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Biological Terrorism

Biological Terrorism. Academy of Medicine of New Jersey Medical Society of New Jersey New Jersey Department of Health and Senior Services . Biological Terrorism. Overview History Agents and Disease Detection and Response Physicians are the key to ongoing surveillance.

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Biological Terrorism

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  1. BiologicalTerrorism Academy of Medicine of New Jersey Medical Society of New Jersey New Jersey Department of Health and Senior Services

  2. Biological Terrorism • Overview • History • Agents and Disease • Detection and Response • Physicians are the key to ongoing • surveillance

  3. Categories of Weapons Used by Terrorists • Conventional • Biologic • Chemical • Nuclear • Cyber

  4. Features of Bioterrorism • Weapon: Microbe or Toxin • Premeditation • Goals: Political, Religious, Ideological • Motivation: Fear, Disruption, Instability

  5. Desirable Features of Biological Agents as Weapon • Inexpensive • Available • Easily transported/concealed and dispersed • Incubation period “Hides Tracks” of perpetrator • Modifiable (resistance, virulence)

  6. Uniqueness ofBiological Attacks • Biological • Onset - incubation, primary cases • Secondary Cases – contagion, contamination • Responders - medical • Response System – untested • Medical System may be a target

  7. Myths of Deterrence Against Bioterrorism • Morally Repugnant • Effective Treaties • Consequences too numerous or terrible • Science too difficult • Not easily weaponized

  8. Historyof Bioterrorism 12th Century – Romans, Greeks, Persians Polluted drinking water with decaying animals. 14th Century – Ukraine city of Kaffa Tartar forces catapulted bodies of plague victims. 18th Century – British Troops, North America Blankets of smallpox victims were given to Native Americans. 19th Century – U.S. Civil War Dead animals were put into drinking water.

  9. History of Bioterrorism 1973 Biopreparat sites, Russia 52 sites; 30,000 people - Engineered agents and delivery systems - 30 tons of Anthrax spores 1979 Sverdlovsk, USSR Accidental release of anthrax spores - 75 deaths 1984 Dalles, Oregon 751 cases of Salmonella from salad bars 2001USA 22 cases of Anthrax (5 deaths, 11 inhalational, 11 cutaneous)

  10. Keep Alert • Early detection • High index of suspicion • Immediate reporting of suspected cases to NJDHSS - During normal business hours (Mon-Fri, 8am-5pm) call (609) 588-7500 and ask for Bioterrorism Unit. • During nights, weekends and holidays, contact the NJDHSS emergency number at • (609) 392-2020

  11. Clues to Bioterrorism • Severe disease manifestations in previously healthy people • Higher than normal number of patients with fever and respiratory/G.I. Complaints • Multiple people with similar complaints from a common location • An endemic disease appearing during an unusual time of year

  12. Clues to Bioterrorism • Unusual number of rapid fatal cases • Greater number of ill/dead animals • Rapid rising and falling epidemic curve • Greater numbers of patients with: • 1) Severe pneumonia • 2) Sepsis • 3) Sepsis with coagulopathy • 4) Fever with rash • 5) Diplopia with progressive weakness

  13. Standard Infection Control (I.C.) Precautions (for all bio-terrorist threats) • Wash hands and Wear gloves • Wear face shield • Wear cap/gown • Process contaminated equipment and linen • Clean and disinfect environmental surfaces • Adhere to occupational health and blood-borne pathogen requirements • Place patients at risk for environmental contamination in private or cohort location

  14. Airborne Infection Control (I.C.) Precautions (Smallpox and Hemmorhagic Fever) • Place patient in negative pressure room, when possible • Apply high-intensity air filter respiratory protection • Limit patient transport • Place tight sealing mask on patient when transporting

  15. Highest Concern CDC designated “A” List of Biologic Agents • Anthrax • Plague • Smallpox • Botulism • Tularemia • Viral Hemorrhagic Fever

  16. Investigation of Bioterrorism-Related Anthrax - United States, 2001 Epidemiologic Findings Epidemic curve for 22 cases of bioterrorism-related anthrax, U.S. 2001

  17. Epidemiological Investigation of Bioterrorism-Related Anthrax New Jersey, 2001 Blue box indicates cutaneous anthrax; Red box indicates inhalational anthrax

