Bioterrorism: A Public Health Challenge

Sept. 2007

The Dental Learning Network

Bioterrorism: A Public Health Challenge 5.0 Homestudy Credit Hours

Jean Sheridan Copyright © Corexcel. All Rights Reserved.

The Dental Learning Network is a recognized ADA CERP provider The Dental Learning Network 1474 North Point Village Center - #234 Reston, VA 20194

800-522-1207 [email protected] www.DentalLearning.org

Bioterrorism: A Public Health Challenge (5.0 Credit Hours - $49.50) Please mark your answers to the course exam below, then fax this page to 703-935-2190 for scoring and certificate issuance. Or, if you wish to receive your certificate immediately, click here to take this exam online. Payment will be accepted at the time you submit the exam for scoring. If you've already paid for this course and wish to take the exam online, but you don't have a user name and password, send an email request to [email protected]. 1. 2. 3. 4.

_____ _____ _____ _____

5. 6. 7. 8.

_____ _____ _____ _____

9. _____ 10. _____ 11. _____ 12. _____

13. _____ 14. _____ 15. _____ 16. _____

Name: D.D.S.

D.M.D.

License State:

R.D.H.

R.D.A.

License Number:

C.D.A.

C.O.A.

D.A.

A.Q.P.

Expiration Date

(MM/YY)

Address 1: Address 2: City: Telephone Number:

State:

Zip Code: Fax Number:

E-mail: Please help us improve: Ordering experience was convenient: I received my workbook or file in a timely manner: Course text and test clear and understandable: I’ll use the course information in my daily practice: Overall, I would give this course a grade of _________.

Yes Yes Yes Yes

No No No No

Fax your completed exam to 703-935-2190 If you have downloaded this course off the Internet and need to provide your credit card information for payment please do so here: Card type _______________ Card number ____________________________________ Exp. Date _____________ Name as it appears on card __________________________

Instructions Read the course material and enter your test answers on the one-page answer sheet included with this book. You earn course credit for every test answer sheet with at least 70% correct answers. We notify failing students within 7 days and give them an opportunity to take a new test. To claim your credits, return your answers by: •

Taking the test online (only if you have not purchased the coursebook separately, you will need to provide credit card information at the time you submit your exam online for scoring).

•

Writing your answers on the one-page answer sheet included with this book, then fax or mail them to: The Dental Learning Network 1474 North Point Village Center - # 234 Reston, VA 20194 Phone: 800-522-1207 Fax: 703-935-2190

We grade all tests in a timely manner; so if you do not receive your certificate within five days, please send an email to [email protected] There is no time limit for return of your answer sheet. Completion dates are taken from the test answer sheet envelope postmark or the finish date recorded in the computer when you do an online exam, and must be in the licensing cycle you wish to use the credits. If you are dissatisfied with the course for any reason, please return the printed materials within 30 days of purchase and we will refund your full tuition. Shipping charges are nonrefundable. If someone else would like to use this material after you are done, he or she may register with us and take advantage of the “sharing discount” workbook tuition charge. Courses downloaded from the Internet can be shared at the same tuition rate as currently available on our website. Please call us if you need an extra answer sheet or download one from our website. There is no “sharing discount” for online exams. Keep in mind several States have specific requirements on subject matter as well as credits earned through different educational methods for license renewal. You are responsible to know of these limitations. The author and The Dental Learning Network have made every effort to include information in this course that is factual and conforms to accepted standards of care. This course is not to be used as a sole reference for treatment decisions. It is your responsibility to understand your legal obligations and license requirements when treating patients. The Dental Learning Network is not responsible for the misuse of information presented in this course. The material in this course cannot be reproduced or transmitted in any way without the written consent of The Dental Learning Network.

Bioterrorism: A Public Health Challenge Learning Objectives At the end of the program, the participant will be able to: 1. Describe the federal governmental entities responsible for addressing outbreaks and what roles each play. 2. Identify the possible biological and chemical agents that pose a risk to the United States' population. 3. List the symptoms associated with biological or chemical agents. 4. Discuss the use of agents in 21st Century warfare. 5. Discuss treatment options for the five potential pathogens. 6. List the measures that first-responders to a chemical attack should take. 7. Identify the environmental signs that an intentional release of a lethal chemical has taken place. 8. Evaluate the preparedness of government agencies to respond to bioterrorist attacks.

© Corexcel, All Rights Reserved.

Page 2

Content Outline

I.

What Comprises the Public Health Infrastructure? A. B. C. D. E.

II.

"Bugs" That Concern Health Officials Most A. B. C. D. E.

III.

Centers for Disease Control and Prevention National Institutes of Health Food and Drug Administration Department of Agriculture Department of Defense

Anthrax Smallpox Plague Botulism Tularemia

Chemical Agents A. Nerve agents B. Mustard agents C. Hydrogen cyanide

IV.

Measures of Decontamination for First-Responders

V.

Are We Prepared?

© Corexcel, All Rights Reserved.

Page 3

Introduction On September 11, 2001, America's relative peace and security were shattered, perhaps forever, when foreign terrorists hijacked domestic airliners and rammed them into the World Trade Center in New York City and the Pentagon in Arlington, Virginia. People had barely absorbed the horror of these events, when anthrax slowly invaded the most unlikely place: the United States Postal System. This course will cover: •

The federal agencies that will lead the defense against possible biological and chemical threats;

•

Potential biological and chemical threats to the U.S. population; and

•

State of preparedness among federal agencies.

Public health infrastructure Although broad-based federal responses have been deployed in the past to deal with natural disasters, the federal government has little or no real-world experience with the deliberate release of harmful pathogens or deadly chemical agents. A host of federal agencies are responsible for responding to medical emergencies, many of which receive overall direction and coordination from the U.S. Department of Health and Human Services (HHS). The country's medical "911" is the Office of Emergency Preparedness (OEP). It coordinates the federal response to natural and man-made catastrophes. Some examples follow: •

airline disasters;

•

the Olympic games in Atlanta, GA;

•

World Trade conferences;

•

the Oklahoma City bombing; and

•

terrorist attacks against U.S. embassies in Africa.

Responding to a massive biological or chemical attack on U.S. residents would result in utilization of all HHS resources including: •

Centers for Disease Control and Prevention (CDC);

•

National Institutes of Health (NIH); and

•

Food and Drug Administration (FDA)

The Departments of Agriculture and Defense also would play a role.

