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120 Peter M Small Bill and Melinda Gates Fndn, Seattle, WA, USA and Stanford Univ Med Ctr, CA, USA |
Background: The challenges in confronting tuberculosis (TB) in the context of HIV are well known to this audience. This plenary talk will address the question, “Is there a scientific basis for hope in understanding why TB is so problematic and for how to improve the situation, either by preventing or treating tuberculosis?” Stated another way, over the past decade a combination of resources (e.g., NIH research money) and knowledge (genome sequence) have put TB on the cutting edge of microbiology, but what do we really have we to show for it? The epidemiology is clear, TB is out of control in the context of HIV. Recent molecular epidemiologic studies provide some parameters for models that provide a conceptual framework for exploring various responses. In sum, there is scientifically based hope for preventive therapy and improved case finding to decrease TB with readily available tools. There are clear data that the efficacy of bacillus Calmette-Geurin (BCG) is variable at best. Comparative genomics of BCG strains provided some insight into why and clues for how to make improved vaccines. There are 5 scientifically compelling reasons to be upbeat about the development and testing of improved vaccines. A major problem is the required duration of TB treatment regimes. The working hypothesis is that this is due to mycobacterial latency. Microarray analysis is providing insights into the biology of latency. Drugs designed to target essential metabolic pathways of latency may dramatically shorten therapy or cure latent infection. This provides a rational path to drug development. Conclusions: In sum, there have been exciting fundamental insights into the fundamental biology of Mycobacterium tuberculosis with practical implications. It’s up to all of us to commit to translate knowledge into improved health.
Keywords: liver histology; hepatic fibrosis; hepatitis C virus
