CDC Logo Tuberculosis Information CD-ROM   Image of people
     
jump over main navigation bar to content area
Home
TB Guidelines
Surveillance Reports
Slide Sets
TB-Related MMWRs and Reports
Education/Training Materials
Newsletters
Ordering Information
Help

 

U.S. Department of Health and Human Services

  

Education Materials > Publications > Self-Study Modules on TB > Module 3 > Diagnosis of TB Infection

Self-Study Modules on Tuberculosis

This is an archived document. The links are no longer being updated.

Module 3: Diagnosis of Tuberculosis Infection and Disease

Diagnosis of TB Infection: The Tuberculin Skin Test

The tuberculin skin test is used to determine whether a person has TB infection. In this test, a substance called tuberculin is injected into the skin. Tuberculin is protein derived from tubercle bacilli that have been killed by heating. In most people who have TB infection, the immune system will recognize the tuberculin because it is similar to the tubercle bacilli that caused infection. This will cause a reaction to the tuberculin. Tuberculin is used for diagnosing TB infection; it is not a vaccine.

Tuberculin testing is useful for

  • Examining a person who is not sick but who may have TB infection,such as a person who has been exposed to someone who has TB. In fact, the tuberculin skin test is the only way to diagnose TB infection before the infection has progressed to TB disease.
  • Screening groups of people for TB infection
  • Examining a person who has symptoms of TB disease
Different types of tuberculin tests are available, such as the Mantoux tuberculin skin test and the multiple-puncture test. The Mantoux tuberculin skin test is the preferred type because it is the most accurate.

Mantoux Test

The Mantoux skin test is given by using a needle and syringe to inject 0.1 ml of 5 tuberculin units of liquid tuberculin between the layers of the skin (intradermally), usually on the forearm (Figure 3.1). A tuberculin unit is a standard strength of tuberculin.

The tuberculin used in the Mantoux skin test is also known as purified protein derivative, or PPD. For this reason, the tuberculin skin test is sometimes called a PPD skin test.

With the Mantoux skin test, the patient's arm is examined 48 to 72 hours after the tuberculin is injected. Most people with TB infection have a positive reaction to the tuberculin. The reaction is an area of induration (swelling that can be felt) around the site of the injection. The diameter of the indurated area is measured across the forearm (Figure 3.2); erythema (redness) around the indurated area is not measured, because the presence of erythema does not indicate that a person has TB infection (Figure 3.3).

Figure 3.1 Giving the Mantoux tuberculin skin test. This is a picture of the administration of the Mantoux skin test.

Figure 3.2 Only the induration is being measured. This is CORRECT. This is a picture of the correct reading of the tuberculin skin test when only the induration is measured.

Figure 3.3 The erythema is being measured. This is INCORRECT. This is a picture of the incorrect reading of the tuberculin skin test when the erythema is measured.

Multiple-Puncture Test

Multiple-puncture tests (for example, the Tine test) are done by puncturing the skin of the forearm with a set of short prongs or tines coated with tuberculin. Multiple-puncture tests are easy to give, and they are convenient because they do not require a needle and syringe. However, in the multiple-puncture test the amount of tuberculin that actually enters the skin cannot be measured. Because the amount of tuberculin can always be measured during a Mantoux test, this type of test is more accurate, and it is the preferred method.

Positive reactions to multiple-puncture tests should always be confirmed with a Mantoux test (except when there is blistering at the site of the injection).
 

Study Questions 3.1-3.2

3.1. What is the tuberculin skin test used for?

3.2. How is the Mantoux tuberculin skin test given?

Answers


 
Study Questions 3.3-3.5

3.3. With the Mantoux skin test, when is the patient’s arm examined?

3.4. How is the induration measured?

3.5 Why is the Mantoux skin test preferable to multiple-puncture tests?

Answers

Classifying the Reaction

Whether a reaction to the Mantoux tuberculin skin test is classified as positive depends on the size of the induration and the person's risk factors for TB (Table 3.1).

