Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (M.tb), an airborne pathogen predominantly transmitted from person to person via inhalation of infected droplet nuclei. Tuberculosis disease can be treated, prevented and controlled using currently available interventions, if implemented comprehensively.

Approximately 212 000 TB cases were notified in South Africa (SA) in 2023, of which 7% were children under the age of 15 years and 37% were among women or adolescent girls of child-bearing potential.¹ A previous episode of TB disease increases the risk of future TB disease episodes, and approximately 20% of people diagnosed with TB each year have been previously treated for TB.²

Drug-resistant (DR)-TB is a disease caused by M.tb strains that are resistant to at least rifampicin and/or isoniazid, the two most important first-line drugs used for treating drug-susceptible (DS)-TB. Drug-resistant TB accounts for approximately 3% of SA’s annual burden of new TB cases but demands up to 33% of the total budget for national TB control.³ Although a prior diagnosis of any strain of TB is a clear risk factor for future diagnosis of DR-TB, most people diagnosed with DR-TB nationwide have never before received TB treatment, indicating that the majority of incident DR-TB cases are transmitted from person to person within the community (rather than acquired within an individual through suboptimal adherence or inadequate treatment of DS-TB disease).⁴ Furthermore, it was estimated that 13 365 people were diagnosed with DR-TB in SA in 2023 but only 7626 DR-TB cases were notified and started second-line TB treatment^1,5; this diagnostic-treatment gap contributes considerably to ongoing community transmission of this pathogen.⁶

Transmission of M.tb is predominantly airborne in congregate settings, and children, adolescents, and pregnant and postpartum women (CAPPW) with significant TB exposure are at increased risk of TB infection and subsequent progression to TB disease. Other high-risk groups in SA include people living with HIV (PLWHIV), miners, inmates, immunocompromised individuals, those with silicosis and healthcare workers.⁷

Children who are infected and go on to develop TB disease usually do so within 12 months following exposure to someone with pulmonary TB.⁸ Younger age, human immunodeficiency virus (HIV) exposure, HIV infection, and severe malnutrition are risk factors for developing TB disease following significant TB exposure and infection.^9,10,11 Compared with adults, children are more likely to have successful TB treatment outcomes, but the relatively longer delays in TB diagnosis and appropriate treatment initiation increase their risk of progression to more severe disease. Infants and young children (under 5 years of age) may experience more rapid onset with more severe forms of pulmonary and extrapulmonary TB disease than older children and adolescents (aged 10–19 years) who tend to present with more adult-type (cavitary) pulmonary disease.^9,12

Adolescents are a unique group of individuals with an increasing desire for autonomy and wider social interactions and are therefore also at risk of TB exposure outside of the household. The risk of progression from TB infection to TB disease increases considerably from the age of 10 years,⁸ and adolescents with significant TB exposure may have distinctly different needs during their developmental transition from children to adults. Clinicians managing adolescents exposed to TB should be mindful of potential challenges associated with their changing perceptions of risk (e.g. experimentation with substance use, engagement in harmful behaviours), willingness to give consent or assent for medical interventions, adherence to treatment or medical advice, and the effects of social isolation and stigma.¹³

Pregnant women infected with TB appear to be at increased risk (compared with non-pregnant women) of progression to TB disease, with an even higher risk during the postpartum period.¹⁴ Pregnant women with TB disease in SA are more likely to experience unsuccessful TB treatment outcomes compared with non-pregnant women with TB, as well as unfavourable maternal and infant outcomes compared with pregnant women without TB.^15,16 While the diagnosis and treatment of TB disease during pregnancy and postpartum are clearly beneficial, the optimal management of TB infection during this period remains controversial.¹⁴

Reducing TB transmission, limiting TB infection, and preventing progression to TB disease among CAPPW are critical to prevent significant morbidity associated with both the disease and the currently available treatment options in these populations. This can be achieved through a combination of multisectoral approaches to promote TB education and awareness, prevent and control M.tb transmission, increase antiretroviral therapy (ART) coverage, facilitate routine TB screening, improve diagnosis, prompt initiation of effective TB treatment, and enhance psychosocial support for people and families affected by TB. Provision of TB preventive therapy (TPT) is only one component in the overall approach to achieve control of the TB epidemic in SA. Given the emerging evidence for TPT from international clinical trials and the importance of preventing TB disease in priority populations, this article aims to provide healthcare workers in primary care settings in SA a brief overview of the approach to TB prevention and current TPT recommendations for CAPPW.

