Introduction

1. Epidemiology in Times of BioterrorismPartnerships for PreparednessAAVMC/AASPH Joint SymposiumApril 22-24, Atlanta, GABy1Sasanya, JJ and 2Khaitsa, ML1Great Plains Institute of Food Safety2Dept. of Veterinary & Microbiological SciencesNorth Dakota State University

2. Introduction • What is Bioterrorism? • Deliberate release of viruses/bacteria/other germs to cause death in people/animals/plants (CDC, 2006) • Deliberate contamination of human food with chemical/biological/radionuclear agents = injury/death to civilian populations and/or disrupt social, economic or political stability (Khan et al. 2001) • The threat of biological terrorism depends on: • Availability of weaponizable agents • Production costs • Willing users • What are the agents of concern? http://www.pbs.org/wgbh/nova/bioterror/about_p.html

3. Categories of Agents - CDC A=High priority agents = highest risk to public/national security: Bacillus anthracis, Yersinia pestis, Variola virus,Filoviruses and Clostridial species B= Second highest priority: Salmonella, Escherichia, Brucella, etc Moderate ease of spread; illness/low death rates Specific enhancements of laboratory capacity; enhanced disease monitoring C= Third highest: Emerging pathogens + genetic engineering for mass spread Ease of access, production, spread; potential for high morbidity/mortality; major health impact

4. Ebola case in Intensive care Examples of diseases caused by agents Smallpox photo World Health Organization http://www.ph.ucla.edu/epi/bioter/hemfevapha_id.html Pneumonic Plague CDC Close-up of anthrax pustule Inhalation anthrax CDC

5. Anthrax attacks of 2001 in the US Bioterrorism is a reality Challenged preparedness understanding biothreat agents. To remain unprepared is disastrous(Henderson, 1999) Preparedness/response Epidemiology is essential Bioterrorism Preparedness and Response www.pbs.org/newshour/health/images/anthrax/.jpg

6. Broader Role of Epidemiology in Public Health • Determining disease origin/known cause • Investigate/control disease = known cause/poorly understood • Information on ecology/natural history • Planning/monitoring disease control programs • Assess economic benefits; benefits of alternative

7. Epidemiology in Times of Bioterrorism • Disease outbreak Investigation • Epidemiologic Clues • Surveillance • Epidemiologic Modelling (Simulations) • Management of outbreaks • Research & Policy • Categorizing/evaluate list of bioterrorist agents; matters • Generating reference documents, Bioterrorism Readiness Plan(English et al, 1999).

8. Disease Outbreak Investigation Epidemiologic Clues: (Wheelis, 2000; Treadwell et al. 2003) • Epidemic curve; Incubation periods (cause/mode) • Steepness; Bimodal curve two continued exposure(anthrax attack) • Several simultaneous point sources(Salad bar/Salmonella) • Odd patterns/organisms • Unusual/atypical illness: Adult measles-like/chicken pox; community based smallpox • Unusual temporal/geographic pattern:Summer influenza • Unusual strains/variants; antimicrobial resistance patterns

9. Odd patterns/organisms • Naturally not transmissible without natural vector (Unnatural phenomena) pneumonic plague • Zoonoses/exotic disease outbreaks (e.g. pneumonic plague, hemorrhagic fevers) (Ashford et al. 2003; Lathrope and Mann, 2001) • Large epidemics with greater cases than expected (discrete population) (Bellamy and Freedman, 2001) • Multiple simultaneous epidemics of different diseases (Pavlin, 1999) • Unusual severity; route of exposure

10. Epidemiologic clues: Significance • Combining clues facilitates early/further/rapid investigation, early implementation of control measures • Giving clues about source also supports the entire public health system; public • mitigate/ameliorate consequences of attack; Minimize resources; Avoids panic/paralysis of services • Builds credibility; Strengthen intelligence

11. Disease Outbreak Investigation • Molecular epidemiology: geographic origin; relatedness of outbreaks (natural vs genetic modification) • Field epidemiology: Timely response (IBS, 2004; CDC, 2001; Gregg, 2002) • Understand possible risk factors, vehicles, and agents for bioterrorism(Treadwell, 2003).

