10181 - Identification of Bioterrorism Agents Rashid A....

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Unformatted text preview: Identification of Bioterrorism Agents Rashid A. Chotani, M.D., MPH Assistant Professor of Medicine & Public Health Director, Global Infectious Disease Surveillance & Alert System Johns Hopkins University President, Pakistan Public Health Foundation GIDSAS rchotani@jhsph.edu History of Biological Warfare s s s s s 6th Century BC Assyrians poison the wells of their enemies with rye ergot 6th Century BC Solon of Athens poisons the water supply with hellebore (skunk cabbage) an herb purgative, during the siege of Krissa 184 BC Hannibal forces hurled earthen pots filled with serpents upon enemy 1346 Tatar army hurls its plague ridden dead over the walls of the city 1422 Battle of Carolstein, bodies of plague ridden soldiers plus 2000 cartloads of excrement are hurled into the enemy ranks Chotani, 2003 History of Biological Warfare s 14th Century: Plague at Kaffa Chotani, 2003 History of Biological Warfare 15th Century Pizarrio's army presented South American natives clothing laden with the variola virus s 1710 Russian troops hurl the corpses of plague victims over the city wall (Russian Sweden war) s Chotani, 2003 History of Biological Warfare - US s 18th Century: Smallpox Blankets Chotani, 2003 History of Biological Warfare - US s 20th Century: 1943: USA bio program launched 1953: Bio Defensive program established 1969: Bio Offensive program disbanded Chotani, 2003 History of Biological Warfare - Globally s s 1925 1972 Geneva Protocol Biological Weapons Convention signed by 103 nations s 1975 Geneva Conventions Ratified Chotani, 2003 Biological Terrorism A New Trend? s 1978: Bulgarian exile injected with ricin in s s s s s s s s s Chotani, 2003 s London 1979: Sverdlovosk, USSR accidental anthrax released 40 fatalities 1984: Oregon, Salmonella Rajneeshee cult 1991: Minnesota, ricin toxin 1994: Tokyo, Sarin and biological attacks 1995: Arkansas, ricin toxin 1995: Indiana, Y. pestis purchase 1997: Washington DC, `Anthrax/plague' hoax 1998: Nevada , nonlethal strain of B. anthracis 1998-9: Multiple `Anthrax' hoaxes 2001: Anthrax Outbreak USA Bioterrorism Basics Definition: The unlawful use, or threatened use, of microorganisms or toxins derived from living organisms to produce death or disease in humans, animals, or plants. The act is intended to create fear and/or intimidate governments or societies in pursuit of political, religious, or ideological goals. Chotani, 2003 Bioterrorism Basics What makes the use of biological agents so attractive to the terrorist? Ease of Acquisition Information readily accessible on World Wide Web American Type Culture Collection, other sources Only basic microbiology equipment necessary Small labs require no special licensing Investment to cause 50% casualty rate per sq. km: Conventional weapon $2000, nuclear $800, anthrax $1 Ease and Economy of Production Lethality Chotani, 2003 50 kg aerosolized anthrax = 100,000 mortality Sverdlovsk experience, former USSR Bioterrorism Basics What makes the use of biological agents so attractive to the terrorist? Stability Infectivity Weaponized agents may be easily spread Clinical symptoms days to weeks after release Low Visibility Ease and Stealth of Delivery Chotani, 2003 Remote, delayed, undetectable release Difficult/impossible to trace origin of agent Bioterrorism Basics Routes of Delivery for Biological Agents Aerosol is most likely method of dissemination Easy, silent dispersal Maximum number of victims exposed Inhalation is most efficient and contagious route of infection Food/Water-borne dispersal less likely Less stable, ineffective for some agents Inefficient compared to aerosol Chotani, 2003 Bioterrorism Basics Events Suggesting the Release of a Bioweapon Multiple people ill at the same time (epidemic) Previously healthy persons affected High morbidity and mortality among affected individuals Identification of diseases and pathogens unusual to a particular region Recent terrorist claims or activity Unexplained epizootic of sick or dead animals Chotani, 2003 Bioterrorism Basics Events Suggesting the Release of a Bioweapon Severe respiratory disease in a healthy host An epidemic curve rising and falling rapidly Increase in fever, respiratory, and GI symptoms Lower attacks rates in people working indoors vs. outdoors Seasonal disease during a different time of year Known pathogen with unusual antimicrobial resistance pattern Genetically-identical pathogen in different areas Chotani, 2003 Bioterrorism Basics What Can We Do As Medical Professionals? Maintain a high index of suspicion by including biological agents in differential diagnoses Learn to recognize historical and physical examination findings suggestive of bioweapon exposure Stay informed of local, regional and national epidemiologic trends Be knowledgeable about treatment and prophylaxis of patients exposed to biological agents Know whom to report suspected biological agent exposures and illnesses to (Police, State Intelligence agency, Infectious Disease Specialists, Local and State Health Officials) Chotani, 2003 Agents of Bioterrorism Bacterial Agents Bacillus anthracis (Anthrax) Yersinia pestis (Plague) Francisella tularensis (Tularemia) Brucella spp. (Brucellosis) Coxiella burnetii (Q Fever) Burkholderia mallei (Glanders) Vibrio cholerae (Cholera) Chotani, 2003 Agents of Bioterrorism Viral Agents Variola virus (Smallpox) Venezuelan