Disease: Tuberculosis (TB)

    Tuberculosis (TB) facts

    • TB is an infectious disease that's transmitted from person to person.
    • There are many different types of TB.
    • A bacterium, Mycobacterium tuberculosis, causes the disease.
    • There are many risk factors for TB. Clinical symptoms and signs of pulmonary TB include fever, night sweats, cough, hemoptysis (coughing up blood-stained sputum), weight loss, fatigue, and chest pain.
    • Physicians definitively diagnose TB by culturing mycobacteria from sputum or biopsy specimens, but health-care professionals presumptively diagnose TB by history, physical exam, skin testing, and chest X-rays.
    • Treatment of TB infection is related to the type of TB infection and often requires extended treatments (months) with one or more anti-TB drugs.
    • Complications of TB range from none to death and include lung, kidney, and liver problems that can be severe.
    • The prognosis for appropriately treated TB infection is good. The prognosis declines in people who develop complications or who have had previous TB treatments.
    • Prevention of TB involves both early treatment to reduce transmission and isolation of the infected person until they are no longer contagious. There is a vaccine against TB, but it is not used routinely in the U.S. because of efficacy issues and other problems.

    What is tuberculosis?

    Tuberculosis (TB) is a multisystemic infectious disease caused by Mycobacterium tuberculosis, a rod-shaped bacterium. TB is the most common cause of infectious disease-related mortality worldwide (about 1.1 million to 1.7 million people die from it each year worldwide). TB symptoms can be so diffuse that TB is termed the "great imitator" by many who study infectious diseases because TB symptoms can mimic many different diseases. Additional terms are used to describe TB. The terms include consumption, Pott's disease, active, latent, pulmonary, cutaneous, and others (see the following section), and they appear in both medical and nonmedical publications. In most instances, the different terms refer to a specific type of TB with some unique symptoms or findings. The most common site (about 85%) for TB to develop is in the pulmonary tract. Humans are the only known hosts for Mycobacterium tuberculosis (although animals can get infected).

    TB has likely been infecting humans for many centuries; evidence of TB infections has been found in cadavers that date back to about 8000 BC, so the disease has a long history of infecting humans. The Greeks termed it as a wasting away disease (phthisis). For many European countries, TB caused death in about 25% of adults and was the leading cause of death in the U.S. until the early 1900s. Robert Koch discovered TB's cause, Mycobacterium tuberculosis, in 1882. With increased understanding of TB, public-health initiatives, treatment methods like isolation (quarantine), and the development of drugs to treat TB, the incidence of the disease, especially in developed countries, has been markedly reduced.

    There is a vast amount of detailed information available in the medical literature on all aspects of this potentially debilitating and lethal disease. The goal of this article is to introduce the reader to TB and help them to obtain a general knowledge about TB's cause, transmission, diagnostic tests, treatments, and prevention methods.

    Are there different types of tuberculosis (TB)?

    There are many types of tuberculosis, but the main two types are termed either active or latent TB. Active TB is when the disease is actively producing symptoms and can be transmitted to other people; latent disease is when the person is infected with Mycobacterium tuberculosis bacteria, but the bacteria are not producing symptoms (usually due to the body's immune system suppressing the bacterial growth and spread). People with latent TB usually cannot transfer Mycobacterium tuberculosis bacteria to others unless the immune system fails; the failure causes reactivation (bacterial growth is no longer suppressed) that results in active TB so the person becomes contagious.

    Many other types of TB exist in either the active or latent form. These types are named for the signs and for the body systems Mycobacterium tuberculosis preferentially infect, and these infection types vary from person to person. Consequently, pulmonary TB mainly infects the pulmonary system, cutaneous TB has skin symptoms, while miliary TB describes widespread small infected sites (lesions or granulomas about 1 mm-5 mm) found throughout body organs. It is not uncommon for some people to develop more than one type of active TB. More types will be listed in the symptoms and signs section below.

    What causes tuberculosis?

    The cause of TB is infection of human tissue(s) by the bacterium Mycobacterium tuberculosis (mycobacteria). These bacteria are slow growing, aerobic, and can grow within body cells (an intracellular parasitic bacterium). Its unique cell wall helps protect it from the body's defenses and gives mycobacteria the ability to retain certain dyes like fuschsin (a reddish dye) after an acid rinse that rarely happens with other bacterial, fungal, or parasitic genera.

