Tuberculosis

Definition
Tuberculosis (TB) is a life-threatening infection that primarily affects the lungs. Every
year, tuberculosis kills nearly 2 million people worldwide. The infection is common
— about one-third of the human population is infected with TB, with one new
infection occurring every second.

Tuberculosis has plagued human beings for millennia. Signs of tubercular damage
have been found in Egyptian mummies and in bones dating back at least 5,000 years.
Today, despite advances in treatment, TB is a global pandemic, fueled by the spread
of HIV/AIDS, poverty, a lack of health services and the emergence of drug-resistant
strains of the bacterium that causes the disease.

Tuberculosis spreads through airborne droplets when a person with the infection
coughs, talks or sneezes. In general, you need prolonged exposure to an infected
person before becoming infected yourself. Even then, you may not develop symptoms
of the disease. Or, symptoms may not show up until many years later.

Left untreated, tuberculosis can be fatal. With proper care, however, most cases of
tuberculosis can be treated, even those resistant to the drugs commonly used against
the disease.

Symptoms
Although your body may harbor the TB bacteria, your immune system often can
prevent you from becoming sick. For that reason, doctors make a distinction between:

 TB infection. This condition, sometimes called latent TB, causes no

symptoms and isn't contagious.
 Active TB. This condition makes you sick and can spread to others. However,
the infection may be asymptomatic for years, even though it's active and
causing damage.

Your immune system begins to attack TB bacteria two to eight weeks after you're
infected. Sometimes the bacteria die, and the infection clears completely. In other
cases, the bacteria remain in your body in an inactive state and cause no tuberculosis
symptoms. In still other cases, you may develop active TB.

TB mainly affects your lungs (pulmonary tuberculosis), and coughing is often the
only indication of infection initially. Signs and symptoms of active pulmonary TB
include:

 A cough lasting three or more weeks that may produce discolored or bloody
sputum
 Unintended weight loss
  Fatigue
 Slight fever
 Night sweats
 Chills
 Loss of appetite
 Pain with breathing or coughing (pleurisy)

Tuberculosis also can target almost any part of your body, including your joints,
bones, urinary tract, central nervous system, muscles, bone marrow and lymphatic
system.

When TB occurs outside your lungs, signs and symptoms vary, depending on the
organs involved. For example, tuberculosis of the spine may result in back pain, and
tuberculosis that affects your kidneys might cause blood in your urine. Tuberculosis
can also spread through your entire body, simultaneously attacking many organ
systems.

Causes

Lungs

Mycobacterium tuberculosis, the bacterium that causes tuberculosis,spreads in

microscopic droplets that are released into the air when someone with the untreated,
active form of the disease coughs, speaks, laughs, sings or sneezes.

Although tuberculosis is contagious, it's not especially easy to catch. In general, you
need long-term contact with an infected person to become infected yourself. You're
much more likely to contract tuberculosis from a family member or close co-worker
than from a stranger on a bus or in a restaurant. A person with nonresistant active TB
who's been effectively treated for at least two weeks is generally no longer
contagious. Rarely, a pregnant woman with an active TB disease may pass the
bacteria to her fetus.

TB infection versus active TB

Although TB can affect other organs and tissues, it primarily attacks your lungs.
Approximately two to eight weeks after your lungs are infected with M. tuberculosis,
your immune system springs into action. Macrophages — specialized white blood
cells that ingest harmful organisms — begin to surround and "wall off" the
tuberculosis bacteria in your lungs, much like a scab forming over a wound. If the
macrophages are successful, the bacteria may remain within these walls for years —
alive, but in a dormant state. In this case, you're considered to have TB infection and
you'll test positive on the TB skin test, but you won't feel sick or have symptoms and
you can't transmit the disease to others.

But sometimes your immune defenses fail, even if you're otherwise healthy and don't
have a compromised immune system. In that case, TB bacteria actually begin to
exploit macrophages for their own survival, causing the white blood cells to form into
tightly packed groups called granulomas. The bacteria multiply inside the granulomas,
which eventually may enlarge into noncancerous tumor-like nodules. The centers of
these nodules have the consistency of soft, crumbly cheese.

