Tuberculosis screening

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Marjan Khan M.B.B.S.[3]

Overview

Screening for tuberculosis is generally done with using a mantoux tuberculin skin test, also known as a tuberculin skin test or a PPD. The test involves injecting a small amount of a purified protein derivative of the tuberculosis bacterium intradermally, and watching for a reaction in the following days.

Screening

Mantoux Tuberculin Skin Test

The Mantoux tuberculin skin test (TST) is the standard method of determining whether a person is infected with Mycobacterium tuberculosis. Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice. The TST is performed by injecting 0.1 ml of tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The injection should be made with a tuberculin syringe, with the needle bevel facing upward. The TST is an intradermal injection. When placed correctly, the injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter.

The skin test reaction should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will need to be rescheduled for another skin test.

The reaction should be measured in millimeters of the induration (palpable, raised, hardened area or swelling). The reader should not measure erythema (redness). The diameter of the indurated area should be measured across the forearm (perpendicular to the long axis).

TST is contraindicated only for persons who have had a severe reaction (e.g., necrosis, blistering, anaphylactic shock, or ulcerations) to a previous TST. It is not contraindicated for any other persons, including infants, children, pregnant women, persons who are HIV-infected, or persons who have been vaccinated with BCG.

In some persons who are infected with M. tuberculosis, the ability to react to tuberculin may wane over time. When given a TST years after infection, these persons may have a false-negative reaction. However, the TST may stimulate the immune system, causing a positive, or boosted reaction to subsequent tests. Giving a second TST after an initial negative TST reaction is called two-step testing.

Two-step testing is useful for the initial skin testing of adults who are going to be retested periodically, such as health care workers or nursing home residents. This two-step approach can reduce the likelihood that a boosted reaction to a subsequent TST will be misinterpreted as a recent infection.

Classification of Tuberculin Reaction

Skin test interpretation depends on two factors:

  • Measurement in millimeters of the induration.
  • Person’s risk of being infected with TB and of progression to disease if infected.
Image from Public Health Image Library (PHIL)
Image from Public Health Image Library (PHIL)
Image from Public Health Image Library (PHIL)
Tuberculin Reaction Considered a Positive Result in:
≥ 5 mm
≥ 10 mm
  • Recent arrivals (less than 5 years) from high-prevalent countries
  • Injection drug users
  • Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters)
  • Mycobacteriology lab personnel
  • Persons with clinical conditions that place them at high risk (e.g., diabetes, prolonged corticosteroid therapy, leukemia, end-stage renal disease, chronic malabsorption syndromes, low body weight)
  • Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories
≥ 15 mm
  • Persons with no known risk factors for TB
Table adapted from CDC[1]


False-Positive Reactions False-Negative Reactions
Some persons may react to the TST even though they are not infected with M. tuberculosis. The causes of these false-positive reactions may include, but are not limited to, the following:
  • Infection with nontuberculosis mycobacteria
  • Previous BCG vaccination
  • Incorrect method of TST administration
  • Incorrect interpretation of reaction
  • Incorrect bottle of antigen used

Some persons may not react to the TST even though they are infected with M. tuberculosis. The reasons for these false-negative reactions may include, but are not limited to, the following:

  • Cutaneous anergy (anergy is the inability to react to skin tests because of a weakened immune system)
  • Recent TB infection (within 8-10 weeks of exposure)
  • Very old TB infection (many years)
  • Very young age (less than 6 months old)
  • Recent live-virus vaccination (e.g., measles and smallpox)
  • Overwhelming TB disease
  • Some viral illnesses (e.g., measles and chicken pox)
  • Incorrect method of TST administration
  • Incorrect interpretation of reaction
Table adapted from CDC[1]

Recommendations for Human Immunodeficiency Virus (HIV) Screening in Tuberculosis Clinics Adapted from CDC[2]

  • CDC recommends HIV screening for all TB patients after the patient is notified that testing will be performed, unless the patient declines (i.e., opt-out screening). This includes persons with TB disease and persons with latent TB infection.
  • Routine HIV testing is also recommended for persons suspected of having TB disease, persons diagnosed with latent TB infection, and contacts to TB patients.
  • Prevention counseling and separate written consent for HIV testing should no longer be required.
  • These recommendations are aimed at eliminating missed opportunities for HIV screening and reducing significant barriers to HIV testing in health care settings by:
  • Using opt-out HIV screening.
  • Annually screening persons at high risk for HIV.
  • Eliminating the need for separate written consent for HIV testing.
  • Eliminating the need for prevention counseling as part of routine HIV screening.
  • Opt-out screening is defined as performing HIV testing after notifying the patient that the test will be performed, and although the patient may decline or defer testing, it is strongly recommended. Assent is inferred unless the patient declines testing.

