Original Article: http://www.mayoclinic.com/health/tuberculosis/DS00372

 

Tuberculosis

 

Introduction

 

Tuberculosis (TB) is a life-threatening infection that primarily affects your 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.

 

Signs and 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

 

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.

 

Screening 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.

 

Treatment

 

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 skills

 

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.

By Mayo Clinic Staff

Dec 21, 2006 © 1998-2007 Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. A single copy of these materials may be reprinted for noncommercial personal use only. "Mayo," "Mayo Clinic," "MayoClinic.com," "EmbodyHealth," "Reliable tools for healthier lives," "Enhance your life," and the triple-shield Mayo Clinic logo are trademarks of Mayo Foundation for Medical Education and Research.

 

 

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