Tuberculosis (TB)

In the first few weeks of the infection, some bacteria may travel from the lungs to nearby lymph nodes. These lymph nodes are located just outside the lungs, where the bronchial tubes enter the lungs. In most people, the infection goes no further, and the bacteria become dormant (inactive) and do not cause any symptoms.

However, primary infection in very young children (who have weaker defenses against infection) and people with a weakened immune system may result in pneumonia and/or tuberculosis that affects other parts of the body (extrapulmonary tuberculosis). Also, in young children, the affected lymph nodes may become large enough to compress the bronchial tubes and cause symptoms.

Usually, the infection is not contagious during primary infection.

During latent infection, bacteria remain alive but in a dormant state inside macrophages for many years. The body walls off the bacteria inside a collection of cells, which form tiny scars. The dormant bacteria do not multiply or cause symptoms. In most cases, these bacteria remain dormant and never cause any further problems.

The infection is not contagious during latent infection.

In a small percentage of infected people, the dormant tuberculosis bacteria eventually start to multiply and cause active disease. This change from a dormant state is called reactivation. At this stage, infected people actually become sick and can spread the disease.

More than half the time, dormant bacteria reactivate within the first 2 years after the primary infection, but they may not reactivate for a very long time, even decades.

Usually, doctors do not know why the dormant bacteria reactivate, but reactivation is more likely to occur when the person’s immune system becomes impaired, especially by HIV infection.

Other risk factors that make reactivation more likely include the following:

• Diabetes

• Head and neck cancer

• Surgery to remove part or all of the stomach

• Severe chronic kidney problems

• Use of tobacco

• Substantial weight loss

• Very advanced age

Like many infectious diseases, tuberculosis spreads more quickly and is much more dangerous in people who have a weakened immune system. For such people, tuberculosis can be life threatening.

Mycobacterium tuberculosis can live only in people. These bacteria are not normally transmitted by animals, insects, soil, or other nonliving objects. People are infected with tuberculosis almost exclusively by breathing air contaminated by a person who has active tuberculosis. Touching someone who has the disease does not spread it because Mycobacterium tuberculosis bacteria are spread almost exclusively through the air.

People with active tuberculosis in their lungs or voice box (larynx) can contaminate the air with bacteria when they cough, sneeze, or even speak or sing. These bacteria can stay in the air for several hours. If another person breathes them in, that person may become infected. Thus, people who have contact with a person who has active tuberculosis (such as family members or health care practitioners who treat such a person) are at increased risk of getting the infection. However, once people begin effective treatment, the risk of spreading the infection quickly decreases, usually after about 2 weeks.

People who have latent infection or tuberculosis that is not in their lungs or larynx do not expel bacteria into the air and cannot spread the infection.

Although Mycobacterium tuberculosis lives only in people, there are related mycobacteria that affect animals. Mycobacterium bovis is one of these related mycobacteria. It most commonly infects cattle and occasionally causes infection in people who drink unpasteurized milk from infected cows. In countries where cattle are tested for tuberculosis and milk is pasteurized, infection caused by these bacteria is rarely a problem. However, cheese made from unpasteurized milk from infected cattle is sometimes illegally brought into the United States from other countries and sometimes results in infection. If Mycobacterium bovis infects the lungs, people can spread the bacteria to others when they cough or sneeze. People who work in slaughterhouses are also at risk of infection.

The progression of tuberculosis from latent infection to active disease varies greatly. Progression to active disease is far more likely and much faster in people with HIV infection and other risk factors. If people with HIV infection become infected with Mycobacterium tuberculosis and are not receiving appropriate HIV treatment, they have about a 10% chance of developing active disease each year. In contrast, people who have latent tuberculosis but do not have HIV infection have about a 5 to 10% chance of developing active disease during their lifetime.

In people with a fully functioning immune system, active tuberculosis is usually limited to the lungs (pulmonary tuberculosis).

Extrapulmonary tuberculosis (tuberculosis outside the lungs) usually results from pulmonary tuberculosis that has spread from the lungs through the blood to affect other parts of the body. As in the lungs, the infection may not cause disease, but the bacteria may remain dormant in a very small scar. Dormant bacteria in these scars can reactivate later in life, leading to symptoms related to the organs involved.

