The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10 -27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people. latent infection ͉ novel interventions ͉ transmission model ͉ latent therapy T he Bill and Melinda Gates Foundation (BMGF) supports an ambitious portfolio of novel vaccines, treatment regimens, and diagnostic tools for tuberculosis (TB). Funded by BMFG and other sources, the Aeras Global TB Vaccine Foundation oversees vaccine development (1), the TB Alliance seeks novel drug regimens (2), and the Foundation for Innovative New Diagnostics (FIND) looks for new diagnostic tools (3). The current cornerstone of TB intervention is directly observed short-course therapy (DOTS), lasting generally 6 months and prone to dropout (4). DOTS is currently implemented in the 184 countries where 99% of all estimated TB cases occurred and 93% of the world population lived in 2006 (5). Cases are passively ascertained. Sputum smear light microscopy has been the mainstay of TB diagnosis for more than a century, but has important limitations (3). Delays between the patient visit to the clinic and diagnosis often lead to delays in treatment. Neonatal vaccination with bacillus Calmette-Guérin (BCG) vaccine is part of the expanded program of immunization in many countries, but its efficacy against pulmonary TB is poor (1). Despite these efforts, in large parts of Asia, Africa, Eastern Europe, and Latin America, incidence remains 2 orders of magnitude (5) above the Stop TB Partnership goal to eliminate TB as a public health problem, defined as Ͻ1 ...

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Denosumab's efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.