Biological Weapons: Essential Information on Category A Agents

1. Biological Weapons: Essential Information on Category A Agents Felissa R. Lashley, RN, PhD, FAAN, FACMG Professor, College of Nursing, and Interim Director, Nursing Center for Bioterrorism and Infectious Disease Preparedness College of Nursing Rutgers, The State University of New Jersey

2. This module on the use of biological agents as bioweapons covers general material, the classification of biological agents as to their use in bioterrorism and gives the most important information regarding the Category A Agents according to the Centers for Disease Control and Prevention (CDC) classification. Separate modules address Category B and Category C agents. This module was supported in part by USDHHS, HRSA Grant No. T01HP01407.

3. The format and information in this module focuses on the use of the agent or outbreak of disease particularly in regard to bioterrorism including emphasis on management with nursing applications and infection control material. Detailed material on general transmission of disease, infection control and isolation precautions is in a separate module and this should be consulted. Aspects of preparedness are also in a separate module. Note that for the care of persons exposed to any biological agent, the nurse should be sure he/she is adequately protected first.

4. Objectives At the completion of this module, participants will be able to: 1. Identify at least 10 factors that make a biological agent or biological toxin suitable for use as a bioterror agent. 2. List the 3 CDC categories for critical biological agents and why they are so categorized. 3. Identify and list CDC Category A biological agents with potential for use in a bioterrorism attack. 4. Describe the signs and symptoms of infection with Category A agents. 5. Discuss isolation precautions for each Category A agent.

5. Using Biological Agents as Bioweapons

6. Biological Agents and Bioterrorism • Includes microorganisms, especially certain bacteria and viruses, and biological toxins such as botulinum toxin, which act like chemical agents. • May be directed at humans, plants, animals, and be a threat to crops, livestock, food products (agroterrorism) during processing, distribution, storage and transportation which could cause illness and also have severe economic consequences such as bovine spongiform encephalopathy, and foot and mouth disease.

7. Biological Agents and Bioterrorism-2 • Biological agents can be used as weapons in: • Biocrimes • Bioterrorism • Biowarfare • Definition: North Atlantic Treaty Organization (NATO) defines a biological weapon as “the provision of any infectious agent or toxin by any means of delivery in order to cause harm to humans, animals, or plants.”

8. Biological Agents and Bioterrorism-3 • Various definitions for bioterrorism have been given. The following may be used: “the intentional use or threat of use of biological agents on a population to achieve political, social, religious, ethnic, or ideological ends by causing illness, death and wide scale panic and disruption.” The aim may not be maximum damage but rather a political statement.

9. Biological Agents and Bioterrorism-4 • The technology exists to modify existing biological agents, or weaponize them, to, for example, make it easier to disseminate and/or cause greater harm in their dissemination. • The use of biological agents for bioterrorism has been referred to as the “poor man’s nuclear bomb.” • All involve the use of biological agents in order to obtain an outcome: political, social, economic, theological, personal.

10. Agents with Potential for USE in BIOTERRORISM • Varies according to source • NATO handbook lists 39 agents • World Health Organization (WHO) has another list • CDC lists biological agents in various categories, A, B, and C • National Institute for Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) also lists categories A, B, and C, but they differ somewhat from how CDC categorizes agents and lists a greater number of agents • Others

11. The Following are Desirable Characteristics for Biological Agents to be Used for Harmful Intent • Generate high levels of panic among population • Easy to obtain • Inexpensive • Easy to produce in mass quantities • Can be relatively easily “weaponized” or altered for maximum effect (even with genetic manipulation) • High infectivity • High person-to-person contagion • High mortality

12. The Following are Desirable Characteristics for Biological Agents to be Used for Harmful Intent-2 • Lack of effective treatment • Need for intensive care, straining resources • High potential for casualties/morbidity • Result in lengthy illness with prolonged care needed • Non-specific symptoms, especially early, delaying recognition • Long incubation periods • Hard to diagnose • Great degree of helplessness from effect

13. Examples of Historical Uses of the Deliberate Release of Biological Agents • Known as early as the 6th century BC • Soldiers dropped corpses of those who died of plague over city walls during siege of Kaffa to start a plague epidemic and force surrender. • British soldiers used variola contaminated blankets to spread smallpox to American Indians during the French and Indian Wars (1754-1767).