Miliary tuberculosis develops if a large number of the bacteria travel through the bloodstream and spread throughout the body. This type of tuberculosis may be life threatening.

Primary infection rarely causes symptoms, but when symptoms occur, they typically include fatigue, cough, and low-grade fever. The thin, two-layered membrane that covers the lungs can become inflamed and causes chest pain.

People with latent infection do not have symptoms.

Some people with active pulmonary tuberculosis have no symptoms, except for not feeling well, fatigue, loss of appetite, and weight loss. These symptoms develop gradually over several weeks. Other people also have symptoms that suggest a lung infection, such as cough.

Cough is the most common symptom of pulmonary tuberculosis. Because the disease develops slowly, infected people at first may blame the cough on smoking, a recent episode of flu, the common cold, or asthma. The cough may produce a small amount of green or yellow sputum, usually when people awaken in the morning. Eventually, the sputum may be streaked with blood, although large amounts of blood are rare.

People may awaken in the night and be drenched with a cold sweat, with or without fever. Sometimes there is so much sweat that people have to change nightclothes or even the bed sheets. However, tuberculosis does not always cause night sweats, and many other conditions can cause night sweats.

Rapidly developing shortness of breath plus chest pain may signal the presence of air (pneumothorax) or fluid (pleural effusion) in the space between the lungs and the chest wall. About one third of tuberculosis infections first show up as pleural effusion. Eventually, many people with untreated tuberculosis develop shortness of breath as the infection spreads in the lungs.

Probably, the most common sites for tuberculosis that develops outside the lungs are

• Lymph nodes

• Kidneys

Tuberculosis can also affect the bones, brain, abdominal cavity, two-layered membrane around the heart (pericardium), joints (especially weight-bearing joints, such as the hips and knees), and reproductive organs. Tuberculosis in these areas can be difficult to diagnose.

Symptoms of extrapulmonary tuberculosis are vague, usually fatigue, poor appetite, intermittent fevers, sweats, and possibly weight loss.

Sometimes the infection causes pain, discomfort, a collection of pus (abscess), or other symptoms, depending on the area involved:

• Lymph nodes: In a new tuberculosis infection, the bacteria may travel from the lungs to the lymph nodes that drain the lungs. If the body’s natural defenses can control the infection, it goes no further, and the bacteria become dormant. However, very young children have weaker defenses. In them, the lymph nodes that drain the lungs may become large enough to compress the bronchial tubes, causing a brassy cough and possibly a collapsed lung. Occasionally, bacteria spread from these lymph vessels to lymph nodes in the neck. An infection in lymph nodes in the neck may break through the skin and discharge pus. Sometimes bacteria travel in the bloodstream to lymph nodes in other parts of the body.

• Kidneys and bladder: Infection of the kidneys may cause fever, back pain, and pus and sometimes blood in the urine. Infection commonly spreads to the bladder, making people have to urinate more frequently and making urination painful.

• Genitals: Tuberculosis can also spread to the genitals. In men, genital tuberculosis causes the scrotum to enlarge. In women, it causes chronic pelvic pain and sterility and increases the risk of a pregnancy in an abnormal location (ectopic pregnancy).

• Brain: Tuberculosis that infects the tissues covering the brain (tuberculous meningitis) is life threatening. In the United States and other developed countries, tuberculous meningitis most commonly occurs among older people or people with a weakened immune system. In areas where tuberculosis is common among children, tuberculous meningitis is most common among children between birth and 5 years of age. Symptoms include fever, constant headache, neck stiffness, nausea, confusion, and drowsiness that can lead to coma. Tuberculosis may also infect the brain itself, forming a mass called a tuberculoma. The tuberculoma may cause symptoms such as headaches, seizures, or muscle weakness. Tuberculomas are also more common and more destructive in people with HIV infection.

• Pericardium: In tuberculous pericarditis, the pericardium (the two-layered membrane around the heart) thickens and sometimes leaks fluid into the space between the pericardium and the heart. These effects limit the heart’s ability to pump and cause fever, chest pain, enlarged neck veins, and difficulty breathing. In parts of the world where tuberculosis is common, tuberculous pericarditis is a common cause of heart failure.