Equine Encephalitis Virus (VEE) Hemorrhagic Fever Viruses: Ebola, Marburg, Lassa Fever, Argentine and Bolivian Hemorrhagic Fever Viruses, Hantavirus, Congo-Crimean Virus, Rift Valley Fever Virus, Yellow Fever Virus, Dengue Virus Chotani, 2003 Agents of Bioterrorism Biological Toxins Botulinum Toxins Staphylococcal Enterotoxin B Ricin Mycotoxins (T2) Chotani, 2003 Characteristics of BT Agents Agent Anthrax Plague Tuleram ia Brucellosis Q Fever Type Bacteria Bacteria Bacteria Bacteria Rickettsia Minimum Dose 8,000 (spores) 100 organisms Incubation Initial Duration period Symptoms of illness 1-6 days Flu-like Pneumonia / Flu-like Flu-like Flu-like Flu-like Flu-like Flu-like 3-5 days 1-6 days >=2 w eeks Weeks to months 2-14 days 4 w eeks days to w eeks Lethality High 90% Animal Indicator Yes 2-3 days 2-10 days 10 organisms (avg. 3-5) 10 organisms 5-60 days 1 organisms 10-40 days 7-17 days 10 organisms (avg. 12) 10 organisms 2-6 days High 90-100% Yes Moderate 5-30% Yes Low 2-10% Low 4% High 30% Yes Yes Animal Varients Sm allpox Virus Encephalitides VEE, EEE, WEE Virus Hem orrhagic Fevers Ebola, Marburg Virus Botulinum Toxin 1 organism 100 ng 4-21days 1-5 days Flu-like muscle w eakness 7-16 days 24-72 hours low Yes High Marburg 25% Ebola 50-90% Yes High 30% Yes Chotani, 2003 Anthrax Caused by contact with spores of Bacillus anthracis, a spore-forming, gram-positive rod Three distinct forms of clinical illness: Cutaneous by inoculation of skin lesions with spores; common, easily recognized and treated Inhalation by inhalation of spores into the lower respiratory tract; rare, difficult to recognize, > 80% mortality (classic description = Woolsorter's disease) Gastrointestinal by ingestion of spores in contaminated meat; rarely encountered but highly lethal Chotani, 2003 Cutaneous Anthrax A nondescript, painless, pruritic papule develops 3 to 5 days after introduction of B. anthracis endospores In 24 to 36 hours, the lesion forms a vesicle that undergoes central necrosis and drying, leaving a characteristic black eschar surrounded by edema and a number of purplish vesicles: resolves without scarring 80-90% resolve without treatment, but mortality can approach 20%, so cases usually treated Chotani, 2003 Anthrax: Cutaneous Vesicle development Day 2 Day 6 Day 4 Day 10 Eschar formation Chotani, 2003 Anthrax: Cutaneous Left, Forearm lesion on day 7--vesiculation and ulceration of initial macular or papular anthrax skin lesion. Right, Eschar of the neck on day 15 of illness, typical of the last stage of the lesion. From Binford CH, Connor DH, eds. Pathology of Tropical and Extraordinary Diseases. Vol 1. Washington, DC: AFIP; 1976:119. AFIP negative 71-12902. Chotani, 2003 Anthrax: Cutaneous Chotani, 2003 NEJM 1999; 341: 815 826 Anthrax: Cutaneous Healing after treatment Chotani, 2003 Anthrax: Cutaneous Notice the edema and typical lesions Chotani, 2003 Cutaneous Anthrax: Diagnosis Gram stain, polymerase chain reaction (PCR), or culture of vesicular fluid, exudate, or eschar Blood culture if systemic symptoms present Biopsy for immunohistochemistry, especially if person taking antimicrobials Chotani, 2003 Differential Diagnosis of Cutaneous Anthrax Spider bite s Ecthyma gangrenosum s Ulceroglandular tularemia s Plague s Staphylococcal or streptococcal cellulitis s Herpes simplex virus s Chotani, 2003 Inhalational Anthrax Pathogenesis 1-5 micron Anthrax spore size is optimal for deposition into alveoli Inhaled spores are ingested by alveolar macrophages and transported to mediastinal and peribronchial lymph nodes, spores germinating en route Anthrax bacilli multiply in lymph nodes, causing hemorrhagic mediastinitis, and spread throughout the body in the blood Chotani, 2003 Chotani, 2003 Inhalational Anthrax Clinical Presentation 10 days to 6 weeks after inhalation of spores, infected patients develop fever, nonproductive cough, myalgia and malaise Early in the course of the disease, chest radiographs show a widened mediastinum, which is evidence of hemorrhagic mediastinitis, and marked pleural effusions After 1-3 days, the disease takes a fulminant course with dyspnea, strident cough, and chills, culminating in hypotension, shock, and death Chotani, 2003 Anthrax: Inhalational Mediastinal widening JAMA 1999;281:17351745 Chotani, 2003 Mediastinal Widening and Pleural Effusion on Chest X-Ray in Inhalational Anthrax Chotani, 2003 Inhaltional Anthrax: Diagnosis Chest X-ray--widened mediastinum, pleural effusions, infiltrates, pulmonary congestion Affected tissue biopsy for immunohistochemistry Any available sterile site fluid for Gram stain, PCR, or culture Pleural fluid cell block for immunohistochemistry Chotani, 2003 Differential Diagnosis of Inhalational Anthrax s s s s s Mycoplasmal pneumonia Legionnaires' disease Psittacosis Tularemia Q fever s s Viral pneumonia Histoplasmosis (fibrous mediastinitis) Coccidioidomycosis Malignancy s s Chotani, 2003 Gastrointestinal Anthrax Fever and diffuse abdominal pain with rebound tenderness develop 2-5 days after ingestion of spores in contaminated meat Melenic or blood-tinged stools, bloodtinged or coffee-ground emesis, and ascites develop Death results from fluid and electrolyte imbalances, blood loss, shock, intestinal perforation or anthrax toxemia Chotani, 2003 Gastrointestinal Anthrax Chotani, 2003 Gastrointestinal Anthrax: Diagnosis Blood cultures s Oropharyngeal (OP) swab collection s Chotani, 2003 ...
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