Over time, the centers can liquefy and break through the granulomatous wall
surrounding them, spilling bacteria into your lungs' airways and causing large air
spaces (cavities) to form (active TB). Filled with oxygen, the air spaces make an ideal
breeding ground for the bacteria, which multiply in enormous numbers. The bacteria
may then spread from the cavities to the rest of your lungs as well as to other parts of
your body.

Active TB is contagious and serious

If you have active TB, you're likely to feel sick, although it's possible to have an
active infection in your lungs without having symptoms. But even if you don't feel
sick, if the disease is active you still can transmit it to others by coughing, sneezing or
talking.

Without treatment, many of the people with active TB die. Those who survive
develop chronic, debilitating symptoms, such as chest pain and a cough with bloody
sputum, or their immune system recovers and the disease goes into remission.

Sometimes active TB can develop years after the initial infection. This occurs when
your immune system can't keep dormant TB bacteria at bay, and the walled-off germs
become active. A number of factors can weaken your immune system, including
aging, drug or alcohol abuse, malnutrition, chemotherapy, prolonged use of
prescription medications such as corticosteroids, and diseases such as HIV/AIDS.
About one in 10 people who have TB infection goes on to develop active TB
sometime inhis or her life. The risk is greatest in the first year after infection, but the
disease may not resurface for decades.
Why is TB on the rise?
In the United States, cases of tuberculosis began declining steadily in the 1940s and
1950s mainly because of antibiotic therapy and improved public health programs. Yet
the disease is still a serious health problem. Millions of Americans are infected with
TB without having symptoms, and some of them will go on to develop active TB.

The situation in other countries is far worse. Overall, about one-third of the world's
population is infected with tuberculosis. New infections and deaths from the disease
are increasing. Hardest hit are sub-Saharan Africa and Southeast Asia. A number of
factors have contributed to the global TB crisis, but the leading cause is the spread of
HIV, the virus that causes AIDS. Tuberculosis and HIV have a deadly relationship —
each fuels the progress of the other.

Infection with HIV suppresses the immune system, making it difficult for the body to
control TB bacteria. As a result, people with HIV are many times more likely to
progress from dormant to active disease than are people who aren't HIV-positive.

TB is one of the leading causes of death among people living with AIDS — not only
because they're more susceptible to TB, but also because TB can increase the rate at
which the AIDS virus replicates. One of the first indications of HIV infection may be
the sudden onset of TB — often in a site outside the lungs (extrapulmonary TB).

Other factors contributing to the spread of TB in the United States and elsewhere
include:

 Crowded living conditions. TB spreads most easily in cramped, crowded, poorly ventilated
spaces. Incidence rates in prisons, juvenile detention centers and homeless shelters are
higher than that in the general population. TB bacteria also can flourish in nursing homes
because older adults often have immune systems weakened by illness or aging.
 Increased numbers of foreign-born nationals. Although TB rates for people born in the
United States are declining, the incidence among people from other parts of the world,
especially Africa, Asia and Latin America, is increasing. More than half of the reported TB
cases in the United States are in people born outside the country.
 Increased poverty and lack of access to medical care. The world's poor, in America and in
other countries, are more likely to have TB but the least likely to receive medical care. The
problem is compounded because people living in poverty and in unstable political situations
often move or migrate and therefore may not complete their treatment, leading to drug-
resistant forms of the disease.
 Increase in drug-resistant strains of TB. For each major TB medication,
there's a TB strain that resists its treatment. Even more dangerous are strains
that are resistant to at least two anti-TB drugs, leading to a condition called
multidrug-resistant TB (MDR-TB). People with untreated MDR-TB are highly
contagious and can transmit this serious type of TB to others.