An induration of 5 or more millimeters is considered a positive reaction for the following people:

  • People with HIV infection
  • Close contacts of people with infectious TB
  • People with chest x-ray findings suggestive of previous TB disease
  • People who inject illicit drugs and whose HIV status is unknown

An induration of 10 or more millimeters is considered a positive reaction for the following people:

  • People born in areas of the world where TB is common (foreign-born persons)
  • People who inject illicit drugs but who are known to be HIV negative
  • Low-income groups with poor access to health care
  • People who live in residential facilities (for example, nursing homes or correctional facilities)
  • People with medical conditions that appear to increase the risk for TB (not including HIV infection), such as diabetes
  • Children younger than 4 years old
  • People in other groups likely to be exposed to TB, as identified by local public health officials

An induration of 15 or more millimeters is considered a positive reaction for people with no risk factors for TB. In most cases, people who have a very small reaction or no reaction probably do not have TB infection.

For people who may be exposed to TB on the job (such as health care workers and staff of nursing homes or correctional facilities), the classification of the skin test reaction as positive or negative depends on

  • The size of the induration
  • The employee's individual risk factors for TB
  • The risk of exposure to TB in the person's job

Therefore, in facilities where the risk of exposure to TB is very low, 15 or more millimeters of induration may be considered a positive reaction for employees with no other risk factors for TB. In facilities where TB patients receive care, 10 or more millimeters of induration may be considered a positive reaction for employees with no other risk factors for TB.

Most people who have a positive skin test reaction will have a positive reaction if they are skin tested later in their lives, regardless of whether they receive treatment. This is because the tuberculin skin test detects the immune response to tuberculin, not the presence of tubercle bacilli in the body (see Diagnosis of TB Infection: The Tuberculin Skin Test).
 

Table 3.1
Classifying the Tuberculin Skin Test Reaction
5 or more millimeters 10 or more millimeters 15 or more millimeters

An induration of 5 or more millimeters is considered positive for

  • People with HIV infection
  • Close contacts
  • People who have had TB disease before
  • People who inject illicit drugs and whose HIV status is unknown

An induration of 10 or more millimeters is considered positive for

  • Foreign-born persons
  • HIV-negative persons who inject illicit drugs
  • Low-income groups
  • People who live in residential facilities
  • People with certain medical conditions
  • Children younger than 4 years old
  • People in other groups as identified by local public health officials

An induration of 15 or more millimeters is considered positive for

  • People with no risk factors for TB

 
Study Questions 3.6-3.7

3.6. What two factors are considered when classifying a skin test reaction as positive or negative? What additional factor is considered for people who may be exposed to TB on the job?

3.7. For which groups of people is 5 or more millimeters of induration considered a positive reaction? Name four.

Answers


 
Study Questions 3.8-3.9

3.8. For which groups of people is 10 or more millimeters of induration considered a positive reaction? Name seven.

3.9. For which group of people is 15 or more millimeters of induration considered a positive reaction?

Answers


 
Case Study 3.1

Which of the following patients have a positive tuberculin skin test reaction?

  1. Mr. West, 36 years old, HIV infected, 08 mm of induration
  2. Mr. Hernandez, 26 years old, native of Mexico, 07 mm of induration
  3. Ms. Jones, 56 years old, has diabetes, 12 mm of induration
  4. Mr. Sung, 79 years old, resident of a nursing home, 11 mm of induration
  5. Mr. Williams, 21 years old, no risk factors, 13 mm of induration
  6. Ms. Marcos, 42 years old, chest x-ray findings suggestive of previous TB, 06 mm of induration
  7. Ms. Rayle, 50 years old, husband has pulmonary TB, 09 mm of induration

Answers

False-Positive Reactions

The skin test is a valuable tool, but it is not perfect. Several factors can affect the skin test reaction. Two factors are infection with nontuberculous mycobacteria (mycobacteria other than M. tuberculosis) and vaccination with BCG. BCG (bacillus Calmette-Guérin) is a vaccine for TB disease that is used in many countries. However, it is rarely used in the United States because studies have shown that it is not completely effective. People who are infected with nontuberculous mycobacteria or who have been vaccinated with BCG may have a positive reaction to the tuberculin skin test even if they do not have TB infection. This is called a false-positive reaction.

There is NO RELIABLE WAY to distinguish a positive tuberculin reaction caused by vaccination with BCG from a reaction caused by true TB infection. However, the reaction is more likely to be due to TB infection if any of the following are true:

  • The reaction is large
  • The person was vaccinated a long time ago
  • The person comes from an area of the world where TB is common
  • The person has been exposed to someone with infectious TB disease
  • The person's family has a history of TB disease

People who have a positive reaction should be further evaluated for TB disease, regardless of whether they were vaccinated with BCG.
 