© Corexcel, All Rights Reserved.

Page 4

Centers for Disease Control and Prevention (CDC) CDC is the first line of defense in the federal response to Bioterrorism. Established in 1946 to combat malaria, typhus and other infectious diseases, the agency has grown to 8,500 employees, who are based across the country and at its headquarters in Atlanta, Georgia. Table 1 presents milestones in the CDC's evolution to premier disease-fighting entity. Table 1. Important Events in CDC's History Date 1946 1951 1955 1961 1966 1970 1977 1978 1992

Action Communicable Disease Center established Epidemic Intelligence Service launched Polio surveillance initiated Publication of Morbidity & Mortality Weekly Reports begin Worldwide smallpox eradication effort begun with WHO Name changed to Centers for Disease Control Last cases of endemic smallpox reported in Somalia Maximum-containment laboratory opened Name changed to Centers for Disease Control and Prevention

CDC's primary mission is to monitor and protect the health of the civilian population through: •

detection of illness through surveillance;

•

diagnosis of illness;

•

rapid response to disease outbreaks; and

•

prevention of disease.

A major part of the CDC's response is the Epidemic Intelligence Service (EIS). Using epidemiological tools, EIS officers investigate outbreaks and help local health teams to control further spread. An integral part of EIS activities is a two-year, postgraduate training program for health professionals. Nurses who have attained a Masters of Public Health or equivalent degree are invited to apply. Perhaps the CDC's most ambitious undertaking, the Health Alert Network (HAN) is intended to allow state and federal health authorities to communicate rapidly with each other and with law enforcement agencies. Features of HAN include: •

high-speed, continuous, secure connection to the Internet;

•

access to public health information;

•

distance-learning capacity, using satellite- and web-based technologies for continuous upgrading of skills to prepare for threats;

•

early warning systems to alert local and federal authorities and the media about threats; and

•

instantaneous access and sharing of disease reports, response plans and CDC diagnostic and treatment guidelines among local health officials.

© Corexcel, All Rights Reserved.

Page 5

CDC maintains the National Pharmaceutical Stockpile, a collection of life saving pharmaceuticals, chemical interventions and medical/surgical supplies. Experts consulted by CDC officials prioritized the biological agents most likely to be used against citizens: smallpox, anthrax, pneumonic plague, tularemia and botulism toxin. Antibiotics for anthrax, plague and tularemia are immediately available for distribution. Approximately 12 million doses of smallpox vaccine currently are available, with the expectation that enough to vaccinate every citizen will be available by the fall of 2002. Eight 12-ton Push Packages are available for delivery within 12 hours of a federal decision to release them. Packages contain 50 tons of material that permit emergency medial staff to treat a variety of different agents.

Metropolitan Medical Strike Team In the event of a nuclear, biological or chemical attack, the Metropolitan Medical Strike Team (MMST) will be mobilized to respond on a local, state and national basis. It falls under the jurisdiction of the OEP. If there is a significant man-made disaster, coordinated assistance by the team will focus on the following areas: •

assessments of health and medical needs;

•

health surveillance;

•

medical care personnel;

•

health/medical equipment and supplies;

•

patient evacuation;

•

in-hospital care;

•

food/drug/medical safety;

•

worker health safety;

•

radiologic hazards;

•

biological hazards;

•

chemical hazards;

•

mental health;

•

public health information;

•

vector control;

•

potable water/wastewater and solid waste disposal; and

© Corexcel, All Rights Reserved.

Page 6

•

victim identification/mortuary services.

National Institutes of Health The National Institutes of Health (NIH) is the federal nexus of medial research in the U.S. Its mission is four-fold: •

to conduct research in its own laboratories;

•

to support the research of non-Federal scientists in universities, medical schools, hospitals and research institutions throughout the country and abroad;

•

to help in the training of research investigators; and

•

to foster communication of medical information.

The institute most closely involved with the Bioterrorism threat is the National Institute of Allergy and Infectious Disease (NIAID). Its most relevant component is a unit that develops vaccines. To date, NIAID support has led to vaccines for rabies, meningitis, whooping cough, hepatitis A and B, chickenpox and pneumococcal pneumonia.

Food and Drug Administration Protection of the nation's food supply is shared among the Food and Drug Administration (FDA), the Food Safety and Inspection Service of the U.S. Department of Agriculture (USDA) and the Environmental Protection Agency (EPA). These agencies are augmented by the Department of Treasury's Customs Service, which checks and occasionally detains imported food. The FDA is responsible for protecting consumers against impure, unsafe, and fraudulently labeled food other than in areas regulated by the agriculture department's food inspection program. Agricultural inspectors are charged with the safety of meat, poultry and egg products. Protection against plant and animal pests and disease also falls under the jurisdiction of the agriculture department.

Department of Agriculture Prevention, containment and eradication of harmful plant and animal diseases entering the country are the principal objectives of the USDA. The agency works together with the CDC, FDA, and U.S. Custom's Service and law enforcement agencies. Activities focus on ports of entry, food processing plants and research laboratories. Inspectors are not all two-legged; USDA employs a cadre of dogs specially trained to sniff for food and plant imports.

© Corexcel, All Rights Reserved.

Page 7

(Fig. 1)

Source: USDA, Animal and Plant Health Inspection Service, Washington, DC.

USDA's emergency funding increase of $45.2 million for the current fiscal year will: •

improve security at USDA facilities;

•

provide technical assistance to government and private sector agencies to enhance security; and

•

improve data collection and dissemination.

Department of Defense Fort Detrick, MD is home to the U.S. Army Medical Research Institute of Infectious Disease (USAMRID). The facility has the only Department of Defense laboratory equipped to study highly hazardous viruses at biosafety level 4. It collaborates with the CDC and the WHO in conducting research and developing vaccines, drugs and diagnostics for laboratory and field use. Although the institute's primary focus is protecting military service personnel, its investigations are widely shared to benefit the civilian population as well. What Are the "Bugs" That Concern Health Officials? Near unanimity exists among physicians and public health groups concerning the most likely biological agents for possible intentional release into civilian population. Agents include: •

anthrax;

•

smallpox;

•

plague;

•

toxins, especially botulism; and

•

tularemia.

Genetic alteration of an existing pathogen or creation of a new one is also possible. Despite the Biological Weapons and Toxins Convention's prohibitions against the use of extensive agents during warfare, agreed to by most countries during 1972, the former Soviet Union and Iraq later acknowledged maintaining a biowarfare program. At least 17 other countries are believed to work on such programs as well.