Although MDR-TB can be successfully treated, it's much harder to combat

than regular TB and requires long-term therapy — up to two years — with
drugs that can cause serious side effects. MDR-TB bacteria can develop when
people don't complete their entire course of medication or fail to take their
medications as prescribed, when health care professionals prescribe the wrong
kinds of treatment, or when the drug supply is inconsistent — a particular
problem in impoverished or war-torn nations.
Risk factors
Anyone of any age, race or nationality can contract TB, but certain factors increase
your risk of the disease. These factors include:

 Lowered immunity. When your immune system is healthy, macrophages can

often successfully wall off TB bacteria, but your body can't mount an effective
defense if your resistance is low. A number of factors can weaken your
immune system. Having a disease that suppresses immunity, such as
HIV/AIDS, diabetes or the lung disease silicosis, and receiving treatment with
corticosteroids, arthritis medications or chemotherapy drugs can damage your
body's ability to protect itself.
 Close contact with someone with infectious TB. In general, you need to
spend an extended period of time with someone with untreated, active TB to
become infected yourself. You're most likely to catch the disease from a
family member, roommate, friend or close co-worker.
 Nationality. People from regions with high rates of TB — especially Africa,
Asia and Latin America, and in the case of MDR-TB, the former Soviet Union
— are more likely to develop TB.
 Age. Older adults are at greater risk of TB because normal aging or illness
may weaken their immune systems. They're also more likely to live in nursing
homes, where miniepidemics of TB can occur.
 Substance abuse. Long-term drug or alcohol use weakens your immune
system and makes you more vulnerable to TB.
 Malnutrition. A poor diet or one too low in calories puts you at greater risk of
TB.
 Lack of medical care. If you are on a low or fixed income, live in a remote
area, have recently immigrated to the United States, or are homeless, you may
lack access to the medical care you need to diagnose and treat TB.
 Living or working in a residential care facility. People who live or work in
prisons, immigration centers or nursing homes are all at risk of TB. That's
because the risk of the disease is higher anywhere there is overcrowding and
poor ventilation.
 Living in a refugee camp or shelter. Weakened by poor nutrition and ill
health and living in crowded, unsanitary conditions, refugees are at especially
high risk of TB infection.
 Health care work. Regular contact with people who are ill increases your
chances of exposure to TB bacteria. Wearing a mask and frequent hand
washing greatly reduce your risk.
 International travel. As people migrate and travel widely, they may expose
others or be exposed to TB bacteria.

When to seek medical advice

See your doctor immediately if you have a fever, unexplained weight loss, night
sweats and a persistent cough. These are often signs of TB, but they can also result
from other medical problems. Your doctor can perform tests to help determine the
cause. TB can be diagnosed by your primary care doctor as well as by a doctor who
specializes in lung diseases (pulmonologist) or by an infectious disease specialist. If
you don't have a doctor, your local public health department can help.

Even if you don't have signs or symptoms, experts advise being tested for TB if you:

 Have HIV. Everyone who is HIV-positive should have a skin test for TB soon
after a diagnosis of HIV. If you test positive for TB, you'll also need a chest
X-ray and other appropriate tests to make sure you don't have an active
infection. Because TB is especially dangerous for people with HIV/AIDS, see
your doctor immediately if you develop any respiratory symptoms such as
coughing, shortness of breath, or any other problems that might indicate TB
infection.
 Have close daily contact with someone who has contagious TB. This could
be a family member, friend or co-worker. In general, only pulmonary TB is
contagious.
 Work in a residential facility such as a prison or nursing home. Often,
people who work in hospitals, prisons, nursing homes or schools are required
to have TB tests.

Tests and diagnosis

The most commonly used diagnostic tool for TB is a simple skin test. Although there
are two methods, doctors consider the Mantoux test the more accurate.

For the Mantoux test, a small amount of a substance called PPD tuberculin is injected
within the skin of your inside forearm. You should feel only a slight needle prick.
Within 48 to 72 hours, a health care professional will check your arm for a local
reaction to the injected material. Depending on your response, the test is diagnosed as
positive or negative. A positive response — usually shown by a hard, raised bump at
the injection site — means you're likely to have TB infection.