  18. Bioterrorism Related Anthrax - NJ, 2001 Patients Patient Status Conditions Kuser Road Hamilton officer worker West Trenton Postal worker Route 130 Hamilton Mail Processing Facility worker Route 130 Hamilton Mail Processing Facility worker Route 130 Hamilton Mail Processing Facility worker Route 130 Hamilton Mail Processing Facility worker Confirmed Cutaneous case by CDC on 10/29 Confirmed Cutaneous case by CDC on 10/18 Listed as Suspected* Cutaneous case by CDC on 10/18 Listed as Confirmed Cutaneous case 10/19 by PA Dept of Health Confirmed Inhalational case by CDC on 10/28 Confirmed Inhalational case by CDC on 10/29 Released from hospital and recovering Recovered Recovered Recovered Released from hospital and recovering Released from hospital and recovering *Suspected case

  19. Bacillus anthracis • Disease known for thousands of years • Organism first described in mid-1800s • Used as proof of Henle’s postulates by Koch • First vaccines developed by Greenfield and Toussaint; public demonstration by Pasteur in 1881 • Livestock and human vaccines

  20. Bacillus anthracis • Aerobic, spore forming, Gram-positive capsulated rod • The spore has a capacity to survive in the environment for decades • It is a relative of B cereus/thuringensis • Pathogenicity depends on two plasmids, pX01 & pX02

  21. Bacillus Anthrax Pathogenesis • Spore enters skin, GI tract, or lung • Germinates in macrophage locally or is • transported to regional lymph nodes • Local production of toxins leads to edema • and necrosis • Spread from node with bacteremia and • toxemia

  22. Bacillus Anthrax Toxin production • Protective antigen (PA) binds to host cell receptor • Furin cleaves and releases PA20 • PA63 forms a heptamer • The toxin enzymes bind to PA63 • Receptor-mediated endocytosis • Endosome acidification leads to • membrane insertion of PA63 • Translocation of toxic enzymes • into the cytosol; LF, lethal factor; • OF, oedema factor Nature (1997) 385:833-838

  23. Anthrax (Bacillus anthracis) Meningitis (Hemorrhagic CSF in 50%) Stridor Inhalational: Pleural Effusions Widened Mediastinum Hemorrhagic Mediastinitis Respiratory Distress Septic Shock Cyanosis Elevated WBC Edema Syndromes INFLUENZA PULMONARY Cough Chest Pain Dyspnea (G.I.): Nausea Bloody Diarrhea Abdominal Pain Myalgia Cutaneous: Painless, Necrotic Ulcers with Black Base (direct dermal contact) Early Symptoms Delayed Symptoms Fever, Malaise, Fatigue, Chills

  24. Anthrax (Inhalational) (bacillus anthracis) Characteristics Bio-warfare Mode: Aerosol Incubation Period: 1-6d (usually within 48hrs) Onset: Abrupt Duration: Days Lethality: High (80-90%) Transmission: Not transmissible person to person

  25. Anthrax (Inhalation) (Bacillus anthracis) Diagnosis Samples: Bld & spt cult, PCR Chest x-ray: mediastinal widening, pleural effusion, and pneumonia Differential: Tularemia, Plague, Diphtheria, Viral syndrome

  26. Anthrax (Inhalation) (bacillus anthracis) Mediastinal Widening Pleural Effusion

  27. Anthrax (Inhalational) (bacillus anthracis) Primary Therapy 1. Ciprofloxacin 400mg IV q 8-12h (Peds: 20-30mg/kg/d IV dosing up to 1 Gm). Consult ID for alternate quinolones. OR 2. Doxycycline 200mg IV (1dose) then 100mg IV q 8-12h x 4wk (Peds: 2.5 mg/kg IV q 12h) OR 3. *Penicillin G 4 million units IV q 4h (Peds: if<12y, PCN G 50,000U/kg IV q 6h; if > 12y, 4 million U IV q 4h) Amoxicilin 500mg q 8h in mass casualty setting * Was the therapy of choice, but due to documented resistance, should be used only if cultures are PCN-sensitive.