Anthrax

© Corexcel, All Rights Reserved.

Page 8

Bacillus anthracis is an aerobic, gram-positive, spore-producing bacterium. The word "anthrax" comes from the Greek word "anthrakis" or coal, because the cutaneous form of the disease causes lesions that may turn black in color. Chilling estimates from the World Health Organization (WHO) suggest that a theoretical release of 50 kg. of anthrax over an urban population of 5 million people would result in 250,000 cases (1). Long a threat to animals, serious disease in humans has been uncommon. (2) The largest known epidemic of inhalation anthrax occurred during 1979 in the former Soviet Union at Sverdlovsk. A research facility that was "weaponizing" anthrax accidentally released anthrax spores into the atmosphere, killing at least 66 people (3). The preparation was weaponized by finely milling it, rendering it nonclumping or electrostatically neutral which is optimal for dissemination and inhalation. Animals and animal products are the primary source for naturally occurring anthrax. Plant or grass-eating animals ingest spores from the soil. Animal vaccination programs have greatly reduced mortality from anthrax. Among humans, there are three types of infection: •

cutaneous;

•

inhalation; and

•

gastrointestinal.

Cutaneous anthrax is the most common form of the disease; some 2,000 cases occur annually worldwide. (4) The features of cutaneous anthrax in humans include: •

local skin involvement, most commonly head, forearms or hands after direct contact with spores or bacilli;

•

localized itching, followed by a papular lesion that turns vesicular, and within 2 to 6 days develops into a black eschar (or ulcer);

(Fig. 2)

Source: Anthrax. In Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General; 1997. Textbook of Military Medicine.

The incubation period for cutaneous anthrax ranges from 1-7 days following exposure; however, the disease can occur as late as 12 days after exposure. It is usually non-fatal if treated with antibiotics.

© Corexcel, All Rights Reserved.

Page 9

Pulmonary anthrax is more serious than the cutaneous form. Clinical features include: •

nonspecific prodrome of flu-like symptoms;

•

an abrupt onset of respiratory failure and hemodynamic collapse two to four days after flulike symptoms may occur and be accompanied by thoracic edema and a widened mediastinum on chest x-ray;

•

gram-positive bacilli on blood culture, which usually appears 2 to 3 days after the onset of illness; and

•

high mortality if antibiotics are delayed until respiratory symptoms appear.

The median lethal inhalation dose for humans, extrapolated from primate studies, ranges from 1,500 to 55,000 spores. (5) Gastrointestinal anthrax Outbreaks have been reported in Africa and Asia (4); however, this form of the disease is fairly uncommon. It follows the ingestion of insufficiently cooked meat that has been contaminated. Clinical features are: •

abdominal pain, nausea, vomiting and fever;

•

bloody diarrhea, hematemesis;

•

gram-positive bacilli on blood culture, normally 2 to 3 days following onset;

•

usually fatal after progression to toxemia and sepsis.

Treatment Treatment of anthrax is somewhat controversial in the context of the U.S. outbreak. Because of the infrequency of cases, there are no clinical studies of the optimal treatment of inhalation anthrax. Penicillin and, less frequently, doxycycline historically have been the preferred therapies (5). Both have been approved by the FDA for the treatment of naturally occurring strains. Of the fluoroquinolone class of antibiotics, only ciprofloxacin (commonly referred to as "Cipro") has been studied in animals. Levofloxacin and ofloxacin were not studied in vivo and are not recommended. On October 31, 22001, the CDC issued a health advisory on the use of ciprofloxacin and doxycycline for postexposure prophylaxis following inhalation anthrax. The advisory stresses that Cipro resistance is not usual among common pathogens that are resistant to doxycycline. Caution is urged in the wide use of Cipro because it may result in increased resistance of other bacterial agents and limit its efficacy. (6) Possible side effects of ciprofloxacin include: •

central-nervous-system effects (dizziness, confusion, tremor, hallucination, depression, increased risk of seizures);

© Corexcel, All Rights Reserved.

Page 10

•

allergic reaction manifested by difficulty with breathing, closing of throat, swelling of lips, tongue and face, and hives;

•

pain, inflammation or rupture of a tendon; and

•

increased sensitivity of the skin to sunlight (7)

Vaccination Only one company (Bioport Corp., Lansing, MI) produces an anthrax vaccine in the U.S. At present, it is mandated for all U.S. military active and reserve duty personnel. Although a live, attenuated vaccine is used in countries of the former Soviet Union, such a vaccine is deemed unsuitable for use in the U.S. (8). Modes of transmission Traditional modes of transmission include: •

inhalation of spores;

•

cutaneous contact with spores or spore-contaminated materials;

•

ingestion of contaminated food.

Before September 11, 2001, conventional wisdom was that anthrax would need to be released in a massive aerosol form in order to affect the civilian population. However, when the first cases of anthrax began to appear, spores apparently were placed in an envelope and mailed though the US Postal System. Initial targets were high-profile media figures and a senator in Washington, DC. Scores of buildings in the District of Columbia and elsewhere tested positive for trace amounts of anthrax. As a precautionary measure, thousands of postal workers in New York, New Jersey, Washington, DC, and Virginia began prophylactic treatment with antibiotics. As of this writing, five people have died from inhalation anthrax. Evidence seems to suggest cross-contamination as anthrax-containing envelopes moved through the postal system, perhaps contaminating other mail and mail room machinery. Two fatal cases occurred in New York City and a small Connecticut town, confounding epidemiologists, since initial investigations found no linkage between the victims and extensive contact with mail.

Smallpox Smallpox is a DNA virus and a member of the genus orthopoxvirus which also includes monkeypox, vaccinia and cowpox. However, only smallpox is readily transmitted from person to person (9). Smallpox was used as a biological weapon in the mid-18th century during the French and Indian War. A massive global eradication program was launched by the WHO and the CDC in 1966 and concluded successfully in 1977, when the last cases were isolated to Somalia. In 1980, the WHO recommended that all countries cease vaccination.

© Corexcel, All Rights Reserved.

