Category | A | Biological Agents

1. Category |A| Biological Agents Louisiana Office of Public Health Center for Community Preparedness

2. Training Objectives • Describe the CDC’s Category A biological threat agents. • Describe the public health considerations involved in the release of a biological threat agent. • Discuss the recognition of potential bioterrorism events and the formulation of an appropriate response strategy. OPH Center for Community Preparedness

3. Category |A| Biological Agents Biological Weapons OPH Center for Community Preparedness

4. Biological Weapons • Biological warfare (BW), also known as germ warfare, is the deliberate use of disease-causing biological agents such as protozoa, fungi, bacteria, protists, or viruses, to kill or incapacitate humans, other animals, or plants. • Biological weapons (bioweapons) are living organisms or replicating entities (virus) that reproduce or replicate within their host victims. OPH Center for Community Preparedness

5. Biological Weapons | Uses • Mass casualties • Morbidity • Mortality • Destruction of resources • Agriculture • Drinking water • Societal disruption • Overwhelm local resources • Breakdown of order • Panic and fear • Economic hardship OPH Center for Community Preparedness

6. Biological Weapons | Historical • Offensive biological warfare (developing and stockpiling bioweapons) was outlawed in 1972 by the Biological Weapons Convention (BWC). As of 2009, 163 nations had ratified the BWC. • The United States’ biological weapons program ran from 1943 to 1969. • Biodefense research is now conducted by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick in Maryland. • The Soviet Union’s biological weapons program began in the 1920’s and was know as Biopreparat after 1973. Program was reportedly ended in 1992. • Both the United Kingdom and Japan have developed advanced bioweapon programs. OPH Center for Community Preparedness

7. Category |A| Biological Agents Biological Agent Categories OPH Center for Community Preparedness

8. CDC Biological Agent Categories Category A High-priority agents include organisms that pose a risk to national security because they: • 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. Agents • Anthrax (Bacillus anthracis) • Botulism (Clostridium botulinum toxin) • Plague (Yersiniapestis) • Smallpox (variola major) • Tularemia (Francisellatularensis) • Viral hemorrhagic fevers (Ebola, Marburg, Lassa, Machupo) OPH Center for Community Preparedness

9. CDC Biological Agent Categories Category B Second highest priority agents include those that • 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 disease surveillance. Agents • Brucellosis (Brucella species) • Epsilon toxin of Clostridium perfringens • Food safety threats (e.g., Salmonella species, Escherichia coli O157:H7, Shigella) • Glanders (Burkholderiamallei) • Melioidosis (Burkholderiapseudomallei) • Psittacosis (Chlamydia psittaci) • Q fever (Coxiellaburnetii) • Ricin toxin from Ricinuscommunis(castor beans) • Staphylococcal enterotoxin B • Typhus fever (Rickettsiaprowazekii) • Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]) • Water safety threats (e.g., Vibriocholerae, Cryptosporidium parvum) OPH Center for Community Preparedness

10. CDC Biological Agent Categories Category C • 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; and • Potential for high morbidity and mortality rates and major health impact. Agents • Emerging infectious diseases such as Nipah virus (found in fruit bats). OPH Center for Community Preparedness

11. Biological Agents | Characteristics As a bioweapon • Effectiveness • Morbidity and Mortality • Transmission • Environmental • Person-to-person • Ease of Use • Special handling • Production complexity • Accessibility • Commonly available • Few legal controls • Prevention As a disease • Symptoms • Diagnosis • Clinical • Laboratory • Transmission • Environmental • Person-to-person • Treatment • Curative • Supportive OPH Center for Community Preparedness

12. Category |A| Biological Agents The Agents OPH Center for Community Preparedness

13. Category |A| Biological Agents Anthrax OPH Center for Community Preparedness

14. Anthrax | Description Anthrax: An infection caused by the spore-forming bacteria Bacillus anthracis. Also called “wool sorter’s disease.” Types • Inhalational (rare) • Acquired by inhaling anthrax spores. This is the form most likely caused by a biological attack using aerosolized anthrax spores. • Cutaneous (more common) • Acquired when anthrax bacteria enter a break in the skin. • Gastrointestinal (rare) • Acquired by eating food contaminated with anthrax bacteria. OPH Center for Community Preparedness

