In 2021, a global tuberculosis vaccine research and development roadmap proposed a series of actions to accelerate the development of new, effective, and affordable vaccines that are urgently needed to eliminate tuberculosis globally. Since then, the pipeline has diversified, several candidates are currently in phase 3 clinical trials, and many low-income and middle-income countries have made important steps in anticipating regulatory approval. However, the number of candidates in active clinical trials is small and product development challenges persist. Engagement with vaccine manufacturers has increased but is hampered by unclear demand and insufficient committed procurement. Investment in tuberculosis vaccine research and development therefore remains risky and inadequate. In parallel, more work is needed to identify and plan for cost-effective implementation while mitigating potential hesitancy and stigma to ensure uptake of new tuberculosis vaccines once licensed. Increased diversification of funders and strategic coordination of multiple stakeholders is needed more than ever.
BACKGROUND: Tuberculosis (TB) remains a leading cause of mortality, particularly among people with HIV (PWH). In South Africa, the targeted universal TB testing (TUTT) strategy was introduced to shift from symptom-based to symptom-agnostic screening to improve early case detection in PWH. However, limited research has explored provider perceptions of the TUTT strategy. We explored healthcare professionals’ perceptions of the introduction, feasibility, challenges, and potential solutions for implementing TUTT. METHODS: We conducted a qualitative study using in-depth interviews with 11 purposively selected healthcare professionals (nurses, program managers, and doctors) involved in integrated TB/HIV care in KwaZulu-Natal Province, South Africa. Interviews were audio-recorded, transcribed, and analysed through inductive thematic analysis. RESULTS: Four thematic categories with eight overarching themes were identified. TUTT introduction was characterised by largely informal communication, which contributed to variable understanding, while structured dissemination and mentorship supported clearer uptake. TUTT feasibility was shaped by facility capacity, with adequate staffing, diagnostic resources, and workflow organisation enabling smoother integration, whereas under-resourced facilities struggled. Implementation challenges included sputum collection difficulties, especially among asymptomatic PWH, staff shortages, heavy workloads, and fragmented TB/HIV data systems. Proposed solutions centred on expanding access through alternative triage tools such as mobile digital chest X-rays, point-of-care tests, community-based testing, and strengthening provider training, role clarity, and patient education. CONCLUSION: TUTT is perceived as a valuable strategy to improve TB detection in PWH, but its success hinges on addressing operational, infrastructural, and patient engagement barriers. Strengthening resources, integrating data systems, and adopting locally tailored, patient-centred approaches are essential to bridge the gap between policy and practice, thereby optimizing TUTT.
Tuberculosis (TB) remains a leading cause of morbidity and mortality in South Africa despite substantial progress in diagnosis and treatment. Several candidate vaccines targeting adolescents and adults are now in advanced clinical development, raising the prospect that a new TB vaccine could become available as early as 2029. However, translating clinical trial success into population-level impact will require early policy planning, health system preparedness, and coordinated national action. To support these efforts, the South African National Department of Health and the World Health Organization convened a national TB Vaccine Preparedness Workshop in Johannesburg in July 2025, bringing together policymakers, researchers, regulators, manufacturers, and civil society and community representatives. The workshop aimed to align stakeholders on priority populations and delivery strategies for future TB vaccines, identify evidence needs to inform national policy decision-making, and outline actions required to ensure timely and equitable introduction. Discussions highlighted that successful introduction of a TB vaccine for adolescents and adults will depend on coordinated readiness across delivery systems, regulatory and manufacturing processes, financing mechanisms, and public trust. Participants emphasised pursuing a broad population-level vaccination strategy for adolescents and adults, building on existing immunisation and primary healthcare platforms while adapting delivery strategies to reach these populations. Priorities included generating South Africa-specific evidence to inform policy and financing decisions, engaging early with regulatory authorities and manufacturing partners, strengthening data systems for safety monitoring and evaluation of vaccine impact, developing sustainable financing approaches, and fostering community engagement to build vaccine confidence. These insights provide a foundation for coordinated national planning to ensure timely and equitable introduction of future TB vaccines in South Africa.