Page 11

Two repositories of smallpox virus exist: one at the CDC in the U.S and a laboratory in Russia. Both are approved and inspected by the WHO. Debate about retention of smallpox virus was intense. Proponents of retaining samples of the virus maintained that even if repositories were eliminated, other sources existed. Opponents of retaining stories cited political instability in Russia and accidental or intentional release as reasons to eliminate them. Symptoms Initial symptoms which follow a 7-17-day incubation period are: •

high fever;

•

malaise;

•

backache;

•

headache (10)

Abdominal pain and delirium may be present. These symptoms are followed by the appearance of a maculopapular rash on the mucosa of the mouth and pharynx, face and forearms, spreading to the trunk and legs. Initially, the rash is vesicular but after a day or two becomes pustular. (Fig. 3)

Source: CDC. Emerging Infectious Diseases. http://www.cdc.gov/ncidod/eid/vol5no4/hendersonG.htm

By the time fever appears, the virus has already begun to multiply in the regional lymph nodes, produced an asymptomatic viremia, began multiplying in the spleen and bone marrow and caused a second viremia to develop. Pustules are deeply embedded in the dermis; by the 8th day of rash crusts begin to form which eventually begin to separate, leaving pitted scarring on the skin. Diagnosis Smallpox can mimic chickenpox (varicella), but there are marked differences: •

there is minimal to no prodromal symptoms in varicella;

•

the incubation period is 14-21 days for varicella vs. 7-17 days for smallpox;

© Corexcel, All Rights Reserved.

Page 12

•

varicella scabs appear 4-7 days after rash begins, while they appear 10-14 days of rash onset in smallpox;

•

period of infectivity starts from a day before rash until all vesicles form scab in varicella and from onset of rash until all scabs separate in variola (11);

•

varicella lesions are centripetal, appearing more frequently on the trunk, while smallpox lesions are distributed centrifugally and tend to cluster on the extremities. (10)

Rapid laboratory diagnosis is essential when smallpox is suspected. It should be carried out in a high-containment facility. Collection of specimens for laboratory diagnosis should be performed by a person who has been vaccinated recently. Gloves and a mask are necessary. Vesicular or pustular fluid can be obtained by opening lesions with the blunt edge of a scalpel. Definitive identification of the virus will involve its growth in cell culture followed by the use of bioassays. The process can be accomplished in a few hours (10). Treatment No proven treatment exists for smallpox. Patients with the disease do benefit from supportive therapy including: •

intravenous fluids;

•

drugs to control fever and pain;

•

antibiotics to treat secondary bacterial infections.

Vaccination Routine vaccination against smallpox in the U.S. ceased in 1972. Therefore, any individual 30 years of age or younger has no immunity to the disease (10). According to the U.S. Census Bureau, about 42% of the U.S. population were aged 29 years or younger in 1998. (10) Neutralizing antibodies which reflect levels of protection decline markedly 5 to 15 years after vaccination. Most children who were vaccinated at the age of one year were given a single dose of vaccine. Lifelong immunity was not conferred on most people unless they received booster shots. (10) The incidence of adverse reactions following widespread vaccination is estimated to be 150 in 1 million people vaccinated. Certain groups are at risk for complications arising from smallpox vaccination. However, most experts agree that under epidemic conditions, risks of vaccination should be weighed against the risks caused by contracting smallpox. Vaccinia immune globulin, limited supplies of which are maintained at the CDC, can be administered at the time of vaccination to ward off complications in susceptible people. Access to vaccinia immune globulin is through individual state health departments. Modes of transmission In naturally occurring epidemics, smallpox spreads from person to person by droplet or aerosols from the oropharynx of infected people. Clothing or bed linens that are contaminated with the virus are also ways of spreading the virus (12). The rapidity of the spread was illustrated in a

© Corexcel, All Rights Reserved.

Page 13

European outbreak during the 1960s and 1970s where 10 to 20 cases occurred from a single infected patient.

Botulism Botulism has a long history of use in biowarfare, dating back 60 years (13. Iraq is said to have produced 19,000 liters of concentrated botulism toxin; 10,000 liters were loaded into military weapons during the Gulf War but were never used. Nineteen thousand liters of toxin are three times the amount needed to kill the entire human population. Although intentional release of botulism toxic could have a devastating impact on the U.S. civilian population, experts tend to minimize its potential as a bioweapon because concentrating and stabilizing the toxin for aerosol release would be technically difficult Like anthrax, Clostridium botulinum is a bacterium that forms spores. Its natural habitat is soil. Several antigenic types of botulism toxin exist; they are designated by the letters A though F. Three forms of naturally occurring human botulism exist: •

foodborne;

•

wound; and

•

intestinal.

In the U.S., fewer than 200 cases of all forms of human botulism occur annually. Foodborne botulism occurs when an individual ingests preformed toxin from improperly canned food. Wound botulism results when wounds infected with the C. botulinum secrete the toxin. Intestinal botulism arises in the intestinal tracts of susceptible infants and adults who harbor the toxin. Symptoms Once botulism enters the system, the bloodstream carries it to the neuromuscular junction, where it binds. Therefore, most of the signs of botulism are neurological. Cranial nerve palsies are a common feature. However, in the foodborne type, signs may be preceded by abdominal cramps, nausea, vomiting and diarrhea. If purified toxin is intentionally released in food or aerosol form, the abdominal symptoms may not occur. Symptoms tend to descend through the body and include: •

double vision and blurred vision;

•

drooping eyelids;

•

slurred speech;

•

difficulty swallowing; and

•

dry mouth;

•

muscular weakness, affecting the shoulder first, followed by the upper arms, lower arms, thighs and calves.

© Corexcel, All Rights Reserved.

Page 14

Paralysis of breathing muscles can occur. The incubation period for foodborne botulism ranges from 6 hours to 2 weeks; most commonly it ranges between 12 and 36 hours. The disease does not spread from person to person. Diagnosis Clinical diagnosis supercedes laboratory diagnosis, because the latter often takes days to complete and test results are often unremarkable. Botulism is frequently misdiagnosed and mistaken for Guillain-Barre syndrome, myasthenia gravis or a disease of the central nervous system. Diagnostic testing is available at the CDC and at about 20 state laboratories. Diagnostic samples may include 30 mL or less of blood, stool, gastric aspirates and vomitus. (13) Suspected foods, if available, can be tested by public health laboratories, the FDA or agriculture department. Treatment Supportive care and passive immunization with antitoxin are recommended therapies for botulism. Antitoxin should be administered to patients with neurological signs of botulism as soon as possible after clinical diagnosis (13). The antitoxin is available from the CDC through state and local health departments. Fluid and nutritional support and assisted ventilation for patients with paralysis that doesn't recede may be necessary for weeks or months. Antibiotics are not known to have a direct effect on botulism toxin but may become necessary to treat secondary bacterial infections. Modes of transmission Foodborne botulism is always transmitted by foods that are improperly heated or not heated thoroughly. In the U.S., the most commonly implicated foods are vegetables such as beans, peppers, carrots and corn. (13), presumably because of their higher pH content. Outbreaks have been known to occur with commercial foods, such as yogurt, cream cheese and jars of peanuts.