• Intestine: Intestinal tuberculosis occurs mainly in countries in which tuberculosis in cows is a problem. It is acquired by eating or drinking unpasteurized dairy products contaminated with Mycobacterium bovis. This infection can cause pain, diarrhea, blockage of the intestine, and passage of bright red blood from the anus. Tissues in the abdomen may swell. This swelling may be mistaken for cancer.

• Skin: Tuberculosis may spread from another site, such as the lymph nodes or bones, to the skin (called cutaneous tuberculosis). It may cause painless, firm lumps to form. Eventually, these lumps enlarge and form open sores. Channels may form between the infected area within the body and the skin, and pus may drain through them.

When Tuberculosis Affects the Skin

Image

© Springer Science+Business Media

In people with tuberculosis, a chest x-ray is typically abnormal. However, the abnormal findings in tuberculosis often resemble those in other disorders, so the diagnosis may depend on the results of the tuberculin skin test and examination of sputum for Mycobacterium tuberculosis.

The sputum sample is examined under a microscope to look for tuberculosis bacteria and is used to grow the bacteria in a culture. Microscopic examination provides results much faster than a culture but is less accurate. It detects only about half the cases of tuberculosis identified by culture. However, traditional cultures do not provide results for many weeks because tuberculosis bacteria grow slowly. For this reason, treatment of people who may have tuberculosis is often begun while doctors wait for results of sputum examination and culture. A widely available culture test can routinely identify Mycobacterium tuberculosis growth within 21 days.

Lab Test

Acid-Fast Bacillus (AFB) Tests

Tests that increase the amount of the bacteria's genetic material (called nucleic acid amplification tests) can confirm the presence of Mycobacterium tuberculosis in 24 to 48 hours. A new version of this test can produce results in 2 hours. A sample of sputum is often used, but samples of other tissues such as a lymph node can be used if needed.

Genetic tests can also rapidly tell whether tuberculosis bacteria are resistant to some of the usual drugs used to treat tuberculosis and thus can help doctors choose effective treatment. These tests detect mutations in the bacteria's genes that enable them to resist treatment with certain drugs.

A tuberculin skin test (also called a Mantoux test) using purified protein derivative (PPD) is done by injecting a small amount of protein derived from tuberculosis bacteria between the layers of the skin, usually on the forearm. A pale bump appears immediately, then goes away in a few hours. This bump means only that the test was done correctly. About 2 or 3 days later, the injection site is checked. Swelling that feels firm to the touch and is larger than a certain size indicates a positive result. Redness around the site without swelling is not positive.

Some people who are very ill or who have a weakened immune system (such as those with HIV infection) may not respond to the skin test even if they are infected with tuberculosis.

Although a tuberculin skin test is one of the most useful tests for diagnosing tuberculosis, it indicates only that a person was infected by Mycobacterium tuberculosis or related bacteria or received a tuberculosis vaccine at some point. It does not indicate whether the infection is definitely tuberculosis or that the infection is currently active.

That is, results may indicate tuberculosis when it is not present (false-positive results) because people have a closely related infection (which is usually harmless) or have been recently vaccinated against tuberculosis.

Results may also indicate no tuberculosis when it is present (false-negative). But usually, results are false-negative only in people who

• Have a fever

• Are very ill

• Are older

• Have a disorder that weakens the immune system, such as HIV infection

• Are taking a drug that suppresses the immune system, such as a corticosteroid

The interferon-gamma release assay (IGRA) is a blood test that can detect tuberculosis. For this test, a sample of blood is mixed with synthetic proteins similar to those produced by the tuberculosis bacteria. If people are infected with tuberculosis bacteria, their white blood cells produce certain substances (interferons) in response to the synthetic proteins. The blood is then checked for the presence of interferons to determine whether tuberculosis infection is present.

This test, unlike tuberculin skin testing, does not cause a false-positive test result in people who have been vaccinated against tuberculosis.

A sample of sputum is usually adequate, but occasionally a doctor needs to obtain a sample of lung fluid or tissue to make the diagnosis. An instrument called a bronchoscope is inserted through the mouth or nostril and into the airways. It is used to inspect the bronchial tubes and to obtain a sample of lung fluid or tissue. This procedure is most often done when other disorders, such as lung cancer, are suspected.

