Bioterrorism and Biological warfare

1. Bioterrorism and Biological warfare Dr. Evan Hermel Dr. Chitra Pai

2. Objectives After completion of this activity, medical students will be able to • Define bioterrorism and biological weapon • Define the three categories of biological agents • List all biological agents from category A • Describe each Category A agent’s microscopic appearance and general characteristics • Explain how these pathogens cause disease • Discuss how these pathogens are transmitted and what makes them candidates for bioterrorism agents • Describe the primary clinical features of the diseases associated with these etiologic agents and how they are treated

3. Emergency Preparedness and Response • Personal • Up to date with vaccinations • Good personal hygiene • Personal protective equipment • Competent in diagnosing and treating conditions caused by bioterrorism attack • Knowledge of post-exposure management • Aware of system to report disease to state and local health departments

4. Speak the Language • Bioterrorism • Deliberate release of microorganism/toxin to cause illness or death in large number of people, animals, or plants • Goal is to cause death, disruption, panic • Inspired by ideological, religious, or political beliefs • Biocrime • Use of a microbe/toxin to cause illness or death in a person or small group of people • Inspired by revenge or money

5. Biological Weapons • Microorganisms • AKA: agent, pathogen, bacteria, virus… • Also includes toxins and biological products • Typically found in nature but can be altered to • Increase ease of spread in environment • Increase pathogenicity • Increase resistance to therapy • Delivery • Direct contact • Humans, animals, or vectors • Food or water contamination • Airborne

6. Biological Weapons • Microorganisms • AKA: agent, pathogen, bacteria, virus… • Also includes toxins and biological products • Typically found in nature but can be altered to • Increase ease of spread in environment • Increase pathogenicity • Increase resistance to therapy • Delivery • Direct contact • Humans, animals, or vectors • Food or water contamination • Airborne

7. Clues to Possible Event • Higher morbidity or mortality than expected • Geography, time or scope of disease is unusual • People at same event • Unusual disease for area • Unusual disease for season • Multiple outbreaks • Increase in disease incidence • Dead animals • Zoonotic diseases

8. Laboratory Identification BioSafetyLevel 4 Prevent expose to airborne/ potentially fatal organisms, limited number of labs BSL 3 Prevent exposure to airborne pathogens, available in reference labs BSL 2 Most hospital labs, which also serve as sentinel labs Laboratory Response Network

9. Identification of a Microbe • Collect sample • Microscopic exam • Culture • Identification and antimicrobial susceptibility testing

10. Category A These high-priority agents include organisms or toxins that pose the highest risk to the public and national security because: • They can be easily spread or transmitted from person to person • They result in high death rates and have the potential for major public health impact • They might cause public panic and social disruption • They require special action for public health preparedness.

11. Category B These agents are the second highest priority because: • They are moderately easy to spread • They result in moderate illness rates and low death rates • They require specific enhancements of CDC's laboratory capacity and enhanced disease monitoring.

12. Category C These third highest priority agents include emerging pathogens that could be engineered for mass spread in the future because: • They are easily available • They are easily produced and spread • They have potential for high morbidity and mortality rates and major health impact.

13. Diseases/Biological Agents Category A Category B • Anthrax (Bacillus anthracis) • Botulism (Clostridium botulinumtoxin) • Plague (Yersiniapestis) • Smallpox (variola major) • Tularemia (Francisellatularensis) • Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]) • Brucellosis (Brucellaspecies) • Epsilon toxin of Clostridium perfringens • Food safety threats (e.g., Salmonella species, E. coli O157:H7, Shigella) • Glanders (Burkholderiamallei) • Melioidosis (Burkholderiapseudomallei) • Psittacosis (Chlamydia psittaci) • Q fever (Coxiellaburnetii) • Ricin toxin from Ricinuscommunis (castor beans) • Staphylococcal enterotoxin B • Typhus fever (Rickettsiaprowazekii) • Viral encephalitis (alphaviruses) • Water safety threats (e.g., Vibriocholerae, Cryptosporidium parvum)

14. Smallpox • Variolavirus • Highly contagious • ~30% mortality rate • No specific treatment • Live attenuated vaccine for prevention

15. Smallpox • Smallpox • Onset 10-12 days • Fever, aches, and rash • Mortality rate ~ 30% • Eradicated 1979

16. Viral hemorrhagic fevers (VHFs) VHFs are caused by viruses of four distinct families: Filoviridae: Ebola and Marburg viruses Arenaviridae: Lassa fever virus and a group of viruses referred to as the New World arenaviruses (eg, Junin, Machupo, Guanarito, and Sabia viruses) Bunyaviridae: Crimean Congo hemorrhagic fever virus, Rift Valley fever virus, and a group of viruses known as the “agents of hemorrhagic fever with renal syndrome” (eg, Hantaan, Dobrava-Belgrade, Seoul, and Puumala viruses) Flaviviridae: yellow fever, dengue,Omsk hemorrhagic fever, and Kyasanur Forest disease viruses.