Plague Three major pandemics have occurred in recorded history. The first one began in Egypt in AD541 and spread across Europe, North Africa and parts of Asia, resulting in deaths among 50 to 60% of the population. A second pandemic known as the "Black Death" began in 1346 and killed approximately a third of the European population. This pandemic lasted 130 years. A third pandemic started in China during the mid-19th Century, eventually struck all inhabited continents and killed more than 12 million people in India and China (14). In wartime, it was used by the Japanese army in over-populated areas of China. The U.S. and the former Soviet Union are said to have developed techniques to aerosolize plague directly. Naturally occurring plague results when infected fleas bite humans who go onto develop bubonic plague. This is usually preceded by the death of large numbers of rats, prompting fleas to leave the natural rat reservoir and move to humans. Plague continues to occur worldwide except in Australia. It is dependent on enzootic infection of rats, ground squirrels, prairie dogs and other rodents. Some 390 cases of plague were reported in the U.S. from 1947 to 1996 in the states of New Mexico, Arizona, Colorado and California. (14).

© Corexcel, All Rights Reserved.

Page 15

Y pestis is a gram-negative bacillus and member of the Enterobacteriaceae family. Symptoms Naturally occurring plague follows the bite of an infected flea. This leads to the inoculation of thousands of organisms into a patient's skin. Bacteria travel through cutaneous lymphatics to regional lymph nodes. This is followed by rapid multiplication, which causes destruction and necrosis of the lymph node architecture. Bacteremia, septicemia and endotoxemia, finally leading to shock, disseminated intravascular coagulation and coma may ensue. (14) Two to 8 days after infected flea's bite, patients with bubonic plague develop sudden onset of fever, chills and weakness. About a day or less later, they develop an acutely swollen lymph node, or bubo. Buboes range from 1 to 10 cm. In diameter; the overlying skin is erythematous (JAMA-21). Septicemia also may develop secondary to bubonic plague. In a minority (12 %) of patients with bubonic or primary seppticemic plague, secondary pneumonic plague may develop. These patients will have symptoms of severe bronchopneumonia, chest pain, dyspnea, cough and hemoptysis. Primary pneumonic plague is exceedingly uncommon in the U.S. Plague following an intentional biological release would be quite different than naturally occurring cases. Aerosolized bacilli would cause primary pneumonic plague only. Other differences would include: • •

a shortened incubation period, most likely 2 to 4 days; a prodrome consisting of fever, cough and dyspnea;

•

prominent gastrointestinal symptoms; and

•

absence of buboes.

Preceding the era of antibiotics, the mean time from respiratory exposure to death in humans was 2 to 4 days. Diagnosis No rapid diagnostic tests for plague are widely available. The CDC, some state health departments and military laboratories are set up to confirm a suspected diagnosis, using antigen detection, IgM enzyme immunoassay, immunostaining or polymerase chain reaction. A Gram stain of sputum or blood may show gram-negative bacilli or coccobacilli. Treatment As might be expected, limited studies of antibiotics for plague in humans or animals have been carried out. A number of drugs have been employed with varying success in the treatment of plague, including: •

streptomycin;

•

gemtamicin;

•

tetracycline and doxycycline;

© Corexcel, All Rights Reserved.

Page 16

•

ciprofloxacin; and

•

chloramphenicol.

Of these drugs, only streptomycin, tetracycline and doxycycline have been approved by the FDA to treat plague. Vaccine A formaldehyde-killed whole bacilli vaccine was licensed by the U.S. but was discontinued by manufacturers in 1999. The vaccine was capable of preventing and ameliorating bubonic but not primary pneumonic plague. Modes of transmission The only mode of intentional transmission for plague in the U.S. would be in aerosolized form. In a worst-case scenario, the WHO has postulated that if 50 kg. of Y pestis were released over a city of 5 million inhabitants, as many as 150,000 people would contract pneumonic plague. Some 136,000 would be expected to die. (1).

Tularemia Francisella tularensis is a gram-negative, coccobacillus. It exists in two forms: type A and type B.

As a biological weapon it was considered for use by warring countries, but there is no direct evidence of its use.

Tularemia is found in North America and Europe. Every U.S. state, with the exception of Hawaii, has reported cases, but cases are more common in the south central and western states. Voles, mice, water rats, squirrels, rabbits and hares are natural reservoirs of infection. These animals acquire infection through ticks, fleas and mosquitoes. F tularensis also has been recovered from contaminated water, soil and vegetation. Incidence of tularemia in the U.S. is about 200 cases per year. A majority of cases occur from June through September. Hunters, trappers and farmers are particularly susceptible to the disease. A large outbreak of inhalation tularemia occurred in a farming area of Sweden during 1966-1967. Affected farm workers were sorting and moving rodent-infested hay from storage sites to barns. (15) Symptoms Tularemia can affect humans through skin, mucous membranes, the gastrointestinal tract and lungs. Onset of the disease is abrupt, presenting with: •

fever;

•

headaches;

•

chills;

© Corexcel, All Rights Reserved.

Page 17

•

generalized body aches;

•

coryza; and

•

sore throat.

The disease can manifest itself in a number of presentations, including: •

ulceroglandular, in which a local cutaneous papule appears at a bite site, and ulcerates within a few days;

•

oropharyngeal, in which the patient may commonly develop exudative pharyngitis or tonsillitis;

•

pneumonic;

•

septic, which is potentially severe and fatal.

