TUBERCULIN Solution for injection Ref.[7657] Active ingredients: Tuberculin

The Mantoux test is performed by injection intradermally, with a syringe and needle, 0.1ml of PPD Tuberculin. For the intradermal (Mantoux) tuberculin test, the standard dose is 5 TU in 0.1ml.

Appointing and reading the skin tuberculin reaction and its interpretation is complete from a medical doctor.

Method of Administration

1. The site of the test is the flexor surface of the forearm dorsal or volar site, distant from blood vessels.
2. The skin of the forearm is first cleansed with alcohol and allowed to dry.
3. The test dose (0.1 ml) of PPD Tuberculin is administered with a 1 ml syringe calibrated in tenths and fitted with a short, one-half inch 26 or 27 gauge needle.
4. Disposable sterile syringes and needles may be used.
5. Wipe the rubber cap of the vial with an alcohol swab. The needle is then inserted gently through the cap and 0.1 ml of PPD Tuberculin is drawn into the syringe.
6. The point of the needle is inserted into the most superficial layers of the skin with the needle bevel pointing upward. If the intradermal injection is performed properly, a definite pale bleb will rise at the needle point, about 10 mm in diameter. This will disappear within minutes.
7. A separate sterile syringe and needle must be used for each individual injection to prevent the possibility of transmission of viral hepatitis or other infectious agents from one person to another. In particular, the same needle and/or syringe must never be used to re-enter a multi-dose vial to withdraw product even when it is to be used for testing of the same patient. This may lead to contamination of the vial contents and infection of patient who subsequently receive product from the vial.

In the event of an improperly performed injection (i.e. no bleb formed), the test should be repeated immediately at another site.

Interpretation of the Test

The test should be read 72 hours after administration of the tuberculin. Sensitivity is indicated by induration only; redness should not be measured. The diameter of induration should be measured transversely to the long axis of the forearm and recorded in millimetres (mm). Presence of oedema or necrosis should also be recorded, although it is not used in the interpretation of the test.

How to read the Mantoux Test. Diameter of induration in millimetre:

A positive reaction indicates a response of the immune system due to one or more of the following reasons:

• Infection with Mycobacterium tuberculosis complex ( M. tuberculosis, M. bovis, M. africanum or M. microti)
• Infection with non-tuberculous mycobacteria.
• Previous BCG vaccination (BCG vaccinated persons normally become tuberculin positive after 4–8 weeks). Postvaccinal allergy is usually with sizes of about 6–13 mm. The skin reaction is pale with smoothly outlines and hasn’t infectious aspect. Postvaccinal allergy gradually diminished.

In countries were is take the BCG vaccination, children respond with negative reaction (induration of less than 5 mm) to the usual tuberculin test (5 TU/0.1 ml) are reimmunized with BCG vaccine, according to National immunization programme.

• Reactions with a diameter larger than 15 mm are defined as strongly positive and give a strong indication of infection with Mycobacterium tuberculosis complex.

Those individuals giving a positive tuberculin reaction may or may not show evidence of tuberculosis disease. Chest x-ray examination and microbiological examination of the sputum in these cases are recommended as a means of determining the presence or absence of pulmonary tuberculosis.

BCG vaccination may produce a PPD reaction that cannot be distinguished reliably from a reaction caused by infection with M. tuberculosis. For a person who was vaccinated with BCG, the probability that a PPD reaction results from infection with M. tuberculosis increases a) as the size of the reaction increases, b) when the person is a contact of a person with TB, c) when the person’s country of origin has a high prevalence of TB, and d) as the length of time between vaccination and PPD testing increases (2, 4).

For example, a PPD test reaction of 10 mm probably can be attributed to M. tuberculosis infection in an adult who was vaccinated with BCG as a child and who is from a country with high prevalence of TB.

False-Negative Reactions

False-negative tuberculin skin-test reactions have many potential causes (6; 11; 22).

Anergy: When a person’s immune system is weakened by a disease such as HIV, cancer or even severe tuberculosis it self, the body may not be able to react to the tuberculin skin test (3; 24).

Recent tuberculous infecion: If a person has been infected with the past ten weeks, the tuberculin Mantoux test can not detect a tuberculous infection.

Age: Babies less than 6 months old may have false negative Mantoux test results because their immune system is not fully developed yet.

Test administration: A false result may occur if the tuberculin skin test is not administered correctly.

Booster Effect

The “Booster Phenomenon” in Purified Protein Derivative (PPD) tuberculosis testing occurs when a person’s immune system has “forgotten” about an infection by Mycobacterium tuberculosis until years later when the person is tested again for tuberculosis; the PPD test “reminds” the immune system about the infection. Although the initial PPD test was negative, a second PPD test performed year later, may “boost” the immune system’s ability to react to the tuberculin. Therefore, there is no way of knowing if the positive result was due to the booster phenomenon. The best way to avoid this from happening is to perform a two step test.

The two-step tuberculin test involves a person getting re-tested one week after the initial Mantoux test. If both tuberculin tests are negative, the person is unlikely to have tuberculosis. Furthermore, if a future tuberculosis test is positive, it can be concluded that the tuberculosis infection is new and not due to the tuberculosis “booster phenomenon” (29).

No case of overdose has been reported.

Shelf life: 2 years from the last satisfactory Potency test.

Multi-dose vials of Tuberculin PPD from which one or more doses have been removed, may be used for up to a maximum of 4 weeks, provided that all of the following conditions are met (as described in the WHO policy statement: The use of opened multi dose vials in subsequent immunization sessions. (36). WHO/V&B/00.09:

• The expiry date has not passed;
• The Tuberculin PPD is stored under appropriate cold chain conditions (in the dark at temperature +2⁰C to +8⁰C);
• The product vial septum has not been submerged in water
• Aseptic technique has been used to withdraw all doses;

Tuberculin PPD should be stored between +2°C to +8°C.

DO NOT FREEZE. Discard product if exposed to freezing.

Tuberculin solutions can be adversely affected by exposure to light (16).

The product should be stored in the dark.

Once opened, multi-dose vials should be kept between +2°C and +8°C.

Do not use after the expiry date.

Type I glass vials (14):

0,2 ml ( 2 doses) containing 10 TU of PPD = 5 TU/0.1 ml
1 ml (10 doses) containing 50 TU of PPD = 5 TU/0.1 ml
1,5 ml (15 doses) containing 75 TU of PPD = 5 TU/0.1 ml
2 ml (20 doses) containing 100 TU of PPD = 5 TU/0.1 ml

Tuberculin PPD solutions do not require future dilution.

No special requirements.