Laboratory Preparedness and Management of Biothreat and Emerging Infectious Disease Agents

1. Laboratory Preparedness and Management of Biothreat and Emerging Infectious Disease Agents ISM: May 7-8, 2013 James W. Snyder, Ph.D. University of Louisville

2. Faculty Disclosure The Association of Public Health Laboratories adheres to established standards regarding industry support of continuing education for healthcare professionals. The following disclosures of personal financial relationships with commercial interests within the last 12 months as relative to this presentation have been made by the speaker: James W. Snyder, Ph.D., D(ABMM), F(AAM) “Nothing to disclose”.

3. OBJECTIVES • Biosafety • Biosecurity • Select Agent Rule • Definition of the LRN Sentinel Clinical Laboratory • Role of Sentinel Clinical Laboratories in the LRN Biological Threat Preparedness • Responsibilities of the Sentinel Clinical Laboratory • LRN Sentinel Level Laboratory Testing Protocols

4. Biosafety • Reduce or eliminate exposure of staff and environment to potentially hazardous biological agents • Implementing various degrees of laboratory control and containment through: - lab design and access - personnel expertise and training - use of containment equipment - use of safe methods of managing infectious materials in the laboratory setting • Packing and Shipping Infectious biological materials

5. Biosecurity • Prevent loss, theft or misuse of microorganisms, biological materials • Limiting access to facilities • Biosafety and Biosecurity not mutually exclusive of each other; share common components

6. Biosecurity Risk Assessment and Management Process • Identify and Prioritize Biological Materials • Identify and Prioritize the threat to biological materials • Analyze the risk of specific security scenarios • Develop an overall risk management program • Re-evaluate the Institution’s risk posture and protection objectives

7. Elements of a Biosecurity Program • Program management • Physical security • Personnel management • Inventor and accoutability • Information security • Transport of biological agents • Accident, injury and response plan • Reporting and communication • Training and practice drills • Security updates and re-evaluations

8. Select Agents and Toxins* denotes Tier I Agents • Abrin • Botulinum neurotoxins • Botulinum neurotoxin producing species of Clostridium • Conotoxins (Short, paralytic alpha conotoxins containing the following amino acid sequence X1CCX2PACGX3X4X5X6CX7) • Coxiella burnetii • Crimean-Congo haemorrhagic fever virus • Diacetoxyscirpenol • Eastern Equine Encephalitis virus1 • Ebola virus* • Francisella tularensis • Lassa fever virus Lujo virus Marburg virus • Monkeypox virus1 • Reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments (Reconstructed 1918 Influenza virus) http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html

9. Select Agents and Toxins (cont.) • Ricin • Rickettsia prowazekii • SARS-associated coronavirus (SARS-CoV) Saxitoxin • South American Haemorrhagic Fever viruses: Chapare • Guanarito • Junin • Machupo • Sabia • Staphylococcal enterotoxins A,B,C,D,E subtypes • T-2 toxin • Tetrodotoxin • Tick-borne encephalitis complex (flavi) viruses: • Far Eastern subtype • Siberian subtype • Kyasanur Forest disease virus • Omsk hemorrhagic fever virus • Variola major virus (Smallpox virus) • Variola minor virus (less virulent form of smallpox) • Yersinia pestis http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html

10. OVERLAP SELECT AGENTS AND TOXINS* • Bacillus anthracis • Bacillus anthracis Pasteur strain • Brucella abortus • Brucella melitensis Brucella suis Burkholderia mallei • Burkholderia pseudomallei • Hendra virus • Nipah virus • Rift Valley fever virus • Venezuelan equine encephalitis virus1 *have the potential to pose a severe threat to public health and safety, to animal health, or to animal products http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html

11. Categorization of Infectious Substances • Category A substance:- an infectious substance or microorganism which is transported in a form that, when exposure to it occurs, is capable of causing permanent disability or life-threatening or fatal disease in an otherwise healthy human or animal • Biological Substance, Category B - formerly known as Clinical Specimen or Diagnostic Specimen; an infectious substance not in a form generally capable of causing disability, life-threatening illness, or fatal disease

12. LRN Today • Federal • State and Local Public Health • Military • Food Testing • Environmental • Veterinary • International • Sentinel (private, community-based)

13. Partnership between Government and Private Organizations • APHL • FBI (Department of Justice) • The American Association of Veterinary Laboratory Diagnosticians • The American Society for Microbiology (ASM) • EPA • USDA • USFDA • Dept of Homeland Security

14. National, reference, and sentinel laboratories work as an integrated network that builds upon individual laboratory capacity in order to respond to pubic health emergencies

15. Definition of Sentinel Clinical Laboratory • Certified to perform High Complexity Testing under CLIA 88 by CMS for the applicable Microbiology Speciality; laboratory in-house testing includes Gram stains and at least one of the following: lower respiratory tract, wound, or blood cultures • AAVLD Certification: Veterinary Labs only • Basic/Advanced Sentinel: eliminated

16. Role of Sentinel Clinical Laboratories in the LRN • Partner and work closely with local and state public health and federal laboratories to recognize agents of terrorism and other emerging threats to public health • Rule-out or Refer to LRN Reference Laboratory • Reportable Diseases

17. Responsibilities of the Sentinel Clinical Laboratory • Familiar with reportable disease guidelines in its jurisdiction; has policies and procedures in place to refer diagnostic specimens or isolates suspected to contain agents of public health significance to local or state public health laboratory in its jurisdiction • Ensures personnel have met the applicable federal regulations for packing and shipping of infectious substances • Policies and procedures for referral of suspect biothreat agent specimens and/or isolates to the LRN Reference Laboratory in its jurisdiction that reflect the ASM Sentinel Level Laboratory Guidelines for Suspected Agents of Bioterrorism and Emerging Infectious Diseases (www.asm.org)

