UCLA Center for Public Health and Disasters Bioterrorism

UCLA Center for Public Health and Disasters Bioterrorism Training for Physicians Updated March 2003 Over 1700 Downloads Since Going Online October 2001 Available at: http: //www. ph. ucla. edu/cphdr/bioterrorism

BIOTERRORISM: Are You Prepared?

Bioterrorism 101 Why is this a problem? Who and what are the agencies worrying about?

Biological Terrorism Intentional or threatened use of viruses, bacteria, fungi or toxins from living organisms to produce death or disease in humans, animals or plants

Anthrax Mail Attacks - 2001

Biological Terrorism – Why? Small amounts – devastating effects Invisible, odorless, tasteless Easy to obtain Difficult to detect Civilian populations unprotected Delayed onset - difficult to trace Publicity, fear, chaos

What Happens in a Bioterrorism Incident? That depends on whether the attack is: OVERT or COVERT

Overt Attack Threat Validation Coordinated System Response Traditional First Responders: Fire, Police, EMS Hospitals Community Practitioners Public Health - Information Management Law Enforcement

Overt Attack Problems: Verifying if an attack has taken place Fear, chaos Large numbers of “worried well” Decontamination Limited supply of treatment, prophylactic drugs, and vaccines

Real or Hoax? Public health and law enforcement will determine credibility, and need for decontamination or prophylaxis Test results may take 24 -48 hours

Covert Attack EMS system may be used by cases (not yet recognized as a bioterrorist event) Likely detected through hospitals, medical care practitioners Clinical labs contact local PH department refers to State or CDC

Covert Attack Problems with recognition: Symptoms overlap common illnesses Delayed onset of symptoms Victims present to different centers Secondary spread may occur before attack is recognized

Likely Scenarios Aerosol release Major city, large event, or key function Victims presenting to different centers Recognition of attack through symptoms, epidemiologic patterns or microbio lab

Aerosol Delivery Considered the most likely route for BT Aim is to generate invisible clouds of particles 0. 5 -10 microns in diameter Can stay suspended for long periods of time Perfect size to reach the alveoli in lungs Aerosols of most agents produce systemic disease

Key Indicators of a BT Event Sudden increase in severity or incidence of illness Appearance of unusual (non-endemic) illness or syndrome in your community Geographic and/or temporal pattern of illness Occurrence of vector-borne disease where there is no vector

Key Indicators of a BT Event Cluster of sick or dead animals Atypical seasonality Unusual expression of endemic disease Multi drug-resistant pathogens

Bioterrorism: The Agents Category A: Top Priority Easily disseminated or transmitted High mortality Causes social disruption Special preparation needed Category A Agents: Anthrax Botulism Plague Smallpox Tularemia Viral Hemorrhagic Fevers

Bioterrorism: The Agents Category B Q Fever Brucellosis Viral encephalitides Staphylococcal enterotoxin B Food/Waterborne Ricin Category C Nipah virus Hantavirus Tickborne hemorrhagic fever Yellow fever Multidrug-resistant TB

Overview of the Agents: Clinical Manifestations and Treatment

Pneumonic Syndromes: Inhalational Anthrax Pneumonic Plague Pneumonic/Typhoidal Tularemia

Anthrax Source: Bacillus anthracis Bacterial spores and toxins Cutaneous, inhalational and intestinal

Cutaneous Anthrax

Cutaneous Anthrax Incubation 1 -12 days Papule > vesicle or ulcer > black center over several days Diagnosis: Gram stain and culture of unroofed vesicle, base of ulcer, under edge of eschar Usually responds well to treatment

Inhalational Anthrax Incubation: 1 - 6 days (rarely up to > 60 days) Prodrome: 1 -2 d fever, malaise, dry cough Severe respiratory distress, septic shock, may have meningitis Diagnosis Hemorrhagic mediastinitis – wide on CXR Isolation Standard; not contagious