14. Examples of Historical Uses of the Deliberate Release of Biological Agents-2 • Followers of Bhagwan Shree Rajneesh intentionally contaminated salad bars in the The Dalles, Oregon with Salmonella. The purpose was to keep people from voting in a local election in November, 1984. More than 750 people were affected. • The Aum Shinrikyo group in Japan attempted to carry out attacks using aerosolized anthrax spores and botulinum toxin before releasing sarin in the Tokyo subway in 1995.

15. Examples of Historical Uses of the Deliberate Release of Biological Agents-3 • Intentional distribution of anthrax spores mainly through the US mail to various people occurred in the fall of 2001. In all, there were 22 known cases of anthrax; 11 were inhalational. Picture from CDC. Inhalational anthrax.

16. Categories of Critical Biological Agents as Specified by CDC • Three Categories of Agents: • Category A Agents: Pose the greatest threat to national security • Category B Agents: Second highest priority to national security. • Category C Agents: Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future.

17. Category A Agents • Pose a threat to national security because they: • Can be easily disseminated or transmitted person-to-person • Cause high mortality with potential for major public health impact • Might cause public panic and social disruption • Require special action for public health preparedness

18. Category B Agents • Second highest priority to national security: • Are moderately easy to disseminate • Cause moderate morbidity and low mortality • Require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance

19. Category C Agents • Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of: • Availability • Ease of production and dissemination • Potential for high morbidity and mortality and major health impact

20. Category A Agents • These agents include the following diseases, with the organism in parentheses. Discussion of each individual organism listed below follows: • Anthrax (Bacillusanthracis) • Botulism (Clostridiumbotulinum) • Ebola hemorrhagic fever (Ebola virus) • Lassa Fever (Lassa virus) • Marburg hemorrhagic fever (Marburg virus) • Plague (Yersiniapestis) • Smallpox (Variola virus) • Tularemia (Francisellatularensis)

21. Category A Agents-2 • Other hemorrhagic fever viruses, such as: • Junin virus (Argentine hemorrhagic fever) • Guanarito virus (Venezuelan hemorrhagic fever) • Machupo virus (Bolivian hemorrhagic fever) • Sabia virus (Brazilian hemorrhagic fever)

22. Anthrax (Bacillusanthracis) • Etiology: • A gram-positive rod-like bacteria, B.anthracis • Capable of aerobic spore formation • Spores can last 40 years or more • Non-motile • Forms capsule

23. Anthrax-2 • Description – has several clinical types: • Cutaneous (skin) anthrax most common. • Gastrointestinal (GI) anthrax • Rare in developed countries • Results from infected meat that is undercooked or raw • Can affect oropharynx or esophagus, causing ulcers • Inhalational (respiratory) anthrax • Abrupt respiratory distress • No person-to-person transmission • Other names – • Was known as woolsorters or ragpickers disease.

24. Anthrax-3 • Epidemiology: • A zoonotic disease, primarily of animals such as cattle, sheep, goats, deer and horses. • Worldwide there can be up to 100,000 cases per year. Most natural cases occur in the Middle East, India, Asia, Africa and Latin America. Usually rare in the US and western Europe. • Until the deliberate release of anthrax spores in the US in 2001, inhalational anthrax had not been reported in the US for more than 20 years. In 2001, 22 cases of human anthrax were reported in the US, 2 in 2002, none in 2003, 2004, and 2005, 1 in 2006, and none in 2007.

25. Anthrax-4 • Transmission: • Animals become infected through ingestion of spores in soil which germinate and produce toxins. • Humans usually contract anthrax from contact with anthrax infected animals or contaminated animal hair, hides, flax, wool, excretions, blood and products such as bone meal. • Direct contact from infected person’s skin lesions. • Inhalational anthrax is acquired by inhaling aerosolized spores. • Gastrointestinal anthrax results from eating undercooked or raw meat or dairy products from infected animals. • Inhalational and gastrointestinal anthrax are not known to be transmitted person-to-person. • Humans may also become infected through intentional exposure.

26. Anthrax-5 • Transmission cont.: • Occupational exposure in humans has been the most usual way in which anthrax was acquired. • Examples include farm workers, laboratory workers or industrial exposure (see below). • Cutaneous and inhalational anthrax cases formerly occurred during the manufacturing process of infected wool, hair and hides. In 2006, one case occurred in a man who acquired the disease from an infected animal hide he brought back from Africa to make drums.

