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{{SI}}
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{{SK}} PPD, TB skin test, TST, tst


{{SK}} PPD, TB skin test
==Overview==
==Overview==
[[Image:Mantoux tuberculin skin test.jpg|thumb|left|The Mantoux skin test consists of an intradermal injection of exactly one tenth of a milliliter (mL) of PPD tuberculin.]]
The [[Mantoux tuberculin skin test]] (TST) is the standard method of determining whether a person is infected with [[Mycobacterium tuberculosis]]. Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice.
 
[[Image:Mantoux_test.jpg|thumb|The size of induration is measured 48-72 hours later.]]
 
The '''Mantoux test''' (or '''Mantoux screening test''',  '''Tuberculin Sensitivity Test''',  '''Pirquet test''', or '''PPD test''' for Purified Protein Derivative) is a diagnostic tool for [[tuberculosis]]. The Mantoux test is used in the [[United States]] and is endorsed by the [[American Thoracic Society]] and Centers for Disease Control and Prevention ([[Centers for Disease Control and Prevention|CDC]]).  Multiple puncture tests such as the [[Tine test]] are not recommended. The Mantoux test is one of the two major [[tuberculin]] skin tests for [[tuberculosis]] used in the world. Until 2005, the [[Heaf test]] was used in the [[United Kingdom]] but the Mantoux test is now used.
 
==History==
[[Tuberculin]] is a glycerine extract of the tubercule bacilli.  Purified protein derivative (PPD) tuberculin is a precipitate of non-species-specific molecules obtained from filtrates of '''sterilized''', concentrated cultures. It was first described by [[Robert Koch]] in 1891. The test is named after [[Charles Mantoux]], a French physician who developed on the work of Koch and [[Clemens von Pirquet]] to create his test in 1907.


==Procedure==
==Procedure==
A standard dose of 5 Tuberculin units (0.1 mL)<ref>http://www.cdc.gov/tb/pubs/Mantoux/part1.htm</ref> (The standard Mantoux test in the UK consists of an intradermal injection of 2TU of Statens Serum Institute (SSI) tuberculin RT23 in 0.1ml solution for injection. <ref>http://www.immunisation.nhs.uk/files/mantouxtest.pdf</ref>) is injected intradermally (into the skin) and read 48 to 72 hours later. A person who has been exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins.
The TST is performed by injecting 0.1 ml of tuberculin purified protein derivative ([[PPD]]) into the inner surface of the forearm.  The injection should be made with a tuberculin syringe, with the needle bevel facing upward. The TST is an intradermal injectionWhen placed correctly, the injection should produce a pale elevation of the skin (a [[wheal]]) 6 to 10 mm in diameter.
 
The reaction is read by measuring the diameter of [[induration]] (palpable raised hardened area) across the forearm (perpendicular to the long axis) in millimetersNo induration should be recorded as "0 mm".  Erythema (redness) should not be measured. 
 
If a person has had a history of a positive tuberculin skin test, another skin test is not needed.
 
==Classification of tuberculin reaction==
The results of this test must be interpreted carefullyThe person's medical risk factors determine at which increment (5 mm, 10 mm, or 15 mm) of induration <ref>From the CDC team of the CDC team at the Saskatchewan Lung Association, [http://www.lung.ca/tb/tbtoday/tbdiagnosis/skin_test.html photos of a PPD bump].</ref> the result is considered positive. A positive result indicates TB exposure.
 
*5 mm or more is positive in
**HIV-positive person
**Recent contacts of TB case
**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 (less than 5 years) from high-prevalence countries
**Injection drug users
**Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters, etc.)
**[[Mycobacteria|Mycobacteriology]] lab personnel
**Persons with clinical conditions that place them at high risk (e.g., [[diabetes]], prolonged [[corticosteroid]] therapy, [[leukemia]], [[renal failure|end-stage renal disease]], chronic [[malabsorption]] syndromes, low body weight, etc)
**Children less than 4 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 2-year period, regardless of age
The skin test reaction should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will need to be rescheduled for another skin test.


==False positive result==
The reaction should be measured in millimeters of the induration (palpable, raised, hardened area or swelling). The reader should not measure [[erythema]] (redness). The diameter of the indurated area should be measured across the forearm (perpendicular to the long axis).
False positive result may be caused by [[nontuberculous mycobacteria]] or previous [[Bacillus Calmette-Guerin|BCG]] vaccine. Prior [[Bacillus Calmette-Guerin|BCG]] may result in a false-positive result for many years afterwards<ref>{{cite journal | author=Chaturvedi N, Cockcroft A | title=Tuberculosis screening among health service employees: who needs chest X-rays? | year=1992 | journal=J Soc Occup Med | volume=42 | pages=179-82 }}</ref>.


