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Emerging Infectious Diseases (EID). Where do they originate? What do we do? Why do we care?

Emerging Infectious Diseases (EID). Where do they originate? What do we do? Why do we care?. Global richness map of the geographic origins of EID events from 1940 – 2004. http://www.ucsd.tv/search-details.aspx?showID=23137. The Realities in Global Trends.

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Emerging Infectious Diseases (EID). Where do they originate? What do we do? Why do we care?

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  1. Emerging Infectious Diseases (EID). Where do they originate? What do we do?Why do we care? Global richness map of the geographic origins of EID events from 1940 – 2004. http://www.ucsd.tv/search-details.aspx?showID=23137

  2. The Realities in Global Trends •EIDs are a significant burden on global economies & public health. •EID emergence thought to be driven by socio-economic environmental & ecological factors. http://www.prweb.com/releases/2005/03/prweb220610.htm

  3. Definition of a Pandemic: Tracking Swine Flu using Google Maps http://www.gadgetlite.com/2009/04/27/tracking-swine-flu-pandemic-google/ pandemic – occurring over wide geographical area and affecting an exceptionally high proportion of the population.

  4. zoonotic diseases or zoonosis: infectious diseases that can be transmitted from other vertebrate animals to humans. May be direct or via a vector. http://www.avma.org/onehealth/appendix_c.asp

  5. Zoonotic Diseases: Five Stages through which pathogens of animals evolve to cause disease in humans. Critical transitions: •Stage 1 to Stage 2: from animal to human •Stages 3 & 4: pathogen’s ability to sustain cycles of human to human transmissions Ex. modern Ebola outbreaks are stage 3. 2007 Nature 447, 279-283.

  6. Global Trends Results •EIDs events have risen significantly over time. •Peak 1980s attributed to HIV. •EIDs dominated by zoonoses (60.3%). •71.8% of zoonoses originate in wildlife (SARs, Ebola) and this trend is increasing. •54.3% caused by bacteria or rickettsia. •25.4% by viruses or prions. •Drug-resistant microbes are Increasing. •Data reveal substantial risk of zoonotic & vector-borne EIDs at lower altitudes (below equator) where reporting effort low. 2008 Nature 451, 990-994

  7. List of NIAID Emerging and Re-emerging Diseases Group I—Pathogens Newly Recognized in the Past Two Decades AcanthamebiasisAustralian bat lyssavirusBabesia, atypicalBartonellahenselaeEhrlichiosisEncephalitozooncuniculiEncephalitozoonhellemEnterocytozoonbieneusiHelicobacter pyloriHendra or equine morbilli virusHepatitis CHepatitis EHuman herpesvirus 8Human herpesvirus 6Lyme borreliosisParvovirus B19 Group II—Re-emerging Pathogens Enterovirus 71Clostridium difficileMumps virusStreptococcus, Group AStaphylococcus aureus

  8. Why are many EIDs linked to Viruses? Viruses have •High rate of mutation, contact between species, spread from isolated populations. •RNA viruses – unusually high rates of mutation lack the proofreading mechanisms seen in DNA replication •Examples of RNA virus EIDs: common cold, measles, mumps, polio HIV or AIDs Ebola – hemorrhagic fever West Nile & other emerging viruses causing encephalitis SARS – severe acute respiratory syndrome (2002-2003) •Examples of DNA virus EIDs: hepatitis, chicken pox, herpes infections Ebola virus

  9. Infectious Disease Cycle & Persistence Dependent on duration of infectivity in host. •Rate of infection of new hosts. •Rate of development of host protective immunity •Population density, size, and structure: may eradicate locally but persists regionally.