15. Inhalational Anthrax | As a Disease Organism – Bacillus anthracis Incubation Period – less than 1 week (range 1 to 60 days) Symptoms - • low-grade fever • nonproductive cough • malaise • fatigue • myalgias • profound sweats • chest discomfort OPH Center for Community Preparedness

16. Inhalational Anthrax | As a Disease Later Symptoms • 1–5 days after onset of initial symptoms . • May be preceded by 1–3 days of improvement. • Abrupt onset of high fever and severe respiratory distress. • Shock, death within 24–36 hours . OPH Center for Community Preparedness

17. Inhalational Anthrax | As a Disease Diagnosis • Specific chest X-Ray findings (Ex. widened mediastinum) • Gram-positive bacilli in blood or cerebrospinal fluid. • Aerobic blood culture growth of large, Gram-positive bacilli provides preliminary identification of Bacillus species. • Confirmation by polymerase chain reaction (PCR) Treatment • Antibiotics (doxycycline, ciprofloxacin) • Survival chances decrease dramatically if not treated within 48 hours of exposure. OPH Center for Community Preparedness

18. Inhalational Anthrax | As a Bioweapon • Effectiveness • In the 20th century, 18 cases of (natural exposure) anthrax in the US had a case-fatality rate of 85%. • In the 2001 anthrax attacks, where the victims received aggressive supportive and antibiotic therapy, the case fatality rate was 45%. • The 2001 anthrax attacks caused widespread panic and fear. • Transmission • No person-to-person transmission. • Spores can survive for decades in the environment. • Weaponized varieties remain suspended in air for substantial periods. • Ease of Use • Multiple distribution methods available. OPH Center for Community Preparedness

19. Inhalational Anthrax | As a Bioweapon • Accessibility • Occurs naturally in the soil. • Is a common disease in livestock in some parts of the world. • The technology is available on the open market with few controls to purchase. • Prevention • A vaccine is available, but not widely used outside the military. • Detection methods include air-sampling machinery, and indirect methods such as syndromic surveillance and other pattern-recognition methods. These are only useful after an anthrax release has occurred. OPH Center for Community Preparedness

20. Inhalational Anthrax | Public Health Actions Detection • Direct detection of agent • Clinician reports to state health department. • Syndromic detection of illness • Laboratory confirmation Isolation and quarantine • Not useful for this illness (not person-to-person) Prophylaxis • Treatment more useful to those not yet exhibiting symptoms. • Delays in treatment greatly increase mortality. Decontamination • People and clothing can be washed. • Contaminated possessions may need to be incinerated. • Environmental cleaning difficult and expensive. OPH Center for Community Preparedness

21. Inhalational Anthrax | Historical Notes • Used against Russian forces in Finland in 1916 by Scandinavian freedom fighters (sponsored by Germany). • First extensively developed as a bioweapon by Unit 731 (Japan) in Manchuria in the 1930’s. The USSR later captured the labs used in this project, thus beginning that nation’s bioweapon program. • In 1942 the United Kingdom conducted anthrax bioweapon trials on Gruinard Island in Scotland, making the isle uninhabitable until it was decontaminated in 1990. • Sverdlovsk, Russia – April 2nd 1969, weaponized anthrax spores accidentally released in the city of Sverdlovsk. At least 94 people were infected, and at least 68 died. • In 1990, Iraq deployed two 600 km range missiles loaded with anthrax. OPH Center for Community Preparedness

22. Category |A| Biological Agents Botulism OPH Center for Community Preparedness

23. Botulism | Description Botulism – a disease caused by the toxin-producing bacteria Clostridium botulinum. Types • Botulinum Intoxication occurs when a person ingests or inhales a pre-formed toxin that leads to illness within a few hours to days. This toxin is used in the production of biological weapons. • Infant botulism occurs in a small number of susceptible infants each year who harbor C. botulinum in their intestinal tract. • Wound botulism occurs when wounds are infected with C. botulinum that secretes the toxin. OPH Center for Community Preparedness

