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Tuberculosis (TB)

By

Dylan Tierney

, MD, MPH , Harvard Medical School;


Edward A. Nardell

, MD, Harvard Medical School

Last full review/revision May 2018| Content last modified Jun 2018
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Tuberculosis is a chronic contagious infection caused by the airborne bacteria Mycobacterium tuberculosis. It usually affects the lungs.

  • Tuberculosis is spread mainly when people breathe air contaminated by a person who has active disease.

  • Cough is the most common symptom, but people may also have a fever and night sweats, lose weight, feel generally unwell, and, if tuberculosis affects other organs, have various other symptoms.

  • The diagnosis usually involves a tuberculin skin test or a blood test, a chest x-ray, and examination and culture of a sputum sample.

  • Two or more antibiotics are always given to reduce the chances of bacterial resistance.

  • Early diagnosis and treatment plus isolation of people with active disease until they have responded to treatment help prevent tuberculosis from spreading.

Tuberculosis usually affects the lungs, although it can affect almost any organ in the body.

Tuberculosis is caused by bacteria called Mycobacterium tuberculosis. Other related bacteria (called mycobacteria), such as Mycobacterium bovis or Mycobacterium africanum, occasionally cause a similar disease. These bacteria plus Mycobacterium tuberculosis and some others are called the mycobacterium tuberculosis complex.

Other mycobacteria, particularly the group called mycobacterium avium complex (MAC), also cause disease in people. These diseases they cause are different from tuberculosis.

Leprosy is caused by other mycobacteria.

Tuberculosis worldwide

Tuberculosis has been a serious public health problem for a long time. In the 1800s, the disease caused more than 30% of all deaths in Europe. With the advent of antituberculosis antibiotics in the late 1940s, the battle against tuberculosis seemed to be won. However—because of factors such as inadequate public health resources, reduced immune response due to AIDS, the development of drug resistance, and extreme poverty in many parts of the world—tuberculosis continues to be a deadly disease worldwide, as the following statistics from 2016 show:

  • There were an estimated 10.4 million new cases of symptomatic tuberculosis and 1.7 million deaths from the disease.

  • Most new cases occurred in Southeast Asia (45%), which includes India and Pakistan, followed by Africa (25%) and the Western Pacific (17%), which includes China, Japan, the Philippines, and Australia.

  • The number of new cases varies widely by country, age, race, sex, and socioeconomic status. In 2016, 64% of new cases occurred in seven countries. Most new cases occurred in India, followed by Indonesia, China, the Philippines, Pakistan, Nigeria, and South Africa.

  • An estimated 1 million new cases occurred in children, and 250,000 children died of tuberculosis.

About one fourth of all the people in the world are thought to be infected. Most have a dormant (latent) tuberculosis infection. Only a small percentage of these infections progress to active tuberculosis. At any one time, about 15 million people worldwide have active tuberculosis.

Worldwide, tuberculosis is the ninth leading cause of death. It is the leading cause of death from an infectious disease, followed by human immunodeficiency virus (HIV) infection.

In areas of the world where both infections are common, having HIV infection or AIDS greatly increases the risk of getting tuberculosis and dying, In 2016, about 0.4 million people with HIV infection died of tuberculosis. Tuberculosis is a common cause of death among people with HIV infection, causing about 40% of their deaths.

Did You Know...

  • Tuberculosis caused 1.7 million deaths worldwide in 2016.

Tuberculosis in the United States

In the United States, the rate of new cases has decreased from 1994 to 2014. In 2016, 9,287 cases (about 2.9 cases per 100,000 people) were reported. In 2017, the number of new cases decreased to an estimated 9,093 (about 2.8 cases per 100,000 people)—the lowest number on record. However, incidence varies from state to state: from 8.1 per 100,000 people in Hawaii to 0.3 per 100,000 in Montana and Wyoming.

Over half of new cases in the United States occurred in people born outside the United States in areas where tuberculosis is relatively common (such as Africa, Asia, or Latin America). Risk of being infected is increased for people who live in group facilities, such as shelters, long-term care facilities, jails, or prisons, and for those who have been homeless in the past year. In the United States, minorities are disproportionately affected. The number of cases per 100,000 people ranges from 4 to 16 times higher in minorities than in whites.

