Executive Summary
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Rationale for expanded eligibility for TPT: A TB test and treat approach
Children ≥25kg, adolescents and adults
Rationale for expanded eligibility for TPT: A TB test and treat approach
It is essential that TB preventive treatment (TPT) is scaled up to reduce the burden of TB in South Africa. Previously, TPT was offered only to people who were at the highest risk of progressing to TB disease after exposure (i.e., children younger than five years of age, and all people living with HIV, regardless of age). However, to achieve TB elimination, it is imperative to implement TPT more comprehensively for everyone with significant TB exposure and all other individuals at high risk of TB. Diagnostic evaluation processes, TPT initiation processes, TPT regimens, and clinical evaluation at follow-up will vary by age, HIV status, and pregnancy status. However, TB testing and TPT should be offered to all people with significant TB exposure or who have a high risk of TB disease progression – i.e. a TB test and treat (offering either TPT or active TB treatment) approach. The use of shorter duration TPT regimens, where possible, will reduce the burden of TPT treatment on individuals, households and on health services.
In most instances, people who should be offered TPT will share a household with at least one person who is concurrently on TB treatment. Therefore, where possible, a ‘family-centred’ approach to TPT initiation and adherence support should be adopted by integrated healthcare worker teams or health services where possible. It is also important to consider the context of the household, and to offer similar regimens to affected household members, where possible.
TB test and treat approach: It is essential to rule out TB disease before initiating TPT. Therefore, all individuals (adults, adolescents, children and infants) should always be evaluated for TB disease before initiating TPT, including testing for active TB disease. Thereafter, the next decision, in the presence of significant TB exposure or TB risk, is to either offer TB treatment (in the presence of disease) or to offer TPT. In the past, uncertainty over diagnostic requirements and the limited availability of diagnostic tools were significant barriers to TPT access. The guiding principle for these revised guidelines is to help overcome several of these barriers.
All people considered for TPT should undergo clinical evaluation (symptom check and physical examination) and be tested with GeneXpert (Xpert), even if asymptomatic. TB testing strategies will vary by age as younger children cannot spontaneously expectorate sputum. Other clinically relevant samples should be considered in children (gastric aspirates, fine needle aspirates, stool). In children without symptoms, neither sputum testing nor chest x-ray (CXR) are therefore requirements to start TPT. Sputum testing should be attempted in children who can expectorate spontaneously (typically >=25kg), but if they are well (without symptoms) and unable to expectorate, they should start TPT, even if no CXR or sputum testing is available.
If unable to produce sputum, people considered for TPT should undergo clinical evaluation as a minimum, and a CXR where available. Other samples should be considered as clinically relevant. CXR is a valuable tool to rule out TB disease in adults and in children, but its absence should not pose a barrier to starting TPT in anyone – especially in children, if they are well and have no symptoms.
If test availability varies by setting, TB testing deficiencies should be urgently addressed in parallel to excluding active TB disease and encouraging TPT access. The National TB Prevalence Survey1 has highlighted the high burden of asymptomatic TB amongst adults and adolescents, reflecting the importance of having a low threshold for testing people for active TB, especially before offering TPT, including in people not historically considered to be at high risk of TB disease.
It is important to recognise the difference between testing for TB infection (e.g., TST, IGRA) and testing for TB disease (Xpert/culture, chest x-ray, LF-LAM). Tests for TB infection are useful to detect TB infection, and to predict who is at the highest risk of developing TB disease, but are not a requirement to starting TPT. If tests of infection are not available, this should not pose a barrier to TPT initiation. A positive test of TB infection means that the person is (or was previously) infected with M.tb, but does not indicate (or exclude) TB disease. Also, a negative test of TB infection does not mean that the person is not actually infected with M.tb or is not at risk for developing TB disease in the near future. Therefore, tests of TB infection are no longer listed in these algorithms and not are not requirement to initiate TPT. Any lack of availability of tests of TB infection should not impact whether somebody is offered TPT or not. In individual clinical scenarios, tests of TB infection may be used by clinicians as available as useful tests to determine TB infection status and the risk future disease progression.
