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Tuberculosis

Health    Tuberculosis

Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine, and brain. Not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection (LTBI) and TB disease. If not treated properly, TB disease can be fatal.

How TB Spreads

TB bacteria are spread through the air from one person to another. The TB bacteria are put into the air when a person with TB disease of the lungs or throat coughs, speaks, or sings. People nearby may breathe in these bacteria and become infected.

TB is not spread by

  • shaking someone's hand
  • sharing food or drink
  • touching bed linens or toilet seats
  • sharing toothbrushes
  • kissing

When a person breathes in TB bacteria, the bacteria can settle in the lungs and begin to grow. From there, they can move through the blood to other parts of the body, such as the kidney, spine, and brain.

TB disease in the lungs or throat can be infectious. This means that the bacteria can be spread to other people. TB in other parts of the body, such as the kidney or spine, is usually not infectious.

People with TB disease are most likely to spread it to people they spend time with every day. This includes family members, friends, and coworkers or schoolmates.

Latent TB Infection and TB Disease

Not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection and TB disease.

Latent TB Infection

TB bacteria can live in the body without making you sick. This is called latent TB infection. In most people who breathe in TB bacteria and become infected, the body is able to fight the bacteria to stop them from growing. People with latent TB infection:

  • Have no symptoms
  • Don't feel sick
  • Can't spread TB bacteria to others
  • Usually have a positive TB skin test reaction or positive TB blood test
  • May develop TB disease if they do not receive treatment for latent TB infection

Many people who have latent TB infection never develop TB disease. In these people, the TB bacteria remain inactive for a lifetime without causing disease. But in other people, especially people who have a weak immune system, the bacteria become active, multiply, and cause TB disease.

TB Disease

TB bacteria become active if the immune system can't stop them from growing. When TB bacteria are active (multiplying in your body), this is called TB disease. People with TB disease are sick. They may also be able to spread the bacteria to people they spend time with every day.

Many people who have latent TB infection never develop TB disease. Some people develop TB disease soon after becoming infected (within weeks) before their immune system can fight the TB bacteria. Other people may get sick years later when their immune system becomes weak for another reason.

For people whose immune systems are weak, especially those with HIV infection, the risk of developing TB disease is much higher than for people with normal immune systems.

The differencve between Latent TB Infection (LTBI) and TB Disease

Table

A Person with Latent TB Infection A Person with TB Disease
Has no symptoms
Has symptoms that may include:
* a bad cough that lasts 3 weeks or longer
* pain in the chest
* coughing up blood or sputum
* weakness or fatigue
* weight loss
* no appetite
* chills
* fever
* sweating at night
Does not feel sick Usually feels sick
Cannot spread TB bacteria to others May spread TB bacteria to others
Usually has a skin test or blood test result indicating TB infection Usually has a skin test or blood test result indicating TB infection
Has a normal chest x-ray and a negative sputum smear May have an abnormal chest x-ray, or positive sputum smear or culture

Signs & Symptoms

Symptoms of TB disease depend on where in the body the TB bacteria are growing. TB bacteria usually grow in the lungs (pulmonary TB). TB disease in the lungs may cause symptoms such as

  • a bad cough that lasts 3 weeks or longer
  • pain in the chest
  • coughing up blood or sputum (phlegm from deep inside the lungs)

Other symptoms of TB disease are

  • weakness or fatigue
  • weight loss
  • no appetite
  • chills
  • fever
  • sweating at night

Symptoms of TB disease in other parts of the body depend on the area affected.

People who have latent TB infection do not feel sick, do not have any symptoms, and cannot spread TB to others.

Exposure to TB

What to Do If You Have Been Exposed To TB

You may have been exposed to TB bacteria if you spent time near someone with TB disease. The TB bacteria are put into the air when a person with active TB disease of the lungs or throat coughs, sneezes, speaks, or sings. You cannot get TB from

  • Clothes
  • Drinking glass
  • Eating utensils
  • Handshake
  • Toilet
  • Other surfaces

If you think you have been exposed to someone with TB disease, you should contact your doctor or local health department about getting a TB skin test or a special TB blood test. Be sure to tell the doctor or nurse when you spent time with the person who has TB disease.

It is important to know that a person who is exposed to TB bacteria is not able to spread the bacteria to other people right away. Only persons with active TB disease can spread TB bacteria to others. Before you would be able to spread TB to others, you would have to breathe in TB bacteria and become infected.

Then the active bacteria would have to multiply in your body and cause active TB disease. At this point, you could possibly spread TB bacteria to others. People with TB disease are most likely to spread the bacteria to people they spend time with every day, such as family members, friends, coworkers, or schoolmates.

Some people develop TB disease soon (within weeks) after becoming infected, before their immune system can fight the TB bacteria. Other people may get sick years later, when their immune system becomes weak for another reason. Many people with TB infection never develop TB disease.

