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Lecture 4 Bioterrorism Dunne

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Published on November 17, 2007

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Epidemiology and Control of Zoonotic Infections Lecture 3: Bioterrorism Anthrax, Plague, and Tularemia :  Epidemiology and Control of Zoonotic Infections Lecture 3: Bioterrorism Anthrax, Plague, and Tularemia Gundula Dunne, DVM, MPVM February 1, 2004 Slide2:  Bioterrorism Overview 3 main diseases Anthrax Plague Tularemia Disease Biology Clinical Signs Humans Animals Prevention & Treatment Bioterrorism Preparedness Bioterrorism:  Bioterrorism Terrorism The use of force or violence against persons or property in violation of criminal laws for purposes of intimidation, coercion, or ransom Bioterrorism (BT) The use of biological agents in terrorism. This includes the use of bacteria, viruses, or toxins to harm people, animals, or plants Bioweapon The use of a biological agent as a weapon “Weaponization” of Agents:  “Weaponization” of Agents Alter characteristics of a pathogen to make it a more effective weapon Enhance transmission Increase virulence Resistant to antibiotics Evade vaccine protection Alter clinical signs BT: Introducing an Agent:  BT: Introducing an Agent Multiple methods of delivery/insertion Covert vs. overt Simultaneous introduction in multiple areas Accidental by tourists, products Natural vs. intentional Real vs. hoax Lack of consumer confidence Panic BT: Indicators:  BT: Indicators Atypical Conditions Clinical symptoms Timing/Season Age Groups Healthy Persons affected No risk factors BT: Indicators:  BT: Indicators Traceback a dead-end No shared factors History indicates a BT Other concurrent outbreaks High mortality or morbidity BT: Factors for Control & Prevention:  BT: Factors for Control & Prevention Delay of disease detection Days to weeks Non-specific disease symptoms Release difficult to detect Dissemination may cover large area Secondary spread Difficulties in catching perpetrator BT and Zoonoses :  BT and Zoonoses Most BT agents are Zoonoses Natural vs. Intentional Infections Collaboration with Animal Health Agencies Bioterrorism: Terrorist Goals:  Bioterrorism: Terrorist Goals Target = Humans Secondary Animal Cases Target = Animals Secondary Human Cases Plan for Investigation & Control BT: Animal Targets:  BT: Animal Targets Not as emotional as human targets Less chance of retaliation Agent may go undetected for days, weeks Difficult to trace “Plausible deniability” Some infectious agents not zoonotic Safe to work with BT: Animal Vulnerabilities:  BT: Animal Vulnerabilities High density husbandry Auction markets, transport of animals Limited immunity to BT diseases Centralized feed supply and distribution BT: Enhanced Animal Biosecurity:  BT: Enhanced Animal Biosecurity Identify high risk factors on each farm Regulate visitors Implement insect, bird, and animal control Secure water, feed and nutrient sources BT: Goal of Animal Biosecurity:  BT: Goal of Animal Biosecurity Stop the introduction and spread of infectious agents Prevent domestic and exotic animal diseases BT: Animal Disease Control:  BT: Animal Disease Control Maintain healthy herd Vaccinate Proper hygiene for animals and handlers Purchase from reputable sources Quarantine newly purchased animals Separate sick animals BT: Animal Disease Control:  BT: Animal Disease Control Change high risk management practices Avoid animal collection and dissemination points Auction markets, shows Nationwide animal identification and tracking system Goal: Premise identification system in place by July 2004 BT: Animal Response :  BT: Animal Response World Organisation for Animal Health - OIE Early Warning System Disease reported within 24 hours Informs countries at risk Trade shut down until further notice BT Agent Classification:  BT Agent Classification Requested by Congress in 1999 CDC and Nation Experts Categories A, B, & C Priority to agents previously used as bioweapons Not a federally legislated list BT