In contrast, testing (clinical evaluation and other test) for TB disease is required before disease can be ruled out and should be made available to all people before being offered TPT (refer to the section on children for exceptions as clinically relevant).
People who require TPT
TB contacts: All adults, adolescents and children (including newborns or infants) exposed to TB require TPT once TB disease has been excluded through evaluation – irrespective of HIV status, pregnancy, or previous TB disease or treatment status. Significant TB exposure can occur in any setting, e.g. in the household, workplace, place of learning or care, or other. Therefore, the term “household contact” is confusing (the definition is too narrow) and should no longer be used. Going forward, the term “TB contacts” should therefore be used. After each TB exposure, the exposed person must be evaluated for TB again and either TB treatment or TPT should offered (e.g., repeat TB test and treat approach after each significant TB exposure). TPT is only effective while it is being given, so previous TPT does not protect against a new TB exposure.
All pregnant women with significant TB exposure (irrespective of age or HIV status) should be offered TPT once TB disease has been excluded through testing. TPT should therefore not be deferred to the post-partum period. TB disease should be ruled out repeatedly during pregnancy, through initial evaluation as described above, and by using symptom screening during subsequent antenatal visits. Further evaluation should be based on symptoms, the clinical picture and any new information on TB exposure.
People living with HIV (PLHIV): All adults, adolescents and children including infants living with HIV (irrespective of a known significant TB exposure) should receive a course of TPT once TB disease has been excluded through testing. People newly diagnosed with HIV should always be tested for TB prior to initiating antiretroviral treatment (ART). PLHIV who are already on ART, but who have not taken TPT before, should also be tested for TB. TPT should then be offered if no evidence of TB disease is found in PLHIV. Initiating ART should be prioritised and TPT should be started within the next two weeks. If PLHIV interrupted their ART, ART counselling should be undertaken and ART re-initiated.
Other high-risk groups
Inmates in correctional facilities remain a priority group for treatment of TB infection because the confined indoor spaces they share with other people often practically mean they that meet the criteria of ‘significant TB exposure’.
Healthcare workers have a very high risk of TB and should be considered for treatment of TB infection within TB and HIV occupational health services. At the minimum, setting-appropriate annual or bi-annual testing is recommended and additional evaluation, based on clinical indications (e.g. symptoms, new TB exposure) should be undertaken.
People who have previously had TB (TB survivors) are at higher risk of getting TB again and should be considered for treatment of infection after another significant TB exposure.
Silicosis: People with silicosis have a significant risk of developing TB disease and should be considered for treatment of infection regardless of significant TB exposure.
Choice of regimen
In South Africa, the current TPT options include isoniazid and rifapentine given once weekly for three months (3HP), daily rifampicin and isoniazid for three months (3RH), daily isoniazid for six months (6H) or daily isoniazid for 12 months (12H). As a rule, shorter treatment options should be offered where feasible and available. If 3HP is not available (or contra-indicated), 3RH or 6H should be offered for people who tested negative for HIV, and 12H for PLHIV (6H for children with HIV) and 3RH for children <25kg. 3HP is not yet available in children <25kg in South Africa, 3RH should therefore be used, unless contra-indicated. Fixed-dose combinations (FDCs) for 3RH that are dispersible, scored and child-friendly, are routinely available in the country.
Options for TPT regimens will be revised immediately once new evidence regarding safety, efficacy, appropriate dosing and the required patient-friendly formulations become available. The TPT regimen chosen will depend on the patient’s weight (in the case of children); HIV status; unique individual, household or family considerations; assessment of potential drug interactions with other medications (including ART); availability of TPT formulations and the current evidence. A child-friendly fixed-dose dispersible formulation of rifampicin and isoniazid (3RH) is already widely available, while a child-friendly rifapentine (P) formulation is not available yet. Therefore, 3RH is the preferred regimen for HIV-negative children <25kg, who are not yet eligible for the 3HP regimen.