Diagnosis Rapid diagnostic testing is not widely available. Suspicion of inhalation tularemia should prompt collection of respiratory secretions and blood and rapid transmittal to a laboratory equipped to diagnose the disease. Treatment Streptomycin is the drug of choice, and gentamicin is an acceptable alternative. (15) Although a higher relapse rate and primary treatment failures have occurred with tetracycline and chloramphenicol, these two drugs have been used. However, they should be used for at least 14 days to lessen the chance of relapse. Vaccine A live, attenuated vaccine has been used to protect laboratory employees working with bacteria. Its future availability on a widespread basis is undetermined. Modes of transmission Aerosolized dissemination of organisms would be the most likely way to infect the civilian population. The WHO suggests that an aerosol dispersal of 50 kg over an area of 5 million inhabitants would cause 250,000 cases, with an estimated 19,000 deaths. Chemical Weapons A broad-based definition of chemical warfare describes it as a chemical substance whether gaseous, liquid or solid, which might be employed because of its toxic effects on man, animals or plants. Thankfully, although there are thousands of poisonous substances, only a few are considered potential weapons of mass destruction because of their difficulty in development and dispersal. To be considered by terrorists for intentional release, the chemical agent must be: •

highly toxic;

© Corexcel, All Rights Reserved.

Page 18

•

risk-free to the saboteur;

•

capable of storage for long periods in containers without degrading them;

•

relatively resistant to water and oxygen; and

•

able to withstand the heat developed when dispersed.

Chemical weapons can be dispersed in the air, in which case they are classified as volatile substances. Other chemicals are involatile and only cover surfaces. Many chemicals are simply incapacitating, causing nausea or visual problems. Table 2. Indicators of a Possible Chemical Incident Dead animals/birds/fish Lack of insect life

Physical symptoms

Mass casualties

Definite pattern of casualties Illness associated with confined geographic area Unusual liquid droplets Areas that look different in appearance

Unexplained odors

Low-lying clouds Unusual metal debris

© Corexcel, All Rights Reserved.

Not just occasional road kill, but numerous animals (wild and domestic, small and large), birds and fish in the same area If normal insect activity (ground, air, and/or water) is missing, then check the ground/water surface/shore line for dead insects. If near water, check for dead fish/aquatic birds. Numerous individuals experiencing unexplained water-like blisters, wheals (like bee stings), pinpointed pupils, choking respiratory ailments and/or rashes. Numerous individuals exhibiting unexplained serious health problems ranging from nausea to disorientation to difficulty in breathing to convulsions to death. Casualties distributed in a pattern that may be associated with possible agent dissemination methods. Lower attack rates for people working indoors versus outdoors, or outdoors versus indoors. Numerous surfaces exhibit oily droplet/film, numerous water surfaces have an oily film. (No recent rain). Not just a patch of dead weeds, but trees, shrubs, bushes, food crops, and/or lawns that are dead, discolored, or withered. (No current drought). Smells may range from fruity to flowery to sharp/pungent to garlic/horseradish-like to bitter almonds/peach kernels to new mown hay. It is important to note that the particular odor is completely out of character with its surroundings. Low-lying clouds/fog-like condition that is not explained by its surroundings. Unexplained bombing/munitions-like material, especially if it contains a liquid. (No recent rain).

Page 19

Source: Chemical/Biological/Radiologic Incident Handbook. 1998; Washington, DC: Central Intelligence Agency.

For purposes of this course, only those agents that are considered to be lethal will be discussed, since the U.S.'s enemies have stated their intent to kill, and not incapacitate, citizens. Experts in the field of chemical warfare believe that three types of agents are most likely to be deployed if terrorists choose this course of action: 1. nerve agents; 2. mustard agents; and 3. hydrogen cyanide.

Nerve agents Nerve agents are similar to insecticides because they are derived from organophosphorous compounds and are very toxic. Their military names and year they were first made follow: •

GA (tabun), 1936;

•

GB (sarin), 1938;

•

GD (soman), 1944; and

•

VX, 1952 (16)

VX is the most lethal of the nerve gases. Most of the information that is known comes from reports of battlefield exposures, accidental exposures among workers and an intentional release of sarin in the subway of Tokyo during 1995. Nerve agents have no color and emit no odor except for a faint, slightly sweet aroma. They can enter the body through inhalation or through direct contact on the skin. Symptoms Low dose exposure to a nerve agent may cause the following: •

increased production of saliva;

•

runny nose;

•

feeling of pressure on the chest;

•

contracted pupils;

•

reduced accommodation capacity of the eye;

•

pain in the eye; and

•

headache.

Less commonly, tiredness, slurred speech, hallucinations and nausea may occur. More dramatic symptoms result from high dose exposure to nerve gas, namely:

© Corexcel, All Rights Reserved.

Page 20

•

muscle paralysis

•

convulsions; and

•

loss of consciousness.

Treatment Because nerve agents have such rapid effects, medical treatment must be instituted immediately. One of the most important principles of treating someone exposed to nerve gas is that the first responder is protected from contamination. This can be achieved by donning a mask, gloves and a protective outer garment and decontamination of the victim. Decontamination prevents the further absorption of the agent and also prevents the spread to others, especially medical personnel. Decontamination also involves, if possible, a complete washing of the eyes and skin with water. Since the late 1940s, atropine has been the antidote of choice to treat casualties, based on wartime experience. On the field of battle, it can be self-administered or given by a buddy, using an automatic injector containing. The other antidote to nerve poisoning is an oxine, which directly reacts with the cause of the injury. In other words, it restores or reactivates an enzyme, which is impaired by the nerve gas. Oxines work primarily on the peripheral nervous system. Modes of transmission Nerve agents can be dispersed through bombs, missiles, spray tanks, rockets and land mines.

Mustard agents Use of mustard agents as chemical weapons go back to the latter part of WWI. During the Iran and Iraq war of 1979-88, Iraq is said to have used mustard gas, which may have killed at least 1,000 Iranian soldiers. Dumping of chemical weapons in waters off the Danish and Swedish coasts resulted in unsuspecting fishermen being exposed when they brought fishing nets to the surface. With the use of mustard as a weapon, the medical system can be overburdened with injured who require long and demanding care. Mustard gas is colorless, oily and gives off a sweet, garlic-like odor. These agents are often referred to as "blistering agents" because exposure can cause burns and blisters. Other effects of exposure include eye damage, respiratory damage and damage to internal organs. Long-term effects can include: •

chronic respiratory diseases (asthma, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, chronic laryngitis);

•

respiratory cancers (nasopharyngeal, laryngeal and lung);

•

pigmentation abnormalities of the skin;

•

chronic skin ulceration and scar formation;

© Corexcel, All Rights Reserved.