12. Survey team collecting blood, 1976-Congo CDC/Conrad Surveillance • Traditional surveillance • Background rates of disease (Eitzen, 1997). Use/study of secular trends: Mortality/morbidity; project disease occurrence(Friis and Sellars, 2004). • Laboratory confirmation • Syndromic surveillance real time or Near-real time • Timeliness, High sensitivity and specificity, (Bravata et al, 2004) • Identifying isolated cases (Manhattan hospital employee) (O’Toole, 1999; Bardi et al, 1999); unexpected (cross contamination)

13. Examples of surveillance systems • Real-time Outbreak Detection System (RODS) • Electronic Surveillance System for Early Notification of Community-Based Epidemics (ESSENCE) • Generalized linear mixed models (GLMM) Clustered attacks (small areas) (Kleinmann et al. 2004) • Lightweight Epidemiology Advanced Detection and Emergency Response System (LEADERS), The “drop-in, World Trade Organization Summit, 1999 • Integrated System of Bio-hazard Surveillance and Detection

14. Simulations/Epidemic models • Limited attacks/data; understand the threat(Mandl et al, 2004) • Useful in planning public health responses; • Reveal hidden risks of public health decisions • Emphasize the importance of early detection for rapid response/intervention (Meltzer et al, 2001)

15. Examples Simulations/Epidemic models • Anthrax: Aerial attack 5 pounds spores, metropolitan area; 62,000 deaths/50%(IBS, 2004) Aerosal anthrax, packed football stadium (74,000), passing truck 1 mile, 3 seconds, affect 1,850 audience and 1/8 of neighborhood • Smallpox:10 infected people; infect 2.2 million/9 months; 774 billion/ year(Modelling infectivity) (IBS, 2004) • “Dark Winter”, governments’ reaction: smallpox attack > 16,000 cases, 25 states,10 countries,1,000 deaths(Modelling reaction)

16. Simulations • Plague: 4 days of first case, 3,000 deaths, 15,000 ill with plague-like symptoms (O’Toole and Inglesby, 2001) • Modelling readiness response, multiple geographic locations); “Toppoff”, Yesinia pestis(Inglesby et al, 2001) • Botulism: A model of cows-to-consumer supply chain; Several hundred thousand poisoned individuals if early detection is not timely (Weis and Liu e t al, 2005) Gangrene and plague Toppoff demo

17. Management of contagious diseases Identify cases; Isolation (Vaccination); Quarantine; Response/Recovery (2º) Coordination = command/control structures Incident Command System (manage scene) /Unified Command (integrate resources)(CDC, 2001) Liaise with response partners; complex(Koplan, 2001; CDC, 2001) Management of cases/attacks http://phil.cdc.gov/phil/details.asp (CDC/Lloyd); Red Cross, disinfecting body, Kikwit, DR Congo, 1995)

18. Management: Communication and awareness(Watching the media storm/public out rage) • Inform/educate public about realities of bioterrorism • Prepare to communicate(Lathrope and Mann, 2001) • “Evidence-based” communication style vs “adaptive-style” for fast moving emergencies • “We’ll tell you what we know today, and acknowledge that it may change by tomorrow” Gerberding (2001)

19. Communication and awareness • With and educating policy makers • Networks health workers/support personnel(Jernigan, 2002). • Health Alert Network (HAN) • Epidemic Information Exchange program (Epi-X) • Early Aberration Reporting System (EARS)

20. Research & Policy matters • 44% potential bioterrorist agents; 41% unknown causes globally(Ashford, et al. 2003) • Uncover unknown etiology of disease outbreaks (Legionnaire-philadelphia; Hanta virus-4 corners, NM) • Categorizing/evaluate list of bioterrorist agents • Evaluation/provision of guidelines to prioritize potential bioterrorist investigations • Determine etiology of deliberate attacks (Zilinskas, 2002) • Developing documents, Bioterrorism Readiness Plan

