Core Curriculum on Tuberculosis, 2000
Testing for TB Disease and Infection
Tuberculin Skin Testing
Administration of the Tuberculin Test
The Mantoux tuberculin skin test is the standard
method of identifying persons infected with M. tuberculosis.
Multiple puncture tests (MPTs) should not be used to determine whether
a person is infected. MPTs are not reliable because the amount
of tuberculin injected intradermally cannot be precisely controlled.
Tuberculin skin testing is both safe and reliable throughout the
course of pregnancy.
The Mantoux tuberculin test is performed by placing an intradermal
injection of 0.1 ml of purified protein derivative (PPD) tuberculin
containing 5 tuberculin units (TU) into the inner surface of the
forearm. The injection should be made with a disposable tuberculin
syringe, just beneath the surface of the skin, with the needle bevel
facing upward. This should produce a discrete, pale elevation of
the skin (a wheal) 6 mm to 10 mm in diameter.
To prevent needle stick injuries, needles should not be recapped,
purposely bent or broken, removed from disposable syringes, or otherwise
manipulated by hand. After they are used, disposable needles and
syringes should be placed in puncture-resistant containers for disposal.
Institutional guidelines regarding universal precautions for infection
control (e.g., the use of gloves) should be followed.
The reaction to the Mantoux test should be read by a trained health
care worker 48 to 72 hours after the injection. Patients should
never be allowed to read their own tuberculin skin test results.
If a patient fails to show up for the scheduled reading, a positive
reaction may still be measurable up to 1 week after testing. However,
if a patient who fails to return within 72 hours has a negative
test, tuberculin testing should be repeated.
The area of induration (palpable raised hardened area) around the
site of injection is the reaction to tuberculin. The diameter of
the indurated area should be measured across the forearm (perpendicular
to the long axis). Erythema (redness) should not be measured. All
reactions should be recorded in millimeters, even those classified
as negative. If no induration is found, "0 mm" should
be recorded. A tuberculin skin test conversion is defined as an
increase of ³10 mm of induration within a 2-year period regardless
Classification of the Tuberculin Reaction
A tuberculin reaction of ³5 mm of induration is classified
as positive in the following groups:
- HIV-positive persons
- Recent contacts of TB case
- Persons with fibrotic changes on chest radiograph consistent
with old healed TB
- Patients with organ transplants and other immunosuppressed
patients (receiving the equivalent
of ³15 mg/day of prednisone for ³1 month)
A tuberculin reaction of ³10 mm of induration is classified
as positive in persons who do not meet the preceding criteria but
who have other risk factors for TB. These include:
- Recent arrivals (< 5 years) from high-prevalence countries
- Injection drug users
- Residents and employees of high-risk congregate settings: prisons
and jails, nursing homes and other long-term facilities for the
elderly, hospitals and other health-care facilities, residential
facilities for AIDS patients, and homeless shelters
- Mycobacteriology laboratory personnel
- Persons with clinical conditions that place them at high risk
(see Transmission and
- Children < 4 years of age, or children and adolescents exposed
to adults in high-risk categories.
A tuberculin reaction of ³15 mm of induration is classified
as positive in persons with no known risk factors for TB. However,
targeted skin testing programs should only be conducted among high-risk
In general, these guidelines for interpreting skin test reactions
should also be applied to persons who may have occupational exposure
to TB (e.g., health care workers or staff of nursing homes, drug
treatment centers, or correctional facilities). Thus, the appropriate
cutoff for defining a positive reaction depends on the employee's
individual risk factors for TB, including recent TB exposure, and
the prevalence of TB in the facility. In facilities where the risk
of exposure is very low, ³15 mm may be an appropriate cutoff
for employees with no other risk factors. In facilities where TB
patients receive care, ³10 mm may be an appropriate cutoff for
employees with no other risk factors.
The tuberculin skin test is a valuable tool, but it is not perfect.
Several factors can affect the skin test reaction (see Table 1).
Infection with mycobacteria other than M. tuberculosis
(nontuberculous mycobacteria) and vaccination with bacille Calmette-Guérin
(BCG) can lead to false-positive reactions (a positive skin test
reaction in a person not infected with M. tuberculosis).
See BCG Vaccination
for further information on interpreting tuberculin reactions in
persons with a history of BCG vaccination.
Vaccination with live viruses may also interfere with tuberculin
skin test reactivity and cause false-negative reactions (a negative
skin test reaction in a person infected with M. tuberculosis).
The Advisory Committee on Immunization Practices recommends that
tuberculin skin testing be done on either the same day as vaccination
with live-virus measles vaccine or 4-6 weeks after measles vaccination.
1 Other factors,
such as anergy and overwhelming TB disease, can also lead to false-negative
Table 1. Factors that may cause false-positive
ad false-negative reactions to the tuberculin skin test.
|Type of reaction
Recent TB infection
Very young age (< 6 months old)
Overwhelming TB disease
The absence of a reaction to the tuberculin skin test does not
rule out the diagnosis of TB disease or infection. In immunosuppressed
persons, delayed-type hypersensitivity responses such as tuberculin
reactions may decrease or disappear. This condition, known as anergy,
may be caused by many factors, such as HIV infection, severe or
febrile illness, measles or other viral infections, Hodgkin’s disease,
sarcoidosis, live-virus vaccination, or the administration of corticosteroids
or immunosuppressive drugs. On average, 10% to 25% of patients with
TB disease have negative reactions when tested with a tuberculin
skin test at diagnosis before treatment.
Anergy is detected by administering at least two other delayed-type
hypersensitivity antigens by the Mantoux method of intradermal injection.
The lack of standardization and outcome data limit the evaluation
of the effectiveness of anergy testing. The use of anergy testing
in conjunction with tuberculin skin testing is no longer routinely
recommended for testing programs for M. tuberculosis infection
conducted among HIV-positive persons in the United States.
In some people who are infected with M. tuberculosis, delayed-type
hypersensitivity to tuberculin may wane over the years. When these
people are skin tested many years after infection, they may have
a negative reaction. However, this skin test may stimulate (boost)
their ability to react to tuberculin, causing a positive reaction
to subsequent tests. This boosted reaction may be misinterpreted
as a new infection. The booster phenomenon may occur at any age;
its frequency increases with age and is highest among older persons.
Boosted reactions may occur in persons infected with nontuberculous
mycobacteria or in persons who have had a prior BCG vaccination.
Two-step testing is used to reduce the likelihood that a boosted
reaction will be misinterpreted as a recent infection. If the reaction
to the first test is classified as negative, a second test should
be done 1 to 3 weeks later. A positive reaction to the second test
probably represents a boosted reaction (past infection or prior
BCG vaccination). On the basis of this second test result, the person
should be classified as previously infected and cared for accordingly.
This would not be considered a skin test conversion. If the second
test result is also negative, the person should be classified as
uninfected. In these persons, a positive reaction to any subsequent
test is likely to represent new infection with M. tuberculosis
(skin test conversion). Two-step testing should be used for the
initial skin testing of adults who will be retested
periodically, such as health care workers.
Because of cross-reactions with other mycobacteria, the specificity
of the tuberculin test is less when serial skin testing is performed
than when a single test is administered. Thus, serial skin-testing
programs tend to overestimate the incidence of new TB infection
in the tested population. Because of this potential for overestimation
of new infections, serial skin-testing programs should be targeted
to populations at high risk for continued exposure to infectious