Mantoux test - Principle, Procedure, Result, Interpretation, Limitation, History
Introduction to Mantoux test
Mantoux test is one of the major tuberculin skin procedures used for screening as well as diagnosis of tuberculosis caused by Mycobacterium tuberculosis. Since its innovation in the 1940s by biochemist Florence B. Seibert, it has been endorsed by the Centers for Disease Control and Prevention (CDC) and the American Thoracic Society.
Mantoux test has replaced multiple-puncture tests such as the tine test which was used widely until 2005. Other names of the Mantoux test include
Mendel–Mantoux test
Mantoux screening test
Tuberculin sensitivity test
Pirquet test
Purified protein derivative (PPD) test
History of Mantoux test
In 1980, German physician and microbiologist Heinrich Hermann Robert Koch first described the tuberculin reaction. About two decades later, in 1907, a French physician Charles Mantoux, developed the test but due to impurities in tuberculin, the test was unreliable and caused false results.
And in 1908, German physician Felix Mendel first improved the test and named it the Mantoux test after Charles Mantoux.
Researchers Esmond R. Long and Florence B. Seibert identified tuberculin's active agent to be a protein. Seibert worked on the Mantoux test for years to obtain the purified protein derivative (PPD), which made the test more reliable. And by the 1940s, Seibert's PPD had been internationally accepted.
Principle of Mantoux test
The principle of the Mantoux test is based on the glycerol extract of M. tuberculosis called tuberculin (also known as purified protein derivative; PPD). The tuberculin is obtained after filtrates of sterilized, concentrated Mycobacterium tuberculosis cultures are precipitated to form species-nonspecific molecules.
After infection by Mycobacterium tuberculosis, the individual develops a delayed hypersensitivity to the tuberculin of the pathogen. So, if tuberculin (PPD) is administered intracutaneously, induration can be observed. The diameter of such induration is measured to determine if the infection is present or absent.
Procedure of Mantoux test
The procedure of the Mantoux test is as follows:
Take 0.1 ml culture extract of Mycobacterium tuberculosis i.e. PPD of tuberculin containing 5 TU (according to CDC) or 2 TU of SSI (according to NHS) and inject it intracutaneously on the left forearm.
Option: 0.1ml of sterile normal saline is injected intracutaneously into the right forearm as a control
Delayed type hypersensitivity reaction to PPD is observed after 48-72 hours and characterized by erythema (redness) and firmness
Its firmness (induration) is measured and interpreted
* TU = Tuberculin Units
* SSI = Statens Serum Institute
*(If the test is negative using 5 TU, can be repeated using 10 TU or 100 TU)
Result, Interpretation of Mantoux test
The result and interpretation of the PPD test are determined according to the increment of the induration- 5 mm, 10 mm, or 15 mm.
Alternative induration criteria of 6, 12, 15, or 18 mm can also be used.
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Fig: PPD test induration measurement (Source: CDC)
Positive
In the following cases, 5 mm or more is positive for tuberculosis
HIV positive patients
patients with immunocompromised state including organ transplant recipients
relapsed patients with nodular or fibrotic changes visible on chest X-ray
10 mm or above is positive for tuberculosis in cases of
immigrated/moved from countries with high TB cases (less than five years)
IV drug abusers
people employed in medical care- nurses, microbiology lab personnel, doctors
children aged less than four years old
individuals exposed to TB patients
individuals living in crowded spaces- prisons, hospitals, nursing homes, military
patients with health conditions- diabetes, leukemia, undergoing long-term corticosteroid therapy, underweight
In cases of individuals who has no known risk factors for tuberculosis, if the PPD shows 15mm induration, then the test is positive.
Negative
In cases of PPD with 5 mm or less in duration, tuberculosis infection is negative.
For induration measuring 6-9 mm, the result is equivocal/ambiguous.
Limitation of Mantoux test
The limitation of Mantoux test are as follows:
PPD test is not 100% specific or sensitive.
DTH (delayed-type hypersensitivity) is observed in patients who have had the BCG vaccine
False-negative test (anergy) can be seen in conditions such as
miliary tuberculosis
convalescence form of some viral infection like measles
lymphoreticular malignancy
severe malnutrition
impaired CMI
immunosuppressive therapy/condition
recent TB infection (8-10 weeks)
Corticosteroid therapy
Sarcoidosis
Live virus vaccine- Sabin vaccine (polio), MMR vaccine (measles, mumps, rubella)
Hodgkin's disease
Upper respiratory tract infection (URTI)- usually during a viral infection