How Tuberculosis Develops

With most infectious diseases (such as strep throat or pneumonia), people become sick right after the microorganism enters the body and are noticeably ill within 1 or 2 weeks. Tuberculosis does not follow this pattern.

Tuberculosis occurs in stages:

  • Primary infection

  • Latent infection

  • Active disease

Except for very young children and people with a weakened immune system, few people become sick immediately after tuberculosis bacteria enter their body (this stage is called primary infection). In most cases, tuberculosis bacteria that enter the lungs are immediately killed by the body’s defenses. Bacteria that survive are engulfed by white blood cells called macrophages. The engulfed bacteria can remain alive inside these cells in a dormant state for many years (this stage is called latent infection). In 90 to 95% of cases, the bacteria never cause any further problems, but in about 5 to 10% of infected people, the bacteria eventually start to multiply and cause active disease. At this stage, infected people actually become sick and can spread the disease.

Primary infection

In the first few weeks of the infection, some bacteria may travel from the lungs to nearby lymph nodes that drain the lungs. 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 (latent) and do not cause any symptoms.

However, very young children (who have weaker defenses against infection) and people with a weakened immune system may develop 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.

Latent 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. In 90 to 95% of cases, these bacteria never cause any further problems.

The infection is not contagious during latent infection.

Active disease

In about 5 to 10% of infected people, the dormant tuberculosis bacteria eventually start to multiply and cause active disease. 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—for example, because of the following:

  • Very advanced age

  • Use of corticosteroids

  • Use of some of the new prescription anti-inflammatory drugs such as adalimumab, etanercept, and infliximab

Other conditions that make reactivation more likely include the following:

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.

Transmission of infection

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.

Mycobacterium bovis, which can live in animals and which occasionally causes a similar disease, is different. In developing countries, people become infected with Mycobacterium bovis by drinking unpasteurized milk from infected cattle. In developed countries, this type of tuberculosis is rarely a problem because cattle are tested for tuberculosis and milk is pasteurized. However, cheese made from unpasteurized milk from infected cattle is sometimes illegally brought into the United States from other countries and sometimes results in disease. If Mycobacterium bovis infects the lungs, people can spread the bacteria to others when they cough or sneeze.

Did You Know...

  • People with active tuberculosis often contaminate the air when they cough, sneeze, or even talk or sing.

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.

Progression and spread 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 conditions (including use of drugs) that weaken the immune system. If people with HIV infection become infected with Mycobacterium tuberculosis, 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 only 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 usually comes 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.

Symptoms and Complications

Pulmonary tuberculosis

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 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.

Extrapulmonary tuberculosis

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: Infection of the kidneys may cause fever, back pain, 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 pelvic pain and menstrual irregularities 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 developing countries, tuberculous meningitis is most common among children from birth to age 5. 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 developing 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.

Table
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Tuberculosis: A Disease of Many Organs

Site of Infection

Symptoms or Complications

Abdominal cavity

Fatigue, swelling, slight tenderness, and appendicitis-like pain

Bladder

Painful urination and blood in urine

Bones (mainly in children)

Swelling and minimal pain

Tissues covering the brain and spinal cord (meninges)

Fever, headache, nausea, drowsiness, confusion, a stiff neck, and, if untreated, coma

Pericardium (the two-layered membrane around the heart)

Fever, chest pain, enlarged neck veins, shortness of breath

Joints

Arthritis-like symptoms

Kidneys

Kidney damage with fever, back pain, and white blood cells (pus) and blood in the urine

Lymph nodes

Swollen lymph nodes, which may become inflamed and tender and drain pus

Reproductive organs in men

Lump in the scrotum

Reproductive organs in women

Chronic pelvic pain and sterility or a mislocated (ectopic) pregnancy

Spine

Worsening or constant back pain, collapsed vertebrae, and leg paralysis

Spotlight On Aging: Tuberculosis

If latent tuberculosis reactivates in older people, it may cause few symptoms. Thus, doctors may not suspect it for weeks or months. In older people, the presence of other disorders also makes it hard to diagnose reactivated tuberculosis.

