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Home , Bubonic plague, Plague (disease), Q fever, Tularemia

Bioterrorism (, , Q )

CVM 6923 Gus Brihn, BVMS Veterinary & Preventive Medicine Resident Learning objectives

● Describe how agents are classified in the U.S. and what the classification is based on ● Define three potential bioterrorism agents and explain their methods of transmission ● Outline two preventive practices for each to reduce the risk of in Brief history of bioweapons and bioterrorism

● Biological agents have been used in warfare for more than 2,000 years ● Polluting water sources and wells

USA ● 1984 Rajneeshee bioterror attack, Oregon 2001

● A week after 9/11, Bacillus anthracis spores were sent in letters to several news media offices and two U.S. Senators ○ Mail handlers also exposed ○ 22 people became ill and 5 people died

→ Mail sent to government offices is irradiated Bio and agroterrorism

- “A biological attack is the intentional release of a pathogen or

biotoxin against humans, plants, or ” - Agroterrorism: Biological weapons targeting animals or crops

with the purpose to disrupt local economies - Dissemination through

- Aerosols - Infected animals

- Food/water - Insects

- Infectious carriers - Physical distribution Characteristics of a Biological Attack

● Difficult to detect release ● Dissemination may cover

large area ● Recognition of agent may be

delayed days to weeks ● Difficulties in catching

perpetrator How are bioterrorism agents categorized? - ABC

Category A: High-priority agents that pose risk to national security

● Can be easily disseminated or transmitted from person to person;

● Result in high mortality rates and have the potential for major public

health impact;

● Might cause public panic and social disruption; and

● Require special action for public health preparedness Category A agents/diseases

● Anthrax (Bacillus anthracis) ● ( botulinum ) ● Plague ( pestis)

● (variola virus) ● Tularemia ( tularensis)

● Viral hemorrhagic , including

○ Filoviruses (, Marburg)

○ Arenaviruses (Lassa, Machupo) Category B: Second highest priority agents

● Are moderately easy to disseminate;

● Result in moderate morbidity rates and low mortality rates; and

● Require specific enhancements of CDC’s diagnostic capacity

and enhanced Category B agents/diseases

● ( species) ● toxin from Ricinus communis (castor

● Epsilon toxin of Clostridium beans)

perfringens ● Staphylococcal enterotoxin B

● Food safety threats (Salmonella ● fever ( prowazekii)

species, O157:H7, ● Viral encephalitis (alphaviruses, such as

Shigella) eastern equine encephalitis, Venezuelan ● () equine encephalitis, and western equine

● (Burkholderia encephalitis])

pseudomallei) ● Water safety threats (, ● ( psittaci) Cryptosporidium parvum) ● ( burnetii) Category C: Third highest priority agents

Emerging that could be engineered for mass dissemination in the future because of ● Availability;

● Ease of production and dissemination; and

● Potential for high morbidity and mortality rates and major health impact.

- Emerging infectious diseases such as Nipah virus and hantavirus Summary

Category Dissemination Mortality Other Disease/agent example

A Easy High Public panic Tularemia Plague

B Moderately easy Low Enhanced Q Fever surveillance

C Possibly easy Potentially high Emerging Hantavirus diseases Milngavie Disease Incubation Symptoms Transmission Person to (agent) period* person

Tularemia 1–21 days Fever, cough, Insects (, biting NO (Francisella (avg 3–6) , flies, mosquitoes), tularensis) direct contact, ingestion, aerosols Plague (Yersinia 1–7 days Fever, cough, bites, direct YES pestis) (usually 2–3 days) shortness of breath, contact, inhalation sore lymph nodes (rare)

Q fever (Coxiella 7–41 days Flu-like illness that Aerosols, direct NO burnetii) can lead to contact, raw , pneumonia and blood transfusion * might be different for agents used as weapons Tularemia as a biological weapon

F tularensis considered a dangerous potential biological weapon because of its extreme infectivity, ease of dissemination, and substantial capacity to cause illness and death

● 1950s and 1960s - US military developed weapons that would disseminated F tularensis aerosol ● 1969 - World Health Organization expert committee estimated that an aerosol dispersal of 50 kg of virulent F tularensis over a metropolitan area with 5 million inhabitants would result in 250,000 incapacitating casualties, including 19,000 deaths. ● Very small infectious dose (10-50 organisms). ● A weapon using airborne tularemia would likely result 3-5 days later in an outbreak of acute disease Tularemia

