Dec 09, 2020

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosisTB primarily affects the lungs (pulmonary TB). Other parts of the body may become involved as well, however, either as part of the initial infection or, more commonly, as part of a late widespread infection. Photo source: National Institute of Allergies and Infectious Diseases

TB is spread when a person with active, infectious TB disease coughs, sneezes, or spits, releasing droplets containing TB bacteria into the air, which are then inhaled by someone else. A single cough from a person with active pulmonary TB may contain 3,000 droplets with TB bacteria. If as few as 10 of those bacteria are inhaled by someone nearby, that person can become infected. An individual with active pulmonary TB disease may infect 10-15 other people through close contact over the course of a year.

Not everyone who is exposed to TB bacteria will develop an infection, and not all of those who become infected will develop symptoms of TB disease. Those who are infected but have no symptoms are said to have a latent TB infection. Those who do become sick have an active infection.

  • People with latent TB usually have strong natural defense (immune) systems that prevent the TB bacteria from multiplying. They do not have TB symptoms and cannot spread TB to others. It is possible, however, for a person with a latent infection to develop an active infection in which TB bacteria are “reactivated” and start multiplying. This happens to about 10% of people with untreated latent TB infections who are otherwise in good health. A greater percentage of people with compromised immune systems, such as those suffering from malnutrition, tobacco users, those with diabetes, and especially those with HIV infection, will develop active TB disease.

  • An active TB infection means the TB bacteria are multiplying, either in the lungs or elsewhere in the body. This will cause a person to have symptoms of TB disease. Active TB is highly contagious.

Both latent and active TB can be treated and cured with a combination of antibiotics that must be taken for several months. Without treatment, active TB disease may cause serious illness or even death.

TB has been a leading cause of death for thousands of years. In the days before the discovery of antibiotics, it was called consumption, and those who contracted it were put into long-term hospitals called sanatoriums for the rest of their lives. Although its frequency has decreased dramatically in the United States, the World Health Organization (WHO) estimates that one-third of the world’s population has latent TB. Worldwide, active TB disease is the most common cause of infectious disease-related death, especially among those who are living with HIV, killing about 1.5 million people a year.

In the U.S., there were more than 9,400 reported cases of TB in 2014. This represents about 2.6 cases per 100,000 persons, the lowest recorded since reporting began in 1953. There was resurgence in new cases in the early 1990s, but the rate of TB infections has been steadily declining since then. Nevertheless, certain populations within the U.S. are at higher risk of infection. These include:

  • International travelers

  • African Americans continue to be disproportionately affected.

  • Those living in correctional facilities and other group living situations

  • The homeless

While the numbers of new cases of active TB have again declined in the U.S. due to constant vigilance by the medical community, TB remains a significant national and global public health problem.

One of the many challenges in managing TB worldwide is the number of new cases that are cannot be cured with the standard antibiotics used to treat the disease. This is known as multidrug-resistant tuberculosis (MDR-TB).

  • Inappropriate or incorrect use of the standard antibiotics, or use of poor quality medicines, can cause MDR-TB.

  • Once identified, MDR-TB can be treated and cured using a different combination of antibiotics. However, these “second-line” treatment options are limited and the recommended antibiotics may not be always available. Second-line therapeutic agents require a longer course of treatment (up to 2 years) and are more costly than standard treatment regimens, and the drugs may be associated with more severe adverse side effects.

  • Some cases of TB are resistant to even the most effective second-line anti-TB drugs. This is known as extensively drug-resistant TB (XDR-TB) and is an emerging public health concern. XDR-TB has been defined by WHO and the U.S. Centers for Disease Control and Prevention (CDC) as M. tuberculosis that is resistant to the drugs isoniazid and rifampin, to the drug class fluoroquinolone, and to at least one of three injectable “second-line” drugs (amikacin, kanamycin, or capreomycin). Cases of XDR-TB are being closely monitored by the world medical community and measures are being taken in hopes of limiting its spread.

Laboratory Tests

Screening Tests

Testing for Mycobacterium tuberculosis infection may begin with a TB screening test. These screening tests are not diagnostic; they do not tell whether a person has latent TB or an active infection. Additional exams and tests (see Tests to Diagnose Active TB below) must be performed in follow up to a positive screening result.

