
common sites affected by the spread of TB beyond the lungs.
What are the symptoms of tuberculosis?

It may take many months from the time the infection initially gets into the lungs until symptoms
develop. The usual symptoms that occur with an active TB infection are a generalized tiredness
or weakness, weight loss, fever, and night sweats. If the infection in the lung worsens, then
further symptoms can include coughing, chest pain, coughing up of sputum (material from the
lungs) and/or blood, and shortness of breath. If the infection spreads beyond the lungs, the
symptoms will depend upon the organs involved.

How does a doctor diagnose tuberculosis?

TB can be diagnosed in several different ways, including chest X-rays, analysis of sputum, and
skin tests. Sometimes, the chest X-rays can reveal evidence of active tuberculosis pneumonia.
Other times, the X-rays may show scarring (fibrosis) or hardening (calcification) in the lungs,
suggesting that the TB is contained and inactive. Examination of the sputum on a slide (smear)
under the microscope can show the presence of the tuberculosis-like bacteria. Bacteria of the
Mycobacterium family, including atypical mycobacteria, stain positive with special dyes and are
referred to as acid-fast bacteria (AFB). A sample of the sputum also is usually taken and grown
(cultured) in special incubators so that the tuberculosis bacteria can subsequently be identified as
tuberculosis or atypical tuberculosis.

Several types of skin tests are used to screen for TB infection. These so-called tuberculin skin
tests include the Tine test and the Mantoux test, also known as the PPD (purified protein
derivative) test. In each of these tests, a small amount of purified extract from dead tuberculosis
bacteria is injected under the skin. If a person is not infected with TB, then no reaction will occur
at the site of the injection (a negative skin test). If a person is infected with tuberculosis,
however, a raised and reddened area will occur around the site of the test injection. This reaction,
a positive skin test, occurs about 48-72 hours after the injection. When only the skin test is
positive, or evidence of prior TB is present on chest X-rays, the disease is referred to as "latent
tuberculosis." This contrasts with active TB as described above, under symptoms.

Remember, however, that the TB skin test cannot determine whether the disease is active or not.
This determination requires the chest X-rays and/or sputum analysis (smear and culture) in the
laboratory. The organism can take up to six weeks to grow in culture in the microbiology lab. A
special test to diagnose TB called the PCR (polymerase chain reaction) detects the genetic
material of the bacteria. This test is extremely sensitive (it detects minute amounts of the
bacteria) and specific (it detects only the TB bacteria). One can usually get results from the PCR
test within a few days.

Is there a vaccine against tuberculosis?

Bacille Calmette Guérin, also known as BCG, is a vaccine given throughout many parts of the
world. It is derived from an atypical Mycobacterium but offers some protection from developing
active tuberculosis, especially in infants and children. This vaccination is believed to be
important in parts of the world where TB is quite common. This is not the case in the United
States. When BCG has been administered, future PPD and Tine skin tests remain positive and
can cause some confusion when trying to diagnose TB. It is also important to realize that even
with a BCG vaccine in childhood, tuberculosis can still occur in an adult exposed to the
tuberculosis bacteria, which calls into question the real utility and effectiveness of this
vaccination.

A new blood test is now available that can help distinguish between a prior BCG vaccine and a
positive PPD due to TB infection. This test involves mixing the patient's blood with substances
that produce a TB-like immune response. After a period of time, the immune cells, if infected
with TB, produce interferon-gamma, a protein produced by the body to defend against an
infection. This test, like most, is not perfect, but with the proper clinical information can help
distinguish a real TB infection from a positive reaction on the test due to a prior BCG vaccine.

How is tuberculosis treated?

A person with a positive skin test, a normal chest X-ray, and no symptoms most likely has only a
few TB germs in an inactive state and is not contagious. Nevertheless, treatment with an
antibiotic may be recommended for this person to prevent the TB from turning into an active
infection. The antibiotic used for this purpose is called isoniazid (INH). If taken for six to 12
months, it will prevent the TB from becoming active in the future. In fact, if a person with a
positive skin test does not take INH, there is a 5%-10% lifelong risk that the TB will become
active.