18. Responsibilities of the Sentinel Clinical Laboratory, con’t • Demonstrates annual competency by participation in proficiency testing or exercises, Example: CAP sponsored Laboratory Preparedness Exercise (LPX) or state developed challenge sets • Class II or higher Certified Biological Safety Cabinet • Complies with Biosafety Level II (BSL-2) practices per the Biosafety in Microbiological and Biomedical Laboratories guidelines • Complies with applicable OSHA regulations for respiratory protection • Complies with the rules and regulations of the Select Agent Program

19. Responsibilities of the LRN Reference Public Health Laboratory • Identifies all qualified sentinel clinical laboratories within the appropriate jurisdiction • Provides training or assures access to training to sentinel clinical laboratories encouraging them to maintain competent staff knowledgeable in the ASM Sentinel Level Clinical Microbiology Laboratory Guidelines for Suspected Agents of Bioterrorism and Emerging Infectious Diseases • Training must encompass the following subjects: - recognition, rule-out testing and referral of potential biothreat agents, packing and shipping of infectious specimens and isolates following applicable federal regulations, chain of custody, biosafety and risk assessment

20. Responsibilities, con’t • Develops and maintains a sentinel clinical laboratory database that includes the following required elements: - Laboratory CLIA number - Laboratory Name - Laboratory Mailing Address - Laboratory Physical Address - 24/7 Emergency Contact (phone/pager/answering service

21. Responsibilities con’t Biosafety precautions: - highest biosafety level (BSL-2, BSL-3, Other/don’t know List of each method for receiving emergency alerts and communications Total number of personnel in Microbiology Total number of personnel currently competent to apply the ASM Sentinel Level Protocols

22. Recommended List of Common Database Elements • Secondary Contact (Name, title, e-mail, phone, fax) • Number of Class II BSCs • Testing capabilities (e.g. Molecular, Sequencing, AFB, Virology) • Participation in a Competency Assessment (CAP/LPX, State Issue Challenge Set, Other) • Additional Respiratory Protection Information such as N-95 or P-100 fit testing

23. Recommended List of Common Database Elements, con’t • Develops and implements exercises to test the functionality of the system, such as the ability of sentinel clinical laboratories in their jurisdiction to correctly refer samples to the local or state public health laboratory • Assures 24/7 availability for technical consultations, confirmatory testing and serves as an information resource for sentinel clinical laboratories • Ensures a robust electronic system for communication of routine and emergency alerts and critical information to all of the sentinel clinical laboratories within their jurisdiction.

24. Updated/Revised LRN Sentinel Level Protocols

25. Biothreat Agents and Emerging Pathogens (Sentinel Protocols) • Biothreat - Anthrax (Bacillus anthracis) - Brucellosis (Brucella spp) - Plague (Yersinia pestis) - Tularemia (Francisella tularensis) - Glanders/Meliodosis (Burkholderia mallei/pseudomallei) - Q Fever (Coxiella burnetii) - Smallpox (Variola major/minor)

26. Biothreat Agents and Emerging Pathogens (Sentinel Protocols) • Biothreat agents - Botulism (Clostridium botulinum) - Staphylococcal enterotoxins (S. aureus) • Emerging Pathogens - Novel Influenza strains • Packing and Shipping • Laboratory Preparedness Template

27. Major Revisions to Sentinel Level Protocols • Introduction and General Recommendations: New Section • CLSI Format (Pre Analytical, Analytical, Post Analytical) • Sentinel Clinical Level (formerly Level A) • Do not perform identification and susceptibility testing • Emphasis on avoiding use of kit-based and automated ID/Susceptibility systems • Updated information on acceptable sample types • Chain of custody: starts when the specimen is identified as an agent of bioterrorism by the LRN Reference Laboratory - hospital personnel may be called upon to testify, but routine practices for specimen handling sufficient for chain of custody • Guidance on destruction of organisms • BSL-3 or BSL-2 with BSL-3 precautions • UpdatedImagesforGramStain,colonymorphology,biochemical tests • Updated Web Links • Guidance regarding therapy/references

29. Biochemical Procedures combined in a separate section

33. Summary • Practice Biosecurity (Risk Assessment) • Understand and Practice Biosafety • Perform manipulations in BSC - small, tiny Gram-negative bacilli that fails to grow on MacConkey/EMB • Training - packing/shipping - agent characteristics - LPX Proficiency Program • Avoid Kit-based/Automated Instruments • Comply with LRN Protocols • Establish/maintain communication with designated LRN Reference Laboratory

34. Acknowledgements ASM SMEs David Craft Peter Gilligan Larry Gray Mike Loeffelholz Judy Lovchik Scott Riddel Barbara Robinson-Dunn Mike Saubolle Sue Schifflet Susan Sharp Alice Weissfeld David Welch Mary York

35. Acknowledgements • APHL Tricia Blevins Erin Bowles Mary DeMartino Amanda Moore Jim Rudrik Moe Sullivan Christopher Chadwick Chris Mangal Kara MacKeil • CDC (Harvey Holmes) • ASM (Kimberly Walker, Professional Affairs) • ASCP (William Becker)

36. Thank You!!!!“Teamwork is the fuel that allows common people to attain uncommon results”

37. QUESTIONS?