● Category A disease ● Also known as fever and deer-fly fever ● Etiology:

○ Small, gram-negative ● Numerous transmission routes and a large number of hosts Worldwide distribution Transmission - Francisella tularensis Transmission in North America continues

● Contact with infected animals or carcasses

○ Usually , hares, voles, muskrat,

○ , other domestic species? ● Ingestion of contaminated water or food ● Inhalation of contaminated aerosols or agricultural dusts

● Bite of infected insect (ticks, deerflies) transmission in North America - F. tularensis

● bites ○ American tick, variabilis (Minnesota) ○ Rocky Mountain wood tick, ○ Lone Star tick, americanum ● Biting flies, especially deer-flies ● Mosquitoes Disease in humans - F. tularensis

● Symptoms vary depending how the enter the body ● Initial presentation nonspecific ● Abrupt onset fever, , headache, , lethargy, sore throat, skin ulcers ● Incubation period: 3 to 5 days (range 1-14 days) ● Case fatality <2% in the United States Reported cases U.S. 2001-2015, age & sex

● Most cases between May and September Reported tularemia cases in the U.S. in 2016 Tularemia in MN in 2017

● 6 human cases ● 4 cases likely acquired tularemia from a tick or deerfly bite, 1 from a bite, and 1 acquired tularemia by inhaling the bacteria, likely while mowing his lawn. ● MN Department of Health issued a health advisory for healthcare providers ○ Consider tularemia in patients with fever and skin ulcers ○ Start treatment before laboratory confirmation Tularemia in cats

● Acute ● ● Oral ulcers ● History of recent ingestion of wild prey Case 1 - Tularemia human case in MN

● 60-year old woman was bit by a stray cat on May 10, 2017

What are your differentials? ● On May 13, the bite wound got infected ● Her symptoms got worse with headache, , worsening wound infection, regional lymphadenopathy, and fever ● Hospitalized twice, 6 days in total ● F. tularensis isolated from the wound Case 2 - Martha’s Vineyard

● July 2000, five cases of pneumonic tularemia reported ● Active surveillance for tularemia begins ● By August, 6 additional cases of pneumonic tularemia reported ● One patient cut brush over a rabbit, and six other patients mowed lawns or cut brush within one week before becoming ill. ● Concluded mowing lawns and cutting brush were risk factors for primary pneumonic tularemia. Prevention

● Avoid contact with wild animals

● Wear gloves when handling wild animals

● Use , remember pets

● Avoid tick infested areas ● Keep cats indoors and don’t allow pets to

hunt small animals

● Cook wild game thoroughly Bruichladdich What is NOT a route of transmission of F. tularensis?

A) Direct contact B) Aerosol C) Vector D) Ingestion E) None of the above Plague Plague as biological weapon

● Y pestis as used in aerosol attack could cause ○ Pneumonic plague can perpetuate human-to-human ● National and state public health officials have large supplies of drugs needed in the event of a bioterrorism attack. These supplies can be sent anywhere in the United States within 12 hours. ● Historical uses: ○ 1346 - Tatar army catapulted plague infected corpses at Genoese sailors ○ WWII - Japan establish secret research unit in ■ 1940s Japanese planes suspected to airdrop Y pestis contaminated rice and grain into Vietnam and ○ 1995 - A white supremacist and microbiologist faudrantly purchase Y pestis - intended use never determined unknown Plague

● Category A disease ● Etiologic agent: ○ Gram negative bacterium ● throughout the western United States – wild reservoir ● Transmission ○ Bite of infected flea ○ Contact with infected tissues ○ Inhalation (rare)

● Common form ● Acquired through flea bite ● Fever and characteristic ● Swollen, extremely tender ● Incubation period: 2-7 days

● Less common ● Primary: no discernible bubo ● Secondary: untreated bubonic plague ● of acral regions, hypotension ● Incubation period: 2-7 days Pneumonic Plague

● Rare form ● Primary: inhalation, person-to-person ● Secondary: untreated bubonic plague ● Pneumonia, hemoptysis ● High mortality if not treated promptly ● Incubation period: 2-4 days (1-6 days) Worldwide Distribution of Plague Reported cases of human plague 1970-2016 Plague in in 2017

