The Mantoux test or Mendel-Mantoux test is a screening tool for tuberculosis. It is one
of the major tuberculin skin tests used around the world, largely replacing multiple-puncture
tests such as the Tine test. The Heaf test was used until 2005 in the UK, when it was
replaced by the Mantoux test. It is endorsed by the American Thoracic Society and Centers
for Disease Control and Prevention. It was also used in the USSR and is now prevalent
in most of the former Soviet states.
History Tuberculin is a glycerol extract of the tubercle
bacillus. Purified protein derivative tuberculin is a precipitate of species-nonspecific molecules
obtained from filtrates of sterilized, concentrated cultures. The tuberculin reaction was first
described by Robert Koch in 1890. The test was first developed and described by the German
physician Felix Mendel in 1908 It is named after Charles Mantoux, a French physician
who built on the work of Koch and Clemens von Pirquet to create his test in 1907.
In 1939, M. A. Linnikova in the USSR created a modified version of PPD. In 1954, the Soviet
Union started mass production of PPD-L, named after Linnikova.
Procedure A standard dose is 5 tuberculin units tuberculin
RT23 in 0.1 ml solution for injection.) is injected intradermally and read 48 to 72 hours
later. This intradermal injection is termed the Mantoux technique. A person who has been
exposed to the bacteria is expected to mount an immune response in the skin containing
the bacterial proteins. The reaction is read by measuring the diameter
of induration across the forearm in millimeters. If there is no induration, the result should
be recorded as "0 mm". Erythema should not be measured.
If a person has had a history of a positive tuberculin skin test, or had a recent tuberculin
skin test, another skin test should be used. Classification of tuberculin reaction
The results of this test must be interpreted carefully. The person's medical risk factors
determine at which increment of induration the result is considered positive. A positive
result indicates TB exposure. 5 mm or more is positive in
An HIV-positive person Persons with recent contacts with a TB patient
Persons with nodular or fibrotic changes on chest X-ray consistent with old healed TB
Patients with organ transplants, and other immunosuppressed patients
10 mm or more is positive in Recent arrivals from high-prevalence countries
Injection drug users Residents and employees of high-risk congregate
settings Mycobacteriology lab personnel
Persons with clinical conditions that place them at high risk
Children less than four years of age, or children and adolescents exposed to adults in high-risk
categories
15 mm or more is positive in Persons with no known risk factors for TB
(Note: Targeted skin testing programs should only be conducted among high-risk groups)
A tuberculin test conversion is defined as an increase of 10 mm or more within a two-day
period, regardless of age. Alternate criteria include increases of 6, 12, 15 or 18 mm.
False positive result TST positive is measured by size of induration.
The measurement of the induration is determined to be positive depending on risk factors.
For example, a low-risk patient must have a larger induration for a positive than a
high-risk patient. High-risk groups include recent contact, HIV, chest radiograph with
fibrotic changes, organ transplant recipient, and immunosuppression.
According to the Ohio Department of Health and US Department of Health, the Bacillus
Calmette–Guérin vaccine does not protect against TB infection. It does, though, give
80% of children protection against tuberculous meningitis and miliary tuberculosis. Therefore,
a positive TST/PPD in a person who received BCG vaccine is interpreted as latent TB infection.
Due to the test's low specificity, most positive reactions in low-risk individuals are false
positives. A false positive result may be caused by nontuberculous mycobacteria or previous
administration of BCG vaccine. Prior vaccination with BCG may result in a false-positive result
for many years afterwards. False positives can also occur when the injected
area is touched, causing swelling and itching. Another source of false positive results can
be from allergic reaction or hypersensitivity. Although rare, about 0.08 reported reactions
per million doses of tuberculin, these reactions can be dangerous and precautions should be
taken by having epinephrin available. False negative result
The result of PPD or tuberculin test is suppressed by the following conditions:
Infectious mononucleosis Live virus vaccine - The test should not be
carried out within 3 weeks of live virus vaccination and should be rearranged.
Sarcoidosis Hodgkin's disease
Corticosteroid therapy/Steroid use Malnutrition
Immunologically compromised - Those on immuno-suppressive treatment or those with HIV and low CD4 T
cell counts, frequently show negative results from the PPD test.
This is because the immune system needs to be functional to mount a response to the protein
derivative injected under the skin. A false negative result may occur in a person who
has been recently infected with TB, but whose immune system hasn't yet reacted to the bacteria.
Upper respiratory virus infection In case a second tuberculin test is necessary
it should be carried out in the other arm to avoid hypersensitising the skin.
BCG vaccine and the Mantoux test The role of Mantoux testing in people who
have been vaccinated is disputed. The US recommends tuberculin skin testing is not contraindicated
for BCG-vaccinated persons, and prior BCG vaccination should not influence the interpretation
of the test. The UK recommends interferon-γ testing should be used to help interpret positive
Mantoux tests, and serial tuberculin skin testing must not be done in people who have
had prior BCG vaccinations. In general, the US recommendation results in a much larger
number of people being falsely diagnosed with latent tuberculosis, while the UK approach
probably misses patients with latent tuberculosis who should be treated.
According to the US guidelines, latent tuberculosis infection diagnosis and treatment is considered
for any BCG-vaccinated person whose skin test is 10 mm or greater, if any of these circumstances
are present: Was in contact with another person with infectious
TB Was born or has lived in a high TB prevalence
country Is continually exposed to populations where
TB prevalence is high Anergy testing
In cases of anergy, a lack of reaction by the body's defence mechanisms when it comes
into contact with foreign substances, the tuberculin reaction will occur weakly, thus
compromising the value of Mantoux testing. For example, anergy is present in AIDS, a
disease which strongly depresses the immune system. Therefore, anergy testing is advised
in cases where suspicion is warranted that it is present. However, routine anergy skin
testing is not recommended. Two-step testing
Some people who were previously infected with TB may have a negative reaction when tested
years after infection, as the immune system response may gradually wane. This initial
skin test, though negative, may stimulate the body's ability to react to tuberculin
in future tests. Thus, a positive reaction to a subsequent test may be misinterpreted
as a new infection, when in fact it is the result of the boosted reaction to an old infection.
Use of two-step testing is recommended for initial skin testing of adults who will be
retested periodically. This ensures any future positive tests can be interpreted as being
caused by a new infection, rather than simply a reaction to an old infection.
The first test is read 48–72 hours after injection.
If the first test is positive, consider the person infected.
If the first test is negative, give a second test one to three weeks after the first injection.
The second test is read 48–72 hours after injection.
If the second test is positive, consider the person previously infected.
If the second test is negative, consider the person uninfected.
A person who is diagnosed as "infected" on two-step testing is called a "tuberculin reactor".
The US recommendation that prior BCG vaccination be ignored results in almost universal false
diagnosis of tuberculosis infection in people who have had BCG.
Recent developments As a replacement for the Mantoux test, several
other tests are being developed. The QuantiFERON-TB Gold blood test measures the patient’s immune
reactivity to the TB bacterium, and is useful for initial and serial testing of persons
with an increased risk of latent or active tuberculosis infection. Guidelines for its
use were released by the CDC in December 2005. QuantiFERON-TB Gold is FDA-approved in the
United States, has CE Mark approval in Europe and has been approved by the MHLW in Japan.
Heaf test
The Heaf tuberculin skin test was used in the United Kingdom, but discontinued in 2005.
The equivalent Mantoux test positive levels done with 10 TU are
<5 mm induration 5–15 mm induration
>15 mm induration See also
Tuberculosis Latent tuberculosis
QuantiFERON Tine test
References