17. Viral hemorrhagic fevers (VHFs) • All enveloped RNA viruses • All are zoonotic or arboviral infections and occur in the wild.Human cases or outbreaks of VHFs are sporadic. • All VHFs are geographically restricted to the areas where their host species live. None of the HF viruses occurs naturally in the United States. • Humans are not the natural reservoir for any of these viruses. Humans are infected when they come into contact with infected hosts. However, with some VHFs, human to human transmission does occur. • With a few noteworthy exceptions, there is no cure or established drug treatment for VHFs.

18. Viral hemorrhagic fevers (VHFs) • Insidious and non-specific onset. Specific signs and symptoms vary by the type of VHF, but initial signs and symptoms often include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. • Main symptoms are fever, myalgias and/or arthralgias, and rash. Mechanisms and symptoms for each disease are slightly different, but infection with any of these viruses may lead to thrombocytopenia and coagulation abnormalities and bleeding disorders. • Patients with severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from body orifices. • Severely ill patient cases may also show shock, nervous system malfunction, coma, delirium, and seizures. Some types of VHF are associated with renal failure. • High mortality rates: 10-90%

19. Viral hemorrhagic fevers (VHFs) • Some VHFs are considered to be a significant threat for use as biological weapons due to their potential for causing widespread illness and death. • Because of their infectious properties, associated high rates of morbidity and mortality, and ease of person-to-person spread, the following VHFs are considered category A bioweapon agents by the U.S. CDC: • Ebola, Marburg(filovirus) • Junin(arenavirus) • Rift Valley fever (bunyavirus) • yellow fever viruses (flavivirus)

20. Viral hemorrhagic fevers (VHFs) • Following aerosol dissemination of any of the VHFs of concern, cases would likely appear within 2-21 days after exposure, depending on the specific virus involved. Patients would present with fever, rash, body aches, headaches, and fatigue; internal and external bleeding could occur later. • Diagnosis of VHF is based on clinical presentation of symptoms and confirmed by laboratory testing. This can be challenging because numerous symptoms might be present. There are no rapid clinical diagnostic tests available. • Because these illnesses are not endemic to the U.S., the diagnosis of any case of VHF in a person without travel and exposure risk factors (mentioned above) would be cause for suspicion of bioterrorism. • Suspected cases of viral hemorrhagic fever should be reported immediately to a local or state health department. • Barrier precautions should be instituted immediately.

21. Most likely suspects WANTED Bacillus anthracis Alias: Anthrax Clinical: Necrosis and hemorrhage Zoonotic: Cattle, sheep, goats, aerosol Treatment: ciprofloxacin spores

22. Most likely suspects WANTED Yersiniapestis Alias: Plague, Black Death Clinical: Necrosis and hemorrhage (buboes) Zoonotic: Fleas, rats, gophers, aerosol Treatment: streptomycin, gentamicin Safety pin

23. Most likely suspects WANTED Clostridium botulinum Alias: Botulism Clinical: Blurry vision, paralysis Source: Dirt, food, water, aerosol Description: spore-forming, GPR, strict anaerobe Treatment: anti-toxin spores Droopy eyelids – initial sign of paralytic activity of toxin

24. Botulinum Toxin Ingestion of organism which produces toxin or ingestion of pre-formed toxin Botulinum toxin is a intracellular-acting neurotoxin, acting to block release of acetylcholine from peripheral nerves = flaccid paralysis

25. Most likely suspects WANTED Francisellatularensis Alias: Tularemia, rabbit fever Clinical: Ulcers, pneumonia, lymphadenopathy Source: zoonotic (rabbits), insect bites, aerosol Treatment: streptomycin, gentamicin

26. Summary Table (Excel Sheet)

27. References • Murray’s Medical Microbiology 8th edition • Chpt 20, Bacillus anthracis • Chpt 25, Yersinia pestis • Chpt30, Clostridium botulinum • Chpt29, Francisellatularensis • CDC – Center for Disease Control and Prevention • https://emergency.cdc.gov/bioterrorism/factsheets.asp • https://emergency.cdc.gov/health-professionals.asp • UpToDate