The Mantoux test isn't perfect — it's possible to have either a false-positive or false-
negative test. A false-positive test suggests that you have TB when you really don't.
This is most likely to occur if you're infected with a mycobacterium other than the one
that causes TB or if you've ever been vaccinated with bacillus Calmette-Guerin, also
known as BCG, a TB vaccine that's seldom used in the United States, but widely used
in countries with high TB infection rates.

A blood test that detects the presence of TB bacteria has been approved by the Food
and Drug Administration. Called QuantiFERON-TB Gold (QFT) , results may be
available in as soon as one day. The test is not yet widely available, however.

Researchers in October 2006 also reported encouraging results from another test
under investigation for use primarily in developing countries. It's called the
microscopic-observation drug-susceptibility (MODS) assay and relies on sputum
samples to detect the presence of TB bacteria. MODS produces very accurate results
in as little as seven days. Additionally, the test can identify drug-resistant strains of
the TB bacteria.
Further testing
If the results of a TB test are positive, you may have further tests to help determine
whether you have active TB disease:

These tests may include:

 Chest X-ray. If you've had a positive skin test, your doctor is likely to order a
chest X-ray. In some cases, this may show white spots where your immune
system has walled off TB bacteria. In others, it may reveal a nodule or cavities
in your lungs caused by active TB.
 Culture tests. If your chest X-ray shows signs of TB or a urine sample
indicates infection, your doctor may take a sample of your stomach secretions
or sputum — the mucus that comes up when you cough. The samples are
tested for TB bacteria, and your doctor can have the results of special smears
in a matter of hours.

Although it takes longer, samples may also be sent to a laboratory where they're
examined under a microscope as well as placed on a special medium that encourages
the growth of bacteria (culture). The bacteria that appear are then tested to see if they
respond to the medications commonly used to treat TB. Your doctor uses the results
of the culture tests to prescribe the most effective medications for you.

What if my test is negative?

Having little or no reaction to the Mantoux test usually means that you're not infected
with TB bacteria. But in some cases it's possible to have TB infection in spite of a
negative test. Reasons for a false-negative test include:

 Recent TB infection. It can take eight to 10 weeks after you've been infected
for your body to react to a skin test. If your doctor suspects that you've been
tested too soon, you may need to repeat the test in a few months.
 Severely weakened immune system. If your immune system is compromised
by an illness, such as HIV, or by corticosteroid or chemotherapy drugs, you
may not respond to the Mantoux test, even though you're infected with TB.
Diagnosing TB in HIV-positive people is further complicated because many
symptoms of AIDS are similar to TB symptoms.
 Vaccination with a live virus. Vaccines that contain a live virus, such as the
measles or smallpox vaccine, can interfere with a TB skin test.
 Overwhelming TB disease. If your body has been overwhelmed with TB
bacteria, it may not be able to mount enough of a defense to respond to the
skin test.
 Improper testing. Sometimes the PPD tuberculin may be injected too deeply
below the surface of your skin. In that case, any reaction you have may not be
visible. Be sure that you're tested by someone skilled in administering TB
tests.

Diagnosing TB in children
It's harder to diagnose TB in children than in adults — they're far less likely than
adults to have signs and symptoms of the disease, even when they're quite sick.
Children also may swallow sputum, rather than coughing it out, making it harder to
take culture samples. And infants and young children may not react to the skin test.
For these reasons, tests from an adult who is likely to have been the cause of the
infection may be used to help diagnose TB in a child.

Diagnosing TB in people with HIV/AIDS

Diagnosing TB in HIV-positive people can be challenging, in part because signs and
symptoms of HIV/AIDS are often similar to those of TB. What's more, people with
HIV may not react to a standard TB skin test, and X-rays, sputum tests and other
exams may fail to show evidence of early TB infection.

Complications
Pulmonary TB can cause permanent lung damage when it's not diagnosed and
treated early. Untreated active disease can also spread to other parts of the body where
it can lead to serious or life-threatening complications. TB that infects the bone, for
example, can cause severe pain, abscesses and joint destruction.

Meningeal TB, which occurs when TB infects your brain and central nervous system,
and miliary TB, which occurs when TB bacteria spread throughout your entire body,
are particularly dangerous forms of the disease. Children are especially susceptible to
both meningeal TB and miliary TB.

