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Biological Threats Robert Geller, MD, FAAP, FACMT Medical Director, Georgia Poison Center; Chief, Pediatrics, Hughs Spalding Medical Center Case Presentation • A 25-year-old male patient presents with fever, chills and malaise. • He also complains of an unusual rash… • As you prepare to see him, your colleagues say that they have seen 5 patients today with a similar presentation. 2 COULD THIS BE A BIOTERRORIST EVENT? 3 Chemical versus Biological Event • Chemical – Rapid onset (obvious) – Field first response • Police and Fire • EMS – Decon critical – Antidotes • Biological – Slow onset (insidious) – Medical response • Hospital • Office – Decon usually not needed – Antibiotics and vaccines 4 5 Relative cost of Terrorism Agents • • • • Cost per km2: Conventional $2000 Nuclear $800 Chemical $600 Biological $1 Biological Weapons are Dirt-Cheap! Early Biological Warfare • 1941 - Unit 731 spread plague in China, killing tens of thousands • 1979 - explosion at a plant in Sverdlosk was followed by a massive outbreak of anthrax • 1978 death of Georgi Markov from ricin Bubonic plague - cause of the end of the Roman Empire? 7 “Advantages” of Biological Agents as Weapons • Large quantities of weapon material can be produced in a short period of time • Access to biological agents not difficult – Aum Shinrikyo cult in Zaire • Lower level of technical training required* . • Psychological impact considerable 8 Domestic Biological Terrorism • 1984: The Dalles, Oregon, Salmonella (salad bar) • 1997: Washington DC, “Anthrax” (hoax) • 2001: US Anthrax Mailings 9 Biological Agents • Bacteria • Anthrax • Plague • Tularemia • Viruses • Smallpox • Filoviruses • Toxins • Botulinum • Ricin Mechanisms of Exposure • Aerosol (Primary or Secondary) – Primary route of exposure – Must be dispersed in particles 1-5 microns in diameter • Ingestion • Cutaneous 11 CDC Agent Classification Basis for classification – Public health impact based on illness and death; – Delivery potential – Public perception – Special public health preparedness needs 12 CDC Agent Classification • Category A – – – – Easily disseminated or transmitted person to person Cause high rates of mortality Could cause public panic Requires special attention and public health awareness • Category B – Moderately easy to disseminate – Moderate morbidity and lower mortality – Require enhanced disease surveillance • Category C – Emerging pathogens; based on availability, ease of production and dissemination, and potential for high morbidity and mortality 13 CDC Category A agents • Bacillus anthracis (anthrax) • Clostridium botulinum toxin (botulism) • Yersinia pestis (plague) • Francisella tularensis (tularemia) • Variola major virus (smallpox) • Ebola, Marburg, Lassa, and South American hemorrhagic fever viruses (viral hemorrhagic fever) 14 CDC Category B and C Agents • Category B agents – – – – – – – – – – – • Category C agents – emerging infectious diseases including; Coxiella burnetti (Q fever) Brucella species (brucellosis) Burkholderia mallei (glanders) Alphaviruses (VEE, EEE, WEE, WNE) Ricin toxin Staphylococcus enterotoxin B Foodborne or waterborne agents Meliodosis Cl. Perfringens epsilon toxin Psittacosis Typhus – Nipah virus – Hantaviruses – Tickborne hemorrhagic fever viruses – Tickborne encephalitis viruses – Yellow fever virus – Multidrug-resistant Mycobacterium tuberculosis 15 Clinical Effects of These Agents “Flu-like” illness (fever, sweats, nausea) Cough and/or pneumonia Skin ulcers (anthrax, tularemia, plague) Rashes (smallpox, Ebola) Paralysis (botulism) Diarrhea & vomiting (food- and water-borne agents) • Headache, confusion • • • • • • 16 Anthrax: Overview • Hardy spore exists in soil reservoir • Humans “naturally” infected by contact with infected animals or contaminated animal products • No person-to-person