24. Botulism | As a Disease Organism – Clostridium botulinum Incubation Period – 12 to 36 hours (range 6 hours to 10 days) Symptoms – • Double vision • Blurred vision • Drooping eyelids • Slurred speech • Dry mouth • Muscle weakness (paralysis) moving down the body • Paralysis of breathing muscles can lead to death OPH Center for Community Preparedness

25. Botulism | As a Disease Diagnosis • Based on symptoms • Although this disease resembles Guillain-Barré syndrome, stroke, and myasthenia gravis. • Neurologic tests • Testing for botulinum toxin can be performed at some state health departments and the CDC. Treatment • Supportive care (such as mechanical breathing assistance). • Antitoxin is available from CDC (at no cost). • Immune globulin for infant botulism is available from California Department of Public Health ($45,300 per dose) OPH Center for Community Preparedness

26. Botulism | As a Bioweapon Effectiveness • Botulinum toxin is the most poisonous substance known. A single gram of crystalline toxin, evenly dispersed and inhaled, is sufficient to kill more than 1 million people. • Case fatality rate for untreated botulism (toxin) is 60%. Transmission • Not person-to-person. • Must be ingested or inhaled. Ease of Use • Distribution accomplished through simple methods. • Direct contamination of food or water. • Spraying of aerosolized toxin. OPH Center for Community Preparedness

27. Botulism | As a Bioweapon Accessibility • Bacterium occurs naturally in the soil. • Production methods are relatively unsophisticated for contaminating food and water sources. Aerosolization of the toxin is more difficult. Prevention • No vaccine available. OPH Center for Community Preparedness

28. Botulism| Public Health Actions Detection • Clinician report to state health department. • Syndromic detection of illness. • Laboratory confirmation. Isolation and quarantine • Not useful for this illness (not person-to-person) Prophylaxis • Effectively none, although antitoxin might be used in some cases as prophylaxis. • No patient-contact prophylaxis necessary. Decontamination • Destruction of contaminated food. • Standard healthcare sanitization of surfaces and durable equipment. • Standard healthcare sanitization of bedding and clothing. OPH Center for Community Preparedness

29. Botulism | Historical Notes • Tested as a bioweapon by Unit 731 (Japan) in Manchuria in the 1930’s. C. botulinum cultures were fed to prisoners. • Aerosolized C. botulinum was dispersed on at least three occasions in Japan by AumShinrikyō. • Believing that Nazi Germany had developed weaponizedbotulinum toxin, the US created 1 million doses of botulinum toxoid vaccine to protect Allied soldiers participating in the invasion of Normandy (June 6th 1944). • By 1991, Iraq had produced 19,000 liters of botulinum toxin, 10,000 liters of which were in weapons. This is approximately three times the amount necessary to kill the entire population of the Earth. OPH Center for Community Preparedness

30. Category |A| Biological Agents Plague OPH Center for Community Preparedness

31. Plague | Description A disease caused by the bacterium Yersiniapestis, which is carried by rodents and their fleas. • Bubonic plague occurs when an infected flea bites a person or when materials contaminated with Y. pestis enter through a break in a person's skin. Patients develop swollen, tender lymph glands (called buboes) and fever, headache, chills, and weakness. Bubonic plague does not spread from person to person. An epidemic in 14th century Europe is known as “the Black Death.” • Pneumonic plague occurs when Y. pestis infects the lungs. This type of plague can spread from person-to-person through the air. Pneumonic plague may also occur if a person with bubonic or septicemic plague is untreated and the bacteria spread to the lungs. This form of the illness will be the most likely result of a biological attack involving Y. pestis. • Septicemic plague occurs when plague bacteria multiply in the blood. It can be a complication of pneumonic or bubonic plague or it can occur by itself. Septicemic plague does not spread from person to person. OPH Center for Community Preparedness

