Diagnosis

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.

WHO policy guidance on TB diagnostics and laboratory strengthening

WHO consolidated guidelines on tuberculosis. Module 3: Diagnosis – rapid diagnostics for tuberculosis detection, third edition. Geneva: World Health Organization; In press.WHO End TB Strategy: global strategy and targets for tuberculosis prevention, care and control after 2015. Geneva: World Health Organization; 2015 (https://www.who.int/publications/i/item/WHO-HTM-TB-2015.19).

The DOI forms submitted by the experts reviewing this handbook and information retrieved from the internet, were examined by WHO staff members Nazir Ismail and Carl-Michael Nathanson to assess whether there were, or might be, actual or perceived conflicts of interest and, if so, whether a management plan was required. This evaluation process, and resultant management plans, were based on the Guidelines for declaration of interests (WHO experts) and the WHO handbook for guideline development (2nd edition).

The World Health Organization (WHO) recently published The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual (1) which provides practical guidance on planning and implementing next-generation sequencing (NGS) technology for characterization of Mycobacterium tuberculosis complex (MTBC) bacteria. In this manual, the focus is on the detection of mutations associated with drug resistance for the surveillance of drug resistance in tuberculosis (TB).