TB Prevention

Preventing Latent TB Infection from Progressing to TB Disease

Many people who have latent TB infection never develop TB disease. But some people who have latent TB infection are more likely to develop TB disease than others. Those at high risk for developing TB disease include:

  • People with HIV infection
  • People who became infected with TB bacteria in the last 2 years
  • Babies and young children
  • People who inject illegal drugs
  • People who are sick with other diseases that weaken the immune system
  • Elderly people
  • People who were not treated correctly for TB in the past

If you have latent TB infection and you are in one of these high-risk groups, you should take medicine to keep from developing TB disease. There are several treatment options for latent TB infection. You and your health care provider must decide which treatment is best for you.

If you take your medicine as instructed, it can keep you from developing TB disease. Because there are less bacteria, treatment for latent TB infection is much easier than treatment for TB disease. A person with TB disease has a large amount of TB bacteria in the body. Several drugs are needed to treat TB disease.

Preventing Exposure to TB Disease While Traveling Abroad

Travelers should avoid close contact or prolonged time with known TB patients in crowded, enclosed environments (for example, clinics, hospitals, prisons, or homeless shelters).

Although multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are occurring globally, they are still rare. HIV-infected travelers are at greatest risk if they come in contact with a person with MDR or XDR TB.

Air travel itself carries a relatively low risk of infection with TB of any kind. Travelers who will be working in clinics, hospitals, or other health care settings where TB patients are likely to be encountered should consult infection control or occupational health experts. They should ask about administrative and environmental procedures for preventing exposure to TB. Once those procedures are implemented, additional measures could include using personal respiratory protective devices.

Travelers who anticipate possible prolonged exposure to people with TB (for example, those who expect to come in contact routinely with clinic, hospital, prison, or homeless shelter populations) should have a TB skin test or a TB blood test before leaving the own country. Additionally, annual testing may be recommended for those who anticipate repeated or prolonged exposure or an extended stay over a period of years.

Because people with HIV infection are more likely to have an impaired response to TB tests, travelers who are HIV positive should tell their physicians about their HIV infection status.

Vaccines

TB Vaccine (BCG)

Bacille Calmette-Guérin (BCG) is a vaccine for tuberculosis (TB) disease.

Children

BCG vaccination should only be considered for children who have a negative TB test and who are continually exposed, and cannot be separated from adults who

  • Are untreated or ineffectively treated for TB disease, and the child cannot be given long-term primary preventive treatment for TB infection; or
  • Have TB disease caused by strains resistant to isoniazid and rifampin.

Health Care Workers

BCG vaccination of health care workers should be considered on an individual basis in settings in which

  • A high percentage of TB patients are infected with TB strains resistant to both isoniazid and rifampin;
  • There is ongoing transmission of drug-resistant TB strains to health care workers and subsequent infection is likely; or
  • Comprehensive TB infection-control precautions have been implemented, but have not been successful.

Health care workers considered for BCG vaccination should be counseled regarding the risks and benefits associated with both BCG vaccination and treatment of latent TB infection.

Testing for TB in BCG-Vaccinated People

People who were previously vaccinated with BCG may receive a TB skin test to test for TB infection. Vaccination with BCG may cause a positive reaction to a TB skin test. A positive reaction to a TB skin test may be due to the BCG vaccine itself or due to infection with TB bacteria.

TB blood tests (IGRAs), unlike the TB skin test, are not affected by prior BCG vaccination and are not expected to give a false-positive result in people who have received BCG.

For children under the age of five, the TB skin test is preferred over TB blood tests.

A positive TB skin test or TB blood test only tells that a person has been infected with TB bacteria. It does not tell whether the person has latent TB infection or has progressed to TB disease. Other tests, such as a chest x-ray and a sample of sputum, are needed to see whether the person has TB disease.

TB and HIV Coinfection

Tuberculosis is a serious health threat, especially for people living with HIV. People living with HIV are more likely than others to become sick with TB. Worldwide, TB is one of the leading causes of death among people living with HIV.

Without treatment, as with other opportunistic infections, HIV and TB can work together to shorten lifespan.

  • Someone with untreated latent TB infection and HIV infection is much more likely to develop TB disease during his or her lifetime than someone without HIV infection.
  • Among people with latent TB infection, HIV infection is the strongest known risk factor for progressing to TB disease.
  • A person who has both HIV infection and TB disease has an AIDS-defining condition.

People infected with HIV who also have either latent TB infection or TB disease can be effectively treated. The first step is to ensure that people living with HIV are tested for TB infection. If found to have TB infection, further tests are needed to rule out TB disease. The next step is to start treatment for latent TB infection or TB disease based on test results.

Treatment

Untreated latent TB infection can quickly progress to TB disease in people living with HIV since the immune system is already weakened. And without treatment, TB disease can progress from sickness to death.

Fortunately, there are a number of treatment options for people living with HIV who also have either latent TB infection or TB disease.