Recurrence
The most serious complication, however, is the recurrence of TB after the initial
infection and the development of drug-resistant strains of the disease.

Treatments and drugs

Until the mid-20th century, people with tuberculosis were routinely cared for in
sanitariums — often for years — where the clear, cold air, abundant food and
enforced rest were believed to heal the lungs and halt the wasting that's characteristic
of the disease. Often, the treatment not only helped cure TB, but also prevented its
spread.

Today, medications are the cornerstone of tuberculosis treatment. The therapy is

lengthy. Normally, you take antibiotics for six to 12 months to completely destroy the
bacteria. The exact drugs and length of treatment depends on your age, overall health,
the results of susceptibility tests, and whether you have TB infection or active TB.

Treating TB infection
If tests show that you have TB infection but not active disease, your doctor may
recommend preventive drug therapy to destroy dormant bacteria that might become
active in the future. In that case, you're likely to receive a daily dose of the TB
medication isoniazid (INH). For treatment to be effective, you usually take INH for
six to nine months. Long-term use can cause side effects, including the life-
threatening liver disease hepatitis. For that reason, your doctor will monitor you
closely while you're taking INH. During treatment, avoid using acetaminophen
(Tylenol, others) and avoid or limit alcohol use. Both greatly increase your risk of
liver damage.
Treating active TB disease
If you're diagnosed with active TB, you're likely to begin taking four medications —
isoniazid, rifampin (Rifadin, Rimactane), ethambutol (Myambutol) and pyrazinamide.
This regimen may change if susceptibility tests later show some of these drugs to be
ineffective. Even so, you'll continue to take several medications. Depending on the
severity of your disease and whether there is drug resistance, one or two of the four
drugs may be stopped after a few months.

Sometimes the drugs may be combined in a single tablet such as Rifater, which
contains isoniazid, rifampin and pyrazinamide. This makes your therapy less
complicated while ensuring that you get the different drugs needed to completely
destroy TB bacteria.

Another drug that may make treatment easier is rifapentine (Priftin), which is taken
just once a week during the last four months of therapy. Sometimes you may be
hospitalized for the first two weeks of therapy or until tests show that you're no longer
contagious.

Completing treatment is essential

Because TB bacteria grow slowly, treatment for an active infection is lengthy —
usually six to 12 months. After a few weeks, you won't be contagious and may start to
feel better, but it's essential that you finish the full course of therapy and take the
medications exactly as prescribed by your doctor. Stopping treatment too soon or
skipping doses can create drug-resistant strains of the disease that are much more
dangerous and difficult to treat. Drug-resistant strains that aren't treated can quickly
become fatal, especially in people with impaired immune systems.

In an effort to help people stick with their treatment regimen, some doctors and clinics
use a program called directly observed therapy short-course (DOTS). In this
approach, a nurse or other health care professional administers your medication so
that you don't have to remember to take it on your own.

Treatment side effects

Side effects of TB drugs aren't common, but can be serious when they do occur. All
TB medications can be highly toxic to your liver. Rifampin can also cause severe flu-
like signs and symptoms — fever, chills, muscle pain, nausea and vomiting. When
taking these medications, call your doctor immediately if you experience any of the
following:

 Nausea or vomiting
 Loss of appetite
 A yellow color to your skin (jaundice)
 A fever lasting three or more days that has no obvious cause, such as a cold or
the flu
 Tenderness or soreness in your abdomen
 Blurred vision or colorblindness

Treating drug-resistant TB
Multidrug-resistant TB (MDR-TB) is any strain of TB that can't be treated by the two
most powerful TB drugs, isoniazid and rifampin. Extensive drug-resistant TB (XDR-
TB) is a newly developed strain of TB that's resistant to the same treatments that
MDR-TB is, and additionally XDR-TB is resistant to three or more of the second-line
TB drugs.

Both strains develop as a result of partial or incomplete treatment — either because

people skip doses or don't finish their entire course of medication or because they're
given the wrong treatment regimen. This gives bacteria time to undergo mutations
that can resist treatment with first-line TB drugs.

