Operational Handbooks

3.3.6. Options for TB preventive treatment regimens: drug-resistant TB

Household contacts of people with MDR-TB or isoniazid monoresistance are at higher risk of TB infection than contacts exposed to people with drug-susceptible TB. The risk of progression to TB disease does not differ among contacts in either group (67). Studies have reported approximately 90% reduction in MDR-TB incidence with TPT after known exposure (68). WHO recommends using TPT for contacts exposed to people with MDR-TB following consideration of the intensity of exposure, confirming the source patient and their drug resistance pattern (i.e.

3.3.5.2. Dosages

The WHO task force on pharmacokinetics and pharmacodynamics analysed available evidence from clinical trials of rifapentine and suggested a simplified dose for various weight bands for 3HP and 1HP for the 2020 WHO consolidated guidelines on tuberculosis. Module 1: prevention – tuberculosis preventive treatment (28). Table 3.2 presents standard dosing for the recommended TPT regimens by age and body weight.

3.3.5.1. Implementation considerations

The choice of TPT regimen depends on the age of the child, the HIV and ART status, and the availability and affordability of suitable (child-friendly) formulations.14 Rifampicin- and rifapentine-containing regimens should be prescribed with caution in children and adolescents living with HIV and on ART because of potential drug–drug interactions (see Section 7.1 and Tables 7.2 and 7.3). Table 3.1 summarizes the options for different target and age g

3.3.5. Options for TB preventive treatment regimens: drug-susceptible TB

The following options for TPT are recommended by WHO for use in children and adolescents:

  • 6 months or 9 months of isoniazid daily (6H or 9H) (all ages); or
  • 3 months of isoniazid plus rifapentine weekly (3HP) (age 2 years and over); or
  • 3 months of isoniazid plus rifampicin daily (3HR) (all ages).

1 month of daily isoniazid plus rifapentine (1HP) (aged 13 years and over) or 4 months of daily rifampicin (4R) (all ages) may be offered as alternative regimens.

3.3.4.2. Interferon-gamma release assay

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.

3.3.4.1. Tuberculin skin testing

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.

3.3.4. Testing for TB infection

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).

3.3.3.3. Children and adolescents living with HIV

Children and adolescents living with HIV should be screened for TB disease at every visit to a health facility or interaction with a health worker, using standard screening questions, as part of routine clinical care (see Chapter 2). Those who do not have any of the symptoms in the questionnaire are unlikely to have TB disease and should be offered TPT, regardless of their ART status. CXR may be offered to adolescents living with HIV and on ART; if there are no abnormal radiographic findings, they may be given TPT.

3.3.3.2. HIV-negative household and close contacts of a person with pulmonary TB: children and adolescents aged 5 years and over

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).

3.3.3.1. HIV-negative household and close contacts of a person with pulmonary TB: infants and children aged under 5 years

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.