TB Terms

TB Disease

An illness in which TB bacteria are multiplying and attacking a part of the body, usually the lungs The symptoms of TB disease include weakness, weight loss, fever, no appetite, chills, and sweating at night. Other symptoms of TB disease depend on where in the body the bacteria are growing.

If TB disease is in the lungs (pulmonary TB), the symptoms may include a bad cough, pain in the chest, or coughing up blood. A person with TB disease may be infectious and spread TB bacteria to others.

BCG

A vaccine for TB named after the French scientists who developed it, Calmette and Guérin.

Chest x-ray

A picture of the inside of your chest. A chest x-ray is made by exposing a film to x-rays that pass through the chest. A doctor can look at this film to see whether TB bacteria have damaged the lungs.

Contact

A person who has spent time with a person with infectious TB.

Culture

A test to see whether there are TB bacteria in your phlegm or other body fluids. This test can take 2 to 4 weeks in most laboratories.

Directly observed therapy (DOT)

A way of helping patients take their medicine for TB. If you get DOT, you will meet with a health care worker every day or several times a week. You will meet at a place you both agree on. This can be the TB clinic, your home or work, or any other convenient location. You will take your medicine while the health care worker watches.

Extensively drug-resistant TB (XDR TB)

XDR TB is a rare type of TB disease that is resistant to nearly all medicines used to treat TB.

Extrapulmonary TB

TB disease in any part of the body other than the lungs (for example, the kidney, spine, brain, or lymph nodes).

HIV infection

Infection with the human immunodeficiency virus, the virus that causes AIDS (acquired immunodeficiency syndrome). A person with both latent TB infection and HIV infection is at very high risk for developing TB disease.

Isoniazid (INH)

A medicine used to prevent TB disease in people who have latent TB infection. INH is also one of the four medicines often used to treat TB disease.

Latent TB infection

A condition in which TB bacteria are alive, but inactive in the body. People with latent TB infection have no symptoms, don't feel sick, can't spread TB to others, and usually have a positive TB skin test or positive TB blood test reaction. But they may develop TB disease if they do not receive treatment for latent TB infection.

Multidrug-resistant TB (MDR TB)

TB disease caused by bacteria resistant to two of the most important medicines: INH and RIF.

Mycobacterium tuberculosi

A bacteria that cause latent TB infection and TB disease.

Negative

Usually refers to a test result. If you have a negative TB skin test reaction or negative TB blood test reaction, you probably do not have TB infection.

Positive

Usually refers to a test result. If you have a positive TB skin test reaction or positive TB blood test reaction, you probably have TB infection.

Pulmonary TB

TB disease that occurs in the lungs, usually producing a cough that lasts 3 weeks or longer. Most TB disease is pulmonary.

Resistant Bacteria

A bacteria that can no longer be killed by a certain medicine.

Rifampin (RIF)

One of the four medicines often used to treat TB disease. It is considered a first-line drug.

Rifapentine (RPT)

One of two medicines used to treat latent TB infection.

Smear

A test to see whether there are TB bacteria in your phlegm. To do this test, lab workers smear the phlegm on a glass slide, stain the slide with a special stain, and look for any TB bacteria on the slide. This test usually takes 1 day to get the results.

Sputum

A phlegm coughed up from deep inside the lungs. Sputum is examined for TB bacteria using a smear; part of the sputum can also be used to do a culture.

TB Blood Test

A test that uses a blood sample to find out if you are infected with TB bacteria. The test measures the response to TB proteins when they are mixed with a small amount of blood.

TB Skin Test

A test that is often used to find out if you are infected with TB bacteria. A liquid called tuberculin is injected under the skin on the lower part of your arm. If you have a positive reaction to this test, you probably have TB infection. Other tests will be needed to find out if you have latent TB infection or TB disease.

Tuberculin or PPD

A liquid that is injected under the skin on the lower part of your arm during a TB skin test. If you have latent TB infection, you will probably have a positive reaction to the tuberculin.

Infection Control

Infection Control in Health Care Settings

Tuberculosis (TB) transmission has been documented in health care settings where health care workers and patients come in contact with people who have TB disease.

People who work or receive care in health care settings are at higher risk for becoming infected with TB; therefore, it is necessary to have a TB infection control plan as part of a general infection control program designed to ensure the following:

  • prompt detection of infectious patients,
  • airborne precautions, and
  • treatment of people who have suspected or confirmed TB disease.

In all health care settings, particularly those in which people are at high risk for exposure to TB, policies and procedures for TB control should be developed, reviewed periodically, and evaluated for effectiveness to determine the actions necessary to minimize the risk for transmission of TB.

The TB infection control program should be based on a three-level hierarchy of control measures and include:

  1. Administrative measures
  2. Environmental controls
  3. Use of respiratory protective equipment

Treatment

Not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection and TB disease. Both latent TB infection and TB disease can be treated.

Without treatment latent TB infection can progress to TB disease. If not treated properly, TB disease can be fatal.