27. Anthrax-6 Incubation period: • Cutaneous anthrax: a few hours to 12 days • Gastrointestinal anthrax: 1 to 7 days • Inhalational anthrax: Less than 7 days (usually 4-6 days) but up to 2 months.

28. Anthrax-7 • Clinical manifestations: • Cutaneous anthrax • Local response is itching followed by small red macule progressing to papule formation (3-5 days usual), resembling an insect bite. • This becomes a vesicle with a painless ulcer formation that may enlarge to 1 to 3 cm. • Black eschar develops within 7-10 days with surrounding edema. • Typically seen on arms, hands, head or neck. • May also have lymphadenitis and fever, malaise and headache. • Septicemia can occur.

29. Cutaneous Anthrax(Notice the edema and typical lesions)Photos from CDC. Notice the edema and typical lesions

30. Further examples of Cutaneous Anthrax lesions Photos from CDC. Black eschar, redness remains Ulcer and vesicle ring

31. Anthrax-8 • Clinical manifestations cont.: • Gastrointestinal anthrax • Symptoms initially are nausea, vomiting, anorexia, fever, followed by abdominal pain, hematemesis and bloody diarrhea. • Symptoms depend on site of lesions. • If there are lesions in oral pharynx, may swell to affect the airway, and there may be dysphagia and throat pain. • In gastrointestinal anthrax, ascites may develop as may septicemia within 5 days after onset.

32. Anthrax-9 • Clinical manifestations cont.: • Inhalational anthrax • There are usually two phases. • Initial symptoms are nonspecific and consist of malaise, low grade fever, nonproductive cough and gastrointestinal complaints such as nausea and/or vomiting. • Sometimes there is improvement for a few days followed by a second phase with dry cough, dyspnea, high fever, chills, diaphoresis, tachypnea and respiratory distress. • Bacteria enter the blood causing bacteremia, and seeding of the meninges and gastrointestinal tract. • Abdominal pain, hematemesis, melena, cyanosis, confusion and hemorrhagic, purulent meningitis develop.

33. Anthrax-10 • Clinical manifestations cont.: • Inhalational anthrax cont. – • Meningitis occurs in about 50%. • Cardiovascular collapse and death follow if untreated. • Because early symptoms are non-specific, the presence of nausea and vomiting and neurological symptoms help to differentiate it from other disorders and a widened mediastinum on x-ray is suggestive of inhalational anthrax.

34. Inhalational Anthrax Mediastinal widening and pleural effusion on Chest X-Ray in inhalational anthrax

35. Anthrax-11 • Diagnosis: • For all, blood cultures may be done if organism has spread. • Lab may do rapid screening followed by confirmatory testing. • Combine lab testing with clinical findings.

36. Anthrax-12 • Diagnosis cont.: • Cutaneous – • Gram stain, PCR, culture of exudate or eschar • Should be done before antibiotic therapy • Gastrointestinal – • Blood cultures • Oropharyngeal swabs • Inhalational – • Chest x-ray findings especially widened mediastinum, pleural effusions, and pulmonary congestion • Tissue biopsy • Fluid for gram stain, PCR or culture if from sterile site

37. Anthrax-13 • Mortality: • Cutaneous - if untreated can be 10%-20%, less than 1% with treatment • Gastrointestinal - depends on site, 25%-60% • Inhalation - mortality can be 45%-97% with antibiotic therapy. The case fatality rate may be as high as 75%.

38. Anthrax-14 • Treatment: • Cutaneous anthrax – • Initial therapy in adults is usually ciprofloxacin or doxycycline; in children both are also used, although care must be taken in children as doxycycline may discolor teeth. • Therapy may be oral. • Inhalational anthrax – • For adults and children, ciprofloxacin or doxycycline are used with one or two additional antimicrobials. • Initial therapy is IV, switching to oral therapy when appropriate. • Therapy may be as long as 60 days. • Therapy may be combined with a 3 dose regimen of anthrax vaccine for prophylaxis.

39. Anthrax-15 • Treatment cont.: • Gastrointestinal anthrax – • May be treated with the same antibiotic regimens as inhalation because of potential to spread to respiratory tract. • Note: Post-exposure prophylaxis may be given to those exposed to an initial release of anthrax as soon as possible after exposure. This is usually administered orally for 60 days with ciprofloxacin and doxycycline being the most desired followed by amoxicillin which is preferred for pregnant women. If organism is susceptible, children may also be switched to amoxicillin.