Inhalational Anthrax: Mediastinal Widening

Anthrax vs. Viral Illness Anthrax Elev. Temp 70% Cough 90 SOB 80 Pleuritic Pain 60 Headache 50 Sore Throat 20 Rhinorrhea 10 Nausea / Vom. 80 MMWR Nov 9 2001; 50: 984 Flu Other Viral 68 -77% 40 -73% 84 -93 72 -80 6 6 35 23 84 -91 74 -89 64 -84 79 68 12 12

Evaluation of Possible Inhalation Anthrax History of exposure or risk + Symptoms: WBC (bandemia), Blood culture – highest yield ü CXR – wide mediastinum, effusion, or infiltrate Consider CT if CXR normal ü If results abnormal or pt. seriously ill: Multi-drug treatment If results normal and pt mildly ill: Observe and initiate single-drug prophylaxis

Anthrax - Treatment Combination Rx for seriously ill: Cipro or Doxy + other drug(s) Other drugs with activity include: Rifampin, Vancomycin, Clindamycin, Imipenem, Clarithromycin, PCN Post-Exposure Prophylaxis: Cipro or Doxy X 60 d (X 30 d if given with vaccine)

Anthrax Exposure? Most patients need only reassurance Higher risk: Threatening message Sandy brown color powder Suspicious letter or package High-profile person or postal worker If exposure is credible, contact police Nasal swab NOT sensitive enough to r/o exposure for an individual

Plague Source Bacterium: Yersinia pestis Forms Bubonic, septicemic, and pneumonic** ** Suspect Bioterrorism

Pneumonic Plague Incubation: 2 -3 d Symptoms Fulminant pneumonia, bloody sputum, septic shock, high fever, chills, headache, possible disseminated intravascular coagulation Diagnosis Laboratory: Gram stain blood, sputum, node Small, Gram-neg, bipolar (‘safety-pin’), poorly staining coccobacilli

Pneumonic Plague Isolation Highly contagious Strict respiratory isolation until Rx for 3 d Followed by standard respiratory droplet precautions (masks, gown, gloves, eye protection) Treatment Streptomycin, doxycycline, or chloramphenicol High mortality, but may respond to early treatment

Tularemia Source Bacterium: Francisella tularensis Gram neg. coccobacillus Zoonotic (‘rabbit fever’) Forms Ulceroglandular and typhoidal/pneumonic** **Suspect Bioterrorism

Tularemia Incubation: 2 -10 days Prodrome: Fever, headache, chills, myalgia, cough, nausea, vomiting, diarrhea May present as pneumonia Diagnosis Laboratory: Culture/Gram stain blood, sputum, node Culture can be difficult and is risky to lab personnel

Tularemia Isolation Standard; not contagious No human-human transmission Treatment Streptomycin, gentamicin, or doxycycline If exposed: watch for 7 days, treat if fever develops Vaccine under review by FDA Mortality 30% untreated; < 10% treated

Paralytic Syndrome: Botulism

Botulism Source: Clostridium botulinum neurotoxin Types A, B, E, and F Most potent toxin known Lethal dose 1 ng/kg 100, 000 times more toxic than sarin

Botulism Incubation: 1 -5 days Symptoms Blocks cholinergic synapses Dry mouth, blurred/diplopia, muscle weakness, dysphagia Descending flaccid paralysis can last for weeks to months Diagnosis Clinical A few labs can do serum toxin assay Death from respiratory failure

Botulism Isolation Standard; not contagious No human-human transmission Decontaminate clothing, skin with soap and water Treatment Ventilatory support Botulinum antitoxin - equine Skin test for horse serum sensitivity More effective if given early – will not reverse paralysis that has already occurred

Rash and Fever Syndromes: Smallpox Viral Hemorrhagic Fevers

Smallpox: Variola major

Smallpox: Presentation Incubation: ~ 12 days (up to 17 days) Early symptoms nonspecific Fever, malaise, aches for 2 -4 days; then severe illness Rash then appears on extremities with uniform appearance Scabs over in 1 -2 weeks Contagious until ALL scabs have fallen off