Deciding When to Treat Latent TB Infection

People with latent TB infection do not have symptoms, and they cannot spread TB bacteria to others. However, if latent TB bacteria become active in the body and multiply, the person will go from having latent TB infection to being sick with TB disease. For this reason, people with latent TB infection should be treated to prevent them from developing TB disease.

Treatment of latent TB infection should start after excluding the possibility of TB disease.

Groups Who Should be Given High Priority for Latent TB Infection Treatment include:

  • People with a positive TB blood test (interferon-gamma release assay or IGRA).
  • People with a tuberculin skin test (TST) reaction of 5 or more millimeters who are:
    • HIV-infected persons.
    • Recent contacts to a patient with active TB disease.
    • Persons with fibrotic changes on chest radiograph consistent with old TB.
    • Organ transplant recipients.
  • People with a TST reaction of 10 or more millimeters who are:
    • From countries where TB is common, including Mexico, the Philippines, Vietnam, India, China, Haiti, and Guatemala, or other countries with high rates of TB. (Of note, people born in Canada, Australia, New Zealand, or Western and Northern European countries are not considered at high risk for TB infection, unless they spent time in a country with a high rate of TB.)
    • Injection drug users.
    • Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities).
    • Mycobacteriology laboratory personnel.
    • Children under 4 years of age, or children and adolescents exposed to adults in high-risk categories.

Persons with no known risk factors for TB may be considered for treatment of LTBI if they have either a positive IGRA result or if their reaction to the TST is 15 mm or larger. However, targeted TB testing programs should only be conducted among high-risk groups. All testing activities should be accompanied by a plan for follow-up care for persons with latent TB infection or disease.

Treatment Regimens for Latent TB Infection (LTBI)

The four treatment regimens for latent TB infection (LTBI) use isoniazid (INH), rifapentine (RPT), or rifampin (RIF). While all the regimens are effective, healthcare providers should prescribe the more convenient shorter regimens, when possible. Patients are more likely to complete shorter treatment regimens.

Treatment must be modified if the patient is a contact of an individual with drug-resistant TB disease. Consultation with a TB expert is advised if the known source of TB infection has drug-resistant TB.

Treatment for TB Disease

When TB bacteria become active (multiplying in the body) and the immune system can't stop the bacteria from growing, this is called TB disease. TB disease will make a person sick. People with TB disease may spread the bacteria to people with whom they spend many hours.

It is very important that people who have TB disease are treated, finish the medicine, and take the drugs exactly as prescribed. If they stop taking the drugs too soon, they can become sick again; if they do not take the drugs correctly, the TB bacteria that are still alive may become resistant to those drugs. TB that is resistant to drugs is harder and more expensive to treat.

TB disease can be treated by taking several drugs for 6 to 9 months. Of the approved drugs, the first-line anti-TB agents that form the core of treatment regimens are:

  • isoniazid (INH)
  • rifampin (RIF)
  • ethambutol (EMB)
  • pyrazinamide (PZA)

TB Regimens for Drug-Susceptible TB

Regimens for treating TB disease have an intensive phase of 2 months, followed by a continuation phase of either 4 or 7 months (total of 6 to 9 months for treatment).

Drug Susceptible TB Disease Treatment Regimens

Table for Intensive Phase

Regimen Drugs Interval and Dose (minimum duration) Comments Regimen Effectiveness
1 Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), Pyrazinamide (PZA) 7 days/week for 56 doses (8 weeks) or 5 days/week for 40 doses (8 weeks) This is the preferred regimen for patients with newly diagnosed pulmonary TB. Most Effective
2 Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), Pyrazinamide (PZA) 7 days/week for 56 doses (8 weeks) or 5 days/week for 40 doses (8 weeks) Preferred alternative regimen in situations in which more frequent DOT during continuation phase is difficult to achieve. Effective
3 Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), Pyrazinamide (PZA) 3 times weekly for 24 doses (8 weeks) Use regimen with caution in patients with HIV and/or cavitary disease. Missed doses can lead to treatment failure, relapse, and acquired drug resistance. Less Effective
4 Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), Pyrazinamide (PZA) 7 days/week for 14 doses then twice weekly for 12 doses Do not use twice-weekly regimens in HIV-infected patients or patients with smear positive and/or cavitary disease. If doses are missed then therapy is equivalent to once weekly, which is inferior. Least Effective