  28. Anthrax (Inhalational) (Bacillus anthracis) Alternate Therapy • Gentamicin, Erythromycin, Clindamycin, Chloramphenicol • Efficacy not evaluated by human or animal studies. • Therapy should continue for 60 days • Therapy may be decreased to 30-45 days if the full series of the vaccine has been given. • In mass-casualty settings, oral therapy with standard doses of Ciprofloxacin, Doxycycline, Amoxicillin may be utilized.

  29. Anthrax (Inhalational) (bacillus anthracis) Prophylaxis • Ciprofloxacin500mg PO bid x 4wk (8wk without vaccine) • Peds: 20-30mg/kg/d bid dosing up to 1 Gm/d • Levofloxacin500mg/d x 4-8wk (no Peds) • Ofloxacin400mg/bid x 4-8wk (no Peds) • Doxycycline100mg PO bid x 4wk (8wk without vaccine) • Peds:5mg/kg/d bid dosing • Amoxicillin40mg/kg/d up to 1500mg/d • Peds: Use tid dosing once cultures return as • PCN-sensitive • Vaccine0.5cc SQ @ 0,2, 4wk, then 6, 12, 18mo • Approved for patients between 18-65

  30. Anthrax (Inhalational) (bacillus anthracis) Isolation/Decon Precautions 1.) Victim: Undress, soap/shower for gross or visible contamination 2.) Responder/See Standard Infection Control Caregiver: (I.C.) Precautions. To protect from spores, respirators are needed. 3.) Environment: New methods are under investigation Equipment can be decontaminated with 1 part household bleach to 10 parts of water.

  31. Anthrax (Cutaneous) (Bacillus anthracis) Characteristics Bio-warfare Mode: Contact Incubation Period: 1-6d (usually within 48hrs) Onset: Abrupt Duration: Days Lethality: Without antibiotics, as high as 20%; with antibiotics, rare. Transmission: Low (cutaneous anthrax only)

  32. Anthrax (Cutaneous) (bacillus anthracis) This is a pathognomonic skin lesion … with a raised vesiculated edge, inflamed, and with a black base to the ulcer, eschar

  33. Anthrax (Cutaneous) (Bacillus anthracis)

  34. Anthrax (Cutaneous) (Bacillus anthracis)

  35. Pneumonic Plague Primary(Yersinia pestis) Syndromes INFLUENZA PULMONARY DERMATOLOGICAL Headaches Stridor Cough Dyspnea Vomiting Cramps Diarrhea Myalgia Bubo (dermal contact only) Acral Gangrene Meningitis (6%) (rare, mostly in children) Hemoptysis Patchy/Consolidated Infiltrates (pneumonia) Shock Cyanosis Hepatic Damage Elevated WBC, DIC Ecchymosis Purpura Petechiae Early Symptoms Delayed Symptoms Classic Symptoms Fever, Chills, Malaise

  36. Pneumonic Plague Primary(Yersinia pestis) Characteristics Bio-warfare Mode: Aerosol Incubation Period: 1-6 days (typically 2-3 days) Onset: Rapid Duration: 1-6 days Lethality: High (90-100%) without treatment within 24 hours of symptoms Transmission: High (person to person)

  37. Pneumonic Plague Primary(Yersinia pestis) Diagnosis Samples: Blood culture, sputum, CSF, lymph node biopsy Chest x-ray: Patchy bronchopneumonia, cavities, or confluent consolidation Differential: Tularemia, Cat Scratch Fever, Meningococcemia

  38. Pneumonic Plague Primary(Yersinia pestis) • Therapy • 1. Streptomycin15mg/kg bid IM x 10d (up to 1Gm bid) no pregnancy • OR • 2. Gentamicin5mg/kg IM or IV qd x 10d (Peds: 2.5mg/kg IM or IV tid) • OR • 3. Alternates: • Doxycycline100mg IV bid x 10d • (Peds: 2.2mg/kg IV bid, up to 200mg/d x 10d) • Ciprofloxacin400mg IV bid x 10d • (Peds: 15mg/kg IV bid up to 1Gm/d x 10d) • Chloramphenicol25mg/kg IV qid (may be added with Meningitis) • (Peds: 25mg/kg IV) • Therapy during Pregnancy • No streptomycin (same as non pregnant adults)