==BCG vaccine and the Mantoux test==
==Classification of Tuberculin Reaction==
There is disagreement about the role of Mantoux testing in people who have been vaccinated.  The US recommendation is that tuberculin skin testing is not contraindicated for [[Bacillus Calmette-Guérin|BCG]]-vaccinated persons and that prior BCG vaccination should not influence the interpretation of the test.  The UK recommendation is that interferon-γ testing should be used to help interpret positive Mantoux tests, and that serial tuberculin skin testing must not be done in people who have had prior BCG vaccination.  Please refer to the chapter on [[latent tuberculosis]] for a discussion of the two approaches.  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.
Skin test interpretation depends on two factors:
* Measurement in millimeters of the induration.
* Person’s risk of being infected with [[TB]] and of progression to disease if infected.


According to the US guidelines, latent TB infection (LTBI) diagnosis and treatment for LTBI is considered for any BCG-vaccinated person whose skin test is 10 mm or greater, if any of these circumstances are present:
<div style="float: right;">
*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 principle, in cases of [[anergy]], a lack of reaction by the body's defence mechanisms when foreign substances come into contact with the body, the tuberculin reaction will occur weakly, thus compromising the value of Mantoux testing. Anergy is present, for example, 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. [http://www.annals.org/cgi/content/full/119/3/185]
|valign=top|
[[File:Mantoux tuberculin skin test.jpg|thumb|none|200px|Image from Public Health Image Library (PHIL)]]
[[File:Mantoux test.jpg|thumb|none|200px|Image from Public Health Image Library (PHIL)]]
|}</div>
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|valign=top|
|+
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Tuberculin Reaction}}
! style="background: #4479BA; width: 450px;" | {{fontcolor|#FFF|Considered a Positive Result in:}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''≥ 5 mm '''
| style="padding: 5px 5px; background: #F5F5F5;" | 
*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
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''≥ 10 mm  '''
| style="padding: 5px 5px; background: #F5F5F5;" |
*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|corticosteroid therapy]], [[leukemia]], [[end-stage renal disease]], [[malabsorption|chronic malabsorption syndromes]], low body weight)
*Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''≥ 15 mm '''
| style="padding: 5px 5px; background: #F5F5F5;" |
*Persons with no known risk factors for TB
|-
| style="padding: 5px 5px; background: #F5F5F5;"colspan="2"| <SMALL>Table adapted from CDC<ref name="CDC TST">{{cite web|url= http://www.cdc.gov/tb/publications/factsheets/testing/skintesting.htm|title= CDC Tuberculin Skin Testing| }}</ref></small>
|}


==Two-step testing==
==Contraindications==
Some people with LTBI may have negative skin test reaction when tested years after the infection. Initial skin test may stimulate (boost) the ability to react to tuberculin. Positive reactions to subsequent tests may be misinterpreted as a new infection.
TST is contraindicated only for persons who have had a severe reaction (e.g., necrosis, blistering, anaphylactic shock, or ulcerations) to a previous TST. It is not contraindicated for any other persons, including infants, children, pregnant women, persons who are [[HIV]]-infected, or persons who have been vaccinated with [[BCG]].  


Use two-step testing for initial skin testing of adults who will be retested periodically (e.g., health care workers). 
==False-Poisitve and False-Negative Reactions==
* Return to have first test read 48-72 hours after injection
In some persons who are infected with [[M. tuberculosis]], the ability to react to tuberculin may wane over time. When given a TST years after infection, these persons may have a false-negative reaction. However, the TST may stimulate the immune system, causing a positive, or boosted reaction to subsequent tests. Giving a second TST after an initial negative TST reaction is called two-step testing.
* If first test is positive, consider the person infected.
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
* If first test is negative, give second test 1-3 weeks after first injection
|+
* Return to have second test read 48-72 hours after injection
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|False-Positive Reactions}}
* If second test is positive, consider person infected
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|False-Negative Reactions}}
* If second test is negative, consider person uninfected
|-
| style="padding: 5px 5px; background: #F5F5F5;" |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
| style="padding: 5px 5px; background: #F5F5F5;" |
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
|-
| style="padding: 5px 5px; background: #F5F5F5;"colspan="2"| <SMALL>Table adapted from CDC<ref name="CDC TST">{{cite web|url= http://www.cdc.gov/tb/publications/factsheets/testing/skintesting.htm|title= CDC Tuberculin Skin Testing| }}</ref></small>
|}