32. Pneumonic Plague| As a Disease Organism – Yersiniapestis Incubation Period – 1 to 6 days Symptoms – • fever • weakness • rapidly developing pneumonia with • shortness of breath • chest pain • cough • sometimes bloody or watery sputum • Nausea, vomiting, and abdominal pain may also occur. • Without early treatment, pneumonic plague usually leads to respiratory failure, shock, and rapid death. OPH Center for Community Preparedness

33. Pneumonic Plague| As a Disease Diagnosis • Lab testing of blood, sputum, or lymph node aspirate. Treatment • Single patient: streptomycin and gentamycin (intravenous). • Mass casualty: doxycycline and ciprofloxacin. OPH Center for Community Preparedness

34. Pneumonic Plague| As a Bioweapon Effectiveness • The mortality rate for untreated pneumonic plague is almost 100%. • Treatment started more than 24 hours after exposure has reduced effectiveness. Transmission • Person-to-person (mainly respiratory secretions). Ease of Use • Aerosolized Y. pestis persists in the air for up to 1 hour after release. • High lethality of the agent requires extreme care in handling. OPH Center for Community Preparedness

35. Pneumonic Plague| As a Bioweapon Accessibility • Available commercially. • Infects many types of rodents. • Endemic in many areas of the world, including the Southwestern U.S. (prairie dogs). Prevention • An approved vaccine exists, but is no longer commercially available. OPH Center for Community Preparedness

36. Pneumonic Plague | Public Health Actions Detection • Clinician report to state health department. • Syndromic detection of illness. • Laboratory confirmation. Isolation and quarantine • Federally mandated isolation and quarantine disease. • Can be as simple as wearing a proper mask. • May require isolation in a hospital negative pressure room. Prophylaxis • Antibiotic treatment of close contacts. Decontamination • Y. pestis is susceptible to sunlight and drying. • Standard healthcare sanitization of surfaces and durable equipment. • Standard healthcare sanitization of bedding and clothing. OPH Center for Community Preparedness

37. Plague| Historical Notes • In ancient China and medieval Europe, infected carcasses were used to contaminate enemy water supplies. • Mongol invasion of Caffa - the bodies of plague victims were launched by catapult into the city during the siege. • Plague of Justinian – in the 6th and 7th centuries is the first recorded plague outbreak. It is estimated that one half of Europe's population died. • Black Death – 1348 to 1350. This epidemic killed between 75 million to 100 million people. • After World War II, both the US and USSR developed techniques for weaponizing plague. • In 1994, an outbreak of suspected pneumonic plague occurred in India, resulting in 52 deaths and large internal migrations. OPH Center for Community Preparedness

38. Category |A| Biological Agents Smallpox OPH Center for Community Preparedness

39. Smallpox | Description A disease caused by the virus variola major. Smallpox as a naturally occurring disease was eradicated in 1979. Types • Ordinary: the most frequent type, accounting for 90% or more of cases. • Modified: mild and occurring in previously vaccinated persons. • Flat: rare and very severe. Occurs more often in children. Usually lethal. • Hemorrhagic: rare and very severe. More common in immuno-deficient individuals. Usually lethal. OPH Center for Community Preparedness

40. Smallpox| As a Disease Organism – variola major (a virus) Incubation Period – 7 to 17 days (not contagious) Symptoms – by phase. • Prodrome: 2 to 4 days duration (possibly contagious) • Fever (101 to 104 °F) • malaise • head and body aches • sometimes vomiting • During this phase, people are generally too sick to carry on daily activities. OPH Center for Community Preparedness

41. Smallpox| As a Disease • Early rash: 4 days duration (most contagious phase) • Small red spots develop on the tongue and in the mouth, which break open and release the virus • At this time, a rash appears on the body, concentrated on the arms and legs, but spreading everywhere within 24 hours. • By the third day, the spots become raised bumps. • By the fourth day, the bumps fill with a thick, opaque fluid and often have a depression in the center that looks like a bellybutton. • Fever usually returns at this point and remains until the bumps scab over. • Pustular rash: 5 days duration (contagious) • Bumps become pustules (sharply raised, round, and firm to the touch). • Pustule feels as though something like a small ball bearing is embedded in it. OPH Center for Community Preparedness