● 1,947 cases as of Nov 7, 2017 ○ 143 deaths ● “Worst outbreak of plague in 50 years” ● Most cases pneumonic ● Public health measures to prevent spread to other countries Surveillance

● Monitoring prevalence of Y. pestis among reservoirs/fleas ● Black-tailed ○ Monitor for die-offs ○ Very susceptible Plague in Companion Animals

Cats Livestock ● Highest risk of infection and ● , horses, , and not clinical disease known to develop illness ● Disease similar to human disease

Dogs ● Serologic evidence of infection less likely to show clinical disease? ● CSU euthanised plague infected - 2017 Case - biologist found deceased in his residence

Biologist conducted a necropsy of a mountain lion in his garage 1 week prior

No use of personal protective equipment.

Three days later, he developed fever and hemoptysis and died approximately 6 days after exposure. Gross examination showed consolidation and hemorrhagic fluid in the

Tissues from the mountain lion tested positive for Y. pestis, and isolates from the biologist and mountain lion were indistinguishable by pulsed-field gel electrophoresis

Biologist likely acquired pneumonic plague through inhalation of aerosols generated during postmortem examination of an infected mountain lion Culzean Castle Is Y. pestis (plague) endemic in areas of the United States?

A) True B) False Q fever as a biological weapon

● Potential to be manufactured on a large scale and remains stable under production, storage, and transportation conditions ● Can be efficiently disseminated ● Highly infectious ● Associated with low mortality but extensive acute and chronic morbidity ○ If used against troops, loss of manpower can range from 23% to 77%, and operational efficiency can be severely impaired. ● Prior to WWII, reportedly manufactured Q fever as biologica weapon ● 1995 - Aum Shinrinkyo cult (deadly sarin gas attack on the Tokyo subway system) was doing research on several other potential biological warfare agents, including C burnetii Q Fever

● Category B disease ● Caused by ○ Rickettsial bacteria ○ Obligate intracellular pathogen ○ Reaches high concentrations in animal tissues ○ Resistant to many disinfectants

Animal Reservoirs

Domestic

● Sheep, cattle, ● Uterus and mammary glands serve as sites of chronic infection ● Common in dairy cattle herds in the U.S. ○ NAHMS Dairy 2007: 77% of herds positive (bulk tank milk) Disease Transmission

● Airborne ○ Via fomites (particles contaminated with the agent) ○ Can be spread by the wind ● Direct contact ○ Infected animals or materials ○ Especially parturient fluids, placenta ● Ingestion ○ Raw milk ● Other ○ Blood transfusion, marrow transplant, transplacental Q Fever Characteristics

● Reactivation of infection occurs in pregnant animals ● Organism can persist in contaminated soils for several months ● Low infectious dose ● Airborne particles can cause infection in susceptible hosts at distances of 0.5 miles Clinical Characteristics - Humans

● 2 to 6 weeks incubation period ● Chronic highest in ● Acute infections are self limited, pregnant, influenza-like illnesses immunocompromised people ● High fever (104-105 F) ● Develop 1-20 yrs later ● Headache ● ● Myalgia ● Chronic hepatitis ● Chronic pulmonary infections Risk Factors

● Endemic areas ● Workers in stockyards ● Meat packing and rendering plants ● Occupational risks: veterinarians, meat workers, sheep and dairy farmers ● Laboratories ● Research facilities using sheep C. burnetii in Veterinarians, AVMA 2006 ● 113 (22%) of 508 veterinarians sampled were positive ● Seropositivity tended to be found among: ○ Older veterinarians (>46 years of age) ○ Men ○ Mixed or food animal practice ○ Ever-lived on a farm ○ Work with cattle, exotic animals, wildlife, or swine Prevention

● Awareness ● Pasteurize milk from cows, goats, and sheep ● Reduce environmental contamination (incinerate infected birth products) ● PPE when assisting in labor

○ Respirator with abortion cases ● Limit sheep research in medical facilities to male or nonpregnant female animals ● No available in the U.S. How far can airborne particles of C. burnetii (Q fever) travel?

A) 10 miles

B) 0.5 miles

C) 0 miles

D) 5 miles Key points ● Veterinarians are key to early detection of outbreaks, including bioterrorism ● What makes Category A agents so dangerous? ● Occupational risk of Q Fever Questions?