There are two classes of tests commonly used to identify patients with<unk> : tuberculin skin tests and IFN-γ (Interferon-gamma) tests. The skin tests currently include the following two: :* Mantoux test :* Heaf test IFN-γ tests include the following three: :* T-SPOT.TB :* QuantiFERON-TB Gold :* QuantiFERON-TB Gold In-Tube Tuberculin skin testing The tuberculin skin test (TST) in its first iteration, the Mantoux Test, was developed in 1908. Conceptually, it's quite simple: tuberculin (also called purified protein derivative or PPD) is a standardised dead extract of cultured TB, injected into the skin to measure the person's immune response to the bacteria. So, if a person has been exposed to the bacteria previously, they should express an immune reaction to the injection, usually a mild swelling or redness around the site. There have been two primary methods of TST: the Mantoux test, and the Heaf test. The Heaf test was discontinued in 2005 because the manufacturer deemed its production to be financially unsustainable, though it was previously preferred in the UK because it was felt to require less training to administer and involved less inter-observer variation in its interpretation than the Mantoux test. The Mantoux test was the preferred test in the US, and is now the most widely used TST globally. Mantoux test :See: Mantoux test The Mantoux test is now standardised by the WHO. 0.1 ml of tuberculin (100 units/ml), which delivers a dose of 5 units is given by intradermal injection into the surface of the lower forearm (subcutaneous injection results in false negatives). A waterproof ink mark is drawn around the injection site so as to avoid difficulty finding it later if the level of reaction is small. The test is read 48 to 72 hours later. The area of induration (NOT of erythema) is measured transversely across the forearm (left to right, not up and down) and recorded to the nearest millimetre. Heaf test :See:Heaf test The Heaf test was first described in 1951. The test uses a Heaf gun with disposable single-use heads; each head has six needles arranged in a circle. There are standard heads and pediatric heads: the standard head is used on all patients aged 2 years and older; the pediatric head is for infants under the age of 2. For the standard head, the needles protrude 2 mm when the gun is actuated; for the pediatric heads, the needles protrude 1 mm. Skin is cleaned with alcohol, then tuberculin (100,000 units/ml) is evenly smeared on the skin (about 0.1 ml); the gun is then applied to the skin and fired. The excess solution is then wiped off and a waterproof ink mark is drawn around the injection site. The test is read 2 to 7 days later. * Grade 0: no reaction, or induration of 3 or less puncture points; * Grade 1: induration of four or more puncture points; * Grade 2: induration of the six puncture points coalesce to form a circle; * Grade 3: induration of 5 mm; or more * Grade 4: induration of 10 mm or more, or ulceration The results of both tests are roughly equivalent as follows: * Heaf grade 0 & 1 ~ Mantoux less than 5 mm; * Heaf grade 2 ~ Mantoux 5–14 mm; * Heaf grade 3 & 4 ~ Mantoux 15 or greater Tuberculin conversion Tuberculin conversion is said to occur if a patient who has previously had a negative tuberculin skin test develops a positive tuberculin skin test at a later test. It indicates a change from negative to positive, and usually signifies a new infection. Boosting The phenomenon of boosting is one way of obtaining a false positive test result. Theoretically, a person's ability to develop a reaction to the TST may decrease over time – for example, a person is infected with<unk>  TB as a child, and is administered a TST as an adult. Because there has been such a long time since the immune responses to TB has been necessary, that person might give a negative test result. If so, there is a fairly reasonable chance that the TST triggers a hypersensitivity in the person's immune system – in other words, the TST reminds the person's immune system about TB, and the body overreacts to what it perceives as a reinfection. In this case, when that subject is given the test again (as is standard procedure, see above) they may have a significantly greater reaction to the test, giving a very strong positive; this can be commonly misdiagnosed as Tuberculin Conversion. This can also be triggered by receiving the BCG vaccine, as opposed to a proper infection. Although boosting can occur in any age group, the likelihood of