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South Africa has half a million mine workers employed in approximately 1,800 mines and quarries across the country. Mine workers in South Africa have the highest TB incidence in the world, estimated at 3,000 per 100,000 people. These numbers surpass the WHO’s threshold for a health emergency: 250 cases of TB per 100,000 people. The challenge of TB in the mining sector in southern Africa has persisted for over 100 years due to a combination of complex factors which include: cross border migration of mine workers, which makes case finding and referrals difficult; multiple health care systems and protocols across countries; a private-sector driven mining industry; regulation of the mining industry by different government ministries; and diverse economic and socio-cultural dimensions which are a challenge to coordinate. Many attempts to solve this service-delivery challenge have been unsuccessful and changing its course requires a new way of thinking. Southern Africa is leading a novel regional approach, with the support of the World Bank, the Global Fund to Fight AIDS, TB and Malaria, and the Stop TB Partnership, to reverse the trajectory of TB in southern Africa over the next five years. A one-day capacity building workshop is being hosted in order to exchange knowledge and share insights from this innovative regional approach and to engage key stakeholders on how to successfully apply the Science of Service Delivery model to address multi-sector, multi-country health system challenges.