INFECTIOUS DISEASE TUBERCULOSIS (TB)

What is Tuberculosis (TB)-

Tuberculosis (TB) is a bacterial infection caused by a germ called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with TB of the lungs or throat coughs, sneezes or talks. If you have been exposed, you should go to your doctor for tests. You are more likely to get TB if you have a weak immune system.

What are signs and symptoms of Tuberculosis?

Symptoms of TB in the lungs may include
•    A bad cough that lasts 3 weeks or longer
•    Weight loss
•    Coughing up blood or mucus
•    Weakness or fatigue
•    Fever and chills
•    Night sweats
If not treated properly, TB can be deadly. You can usually cure active TB by taking several medicines for a long period of time. People with latent TB can take medicine so that they do not develop active TB.

What causes Tuberculosis?

Tuberculosis is caused by an organism called Mycobacterium tuberculosis. The bacteria spread from person to person through microscopic droplets released into the air. This can happen when someone with the untreated, active form of tuberculosis coughs, speaks, sneezes, spits, laughs or sings. Rarely, a pregnant woman with active TB may pass the bacteria to her unborn child.

Although tuberculosis is contagious, it’s not especially easy to catch. You’re much more likely to get tuberculosis from a family member or close co-worker than from a stranger. Most people with active TB who’ve had appropriate drug treatment for at least two weeks are no longer contagious.

TB infection vs. active TB
If you breathe TB bacteria into your lungs, one of four things might happen:
•    You don’t become infected with TB. Your immune system immediately destroys the germs and clears them from your body.
•    You develop latent TB infection. The germs settle in your lungs and begin to multiply. Within several weeks, however, your immune system successfully “walls off” the bacteria in your lungs, much like a scab forming over a wound. 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 a TB skin test. But you won’t have symptoms and won’t transmit the disease to others.
•    You develop active TB. If your immune defenses fail, TB bacteria begin to exploit your immune system cells for their own survival. The bacteria move into the airways in your lungs, causing large air spaces (cavities) to form. Filled with oxygen — which the bacteria need to survive — the air spaces make an ideal breeding ground for the bacteria. The bacteria may then spread from the cavities to the rest of your lungs as well as to other parts of your body.
If you have active TB, you’re likely to feel sick. Even if you don’t feel sick, you can still infect others. Without treatment, many people with active TB die. Those who survive may develop long-term symptoms, such as chest pain and a cough with bloody sputum, or they may recover and go into remission.
•    You develop active TB years after the initial infection. After you’ve had latent TB for years, the walled-off bacteria may suddenly begin multiplying again, causing active TB, also known as reactivation TB. It’s not always clear what triggers this reactivation, but it most commonly happens after your immune system becomes weakened. Your resistance may be lower because of aging, drug or alcohol abuse, malnutrition, chemotherapy, prolonged use of prescription medications such as corticosteroids or TNF inhibitors, and diseases such as HIV/AIDS.

Only about one in 10 people who have TB infection goes on to develop active TB. The risk is greatest in the first two years after infection and is much higher if you have HIV infection.
HIV and TB
Since the 1980s, the number of cases of tuberculosis has increased dramatically because of the spread of HIV, the virus that causes AIDS. Tuberculosis and HIV have a deadly relationship — each drives 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 get TB and to progress from latent to active disease than are people who aren’t HIV-positive.
TB is one of the leading causes of death among people with AIDS, especially outside the United States.  One of the first indications of HIV infection may be the sudden onset of TB, often in a site outside the lungs.

Drug-resistant TB
Another reason TB remains a major killer is the increase in drug-resistant strains of the bacterium. Ever since the first antibiotics were used to fight TB 60 years ago, the germ has developed the ability to survive attack, and that ability gets passed on to its descendants. Drug-resistant strains of TB emerge when an antibiotic fails to kill all of the bacteria it targets. The surviving bacteria become resistant to that particular drug and frequently other antibiotics as well. Today, for each major TB medication, there’s a TB strain that resists its treatment.

The major cause of TB drug resistance is inadequate treatment, either because the wrong drugs are prescribed or because people don’t take their entire course of medication.

How is Tuberculosis diagnosed?

f your doctor suspects TB, you will need a complete medical evaluation and tests for TB infection.
Skin test
The most commonly used diagnostic tool for TB is a simple skin test. Although there are two methods, the Mantoux test is preferred because it’s more accurate.

For the Mantoux test, a small amount of a substance called PPD tuberculin is injected just below 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 swelling at the injection site, indicating a reaction to the injected material. A hard, raised red bump (induration) means you’re likely to have TB infection. The size of the bump determines whether the test results are significant, based on your risk factors for TB.
The Mantoux test isn’t perfect. 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 different type of mycobacterium other than the one that causes tuberculosis, or if you’ve recently been vaccinated with the bacillus Calmette-Guerin (BCG) vaccine. This TB vaccine is seldom used in the United States, but widely used in countries with high TB infection rates.