Agent Classification:  BT Agent Classification Category A: highest priority Easily disseminated or transmitted person-to-person Cause high mortality with potential for major PH impact Might cause public panic Require special action for PH preparedness Category A Agents:  Category A Agents Variola major (smallpox) Bacillus anthracis (anthrax)** Yersinia pestis (plague)** Clostridium botulinum toxin (botulism)** Francisella tularensis (tularemia)** Filoviruses (Ebola, Marburg)** Arenaviruses (Lassa, Junin)** ** Zoonotic ** zoonotic diseases BT Agent Classification:  BT Agent Classification Category B: second highest priority Moderately easy to disseminate Result in moderate morbidity rates Low mortality rates Require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance Category B Agents (partial list):  Category B Agents (partial list) Coxiella burnetti (Q fever) Brucella spp. (brucellosis) Burkholderia mallei (glanders) Alphaviruses (VEE, EEE, WEE) Food- and water-borne pathogens Salmonella spp. Escherichia coli O157:H7 Vibrio cholerae Cryptosporidium parvum BT Agent Classification:  BT Agent Classification Category C: third highest priority Include emerging pathogens Engineering of pathogens for mass dissemination in the future Availability Ease of production and dissemination Potential for high morbidity and mortality rates Potential for major health impact Category C Agents:  Category C Agents Nipah virus Hantaviruses Tickborne hemorrhagic fever viruses Tickborne encephalitis viruses Yellow fever Multidrug-resistant tuberculosis Opportunities:  Opportunities Integration of public and animal health systems Be aware, contribute, assist in development of surveillance programs Report trends in disease and clinical signs Be involved with emergency response plans at all levels BT: Important Contacts:  BT: Important Contacts Local and state veterinarians California = Dr. Ben Sun Phone: (916) 552-9740 Email: bsun@dhs.ca.gov Agriculture Commissioner USDA-APHIS personnel University extension personnel Law enforcement Emergency management division Lecture 3 Part II Bioterrorism: Anthrax :  Lecture 3 Part II Bioterrorism: Anthrax Anthrax:  Anthrax Bacillus anthracis All warm-blooded animals Occurs worldwide Bacteria / Spore Person-to-person transmission rare Anthrax: Bioweapon:  Anthrax: Bioweapon Available & easy to produce Spores infective Aerosolization Low lethal dose (?) High mortality Bacillus anthracis:  Bacillus anthracis From Greek for coal – anthrakis Aerobic & Gram-positive Virulence associated with Antiphagocytic capsule 3 toxins Lethal factor Edema factor Protective antigen Serves membrane translocation function for Lethal factor and Edema factor Anthrax Spores:  Anthrax Spores Sporulation requires Poor nutrient conditions Presence of O2 Very resistant to extremes of heat, cold, desiccation, chemicals, pH, irradiation Can survive for decades Taken up by host and germinate Anthrax: Environmental Cycle:  Anthrax: Environmental Cycle Neutral or alkaline soil Epidemics occur with marked climatic or ecologic change Heavy rainfall Flooding Drought May go for years without any cases Anthrax: Transmission to Animals:  Anthrax: Transmission to Animals Ingestion Most common - contaminated soil Contaminated feed & bone meal Reduced risk with BSE regulations Animal to animal transmission rare Anthrax: Clinical Signs in Animals:  Anthrax: Clinical Signs in Animals Signs differ by species Ruminants at greatest risk Three forms of illness Peracute: ruminants (cattle, sheep, goats, antelope) Acute: ruminants and equine Subacute: swine, dogs, cats Copyright WHO Anthrax: Clinical Signs in Ruminants:  Anthrax: Clinical Signs in Ruminants Peracute infection Sudden death Bloody discharge from orifices Incomplete rigor mortis Rapidly bloat Acute infection 48 hours prior to death High fever, muscle tremors, dyspnea, anorexia, abortions, disorientation, death Chronic infection Localized ventral edema Anthrax: Clinical Signs in Equine:  Anthrax: Clinical Signs in Equine Ingestion Enteritis, severe colic, high