    Mycobacteria that escape destruction by body defenses may be spread by blood or lymphatic pathways to most organs, with preference to those that oxygenate well (lungs, kidneys, and bones, for example). Typical TB lesions, termed granulomas, usually consist of a central necrotic area, then a zone with macrophages, giant Langerhans cells and lymphocytes that become surrounded by immature macrophages, plasma cells, and more lymphocytes. These granulomas also contain mycobacteria. In latent infections, a fibrous capsule usually surrounds the granulomas, and in some people, the granulomas calcify, but if the immune defenses fail initially or at a later time (reactivate), the bacteria continue to spread and disrupt organ functions.

    What are risk factors for tuberculosis?

    There are many risk factors for developing tuberculosis. Certain groups of people have a high risk, such as people who work in hospitals and other areas where TB-infected people may reside (jails, nursing homes, group homes for HIV patients, homeless shelters). Close association with drug users, or people with known TB infections are also at higher risk. Other people at high risk include the following:

    • Visitors and immigrants from areas known to have high incidence of TB
    • Children and the elderly with weakened immune systems (especially those with a positive TB skin test, see below)
    • Patients with HIV infection
    • Drug abusers, especially IV drug abuse
    • Head and neck cancer patients
    • Transplant patients
    • Diabetics
    • Kidney disease patients
    • People undergoing immunosuppressive therapy
    • Silicosis

    What are tuberculosis symptoms and signs?

    Although there are a number of TB types, pulmonary TB is responsible for the majority (about 85%) of TB infections. Consequently, pulmonary TB symptoms and signs may occur with or even before other types of TB are diagnosed. The classical clinical symptoms and signs of pulmonary TB include fever, night sweats, cough, hemoptysis (coughing up blood-stained sputum), weight loss, fatigue, and chest pain. The elderly may just exhibit pneumonitis.

    Other types are loosely classified as extra pulmonary and often have symptoms that are nonspecific but frequently localized to the involved site. The following includes the signs and symptoms of additional types of TB:

    • Skeletal TB (also termed Pott's disease): spinal pain, back stiffness, paralysis is possible
    • TB meningitis: headaches (variable in length but persistent), mental changes, coma
    • TB arthritis: usually pain in a single joint (hips and knees most common)
    • Genitourinary TB: dysuria, flank pain, increased frequency, masses or lumps (granulomas)
    • Gastrointestinal TB: difficulty swallowing, nonhealing ulcers, abdominal pain, malabsorption, diarrhea (may be bloody)
    • Miliary TB: many small nodules widespread in organs that resemble millet seeds (hence its name)
    • Pleural TB: empyema and pleural effusions
    • MDR TB: patients infected with TB bacteria that are resistant to multiple drugs
    • XDR TB: patients infected with TB bacteria that are resistant to some of the most effective anti-TB medications; XDR stands for extensively drug resistant

    How do physicians diagnose tuberculosis?

    Because TB may occur as either a latent or active form, the definitive diagnosis of active TB depends on the culture of mycobacteria from sputum or tissue biopsy. However, it may take weeks for these slow-growing bacteria to grow on specialized media. Since patients with latent TB do not require isolation or immediate drug therapy, it is useful to determine if a person is either not infected, has a latent infection, or is actively infected with transmissible TB bacteria. Consequently, doctors needed a presumptive test(s) that could reasonably assure that the person was infected or not so therapy could begin. After getting a patient's history and physical exam data, the next usual test is the skin test (termed the Mantoux tuberculin skin test or the tuberculin skin test or TST). The test involves injecting tuberculin (an extract made from killed mycobacteria) into the skin. In about 48-72 hours, the skin is examined for induration (swelling) by a qualified person; a positive test (induration) strongly suggests the patient has either been exposed to live mycobacteria or is actively infected. Another test, IGRA (interferon-gamma release assays) can measure the immune response to Mycobacterium tuberculosis. Other quick tests are useful; chest X-rays can give evidence of lung infection while a sputum smear stained with certain dyes that are retained mainly (but not exclusively) by mycobacteria can show the presence of the bacterium. These tests, when examined by a doctor, are useful in establishing a presumptive diagnosis of either latent or active TB, and most doctors will initiate treatment based on their judgment of these tests. In addition, some of these tests are useful in the U.S. and elsewhere only in people who are not vaccinated with a TB vaccine (see below) but are less useful in vaccinated people. For some patients, culture studies still should be completed to determine the drug susceptibility of an infecting TB strain.

