No abstract

The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly understood. Herein, we used a transcriptomic approach to investigate the host cell gene expression profile in M. tuberculosis–infected human macrophages (ΜΦ). We identified 33 genes, encoding proteins involved in angiogenesis, for which the expression was significantly modified during infection, and we show that the potent angiogenic factor VEGF is secreted by M. tuberculosis-infected ΜΦ, in an RD1-dependent manner. In vivo these factors promote the formation of blood vessels in murine models of the disease. Inhibiting angiogenesis, via VEGF inactivation, abolished mycobacterial spread from the infection site. In accordance with our in vitro and in vivo results, we show that the level of VEGF in TB patients is elevated and that endothelial progenitor cells are mobilized from the bone marrow. These results strongly strengthen the most recent data suggesting that mycobacteria take advantage of the formation of new blood vessels to disseminate.

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Drones are increasingly being used globally for the support of healthcare programmes. Madagascar, Malawi and Senegal are among a group of early adopters piloting the use of bi-directional transport drones for health systems in sub-Saharan Africa. This article presents the experiences as well as the strengths, weaknesses, opportunities and threats (SWOT analysis) of these country projects. Methods for addressing regulatory, feasibility, acceptability, and monitoring and evaluation issues are presented to guide future implementations. Main recommendations for governments, implementers, drone providers and funders include (1) developing more reliable technologies, (2) thorough vetting of drone providers’ capabilities during the selection process, (3) using and strengthening local capacity, (4) building in-country markets and businesses to maintain drone operations locally, (5) coordinating efforts among all stakeholders under government leadership, (6) implementing and identifying funding for long-term projects beyond pilots, and (7) evaluating impacts via standardised indicators. Sharing experiences and evidence from ongoing projects is needed to advance the use of drones for healthcare.