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Screening: Primary Care Tools for the Management of TB

Author(s): J. Carey Jackson, MD, MPH; David Roesel, MD

Screening for TB

Main TB Headings:                      

Latent TB Test Image
Photo credit: Greg Knoblach. Image in the Public Helath Image Library and in the public domain.

 

Return to the Main Page of the Clinician's Tool for the Management of TB in the Foreign Born



Learn more about Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born

  1. Take the Pre-test
  2. View the Tutorial: Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born: A new tutorial for primary care providers caring for the foreign-born, includes both screening and treatment information. (54 slides)

    Specific information about local TB data is available for the geographical areas below.  Each site includes 12-15 slides with local information:
  1. Take the Post-test

View all 72 questions of the TB Survey


Additional Resources in EthnoMed

What is latent tuberculosis?

“Latent tuberculosis” is the term used for people who test positive for tuberculosis (most commonly with a positive tuberculin skin test), but do not have any evidence of active infection. Currently one in three people worldwide are felt to harbor tuberculosis bacilli.

Tuberculosis is transmitted through airborne spread of Mycobacterium tuberculosis. When a person with active pulmonary TB coughs, aerosolized droplets containing bacilli can invade the lungs of close contacts. In 90-95% of cases, the infected person's immune system halts growth of the bacteria and active disease does not develop, although skin or serological testing for TB will convert to positive. Once positive, a person's TB test will generally remain positive for life.

Latent TB Image

Approximately one in ten latent infections will later progress to active disease unless treatment is given. Most cases of active tuberculosis result from reactivation of latent TB.

Who should be screened for latent TB?

Persons at high risk for developing TB disease should be tested for latent TB. This includes:

  • Close contacts of a person with infectious TB.
  • Immigrants from countries with high rates of TB.
  • People who live or work in places where TB is more common, such as homeless shelters, migrant labor camps, prisons, jails, hospitals, and some nursing homes.
  • Medically underserved and low-income populations.
  • Children exposed to high-risk adults.
  • People with chest radiographs showing healed TB.
  • Patients with HIV, silicosis, malnutrition, renal failure, or other conditions placing them at higher risk for active TB.
  • Patients on chronic immunosuppressive drugs.
  • Injection drug users.

The CDC discourages testing of people at low risk for infection.

Which people with latent TB are at highest risk of developing active disease?

Latent TB Lung Image

Overall, 5-10 percent of all people with latent tuberculosis will go on to develop active disease. The risk of reactivation is greatest in those with recent TB infection and in people with conditions which weaken the immune system. The following groups are considered to be at high risk:

  • Recent skin test converters (within the past 2 years)
  • Young children. (Infants have a 40% chance of progressing to active disease, and children are more likely to develop life-threatening forms of TB).
  • Immigrants from countries with high rates of TB (within the first 5 years after immigration)
  • People with the following clinical conditions:
    • HIV/AIDS (10% annual risk of developing active TB)
    • Diabetes mellitus
    • Underweight (more than 10% below normal)
    • Chronic kidney disease, esp. hemodialysis patients
    • Gastrectomy or jejunoilial bypass
    • Silicosis
    • Head and neck cancer
    • Solid organ transplant recipients
    • Prolonged use of immunosuppressive drugs (prednisone 15 mg/day > 1 month, TNF-alpha antagonists)
    • Leukemia or lymphoma
    • Chest X-rays with evidence of prior TB
    • Injection drug users

How do you place a TB skin test?

Latent TB Test Image

The Mantoux tuberculin skin test is the standard method of screening for infection with Mycobacterium tuberculosis. It is performed by placing a subcutaneous injection of 0.1 ml tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The test is read 48-72 hours later by measuring in millimeters the degree of induration (not erythema) perpendicular to the long axis of the forearm. Use of controls to test for anergy is not recommended.

TB Test Image

How is a TB skin test interpreted?

A positive test indicates TB infection, but cannot distinguish between latent and active disease. The cut-off point for a positive reaction depends on the person's overall risk:

≥ 5 mm

≥ 10 mm

 

≥ 15 mm

HIV/AIDS patients

Recent immigrants (within 5 years) from
high-prevalence countries

 

All persons

Recent contacts of infectious
TB cases

Staff and residents of high risk congregate settings 2


Fibrosis on chest X-ray from
prior TB

Mycobacteria laboratory workers


Solid organ transplant recipients

Patients with high risk clinical conditions 3


Immunosuppressive medications 1

Injection drug users



Children under 4, and children exposed to high-risk adults


1. Prednisone = 15 mg/day for one month or more; TNF-alpha antagonists (Infliximab, Etanercept).
2. Hospitals, nursing homes, homeless shelters, correctional facilities.
3.Diabetes, silicosis, chronic kidney disease, leukemias and lymphomas, lung cancer, carcinomas of the head and neck, gastrectomy, jejunoileal bypass, underweight by = 10% ideal body weight.