Smallpox Notify Public Health IMMEDIATELY Diagnosis Laboratory Rule out chickenpox – PCR Isolation Strict contact and respiratory isolation (negative pressure) Trace contacts up to 17 days prior to illness Treatment None known effective Questionable effectiveness of Cidofovir Mortality ~ 30%

Smallpox vs. Chickenpox Incubation Prodrome Distribution Progression Scab formation Scab separation Variola 7 -17 d 2 - 4 d extremities similar growth 10 -14 d p rash 14 -28 d p rash Varicella 14 -21 d minimal/none trunk dissimilar growth 4 -7 d p rash <14 d p rash

Smallpox vs Chickenpox Rash: extremities, uniform size Rash: trunk, different stages of development

Smallpox Vaccine Live Vaccinia virus Given intradermal on bifurcated needle Pustule – scab in ~ 1 week, mild fever Can potentially spread to others until scab is gone Lifelong immunity is questionable Vaccinated persons probable reduced risk of mortality Vaccine is effective up to several days AFTER exposure

Administering the Vaccine

Vaccinia: Common Reactions Sore arm Adenopathy Fever Up to 1/3 may have reactions severe enough to miss work, school, or usual activities

Smallpox Vaccine - Reactions Risks for primary vaccinees: Accidental Inoculation: > 500 / million Generalized Vaccinia: 242 / million Eczema Vaccinatum: 12 – 39 / million Progressive Vaccinia: 1 – 2 / million Encephalitis: 3 – 12 / million Death: 1 - 2 / million Risks are much less if previously vaccinated

Vaccinia Immune Globulin-VIG Primary treatment for adverse reactions Produced from plasma of vaccinated individuals Stored at CDC IM forms only at present Indications for use Eczema vaccinatum Progressive vaccinia Accidental implantations (extensive lesions) Generalized vaccinia(severe) Not recommended in vaccinia keratitis

Accidental Inoculation

Generalized Vaccinia

Eczema Vaccinatum

Progressive Vaccinia

Fetal Vaccinia

Viral Hemorrhagic Fever (VHF) Ebola Lassa Marburg Sabia: Brazilian HF Machupo: Bolivian HF Rift Valley Fever Crimean-Congo HF Ebola virus

Viral Hemorrhagic Fever Incubation: 4 -21 days Symptoms vary between viruses Fever, myalgia, prostration Petechiae, hemorrhage, shock Neurologic, pulmonary, hepatic involvement Mortality varies: 10 – 90%

Viral Hemorrhagic Fever Diagnosis Primarily clinical Viral isolation, serology, immunohist. at CDC Isolation Strict contact isolation Strict respiratory isolation Strict bodily fluid isolation

Viral Hemorrhagic Fever Treatment Supportive Fluids, transfusion Watch for pulmonary edema Avoid unnecessary lines, procedures, etc. Ribavirin may be effective for Lassa, Bolivian HF, Crimean-Congo HF, Rift Valley Fever

Risk of Secondary Transmission Agents to worry about: Smallpox Plague Viral Hemorrhagic Fever Isolation is critical if any of these are suspected Notify hospital infection control immediately

Bioterrorism Agents: Decon For most agents, it is very unlikely that anyone would be infected from clothing, skin, etc. Decon when there is: Gross contamination by dust, powders, spray, etc. A body fluid agent, such as in the case of Ebola Generally, no special equipment needed Remove clothing and seal it in plastic bag Shower with soap & water

Laboratory Risks of BT Agents Agent BSL Laboratory Risk B. anthracis Y. pestis 2 low 2 medium Botulinum toxin 2 medium F. tularensis 2/3 high Smallpox 4 high Viral Hemorrhagic Fever 4 high

Laboratory Response Network for Bioterrorism

Special Problems with BT Identifying a covert attack Social disruption Prophylaxis for large populations National Pharmaceutical Stockpile (NPS) Vaccination plans Secondary transmission

Special Problems with BT Specialized labs needed for some agents Risks to laboratory workers Communication between agencies

Limited Health Care Resources Isolation rooms Ventilators Protective Equipment Medications Vaccines Morgue facilities

