Bioterrorism: Practical Aspects Keith S. Kaye, MD, MPH

Overview History and Overview of Bioterrorism Smallpox Update on Anthrax What to expect in event of a Bioterrorism threat What can you do to help?

Bioterrorism: History 1346, Kaffa: Attacking Mongols catapulted cadavers of plague victims into city 1710: Russians used plague victims against Swedes 1767: French and Indian War: Blankets from smallpox hospital provided to Native Americans – resulted in epidemic of smallpox World War I: Germany sent infected horses and mules into Allied lines World War II: Japanese military unit 731 killed thousands of Chinese in Ping Fan, Manchuria, with various agents, including Anthrax 2 incidents in US over past 20 years involving intentional bacterial contamination of food

United States Bioweaons Program 1942 established at Camp Detrick, MD 1950 biological simulant sprayed over San Francisco 1966 biological simulant sprayed in New York City subway system 1969 President Nixon suspends offensive program 1972 U.S, U.K., Soviet Union sign Biological Weapons Convention 1942 - U.S. begins its offensive biological weapons program and chooses Camp Detrick, Frederick, Maryland as its research and development site September, 1950-February, 1951 - In a test of BW dispersal methods, biological simulants are sprayed over San Francisco (Serratia spp) June, 1966 - The United States conducts a test of vulnerability to covert BW attack by releasing a harmless biological simulant into the New York City subway system (Bacillus cereus) November 25, 1969 - President Nixon announces unilateral dismantlement of the U.S. offensive BW program *Agents stockpiled/weaponized by US included anthrax, botulinum toxin, francisella, Brucella, Coxiella, Staph enterotoxin B, VEE, rice blast, ricinm, and wheat stem rust

Soviet Union Bioweapons Program Massive program Many details known through defection of high-ranking scientist Weaponized numerous biological agents Much of offensive research took place after signing biological weapons treaty After dissolution of Soviet Union leaks/dissmination of scientists (known) and bioterrorism agents (suspected) Employed around 60K at peak Mention had a few fatalities in scientists (eg due to marburg) Mention Ken Alibek Mention current unknown status of Iraq’s program after UN inspectors kicked out in 1998

Difficulties in Cultivating Biological Weapons General difficulties in weaponizing a biologic agent Ability to procure a virulent strain (e.g., anthrax, tularemia) Ability to culture large amounts of the agent Ability to process agent into a suitable form (e.g., anthrax spores) Ability to safetly handle and store the agent (may be difficult for hemmorhagic fever viruses)

Why Biological Weapons? Although challenging to develop, still easier and cheaper to obtain than nuclear weapons Soviet scientists with expertise defected to rogue nations Potential to cause destruction and hysteria

Smallpox Virus with person-to-person transmission; rash similar to chicken pox, but can be easily differentiated Naturally occurring disease eradicated in 1977 Routine immunization in US stopped in 1972 US and Russia known to have smallpox stocks; but concerns that other countries have Smallpox as well

Smallpox (cont) Vaccine exists and is effective More vaccine is being made No imminent bioterrorism threat for smallpox, but we want to be prepared Routine vaccination will probably not be reinstated unless new cases emerge Stores of vaccine would be made available for control of outbreaks (bioterrorism)

Anthrax Prior to 2001, no successful bioterrorist attacks Known to be stockpiled by Iraq and possibly by former Soviet states Outbreak due to accidental release, Sverdlovsk (Ekaterinberg, USSR 1979) Increase in hoaxes in US, late 1990s -mention historical significance of anthrax: 5th and 6th plagues likely represented outbreaks of anthrax in cattle and humans; was first disease to fulfill koch’s postulate for causation of disease; first bacterial infection for which there was a vaccine Disease had become quite rare in western countries by the late 20th century, aside from an occasional cutaneous case, inhalational quite rare after banning pakistani wool in 1970s -while numbers of actual cases were decreasing, there was an increase in hoaxes, dramatically increased in late 1990s. Each hoax had cost approx 500K to investigate. For example, Larry Wayne Harris, Ohio microbiologist who in 1995 tried to buy plague. A few years later was arrested for claiming to have enough anthrax to decimate las vegas. Turns out he had a harmless veterinary vaccine strain. -mention aum shinrikyo, who while they released sarin and caused deaths due to that in Japanese subways, they were unsuccessful in causing any illness due to anthrax despite releasing that and botulinum toxin up to 10 times in a similar fashion