the reaction increases with age. Boosting is only likely to be relevant if an individual is beginning to undergo periodic TSTs (health care workers, for example). In this case the standard procedure is called two-step testing. The individual is given their first test and in the event of a negative, given a second test in 1 to 3 weeks. This is done to combat boosting in situations where, had that person waited up to a year to get their next TST, they might still have a boosted reaction, and be misdiagnosed as a new infection. Here there is a difference in US and UK guidelines; in the US testers are told to ignore the possibility of false positive due to the BCG vaccine, as the BCG is seen as having waning efficacy over time. Therefore, the CDC urges that individuals be treated based on risk stratification regardless of BCG vaccination history, and if an individual receives a negative and then a positive TST they will be assessed for full TB treatment beginning with X-ray to confirm TB is not active and proceeding from there. Conversely, the UK guidelines acknowledge the potential effect of the BCG vaccination, as it is mandatory and therefore a prevalent concern – though the UK shares the procedure of administering two tests, one week apart, and accepting the second one as the accurate result, they also assume that a second positive is indicative of an old infection (and therefore certainly<unk> I) or the BCG itself. In the case of BCG vaccinations confusing the results, Interferon-γ (IFN-γ) tests may be used as they will not be affected by the BCG. Interpretation According to the U.S. guidelines, there are multiple size thresholds for declaring a positive result of<unk>  from the Mantoux test: For testees from high-risk groups, such as those who are HIV positive, the cutoff is 5 mm of induration; for medium risk groups, 10 mm; for low-risk groups, 15 mm. The U.S. guidelines recommend that a history of previous BCG vaccination should be ignored. For details of tuberculin skin test interpretation, please refer to the CDC guidelines (reference given below). The UK guidelines are formulated according to the Heaf test: In patients who have had BCG previously,<unk>  TB is diagnosed if the Heaf test is grade 3 or 4 and have no signs or symptoms of active TB; if the Heaf test is grade 0 or 1, then the test is repeated. In patients who have not had BCG previously,<unk>  TB is diagnosed if the Heaf test is grade 2, 3 or 4, and have no signs or symptoms of active TB. Repeat Heaf testing is not done in patients who have had BCG (because of the phenomenon of boosting). For details of tuberculin skin test interpretation, please refer to the BTS guidelines (references given below). Given that the US recommendation is that prior BCG vaccination be ignored in the interpretation of tuberculin skin tests, false positives with the Mantoux test are possible as a result of: (1) having previously had a BCG (even many years ago), and/or (2) periodical testing with tuberculin skin tests. Having regular TSTs boosts the immunological response in those people who have previously had BCG, so these people will falsely appear to be tuberculin conversions. This may lead to treating more people than necessary, with the possible risk of those patients suffering adverse drug reactions. However, as Bacille Calmette-Guérin vaccine is not 100% effective, and is less protective in adults than pediatric patients, not treating these patients could lead to a possible infection. The current US policy seems to reflect a desire to err on the side of safety. The U.S. guidelines also allow for tuberculin skin testing in immunosuppressed patients (those with HIV, or who are on immunosuppressive drugs), whereas the UK guidelines recommend that tuberculin skin tests should not be used for such patients because it is unreliable. Interferon-γ testing The role of IFN-γ tests is undergoing constant review and various guidelines have been published with the option for revision as new data becomes available. CDC:MMWR Health Protection Agency:UK There are currently two commercially available interferon-γ release assays (IGRAs): QuantiFERON-TB Gold and T-SPOT.TB. These tests are not affected by prior BCG vaccination, and look for the body's response to specific
Latent tuberculosis
Primary inoculation tuberculosis
Extensively drug-resistant tuberculosis
Totally drug-resistant tuberculosis
Tuberculosis in relation to HIV
Multidrug-resistant tuberculosis
Tuberculosis
Vietnamese tuberculosis