Challenges in Recognizing a Bioterrorist Attack Delayed onset - hours to weeks Early signs/symptoms nonspecific Physicians/laboratorians not familiar with rare diseases/organisms Current public health surveillance may not be adequate for early detection

Early Detection of a BT Event: Finding a Zebra Among Horses Early detection and control of bioterrorism will depend on alert clinicians reporting unusual illnesses or patterns of illness to Public Health BEFORE definitive diagnosis When you hear hoof beats, think “zebras” (as well as horses)

Public Health Bioterrorism Surveillance Plan Enhance traditional surveillance for all potential BT agents and unusual illnesses Novel surveillance methods Hospital diversion data Medical examiner data Syndrome-based ER/ICU admissions School absences Animal disease surveillance Pharmacy sales

Agencies Responding to a BT Attack Local Public Health Police, Fire, EMS State Public Health Disaster management National Guard Federal CDC FBI, Dept of Justice Homeland Security, FEMA Dept of Defense

BT Hospital Preparedness Issues Develop plans for: Infection control Lab support A large influx of patients: triage, pt placement, pt transport Pharmacy inventories Psychological aspects of BT

BT Hospital Preparedness Issues Develop plans for: Hospital Emergency Incident Command System (HEICS) Internal and external communication Evidence collection Discharging or post-mortem care Decon

Preparation for a BT Attack Familiarize medical staff with BT agents Incorporate into disaster planning Infection control and decontamination Communication plan with key agencies: Public Health Dept Laboratory, CDC, police, FBI, etc. Identify contacts to obtain stockpiled supplies: antibiotics, immune sera, vaccines, antidotes, decon equipment, PPEs, etc. Security preparations

Local Health Department Actions Determine whether situation is “unusual” Case finding/case investigation Laboratory confirmation Alert medical community Identify source of outbreak and at-risk persons Coordinate with State DHS, CDC, FBI, and other authorities

Public Health’s Role in Bioterrorism Event Incorporation of State Epidemiology BT Materials Epi/surveillance Labs Notification Media/Public Information Officer (PIO) Integration with FBI Integration with CDC

Public Health’s Role in Bioterrorism Event Infectious Disease/epidemiology tracks infectious diseases Public Health Laboratories identify agents (either in-house or through referral to State or CDC) Environmental Health assesses sanitation and safety of food and water

Public Health’s Role in Bioterrorism Event Health Officer coordinates information for the public and medical providers Community Health and PH nurses provide education, information to the public and to community providers Treatment and prophylaxis Quarantine

What To Do if You Suspect a Bioterrorist Disease IMMEDIATELY NOTIFY: Hospital Infection Control Isolation: Smallpox, plague, hemorrhagic fevers Laboratory Hospital Administration Local Public Health Department

Case Studies

Case 1 - Dyspnea, Hypotension 46 year old stock trader Fever, malaise, cough 2 days prior Abrupt onset severe dyspnea 38. 1 o 115 86/40 32 O 2 sat 83% Diaphoretic, Disoriented CXR - no infiltrate, + small pleural eff.

Mediastinal Widening

Case 1 - Dyspnea, Hypotension Patient admitted to ICU: Fluids, Intubation, Ceftriaxone, Vanco. , Gent. Later the same day a similar patient presents Also a stock trader in the same building Both patients deteriorate and die the next day

Case 2 - Rapid Progressive Pneumonia 10 y/o boy with fever, dry cough for 1 day 8 y/o sister also ill VS 38. 6 o 110 96/60 91% sat Scattered crackles in both lungs CXR - Bilateral infiltrates Later develops severe dyspnea, hemoptysis, shock

Case 3 - Fever 52 y/o male c/o 3 days malaise, fever, vomiting, myalgias 39. 1 o 92/50 124 28 WBC 18 platelets 45 BUN 48 Creatinine 2. 9 Within hours becomes confused, vomits blood

Case 4 – Vesicular Rash 34 y/o woman with fever, malaise X 2 days Today, a rash appeared 39. 4 o 106/78 116 18 A & O X 3 Lungs clear

