1. New Developments in Biothreats and Biosecurity Clifton R. Lacy, M.D. October 17, 2007

2. A Taste of the New Jersey Experience Imported Lassa Fever Tularemia Severe Acute Respiratory Syndrome (SARS)

3. Emerging Infectious Diseases

4. New Diseases in Past 20 Years AcanthamebiasisAIDSAnthrax Antimicrobial and insecticide resistance Australian Bat Lyssavirus Babesiosis Bartonella henselae BotulismCampylobacteriosis

5. New Diseases in Past 20 Years ChikungunyaCryptosporidiosisCyclosporiasis Prion Disease, Creutzfeldt-Jacob (vCJD) Ebola Hemorrhagic Fever Encephalitozoon cuniculi Encephalitozoon hellem Enterocytozoon bieneusi Ehrlichia chafeensis Ehrlichiosis

6. New Diseases in Past 20 Years Escherichia coli 0157:H7 Enterovirus 71 Guanarito Virus Hantaan Hemorrhagic Fever with Renal Syndrome (HFRS) Hantavirus Pulmonary Syndrome Helicobacter pylori Hendra Virus Hepatitis C

7. New Diseases in Past 20 Years Hepatitis E HIV Human herpesvirus 6 (HHV-6) Human herpesvirus 8 (HHV-8) Human Monkeypox Influenza, H5N1 Lassa Fever Legionnaires Disease Lyme Borreliosis

8. New Diseases in Past 20 Years Sabia Virus SARS Coronavirus Sindbis Sin Nombre Virus Staphylococcal Infection, Methicillin- Resistant, Vancomycin-Resistant Streptococcal Infection (toxic shock syndrome, necrotizing fasciitis, etc.) Tuberculosis (MDR-TB, XDR-TB) Tularemia Malaria, Drug-Resistant

9. New Diseases in Past 20 Years Marburg Hemorrhagic Fever Monkeypox, Human Nipah Virus O’nyong’nyong Fever Oropuche Fever Parvovirus B-19 Plague Rift Valley Fever Rotavirus West Nile Encephalitis Whitewater Arroyo Virus

10. Selected New Infections By Year 1973: Rotavirus 1975: Parvovirus B-19 1976: Cryptosporidium 1977: Ebola 1977: Legionella pneumophilia 1977: Hantaan Virus 1977: Campylobacter jejuni

11. Selected New Infections By Year 1980: HTLV-1 1981: Staphylococcus aureus - Toxic Shock 1982: Escherichia coli 0157: H7 1982: HTLV-2 1982: Borrelia burgdorferi 1983: HIV 1983: Helicobacter pylori 1986: Cyclospora cayatanensis 1988: Human herpesvirus 6 (HHV-6) 1988: Hepatitis E 1989: Ehrlichia chafeensis 1989: Hepatitis C

12. Selected New Infections By Year 1991: Guanarito Virus 1991: Babesia species 1992: Vibrio cholerae 0139 1992: Bartonella henselae 1993: Sin Nombre Virus 1993: Encephalitozoon cuniculi 1993: Hantavirus Pulmonary Syndrome 1994: Sabia Virus 1995: Human herpesvirus 8 (HHV-8) 1996: Creutzfeldt-Jacob disease (vCJD) 1997: H5N1 Influenza 1998: Nipah Virus Encephalitis 1999: West Nile Encephalitis

13. Selected New Infections By Year 2000: Rift Valley Fever 2001: Anthrax Bioterrorism 2002: Vancomycin-Resistant Staphylococcus aureus 2003: SARS Coronavirus 2004: Monkeypox, Human

14. Emerging Diseases Over 2 billion airline passengers in 2006 Potential for faster and farther disease spread than any time before in history Outbreak or epidemic somewhere is only few hours away from being public health threat elsewhere Infectious diseases are emerging more rapidly Since the 1970s, one or more new diseases have been identified each year Over 40 diseases now were unknown 20 years ago Over 1100 epidemic events during last 5 years

15. Causes of Emergence/Re-Emergence Population growth and urbanization –overcrowding, unsanitary living conditions, lack of clean water for drinking and washing, poor hygiene Human encroachment on tropical rain forests –populations with little or no disease resistance now in contact with disease organisms and/or vectors Economic and social exigencies –inadequate health systems and public health infrastructure

16. Causes of Emergence/Re-Emergence Environmental change –deforestation, road and building construction, irrigation, increased crop and animal production, urban sprawl, poor sanitation, pollution Movement and encampment of population displaced by wars, civil instability, or natural disasters –overcrowding, lack of clean water, unsanitary conditions, poor hygiene, malnutrition, exposure to new or re-emerging diseases Human sexual behavior change