    Other tests have been developed. For example, a PCR test (polymerase chain reaction) to detect TB antigens and the LED-FM microscopic technique to identify TB organisms with microscopy may be used. Two other TB blood tests (also called interferon-gamma release assays or IGRAs) have been approved by the FDA and measure how strongly the body's immune system reacts to TB bacteria. IGRAs are recommended in testing patients who have been vaccinated against TB (see prevention section below).

    People with positive symptoms, positive blood tests, sputum smear, or culture positive are considered infected with TB and contagious. Physicians diagnose and treat people with latent TB infections (LTBI) according to the following 2013 CDC criteria:

    • No symptoms or physical findings suggestive of TB disease
    • TST or IGRA result is usually positive
    • Chest radiograph is typically normal
    • If done, respiratory specimens are smear and culture negative
    • Cannot spread TB bacteria to others
    • Should consider treatment for LTBI to prevent TB disease (strongly advised by the CDC)

    What is the treatment for tuberculosis?

    The treatment for TB depends on the type of TB infection and drug sensitivity of the mycobacteria. For latent TB, three anti-TB drugs are used in four different recommended schedules. The drugs are isoniazid (INH), rifampin (RIF; Rifadin), and rifapentine (RPT; Priftin) and the 2013 CDC's four recommended schedules are below and are chosen by the treating doctor based on the patients overall health and type of TB the patient was likely exposed to.

    Latent TB Infection Treatment Regimens Drugs Duration Interval Minimum Doses Isoniazid 9 months Daily
    Twice weekly 270
    76 Isoniazid 6 months Daily
    Twice weekly 180
    52 
 Isoniazid and Rifapentine 3 months Once weekly 12 
 Rifampin 4 months Daily 120 Table reproduced from the CDC; http://www.cdc.gov/tb/topic/treatment/default.htm 
 


    First-line drugs used to treat active TB are INH, RIF, ethambutol (EMB; Myambutol), and pyrazinamide. The CDC offers a guide for the basic treatment schedules for active TB as follows:

    Basic TB Disease Treatment Regimens Preferred Regimen Alternative Regimen Alternative Regimen Initial Phase
    Daily INH, RIF, PZA, and EMB* for 56 doses (8 weeks) Initial Phase
    Daily INH, RIF, PZA, and EMB* for 14 doses (2 weeks), then twice weekly for 12 doses (6 weeks) Initial Phase
    Thrice-weekly INH, RIF, PZA, and EMB* for 24 doses (8 weeks) Continuation Phase
    Daily INH and RIF for 126 doses (18 weeks)
    or
    twice-weekly INH and RIF for 36 doses (18 weeks) Continuation Phase
    Twice-weekly INH and RIF for 36 doses (18 weeks) Continuation Phase
    Thrice-weekly INH and RIF for 54 doses (18 weeks) *EMB can be discontinued if drug susceptibility studies demonstrate susceptibility to first-line drugs; Table reproduced from http://www.cdc.gov/tb/topic/treatment/tbdisease.htm#2

    Treatment of drug-resistant TB can be difficult. Patients with these infections are recommended by the CDC to involve infectious-disease specialists as there are multiple approaches that involve other anti-TB drugs and variable treatment schedules that can be used. In addition, there are new drugs and treatment schedules being developed and approved by the FDA. The infectious-disease consultant may be aware of these newest treatments that may benefit specific patients. For example, bedaquiline (Sirturo) has been approved for treatment of MDR TB.

    In some patients, the lung destruction may be severe and the only treatment left may be surgical resection of the diseased lung tissue.

    What is tuberculosis?