Case 5 - Overt Attack A terrorist group says they have released 10 kg of botulinum toxin over your city Clostridium botulinum neurotoxin Lethal dose 1 ng/kg

Bioterrorism Addendum A: Selected Category B and C Agents

Q Fever Source Bacterium: Coxiella burnetii Resistant to heat, drying and many common disinfectants Incubation 10 -40 d Sx variable - Fever, HA, myalgia, malaise Occ. cough, rales, CXR infiltrate WBC usually normal, but FTs common L Low mortality, but malaise may last months

Q Fever Diagnosis Laboratory: serology, antibody or ELISA Isolation: Standard Treatment Antibiotics will shorten course Tetracyclines Erythromycin, azithromycin, quinolones, Chloramphenicol, TMP/SMX

Brucellosis Source Brucella species Zoonotic Slow-growing gram negative rod Presentation: Incubation 5 -60 d or longer May last weeks or months, but rarely fatal

Brucellosis Diagnosis Serology; Culture of bone marrow, liver or spleen tissue Isolation Standard Contact if open lesions Treatment Combination antibiotics Most recover even without antibiotics

Viral Encephalitis Alphaviruses: Venezuelan, Eastern, Western Equine Encephalitis Presentation: Incubation 2 -14 d Fever, HA, myalgia, photophobia, vomiting Small % of VEE progress to neurologic Sx Delirium, coma, seizures

Viral Encephalitis Diagnosis Viral isolation or serology, PCR for some Isolation: Standard Treatment Supportive analgesics, anticonvulsants Vaccines available, but poorly immunogenic

Ricin

Ricin Source Derived from castor beans (Ricinus communis) 1 million tons of castor beans produced annually worldwide 5% ricin by weight Stable Inhibits protein synthesis via ribosome Toxic via inhalation, ingestion, injection

Ricin was used to assassinate Bulgarian exile Georgi Markov in London in 1978. A weapon disguised as an umbrella was used to implant a ricincontaining pellet

Ricin Symptoms begin in 4 -8 hours: Weakness, fever, cough, hypothermia, sweating Inhalation Severe respiratory symptoms from necrosis and edema, hypoxia with respiratory failure in 36 -72 hours Ingestion Nausea, vomiting, diarrhea, GI hemorrhage, vascular collapse, death in 3 d May cause DIC, multi-organ failure

Ricin Diagnosis Serum ELISA available in few labs Treatment Primarily supportive: O 2, hydration If ingested: Gastric lavage Activated charcoal

Staphylococcal Enterotoxin B Presentation: Incubation 1 -6 hrs Diagnosis Clinical and epidemiological Isolation: Standard Treatment Supportive

Clostridium perfringens Toxin Source Episilon toxin of Clostridium perfringens Organism ubiquitous in soil Present in stool of every vertebrate Can produce gas gangrene, necrotizing enterocolitis, food poisoning Secretes > 12 toxins Could be toxic if inhaled or ingested

C. perfringens Toxin Symptoms within hours GI symptoms prominent, rare fever If inhaled, could cause resp. distress Mortality Death is rare Could result from vascular leaks, lung damage

C. perfringens Toxin Diagnosis: Clinical Stool tests for enterotoxin are not widely available Treatment Supportive Antibiotics active against organism: penicillin, clindamycin

Trichothecene Mycotoxins Source Group of > 40 fungal toxins Produced by Fusarium, other common fungi Stable to heat and UV Inhibits protein and nucleic acid synthesis affecting rapidly proliferating tissues If aerosolized, appears as yellow droplets, “yellow rain” Toxic via inhalation, ingestion, and skin

Trichothecene Mycotoxins Symptoms: onset minutes to 4 hours Skin blistering, eye irritation, nose/throat pain, Cough, dyspnea, chest pain, hemoptysis Abdominal pain, vomiting, bloody diarrhea Bone marrow suppression can lead to diffuse hemorrhage If severe: prostration, ataxia, shock and death in hours to days

