What is the scale of the tuberculosis (TB) problem?
Although effective treatment has been available for over 70 years, TB is the leading cause of death from an infectious disease worldwide. The World Health Organization (WHO) estimates that more than one-third of the world’s population is infected with Mycobacterium tuberculosis. TB continues to be a significant disease due to factors such as immigration, the emergence of drug-resistant TB strains, HIV, and other conditions that weaken the immune system.
How is Tuberculosis (TB) spread?
TB is passed from person to person through the air. Individuals with pulmonary (lung) TB can propel aerosols containing Mycobacterium tuberculosis complex organisms into the air when they cough, sneeze, sing, speak or spit. Persons who then inhale these aerosols can become infected. Factors that determine the probability of infection include the immune status of the exposed individual, infectiousness of the TB contact and the proximity, frequency and duration of exposure.
What is TB infection (Latent Tuberculosis Infection “LTBI” or “latent TB”)?
Individuals with TB infection (“LTBI” or “latent TB”) harbor dormant Mycobacterium tuberculosis complex organisms in their bodies but are not infectious and do not have symptoms of TB disease. TB infected individuals usually have a positive T-SPOT.TB test result; however, assessing the probability of infection requires a combination of epidemiological, historical, medical and diagnostic findings. It is estimated that 10% of immunocompetent persons with latent TB infection will develop TB disease during the course of their lives. Approximately half of these individuals will develop TB disease within the first two years after infection, while the other half are at risk of developing TB disease at some stage in their life. The risk of progressing from TB infection to TB disease is increased in those with a weakened immune system. For example, patients living with HIV/AIDS are at a greatly increased risk of progressing to TB disease, as are patients who have undergone an organ transplant, or are receiving immunosuppressive therapy. When appropriately diagnosed, latent TB infection can be treated with antibiotics. Urgency of treatment is dictated by degree of risk of progression which is derived from consideration of epidemiological, medical and diagnostic findings.
What is TB disease (“active TB”)?
TB disease, or active TB, develops when the immune system cannot prevent Mycobacterium tuberculosis complex organisms from multiplying in the body. After exposure, persons can develop latent TB infection or TB disease. TB disease most commonly occurs in the lungs (pulmonary TB) but may occur in other body organs or spaces, particularly in immunocompromised patients or children, and may be localized or disseminated as occurs in miliary TB. Symptoms of pulmonary TB disease may include fever, cough, night sweats, weight loss, and fatigue. Without treatment, TB mortality rates are high. Individuals with TB disease usually have a positive T-SPOT.TB test result; however, assessing the probability of disease requires a combination of epidemiological, historical, medical and diagnostic findings. The definitive diagnosis of TB disease is made on the basis of isolation and identification of the TB mycobacterium in culture. Identification of the mycobacterium by other means, such as genetic tests of its presence, are increasingly being accepted as proof of infection. Persons with latent TB infection are also at risk for progression to TB disease, with that risk being modulated by age, concomitant illness, medication and other epidemiological factors.
Are certain groups of individuals at an increased risk of exposure to Mycobacterium tuberculosis?
Yes, certain groups are more likely to be exposed to Mycobacterium tuberculosis, which may lead to TB infection and/or disease. These include:
- known close contacts of a person with infectious TB disease, primarily pulmonary TB
- persons living in, immigrating from, or traveling to TB-endemic regions of the world
- persons who work or reside in facilities or settings with individuals who are at high risk for TB (e.g. hospitals, homeless shelters, correctional facilities, nursing homes, boarding schools, or residential facilities for persons living with HIV/AIDS)
Are certain individuals at an increased risk
of progressing from latent TB infection to TB disease?
The risk of progression to TB disease is higher in certain individuals, including:
- Persons with weakened immune systems
- Children under the age of five
- Persons living with HIV/AIDS
- Organ or hematologic transplant recipients
- Persons with radiographic evidence of prior healed TB
- Those undergoing medical treatments with immunosuppressive agents such as systemic corticosteroids, TNF-α antagonists and therapies following transplantation
- Persons with leukemia or cancer of the lung, head or neck
- Cigarette smokers
- Drug or alcohol abusers
- Persons with a low body weight
- Persons with silicosis, diabetes mellitus or chronic renal failure/hemodialysis
- Persons who underwent gastrectomy or jejunoileal bypass
- Persons infected with TB within prior 2 years
How important is treatment for TB disease?
Treatment for TB disease is vital. The goals of treatment include not only curing the patient, but reducing transmission to others. In general, the duration of treatment is 6 – 9 months, but is much longer in those with drug-resistant TB. It is crucial that individuals with TB complete their entire course of treatment even if their symptoms improve. TB that is not adequately treated can reactivate or become resistant to drugs, making it more difficult to treat.