When symptoms suggest tuberculous meningitis, a doctor may need to do a spinal tap (lumbar puncture) to obtain a sample of spinal fluid for analysis. Because tuberculosis bacteria are hard to find in spinal fluid and because cultures usually take weeks, the polymerase chain reaction (PCR) technique may be used on the sample. It produces many copies of a gene, making identification of the bacteria’s DNA easier. Although test results are available quickly, doctors usually begin antibiotic therapy if they have any suspicion of tuberculous meningitis. Early treatment can prevent death and minimize brain damage.

People with pulmonary tuberculosis being treated in a hospital are kept in isolation in a room that is specially designed to minimize the risk of spreading infections through the air. The door is kept closed as much as possible, and the air in the room is changed 6 to 12 times every hour. People who are kept in isolation do not need to wear a surgical face mask if they can cooperate with instructions on how to cover their coughs. However, people who enter the room must wear a respirator (a specially fitted filter device, not a simple surgical mask).

People can move from isolation into a general hospital room when they have clearly responded to treatment—typically, when all of the following occur:

• Their sputum samples have been negative (no tuberculosis bacteria seen) for a period of time.

• They no longer have a fever.

• They have regained their appetite and sense of well-being.

A number of antibiotics are effective against tuberculosis. But because tuberculosis bacteria are very slow-growing, antibiotics must be taken for a long time—for 4 to 6 months or longer. Treatment must be continued long after people feel completely well. Otherwise, tuberculosis tends to recur because it was not fully eliminated. Also, the tuberculosis bacteria may become resistant to the antibiotics.

Most people find it difficult to remember to take their drugs every day for such a long time. Other people, for various reasons, stop treatment as soon as they feel better. Because of these problems, many experts recommend that people with tuberculosis receive their drugs from a health care worker, who watches them take the pills. This approach is called directly observed therapy (DOT). Because DOT ensures that people take every dose, the drugs are often given just 2 or 3 times per week after the first 2 weeks.

Two or more antibiotics that work in different ways are always given because treatment with only one drug can leave behind a few bacteria resistant to that drug. With most other bacteria, a few bacteria would not be enough to cause a relapse, but if tuberculosis is treated with only one drug, the tuberculosis bacteria soon become resistant to that drug.

Until recently, there were two phases of treatment for people who have not been treated before:

• Intensive phase: People take four antibiotics for 2 months.

• Continuation phase: People take only two antibiotics for 4 to 7 more months, depending on the results of sputum tests and chest x-rays.

Today, certain people may be eligible for a treatment regimen that lasts for 4 months and includes only two drugs.

The most commonly used antibiotics are

These four drugs may be used together and are used first (called first-line drugs). All of these drugs have side effects, but most people with tuberculosis are cured with these drugs and do not have any serious side effects.

Second-line drugs are usually used when the bacteria causing tuberculosis have become resistant to first-line drugs or when people cannot tolerate the first-line drugs. Other antibiotics are used as second-line drugs. They include aminoglycosidesfluoroquinolones

Tuberculosis bacteria can easily develop resistance to antibiotics, particularly when people do not take the drugs regularly or for as long as they are supposed to.

Bacteria that resist treatment with antibiotics are causing more and more cases of tuberculosis (called drug-resistant tuberculosis).

Drug resistance is a serious concern because drug-resistant tuberculosis must be treated for a very long time. People typically must take four or five drugs for 18 to 24 months. Drugs used to treat drug-resistant tuberculosis are often less effective, more toxic, and more expensive.

Tuberculosis bacteria that are resistant to antibiotics are classified based on the drugs they are resistant to. The World Health Organization (WHO) classifications are

• Multidrug-resistant tuberculosis (MDR-TB):

• Pre-extensively-drug-resistant tuberculosis (pre-XDR-TB):

• Extensively drug-resistant tuberculosis (XDR-TB):

Surgery to remove a portion of the lung is seldom needed if people faithfully follow the drug treatment plan. However, surgery is sometimes needed to treat people with the following:

• Very drug-resistant infections

• A cough that continuously brings up blood

• Blocked airways

• Pus that has accumulated (to drain it)

When tuberculous pericarditis causes significant restriction of the heart’s motion, the pericardium may need to be removed surgically. A tuberculoma (a mass that develops because of tuberculosis) in the brain may need to be surgically removed.