42. Smallpox| As a Disease • Pustules and scabs: 5 days duration (contagious) • The pustules begin to form a crust and then scab. • By the end of the second week after the rash appears, most of the sores have scabbed over. • Resolving scabs: ~ 6 days duration (contagious) • Scabs begin to fall off. The resulting marks on the skin will eventually become pitted scars. • Most scabs will have fallen off three weeks after the rash first appeared. • The person is contagious until all of the scabs have fallen off. • Scabs resolved (not contagious) OPH Center for Community Preparedness

43. Smallpox| As a Disease Diagnosis • Clinical diagnosis: acute onset of fever >101°F (38.3°C) followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause. • Laboratory confirmation: Polymerase chain reaction (PCR). Treatment • No proven treatment available, though antivirals may be useful in some cases. • Supportive care. • Vaccination can reduce the severity of disease if given within 2 to 3 days of exposure or decreases the symptoms if given within one week of exposure. OPH Center for Community Preparedness

44. Smallpox| As a Bioweapon Effectiveness • In unvaccinated individuals, smallpox is fatal in 30% of cases. • Causes severe illness (most patients are effectively incapacitated). • Transmission rates are high – in past outbreaks, it is estimated that each infected person infected 10 others. Transmission • Person-to-person transmission (mainly respiratory secretions). • Large portions of the global population have no immunity. Ease of Use • Working with smallpox requires highly sophisticated equipment and advanced knowledge. OPH Center for Community Preparedness

45. Smallpox| As a Bioweapon Accessibility • Variola major is not naturally occurring. It was wiped out as a natural disease in 1979 after a long-standing global vaccination campaign. • Viral stocks are maintained by only (reportedly) two nations: the United States and the Russian Federation. Prevention • A vaccine is available, but its use in the general public was discontinued in 1976. • In response to concerns of bioterrorism in the US, a vaccination campaign to immunize medical personnel and first responders was conducted in 2002 - 2003. OPH Center for Community Preparedness

46. Smallpox| Public Health Actions Detection • Clinician reports to state health department. • Syndromic detection of illness. • Laboratory confirmation. Isolation and quarantine • Federally mandated isolation and quarantine disease. • Severity of illness makes isolation at home impractical. Prophylaxis • Vaccination soon after exposure reduces severity of illness. Decontamination • Standard healthcare sanitization of surfaces and durable equipment. • Standard healthcare sanitization of bedding and clothing. OPH Center for Community Preparedness

47. Smallpox| Historical Notes • In the 18th century, smallpox killed approximately 400,000 Europeans. • In 1763, during the French and Indian War, a local trader (and British sympathizer) gave a French-allied Native American tribe (the Delawares) two blankets and a handkerchief from a smallpox hospital. • During World War II, extensive research on the weaponization of smallpox was conducted by the United States, United Kingdom, and Japan. • In 1992, Soviet defector and Biopreparat scientist Ken Alibek revealed that the USSR had stockpiled at least 20 tons of weaponized smallpox, which may have been engineered to reduce the effectiveness of the vaccine. OPH Center for Community Preparedness

48. Category |A| Biological Agents Tularemia OPH Center for Community Preparedness

49. Tularemia | Description A disease caused by the bacterium Francisellatularensis. Also known as “rabbit fever.” • There are approximately 200 reported cases of tularemia in the US each year. • The bacterium is commonly found in rodents, rabbits, and hares. • Routes of infection include: • Hunters being exposed while handling game carcasses. • Being bitten by an infected tick, deerfly, or other insect. • Consuming contaminated food and water. • Inhaling the bacteria. OPH Center for Community Preparedness

50. Tularemia| As a Disease Organism – Francisellatularensis Incubation Period – 3 to 5 days after exposure (range 1 to 14 days). Symptoms • Sudden fever • Chills • Headaches • Diarrhea • Muscle aches • Joint pain • Dry cough • Progressive weakness • Pneumonia with chest pain and bloody sputum OPH Center for Community Preparedness