Quantiferon Gold testing

  • The early detection of infection with Mycobacterium tuberculosis (Mtb) remains a complicated issue pertaining to the control and prevention of TB.[3]
  • For many years, the tuberculin skin test (TST) was the test most commonly used for the diagnosis of TB infection due to its low cost and convenience in most countries.[4]
  • PPD testing has several disadvantages, including poor specificity in people who received the Bacille Calmette-Guerin (BCG) vaccination.[5]
  • In the last decade, interferon gamma release assays (IGRAs) have been introduced to aid in the detection of Latent Tuberculosis.[6]
  • Interferon-gamma release assays (IGRAs) are immunodiagnostics tools in which interferon-gamma (IFN-γ) released by T-cells in response to Mycobacterium tuberculosis-specific antigen is measured.[7]
  • During the past decade, two commercial in vitro IGRAs, including the QuantiFERON-TB Gold In-Tube (QFT-GIT) test and T-SPOT.TB have been introduced for the early detection of M. tuberculosis infection.[7]
  • Innterferon Gold testing include proteins that are almost exclusively present in mycobacterium tuberculosis than those in the purified derivative (PPD) and that are encoded by genes that are not found in mycobacterium bovis, BCG, or most environmental mycobacteria.[8]
  • The QuantiFERON-TB Gold In-Tube test (QFT-GIT) assay measures the IFN-γ concentration in whole blood after stimulation by specific tuberculosis antigens.[8]
  • The Quantiferon Gold test has been largely employed to evaluate the diagnosis of M. tuberculosis infection in developed countries.[6]
  • whether the QFT-GIT will be useful in monitoring the responses to anti-tuberculosis treatment is unclear.[9]

References

  1. 1.0 1.1 "CDC Tuberculin Skin Testing".
  2. "CDC Recommendations for Human Immunodeficiency Virus (HIV) Screening in Tuberculosis (TB) Clinics".
  3. "WHO | Global tuberculosis report 2018, SYSTEM DO NOT MOVE OR EDIT".
  4. Houben RM, Dodd PJ (October 2016). "The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling". PLoS Med. 13 (10): e1002152. doi:10.1371/journal.pmed.1002152. PMC 5079585. PMID 27780211.
  5. Detjen AK, Keil T, Roll S, Hauer B, Mauch H, Wahn U, Magdorf K (August 2007). "Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis". Clin. Infect. Dis. 45 (3): 322–8. doi:10.1086/519266. PMID 17599309.
  6. 6.0 6.1 Lu P, Chen X, Zhu LM, Yang HT (June 2016). "Interferon-Gamma Release Assays for the Diagnosis of Tuberculosis: A Systematic Review and Meta-analysis". Lung. 194 (3): 447–58. doi:10.1007/s00408-016-9872-5. PMID 27039307.
  7. 7.0 7.1 Lalvani A (June 2007). "Diagnosing tuberculosis infection in the 21st century: new tools to tackle an old enemy". Chest. 131 (6): 1898–906. doi:10.1378/chest.06-2471. PMID 17565023.
  8. 8.0 8.1 Dilektasli AG, Erdem E, Durukan E, Eyüboğlu FÖ (November 2010). "Is the T-cell-based interferon-gamma releasing assay feasible for diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country?". Jpn. J. Infect. Dis. 63 (6): 433–6. PMID 21099095.
  9. Dheda K, Pooran A, Pai M, Miller RF, Lesley K, Booth HL, Scott GM, Akbar AN, Zumla A, Rook GA (August 2007). "Interpretation of Mycobacterium tuberculosis antigen-specific IFN-gamma release assays (T-SPOT.TB) and factors that may modulate test results". J. Infect. 55 (2): 169–73. doi:10.1016/j.jinf.2007.02.005. PMID 17448540.

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