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Introduction to Biodefense: Bacterial and Toxin Agents

BIOD 604 Fall 2016

Katalin Kiss, Ph.D., PMP®

kkiss@gmu.edu Office hours by appointment

Course Overview

This course covers the pathology and threat of bacterial and eukaryotic agents and toxins that can be utilized as biological weapons or are emerging public health threats.

Out of scope for this course: Viruses, Chemical, Nuclear and Radiological weapons.

Course Objectives

Students will be introduced to bacteria, fungi and toxins that are potential agents of bioterrorism, warfare and threats to public health.

Students will learn the basics of metabolism, virulence factors, physiology, immunology, genetics, pathology, diagnostics, detection and prevention of disease caused by each agent.

Students will also learn the source, use, mechanism of action, detection, treatment and prevention of intoxication by toxin agents.

Students will discuss the suitability of each organism and toxin as a bioterrorist or biological warfare agent.

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Course Requirements and Grading

Final grade will consist of the sum of three exams, a group presentation, discussion leadership opportunities and in class participation, as follows:

Participation 25% Exam #1 20% Exam #2 20% Exam #3 20% Presentation 15%

Format and Protocol

There will be a lecture for a portion of each class.

Students should feel free to ask questions via discussion boards.

Students are expected to have read the assigned readings and complete the activities each week.

There will be small group presentations that will be posted to the Course site.

Course Materials

Many of our readings will be in the form of journal articles available on the course Blackboard site. In addition, the following text book is available:

o Medical Microbiology, 8 th Ed. 2016. Murray Rosenthal and Pfaller, Eds., Elsevier, Inc., Philadelphia, PA.

Communication Plan:

Communication concerning class must be conducted via a gmu.edu e-mail account. I monitor my account in the afternoon, between 4 and 10 pm.

Class announcements will all be posted on the course Blackboard site or sent out via email. Blackboard is accessible at http://mymasonportal.gmu.edu. Emails generated by the site go to your GMU email so be sure to keep track of them.

Please use “BIOD604” in the subject line of any emails.

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Attendance, Participation & Discussion:

Participation in class is expected!

Everyone brings a unique approach, experience set and perspective to the program. Discussions of the material will allow us to view a similar concept from multiple perspectives. To that end, each student should be prepared to participate in discussions in class.

Classroom Decorum

In this course we will often engage in discussions on topics with no definitive answer and as such differences of opinion will be the norm. I encourage debate but I will also expect respect for opposing viewpoints. To this end I will tolerate neither personal attacks nor inappropriate language.

University Policies & Information

Honor Code: Student members of the George Mason University community pledge not to cheat, plagiarize, steal, or lie in matters related to academic work.

Disabilities: If you are a student with a disability and you need academic accommodations, please see me and contact the Office of Disability Services at 703-993-2474 or ods.gmu.edu. All academic accommodations must be arranged through that office.

Email: Mason uses only Mason email accounts to communicate with enrolled students. Students must activate their Mason email account, use it to communicate with their department and other administrative units, and check it regularly for important university information including messages related to this class.

Writing Center: A114 Robinson Hall; (703) 993-1200; http://writingcenter.gmu.edu

“Ask a Librarian” http://library.gmu.edu/mudge/IM/IMRef.html Counseling and Psychological Services (CAPS): (703) 993-2380; http://caps.gmu.edu

University Catalog, http://catalog.gmu.edu, is the central resource for university policies affecting student, faculty, and staff conduct in university academic affairs. Other policies are available at http://universitypolicy.gmu.edu/. All members of the university community are responsible for knowing and following established policies.

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Week Date Unit Lesson Division Sub-Division Division Reading Assignment Division Activity Assessment

1 29AUG-2SEP

Course Introduction, Introduction to Biological Weapons

Lesson A

History of Microbiology Papagrigorakis,Manolis J. 2013. The Plague of Athens: An Ancient Act of Bioterrorism?, Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 11:3

Explore: http://www.historyofvaccines.org/content/timelines/all Make sure you click on the orange squares and images for additional information.

Exam 1

Introduction to Biological Weapons

Carus, Seth 2015. The History of Biological Weapons Use: What We Know and What We Don’t, Health Security, 13:4.

Explore the timeline: http://www.pbs.org/wgbh/pages/frontline/shows/plague/etc/cron.html There are also other sections on the site you might find interesting.- like the South Africa article.

Examples of Biological Weapons

Explore this website: http://www.selectagents.gov/SelectAgentsandToxins.html How many of the organisms listed for the course are listed as a select agent?

Modern Threat Agents Read McTaggart 2016 http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005475

Governance of Biological Material

Emerging Diseases Play Illsville: http://www.historyofvaccines.org/content/illsville-fight-disease Can you achieve 100 % immunity? Can you end an outbreak without a quarantine?