A person who is diagnosed as "infected" on two-step testing is called a "tuberculin converter".  The US recommendation that prior [[Bacillus Calmette-Guerin|BCG]]-vaccination be ignored results in almost universal false diagnosis of tuberculosis infection in people who have had BCG (mostly foreign nationals).  Please refer to the chapter on [[Bacillus Calmette-Guerin|BCG]] for a discussion of '''boosting'''.  The UK guidelines avoid this error <ref>{{cite web | author=National Institute for Health and Clinical Excellence | title=Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control | url=http://www.nice.org.uk/page.aspx?o=296657 | accessdate=2006-04-07}}</ref>.
==Two-step Testing==
 
Two-step testing is useful for the initial skin testing of adults who are going to be retested periodically, such as health care workers or nursing home residents. This two-step approach can reduce the likelihood that a boosted reaction to a subsequent TST will be misinterpreted as a recent infection.  
==Recent developments==
As a replacement for the Mantoux test, several other tests are being developed. QuantiFERON-TB Gold is a blood test that measures the patient’s immune reactivity to the TB bacteria and is useful for initial and serial testing of persons with an increased risk of latent or active [[tuberculosis]] infection. [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm Guidelines] for the use of QuantiFERON-TB Gold 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==
{{Main|Heaf test}}
 
The [[Heaf test]] is a tuberculin skin test formerly used in the United Kingdom, but discontinued in 2005.
 
The equivalent Mantoux test positive levels done with 10 TU (0.1 mL 100 TU/mL, 1:1000) are
* &lt;5 mm induration (Heaf 0-1)
*5-15 mm induration (Heaf 2)
* &gt;15 mm induration (Heaf 3-4)


==See also==
==See also==
Line 92: Line 98:
==References==
==References==
{{reflist|2}}
{{reflist|2}}
# Norman Markowitz; Nellie I. Hansen; Timothy C. Wilcosky; Philip C. Hopewell; Jeffrey Glassroth; Paul A. Kvale; Bonita T. Mangura; Dennis Osmond; Jeanne M. Wallace; Mark J. Rosen; and Lee B. Reichman. Tuberculin and Anergy Testing in HIV-Seropositive and HIV-Seronegative Persons. ''Annals of Internal Medicine'', 1993;119(3):185-193. [http://www.annals.org/cgi/content/full/119/3/185 Full text]
[[be-x-old:Рэакцыя Манту]]
[[es:Test de Mantoux]]
[[fr:Test Mantoux]]
[[it:Mantoux test]]
[[nl:Mantouxtest]]
[[no:Mantoux-metoden]]
[[pl:Test Mantoux]]
[[ru:Туберкулиновая проба]]


[[Category:Immunology]]
[[Category:Immunology]]
[[Category:Tuberculosis]]
[[Category:Tuberculosis]]
[[Category:Dermatology]]
[[Category:Dermatology]]
[[Category:Infectious disease]]
 


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Synonyms and keywords: PPD, TB skin test, TST, tst

Overview

The Mantoux tuberculin skin test (TST) is the standard method of determining whether a person is infected with Mycobacterium tuberculosis. Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice.

Procedure

The TST is performed by injecting 0.1 ml of tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The injection should be made with a tuberculin syringe, with the needle bevel facing upward. The TST is an intradermal injection. When placed correctly, the injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter.

The skin test reaction should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will need to be rescheduled for another skin test.

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

Classification of Tuberculin Reaction

Skin test interpretation depends on two factors:

  • Measurement in millimeters of the induration.
  • Person’s risk of being infected with TB and of progression to disease if infected.
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[1]

Contraindications

TST is contraindicated only for persons who have had a severe reaction (e.g., necrosis, blistering, anaphylactic shock, or ulcerations) to a previous TST. It is not contraindicated for any other persons, including infants, children, pregnant women, persons who are HIV-infected, or persons who have been vaccinated with BCG.

False-Poisitve and False-Negative Reactions

In some persons who are infected with M. tuberculosis, the ability to react to tuberculin may wane over time. When given a TST years after infection, these persons may have a false-negative reaction. However, the TST may stimulate the immune system, causing a positive, or boosted reaction to subsequent tests. Giving a second TST after an initial negative TST reaction is called two-step testing.

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[1]

Two-step Testing

Two-step testing is useful for the initial skin testing of adults who are going to be retested periodically, such as health care workers or nursing home residents. This two-step approach can reduce the likelihood that a boosted reaction to a subsequent TST will be misinterpreted as a recent infection.

See also

References

  1. 1.0 1.1 "CDC Tuberculin Skin Testing".


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