Children and Adolescents

Adherence to any course of treatment is a complex behaviour influenced by many factors, such as personal motivation, beliefs about health, perceived risks and benefits of treatment, comorbidities, competing demands that conflict with taking medicines, the family environment, complexity of the treatment regimen, toxicity of medicines, and trust and relationship with providers. Effective person-centred strategies to promote adherence to TPT may include the following (15):

Children and adolescents on TPT should be reviewed every month for those on a 3-month regimen (e.g. 3HR or 3HP), or every 2 months for those on a 6-month regimen (e.g. 6H) or DR-TB TPT, ideally at a health care facility or by treatment supporters (see Section 6.4) or by using digital tools such as video-supported treatment (69).

IGRA is a whole-blood test that can help to diagnose M. tuberculosis infection. Like TST, it does not differentiate between TB infection and TB disease. IGRA measures the cell-mediated immune response of people with TB infection. T-cells of infected people are sensitized to TB and respond to stimulation with peptides simulating those expressed by TB bacteria by secreting a cytokine called interferon-gamma. IGRA uses peptides from proteins made almost exclusively by M. tuberculosis and other mycobacteria from the M. tuberculosis complex.

TST is a method to detect TB infection that involves intradermal injection of tuberculin purified protein derivative (PPD). Previous exposure results in a local delayed-type hypersensitivity reaction within 24–72 hours (6). The reaction is identified as palpable induration at the site of injection. It only indicates hypersensitivity to proteins of the TB bacillus as a result of infection with M. tuberculosis or induced by BCG vaccination. A positive TST does not indicate the presence or extent of TB disease.

TST or IGRA can be used to test for TB infection. People living with HIV who are on ART (including adolescents and children) benefit from TPT regardless of whether they test positive or negative for TB infection. People living with HIV who are not on ART and who test positive for TB infection are shown to benefit more from TPT than those who test negative (49).

Target groups for TPT were expanded from the 2018 WHO updated and consolidated guidelines for programmatic management (61) and later versions to include HIV-negative household contacts aged 5 years and over. In this target group, confirmation of TB infection using TST or IGRA, absence of any symptoms of TB, and absence of abnormal findings on CXR may be used to rule out TB disease before starting TPT (28).

Children aged under 5 years who are household contacts of a person with bacteriologically confirmed PTB are usually identified through contact investigation or visits to health care facilities. They should be screened for TB symptoms (current cough, fever, not eating well or anorexia, weight loss or failure to thrive, fatigue, reduced playfulness, decreased activity). Those with any one of the symptoms should be evaluated for TB disease, while those who are asymptomatic should be offered TPT.

Children aged under 5 years who are household contacts of people with bacteriologically confirmed TB have a significantly higher risk of acquiring TB infection and progressing rapidly to TB disease. Children aged under 2 years are also at particularly high risk for severe and disseminated forms of TB with very high risk of morbidity and mortality. TPT is strongly recommended in all TB household contacts aged under 5 years once TB disease is ruled out.

Children and adolescents living with HIV are 8–20 times more likely to develop TB disease than those without HIV infection and should be prioritized for systematic evaluation and TPT in all settings (15, 46). Despite major progress in access to and effectiveness of ART, TB is the most frequent cause of acquired immunodeficiency syndrome (AIDS)-related deaths worldwide (47).

TB infection (previously called latent TB infection) is defined as a “state of persistent immune response to stimulation by M. tuberculosis antigens without evidence of TB disease” (15). The number of people worldwide estimated to have M. tuberculosis infection is 1.7 billion. Further, 7.5 million children aged under 15 years are estimated to be infected with TB every year (11).