Latent TB measure Image

  • A skin test conversion is any increase in induration of 10 mm or more.
  • Known contacts of an active case of tuberculosis should be tested at the time of contact, and then re-tested in 8-10 weeks if the initial test is negative.
  • Pregnancy is not a contraindication to tuberculin skin testing.
  • False-negative tests can occur in the setting of malnutrition, HIV infection, sarcoidosis, concurrent viral infection, and use of immunosuppressive medications. However, there is no proven benefit to anergy testing (use of controls) in immunosuppressed people, and it is not recommended.
  • Recent administration of a live vaccine can also cause a false-negative skin test. To prevent this, the PPD should either be placed the same day as a live vaccine or at least 4 weeks afterwards.
  • It takes 2-8 weeks after infection for the skin test to become positive after a person is infected.
  • False-positive tests can be caused by nontuberculous mycobacteria, and recent BCG vaccination (see separate discussion).

What is two-step testing?

If it has been many years since a person was infected with TB, his or her initial skin test may be negative, because of waning immunity. Subsequent tests may be positive, however, because the initial tuberculin placement stimulates the immune response to the test. This phenomenon is referred to as the “booster effect.” The booster effect can be misinterpreted as a new skin test conversion (i.e. a recent TB infection). To avoid this problem, two-step testing should be used as the initial test in people where repeat testing is anticipated (such as hospital workers or nursing home residents).

To perform two-step testing, a second skin test is placed 1-3 weeks after the initial skin test, if the first test is negative. If the second test remains negative, the person is presumed to be negative for latent tuberculosis, and any subsequent positive tests are the result of new infection. If the second test turns positive, this is a boosted response from prior TB infection. The person should be treated for latent TB if indicated (see separate discussion).

Two-step testing may also be performed to better identify latent TB in older immigrants, who may be decades out from their initial infection and have falsely negative initial tests. One problem with this approach is that two-step testing increases the rate of false-positive results due to BCG vaccination.

There is no booster effect with the QuantiFERON® -TB Gold test, so there is no need for two-step testing if this screening method is used.

What about BCG vaccination?

BCG (Bacille Calmette-Guérin) is a vaccine made from an attenuated strain of Mycobacterium bovis. It provides protection against TB meningitis in children as well as some protection against leprosy, but its ability to protect against pulmonary TB is questionable. The use of BCG is widespread in developing countries (see map).

TB Map Image

Prior vaccination with BCG is not a contraindication to TB skin testing, and the CDC guidelines recommend ignoring BCG status when interpreting skin test results and selecting candidates for latent TB treatment. Although BCG vaccination can turn a skin test positive, reactivity due to BCG vaccination wanes over time. If it has been more than 5 years since vaccination, a positive skin test is more likely due to TB infection than vaccination. Furthermore, the larger the size of the PPD reaction, the less likely it is due to BCG. A recent meta-analysis found that reactive skin tests more than 15 years since vaccination or with more than 15 mm of induration were unlikely to be due to prior BCG vaccination.

Interferon-based blood tests such as the QuantiFERON® -TB Gold avoid the possibility of false-positives occurring from BCG vaccination, since cross-reactivity does not occur.

How do you test for TB with QuantiFERON®-TB Gold?

The QuantiFERON®-TB Gold test (Celestis Inc, Australia) was approved by the FDA in 2005 as a means of diagnosing tuberculosis. The CDC considers the test to be an acceptable alternative to skin testing.

The test is performed by incubating the patient's blood for 16-24 hours with synthetic peptides representing two M. tuberculosis- specific antigens. In the presence of latent or active TB infection, these antigens will stimulate interferon-gamma release from the patient's white blood cells, which is then measured by ELISA. The test must be performed within 12 hours of the blood draw, and results are reported as positive, negative, or indeterminate.

TB Hands Image

Advantages:

  • The patient does not need to return for a reading.
  • Results are available within 24 hours.
  • There is no booster phenomenon.
  • There is no reader bias (as can affect skin test interpretation).
  • The result is not affected by prior BCG vaccination.

Disadvantages:

  • Limited availability.
  • More costly.
  • Uncertain interpretation of indeterminate tests.
  • Limited data in children and in HIV infection.
  • Blood must be tested within 12 hours of being drawn.

 

T-SPOT. TB (Oxford Immunotec, UK) is another interferon-based blood test for the detection of tuberculosis. It is currently being evaluated by the FDA.

What sort of TB screening is done prior to immigration?

Persons wishing to immigrate to the United States undergo mandatory screening for pulmonary tuberculosis prior to receiving a visa. This generally consists of a chest radiograph, with sputum microscopy for acid-fast bacilli if abnormal. The Institute of Medicine has recommended that all prospective immigrants also undergo tuberculin skin testing, and receive treatment for latent TB if they test positive, but this is not yet current practice. There are no health screening requirements for non-immigrant visas (temporary visas issued for purposes of work, study, or tourism).

This information is excerpted from:
"Latent TB: FAQ's" by David J. Roesel, MD,
University of Washington/Harborview Medical Center, Seattle, WA.

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