40. Anthrax-16 • Nursing considerations: • Be sure decontamination has taken place. • Appropriate isolation precautions. • Supportive care as needed for symptoms. • If associated with intentional release, psychosocial support/therapy is needed. • In analysis of survivors of fall 2001 anthrax release, a year later survivors had reported lower health-related quality of life and greater overall psychological distress. Those who had inhalation anthrax reported loss of functional capacity, and some still had respiratory abnormalities. • Adherence may be an issue for persons on long-term antimicrobial therapy and nurses should plan to address this.

41. Anthrax-17 • Isolation Precautions: • Cutaneous anthrax – Standard and the transmission based contact precautions. Avoid any contact with skin lesions or drainage. • Inhalational anthrax – Both standard and contact precautions have been recommended in addition to respurology N95 mask or PAPR & protective clothing for environmental aerolized powder on person. • Gastrointestinal anthrax – Standard precautions.

42. Anthrax-18 • Vaccine: • Multidose vaccine available but currently used for special populations such as the military. • Both live cellular and live acellular vaccines are available. Recombinant vaccines are in development. • Other: • Persons known to be exposed to anthrax spores should remove clothing and shoes and leave at worksite and wash exposed skin including any jewelry and glasses. • Removed clothing should be bagged. • At home, systematic showering with systematic cleaning from hair down should be done if at risk for higher contamination. • Care needs to be taken when removing outer clothing to keep inner clothing from being contaminated. • Biosafety level 2 handling.

43. Anthrax – Special Considerations Re: Bioterrorism • Anthrax is considered one of the most important biological agents with potential for use as a bioterror agent. • It can be weaponized in an aerosolized stable spore form. • One deep breath at the site of intentional release can result in inhalational anthrax with high mortality. • Environmental surveillance and assessment is needed. • Decontamination procedures are needed.

44. Anthrax – Special Considerations Re: Bioterrorism-2 • Anthrax potential for use as bioterror agent cont.: • Pre-exposure immunization available for defined population segments. • If anthrax is suspected, one part of the patient assessment is to assess whether there is an epidemiological linkage to a plausible environmental exposure such as through the person’s occupation. • Antimicrobial prophylaxis will be used for persons potentially exposed to anthrax. In those who are demonstrated not to be exposed, prophylaxis can be discontinued. For others, this will be continued for about 60 days.

45. Botulism(Clostridiumbotulinum toxin) • Etiology: • Toxin from Clostridiumbotulism, a spore- forming bacillus. • Seven known types cause disease. • These toxins are potent neurotoxins. • Toxin prevents acetylcholine release and blocks neuromuscular transmission, presynaptic inhibition affecting autonomic and motor receptors. • Minute quantities of botulinum toxins can cause death, as they are extremely poisonous. • Infective dose: 0.001 micrograms.

46. Botulism-2 • Types: • Foodborne – most common • Wound • Infant • Inhalational - rare, may be intentional • Incubation period: For foodborne botulism: 18-36 hours usual but can be 6 hours to 10 days. • Incubation period for inhalation botulism is 24-72 hours after exposure.

47. Botulism-3 • Epidemiology: • Most cases of foodborne botulism occur through improperly canned or prepared foods especially those that are of low acidity such as corn, beans, tomato sauce. • Improperly heated and stored sauteed onions were the cause of one outbreak in Peoria, Illinois. • Botulinum toxins have been weaponized to be delivered by aerosol means. • Wound and infant botulism are not discussed here.

48. Botulism-4 • Transmission: • Ingestion, inhalation (in deliberate release situation) or absorption. • Not transmissable from person-to- person.

49. Botulism-5 • Clinical manifestations: • Blurred vision • Dilated pupils • Diplopia • Ptosis • Dry mouth, and • Photophobia • These may be followed by: • Dysarthria • Dysphagia • Dysphonia • Generalized weakness, and • A symmetrical descending progressive paralysis leading to respiratory failure.

50. Botulism-6 • Clinical manifestations cont.: • Cranial nerve palsies are responsible for symptoms, such as difficulty in speaking or swallowing. • Symptoms such as constipation and urinary retention may be seen and nausea and vomiting may be present. • Patients are usually alert and afebrile.