    Tuberculosis (TB) is a multisystemic infectious disease caused by Mycobacterium tuberculosis, a rod-shaped bacterium. TB is the most common cause of infectious disease-related mortality worldwide (about 1.1 million to 1.7 million people die from it each year worldwide). TB symptoms can be so diffuse that TB is termed the "great imitator" by many who study infectious diseases because TB symptoms can mimic many different diseases. Additional terms are used to describe TB. The terms include consumption, Pott's disease, active, latent, pulmonary, cutaneous, and others (see the following section), and they appear in both medical and nonmedical publications. In most instances, the different terms refer to a specific type of TB with some unique symptoms or findings. The most common site (about 85%) for TB to develop is in the pulmonary tract. Humans are the only known hosts for Mycobacterium tuberculosis (although animals can get infected).

    TB has likely been infecting humans for many centuries; evidence of TB infections has been found in cadavers that date back to about 8000 BC, so the disease has a long history of infecting humans. The Greeks termed it as a wasting away disease (phthisis). For many European countries, TB caused death in about 25% of adults and was the leading cause of death in the U.S. until the early 1900s. Robert Koch discovered TB's cause, Mycobacterium tuberculosis, in 1882. With increased understanding of TB, public-health initiatives, treatment methods like isolation (quarantine), and the development of drugs to treat TB, the incidence of the disease, especially in developed countries, has been markedly reduced.

    There is a vast amount of detailed information available in the medical literature on all aspects of this potentially debilitating and lethal disease. The goal of this article is to introduce the reader to TB and help them to obtain a general knowledge about TB's cause, transmission, diagnostic tests, treatments, and prevention methods.

    Are there different types of tuberculosis (TB)?

    There are many types of tuberculosis, but the main two types are termed either active or latent TB. Active TB is when the disease is actively producing symptoms and can be transmitted to other people; latent disease is when the person is infected with Mycobacterium tuberculosis bacteria, but the bacteria are not producing symptoms (usually due to the body's immune system suppressing the bacterial growth and spread). People with latent TB usually cannot transfer Mycobacterium tuberculosis bacteria to others unless the immune system fails; the failure causes reactivation (bacterial growth is no longer suppressed) that results in active TB so the person becomes contagious.

    Many other types of TB exist in either the active or latent form. These types are named for the signs and for the body systems Mycobacterium tuberculosis preferentially infect, and these infection types vary from person to person. Consequently, pulmonary TB mainly infects the pulmonary system, cutaneous TB has skin symptoms, while miliary TB describes widespread small infected sites (lesions or granulomas about 1 mm-5 mm) found throughout body organs. It is not uncommon for some people to develop more than one type of active TB. More types will be listed in the symptoms and signs section below.

    What causes tuberculosis?

    The cause of TB is infection of human tissue(s) by the bacterium Mycobacterium tuberculosis (mycobacteria). These bacteria are slow growing, aerobic, and can grow within body cells (an intracellular parasitic bacterium). Its unique cell wall helps protect it from the body's defenses and gives mycobacteria the ability to retain certain dyes like fuschsin (a reddish dye) after an acid rinse that rarely happens with other bacterial, fungal, or parasitic genera.

    Mycobacteria that escape destruction by body defenses may be spread by blood or lymphatic pathways to most organs, with preference to those that oxygenate well (lungs, kidneys, and bones, for example). Typical TB lesions, termed granulomas, usually consist of a central necrotic area, then a zone with macrophages, giant Langerhans cells and lymphocytes that become surrounded by immature macrophages, plasma cells, and more lymphocytes. These granulomas also contain mycobacteria. In latent infections, a fibrous capsule usually surrounds the granulomas, and in some people, the granulomas calcify, but if the immune defenses fail initially or at a later time (reactivate), the bacteria continue to spread and disrupt organ functions.

    What are risk factors for tuberculosis?