On the other hand, some people who are infected with TB — including children, older people and people with AIDS — may have a delayed or no response to the Mantoux test.
Blood tests
Blood tests may be used to confirm or rule out latent or active TB. These tests use sophisticated technology to measure the immune system’s reaction to Mycobacterium tuberculosis. These tests are quicker and more accurate than is the traditional skin test. They may be useful if you’re at high risk of TB infection but have a negative response to the Mantoux test, or if you received the BCG vaccine.
Further testing

If the results of a TB test are positive (referred to as “significant”), you may have further tests to help determine whether you have active TB disease and whether it is a drug-resistant strain.
These tests may include:
•    Chest X-ray or CT scan. 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 in your lungs 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. A computerized tomography (CT) scan, which uses cross-sectional X-ray images, may show more subtle signs of disease.
•    Culture tests. If your chest X-ray shows signs of TB, 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.
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. Because TB bacteria grow very slowly, traditional culture tests can take four to eight weeks.
•    Other tests. Testing called nuclear acid amplification (NAA) can detect genes associated with drug resistance in Mycobacterium tuberculosis. This test is generally available only in developed countries.
A test used primarily in developing countries is called the microscopic-observation drug-susceptibility (MODS) assay. It can detect the presence of TB bacteria in sputum in as little as seven days. Additionally, the test can identify drug-resistant strains of the TB bacteria.

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 AIDS, 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. Children 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.

What is the treatment for Tuberculosis?

Medications are the cornerstone of tuberculosis treatment. But treating TB takes much longer than treating other types of bacterial infections. Normally, you take antibiotics for at least six to nine months to destroy the TB bacteria. The exact drugs and length of treatment depend on your age, overall health, possible drug resistance, the form of TB (latent or active) and its location in the body.
Several promising new TB drugs are in development, and some may become available within the next 10 years.

Treating TB infection (latent TB)
If tests show that you have TB infection but not active disease, your doctor may recommend preventive drug therapy to destroy bacteria that might become active in the future. You’re likely to receive a daily or twice-a-week dose of the TB medication isoniazid. For treatment to be effective, you usually take isoniazid for nine months. Long-term use of isoniazid can cause side effects, including the life-threatening liver disease hepatitis. For this reason, your doctor will monitor you closely while you’re taking isoniazid. During treatment, avoid using Paracetamol and avoid or limit alcohol use. Both 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, ethambutol and pyrazinamide. This regimen may change if 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 the bacteria are drug-resistant, one or two of the four drugs may be stopped after a few months. You may be hospitalized for the first two weeks of therapy or until tests show that you’re no longer contagious.

Sometimes the drugs may be combined in a single tablet such as isoniazid, rifampin and pyrazinamide. This makes your treatment less complicated while ensuring that you get all the drugs needed to completely destroy TB bacteria. Another drug that may make treatment easier is rifapentine, which is taken just once a week during the last four months of therapy, in combination with other drugs.

Treating drug-resistant TB
Multidrug-resistant TB (MDR TB) can’t be cured by the two major TB drugs, isoniazid and rifampin. Extensive drug-resistant TB (XDR TB) is resistant to those drugs as well as three or more of the second line TB drugs. Treating these resistant forms of TB is far more costly than is treating nonresistant TB.
Treatment of drug-resistant TB requires taking a “cocktail” of at least four drugs, including first line medications that are still effective and several second line medications, for 18 months to two years or longer. Even with treatment, many people with these types of TB may not survive. If treatment is successful, you may need surgery to remove areas of persistent infection or repair lung damage.

Treating people who have HIV/AIDS
HIV-positive people are especially likely to develop active TB, and drug-resistant forms of the disease are especially dangerous for them. What’s more, the most powerful AIDS drugs (antiretroviral therapy) 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 antiretroviral therapy 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.

Treating children and pregnant women
Treating TB in children is largely the same as treating adults, except that ethambutol is not used for young children because of the possible side effect of vision problems. Instead of ethambutol, children may take streptomycin.

For pregnant women with active TB, initial treatment often involves three drugs — isoniazid, rifampin and ethambutol. Pyrazinamide isn’t recommended because its effect on the unborn baby isn’t known. Some second line TB medications also aren’t recommended.

Completing treatment is essential
After a few weeks, you won’t be contagious and you may start to feel better. It might be tempting to stop taking your TB drugs. But it is crucial 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 allow the bacteria that are still alive to become resistant to those drugs, leading to TB that is much more dangerous and difficult to treat. Drug-resistant strains of TB can quickly become fatal, especially if your immune system is impaired.

In an effort to help people stick with their treatment, a program called directly observed therapy (DOT) is recommended. 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. Sometimes clinics provide incentives, such as food coupons or transportation, for people to show up for their appointments.

Complications

Without treatment, tuberculosis can be fatal. Drug-resistant strains of the disease are more difficult to treat.
Untreated active disease typically affects your lungs, but it can spread to other parts of the body through your bloodstream. Complications vary according to the location of TB bacteria:
•    Lung damage can occur if TB in your lungs (pulmonary TB) isn’t diagnosed and treated early.
•    Severe pain, abscesses and joint destruction may result from TB that infects your bones.
•    Meningitis can occur if TB infects your brain and central nervous system.
•    Miliary TB is TB that has spread throughout your entire body, a serious complication.

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