Operational Handbooks

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.

The decision to test an individual for TB infection implies an intention to offer TPT. TB infection testing should therefore be reserved for populations in whom the risk of developing TB disease is high and who will benefit the most from TPT. Decisions to start TPT should always consider risk of adverse drug events, in addition to TB symptoms and the TB infection test result. Box 2.1 summarizes the groups WHO recommends should receive TPT, with testing not mandatory for groups 1–3. More detail can be found in Module 1 of the WHO operational handbook on TB (1).

This handbook is intended for use by TB and HIV programmes, and other experts involved in planning and implementing new or expanded programmes for TB infection testing. It is also intended for people involved in training, monitoring and supervision, and providers performing these tests. The annexes provide additional details, and educational materials about TB infection testing for providers and patients.

This handbook reviews who should be tested for TB infection, and why and how they should be tested under programmatic settings. It provides information about the specific TB infection tests, from the original TST to the recently approved TBSTs, and the blood-based IGRAs, which are categorized as tests that measure interferon-gamma production using methods based on enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunosorbent spot (ELISPOT). Finally, programmatic aspects of the implementation and scale-up of TB infection testing are explained.

Identifying, testing, evaluating and treating people with TB infection is a multistep process that has been termed the TB infection cascade of care (15). The cascade is described in detail in Chapter 4. In brief, it comprises several steps that may involve health care personnel in different locations. Losses can occur at every step of the TB infection cascade. A systematic review showed that these losses resulted in less than 20% of those eligible for TPT completing their course of medication (15).

In 1908, Mantoux performed the first intradermal test for TB infection using killed M. tuberculosis (9). The basic principles of this test have not changed in more than 100 years, making the tuberculin skin test (TST) one of the oldest tests still in clinical use. The skin test that is in widespread use today comprises the intradermal injection of a purified protein derivative (PPD) from heat-killed cultures of M. tuberculosis, with measurement of the resultant induration 48–72 hours later.

Tuberculosis (TB) infection is a state of persistent immune response to Mycobacterium tuberculosis antigens with no evidence of clinically manifest TB disease (1). People with TB infection have no signs or symptoms of TB disease, are not infectious, have normal or stable images on chest X-ray (CXR), and have negative microbiological tests, if performed (1). It is estimated that about 25% of the world’s population has been infected with M.