transmission of inhalational anthrax • Last naturally-occurring U.S. case of inhalation anthrax in 2006 CDC 17 Anthrax: Case Definition • An illness with acute onset characterized by several distinct clinical forms – Cutaneous: papule Æ vesicle Æ necrotic lesion (most common) – Pulmonary: highly fatal, hemorrhagic mediastinitis – Intestinal: abdominal pain, fever, septicemia – Oral: mouth, pharynx, lymph nodes 18 Anthrax: Laboratory Diagnosis • Isolation – blood, lung or spinal fluid, skin lesion • Positive serology • Immunofluorescence in clinical specimen • Nasal swabs & serology – for assessing exposure in epidemiologic investigation 19 Inhalational Anthrax: Clinical Features • Incubation period: 1 to 43+ days • Initial flu-like symptoms typically appear in 2-5 days • Late symptoms – Lung hemorrhage, shortness of breath – Possible meningitis – Rapid progression to shock, death 20 Cutaneous Anthrax Clinical Progression Day 5 Day 10-12 Day 7 Day 15 21 CDC Inhalational Anthrax Anthrax: Treatment and Prophylaxis • Treatment of cases – Antibiotics for 100 days – Double or triple therapy for inhalational anthrax or cutaneous anthrax with systemic manifestations • Prophylaxis for those exposed – Antibiotics for 60 – 100 days • Ciprofloxaxin or doxycycline 23 Anthrax: Summary of Key Points • The most likely presentation of anthrax in a BT attack is inhalational disease; cutaneous disease is also possible • Early in the course of illness, inhalational anthrax is not easily distinguished from an influenza-like illness due to other causes • Antibiotic prophylaxis can be used to prevent development of disease in infected persons • Anthrax is not transmitted person to person 24 Plague: Epidemiology • Caused by Yersinia pestis – Gram negative bacillus • About 10-15 cases/year U.S. (mainly SW states) • Human plague occurs from bite of an infected flea (bubonic) or rodent • Only pneumonic form of plague is spread person-toperson 25 Plague: Clinical Forms • Bubonic plague – Most common naturallyoccurring form – Mortality 60% untreated, <5% treated • Septicemic plague • Pneumonic plague – Most likely BT presentation – From aerosol or septicemic spread to lungs – Survival unlikely if treatment not initiated w/in 24 hours of the onset of symptoms 26 27 Bubonic Plague • Incubation: 2-8 days • Sudden onset nonspecific symptoms: fever, chills, malaise, muscle aches, headache • Painful Regional lymphadenitis (buboes) • Diagnosis: Culture 28 Plague: Medical Management • Antibiotic therapy (Streptomycin, Chloramphenicol, Tetracycline • Supportive therapy • Isolation with droplet precautions for pneumonic plague • Vaccine no longer available 29 Plague: Key Points • The most likely presentation in a BT attack is pneumonic plague. • Unlike other forms of plague, pneumonic plague is transmitted person to person, and thus respiratory droplet precautions are indicated in suspected cases until 48 hours after the initiation of antibiotic therapy. 30 Other Category A Agents • Tularemia • Viral Hemorrhagic Fevers • Botulism 31 Tularemia • Causative agent Francisella Tularensis • Bacterium found in diverse animal hosts 32 Tularemia Epidemiology Human infection: – Handling contaminated animal tissues or fluids – Bite of infective deer flies, mosquitoes, or ticks – Direct contact with or ingestion of contaminated water, food, or soil – Inhalation of infective aerosols (most likely BT route) – No person-to-person transmission – About 200 cases/year in the U.S. 33 Tularemia: Clinical Features – – – – Intestinal (intestinal pain, vomiting, diarrhea) Pneumonic* (primary pleuropulmonary disease) Typhoidal (febrile illness without early localizing signs & symptoms Cutaneous lesions *most likely BT presentation MMWR 1997;46(RR-10) 34 Cutaneous exposure to F. Tularensis 35 Pneumonic Tularemia: Clinical Features • Initial clinical picture: systemic illness with