    There are many risk factors for developing tuberculosis. Certain groups of people have a high risk, such as people who work in hospitals and other areas where TB-infected people may reside (jails, nursing homes, group homes for HIV patients, homeless shelters). Close association with drug users, or people with known TB infections are also at higher risk. Other people at high risk include the following:

    • Visitors and immigrants from areas known to have high incidence of TB
    • Children and the elderly with weakened immune systems (especially those with a positive TB skin test, see below)
    • Patients with HIV infection
    • Drug abusers, especially IV drug abuse
    • Head and neck cancer patients
    • Transplant patients
    • Diabetics
    • Kidney disease patients
    • People undergoing immunosuppressive therapy
    • Silicosis

    What are tuberculosis symptoms and signs?

    Although there are a number of TB types, pulmonary TB is responsible for the majority (about 85%) of TB infections. Consequently, pulmonary TB symptoms and signs may occur with or even before other types of TB are diagnosed. The classical clinical symptoms and signs of pulmonary TB include fever, night sweats, cough, hemoptysis (coughing up blood-stained sputum), weight loss, fatigue, and chest pain. The elderly may just exhibit pneumonitis.

    Other types are loosely classified as extra pulmonary and often have symptoms that are nonspecific but frequently localized to the involved site. The following includes the signs and symptoms of additional types of TB:

    • Skeletal TB (also termed Pott's disease): spinal pain, back stiffness, paralysis is possible
    • TB meningitis: headaches (variable in length but persistent), mental changes, coma
    • TB arthritis: usually pain in a single joint (hips and knees most common)
    • Genitourinary TB: dysuria, flank pain, increased frequency, masses or lumps (granulomas)
    • Gastrointestinal TB: difficulty swallowing, nonhealing ulcers, abdominal pain, malabsorption, diarrhea (may be bloody)
    • Miliary TB: many small nodules widespread in organs that resemble millet seeds (hence its name)
    • Pleural TB: empyema and pleural effusions
    • MDR TB: patients infected with TB bacteria that are resistant to multiple drugs
    • XDR TB: patients infected with TB bacteria that are resistant to some of the most effective anti-TB medications; XDR stands for extensively drug resistant

    How do physicians diagnose tuberculosis?

    Because TB may occur as either a latent or active form, the definitive diagnosis of active TB depends on the culture of mycobacteria from sputum or tissue biopsy. However, it may take weeks for these slow-growing bacteria to grow on specialized media. Since patients with latent TB do not require isolation or immediate drug therapy, it is useful to determine if a person is either not infected, has a latent infection, or is actively infected with transmissible TB bacteria. Consequently, doctors needed a presumptive test(s) that could reasonably assure that the person was infected or not so therapy could begin. After getting a patient's history and physical exam data, the next usual test is the skin test (termed the Mantoux tuberculin skin test or the tuberculin skin test or TST). The test involves injecting tuberculin (an extract made from killed mycobacteria) into the skin. In about 48-72 hours, the skin is examined for induration (swelling) by a qualified person; a positive test (induration) strongly suggests the patient has either been exposed to live mycobacteria or is actively infected. Another test, IGRA (interferon-gamma release assays) can measure the immune response to Mycobacterium tuberculosis. Other quick tests are useful; chest X-rays can give evidence of lung infection while a sputum smear stained with certain dyes that are retained mainly (but not exclusively) by mycobacteria can show the presence of the bacterium. These tests, when examined by a doctor, are useful in establishing a presumptive diagnosis of either latent or active TB, and most doctors will initiate treatment based on their judgment of these tests. In addition, some of these tests are useful in the U.S. and elsewhere only in people who are not vaccinated with a TB vaccine (see below) but are less useful in vaccinated people. For some patients, culture studies still should be completed to determine the drug susceptibility of an infecting TB strain.

    Other tests have been developed. For example, a PCR test (polymerase chain reaction) to detect TB antigens and the LED-FM microscopic technique to identify TB organisms with microscopy may be used. Two other TB blood tests (also called interferon-gamma release assays or IGRAs) have been approved by the FDA and measure how strongly the body's immune system reacts to TB bacteria. IGRAs are recommended in testing patients who have been vaccinated against TB (see prevention section below).

    People with positive symptoms, positive blood tests, sputum smear, or culture positive are considered infected with TB and contagious. Physicians diagnose and treat people with latent TB infections (LTBI) according to the following 2013 CDC criteria:

    • No symptoms or physical findings suggestive of TB disease
    • TST or IGRA result is usually positive
    • Chest radiograph is typically normal
    • If done, respiratory specimens are smear and culture negative
    • Cannot spread TB bacteria to others
    • Should consider treatment for LTBI to prevent TB disease (strongly advised by the CDC)

    What is the treatment for tuberculosis?

