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Every year, tuberculosis (TB) — a life-threatening infection that primarily affects the lungs — kills nearly 2 million people worldwide. Experts at the World Health Organization (WHO) predict these numbers will escalate in coming decades. Approximately 2 billion people — one-third of the human population — are currently infected with TB, with one new infection occurring every second.

TB 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 Mycobacterium tuberculosis, the bacterium that causes the disease.

TB 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. Although your body harbors 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 causes no symptoms and isn't contagious.
• Active TB. This condition makes you sick and can spread to others.

If left untreated, active TB can be fatal. With proper care, however, most cases of TB can be treated, even those resistant to the drugs commonly used against the disease. Unfortunately, the world's poor — those most likely to have TB — are also the least likely to receive adequate medical care.

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 symptoms. In still other cases, you may develop active TB.

TB mainly affects your lungs (pulmonary tuberculosis). 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, TB of the spine may result in back pain, and TB that affects your kidneys might cause blood in your urine. Tuberculosis can also spread through your entire body, simultaneously attacking many organ systems.

Tuberculosis in infants
Women who have active TB can transmit the disease to their babies either before or during birth. About half the babies born to women with active TB develop signs and symptoms during the first year of life. These may include:

• Fever
• Poor feeding
• Failure to thrive
• Difficulty breathing
• Swollen liver and spleen

The bacteria that cause TB spread in microscopic droplets that are released into the air when someone with the untreated, active form of the disease coughs, speaks, laughs or sneezes. Although TB is contagious, it's not an especially easy disease to catch. In general, you need long-term contact with an infected person — as much as eight hours a day for up to six months — to become infected yourself. You're much more likely to contract TB from a family member or close co-worker than from a stranger on a bus or in a restaurant, although there have been a number of cases of transmission on plane flights. A person with active TB who's been effectively treated for at least two weeks is no longer contagious and can't spread the bacteria to others.

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 that case, you're considered to have TB infection, but you won't feel sick or have symptoms, and you can't transmit the disease to others. The only way to know you're infected with TB is through a positive skin test.

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 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, serious
If you have active TB, you're likely to feel sick, although it's possible to have an active infection without having symptoms. But even if you're not sick yourself, you still can transmit the disease to others. A person with active TB who doesn't receive treatment can infect an average of 10 to 15 people a year.

Without treatment, about half the people with active TB die. The rest either 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 go on to develop active TB sometime in their lives. The risk is greatest in the first year after infection, but the disease may not resurface for decades.

What caused the current TB pandemic?
In the United States, cases of TB have declined steadily in recent years — mainly because of improved public health programs. Yet the disease is still a serious health problem. An estimated 10 million to 15 million Americans are infected with TB without having symptoms. About 1 million of them will go on to develop active TB.

The situation in other countries is far more dire. Overall, about one-third of the world's population is infected with TB; new infections and deaths from the disease are increasing. Hardest hit are Southeast Asia and sub-Saharan Africa. 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. TB and HIV have a deadly relationship — each fuels the progress of the other.

About one-third of the 38 million people living with AIDS also have TB. Infection with HIV suppresses the immune system, making it difficult for the body to control TB bacteria. As a result, most HIV-positive people who are newly infected with TB progress to active TB. HIV is also likely to reactivate dormant TB bacteria. 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 increases the rate at which the AIDS virus replicates. What's more, TB often strikes people with HIV years before other problems associated with HIV develop. One of the first indications of HIV infection may be the sudden onset of TB — often in a site outside the lungs (extrapulmonary TB).

Additional contributing factors
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. That's one reason it has reached epidemic proportions in some prisons, where the rate of infection may be up to 100 times higher than that in the general population. The incidence of TB is also high in juvenile detention centers, homeless shelters and other places where large numbers of people live together in crowded conditions. 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. In 2000, nearly half the reported cases in the United States occurred in people born outside the country. These numbers point to the global nature of the disease and the need to combat it on a worldwide scale.
• Increased poverty and lack of access to medical care. The world's poor, both in America and in other countries, are the most 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 so may not complete their treatment, leading to drug-resistant forms of the disease.
• Increase in drug-resistant strains of TB. The development of drug-resistant strains of bacteria is one of the most alarming trends in health care. The problem is particularly serious with regard to TB bacteria, which have developed strains that resist treatment with one of each of the major TB medications. 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 either don't complete the 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.