Older people who live in a nursing home are at risk of being infected with tuberculosis. The pneumonia that results may not be recognized as tuberculosis. Thus, it may not be appropriately treated and may spread to other people.

In the United States, miliary tuberculosis most often affects older people. Miliary tuberculosis is a potentially life-threatening type of tuberculosis that occurs when a large number of the bacteria travel through the bloodstream and spread throughout the body.

Tuberculosis that infects the tissues covering the brain (called tuberculous meningitis) is also more common among older people. This life-threatening infection causes fever, constant headache, neck stiffness, nausea, confusion, and drowsiness that can lead to coma.

If older people have long-standing latent tuberculosis, doctors weigh the risk and benefits of using antituberculosis antibiotics to prevent active tuberculosis from developing. The risk that these drugs may have harmful effects may be greater than the risk of developing tuberculosis. In such cases, doctors often consult a tuberculosis expert before they decide whether to use antibiotics.

Diagnosis

  • Chest x-ray

  • Examination, culture, and other tests of a sputum sample

  • Tuberculin skin test

  • Blood tests for tuberculosis

  • Screening tests for people at risk of tuberculosis

Sometimes the first indication of tuberculosis is a positive screening test. Screening tests for tuberculosis are done routinely for people who are at risk of tuberculosis.

Doctors may suspect tuberculosis based on symptoms such as fever, a cough lasting more than 3 weeks, a cough the brings up blood, chest pain, and difficulty breathing.

When doctors suspect tuberculosis, the first tests done are

  • Chest x-ray

  • Microscopic examination and culture of a sputum sample

  • Rapid tests to check for the genetic material (DNA) of Mycobacterium tuberculosis in sputum samples

If the diagnosis is still unclear, the following may be done:

  • Tuberculin skin test

  • Blood tests for tuberculosis

If tuberculosis is diagnosed, blood tests to check for HIV infection (a risk factor for tuberculosis) may be done.

Chest x-ray for tuberculosis

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.

Sputum tests for 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.

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 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 identify bacteria that 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.

Skin test for tuberculosis

A tuberculin skin test (also called a Mantoux test or PPD for purified protein derivative) 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 an infection by the bacteria has occurred some time in the past. It does not indicate whether the infection is currently active.

Also, 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

Blood test for tuberculosis

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, is not influenced by recent vaccination for tuberculosis.

Other tests

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.

Screening Tests for Tuberculosis

Certain tests are done routinely for people who are at risk of tuberculosis. The tests include the tuberculin skin test and the interferon-gamma release assay (IGRA) blood test.

People at risk of tuberculosis include those who

  • Live or work with people who have active tuberculosis (screening is done yearly)

  • Have just emigrated from areas where tuberculosis is common

  • Are starting to take a drug that may weaken the immune system and reactivate latent tuberculosis if present (for example, corticosteroids and cancer chemotherapy)

  • Have signs of possible tuberculosis on a chest x-ray done for another reason

  • Have a weakened immune system (for example, because of HIV infection)

  • Have certain disorders, such as diabetes, kidney disease, or head or neck cancer

  • Are over age 70

  • Inject illegal drugs

If results of a skin test or blood test are positive, people are evaluated by a doctor, and a chest x-ray is taken. If the chest x-ray is normal and people have no symptoms suggesting tuberculosis, they probably have latent tuberculosis. People with latent tuberculosis are treated with antibiotics (see Treating tuberculosis early). If the chest x-ray is abnormal, people are evaluated for active tuberculosis (see Tuberculosis (TB) : Diagnosis).

Treatment

  • Isolation

  • Antibiotics

  • Sometimes surgery or corticosteroids

Most infected people do not need to be hospitalized for treatment. People are hospitalized if they

  • Are seriously ill with tuberculosis

  • Have another serious disorder

  • Need to have diagnostic procedures

  • Do not have an appropriate place to go to (for example, if they are homeless)

  • Live in a group situation where they would regularly encounter previously unexposed people (such as a nursing home)

Isolation

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 at least 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.

Antibiotics

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 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.

Typically, there are 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.