Study Questions 3.10-3.11

3.10. Name two factors that can cause false-positive reactions to the tuberculin skin test.

3.11. Is there a reliable way to distinguish a positive tuberculin reaction caused by vaccination with BCG from a reaction caused by true TB infection?

Answers


 
Case Study 3.2

A 30-year-old man who recently immigrated from India is given a tuberculin skin test and found to have 14 millimeters of induration. He reports that he was vaccinated with BCG as a child. He also says that his wife was treated for pulmonary TB disease last year.

  • Can you tell for sure whether this man has TB infection?
  • What factors make it more likely that this man's positive reaction is due to TB infection?

Answers

False-Negative Reactions

Some people have a negative reaction to the tuberculin skin test even though they have TB infection. These are called false-negative reactions. False-negative reactions may be due to

  • Anergy
  • Recent TB infection (within the past 10 weeks)
  • Very young age (younger than 6 months old)

The most common cause of false-negative reactions is anergy. Anergy is the inability to react to skin tests because of a weakened immune system. Many conditions, such as HIV infection, cancer, or severe TB disease itself, can weaken the immune system and cause anergy. HIV infection is a main cause of anergy.

Because of their risk for anergy and their risk for TB, HIV-infected people may be tested for anergy if they have a negative reaction to the tuberculin skin test. Anergy testing is done by giving skin tests using two substances other than tuberculin. The recommended substances for anergy testing are mumps, Candida (a type of fungus), or tetanus extracts. Most healthy people will have a skin test reaction to one or more of these substances.

People who do not react to any of the substances, including tuberculin, after 48 to 72 hours (that is, people who have less than 3 millimeters of induration to all of the skin tests), are considered anergic. People who have a reaction (3 or more millimeters of induration) to any of the substances are NOT anergic. If a person being evaluated for anergy has a reaction of 5 or more millimeters of induration to tuberculin, he or she is considered to have TB infection, regardless of the reaction to the other substances.

Another cause of false-negative reactions is recent TB infection (infection within the past 10 weeks). It takes 2 to 10 weeks after TB infection for the body's immune system to be able to react to tuberculin. Therefore, after TB has been transmitted, it takes 2 to 10 weeks before TB infection can be detected by the tuberculin skin test. For this reason, close contacts of someone with infectious TB disease who have a negative reaction to the tuberculin skin test should be retested 10 weeks after the last time they were in contact with the person who has TB disease.

A third cause of false-negative reactions is very young age. Because their immune systems are not yet fully developed, children younger than 6 months old may have a false-negative reaction to the tuberculin skin test.

A false-positive reaction or a false-negative reaction may occur when the tuberculin skin test is given incorrectly or the results are not measured properly. False-positive and false-negative reactions to the tuberculin skin test are summarized in Table 3.2.

Any patient with symptoms of TB should be evaluated for TB disease, regardless of his or her skin test reaction. In fact, people with symptoms of TB should be evaluated for TB disease right away, at the same time that the tuberculin skin test is given. The symptoms of pulmonary TB disease include coughing, pain in the chest when breathing or coughing, and coughing up sputum (phlegm from deep in the lungs) or blood. The general symptoms of TB disease (pulmonary or extrapulmonary) include weight loss, fatigue, malaise, fever, and night sweats. The diagnosis of TB disease is discussed in more detail in the next section of this module.
 

Table 3.2
False-Positive and False-Negative Reactions to the Tuberculin Skin Test
Type of Reaction Possible Cause People at Risk Action to Take*
False-positive Nontuberculous mycobacteria People infected with nontuberculous mycobacteria Evaluate for TB disease if person has TB symptoms
BCG vaccination People vaccinated with BCG Assess likelihood of true TB infection (see five factors under False-Positive Reactions)
False-negative Anergy HIV-infected people, other people with weakened immune systems May do anergy testing
Recent TB infection People infected with M. tuberculosis within the past 10 weeks Retest 10 weeks after exposure to TB ended
Very young age Children younger than 6 months old Retest when child is 6 months old and 10 weeks after exposure to TB ended

* Any patient with symptoms of TB should be evaluated for TB disease, regardless of his or her skin test reaction.
 

Study Questions 3.12-3.14

3.12. Name three factors that can cause false-negative reactions to the tuberculin skin test.

3.13. What is anergy?

3.14. How is anergy testing done?

Answers


 
Study Questions 3.15-3.16

3.15. After TB has been transmitted, how long does it take before TB infection can be detected by the tuberculin skin test?