Text Book: pp 2-4

2 5SEP-9SEP

Basic Biology Lesson B

Taxonomy Section 4, Chapters 12-13 Exam 1

DNA and RNA Section 6, Chapters 57

Transcription Section 7, Chapters 68

Translation

Introduction to Bacteriology

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Introduction to Protistology

Introduction to Mycology

3 12SEP-16SEP

Basic Biology Lesson C

The Hygeine Hypothesis Section 1, Chapter 2 Exam 1

The Human Microbiome Section 3, Chapters 7-10 Explore : http://www.scientificamerican.com/article/microbiome-graphic-explore-human-microbiome/

Immune Response pt 1 Read: BMJ. 1989 Nov 18; 299(6710): 1259–1260. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838109/pdf/bmj00259-0027.pdf

Explore the animations in the eBook. Watch: Pathways of Complement Activation; Induction of Tolerance; Steps in Maturation of Lymphocytes; Capture and Presentation of Protein Antigens by Dendritic Cells; Induction and Effector Phases of CMI; Mediated Immune Reactions; Clonal Selection; Sequence of Events in Helper T-Cell-Dependent Antibody Responses; Antibody Mediated Opsonization and Phagocytosis of Microbes; Induction of CD8 T-Cell Response Against Tumors; Immediate Hypersensitivity

Immune Response pt 2

Immune Response pt 3

4 19SEP-23SEP

Basic Biology Lesson D

Pathogenesis Section 1, Chapter 3 Watch: http://www.pbs.org/wgbh/frontline/film/hunting-the-nightmare-bacteria/

Exam 1

Antimicrobials Section 4, Chapter 14-15 &17 Review all four of Koch's postulates: http://www.historyofvaccines.org/content/koch’s-postulates

Antibiotics Section 6, Chapter 58,59, 61

Resistance to anti-microbics

Section 7, Chapter 69,70, 72

5 26SEP-30SEP

Basic Biology Lesson E

Basic Epidimiology Section 2, Chapters 4-6 Explore: Scroll through the entire presentation: http://www.historyofvaccines.org/content/how-vaccines-work

Exam 1

Vaccinations Section 3, Chapter 11

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Bacterial Evasion of Immunity

Section 4, Chapter 16 Watch: http://www.pbs.org/wgbh/nova/body/vaccines-calling-shots.html

Diagnostics/Detection Section 6, Chapter 60 Read: Blog entry http://blogs.plos.org/publichealth/2013/03/11/john-snow-the-first-epidemiologist/

Section 7, Chapter 71

6 3OCT-7OCT

Exam 1

7 10OCT-14OCT

Pathogens/Toxins Lesson F

Toxin Basics Section 4, Chapter 27 Read http://www.cdc.gov/elizabethkingia/outbreaks/index.html

Exam 2

Oppourtinistic Infections/Environmental agents

Pseuodomonas

Acinetobacter Section 4, Chapter 30

Stenotrophomonas Section 6, Chapter 64-65

Elizabethkingia Section 6, Chapter 67

Klebsiella Read: Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States :http://dx.doi.org/10.1371/journal.ppat.1000850

Clostridium

Elizabethkingia

Cryptococcus

Aspergillosis

Pneumocystis

8 17OCT-21OCT

Pathogens/Toxins Lesson G

Food/Waterborne Infections

Listeria Section 4, Chapter 21 Small Group # 1 Presentation due

Exam 2

E.coli Section 4, Chapter 25

Salmonella Section 4, Chapter 26

Shigella Section 4, Chapter 28

Clostridium Section 4, Chapter 30

Vibrio Section 4, Chapter 32

Campylobacter Section 7, Chapter 73

Helicobacter Section 7, Chapter 75

Leptospira

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Entamoeba

Giardia

Cryptosporidium

Nematodes

9 24OCT-28OCT

Pathogens/Toxins Lesson H

Vector Borne Malaria Section 4, Chapter 32 Small Group # 2 Presentation due

Exam 2

Leishmania Section 4, Chapter 25

Babesia Section 4, Chapter 34

Rickettsia Section 7, Chapter 74

Ehrlichia Section 7, Chapter 78

Borrelia

Yersinia

Coxiella

10 31OCT-4NOV

Exam 2

11 7NOV-11NOV

Pathogens/Toxins Lesson I

Sexually Transmitted Pathogens

Treponema Section 4, Chapter 32 Small Group # 3 Presentation due

Exam 3

Neisseria Section 4, Chapter 23

Haemophilus ducreyi

Section 4, Chapter 24

Chlamydia Section 4, Chapter 35

Mycoplasma Section 4, Chapter 33

Trichomonas Section 7, Chapter 73

12 14NOV-18NOV

Pathogens/Toxins Lesson J

Respiratory and Droplet Transmitted Pathogens

Staphylococcus Section 4, Chapter 18 Small Group # 4 Presentation due

Exam 3

Streptococcus Section 4, Chapter 19

Mycobacterium Section 4, Chapter 22

Neisseria Section 4, Chapter 23

Haemophilus Section 4, Chapter 24

Blastomyces Section 6, Chapter 64

Coccidioides

Histoplasma Watch American Experience "The Forgotten Plague" http://www.pbs.org/video/2365422268/

