Tuberculosis screening

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mashal Awais, M.D.[2]; Alejandro Lemor, M.D. [3]; Marjan Khan M.B.B.S.[4]

Overview

Tuberculosis screening is performed using a mantoux tuberculin skin test, also known as a tuberculin skin test or a PPD. This test is done by intradermal injection of a small amount of a purified protein derivative of the tuberculosis bacterium then observing the reaction in the following days.

Screening

Mantoux Tuberculin Skin Test

*The Mantoux tuberculin skin test (TST) is primarily used to evaluate a person whether they are infected with Mycobacterium tuberculosis.

*The TST is done by intradermal injection 0.1 ml of tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The injection is done using a tuberculin syringe, with the needle bevel facing upward. In case of a correct injection, it produces a pale elevation of the skin (wheal) 6 to 10 mm in diameter.

*The reaction is read between 48 and 72 hours after administration. If the patient does not return within 72 hours, another TST should be rescheduled.

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

*The only contraindication for TST is in persons who had any severe reaction (e.g., necrosis, blistering, anaphylactic shock, or ulcerations) to another previous TST.

*TST is not contraindicated for any other individuals, including infants, children, pregnant women, HIV-infected patients, or individuals who received BCG vaccination.

*In some individuals with with previous M. tuberculosis infection, the reaction to tuberculin can wane over time, so if TST is done years after infection, it may yield false-negative reaction. However, the TST may activate the immune system, leading to a positive, or boosted reaction to the following tests. Doing a second TST after an initial negative TST reaction, that is known as two-step testing, is preferred especially for healthcare workers or nursing home residents (retested periodically).

Classification of Tuberculin Reaction

Interpretation of TST is based on on two elements:

• Measurement of the induration in millimeters.
• The individual’s risk of being infected with TB and also 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	HIV-positive person Recent contacts of TB case Persons with nodular or fibrotic changes on CXR consistent with old healed TB Patients with organ transplants and other immunosuppressed patients
≥ 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

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

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

• 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 to test.

Quantiferon Gold testing

• The early detection of infection with Mycobacterium tuberculosis (Mtb) remains a complicated issue pertaining to the control and prevention of TB.
• 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.
• PPD testing has several disadvantages, including poor specificity in people who received the Bacille Calmette-Guerin (BCG) vaccination.
• In the last decade, interferon gamma release assays (IGRAs) have been introduced to aid in the detection of Latent Tuberculosis.
• 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.
• 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.
• 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.
• The QuantiFERON-TB Gold In-Tube test (QFT-GIT) assay measures the IFN-γ concentration in whole blood after stimulation by specific tuberculosis antigens.
• The Quantiferon Gold test has been largely employed to evaluate the diagnosis of M. tuberculosis infection in developed countries.
• whether the QFT-GIT will be useful in monitoring the responses to anti-tuberculosis treatment is unclear.

Comparison of 2005 and 2019 recommendations for tuberculosis (TB) screening and testing of U.S. health care personnel (HCP)

Category	2005 Recommendation	2019 Recommendation
Baseline (preplacement) screening and testing	TB screening of all HCP, including a symptom evaluation and test (IGRA or TST) for those without documented prior TB disease or LTBI.	TB screening of all HCP, including a symptom evaluation and test (IGRA or TST) for those without documented prior TB disease or LTBI (unchanged); individual TB risk assessment (new).
Postexposure screening and testing	Symptom evaluation for all HCP when exposure is recognized. For HCP with a baseline negative TB test and no prior TB disease or LTBI, perform a test (IGRA or TST) when the exposure is identified. If that test is negative, do another test 8–10 weeks after the last exposure.	Symptom evaluation for all HCP when exposure is recognized. For HCP with a baseline negative TB test and no prior TB disease or LTBI, perform a test (IGRA or TST) when the exposure is identified. If that test is negative, do another test 8–10 weeks after the last exposure (unchanged).
Serial screening and testing for HCP without LTBI	According to health care facility and setting risk assessment. Not recommended for HCP working in low-risk health care settings. Recommended for HCP working in medium-risk health care settings and settings with potential ongoing transmission.	Not routinely recommended (new); can consider for selected HCP groups (unchanged); recommend annual TB education for all HCP (unchanged), including information about TB exposure risks for all HCP (new emphasis).
Evaluation and treatment of positive test results	Referral to determine whether LTBI treatment is indicated.	Treatment is encouraged for all HCP with untreated LTBI, unless medically contraindicated (new).
Abbreviations: IGRA = interferon-gamma release assay; LTBI = latent tuberculosis infection; TST = tuberculin skin test. *Jensen PA, Lambert LA, Iademarco MF, Ridzon R. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep 2005;54(No. RR-17). https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5417a1.htm.