prominent signs of respiratory disease • Abrupt onset fever, chills, headaches, muscle aches, nonproductive cough, sore throat • Nausea, vomiting, diarrhea in some cases • Mortality 30% untreated; < 10% treated 36 Tularemia: Summary of Key Points • Naturally occurring tularemia virtually always occurs in a rural setting. • Tularemia is not transmitted person to person • The most likely presentations of tularemia in a BT attack are pneumonic and typhoidal disease, as opposed to naturally occurring cutaneous cases • Tularemia can be treated and prevented with antibiotics 37 Smallpox: Overview • WHO declared smallpox eradicated in 1980 • No effective treatment • Person-to-person transmission (aerosol/contact) • Two strains: variola major and variola minor – Variola minor – milder disease with case fatality typically 1% or less – Variola major – more severe disease with average 30% mortality in unvaccinated 38 Findings: Pustules in same stage 39 Smallpox: Clinical Features • Incubation: 12-14 d (range 7-17 d) • High fever, malaise, headache, backache, prostration – Delirium 15% • Rash starts on face and forearms → trunk and legs • Crusts at day 8-9, scabs separate leaving scars CDC Lesions most abundant on face and extremities, including palms/soles 40 41 Smallpox: Medical Management • Isolation • Antibiotics: – Secondary bacterial infections • Supportive care • Protect yourself 42 Smallpox Vaccine • Made from live Vaccinia virus – • • ~ 200 million doses in U.S. stockpile Intradermal inoculation with bifurcated needle (scarification) Immunity not life-long WHO 43 Smallpox: Vaccination Complications • Most common outcome – Inadvertent inoculation (skin, eye) • Primary vaccination - 1 death/million* • Revaccination - 0.1 deaths/million* 44 Smallpox: Summary of Key Points • transmitted person to person: airborne precautions should be initiated in all suspected cases • infectious from the onset of rash until all scabs have separated. • smallpox vs. chickenpox: differences in lesion progression and distribution, illness course and presence of a febrile prodrome. 45 Viral Hemorrhagic Fevers CDC: Electron micrograph of Ebola virus Viral Hemorrhagic Fevers • Diverse group of viral illnesses • Potential for aerosol dissemination, with human infection via respiratory route (except dengue) • Target organ: vascular bed • Case fatality 0.5 - 90%, depending on agent • Natural vectors virus specific – rodents, mosquitos, ticks • Person-to-person transmission possible – fluids, air (rare) 47 Viral Hemorrhagic Fevers: Summary of Agents Virus Family Virus/Syndrome Geographic occurrence Reservoir or Vector Humanhuman transmission? Arenaviridae Junin (Argentine HF) S.America Rodents Machupo (Bolivian HF) S.America Guanarito (Brazilian HF) S.America Lassa Fever – yes, via body fluids; others – not usually Sabia (Venezuelan HF) S.America Lassa (Lassa Fever) West Africa Yellow Fever Tropical Africa,Latin America Mosquitoes Dengue Fever Tropical areas Yellow Fever – blood infective up to 5d of illness; Others - No Kyanasur Forest Disease India Omsk HF Siberia Flaviridae Ticks 48 Viral Hemorrhagic Fevers: Summary of Agents (cont.) Virus Family Virus/Syndrome Geographic occurrence Reservoir or Vector Human-human transmission? Bunyaviridae Congo-Crimean HF Crimea, parts of Africa, Europe & Asia Ticks Rift Valley Fever Africa Mosquitoes Hantaviruses (Hemorrhagic Renal Syndrome/ Hantavirus Pulmonary Syndrome) Diverse Rodents Congo-Crimean Hemorrhagic Fever – yes, through body fluids; Rift Valley Fever, Hantaviruses – no Ebola HF Africa Unknown Marburg HF Africa Filoviridae Yes, body fluid transmission 49 VHF Surveillance: Clinical Identification of Suspected Cases – Temperature 101°F(38.3°C) for <3 weeks – Severe illness and no predisposing factors for hemorrhagic manifestations – 2 or more of the following: • • • • • • Hemorrhagic or purple