Table For Continuation Phase

Regimen Drugs Interval and Dose (minimum duration) Range of Total Doses Comments Regimen Effectiveness
1 Isoniazid (INH), Rifampin (RIF) 7 days/week for 126 doses (18 weeks) or 5 days/week for 90 doses (18 weeks) 182 to 130 This is the preferred regimen for patients with newly diagnosed pulmonary TB. Most Effective
2 Isoniazid (INH), Rifampin (RIF) 3 times weekly for 54 doses (18 weeks) 110 to 94 Preferred alternative regimen in situations in which more frequent DOT during continuation phase is difficult to achieve. Effective
3 Isoniazid (INH), Rifampin (RIF) 3 times weekly for 54 doses (18 weeks) 78 Use regimen with caution in patients with HIV and/or cavitary disease. Missed doses can lead to treatment failure, relapse, and acquired drug resistance. Less Effective
4 Isoniazid (INH), Rifampin (RIF) Twice weekly for 36 doses (18 weeks) 62 Do not use twice-weekly regimens in HIV-infected patients or patients with smear positive and/or cavitary disease. If doses are missed then therapy is equivalent to once weekly, which is inferior. Least Effective

Continuation Phase of Treatment

The continuation phase of treatment is given for either 4 or 7 months. The 4-month continuation phase should be used in most patients. The 7-month continuation phase is recommended only for the following groups:

  • Patients with cavitary pulmonary TB caused by drug-susceptible organisms and whose sputum culture obtained at the time of completion of 2 months of treatment is positive;
  • Patients whose intensive phase of treatment did not include PZA;
  • Patients with HIV who are not receiving antiretroviral treatment (ART) during TB treatment; and
  • Patients being treated with once weekly INH and rifapentine and whose sputum culture obtained at the time of completion of the intensive phase is positive. (Note: Use of once-weekly therapy with INH 900 mg and rifapentine 600 mg in the continuation phase is not generally recommended. In uncommon situations where more than once-weekly DOT is difficult to achieve, once-weekly continuation phase therapy with INH 900 mg plus rifapentine 600 mg may be considered for use only in HIV uninfected persons without cavitation on chest radiography.)

Treatment for Drug-Resistant TB

Drug-resistant TB is caused by TB bacteria that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF).

Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

Treating and curing drug-resistant TB is complicated. Inappropriate management can have life-threatening results. Drug-resistant TB should be managed by or in close consultation with an expert in the disease.

Adverse Events

Patients on treatment for latent TB infection (LTBI) or TB disease should report any signs and symptoms of adverse drug reactions to their health care provider, including

  • Unexplained loss of appetite, nausea or vomiting, brown urine*, or jaundice (yellowing of skin or eyes)
  • Persistent tingling, numbness, or burning of hands or feet
  • Persistent weakness, fatigue, fever, or abdominal tenderness
  • Easy bruising or bleeding
  • Blurred vision or changed vision

*Patients taking rifampin (RIF) or rifapentine (RPT) should be informed that they will notice an orange discoloration of urine and possibly other body fluids. This is normal.

Patients should provide a list of current medications to avoid drug interactions. Some interactions to note:

  • Isoniazid (INH) increases blood levels of phenytoin (Dilantin) and disulfiram (Antabuse)
  • RIF and RPT decrease blood levels of many drugs including oral contraceptives, warfarin and some other anticoagulants ("blood thinners"), sulfonylureas (used for diabetes), and methadone
  • RIF and RPT are contraindicated in HIV-infected individuals being treated with protease inhibitors (PIs) and most nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Healthcare providers treating patients with the combination regimen of isoniazid and rifapentine in 12 once-weekly doses (3HP) should

  • Inform the patient (parents/legal guardians of pediatric patient) about possible adverse effects and instruct them to seek medical attention when symptoms of possible adverse effects first appear.
  • Conduct monthly evaluations for the findings of treatment-associated adverse events (e.g., symptoms suggestive of systemic drug reactions, loss of appetite, vomiting, yellow eyes, tenderness of the liver, easy bruising, rash).
  • Order baseline liver chemistry blood tests (at least alanine or aspartate aminotransferase ALT or AST, respectively) for patients with specific conditions: HIV infection, liver disorders, postpartum period (≤3 months after delivery), regular alcohol usage, injection drug usage, or taking medications with known possible interactions with either isoniazid or rifapentine. Consider a baseline liver chemistry blood test for older patients on an individual basis, especially for those taking medications for chronic medical conditions.
  • Conduct blood tests at the next clinical visit for patients whose baseline testing is abnormal and for others at risk for liver disease. Discontinue 3HP if a serum ALT/AST concentration is ≥5 times the upper limit of normal in the absence of symptoms, or ≥3 times the upper limit of normal in the presence of symptoms.
  • Be vigilant for drug hypersensitivity reactions, particularly hypotension or thrombocytopenia.
  • In case of a possible severe adverse reaction (e.g., hypotension requiring intravenous fluid support), discontinue 3HP and provide supportive medical care.
  • In case of mild to moderate adverse reaction (e.g., dizziness), use conservative management (e.g., treat dizziness with rest, oral fluids), conduct clinical and laboratory monitoring, and consider continuing 3HP treatment under observation.

Treatment in Specific Populations

Treatment for latent TB infection and TB disease for the following populations have additional considerations.