Antrhax: Clinical Diseases Cutaneous Spores enter through cuts/abrasions Inhalational Spores inhaled NO PERSON-PERSON SPREAD!!! Gastrointestinal Infected meat ingested Incubation period generally 1-12 days

Cutaneous Anthrax Inoculation of spores into cut/abrasion Lesions typically on hand/arm or face Small pruritic papule  ulcer surrounded by vesicles (24-48h)  black eschar Patients typically have local edema, +/- lymphadenopathy, fever and will feel ill Antibiotic treatment extremely effective

Inhalation Anthrax: Manifestations Second stage: rapid deterioration (24 h) Acute dyspnea Cyanosis Stridor Fever Mediastinal hemorrhage CxR: Mediastinal widening Meningismus Septic Shock Coma First stage: insidious onset (1-4 d) Malaise Fatigue Myalgia Nonproductive cough Precordial pressure Fever

US Anthrax Cases as of November 9, 2001 Inhalational-10 Florida: 2 (1 fatality) Washington DC: 5 (2 fatalities) New Jersey: 2 New York: 1 (1 fatality) Cutaneous-12 New York: 7 New Jersey: 5 FL: october 4 CDC notified of possible case of anthrax- pt had travelled to NC, became ill in Durham New York cases: NBC, ABC, CBS, NY Post DC exposures: listed at 28 in Capitol building (2 police, 2 in feingold office, remainder in Daschle’s office NJ: Trenton post office

Clinical Symptoms of 10 Inhalational Anthrax Cases, U.S., 2001 Almost all had links to contaminated mail (postal workers and press) Median age 56 yrs (range 43-73) All presented with fever, chills, malaise 10/10 Cough (often dry) 9/10 Nausea and vomiting 8/10 Paucity of cold symptoms, sore throat All 10 patients had abnormal CxR findings All not receiving antibiotics had + blood cultures 6/10 survived

US Anthrax Cases to Date November 9, 2001 Source of exposure known for almost all cases (mail) ~32,000 people in US were started on antibiotics for prophylaxis in past several weeks and in 5000 persons a full 60 day antibiotic course was advised. 95/490 patients (~20%) receiving prophylaxis reported one or more side effect in one survey

Inhalation Anthrax: Summary Points Almost all patients had clear epidemiologic links to anthrax source (investigations ongoing) All patients had prodromal illness with fever Cold symptoms, sore throat usually absent Anthrax will readily grow in cultures Anthrax is much more treatable than previously thought Anthrax is NOT communicable, person to person Currently NO anthrax cases in NC Harmful effects of unnecessary antibiotics are common

GUIDELINES FOR MANAGEMENT OF POTENTIALLY THREATENING LETTERS Do not open suspicious letter/package Do not shake/empty Do not show to others (don’t sniff, touch etc) Place package on stable surface and alert others in the area Leave area, close doors, prevent others from entering, shut off ventilation system Wash hands/change clothes Contact supervisor, local law enforcement via 911 If possible, create list of persons in room (give to public health personnel) www.bt.cdc.gov

Recommendations for Mail Handlers New recommendations Major focus is use of gloves for workers handling mail Respiratory protection (N95 mask) for workers with mail sorting machinery Follow news for further updates

What to expect in the event of a Bioterrorism Threat Hospitals have plans, but CDC, State will organize response Patients might be triaged at locations outside of local emergency rooms Dispensing of antibiotics and vaccines will be organized through CDC/State, but will utilize local hospitals for support Potential restriction of travel, movement; lock down of hospitals (Smallpox)

How Can You Help ? Don’t crowd emergency rooms if you are not acutely ill Talk with your primary care physician Antibiotics not helpful unless there is a clear indication No role for nasal swabs as diagnostic tool! Have a high index of suspicion for atypical skin lesions, clusters of cases among friends, co-workers

How Can You Help ? (2) Report suspicious letters/packages/powders to police/FBI, HAZMAT teams (911) Report suspicious illnesses/clusters to your physician and county or State Health Department Infection Control within the hospital Follow the news: web sites for reliable, helpful information: www.bt.cdc.gov http://www.usps.com/

How can you help (3) Increased level of awareness, but . . . Remain calm No cases in North Carolina (and in most states) There are effective ways to prevent and treat anthrax once a threat has been recognized Flu season is upon us Let your doctor know if you develop flu symptoms No reason to suspect anthrax, with no anthrax in NC If you are ill, and feel you might have had an exposure, let your physician know Even if you have had flu shot or a negative flu test, you can still might get the flu, or an illness like the flu!