The most commonly used antibiotics are

  • Isoniazid

  • Rifampin

  • Pyrazinamide

  • Ethambutol

These four drugs are typically used together and are used first (called first-line drugs). Streptomycin is sometimes added to this regimen. All of these drugs have side effects, but 95% of people with tuberculosis are cured with these drugs and do not experience any serious side effects.

Table
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Drugs Used to Treat Tuberculosis

Drug

Route

Side Effects

First-line drugs*

Isoniazid

By mouth

Liver injury in 1 person in 1,000, resulting in fatigue, loss of appetite, nausea, vomiting, and jaundice

Sometimes numbness in the limbs (peripheral neuropathy)

Rifampin (and the related drugs rifabutin and rifapentine)

By mouth

Liver injury, particularly when rifampin is combined with isoniazid (but the effects go away when people stop the drug)

Reddish orange discoloration of urine, tears, and sweat

Rarely a low white blood cell or platelet count

Pyrazinamide

By mouth

Liver injury, digestive upset, and sometimes gout

Ethambutol

By mouth

Sometimes blurred vision and decreased color perception (because the drug affects the optic nerve)

Second-line drugs

Aminoglycosides, such as streptomycin, amikacin, and kanamycin

By injection into a muscle

Kidney injury, dizziness, hearing loss (due to damage to nerves of the inner ear), rash, and fever

Fluoroquinolones, such as levofloxacin, moxifloxacin

By mouth

Inflammation or rupture of tendons

Nervousness, tremors, and seizures

Capreomycin

By injection into a muscle

Side effects similar to those of aminoglycosides (but capreomycin is often tolerated better if treatment is needed for a long time)

*First-line drugs are usually the first choice for treatment.

Second-line drugs are usually used when the bacteria causing tuberculosis have become resistant to first-line drugs or when people cannot tolerate one of the first-line drugs.

There are many different combinations and dose schedules for these drugs. Isoniazid, rifampin, and pyrazinamide may be contained in the same capsule, reducing the number of pills people have to take each day and reducing the chance of developing drug resistance. Unlike other antibiotics, those used to treat tuberculosis are usually taken all together at the same time, once a day or 2 or 3 times a week.

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 aminoglycosides(such as streptomycin, kanamycin. and amikacin), capreomycin (which is closely related to aminoglycosides), and fluoroquinolones (such as levofloxacin and moxifloxacin).

Other drugs are sometimes used to treat tuberculosis, but they are less effective and have more side effects. Typically they are used only to treat tuberculosis that is highly resistant to other drugs.

Did You Know...

  • Treatment of tuberculosis must be continued long after people feel well.

Drug resistance

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). In 2016, an estimated 600,000 people developed tuberculosis that was resistant to rifampin (rifampicin). About 490,000 of these cases were also resistant to isoniazid and sometimes other drugs.

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 as

  • Multidrug-resistant (MDR-TB): Resistant to at least isoniazid and rifampin

  • Extensively drug resistant (XDR-TB): Resistant to isoniazid, rifampin, fluoroquinolones, and at least one of three other antibiotics given by injection

Several new tuberculosis drugs (including bedaquiline, delamanid, and sutezolid) are active against resistant strains of tuberculosis bacteria and may help control the epidemic of drug resistance.

Other treatments

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 in the brain may need to be surgically removed.

Doctors sometimes give corticosteroids (such as dexamethasone) when tuberculosis causes a significant amount of inflammation, particularly in people with meningitis, pericarditis, or lung inflammation.

Prevention

Prevention of tuberculosis has three aspects:

  • Stopping the spread of infection

  • Treating infection as early as possible before it becomes active disease

  • Sometimes vaccination

Stopping the spread of tuberculosis

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 is past. 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.

Treating tuberculosis early

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.

The antibiotic isoniazid is very effective at stopping the infection before it becomes active disease. It is given daily for 9 months. For some people, rifampin alone may be prescribed daily for 4 months. In some countries, isoniazid and rifapentine are used together once a week for 3 months as directly observed therapy.

Preventive therapy definitely benefits younger people who have a positive tuberculin skin test. It also is likely to help older people 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.

Vaccination for tuberculosis

In much of the developing world, 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), which is not influenced by the BCG vaccine. This test can also determine whether a positive reaction to a skin test is due to infection with Mycobacterium tuberculosis.

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