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 or chemotherapy drugs can damage your body's ability to protect itself. An increased risk of reactivated TB also has been associated with use of the arthritis drugs infliximab (Remicade) and etanercept (Enbrel).
• 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.
• Your sex. In most of the world, more men than women are infected with TB. Men are also more likely to die of the disease.
• Race. In the United States, Hispanics, American Indians and blacks are at higher risk of TB than are whites. Asian-Americans have the highest TB rate.
• 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 mini-epidemics 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. The disease has reached epidemic proportions in some prisons, where overcrowding, poor ventilation, and inadequate diagnosis and treatment of disease often exacerbate existing health problems.
• Living in a refugee camp or shelter. The World Health Organization estimates that there are at least 23 million refugees in camps and shelters around the world. 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.

Some factors put you at risk of TB infection, but not necessarily active TB disease. This chart explains the difference:

Adapted from: Centers for Disease Control and Prevention

Risk factors in children
Children rarely get TB from other children. Instead, they're much more likely to acquire the disease from an adult. For that reason, children who live in a household with an adult who has active TB or who is at risk of TB are at high risk themselves. Also at risk are children who:

• Have HIV or another illness that weakens their immune system
• Were born in a country where TB is prevalent
• Don't have access to regular medical care
• Are homeless

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 or 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.

The first step in diagnosing TB is a simple skin test. Although there are two methods, doctors consider the Mantoux test the most accurate. For the test, a small amount of a substance called PPD tuberculin is injected just beneath 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. In that case, 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.

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.

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 takes several 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. For that reason, you shouldn't be tested for four to six weeks after being inoculated with a live virus.
• 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.

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 infects the brain and central nervous system, and miliary TB, which occurs when TB bacteria spread throughout the entire body, are particularly dangerous forms of the disease. Children are especially susceptible to both meningeal TB and miliary TB, which makes early diagnosis in infants and children imperative. The most serious complication, however, is the recurrence of TB after the initial infection and the development of drug-resistant strains of the disease.

Until the mid-20th century, people with TB 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 prevented its spread.

Today, medications are the cornerstone of TB treatment, but the therapy is still 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 the 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.

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.

Side effects of TB drugs aren't common, but they're often 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
• Blood in your urine

Compliance improves effectiveness
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.

Since its inception in 1991, millions of people around the world have been treated with the DOTS strategy, leading to a 95 percent cure rate in even the poorest countries. Not only does DOTS save lives and prevent the development of drug-resistant strains of bacteria, it's also a very cost-effective treatment program.

Treating multidrug-resistant TB (MDR-TB)
Multidrug-resistant TB is any strain of TB that can't be treated by the two most powerful TB drugs, isoniazid and rifampin. It develops as a result of partial 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 develop mutations that can resist treatment with first-line TB drugs. Because MDR-TB is spreading rapidly and could potentially make all TB incurable, some experts believe that ineffective treatment is ultimately worse than no treatment at all.

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, about half of 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 infection or repair lung damage. What's more, treating MDR-TB is far more costly than treating nonresistant TB, making therapy unaffordable in many parts of the world.

Treating people who have HIV/AIDS
Treating the estimated 10 million 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.

For millions of people around the world who don't have access to HIV medications, this approach isn't an option. 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. Yet experts say that combining AIDS drugs with TB treatments could save 500,000 lives a year in sub-Saharan Africa alone.

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 hospitalized TB patients. But there are also measures you can take on your own to help protect yourself and others:

• Get tested regularly. Experts advise getting a skin test every six months if you have HIV or another disease that weakens your immune system, live or work in a prison or nursing home, were born in a country where TB is prevalent, or have other risk factors for 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 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.
• 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.

Undergoing treatment for TB 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 painful 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.