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13 21NOV-25NOV

Thanksgiving Break

14 28NOV-2DEC

Pathogens/Toxins Lesson K

Agricultural Threats Phoma glycinicola (formerly Pyrenochaeta glycines)

Haralampos Keremidis, 2013. Historical Perspective on Agroterrorism: Lessons Learned from 1945 to 2012; Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science ; 11:Suppl. 1

Exam 3

Ralstonia solanacearum

Small Group # 5 Presentation due

Rathayibacter toxicus

Sclerophthora rayssiae

Synchytrium endobioticum

Phoma glycinicola (formerly Pyrenochaeta glycines)

Xanthomonas oryzae

15 5DEC-9DEC

Pathogens/Toxins Lesson L

Conventional Threat Agents

Section 4, Chapter 20 Small Group # 6 Presentation due

Section 4, Chapter 25

Section 4, Chapter 29

16 12DEC-16DEC

Exam 3

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Appendix 1:

Group Presentations will focus on groups of bacteria/protists/fungi/toxins that belong to one of categories listed below:

Group Presentation will contain the following information (Think of this as a briefing you are giving to the rest of the class.):

A title slide Taxonomy- a list of all the agents that you will cover in your discussion: growth/ease of manufacture, physiological description of the agents, including genome size, virulence factors/pathogenecity factors/plasmids natural reservoirs, commercial availability, persistence in the environment, mode of natural transmission, infectious/lethal dose, how long before symptoms appear, symptoms, diagnostics, Available countermeasures treatment/antibiotic regimen, known antibiotic resistance, vaccine status (is there a vaccine? Does it work? Why isn’t there a vaccine?), history of epidemics of the disease, recent outbreaks, Year to date occurrence in US and then worldwide (if available), impact of these outbreaks, recommended decontamination (or remediation- for the plant pathogens) Evidence that any of the agents have been used as a weapon? Evidence that any of the agents have been developed as a weapon? What are the factors of the agents that make them candidates as weapons? How could it be spread? How could it be detected? Expected mortality and morbidity rates in the event of an intentional outbreak? What are the factors that discount the use of the agent as weapon?

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references (primary sources)

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Appendix 2: Group Presentations

Offensive team will prepare and present a scenario of the use of a biological agents on multiple targets over a short period of time that will have physical, psychological and economic impacts.

o Presentation must include: how and why you selected the target

and the agent . How did you acquire the agent? how the agent was made, delivered? Explain your choice of delivery, Calculate the cost of reagents used and

where did you obtain funding. Describe the planning and organization of your group.

Explain any strategies to avoid countermeasures.

References used

Defensive team will prepare and present a scenario of the reaction to the event. o The defensive team will not know what the attack will be until 2 Dec. Therefore, the defensive team should meet to

discuss reactions to multiple scenarios. Must include: Describe the response- from detection, involvement of civic agencies, use of countermeasures,

treatment, cost, decontamination, challenges you had to overcome and anything that came up that you did not plan for. How would you handle these

References used.

:

Offensive Team

Defensive Team

Cameron Albert Colleen Tangney

Alison Mann Laramie Bradford

Saskia Popescu Mary Oberlies

Amanda Clark Greg Mercer

Marialyn Lomberk Lisa Leang

Steph Ellis Sadaf Khan

William Long John Obrien

Meagan Prophet Anna Rowe

Scott McAlister Becca Earnhardt

Chris Burton Drew Joyce

Joey Moratto Nick Guerin

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Use this disclaimer for the presentations:

This is a simulation, completed as a part of coursework for BIOD 604, Introduction to Biodefense/Threat Analysis I: Bacterial and Toxin Agents class, within the Biodefense graduate program at George Mason University.

For further information, please contact Dr. Katalin Kiss (kkiss@gmu.edu), or program director, Dr. Trevor Thrall (athrall@gmu.edu).

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levels of achievment

Criteria Sub-par (25%) Novice (50%) Competent (75%) Proficient (100%)

Planning

Organization

Presentation

Acquisition

Intent

Reality

Funding

Delivery

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Rubric Treatment

Detection

Originality