Page 21

•

skin cancer;

•

chronic conjunctivitis;

•

recurrent corneal ulcerative disease;

•

delayed recurrent keratitis

•

leukemia (nitrogen mustard);

•

bone marrow depression and resulting immunosupression;

•

psychological disorders (mood disorders, anxiety disorders and traumatic stress disorders); and

•

sexual dysfunction as a result of scrotal and penile scarring. (17)

Short exposure to small quantities of mustard agents may cause permanent injury or death. The agent is a powerful irritant and produces corrosion and necrosis of the skin, eyes and respiratory tract. Symptoms Signs and symptoms are many: •

dyspnea;

•

cough;

•

fever;

•

headache;

•

severe eye irritation;

•

photophobia;

•

tearing;

•

blindness;

•

irritation or ulceration of the respiratory tract from inhalation;

•

dizziness;

•

malaise;

•

anorexia;

•

lethargy;

•

arrhythnias;

© Corexcel, All Rights Reserved.

Page 22

•

convulsions;

•

nausea, vomiting and diarrhea; and

•

Hemorrhage and anemia. (18)

Treatment Treatment is limited to symptoms only, since no antidote exists. Decontamination of the victim is the most important first step after exposure (see decontamination procedures below). Antibiotics can be given to control infection; local anesthetics can be employed to ease pain. Emergency life-support procedures may have to be employed.

Hydrogen cyanide Highly toxic, hydrogen cyanide was reportedly used by Iraq during its war with Iran and against the Kurds in northern Iraq in the 1980s. (19). A form of hydrogen cyanide was used in the Nazi gas chambers during WWII. A colorless liquid, it can also be found in a gaseous form and as a cyanide salts solution. High concentrations outdoors are difficult to achieve. In confined spaces, however, it can rapidly reach lethal levels. Nonmilitary uses of cyanide are plentiful. It is used in electroplating, plastics processing, gold and silver extraction, tanning, metallurgy and as a fumigant. Cyanide occurs naturally in bitter almonds, apricot pits, lima beans and roots. Symptoms Initial symptoms of inhalation cyanide poisoning are restlessness and increased respiratory rate. They may be followed by giddiness, headache and palpitations. In later stages, there may be vomiting, convulsions, respiratory failure and loss of consciousness. In the event of exposure to extremely high concentrations, a person may just collapse and die within minutes. Depending on the dose and chemical form of cyanide released, route and spread of administration and health status of the exposed individual, cyanide can affect multiple systems in the body, including: •

vascular;

•

visual;

•

pulmonary;

•

central nervous;

•

cardiac;

•

autonomic;

•

endocrine; and

© Corexcel, All Rights Reserved.

Page 23

•

metabolic. (19)

Treatment First steps in treatment should include: •

removal of the victims from the cyanide-containing environment;

•

removal of contaminated clothing;

•

rinsing of skin with soap and water; and

•

gavaging and administering activated charcoal if cyanide was ingested (19)

Supportive actions are especially crucial in treating cyanide poisoning. The lethal effects of cyanide are neutralized by mechanical resuscitation. Intravenous administration of sodium bicarbonate will reduce the risk of lactic acidosis. Administration of anti-convulsants will control seizures. Also crucial is maintaining cardiac rhythm to maintain tissue perfusion and oxygenation. Generally, antidotes are not necessary if the victim is conscious. However, victims with advanced toxicity may require them. In the U.S., the following antidotes are administered intravenously: •

sodium nitrite;

•

sodium thiosulfate;

•

dicobalt edetate; and

•

Hydroxocobalamin. (19)

Measures of decontamination for first responders •

once clear of the contaminated area, remove external clothing and leave outside

•

thoroughly and aggressively wash body with soap and water as soon as practically possible.

•

irrigate eyes with water.

•

wash contaminated areas of skin for 10 to 15 minutes with a 0.5 percent sodium hypochlorite solution, if available (one part household bleach and 10 parts water. and

•

use undiluted household bleach to decontaminated fabric clothes for 30 minutes, even if clothing is to be discarded. (20)

Personal Safety Considerations for First Responders The CIA has set out general guidelines to aid first responders in a chemical or biological incident:

© Corexcel, All Rights Reserved.

Page 24

•

if outside, approach or evacuate upwind of the suspected area.

•

if outside, don available protective mask and clothing immediately. Cover all exposed skin surfaces and protect the respiratory system as much as possible. Overcoats, boots, gloves, hats, self-contained breathing systems and organic vapor respirators will help provide protection.

•

if inside and the incident is inside, evacuate while minimizing passage through the contaminated area; keep windows and doors not used closed.

•

if inside and the incident is outside, stay inside. Turn off air conditioning, seal windows and door with plastic tape.

•

deploy chemical and biological detection equipment, if available.

•

when clear of the area or adequately protected, call specialized expertise if a chemical or biological event is suspected. and

•

report information to authorities. (20)

Are we prepared? The short answer is "yes" and "no." Evidence abounds that the U.S. is not starting from square one in its defense against Bioterrorism: •

A vast military experience with biological and chemical weapons exists, enabling public health experts to use that information in responding to potential civilian disasters. In the forefront of the military's contribution to defense is the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick

•

Public health officials have long been aware of the threat of Bioterrorism, stockpiling pharmaceuticals and medical supplies.

•

Many U.S. communities have conducted mock civilian disaster operations.

•

Federal agencies have the capability to deal with disasters, as evidenced by their response to national and international catastrophes in recent years.

In spite of the many federal agencies and resources available to combat attacks on the population, there is recognition by federal authorities of the challenges that lie ahead: •

Unlike exposure to chemical agents, the release of biological agents could go undetected. An interval of days or even weeks might occur before overt symptoms appear. When symptoms occur, patients might be great distances away from the original source of exposure, delaying identification of the pathogen.

•

The responsibility for responding to medical emergencies will fall on local communities. However, rapid identification of the offending agent or availability of pharmaceuticals to treat it may exceed the capability of communities.

•

The potential for larger numbers of potential victims is enormous, particularly in dense, urban environments.

© Corexcel, All Rights Reserved.

Page 25

•

Producing vaccines and drugs to treat outbreaks of disease cannot be rapidly accelerated due to ethical and safety considerations.

•

Evidence of the continuing attempts to produce biological and chemical weapons is available. More troubling is the potential capability of adversaries to develop new agents based on the latest advances in biotechnology.

•

Eleven nations possess the capability to develop offensive biological weapons while 31 countries have the ability to develop chemical weapons.