    The treatment for TB depends on the type of TB infection and drug sensitivity of the mycobacteria. For latent TB, three anti-TB drugs are used in four different recommended schedules. The drugs are isoniazid (INH), rifampin (RIF; Rifadin), and rifapentine (RPT; Priftin) and the 2013 CDC's four recommended schedules are below and are chosen by the treating doctor based on the patients overall health and type of TB the patient was likely exposed to.

    Latent TB Infection Treatment Regimens Drugs Duration Interval Minimum Doses Isoniazid 9 months Daily
    Twice weekly 270
    76 Isoniazid 6 months Daily
    Twice weekly 180
    52 
 Isoniazid and Rifapentine 3 months Once weekly 12 
 Rifampin 4 months Daily 120 Table reproduced from the CDC; http://www.cdc.gov/tb/topic/treatment/default.htm 
 


    First-line drugs used to treat active TB are INH, RIF, ethambutol (EMB; Myambutol), and pyrazinamide. The CDC offers a guide for the basic treatment schedules for active TB as follows:

    Basic TB Disease Treatment Regimens Preferred Regimen Alternative Regimen Alternative Regimen Initial Phase
    Daily INH, RIF, PZA, and EMB* for 56 doses (8 weeks) Initial Phase
    Daily INH, RIF, PZA, and EMB* for 14 doses (2 weeks), then twice weekly for 12 doses (6 weeks) Initial Phase
    Thrice-weekly INH, RIF, PZA, and EMB* for 24 doses (8 weeks) Continuation Phase
    Daily INH and RIF for 126 doses (18 weeks)
    or
    twice-weekly INH and RIF for 36 doses (18 weeks) Continuation Phase
    Twice-weekly INH and RIF for 36 doses (18 weeks) Continuation Phase
    Thrice-weekly INH and RIF for 54 doses (18 weeks) *EMB can be discontinued if drug susceptibility studies demonstrate susceptibility to first-line drugs; Table reproduced from http://www.cdc.gov/tb/topic/treatment/tbdisease.htm#2

    Treatment of drug-resistant TB can be difficult. Patients with these infections are recommended by the CDC to involve infectious-disease specialists as there are multiple approaches that involve other anti-TB drugs and variable treatment schedules that can be used. In addition, there are new drugs and treatment schedules being developed and approved by the FDA. The infectious-disease consultant may be aware of these newest treatments that may benefit specific patients. For example, bedaquiline (Sirturo) has been approved for treatment of MDR TB.

    In some patients, the lung destruction may be severe and the only treatment left may be surgical resection of the diseased lung tissue.

    Source: http://www.rxlist.com

    There are many types of tuberculosis, but the main two types are termed either active or latent TB. Active TB is when the disease is actively producing symptoms and can be transmitted to other people; latent disease is when the person is infected with Mycobacterium tuberculosis bacteria, but the bacteria are not producing symptoms (usually due to the body's immune system suppressing the bacterial growth and spread). People with latent TB usually cannot transfer Mycobacterium tuberculosis bacteria to others unless the immune system fails; the failure causes reactivation (bacterial growth is no longer suppressed) that results in active TB so the person becomes contagious.

    Many other types of TB exist in either the active or latent form. These types are named for the signs and for the body systems Mycobacterium tuberculosis preferentially infect, and these infection types vary from person to person. Consequently, pulmonary TB mainly infects the pulmonary system, cutaneous TB has skin symptoms, while miliary TB describes widespread small infected sites (lesions or granulomas about 1 mm-5 mm) found throughout body organs. It is not uncommon for some people to develop more than one type of active TB. More types will be listed in the symptoms and signs section below.

    Source: http://www.rxlist.com

    Health Services in

    Define Common Diseases

    Brain and Nerve Center helps you find information, definitaions and treatement options for most common diseases, sicknesses, illnesses and medical conditions. Find what diseases you have quick and now.