Trichothecene Mycotoxins Diagnosis: Urine, blood, tissue samples for liquid chromatographymass spectrometry in specialized labs Treatment: Supportive Remove and isolate clothing, irrigate eyes, wash with soap/water If ingested, Activated charcoal ? Benefit of ascorbic acid, dexamethasone

Case 1 – Headache, Vomiting 39 y/o woman presents with 2 d worsening HA, nausea, vomiting, fever, malaise Better after fluids, acetaminophen and is released Returns following day with confusion, seizure

Case 2 – Vomiting, Diarrhea Multiple patients present to ER with: Vomiting, diarrhea, headache, myalgias, malaise, fever, chills, cough All had been at a large outdoor festival

Case 3: Malaise High numbers of people present to ERs and clinics over several weeks in Nov. - Dec. Fevers, malaise, cough, headaches Some have pneumonia on CXR Most have elevated LFTs Public health department finds no influenza or other pathogens

Bioterrorism Addendum B: Additional Resources and References

Additional Web Resources Centers for Disease Control and Prevention (CDC) www. bt. cdc. gov US Army Medical Research Institute on Infectious Disease (USAMRIID) www. usamriid. army. mil World Health Organization (WHO) Communicable Disease Surveillance and Response (CSR) www. who. int/emc/

Additional Print Resources Emergency Medicine Clinics of North America May 2002 (entire issue devoted to bioterrorism) Kortepeter MG and Parker GW. Potential biological weapons threats. Emerging Infectious Diseases. 1999; 5: 523 -27. Inglesby TV et al. Anthrax as a Biological Weapon, 2002: Updated Recommendations for Management. JAMA. May 01, 2002; 287(17): 2236 -2252. Arnon SS et al. Botulinum Toxin as Biological Weapon: Medical and Public Health Management. JAMA. Feb 8, 2001; 285(8): 1059 -1070, 2081. Inglesby TV et al. Plague as a Biological Weapon: Medical and Public Health Management. JAMA. May 03, 2000; 283(17): 2281 -2290.

Additional Print Resources Henderson DA et al. Smallpox as a Biological Weapon: Medical and Public Health Management. JAMA. June 09, 1999; 281(22): 2127 -2137. Dennis DT et al. Tularemia as a Biological Weapon: Medical and Public Health Management. JAMA. June 02, 2001; 285(21): 2763 -2773. Borio L et al. Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management. JAMA. May 08, 2002; 287(18): 2391 -2405. Franz DR, Jahrling PB, Friedlander DJ et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997; 278(5): 399 -411.

Additional Print Resources Bryan JL, Fields HF. An ounce of prevention is worth a pound of cure – shoring up the public health infrastructure to respond to bioterrorist attacks. Amer J of Infection Control. 1999; 27: 465 -7. CDC. Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response. Recommendations of the CDC Strategic Planning Workgroup. MMWR. April 21, 2000, Vol 49, No. RR-4. Wetter DC, Daniell WE and Treser CD. Hospital preparedness for victims of chemical or biological terrorism. Amer J of Public Health. 2001; 91(5): 710 -16.

Additional Print Resources Pavlin J. Epidemiology of bioterrorism. Emerging Infectious Diseases. 1999; 5: 528 -530 Macintyre AG, Christopher GW, Eitzen E et al. Weapons of Mass Destruction Events with Contaminated Casualties: Effective Planning for Health Care Facilities. JAMA. 2000; 283: 242 -249. Meltzer MI, Damon I, Le. Duc JW, and Millar JD. Modeling potential responses to smallpox as a bioterrorist weapon. Emerging Infectious Diseases. 2001; 7(6): 959 -969. Di. Giovanni C Jr. Domestic terrorism with chemical or biological agents: psychiatric aspects. Am J Psychiatry 1999; 156: 1500 -5.

UCLA Center for Public Health and Disasters 1145 Gayley Avenue, Suite #304 Los Angeles, CA 90024 Tel: 310/794 -0864 Fax: 310/794 -0889 Email: cphdr@ucla. edu http: //www. ph. ucla. edu/cphdr