Children ≥25kg, adolescents and adults
Older children weighing ≥25kg (typically eight years and older) can be offered 3HP if the regimen is available since they can receive adult doses of TB medications. These include children living with HIV, if they are on a dolutegravir-based regimen with a suppressed viral load (VL <1000 in the last six months). Accordingly, the guidelines have been stratified into two weight groups: children under 25kg, and everybody else above or equal to 25kg, including older children, adolescents and adults. If 3HP is not available, 3RH (in HIV-negative individuals) should be used as the priority regimen. 6H also remains an option for people who are not living with HIV, if preferred. 12H should be offered to all PLHIV who are starting a dolutegravir-containing regimen (6H in children with HIV). For individuals already virally suppressed or who are not starting a dolutegravir-containing regimen, 3HP is preferred.
It should be noted that shorter TPT regimens in general, in all people, usually have better completion rates, are safer and are better tolerated than longer regimens, in adults, children, adolescents, pregnant women and PLWH.
Children <25kg
3RH is the preferred regimen for children under 25kg not living with HIV. 6H is preferred (above 3RH) for children under 25kg living with HIV and in infants/ children born to pregnant women living with HIV, due to the risk of drug-drug interactions with ART and the potential for decreasing the effectiveness of prevention of mother-to-child transmission (PMTCT). Once child-friendly rifapentine (P) formulations become available and the appropriate dose and safety of 3HP is known in young children, 3HP may in future become an available option for children <25kg.
Where possible, when considering a TPT regimen, preference should be given to individuals in one household or group receiving the same type of regimen. This should be done to lessen the burden and complexity of TPT on the individuals and the family/ group; reduce the chances of being stigmatised; and facilitate support, monitoring and evaluation of TPT at the programme level.
While the same test and treat approach as that for drug-susceptible TB (DS-TB) should be applied for people exposed to drug-resistant TB (DR-TB), the management of DR-TB contacts must consider all available M. tuberculosis resistance data. Additional drug susceptibility testing should be attempted for known sources/index patients. Please refer to the latest National Drug-resistant TB Treatment Guidelines for the management of DR-TB exposed individuals.
Support for people on TPT
Individuals offered TPT require appropriate education and counselling prior to TPT initiation, with continued support during their TPT journey. Individuals should be educated about the potential options for TPT and about TB testing strategies. A family-centred, household-based approach may support adherence and improve TPT acceptability. Community health workers (CHWs) can and should play a key role in providing home-based person-centred treatment support, as they already do for active TB treatment and for ART. All care providers need to be trained on the updated guidelines, with a special emphasis on scaling up access among previously neglected groups (e.g. in HIV-negative contacts older than five years).
After TPT initiation, clinical follow-up is important to monitor for safety, support adherence, checking the weight and adjusting the dose as needed, and to re-evaluate for TB disease. Monthly monitoring for adherence and adverse effects of TPT is recommended. Patients should be carefully assessed for adverse effects, using standard reporting tools as per the National Pharmacovigilance Centre (Tel: (012) 501 0311 and e-mail: adr@sahpra.org.za).
After completing a course of TPT, individuals should be informed that subsequent TPT is required if another significant TB exposure occurs and that they should access care for TB evaluation.
Children should be weighed at every visit and dosages adjusted based on actual weight to prevent under- or overdosing. Patients and children’s caregivers should be counselled regarding side effects of TB medications. They must be actively encouraged to present for evaluation should they develop new symptoms, such as fever, night sweats or cough, that could indicate TB disease or immune reconstitution inflammatory syndrome (IRIS), or if weight loss (or failure to gain weight, in children) occurs.
Monitoring and evaluation
It is important that programmatic assessments should be conducted to determine whether TPT delivery targets are being met, using existing data collection tools. These include available electronic or other registers, and cascade analysis. Such assessments should establish indicators and outcomes. Refer to Section 12 for more details.
National Guidelines on the Treatment of Tuberculosis Infection, February 2023
Executive Summary