MDR-TB can be treated. But it requires at least two years of therapy with second-line
medications that can be highly toxic. Even with treatment, many people with MDR-
TB may not survive. And when treatment is successful, people with this form of TB
may need surgery to remove areas of persistent infection or repair lung damage.

Treating these resistant forms of TB is far more costly than treating nonresistant TB,
making therapy unaffordable in many parts of the world.

Because these resistant infections are spreading and could potentially make all TB
incurable, some experts believe that ineffective treatment is ultimately worse than no
treatment at all.

Treating people who have HIV/AIDS

Treating people who are co-infected with TB and HIV is a particular challenge. HIV-
positive people are especially likely to develop MDR-TB and to rapidly progress from
latent to active infection. What's more, the most powerful AIDS drugs — protease
inhibitors — interact with rifampin and other drugs used to treat TB, reducing the
effectiveness of both types of medications.

To avoid interactions, people living with both HIV and TB may stop taking protease
inhibitors while they complete a short course of TB therapy that includes rifampin. Or
they may be treated with a TB regimen in which rifampin is replaced with another
drug that's less likely to interfere with AIDS medications. In such cases, doctors
carefully monitor the response to therapy, and the duration and type of regimen may
change over time.

Without treatment, most people living with both HIV and TB will die, often in a
matter of months. In such cases, the primary cause of death is TB, not AIDS.

Prevention
In general, TB is a preventable disease. From a public health standpoint, the best way
to control TB is to diagnose and treat people with TB infection before they develop
active disease and to take careful precautions with people hospitalized with TB. But
there are also measures you can take on your own to help protect yourself and others:

 Keep your immune system healthy. Make sure you eat plenty of healthy
foods, get adequate amounts of sleep and exercise regularly to keep your
immune system in top form.
  Get tested regularly. Experts advise getting a skin test annually if you have
HIV or another disease that weakens your immune system, live or work in a
prison or nursing home, are a health care worker, or have a substantially
increased risk of exposure to the disease.
 Consider preventive therapy. If you test positive for latent TB infection, but
have no evidence of active TB, talk to your doctor about therapy with
isoniazid to reduce your risk of developing active TB in the future. A vaccine,
BCG, is available and has been of some benefit in preventing TB. It's not
widely used in the United States and is more often administered in countries
where TB is more common. The vaccine isn't very effective in adults,
although it can prevent TB from spreading outside the lungs in infants.
Vaccination with BCG also causes a false-positive result on a Mantoux skin
test and for that reason, isn't recommended for general use in the United
States. Researchers are working on developing a more effective TB vaccine.
 Finish your entire course of medication. This is the most important step you
can take to protect yourself and others from TB. When you stop treatment
early or skip doses, TB bacteria have a chance to develop mutations that are
resistant to the most potent TB drugs. The resulting drug-resistant strains are
much more deadly and difficult to treat.

To help keep your family and friends from getting sick if you have active TB:

 Stay home. Don't go to work or school or sleep in a room with other people
during the first few weeks of treatment for active TB.
 Ensure adequate ventilation. Open the windows whenever possible to let in
fresh air.
 Cover your mouth. It takes two to three weeks of treatment before you're no
longer contagious. During that time, be sure to cover your mouth with a tissue
any time you laugh, sneeze or cough. Put the dirty tissue in a bag, seal it and
throw it away. Also, wearing a mask when you're around other people during
the first three weeks of treatment may help lessen the risk of transmission.

Coping and support

Undergoing treatment for TB for a long period of time can be complicated, yet
sticking with therapy is the only way to cure the disease. You may find it helpful to
have your medication administered by a nurse or other health care professional so that
you don't have to remember to take it on your own. In addition, try to maintain your
normal activities and hobbies and stay connected with family and friends.

Keep in mind that your physical health can directly impact your mental health.
Denial, anger and frustration are not uncommon when you learn life has dealt you
something difficult and unexpected. At times, you may need more tools to deal with
these or other emotions. Professionals, such as therapists or behavioral psychologists,
may help you put things in perspective.