Treatment of LTBI and TB for Persons with HIV

People with HIV who also have either latent TB infection or TB disease can be treated effectively. The first step is to ensure that people with HIV are tested for TB infection. If found to have TB infection, further tests are needed to rule out TB disease. The next step is to start treatment for latent TB infection or TB disease based on test results.

Fortunately, there are several treatment options for people living with HIV who also have latent TB infection or TB disease. Consult with your health care provider or state or local health department for treatment options.

Latent TB Infection and HIV

Someone with untreated latent TB infection and HIV infection is much more likely to develop TB disease during his or her lifetime than someone without HIV infection. There are several effective latent TB treatment regimens available for people with HIV. Health care providers should prescribe the more convenient shorter regimens, when possible, as patients are more likely to complete shorter treatment regimens.

  • Twelve weeks of once-weekly isonaizid and rifapentine (3HP), given by self-administered therapy or directly observed therapy, is the newest CDC-recommended treatment regimen for persons with latent TB infection and HIV and who are taking antiretroviral medications with acceptable drug-drug interactions with rifapentine.
  • Four months of daily rifampin is another treatment option. This regimen should not be used in people with HIV who are taking some combinations of antiretroviral therapy. In situations where rifampin cannot be used, sometimes another drug, rifabutin, may be substituted.
  • For those taking antiretroviral medications with clinically significant drug interactions with once-weekly rifapentine or daily rifampin, nine months of daily isoniazid is an alternative treatment.

TB Disease and HIV

The recommended treatment of TB disease in adults infected with HIV is a 6-month daily regimen consisting of:

  • An intensive phase of isoniazid (INH), a rifamycin (see Drug Interactions below), pyrazinamide (PZA), and ethambutol (EMB) for the first 2 months.
  • A continuation phase of INH and a rifamycin for the last 4 months.

Once-weekly INH and rifapentine in the continuation phase should not be used in any patient infected with HIV.

Six months should be considered the minimum duration of treatment for adults with HIV, even for patients with culture-negative TB. In the uncommon situation in which HIV-infected patients do NOT receive antiretroviral therapy during TB treatment, prolonging treatment to 9 months (extend continuation phase to 7 months) is recommended.

Prolonging treatment to 9 months (extend continuation phase to 7 months) for HIV-infected patients with delayed response to therapy (e.g., culture positive after 2 months of treatment) should be considered.

Drug-Resistant TB and HIV

Treatment of drug-resistant TB in persons with HIV infection is the same as for patients without HIV; however, management of HIV-related TB requires expertise in the management of both HIV and TB.

Antiretroviral Therapy During TB Treatment

For persons with HIV who are not already on ART, treatment for HIV should be initiated during treatment for TB disease, rather than at the end, to improve outcomes among TB patients co-infected with HIV. Anti-retroviral therapy should ideally be initiated within the first 2 weeks of TB treatment for patients with CD4 cell counts <50/mm3 and by 8-12 weeks of TB treatment initiation for patients with CD4 cell counts ≥50/mm3.

An important exception is HIV-infected patients with TB meningitis, in whom antiretroviral therapy should not be initiated in the first 8 weeks of anti-tuberculosis therapy.

Drug Interactions

Rifamycins (a category of drugs for TB disease and latent TB infection treatment) can interact with certain medicines (antiretrovirals) used to treat HIV. One concern is the interaction of rifampin (RIF) with certain antiretroviral agents (some protease inhibitors PIs and nonnucleoside reverse transcriptase inhibitors NRTIs). Rifabutin, which has fewer problematic drug interactions, may be used as an alternative to RIF for HIV-infected patients.

As new antiretroviral agents and more pharmacokinetic data become available, these recommendations on managing interactions are likely to be modified.

Case Management

Directly observed therapy (DOT) and other adherence promoting strategies should be used in all patients with HIV-related TB. The care for HIV-related TB should be provided by, or in consultation with, experts in management of both TB and HIV.

The care for persons with HIV-related TB should include close attention to adherence to both regimens of TB and antiretroviral treatment, drug-drug interactions, paradoxical reaction or Immune Reconstitution Inflammatory Syndrome (IRIS), side effects for all drugs used, and the possibility of TB treatment failure or relapse.

TB Treatment & Pregnancy

Untreated tuberculosis (TB) disease represents a greater hazard to a pregnant woman and her fetus than does its treatment. Treatment should be initiated whenever the probability of TB is moderate to high.

  • Infants born to women with untreated TB may be of lower birth weight than those born to women without TB and, in rare circumstances, the infant may be born with TB.
  • Although the drugs used in the initial treatment regimen for TB cross the placenta, they do not appear to have harmful effects on the fetus.

TB Treatment Regimens for Pregnant Women

Contraindications

The following antituberculosis drugs are contraindicated in pregnant women:

  • Streptomycin
  • Kanamycin
  • Amikacin
  • Capreomycin
  • Fluoroquinolones

Drug-Resistant TB

Pregnant women who are being treated for drug-resistant TB should receive counseling concerning the risk to the fetus because of the known and unknown risks of second-line antituberculosis drugs.