Table 1 contains definitions applicable in this article.^7,9

General measures to prevent TB transmission in SA should include: implementation of existing TB infection prevention and control (IPC) policies¹⁷; community-based activities to increase awareness, education and psychosocial support for people exposed to TB^5,18,19; nutritional support programmes for families affected by TB²⁰; optimised Bacillus Calmette-Guérin (BCG) vaccination coverage⁹; and routine TB contact screening and management.⁷

People of all ages with significant TB exposure, children and adolescents living with HIV, and pregnant and postpartum women are at high risk of developing TB disease and should be screened for TB regularly. The South African National Department of Health (SANDoH) has recommended that individuals from high-risk groups be managed with a ‘test and treat’ approach, whereby TPT is offered to those in whom TB disease has been excluded as per Figure 1.^7,9

The theory for providing TPT as a preventive measure is that individuals who do not have TB disease but who are infected with viable M.tb have a very low bacillary load, which can be eradicated with one or two drugs, thereby reducing the risk of developing TB disease.^21,22 Therefore, regardless of whether TPT is provided, clinical follow-up of TB contacts, particularly in the 12 months following significant TB exposure, remains critical for early detection and treatment of incident TB disease to reduce morbidity, mortality, and ongoing M.tb transmission. Contraindications to TPT include severe liver dysfunction, severe peripheral neuropathy, or previous severe adverse reaction to TPT.⁷

Once a decision has been made to provide TPT for TB infection, the optimal choice of drug or drug combination depends on the effectiveness, availability, side effect profile, cost, drug–drug interactions, drug susceptibility profile of the TB index person, and the risk of resistance amplification.²¹ A recent review article by Chihota et al. provides a comprehensive overview of clinical trial evidence supporting current TPT regimen recommendations, as well as ongoing and future TPT studies relevant to CAPPW.²²

Table 2 summarises eligibility, composition, duration, and other characteristics of available TPT regimens for CAPPW in SA. For medication dosing guidance in these populations, refer to the relevant guideline documents,^7,9,23,24 or Section 2 of the Quick Reference Guide.²⁵

In SA, the current TPT options for DS-TB include: isoniazid and rifapentine given once weekly for 3 months (3HP), daily rifampicin and isoniazid for 3 months (3RH), daily isoniazid for 6 months (6H) or daily isoniazid for 12 months (12H). All people receiving TPT should be offered pyridoxine (vitamin B6) for the duration of their TPT: 25 mg/day if ≥ 5 years and 12.5 mg/day if < 5 years. Lack of pyridoxine supply should not be a reason to withhold or postpone TPT.⁷

Rifampicin has significant drug–drug interactions with many ART drugs, and dolutegravir (DTG) dosing should be boosted if given with rifampicin-based TPT (see Table 2). Isoniazid and rifapentine do not interact significantly with DTG and are therefore preferred in PLWHIV. The PLWHIV may be offered 3HP if they are already virally suppressed (viral load < 50 copies/mL) on a DTG-containing regimen. However, those recently initiating DTG-based ART regimens or are virally unsuppressed should rather be offered 12H instead of 3HP. The reason is that rifapentine and DTG are metabolised by the same liver enzymes (CYP3A and UGT1A1). The DOLPHIN trial²⁶ showed that while DTG levels dropped by ~60% during co-administration with 3HP, most participants maintained viral suppression if they were already virally suppressed on DTG-based ART. New evidence to support simultaneous initiation of DTG-based ART and 3HP is emerging,²⁷ and guidelines may be updated to reflect this in future.

The 2023 National Guidelines on the Treatment of Tuberculosis Infection do not include recommendations for preventive therapy regimens for DR-TB.⁷ Although supporting evidence is scarce, the 2019 Clinical Management of Rifampicin-Resistant Tuberculosis guideline does suggest possible options for treatment of DR-TB infection, depending on the resistance pattern of the M.tb strain.²³

For TPT and ART interactions, refer to Table 2. Use interaction checker tools, such as EMGuidance or the SA HIV/TB Hotline application to check for other significant drug–drug interactions with TPT.

Table 2 summarises common side effects and toxicities. Most side effects are mild and can be managed symptomatically. All adverse events should be reported.

People on TPT should be reviewed monthly. For guidance around TPT treatment interruption, refer to Section 6 of the 2023 National Guidelines on the Treatment of Tuberculosis Infection.⁷

Preventing TB among CAPPW requires a co-ordinated and individualised approach. Through timely screening, IPC, psychosocial support, and targeted TPT, primary care providers play a critical role in mitigating TB-related morbidity and community transmission. As evidence evolves, particularly regarding TPT use in CAPPW, ongoing education and guideline adherence remain vital. Empowering clinicians with practical tools and clinical insight will enable safer, more effective TB prevention in SA’s most vulnerable populations.