Federal preparations for attacks are not without critics. Mohammad Akhter, executive director of the American Public Health Association recently criticized federal efforts as inadequate and called for $1 billion in new spending (21). Needs cited by other public health officials include: •

antibiotics;

•

vaccines;

•

better training for public health officials;

•

enhanced communication for public health agencies; and

•

more epidemiologists.

Federal public officials are moving rapidly to combat one potential biological threat. On November 27, 2001 the CDC announced measures to prevent the spread of smallpox, should it occur. CDC's plan is to utilize the "ring" vaccination strategy employed in eradicating smallpox more than 20 years ago. The plan is simple: •

rapidly identify cases;

•

isolate the initial patients; and

•

identify and vaccinate contacts.

If the strategy fails to control the spread, more aggressive measures will be employed: vaccination of an entire city, travel restrictions, a ban on public events and quarantine of whole communities. Key to future U.S. preparedness is coordination of personnel and resources. According to a recent Government Accounting Office report, federal efforts currently are fragmentary. Former governor, Tom Ridge, is the newly appointed director of Homeland Security. He is responsible for coordinating the counter terrorism activities of more than 40 federal agencies and some state and local agencies. Some congressional critics say that the new director lacks the power and operational authority to adequately coordinate the activities of so many agencies. America's response to Bioterrorism is evolving. Responding to multiple threats or perceived threats is complex. Patience and resolve will aid the government and the public health community in developing short-term and long-term solutions.

© Corexcel, All Rights Reserved.

Page 26

References 1. World Health Organization. Health aspects of chemical and biological weapons. Geneva, Switzerland: World Health Organization; 1970: 98-99. 2. Lew, D et al. Bacillus anthracis (anthrax). In Principles and Practices of Infectious Disease. New York, NY: Churchill Livingstone Inc; 1995:1885-1889. 3. Meselson M et al. The Sverdlovsk outbreak of 1979. Science. 1994; 266: 1202-1208. 4. Brachman, PS and Friedlander, A. Anthrax. In Vaccines. Philadelphia, Pa: WB Saunders Co; 1999:629-637. 5. Inglesby, TV et al. Anthrax as a biological weapon. Medical and public health management. JAMA. 1999; 281: 1735-1745. 6. Centers for Disease Control. Use of ciprofloxacin or doxycycline for postexposure prophylaxis for prevention of inhalational anthrax. Atlanta, GA: Centers for Disease Control; October 31, 2001. 7. Food and Drug Administration Center for Drug Evaluation and Research. Cipro (Ciprofloxacin Hydrochloride) for Inhalation Anthrax. Washington, DC: Food and Drug Administration; 2001. 8. Turnbull, PC. Anthrax vaccines: past, present and future. Vaccine. 1991; 9:533-539. 9. Fenner, F et al. Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 1460. 10. Henderson, DA et al. Smallpox as a biological weapon. Medical and public health management. JAMA. 1999; 281: 2127-2137. 11. McClain, DJ. Smallpox. In Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General; 1997. Textbook of Military Medicine. 12. Dixon, CW. Smallpox. London, England: J & A Churchill Ltd; 1962: 1460. 13. Arnon, SS et al. Botulinum toxin as a biological weapon. Medical and public health management. JAMA. 2001; 285: 1059-1070. 14. Inglesby, TV et al. Plague as a biological weapon. Medical and public health management. JAMA. 2000; 283: 2281-2290. 15. Dennis DT et al. Tularemia as a biological weapon. Medical and public health management. JAMA. 2001; 285: 2763-2773. 16. Sidell, FR. Nerve Agents. In Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General: 1997. Textbook of Military Medicine.

17. Sidell, FR, Hurst, CG. Long-term Health Effects of Nerve Agents and Mustard. In Military Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General: 1997. Textbook of Military Medicine. 18. Environmental Protection Agency. Emergency First Aid Treatment Guide for Mustard Gas. (505-60-2) Washington, DC: Environmental Protection Agency. 19. Baskin, SI et al. Cyanide Poisoning. In Military Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General: 1997. Textbook of Military Medicine. 20. Central Intelligence Agency. Chemical/Biological/Radiological Incident Handbook. Washington, DC: Central Intelligence Agency; October 1998. 21. Connolly, C. Bioterrorism defense plan called inadequate. Washington Post, October 23, 2001.

Test Please mark only one best answer to the following questions on the one page answer sheet. This test contains 16 questions. Please mark your answers in spaces numbered 1 through 16 on your answer sheet. 1. The CDC was established in what year? a. b. c. d.

1942 1946 1950 1956

2. The final cases of endemic smallpox were isolated during 1977 in what country? a. b. c. d.

Sudan Iran Somalia Libya

3. Which of the following antibiotics is not recommended in treating anthrax? a. b. c. d.

doxycycline ciprofloxacin levofloxacin penicillin

4. The incubation period for smallpox is: a. b. c. d.

7-17 days 2-3 days 10-14 days 1-3 weeks

5. Approximately what percentage of the U.S. population has no immunity to smallpox? a. b. c. d.

10% 30% 40% 60%

6. Symptoms of poisoning with botulinum toxin can mimic what disease? a. b. c. d.

Parkinson's disease myasthenia gravis multiple sclerosis trigeminal neuralgia

7. The pandemic of "Black Plague" in Europe killed what proportion of the population? a. b. c. d.

1/2 1/5 1/3 1/4

8. Y pestis is a member of the Enterobacteriaceae family. a. True b. False 9. A bubo is: a. b. c. d.

an infected flea a collection of bacilli a rash an acutely swollen lymph node

10. Which of the following animals is not considered to be a reservoir for the tularemia coccobacillus? a. b. c. d.

mouse squirrel rabbit horse

11. Which of the following antibiotics is the drug of choice to treat tularemia? a. b. c. d.

tetracycline streptomycin penicillin ciprofloxacin

12. Large-scale death of cats is an indication of an intentional release of chemicals. a. True b. False 13. Which of the following agents, as far as we know, has Iraq not used against people? a. b. c. d.

mustard gas plague botulism hydrogen cyanide

14. The U.S. and what other country maintain a repository of smallpox virus: a. b. c. d.

Switzerland Russia France China

15. Initial symptoms of inhalation cyanide poisoning are restlessness and: a. b. c. d.

cranial nerve palsies tiredness dyspnea increased respiratory rate

16. Cyanide occurs naturally in lima beans. a. True b. False