Feasibility of novel adult tuberculosis vaccination in South Africa: a cost-effectiveness and budget impact analysis.

Early trials of novel vaccines against tuberculosis (TB) in adults have suggested substantial protection against TB. However, little is known about the feasibility and affordability of rolling out such vaccines in practice. We conducted expert interviews to identify plausible vaccination implementation strategies for the novel M72/AS01E vaccine candidate. The strategies were defined in terms of target population, coverage, vaccination schedule and delivery mode. We modelled these strategies to estimate long-term resource requirements and health benefits arising from vaccination over 2025-2050. We presented these to experts who excluded strategies that were deemed infeasible, and estimated cost-effectiveness and budget impact for each remaining strategy. The four strategies modelled combined target populations: either everyone aged 18-50, or all adults living with HIV, with delivery strategies: either a mass campaign followed by routine vaccination of 18-year olds, or two mass campaigns 10 years apart. Delivering two mass campaigns to all 18-50-year olds was found to be the most cost-effective strategy conferring the greatest net health benefit of 1.2 million DALYs averted having a probability of being cost-effective of 65-70%. This strategy required 38 million vaccine courses to be delivered at a cost of USD 507 million, reducing TB-related costs by USD 184 million while increasing ART costs by USD 79 million. A suitably designed adult TB vaccination programme built around novel TB vaccines is likely to be cost-effective and affordable given the resource and budget constraints in South Africa.

Potential implementation strategies, acceptability, and feasibility of new and repurposed TB vaccines.

Recently, two Phase 2B tuberculosis vaccine trials reported positive efficacy results in adolescents and adults. However, experience in vaccinating these age groups is limited. We identified potential implementation strategies for the M72/AS01E vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility. We conducted in-depth semi-structured interviews among key decision makers to identify implementation strategies and target groups in South Africa, India, and China. Thematic and deductive analysis using a coding framework were used to identify themes across and within settings. In all three countries there was interest in novel TB vaccines, with school-attending adolescents named as a likely target group. In China and India, older people were also identified as a target group. Routine vaccination was preferred in all countries due to stigma and logistical issues with targeted mass campaigns. Perceived benefits for implementation of M72/AS01E were the likely efficacy in individuals with Mycobacterium tuberculosis (Mtb) infection and efficacy for people living with HIV. Perceived challenges for M72/AS01E included the infrastructure and the two-dose regimen required. Stakeholders valued the familiarity of BCG but were concerned about the adverse effects in people living with HIV, a particular concern in South Africa. Implementation challenges and opportunities were identified in all three countries. Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning.

Impact of COVID-19 Disruptions on Global BCG Coverage and Paediatric TB Mortality: A Modelling Study.

The impact of COVID-19 disruptions on global Bacillus Calmette-Guérin (BCG) coverage and paediatric tuberculosis (TB) mortality is still unknown. To fill this evidence-gap and guide mitigation measures, we estimated the impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality. First, we used data from multiple sources to estimate COVID-19-disrupted BCG vaccination coverage. Second, using a static mathematical model, we estimated the number of additional paediatric TB deaths in the first 15 years of life due to delayed/missed vaccinations in 14 scenarios-varying in duration of disruption, and magnitude and timing of catch-up. We estimated a 25% reduction in global BCG coverage within the disruption period. The best-case scenario (3-month disruption, 100% catch-up within 3 months) resulted in an additional 886 (0.5%) paediatric TB deaths, and the worst-case scenario (6-month disruption with no catch-up) resulted in an additional 33,074 (17%) deaths. The magnitude of catch-up was found to be the most influential variable in minimising excess paediatric TB mortality. Our results show that ensuring catch-up vaccination of missed children is a critical priority, and delivery of BCG alongside other routine vaccines may be a feasible way to achieve catch-up. Urgent action is required to support countries with recovering vaccination coverages to minimise paediatric deaths.

Meeting report: Virtual Global Forum on Tuberculosis Vaccines, 20-22 April 2021.

The Global Forum on Tuberculosis (TB) Vaccines was held virtually from 20 to 22 April 2021, marking its 20th anniversary. The Global Forum on TB Vaccines is the world's largest gathering of stakeholders striving to develop new vaccines to prevent TB. The program included more than 60 speakers in 11 scientific sessions, panel discussions, and workshops. It provided an overview of the state of the field, and an opportunity to share the latest research findings, as well as new and innovative approaches to TB vaccine research and development (R&D). This year, it was held against the backdrop of the COVID-19 pandemic and convened researchers, developers, funders, and other stakeholders remotely to discuss opportunities and challenges for TB vaccine R&D in these unprecedented times.

Assessment of training and mentoring for DR-TB care decentralization in Tanzania.

INTRODUCTION: Drug-resistant TB (DR-TB) care shifted from centralized to decentralized care in Tanzania in 2015. This study explored whether DR-TB training and mentoring supported healthcare workers' (HCWs) DR-TB care performance. METHODS: This mixed study assessed HCWs' DR-TB care knowledge, the training quality, and the mentoring around 454 HCWs who were trained across 55 DR-TB sites between January 2016 and December 2017. Pre- and post-training tests, end-of-training evaluation, supervisor's interviews, DR-TB team self-assessment and team focus group discussion were conducted among trained HCWs. Interim and final treatment results of the national central site and the decentralized sites were compared. RESULTS: HCW's knowledge increased for 15-20% between pre-training and post-training. HCWs and supervisors perceived mentoring as most appropriate to further develop their DR-TB competencies. Culture negativity after 6 months of treatment was similar for the decentralized sites compared to the national central site, 81% vs 79%, respectively, whereas decentralized sites had less loss to follow-up (0% versus 3%) and fewer deaths (3% versus 12%). Delays in laboratory results, stigma, and HCWs shortage were reported the main challenges of decentralized care. CONCLUSIONS: Training and mentoring to provide DR-TB care at decentralized sites in Tanzania improved HCWs' knowledge and skills in DR-TB care and supported observed good interim and final patient treatment outcomes despite health system challenges.

BCG vaccination protects against infection with Mycobacterium tuberculosis ascertained by tuberculin skin testing.

OBJECTIVES: There is conflicting evidence as to whether Bacillus Calmette-Guérin (BCG) vaccination offers protection against Mycobacterium tuberculosis infection ascertained by a positive tuberculin skin test (TST). We investigated the association between BCG vaccination status and TST results in a set of surveys at increasing TST cut-off values to take cross-reactions to BCG vaccination into account. METHODS: Secondary analysis of data from three consecutive tuberculin surveys done among schoolchildren in Tanzania between 1990 and 2002. BCG vaccination status was ascertained by the presence of a typical scar. RESULTS: We analyzed data of 277,588 children of whom 77.7% were BCG vaccinated and 8.5% had TST indurations ≥ 15 mm, 5.1% ≥ 17 mm and 2.8% ≥ 19 mm. In the combined analysis, odds ratios for a positive TST were > 1 for children with BCG up to TST cut-off values of 16 mm. For cut-off values > 17 mm crude and adjusted odds ratios were significantly < 1, and decreased with further increasing cut-off values. CONCLUSIONS: Using a methodology that makes use of the differences in TST reaction sizes between specific and non-specific responses, we showed that BCG vaccination was associated with reduced prevalence of M. tuberculosis infection as measured by the tuberculin skin test, suggesting a protective effect.