Why is the treatment period for TB disease so long?
Most antibiotics capable of destroying bacteria can only do so while the bacteria are actively replicating. The replication cycle of Mycobacterium tuberculosis complex organisms is relatively long; therefore, lengthy treatment is required to ensure that all of the bacteria are destroyed. If the treatment is inconsistent or too short, some bacteria may survive, potentially allowing tuberculosis (TB) disease to reactivate or develop drug-resistance.
How important is treatment for TB infection (“LTBI” or “latent TB”)?
Treatment for latent TB infection is fundamental in preventing TB disease and overall TB elimination efforts. Completed treatment regimens reduce the risk of TB disease by up to 90%. Urgency of treatment is dictated by degree of risk of progression which is derived from consideration of epidemiological, medical and diagnostic findings.
In 2015, recognizing latent TB infection testing and treatment as critical components of ultimately eliminating TB disease, the World Health Organization (WHO) set forth its first guidelines on managing latent TB infection.
Is there a test for the detection of TB infection (“LTBI” or “latent TB”)?
There are several methods to detect TB infection, broadly divided into tuberculin skin tests and blood tests:
- A TST, which has been used to detect TB infection for over 100 years, requires an intradermal injection of a small amount of purified protein derivative (PPD) into the In 48-72 hours, the resultant induration is measured.
- More recently, blood-based tests, referred to as interferon-gamma release assays (IGRAs), have been introduced. The technology of the T-SPOT.TB test, an IGRA, is based on the release of interferon-gamma secreted by individual effector T cells (both CD4+ and CD8+) after being stimulated by TB-specific antigens.
Is there a test for the detection of TB disease (“active TB”)?
Identification of individuals with active TB disease is critical to TB control. Those suspected of having TB disease may undergo a number of tests to confirm the diagnosis (e.g. chest x-ray, sputum culture, smear microscopy, PCR). Samples from the sputum or other sites are collected and cultured to categorically confirm the diagnosis of TB and to determine susceptibility of the strain to a range of antibiotics used for treatment. The T-SPOT.TB test may be used as a diagnostic aid in suspected TB disease patients when used in conjunction with radiography and other medical and diagnostic evaluations. The T-SPOT.TB test, like a TST and the ELISA-based TB blood test, detects TB infection but does not differentiate between active TB disease and latent TB infection.
What is Bacille Calmette-Guérin (BCG) vaccination?
The BCG vaccine is used in many countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease, but confers limited protective value in adults. The BCG vaccine is also used as an immunotherapeutic agent for individuals with bladder cancer. BCG- vaccinated individuals may produce a positive TST, even if they are not infected with Mycobacterium tuberculosis complex organisms. This is a common cause of TST inaccuracy.
Is the T-SPOT.TB test affected by previous BCG vaccination?
Unlike a tuberculin skin test, there is no association between BCG vaccination and T-SPOT.TB test results. The BCG vaccine is an attenuated derivative of virulent Mycobacterium bovis, the bovine or animal form of the TB mycobacterium. The T-SPOT.TB test utilizes antigens (ESAT-6 and CFP10) that are located on a genomic region designated as RD1, region of differentiation 1. The RD1 region is present in all virulent M. bovis strains but is deleted from all BCG strains. Because the antigens used in the T-SPOT.TB test are not present in the BCG vaccine, the T-SPOT.TB test does not produce a false-positive result due to BCG vaccination. It should be noted, however, that patients infected with virulent M. bovis are likely to produce a positive T-SPOT.TB result.
What are the advantages of the T-SPOT.TB test?
The T-SPOT.TB has a sensitivity and specificity exceeding 95%. The T-SPOT.TB test is reliable even in challenging testing populations, including BCG- vaccinated and immunocompromised persons, and relies on routine phlebotomy procedures.
What are the advantages of the T-SPOT.TB test over a tuberculin skin test (TST)?
The T-SPOT.TB test has a number of advantages over a TST, including:
- Single visit to complete test (versus 2 – 4 with TST)
- Improved sensitivity (reliable in patients with weakened immune systems)
- Improved specificity (not affected by BCG vaccine and most non-tuberculous mycobacteria)
What happens if my test is positive?
Your healthcare provider will determine the next steps, which may include evaluating if any additional testing, such as a chest x‑ray, is needed. Your provider may also evaluate whether treatment is indicated. A positive test means you may have either latent TB infection or active TB disease.*
*Information provided is not intended as a substitute for medical diagnosis by a trained healthcare provider. You should always consult your healthcare provider about any healthcare questions you may have.