1 / 26

NEIDL Scientific Programs (examples) Antimicrobial resistance (e.g. MDR, XDR tuberculosis)

National Emerging Infectious Diseases Laboratories Institute NIH Blue Ribbon Panel March 13, 2008 Mark S Klempner, M.D. NEIDL Scientific Programs (examples) Antimicrobial resistance (e.g. MDR, XDR tuberculosis) Multivalent vaccines (e.g. hemorrhagic fever viruses/EEE)

caesar
Download Presentation

NEIDL Scientific Programs (examples) Antimicrobial resistance (e.g. MDR, XDR tuberculosis)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. National Emerging Infectious Diseases Laboratories Institute NIH Blue Ribbon Panel March 13, 2008 Mark S Klempner, M.D. • NEIDL Scientific Programs (examples) • Antimicrobial resistance (e.g. MDR, XDR tuberculosis) • Multivalent vaccines (e.g. hemorrhagic fever viruses/EEE) • Acute Lung Injury Repair (e.g. influenza) • Vector transmitted disease interruption (e.g. dengue, hemorrhagic fever viruses) • NEIDL Support for Collaborative Research

  2. Emerging Antibiotic Resistance

  3. Prevalence of Multi-drug Resistant (2 first line drugs) Tuberculosis Among New TB Cases (1994-2002)ANDCountries with Extensively Drug Resistant (XDR, 4 drugs) TB (1/ 2007)

  4. 1. Drug Network Inference 2. KO Off On 3. Gene 1 # of Cells Gene Expression 1 2 3 4 A Network Biology Approach to Antibiotic Action Synthetic Biology Systems Biology

  5. Bactericidal Antibiotics: Stimulate Hydroxyl Radical Formation MA Kohanski et al., Cell 130,1-14, 2007

  6. geneX,Y,Z null Genomics Platform for Studying Antibiotic Action Against Drug Resistant M. tuberculosis GROWTH ASSAY with sub-lethal dose of drug Essential for Growth High Value Targets Essential for Survival SURVIVAL ASSAY with lethal dose of drug

  7. Multidrug resistant M. tuberculosis BSL-3 Extensively drug resistant M. tuberculosis BSL3/4

  8. Avian Influenza (H5N1):Why are we concerned? • Poultry and migratory birds in many countries affected simultaneously • Highly pathogenic • High case fatality among • humans • Majority of human population lacks immunity • Co-circulating human & avian influenza viruses with risk of emergence of pandemic strain July,2006

  9. The Normal Alveolus Type I Epithelial Cell Endothelium (vessel) Type II Alveolar Epithelial Cell Macrophage Blood cells

  10. Inhalation Injury e.g. influenza

  11. Bone Marrow Derived Stem Cell Engraftment in Recipient Lung

  12. Influenza viruses BSL-2 Highly virulent H5 influenza strains BSL3/4

  13. Approaches to Filovirus Vaccines • Inactivated antigens • Whole virion preparations • Liposomes • DNA • Virus-like particles • Replication-defective vectors • Vaccinia • VEEV replicons • Adenovirus • Replicating vectors • Vesicular stomatitis virus • Paramyxovirus

  14. Marburg virus BSL-4 Ebola virus BSL-4

  15. West Nile Virus Infections in the United States: 2005

  16. TakingaBiteOutofVector-TransmittedInfectiousDiseases Klempner MS, Unnasch TR, and Hu LT. N Engl J Med 2007;356:2567-2569

  17. Infection of the niche is an effective strategy for Wolbachia spreading in nature Wolbachia germline Wolbachia at the stem cell niche Frydman et al, Nature 2006

  18. West Nile Virus, Dengue and malaria have a long incubation period in their mosquito vector Only mature mosquitoes transmit diseases Brownstein et al, 2003

  19. Elimination or even slight reductions of the mature vector population show dramatic decrease on disease transmission A naturally occurring strain of the bacteria Wolbachia severely reduces the insect’s lifespan Min and Benzer, PNAS 1977

  20. Dengue,Chickungunya, etc. BSL-3 CCHF and other Hemorrhagic fever viruses BSL-4

  21. National Emerging Infectious Diseases Laboratories March 13, 2008 Mark S Klempner, M.D. • NEIDL Scientific Programs (examples) • Antimicrobial resistance (e.g. MDR, XDR tuberculosis) • Multivalent vaccines (e.g. hemorrhagic fever viruses/EEE) • Acute Lung Injury Repair (e.g. influenza) • Vector transmitted disease interruption (e.g. dengue, hemorrhagic fever viruses) • NEIDL Organization to Support Research Collaboration

  22. National Emerging Infectious Diseases Laboratories March 13, 2008 Mark S Klempner, M.D. • NEIDL Scientific Programs • NEIDL Organization to • Support Research Collaboration

More Related