  10. How does an Influenza Pandemic Occur?

  11. How does an Influenza Pandemic Occur? Video Backup copy of the Video

  12. Schematic diagram of the influenza viral life cycle. Animation: Influenza Virus Replication Figure 2: G Neumann et al.Nature459, 931-939 (2009)

  13. Animation: Influenza Virus Replication original source flash movie

  14. Experts predict next epidemic will start in animals. USA Today. October 22, 2008. First known case Swine Flu (H1N1): March 28, 2009. First known case US: April 17, 2009 April 26th: New Zealand, France, Israel, Brazil, Spain report cases. 86 deaths in Mexico attributed to swine flu. June 11th: Pandemic declared by WHO. The first influenza pandemic in the last 40 years. July 14th: WHO authorizes pharmacy companies to manufacture vaccines. August 27th: US colleges see spike in number of cases. September 4th: WHO announced 625 deaths in the last week. October 5th: vaccine ready. October 24: President declares a national emergency.

  15. Attendance exercise: Why did the President declare a national emergency concerning swine flu? What is the greatest fear of scientists and policy makers?

  16. Swine Flu or H1N1 is an influenza A virus containing 11 viral genes. Genome consists of 8 segments of single stranded RNA. Genes encoded include: polymerase PB2 polymerase PB1& PB1-F2 polymerase PA hemagglutinin HA nuclear protein NP neuraminidase NA matrix proteins M1 & M2 nonstructural proteins NS1 & 2 Neumann et al. 2009. Nature 459, 931-939.

  17. Where did most recent H1N1 come from? Original reservoir was birds 1918: human influenza A (H1N1) pandemic – transfer from chickens 1918: Cedar Rapids Swine Show influenza A transmitted to pigs from humans. 1931: documented infectious transmission 1933: used ferret model to document transmissibility for human & swine viruses. 1918-present: evolution of virus in humans. 1957: H1N1 abruptly disappeared from humans. Morens et al. 2009. NEJM 361. 225-229.

  18. Genesis of 2009 Swine-origin H1N1 Influenza Viruses. Neumann et al. 2009. Nature 459, 931-939.

  19. Monitoring for Influenza viruses MSNBC Video: H1N1 Virus We can watch virus evolution. This requires large-scale sequencing of viruses isolated from patients. After this, bioinformatic analysis shows which ones are evolving most rapidly. These are, on evolutionary principles, the most likely to be problematic in the future. video backup link

  20. MSNBC Video: H1N1 Virus

  21. US Vaccine Evaluation Centers

  22. Prevention and Control Possibility #1

  23. Prevention and Control Possibility #2 A Antiviral drugs interfere with viral specific proteins: adamantanes: block ion channel formed by M proteins (M proteins used for escape from endosome). Oseltamivir (Tamiflu) and aznamivir: neuraminidase inhibitors block release of new virus particles. M protein with 2 adamantanes bound B

  24. Dengue Fever on the watch list. Why? • Video from ABC News • •Caused by one of 4 different, but related viruses. • •Carried by mosquito, Aedesaegypti • •4-6 days for symptoms to appear. • Often referred to as break-back fever + Why? video backup link

  25. Video from ABC News

  26. Antibiotic resistance: MRSA Infections •Methicillin-resistant Staphylococcus aureus. •Resistant to broad range of antibiotics. •Harmless unless enters body through cut or wound. •Deadly to those with weakened immune systems. •Hospitals, assisted living facilities. •Teams, locker rooms. •2M people/year infected in hospitals. ~100,000 deaths. Kellen Winslow, Oct 21, 2008

  27. MRSA Infections – RPI News: August 16, 2010 •Develop antimicrobial coatings for hospital surfaces •Carbon nanotube-enzyme conjugates made with Lysostaphin, a cell wall degrading enzyme •Lysostaphin from non-pathogenic strains of Staph bacteria had >99% MRSA killed within 2 hours. R Pangule et al. JS Dordick 2010 ACS Nano 4, 3993-4000.

  28. Antibiotics: An Uphill Battle www.CEN-ONLINE.org April 14, 2008 •Short period of effectiveness. •Emerging drug-resistant pathogens. •Cost of R&D without promise of profit margin. •Mother nature more clever than humans! •Focus on natural products- novel compounds

  29. The Need for New Ideas Focus on Under Developed Nations •Focus on Tuberculosis- second most lethal infectious disease •Bill and Melinda Gates Foundation – October 21, 2008 •X PRIZE to fight tuberculosis worldwide-effective diagnosis

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