3.16. What should be done if a patient has a negative skin test reaction but has symptoms of TB disease?

Answers


 
Case Study 3.3

Mr. Bell comes to the TB clinic for a tuberculin skin test. He believes that he has been exposed to TB, and he knows he is at high risk for TB because he is HIV infected. He is given a tuberculin skin test, and his reaction is read 48 hours later as 0 millimeters of induration.

  • What are three ways to interpret this result?

Answer

TB Screening Programs and Two-Step Testing

Many residential facilities, health care facilities, and other settings have TB screening programs. This means that employees and residents are periodically given tuberculin skin tests. The purposes of the screening program are to

  • Identify people who have TB infection and possibly TB disease, so that they can be given treatment as needed
  • Determine whether TB is being transmitted in the facility

In a TB screening program, employees or residents are skin tested when they start their job or enter the facility. This is called the baseline skin test. If they have a negative skin test reaction, they may be retested at regular intervals thereafter. (For most employees, repeat testing should be done at least once a year.)

Employees or residents whose skin test reaction converts from negative to positive between screening intervals have probably become infected with M. tuberculosis. These skin test conversions may indicate that TB is being transmitted in the facility. People with skin test conversions are at high risk of developing TB disease because they were infected with M. tuberculosis relatively recently (within the past 2 years). (See Module 1, Transmission and Pathogenesis of Tuberculosis.) In order to detect TB transmission and identify people who have skin test conversions, accurate information must be obtained for every employee's baseline skin test, as well as for additional skin tests.

One factor that can affect the accuracy of the baseline skin test is the booster phenomenon. The booster phenomenon happens because in some people who have TB infection, the ability to react to tuberculin lessens over time. When these people are skin tested many years after they became infected with M. tuberculosis, they may have a negative reaction. However, if they are tested again within a year of the first test, they may have a positive reaction. This is because the first skin test "jogged the memory" of the immune system, boosting its ability to react to tuberculin. It may appear that these people were infected between the first and second skin tests (recent TB infection). Actually, the second, positive reaction is a boosted reaction (due to TB infection that occurred a long time ago). The booster phenomenon occurs mainly among older adults. The booster phenomenon is illustrated in Figure 3.4.

Figure 3.4 The booster phenomenon. This is a flow chart depicting the booster phenomenon.

The booster phenomenon can present a problem in TB screening programs. This is because a negative reaction to the baseline skin test, followed by a positive reaction to a subsequent skin test that is given up to a year later, may be caused by either

  • Recent TB infection in a person who was NOT infected at the time of the baseline skin test, or
  • A boosted reaction in a person who WAS infected at the time of the baseline skin test

To avoid misinterpretation, a strategy has been developed for telling the difference between boosted reactions and reactions caused by recent infection. This strategy, called two-step testing, means that if a person has a negative reaction to an initial skin test, he or she is given a second test 1 to 3 weeks later.

  • If the reaction to the second test is positive, it probably is a boosted reaction (due to TB infection that occurred a long time ago).
  • If the reaction to the second test is negative, the person is considered uninfected. In this person, a positive reaction to a skin test given later on will probably be due to recent infection.

Thus, because it provides accurate information about each employee's baseline skin test reaction, two-step testing is used in many TB screening programs for skin testing employees when they start their job. In particular, two-step testing is often used in hospitals and nursing homes. The procedure for two-step testing is shown in Figure 3.5.

Figure 3.5 Two-step testing. This is a flow chart depicting two-step testing.
 

Study Questions 3.17-3.20

3.17. What is the booster phenomenon?

3.18. What is the purpose of two-step testing?

3.19. In what type of situation is two-step testing used?

3.20. How is two-step testing done?

Answers


 
Case Study 3.4

Ms. Wilson is a 60-year-old nurse. When she started a job at the local hospital, she was given a tuberculin skin test, her first test in 25 years. Her reaction was read 48 hours later as 0 millimeters of induration. Six months later, she was retested as part of the TB screening program in the unit where she works. Her skin test reaction was read 48 hours later as 11 millimeters of induration.

  • What are two ways to interpret this result?

Answer

 


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination - http://www.cdc.gov/tb

Please send comments/suggestions/requests to: hsttbwebteam@cdc.gov, or to
CDC/Division of Tuberculosis Elimination
Communications, Education, and Behavioral Studies Branch
1600 Clifton Rd., NE - Mailstop E-10, Atlanta, GA 30333