17. Causes of Emergence/Re-Emergence Increased global travel, commerce, and terrorism –transport of disease-causing organisms/vectors –global commerce of livestock and foodstuffs Indiscriminate use pesticides/antimicrobials –antibiotic resistance in organisms New strains of all diseases –different immunological characteristics, virulence, contagion, and response to antibiotics Immunosuppressed and compromised hosts

18. AS Fauci Examples of Emerging and Re-Emerging Infectious Diseases

19. Examples of Emerging Infections Henipaviruses –Hendra Virus –Nipah Virus Avian Influenza H5N1

20. Intentional Biothreats Anthrax TerrorismBioterrorism

21. Terrorism Repeated violent action Anxiety-provoking Intimidation, coercion, propaganda Main target not the direct target of violence

22. Assassination / Guerrilla Warfare Assassination: Main target is the direct target of violence Conventional and guerrilla warfare: Violence/threat to create fear only in victims

23. Bioterrorism Deliberate release of biological agents (viruses, bacteria, fungi, etc.) to cause illness and/or death in people, animals, or plants Biological agents are insidious –difficult to detect –illness propagates over hours, days, weeks Some biological agents are infectious and contagious –can be spread from person to person (smallpox) Some biological agents are infectious but not contagious –cannot be spread from person to person (anthrax) Bioterrorism agents are divided into three categories, based on on ease of contagion and severity of illness

24. Select Agents – Category A Category A Agents – highest risk Easily spread or transmitted person-to-person High death rates and potential major public health impact Can cause public panic and social disruption Require special action for public health preparedness

25. Select Agents – Category A Anthrax (Bacillus anthracis) Smallpox (Variola major) Plague (Yersinia pestis) Botulism (Clostridium botulinum toxin) Tularemia (Francisella tularensis) Viral hemorrhagic fevers –filoviruses like Ebola and Marburg –arenaviruses like Lassa and Machupo

26. Select Agents – Category B Category B Agents – second highest priority Moderate illness rates and low death rates Require specific laboratory enhancements and disease monitoring

27. Select Agents – Category B Brucellosis (Brucella species) Glanders (Burkholderia mallei) Melioidosis (Burkholderia pseudomallei) Psittacosis (Chlamydia psittaci) Q Fever (Coxiella burnetii) Epsilon toxin of Clostridium perfringens Food safety threats (Salmonella species, E coli 0157:H7, Shigella) Ricin toxin from Ricinus communis Staphylococcal enterotoxin B Typhus (Rickettsia prowazekii) Viral encephalitis (Alpha viruses: Venezuelan Equine Encephalitis, Eastern Equine Encephalitis, Western Equine Encephalitis) Water supply threats (Vibrio cholerae, Cryptosporidium parvum)

28. Select Agents – Category C Category C Agents – third highest priority Include emerging pathogens that could be engineered for mass spread in the future Easily available Easily produced and spread Potential for high morbidity and mortality rates and major health impact Nipah Virus Hanta virus Multi-Drug-Resistant Tuberculosis.

29. Biowarfare History Poisoned wells Contaminated arrows Venomous snakes Dead/infected animals Dead/Infected humans Infected fomites Infected insects Food poisoning Bioagent release

30. Synthetic Biothreats Genetic engineering of bioagents Creation of bioagents Re-creation of bioagents Purchase of DNA sequences

31. Genomics and Future Biological Weapons Modify infectivity Modify virulence Modify antigenic properties Enhance antibiotic resistance Transfer pathogenic properties Alter to make harder to detect, diagnose, and treat Sneak stealth viruses covertly into genome –Population-specific –Triggered at a later time Target genome of specific population –Design specific pathogen

32. Synthetic Biothreats “…DNA can be synthesized from the [genetic] sequence, and this could be done by any third-rate terrorist.” –Vincent Racaniello Virologist, Columbia University

33. Synthetic Biothreats “The most worrisome thing… is that the field of synthetic biology is going to enable people to create potentially very dangerous diseases that don't otherwise exist or to re-create ones that have been wiped off the face of the earth.” –Edward Hammond, biological weapons expert

34. System Failures and Human Error Mistakes – Accidents – Operator/System Failures –Errors of Commission –Errors of Omission Poor Judgment Carelessness Inadequate or Lapsed Training Unintentional Environmental Releases Intentional Releases Containment Breaches and Security Failures Missing Laboratory Samples or Animals

35. World Health Organization World Health Report 2007 A Safer Future Global Public Health Security in the 21st Century

36. Impact Public Health Commerce and travel Reduced vigilance and lapsed programs False rumors Armed conflict Poverty Resistant organisms Weather and climate Intentional and unintentional releases Industrial accidents Natural phenomena