Because tuberculosis bacteria are airborne, good ventilation with fresh air lowers the concentration of bacteria and limits their spread. Also, germicidal ultraviolet lamps can be used to kill airborne tuberculosis bacteria in buildings where people at risk are gathered, such as homeless shelters, jails, and hospital and emergency department waiting areas. If health care workers handle samples of infected tissue or fluid or interact with people who may be infected, they wear specially fitted masks called respirators, which filter the air, to help protect them.

No precautions are needed if people have no symptoms even if their skin or blood test for tuberculosis is positive.

Most people with active tuberculosis do not need to be hospitalized. However, to help prevent spread of the disease, they should do the following:

• Stay at home

• Avoid visitors (they do not have to avoid family members who have already been exposed)

• Cover their cough with a tissue or cough into their elbow

People should follow these precautions until they are responding to treatment and no longer coughing. After only a week or two of treatment with the correct antibiotics, people are less likely to spread the disease. However, if they live or work with people who are at high risk (such as young children or people with AIDS), repeated analyses of sputum samples may be needed to determine when the danger of spreading the infection has passed. Also, people who continue to cough during treatment, do not take their drugs as instructed, or have highly drug-resistant tuberculosis may need to follow these precautions longer so that they do not spread the disease.

Directly observed therapy (DOT) can also help prevent the spread of infection. Making sure that infected people take the prescribed drugs as instructed increases the chance that the bacteria will be eradicated.

Public health personnel try to determine who might have been infected by a person with tuberculosis and recommend that these people be tested for tuberculosis.

Because tuberculosis is spread only by people with active disease, treatment of latent disease and early recognition and treatment of active disease are among the best ways to stop it from spreading.

Most people who have a positive tuberculin skin or blood test are treated even if they are not yet ill.

Preventive therapy definitely benefits younger people who have a positive tuberculin skin test. It also is likely to help older people with a positive tuberculin skin test if they are at high risk of tuberculosis—for example, if the any of the following apply:

• Their skin or blood test recently changed from negative to positive.

• They have been recently exposed.

• They have a weakened immune system.

For older people with long-standing latent infection, the risk of toxicity from the antibiotics may be greater than the risk of developing tuberculosis. In such cases, doctors often consult an expert in the subject before they decide whether to use preventive therapy.

If people have a positive skin or blood test, the risk of developing active infection is high in the following situations:

• If they become infected with HIV

• If they take corticosteroids or other drugs that suppress the immune system (including some of the newer anti-inflammatory drugs)

Such people usually need treatment of latent tuberculosis infection.

In areas of the world where tuberculosis is common, a vaccine called bacille Calmette-Guérin (BCG) is used to do the following:

• Prevent development of serious complications, such as meningitis

• Help prevent infection in people who are at high risk of becoming infected with Mycobacterium tuberculosis, especially children

Doctors usually do not recommend the BCG vaccine for people living in the United States. However, the vaccine may have a role in protecting health care workers and others (particularly children) exposed to tuberculosis that is resistant to two or more drugs.

Research is under way to develop a more effective vaccine.

People who have received BCG at birth may have a positive reaction to the tuberculin skin test years later, even if they are not infected with tuberculosis bacteria. The effect of BCG vaccination on skin test results is usually smaller than that of tuberculosis, and it lessens with time. About 15 years after BCG vaccination, a positive test result is much more likely to be due to tuberculosis than to BCG vaccination. Nonetheless, people vaccinated at birth often incorrectly attribute a positive skin test later in life to the BCG vaccine. In most countries, tuberculosis is stigmatized, and many people are reluctant to believe that they have even latent infection, much less active disease. Usually, if children who have been vaccinated have a positive tuberculin skin test, doctors presume it is due to tuberculosis and treat it accordingly. Untreated latent infection can have serious complications, especially in children.

However, if possible, people who have been vaccinated with BCG should be tested using the interferon-gamma release assay (IGRA) because the IGRA does not cause a false-positive test result in people who have received the BCG vaccine. This test can also determine whether a positive reaction to a skin test is due to infection with Mycobacterium tuberculosis.