Taking isoniazid can be inadvisable (contraindicated) during pregnancy or for those suffering
from alcoholism or liver disease. Also, isoniazid can have side effects. The side effects occur
infrequently, but a rash can develop, and the individual can feel tired or irritable. Liver damage
from isoniazid is a rare occurrence and typically reverses once the drug is stopped. Very rarely,
however, especially in older people, the liver damage (INH hepatitis) can even be fatal. It is
important therefore, for the doctor to monitor a patient's liver by periodically ordering blood tests
called "liver function tests" during the course of INH therapy. Another side effect of INH is a
decreased sensation in the extremities referred to as a peripheral neuropathy. This can be avoided
by taking vitamin B6 (pyridoxine), and this is often prescribed along with INH.

A person with a positive skin test along with an abnormal chest X-ray and sputum evidencing TB
bacteria has active TB and is contagious. As already mentioned, active TB usually is
accompanied by symptoms, such as a cough, fever, weight loss, and fatigue.

Active TB is treated with a combination of medications along with isoniazid. Rifampin

(Rifadin), ethambutol (Myambutol), and pyrazinamide are the drugs commonly used to treat
active TB in conjunction with isoniazid (INH). Four drugs are often taken for the first two
months of therapy to help kill any potentially resistant strains of bacteria. Then the number is
usually reduced to two drugs for the remainder of the treatment based on drug sensitivity testing
that is usually available by this time in the course. Streptomycin, a drug that is given by
injection, may be used as well, particularly when the disease is extensive and/or the patients do
not take their oral medications reliably (termed "poor compliance"). Treatment usually lasts for
many months and sometimes for years. Successful treatment of TB is dependent largely on the
compliance of the patient. Indeed, the failure of a patient to take the medications as prescribed is
the most important cause of failure to cure the TB infection. In some locations, the health
department demands direct monitoring of patient compliance with therapy.

Surgery on the lungs may be indicated to help cure TB when medication has failed, but in this
day and age, surgery for TB is unusual. Treatment with appropriate antibiotics will usually cure
the TB. Without treatment, however, tuberculosis can be a lethal infection. Therefore, early
diagnosis is important. Those individuals who have been exposed to a person with TB, or suspect
that they have been, should be examined by a doctor for signs of TB and screened with a TB skin
test.

What's in the future for TB?

Conceivably, TB could have been eliminated by effective treatment, vaccinations, and public-
health measures by the year 2000. However, the emergence of HIV changed the whole picture.
Because of HIV, a tremendous increase in the frequency (incidence) of TB occurred in the '80s
and throughout the '90s. This increase in TB happened because suppression of the body's
immune (defense) system by HIV allowed TB to occur as a so-called opportunistic infection.
With the increasing HIV epidemic in Africa, serious concerns are being raised about the
development of MDR-TB and XDR-TB in this population. Hopefully, control of HIV in the
future will check this resurgence of tuberculosis.

Tuberculosis At A Glance

 Tuberculosis (TB) is an infection, primarily in the lungs (a pneumonia), caused by bacteria called
Mycobacterium tuberculosis. It is spread usually from person to person by breathing infected air
during close contact.
 TB can remain in an inactive (dormant) state for years without causing symptoms or spreading
to other people.
 When the immune system of a patient with dormant TB is weakened, the TB can become active
(reactivate) and cause infection in the lungs or other parts of the body.
 The risk factors for acquiring TB include close-contact situations, alcohol and IV drug abuse, and
certain diseases (for example, diabetes, cancer, and HIV) and occupations (for example, health-
care workers).
 The most common symptoms of TB are fatigue, fever, weight loss, coughing, and night sweats.
 The diagnosis of TB involves skin tests, chest X-rays, sputum analysis (smear and culture), and
PCR tests to detect the genetic material of the causative bacteria.
 Inactive tuberculosis may be treated with an antibiotic, isoniazid (INH), to prevent the TB
infection from becoming active.
 Active TB is treated, usually successfully, with Isoniazid (INH) in combination with one or more
of several drugs, including rifampin, ethambutol, pyrazinamide, and streptomycin.
 Drug-resistant TB is a serious, as yet unsolved, public-health problem, especially in Southeast
Asia, the countries of the former Soviet Union, Africa, and in prison populations. Poor patient
compliance, lack of detection of resistant strains, and unavailable therapy are key reasons for
the development of drug-resistant TB.