Breastfeeding

Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis drugs because the concentrations of these drugs in breast milk are too small to produce toxicity in the nursing newborn. For the same reason, drugs in breast milk are not an effective treatment for TB disease or latent TB infection in a nursing infant. Breastfeeding women taking INH should also take pyridoxine (vitamin B6) supplementation.

TB Treatment for Children

Once infected with TB bacteria, children are more likely than adults to get sick with TB disease and to get sick more quickly than adults. In comparison to children, TB disease in adults is usually due to past TB infection that becomes active years later, when a person's immune system becomes weak for some reason (e.g., HIV infection, diabetes).

A pediatric TB expert should be involved in the treatment of TB in children and in the management of infants, young children, and immunocompromised children who have been exposed to someone with infectious TB disease. It is very important that children or anyone being treated for latent TB infection or TB disease take the drugs exactly as instructed by the doctor and finish the medicine.

Latent TB Infection Treatment for Children

Treatment is recommended for children with latent TB infection to prevent them from developing TB disease. Infants, young children, and immunocompromised children with latent TB infection or children in close contact with someone with infectious TB disease, require special consideration because they are at increased risk for getting TB disease. Consultation with a pediatric TB expert is recommended before treatment begins.

Children over 2 years of age can be treated for latent TB infection with once-weekly isoniazid-rifapentine for 12 weeks. Alternative treatments for latent TB infection in children include 4 months of daily rifampin or 9 months of daily isoniazid. The regimens are equally acceptable; however, health care providers should prescribe the more convenient shorter regimens, when possible. Patients are more likely to complete shorter treatment regimens.

TB Disease Treatment for Children

TB disease is treated by taking several anti-TB medicines for 6 to 9 months. It is important to note that if a child stops taking the drugs before completion, the child can become sick again.

If drugs are not taken correctly, the bacteria that are still alive may become resistant to those drugs. TB that is resistant to drugs is harder and more expensive to treat, and treatment lasts much longer (up to 18 to 24 months).

Testing & Diagnosis

Testing

There are two kinds of tests that are used to detect TB bacteria in the body: the TB skin test (TST) and TB blood tests. A positive TB skin test or TB blood test only tells that a person has been infected with TB bacteria.

It does not tell whether the person has latent TB infection (LTBI) or has progressed to TB disease. Other tests, such as a chest x-ray and a sample of sputum, are needed to see whether the person has TB disease.

Diagnosis

If a person is found to be infected with TB bacteria, other tests are needed to see if the person has latent TB infection or TB disease.

Who Should be Tested

Certain people should be tested for TB infection because they are at higher risk for being infected with TB bacteria, including:

  • People who have spent time with someone who has TB disease
  • People from a country where TB disease is common (most countries in Latin America, the Caribbean, Africa, Asia, Eastern Europe, and Russia)
  • People who live or work in high-risk settings (for example: correctional facilities, long-term care facilities or nursing homes, and homeless shelters)
  • Health-care workers who care for patients at increased risk for TB disease
  • Infants, children and adolescents exposed to adults who are at increased risk for latent tuberculosis infection or TB disease

Many people who have latent TB infection never develop TB disease. But some people who have latent TB infection are more likely to develop TB disease than others. Those at high risk for developing TB disease include:

  • People with HIV infection
  • People who became infected with TB bacteria in the last 2 years
  • Babies and young children
  • People who inject illegal drugs
  • People who are sick with other diseases that weaken the immune system
  • Elderly people
  • People who were not treated correctly for TB in the past

TB tests are generally not needed for people with a low risk of infection with TB bacteria.

Testing for TB Infection

There are two types of tests for TB infection: the TB skin test and the TB blood test. A person's health care provider should choose which TB test to use. Factors in selecting which test to use include the reason for testing, test availability, and cost. Generally, it is not recommended to test a person with both a TB skin test and a TB blood test.

TB Skin Test

The TB skin test is also called the Mantoux tuberculin skin test (TST). A TB skin test requires two visits with a health care provider. On the first visit the test is placed; on the second visit the health care provider reads the test.

  • The TB skin test is performed by injecting a small amount of fluid (called tuberculin) into the skin on the lower part of the arm.
  • A person given the tuberculin skin test must return within 48 to 72 hours to have a trained health care worker look for a reaction on the arm.
  • The result depends on the size of the raised, hard area or swelling.

Positive Skin Test

This means the person's body was infected with TB bacteria. Additional tests are needed to determine if the person has latent TB infection or TB disease.

Negative Skin Test

This means the person's body did not react to the test, and that latent TB infection or TB disease is not likely.

There is no problem in repeating a TB skin test. If repeated, the additional test should be placed in a different location on the body (e.g., other arm).

The TB skin test is the preferred TB test for children under the age of five.