BACKGROUND:People with an HIV viral load less than 200 copies per mL cannot transmit HIV sexually, but viral rebound can lead to transmission risk. We aimed to quantify 12-month durability of viral suppression in South Africa's national HIV programme. METHODS:We conducted a retrospective observational cohort study to assess the 12-month durability of viral suppression in South Africa's National Health Laboratory Service National HIV Cohort, a probabilistically linked, de-identified database including all viral loads in the public sector HIV programme. Individuals aged 15-59 years were followed up for 18 months from their first viral load less than 200 copies per mL occurring between July 1, 2021, and June 30, 2022 (baseline). Guidelines specified annual monitoring if viral load was less than 200 copies per mL. The first outcome of our study was viral monitoring at 12 months, defined as any viral load test 6-18 months after baseline. The second outcome of our study was 12-month viral load, categorised according to WHO transmission risk thresholds: less than 200 copies per mL (zero risk), 200-999 copies per mL (almost zero risk), and 1000 copies per mL or greater. We fit modified Poisson regression models to assess predictors of these outcomes. FINDINGS:Our study included 3 584 203 individuals, reflecting all people living with HIV aged 15-59 years with an HIV viral load less than 200 copies per mL in the national HIV programme between July 1, 2021, and June 30, 2022. 2 588 294 (72·2%) individuals were female and 995 909 (27·8%) individuals were male. Of the 3 584 203 individuals with a baseline viral load less than 200 copies per mL, 2 858 992 (79·8%) were virally monitored at 12 months. Of those, 2 605 311 (91·1%) had a 12-month viral load less than 200 copies per mL, and 2 755 122 (96·4%) had a 12-month viral load less than 1000 copies per mL. Individuals with a previous history of viral suppression had the highest rates of monitoring (1 998 198 [87·2%] of 2 291 511 individuals) and continued suppression at less than 1000 copies per mL (1 950 857 [97·6%] of 1 998 198 individuals). Those least likely to remain virally suppressed included young men, young women, and people with previous elevated viral loads. Results were robust to linkage errors and different outcome definitions. INTERPRETATION:People with viral load less than 200 copies per mL who remained on antiretroviral therapy still had zero or almost zero transmission risk 12 months later. People living with HIV with viral load less than 200 copies per mL can rely on Undetectable=Untransmittable as a prevention strategy, so long as they remain on antiretroviral treatment. FUNDING:US National Institutes of Health.
BACKGROUND:Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue (T p pertenue), has evaded eradication, in part due to a high proportion of asymptomatic cases. Repeated mass drug administration (MDA), whereby an entire population is repeatedly treated irrespective of disease, could provide a solution. Here, we aimed to investigate the effect of MDA on the genomic epidemiology of T p pertenue. METHODS:We conducted a retrospective genomic epidemiology study on samples collected during a cluster-randomised trial of mass administration of azithromycin for yaws eradication in the Namatanai District of Papua New Guinea. Participants were in 38 wards (administrative units encompassing several villages) in three local-level government areas (LLGs). The experimental group received an initial round of MDA followed by two further rounds 6 months and 12 months after the first round. The control group received one round of MDA followed by two rounds of treatment targeting clinical cases and contacts only, on the same schedule as the MDA in the experimental group. A follow-up survey on both groups was done 18 months after the first MDA round. Swab samples were collected at each round from ulcerative and nodular skin lesions, and blood was collected by finger-prick for serological testing at 18 months. Metadata on ulcer size (cm) and duration (days) were recorded at each round, and treponemal and non-treponemal antibodies were recorded at 18 months. Samples from swabs positive for T p pertenue underwent library preparation and whole-genome sequencing. We examined the phylogenetic relationships between genomes, linking them with geospatial and patient metadata to understand the impact of MDA on T p pertenue diversity and transmission. FINDINGS:Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality Tp pertenue genomes. We identified 20 sublineages of T p pertenue in the control group and 21 in the experimental group at the beginning of the study. At the end of the study, there were 13 sublineages in the control group and three in the experimental group, of which two persisted in both groups. Three sublineages not detected at baseline were observed in the control group after commencing MDA. The two sublineages that persisted in both groups had non-synonymous mutations in penicillin-binding proteins. One of these sublineages evolved macrolide resistance in three individuals and was associated with lowered treponemal antibody (p=0·0036) and longer ulcer duration (p=0·015). Despite the study taking place within a small island, sublineages were geographically clustered, with pairs of samples from the same ward (odds ratio 7·1, 95% CI 5·7-8·8; p<0·0001) or neighbouring wards (4·3, 3·3-5·4; p<0·0001) more likely to share the same sublineages compared with pairs from different LLGs. Additionally, older individuals were more likely to share sublineages than were younger individuals (1·5, 1·2-1·9; p<0·0001). INTERPRETATION:Repeated MDA was successful in reducing and maintaining the genetic diversity of T p pertenue at a low level but was associated with the development of macrolide resistance. Yaws re-emergence after MDA was attributed to multiple sublineages, of which the majority were detected in the population before MDA. Participants within the same ward were more likely to share sublineages than those that were more widely geographically separated, suggesting that re-emergence was driven by local transmission. These findings could inform future yaws elimination strategies. FUNDING:European Research Council, EU, Provincial Deputation of Barcelona, Barberà Solidària Foundation, Wellcome, and Fundació "la Caixa".