TB screening is not used as a general screening test for all people but is targeted at those who are at a high risk for contracting the disease and those who have signs and symptoms consistent with an active TB infection. TB screening may also be done as part of a physical examination prior to starting school or a new job. There are two types of tests used to screen people at high risk for TB; usually only one of the tests is performed:

  • The tuberculin skin test (TST) is performed by injecting a small amount a substance called purified protein derivative (PPD) just under the skin on a person’s forearm. The person must return to the healthcare provider’s office 2 or 3 days after the PPD is injected so the injection site can be examined. If the person is infected with M. tuberculosis, a firm red bump will form at the injection site.

  • The interferon gamma release assay (IGRA) is a blood test that measures how strongly a person’s immune system reacts to specific TB antigens.

Tests to Diagnose Active TB

Acid-fast bacilli (AFB) testing can be used to identify and confirm active infection with M. tuberculosis as well as other Mycobacterium species. (Mycobacteria are called acid-fast bacilli because they are rod-shaped bacteria (bacilli) that can be seen under the microscope following a staining procedure in which the bacteria retain the color of the stain after an acid wash (acid-fast).) One or more of these tests may be performed when a person has signs and symptoms or TB disease or screened positive for TB infection.

Usually three sputum samples are collected early in the morning on different days. If the affected person is unable to produce sputum, a bronchoscope may be used to collect fluid during a procedure called a bronchoscopy. In children, gastric washings/aspirates may be collected. Depending on symptoms, urine, an aspirate from the site of suspected infection, cerebrospinal fluid (CSF), other body fluids, or biopsied tissue samples may be submitted for AFB smear and culture.

  • AFB smear — a microscopic examination of a specimen that has been stained to detect acid-fast bacteria, such as M. tuberculosis. This test can provide probable (presumptive) results within a few hours. It is a valuable tool in helping make decisions about treatment while culture results are pending.

  • Molecular tests for TB (Nucleic acid amplification test(NAAT) or TB PCR) — detect the genetic components of TB bacteria in a sputum sample and are often done when the AFB smear is positive or TB is highly suspected. Like AFB smears, NAATs can provide a presumptive diagnosis, which can aid in the decision of whether to begin treatment before culture results are available. Results of NAAT are typically available several hours after a sample is collected. One type of NAAT detects within two hours the presence of M. tuberculosis and determines if it is resistant to rifampin, one of the most commonly prescribed drugs used to treat TB. However, NAAT testing does not replace AFB cultures. All samples submitted for AFB testing should be cultured to ensure that any mycobacteria that are present are available for further testing, according to the Centers for Disease Control and Prevention.

  • AFB cultures to grow the bacteria are set up at the same time as the AFB smears. Though more sensitive than AFB smears, results of cultures may take days to several weeks.

  • Susceptibility testing on the acid-fast bacteria grown in the cultures that are positive will determine the bacteria’s susceptibility or resistance to drugs most commonly used to treat TB. Depending on the method used, results may be available in 7 days or can take several weeks. There are molecular tests available that can also be used to detect specific genes in the DNA of the bacteria that confer resistance to certain drugs.

Other Laboratory Tests

  • The adenosine deaminase (ADA) test is not a diagnostic test, but it may be used along with other tests to help determine whether a person has a TB infection in the lining of the lungs (pleurae). Pleural fluid presents a unique problem with detecting M. tuberculosis because there may be a large volume of fluid with a very low number of bacteria present. Though the ADA test is not definitive, it is a rapid test and may be elevated even when there are few bacteria present. ADA results may be used to help guide treatment until results from a culture are available.

  • A culture method called microscopic-observation drug-susceptibility (MODS) assay takes only about 7 days to diagnose TB and detects bacterial resistance to antibiotics. It can recognize the presence of TB bacteria much more quickly than traditional culture and can help healthcare providers diagnose and treat the disease at an earlier stage. It has the potential to help control the spread of TB in resource-limited countries, especially those in which HIV infection and TB are prevalent.

Non-Laboratory Tests

X-rays or CT scans are often performed as a follow-up to positive tuberculin skin or IGRA tests to look for signs of Mycobacterium tuberculosis in the lungs and help determine whether a person has active tuberculosis disease or a latent TB infection. Infection with TB can cause a number of characteristic findings on x-rays, including cavities (holes) and calcification in organs such as the lungs and kidneys.