1. The Galveston NationalLaboratory, a The Galveston National Laboratorynational resourcefor emergingdiseases andbioterrorism threats Dr. Jim LeDucDirectorPresented at the 41st Annual Symposium Global Movement of Infectious Pathogens and Improved Laboratory DetectionEastern PA Branch-American Society for MicrobiologyNovember 17, 2011 Thomas Jefferson University, Philadelphia

2. What are the next emerging virusdiseases to threaten the USA? Objectives for today: Review some of virus diseases of concern aspotentially emerging Introduce the Galveston National Laboratoryas a new national resource to addressemerging infectious diseases Provide examples of whats already underwayat the GNL to address EIDs 3. GNL Mission The mission of the GNL is to assistthe NIAID and the nation byconducting basic and appliedresearch designed to improve theprevention, diagnosis and treatmentof naturally emerging andpurposefully disseminated infectiousdiseases. 4. Building Section Galveston National LaboratoryBSL3 BSL2BSL2 BSL2 ABSL3 IkeSurge BSL4 5. Hedrich Blessing Photography 2009 6. Services DivisionsServices available to researchers in biodefenseand emerging infectious diseases: Aerobiology Assay Development Experimental Pathology Imaging Immunology (currently inactive) Insectaries Services Preclinical Studies 7. BasicProduct DevelopmentResearchNIH R01 andother Funded Proof ofConceptResearch ConceptValidation Pre-clinical/ GLP Studies Human Animal RuleClinical TrialsPhase I: FDA Safety Restricted UsePhase II: ApprovalGNLExpanded SafetyPhase III:UTMBEfficacy FDALicensure 8. West Nile Virus in the United States 1999-2008 9. Influenza A Viruses Human, Avian, Equine, & Swine Influenza viruses Influenza A, B and C B & C viruses infect humans only A viruses ordinary flu & all pandemics Subtyped by surface glycoproteins; change =Antigenic Shift 16 hemagglutinins (HA) and 9 neuraminidases (NA) Current human subtypes: H1N1, H3N2 NAHAwww.pandemicflu.gov www.cdc.gov/flu 10. Emergence of Influenza A Viruses in Humans 1998 1999 *AvianH9*2003 Influenza Viruses H5* 1997 2003- 2011 H7* 1980 1996 200220032004H1H3 H2H1 1977 19151925 1935 1945 195519651975 19851995 2001918 19571968SpanishAsianHongFlu H1N1 Flu H2N2 KongFlu H3N2www.pandemicflu.gov www.cdc.gov/flu 11. Cases of Avian influenza in PeopleYearStrain CountryNo.No. confirmedconfirmedhuman caseshuman deaths1997 A/H5N1Hong Kong 18 61999A/H9N2*Hong Kong2 02003 A/H5N1Hong Kong2 12003A/H9N2*Hong Kong1 02003 A/H7N3Canada 2 02003 A/H7N7Netherlands 84 12003- A/H5N1* Viet Nam,569334 (59%)2011Cambodia*, China,(Nov11) *WHOBangladesh*, Thailandvaccine in Azerbaijan, Djibouti, Egypt**, Indonesia**,prep. Iraq, Myanmar,Thailand, Turkey, www.pandemicflu.govwww.cdc.gov/flu Nigeria, Pakistan,CDC, WHO, 12. Host and lineage origins for the gene segments of the 2009 A(H1N1) virus:PB2, polymerase basic 2; PB1, polymerase basic 1; PA, polymerase acidic; HA,hemagglutinin; NP, nucleoprotein; NA, neuraminidase; M, matrix gene; NS,nonstructural geneR. J. Garten et al., Science 325, 197 -201 (2009) Published by AAAS www.pandemicflu.govwww.cdc.gov/flu 13. Influenza activities at the GNL Evaluation of candidate broadly crossprotective vaccines Testing of antiviral compounds fortreatment of avian influenza High through-put screening of clinicalsamples during H1N1 outbreak Reagent production for WHO 14. Nipah virus disease First recognized in 1998 during outbreak inpigs in Malaysia Annual outbreaks in humans inBangladesh High mortality rate; serious sequelae Potential for person-to-persontransmission (so far not efficient) Animal reservoir host (fruit bats) 15. Breaking the Chain in Bangladesh Science 4 March 2011: vol. 331 no. 6021 1128-1131 16. Pteropus Bats, suspect reservoir of Nipah virus 17. Nipah site in Bangladesh 18. Nipah investigations at GNL Development and validation of NHP modelfor Nipah infection Evaluation of monoclonal antibodies fortreatment of Nipah infection Basic replication studies Vaccine efficacy studies in NHP 19. Rift Valley Fever HistoryKenya, Lake Naivasha 1910 MontgomeryKenya, Lake Naivasha 1930, 33 Daubney et alUganda, Semliki Forest 1948 Smithburn et alSouth Africa 1950-1 Alexander & Dickson 1953 1955-56South Africa 1975 Van Velden et alEgypt1977 Meegan et alMauritania 1987 Digoutte et alEast Africa1997-98MMWRArabian Peninsula2000 MMWR; Madani et alEast Africa2006-07MMWR, Bird et al, 2008Madagascar 2008-Andriamandimby et al,South Africa 2008- 2009 NIV Bulletin, 20102010 2009 20. RVF Epizootiology/Epidemiology Primary vector maintenance Pool breeding Aedes spp. maintain via transovarialtransmission (putative) Can maintain in a silent manner during extended dryperiods Secondary vector species Large populations during periodic/cyclic rainy seasons Initial amplification in vertebrate hosts High viremia levels in many species of vertebratehosts overcome poor vector potential of secondary vectors 21. RVF Egypt 1977-1978GovernorateSheep Cattle HumansSharqiya523615Asyut 402719Qena3821 5Qalubiya3715 6Aswan 3357 6Giza2419 3Fayum 13 0 3Minya 95 4Daqahliya 3 0.41Baheira 21 1Kafr el Sheikh00 3Minufyia0 0.82Beni Suef 00 1 22. Summary of data implicating various animals and humans as amplifying hosts or reservoirs of RVF virus (Meegan, 1981) HostViremia Viremia (peak(length in titer/ml)days) Sheep1010 2-5 Cattle 1092-5 Human108 3-10 Goat 1082-5 Rattus sp.< 103