  39. Pneumonic Plague Primary(Yersinia pestis) Prophylaxis • 1. Doxycycline 100mg PO bid x 7d • (Peds: 5mg/kg/d bid dosing up to adult dose) • 2. Ciprofloxacin 500mg PO bid x 7d • (Peds: 20mg/kg PO bid) • OR • 3. Tetracycline 500mg PO qid x 7d • (Peds: 40mg/kg/d qid dosing) • 4. Alternates • Chloramphenicol 25mg/kg PO qid x 7d (available only outside • US and only to children above 2yrs) • TMP/SMX 20mg/kg Sulfa PO bid x 7d • (no longer recommended by many experts)

  40. Pneumonic Plague Primary(Yersinia pestis) Isolation/Decon Precautions 1. Victim: Undress, soap/shower Contain/discard contaminated clothing 2. Responder/ Standard Infection Control (I.C.) Caregiver: Procedures 3. Environment: Normal cleaning, pest control for fleas and rodent activity

  41. Background on Smallpox 1949 Last documented patient in U.S. 1972 Routine vaccination ends in U.S. 1977 Last documented patient in the world 1980 WHO declares smallpox eradicated 1990s United States military vaccinations ends 1990s-2001 United States debates destroying smallpox stores

  42. Electron micrographs of Variola, Varicella and Vaccinia virions Electron micrographs from top to bottom: Variola virion (forms M and C), Varicella virion and virion core, Vaccinia virion (forms M and C). DNA Virus Infections Vaccinia Smallpox (Variola Major) Poxviridae Infections Chickenpox Content Provider: CDC/Dr. James Nakano (1975) Source Library: PHIL

  43. Smallpox (Variola virus) Encephalitis Corneal Ulcers Delirium (15%) Bronchitis Pulmonary Edema Abdominal Pain Osteomyelitis Arthritis Headache Cough Rash (2-3 days later) 1) Erythema 2) Enanthem 3) Erythema from FACE/ARMS to LEGS then CENTRALLY 4) Macules Papules (1 wk) Pustular Vesicles (SYNCHRONOUS) Scabs (2-3wks) Syndromes INFLUENZA DERMATOLOGICAL Early Symptoms Delayed Symptoms Classic Symptoms Malaise, Fever, Rigors, Vomiting, Backaches

  44. Smallpox (Variola virus) Characteristics Bio-warfare Mode: Aerosol Incubation Period: 17d (10-12d) Onset: Abrupt Duration: 4 weeks Lethality: Moderate (20-40% in unvaccinated; 3% in recently vaccinated) Transmission: High (person to person)

  45. Smallpox (Variola virus) Diagnosis Samples: Pharyngeal swab, scab matter, serum Differenial: Varicella (Chicken pox), Erythema Multiforme, Contact Dermatitis

  46. Smallpox (variola virus) A case of ordinary discrete type

  47. Smallpox (Variola virus)

  48. Differentiating Smallpox (variola) from Chickenpox (varicella) CharacteristicsSmallpox Chickenpox (varicella) Febrile prodrome Severe, 1-4 days Rare in children; older before rash; systemic children and adults may have mild fever, malaise 1-2 days before rash Appearance lesions Hard/firm, well- Superficial vesicles, circumscribed pustules; surrounding erythema may become confluent umbilicated Stage of lesions All in same stage on Different stages (within any part of body 24 hours rash onset papules, vesicles, crusts

  49. Differentiating Smallpox (Variola) from Chickenpox (Varicella) Characteristics Distribution Initial lesions Oral lesions Severity Illness Smallpox Centrifugal (face and extremities; fewer lesions on trunk) Oral mucosa, face, forearms Yes -- early on Very ill; toxic Chickenpox Centripetal (trunk; fewer lesions on extremities, face and scalp) Face and trunk May occur Most not severe; rarely critically ill unless complications develop

  50. Differentiating Smallpox (Variola) from Chickenpox (Varicella) Characteristics Rate evolution rash Lesions on palms or soles Hemorrhagic lesions Exposure to varicella or herpes zoster History of prior chickenpox Smallpox Slow; each stage 1-2 days In majority of cases In highly lethal variant N/A N/A Chickenpox Rapid; macules papules crusts in <24 hours Rare Can occur 50-80% cases aware of exposure 10-21 days before rash onset Second cases very rare--makes varicella less likely

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