rash Bleeding from nose Vomiting blood Blood in stools Other hemorrhagic symptoms No established alternative diagnosis JAMA 2002;287 Adapted from WHO 50 Viral Hemorrhagic Fevers: Summary of Key Points • Viral hemorrhagic fevers can be transmitted via exposure to blood and bodily fluids. • Airborne precautions are recommended for health care workers caring for infected patients. • Ribavirin doesn’t work )only for Lassa fever) • No vaccine for Ebola / Marburg (only for yellow fever) 51 Botulinum toxin • Toxins – “Great for assassinations and cosmetic procedures” Clostridium botulinum • C. botulinum spores worldwide in soil • Toxin causative agent of botulism – Types A-G; A,B&E most commonly associated with human disease – Most potent toxin known (lethal dose 1ng/kg) – Inactivated by chlorine, sunlight and heat – Absorbed via mucosal surface or wound, not intact skin – Interferes with nerve transmission Æ paralysis 53 Botulism Epidemiology • Approximately 100 reported cases/year in the U.S. – Infant most common (72%) – Food-borne not common – Wound contamination • Incubation (food-borne): 12-72hrs (range 2hr-8d) – Dose dependent – Could be less following a BT attack • No person-to-person transmission 54 Botulism: Clinical Features • Early nausea, vomiting, diarrhea without fever • Double vision, paralysis of facial muscles, swallowing and speech difficulty • Progressive flaccid paralysis Æ respiratory failure • Death 60% untreated; <5% treated 55 Botulism: Clinical Features 56 Botulism: Treatment/Prevention • Ventilatory assistance, supportive care • Antibiotics for wound botulism • Vaccine under investigation • Botulinum antitoxin – available from CDC Emergency Operations Center 770 – 488 - 7100 Botulism: Summary of Key Points • An outbreak of botulism with no common food exposure would suggest a deliberate aerosol exposure • Inhalational botulism does not occur naturally and suggests a deliberate source of infection • Botulinum antitoxin must be administered early for optimum results 58 Ricin • A necrotizing cytotoxin • Extracted from castor beans – Grow wild throughout the Southeast http://www.google.com/imgre s?q=castor+beans+ricin Biological attacks in the last decade • 2001 – Anthrax mailed to senators and media • 2003 – Ricin found, addressed to Dept of Transportation • 2003 – Ricin mailed to White House • 2004 – Ricin found in senator’s mail • 2011 – ? Ricin • 0.5 mg is lethal Likely • Inhalation • Pneumonia/pulmonary edema • Injection Possible • Liver/lympid necrosis • Oral Unlikely • Bloody diarrhea / abdominal pain http://news.sky.com/ home/article/122194 05 No Antidote Contagious Agents (Person‐to‐Person Transmission) • Smallpox • Plague pneumonia • Some viral hemorrhagic fevers (e.g., Ebola) • Food- and water-borne agents (e.g., salmonella & shigella) 62 Agents That May Require Antibiotics or Immunization to Prevent Disease • Antibiotics – Anthrax – Plague – Tularemia – Q Fever – Brucellosis • Immunization – Smallpox – Anthrax 63 Infection Control: Standard Precautions • Standard precautions – all cases – – – – Disposable, non-sterile gloves Hand washing after glove removal Disposable gown or apron, faceshield if splashing anticipated Change protective gear between cases • Contact precautions – Standard precautions plus: – Wear gloves and gown, change after contact with infectious material – Dedicate non-critical patient care items (e.g., stethoscope) to a single patient or disinfect between patients 64 Infection Control: Droplet and Airborne Precautions • Droplet precautions – Standard precautions plus: – Wear mask within 6 ft of patient • Airborne precautions – Standard precautions plus: – Patient in negative air pressure room – Wear respiratory protection (such as a HEPA filter mask) 65 Questions? • Bacteria • Anthrax • Plague • Tularemia • Viruses • Smallpox • Filoviruses • Toxins • Botulinum • Ricin