TB Blood Tests

TB blood tests are also called interferon-gamma release assays or IGRAs.

A health care provider will draw a patient's blood and send it to a laboratory for analysis and results.

  • Positive TB blood test: This means that the person has been infected with TB bacteria. Additional tests are needed to determine if the person has latent TB infection or TB disease.
  • Negative TB blood test: This means that the person's blood did not react to the test and that latent TB infection or TB disease is not likely.

TB blood tests are the preferred TB test for:

  • People who have received the TB vaccine bacille Calmette–Guérin (BCG).
  • People who have a difficult time returning for a second appointment to look for a reaction to the TST.

TB blood tests (IGRAs), unlike the TB skin test, are not affected by prior BCG vaccination and are not expected to give a false-positive result in people who have received BCG. TB blood tests are the preferred method of TB testing for people who have received the BCG vaccine.

Frequency of TB Testing

Health care facilities have different TB testing requirements. Facilities should conduct staff TB testing based on risk classification.

Table

Risk classification Frequency of Testing
Low Baseline; then test if TB exposure occurs
Medium Baseline, then annually
Potential ongoing transmission Baseline, then every 8–10 weeks until evidence of transmission has ceased

Baseline Testing

A baseline test should be given prior to employment. The result of this test can be compared with later tests (due to potential exposure or as part of annual testing) to help determine if recent TB transmission has occurred in the facility.

Annual or Serial Testing

You may need to test for TB on a regular basis. To standardize the interpretation of results, the same test should be used for the baseline and the later tests.

Testing During Pregnancy

There is a greater risk to a pregnant woman and her baby if TB disease is not diagnosed and treated.

TB skin testing is considered both valid and safe throughout pregnancy. TB blood tests also are safe to use during pregnancy, but have not been evaluated for diagnosing TB infection in pregnant women. Other tests are needed to show if a person has TB disease.

Diagnosing Latent TB Infection & Disease

Most persons, but not everyone, with TB disease have one or more symptoms of TB disease. All persons with either symptoms or a positive TB test result should be evaluated for TB disease. If a person has symptoms, but a negative TB test result, they should still be evaluated for TB disease.

Diagnosis of Latent TB Infection

A diagnosis of latent TB infection is made if a person has a positive TB test result and a medical evaluation does not indicate TB disease. The decision about treatment for latent TB infection will be based on a person's chances of developing TB disease by considering their risk factors.

Diagnosis of TB Disease

TB disease is diagnosed by medical history, physical examination, chest x-ray, and other laboratory tests. TB disease is treated by taking several drugs as recommended by a health care provider.

TB disease should be suspected in persons who have any of the following symptoms:

If TB disease is in the lungs (pulmonary), symptoms may include:

  • Coughing for longer than 3 weeks
  • Hemoptysis (coughing up blood)
  • Chest pain

If TB disease is in other parts of the body (extrapulmonary), symptoms will depend on the area affected.

People suspected of having TB disease should be referred for a complete medical evaluation, which will include the following:

Medical History

Clinicians should ask about the patient's history of TB exposure, infection, or disease. It is also important to consider demographic factors (e.g., country of origin, age, ethnic or racial group, occupation) that may increase the patient's risk for exposure to TB or to drug-resistant TB. Also, clinicians should determine whether the patient has medical conditions, such as HIV infection or diabetes, that increase the risk of latent TB infection progressing to TB disease.

Physical Examination

A physical exam can provide valuable information about the patient's overall condition and other factors that may affect how TB is treated, such as HIV infection or other illnesses.

Test for TB Infection

The Mantoux tuberculin skin test (TST) or the TB blood test can be used to test for _M. tuberculosis_infection. Additional tests are required to confirm TB disease.

Chest Radiograph

A posterior-anterior chest radiograph is used to detect chest abnormalities. Lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavitation. These abnormalities may suggest TB, but cannot be used to definitively diagnose TB. However, a chest radiograph may be used to rule out the possibility of pulmonary TB in a person who has had a positive reaction to a TST or TB blood test and no symptoms of disease.

Diagnostic Microbiology

The presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates TB disease. Acid-fast microscopy is easy and quick, but it does not confirm a diagnosis of TB because some acid-fast-bacilli are not M. tuberculosis. Therefore, a culture is done on all initial samples to confirm the diagnosis. (However, a positive culture is not always necessary to begin or continue treatment for TB.)

A positive culture for M. tuberculosis confirms the diagnosis of TB disease. Culture examinations should be completed on all specimens, regardless of AFB smear results. Laboratories should report positive results on smears and cultures within 24 hours by telephone or fax to the primary health care provider and to the state or local TB control program, as required by law.

Drug Resistance

For all patients, the initial M. tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment. Drug susceptibility patterns should be repeated for patients who do not respond adequately to treatment or who have positive culture results despite 3 months of therapy.

Susceptibility results from laboratories should be promptly reported to the primary health care provider and to the state or local TB control program.

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