Diagnosis

The original tuberculin material used by Mantoux in his first studies of tuberculin reactions was a highly heterogeneous mix of substances from killed M. tuberculosis(9). This so-called old tuberculin was replaced in 1941 by a standardized preparation of PPD from M. tuberculosis. A single standard lot of this material was produced by Florence Seibert, termed “PPDS” (32); since then, all newly produced tuberculin material has been produced using the same methods and tested against this standard, measuring induration in sensitized guinea pigs.

To avoid barriers or delays created by TB infection testing, and to minimize associated losses in the TB infection care cascade, an integrated person-centred care model is preferred for TB infection diagnosis and treatment. Here, “integrated” means carrying out screening for TB disease and testing for TB infection in parallel, and “person-centred care” means coordination of multiple care activities during the same visits.

Skin testing is not advisable in people with a history of allergic reaction to TST or TBST. Allergic reactions to TST (PPD or equivalent), such as a generalized rash that occurs within the first 24 hours, are seen in less than 1% of recipients (26). If this has been well documented in the past, then it is wise to avoid repeating the test with the same tuberculin material. Currently, it is unclear whether use of an alternative tuberculin material would be safe.

TB infection tests should not be used for the diagnosis of pulmonary or extrapulmonary TB, nor should they be used for the diagnostic work-up of adults (including People with HIV) with presumed TB disease. TB infection tests should not be used for screening or to monitor the response to treatment for TB disease or TB infection.

TB infection testing may result in false negatives in individuals with certain viral illnesses (e.g. measles) or live virus vaccination (e.g. measles or mumps) within the preceding 30 days (23). This has been described with TST, but a similar effect with all TB infection tests is biologically plausible. Hence, it may be appropriate to delay the TB infection test for 30 days after infection or vaccination. Alternatively, a negative TB infection test may be repeated after 30 days.

If a prior positive TB infection test or TB treatment is documented, then repeat TB infection testing will not be useful and should not be done. Depending on the circumstances, the individual may be referred for further medical evaluation. However, if a prior positive result is self-reported and not documented, it is recommended to repeat the test, because studies have documented highly inaccurate self-reporting of prior skin test results (22).

This section sets out the various situations in which TB infection testing is not advised.

Testing for TB infection will be beneficial from an individual and a programmatic perspective if it identifies people who will benefit most from TPT. From a programmatic perspective, investments into capacity for TB infection testing will be justified if this results in greater efficacy and efficiency in the use of resources to provide TPT, increased acceptance and enhanced coverage. This will include not only the cost of drugs but also the human resources for medical evaluation, TPT initiation and follow-up.

Numerous studies have identified risk factors for TB disease in people with positive or negative tests for TB infection; these risk factors may be epidemiological (e.g. contacts), demographical (e.g. age) or clinical (e.g. HIV infection). These studies have recently been summarized, and pooled estimates of absolute and relative risks provided, in an aggregate data meta-analysis (6), and two large-scale individual patient data meta-analyses (4, 5). The risk of TB disease varies widely among those with different epidemiological or clinical risk factors.