21. Epidemiology’s role at global level • Global impact of 2001 anthrax attacks(WHO, 2004) • Spread during incubation periods; Collaborative disease surveillance and early warning systems in all countries • Global Infectious Diseases and Epidemiology Network(GIDEON) • Epidemiology module, every possible differential diagnoses known infectious disease in the world(Felitti, 2005). • Preparedness for Deliberate Epidemics (PDE)Support/advise WHO member states • International Health Regulations (IHR) 2005

22. Global perspective Global distribution of anthrax http://www.vetmed.lsu.edu/whocc/mp_world.htm

23. Global perspective • Training/and networking: Training Programs in Epidemiology and Public Health Interventions Network (TEPHINET) • Applied epidemiology and training programs (AETP)…Ebola 2000 -2001 EIS investigation sites http://www.cdc.gov/eis/about/s2000.htm http:www.who.int/csr/about/partnerships/en

24. Conclusion • Indispensable contribution of epidemiology: Ensuring public health and security; social/economic stability • Leadership (Local/International) • Disease investigations • Collaboration • Policy/decision • Unforeseeable: Giving hope/confidence in a dark era

25. Acknowledgment/Thanks • Dr. Margaret Khaitsa • Dr. Douglas Freeman • Great Plains Institute of Food Safety, NDSU • AAVMC/AASPH • THANK YOU AUDIENCE

26. Reference • Atlas, RM. Bioterrorism: From Threat to Reality. Annual Review of Microbiology. 2002, 56: 167-185. • Centers for Disease Control and Prevention. 2006. Bioterrorism Overview. http://www.bt.cdc.gov/bioterrorism/pdf/bioterrorism_overview.pdf. Last updated 02/26/06. • Felitti VJ. Global Infectious Disease and Epidemiology Network. JAMA, 2005; 293: 1674-1675. • Henderson DA, Smallpox: Clinical and Epidemiologic Futures. Emerg Infec Dis. 1999; 5 (4): 537-539. • Jernigan DB, Raghunatahn Pl, Bell BP, Brechner R, Bresnitz EA, Buler JC, et al. Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings. Emerg Infec Dis. 2002; 8: 1019-1025. • Khan AS, Levitt AM, Sage MJ et al. Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response. Recommendations of the CDC Strategic Planning Workshop. MMWR 2001; April 21, 2000/49 (RR04);1-14. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4904a1.htm. • Koplan J, CDC’s Strategic Plan for Bioterrorism Preparedness and Response. Public Health Reports / 2001 Supplement 2 / 116; 9-16. • Lathrope P, and Mann LM. Preparing for Bioterrorism.Proc (Bayl Univ Med Cent). 2001 July; 14:219-223. • O’Toole T and Inglesby TV. Epidemic response scenario: decision making in a time of plaque. Public Health Rep. 2001; 116 (supplement 2):92-103. • Perkins BA, Popovic T and Yesky K. Public Health in the Time of Bioterrorism. Emerg Infec Dis. 2002; 8: 1015-1018. • Scafer, K, 2001. “LEADERS” (Lightweight Epidemiology Advanced Detection and Emergency Response System)” [online]. http://www.tricare.osd.mil/conferences/2001/agenda.cfm. Accessed 04/22/07 • Treadwell TA, Koo D, Kuker K and Khan AS. Epidemiologic Clues to Bioterrorism. Public Health Reports/ March-April 2003; 118: 92-98. • Wheelis M, Investigating Disease Outbreaks under a Protocol to the Biological and Toxin Weapon Convention. Emerg Infect Dis. 2000; 6: 595-600. • Zilinska RA. Biological Attacks: Lessons of September and October 2001. Chemical and Biological Weapons Nonproliferation Program, Center for Nonproliferation Studies Monterey Institute of International Studies. December 12, 2002