fever, weakness, death within 48-96 hours Injection Hot, painful swelling Spreads to throat, sternum, abdomen, external genitalia Death Copyright WHO Clinical Signs in Dogs & Cats:  Clinical Signs in Dogs & Cats Rare; fairly resistant Ingestion of contaminated raw meat Clinical signs Fever, anorexia, weakness, local inflammation, necrosis and edema of upper GI tract, lymphadenopathy, edematous swelling of head and neck Death due to asphyxia, toxemia and septicemia Anthrax: Diagnosis and Treatment of Animals:  Anthrax: Diagnosis and Treatment of Animals Sample peripheral blood for testing Blood smear Culture Treatment Penicillin Tetracyclines Vaccination Herd Modified live product Anthrax: Prevention and Control:  Anthrax: Prevention and Control Burn or bury carcasses, bedding, other materials Decontaminate soil Remove organic material and disinfect structures Anthrax: Prevention and Control:  Anthrax: Prevention and Control Reportable Disease Quarantine the area Do not open carcass – no necropsy Minimize contact Wear personal protective equipment Latex gloves, face mask Postexposure treatment Animals – vaccination Humans - Chemoprophylaxis Anthrax: Transmission to Humans and Resultant Clinical Presentations:  Anthrax: Transmission to Humans and Resultant Clinical Presentations Three clinical forms Inhalational Tanning hides, processing wool or bone Cutaneous Contact with infected tissues Contact with contaminated hair, wool, hides, soil Gastrointestinal Ingesting contaminated meat Anthrax: Cutaneous:  Anthrax: Cutaneous Accounts for 95% of all cases globally Incubation period: ~3-5 days (< 12 days) Entry through open wound or abrasion Small papule progresses to vesicle in 1-2 days Over 2-3 d. progresses to eschar Dries, loosens, falls off in 1-2 wks (2-6 wks for resolution) Edema often prominent Head, forearms, and hands most common ± Lymphadenopathy, fever, malaise, headache Case-fatality rate 5-20% <1% if treated Anthrax: Inhalational:  Anthrax: Inhalational Incubation 1-6 days (60days ?) High case-fatality 75%-90% if untreated Early dx and tx, increases survival Hemorrhagic thoracic lymphadenitis Hemorrhagic mediastinitis Pleural effusions NOT “anthrax pneumonia” Typical bronchopneumonia does NOT occur Biphasic Anthrax: Inhalational:  Anthrax: Inhalational Initial phase – nonspecific Fever, dyspnea, cough, headache, vomiting, chills, weakness, abdominal pain, chest pain Lasts from hours to a few days May briefly recover or progress to second phase Second phase – develops abruptly Sudden fever, dyspnea, diaphoresis, shock Mediastinal widening on CXR consistent with lymphadenopathy 50% of 2001 cases had hemorrhagic meningitis Rapidly progressive Shock, hypothermia, death 24-36 hrs Anthrax: Gastrointestinal:  Anthrax: Gastrointestinal Incubation 2-5 (1-7) days Consumption of undercooked, contaminated meat 2 forms Distal GI tract Nausea, vomiting, anorexia, fever, abd pain, bloody diarrhea Oropharyngeal form Sore throat, dysphagia, possible pseudomembrane or ulcers Case fatality rate 25-75% GI anthrax not documented in U.S. Anthrax: Diagnosis in Humans:  Anthrax: Diagnosis in Humans Isolation of B. anthracis Blood, skin, resp. secretions Serology – antibodies to protective antigen Radiographic widened mediastinum Nasal swabs Assess exposure Not for diagnosis Not 100% sensitive Anthrax: Treatment :  Anthrax: Treatment Sensitive to numerous antibiotics Penicillin, doxycycline, ciprofloxacin approved by FDA to treat inhalational anthrax Ciprofloxacin treatment of choice in 2001 Convenience of BID dosing No strains known to be resistant Some weaponized strains resistant to penicillin and tetracyclines Anthrax in California:  Anthrax in California CA Dept of Food and Agriculture 34 outbreaks in 12 counties Aug 2004, Merced, 1 cow Oct 2001, Santa Clara County, 21 cattle 1991, Contra Costa County, 28 cattle 1984, San Luis Obispo County 43 cattle 135 sheep Chemoprophylaxis for people with contact exposure to blood of infected animals Sverdlovsk, Russia, 1979:  Sverdlovsk, Russia, 1979 City of 1.2 million Soviet Union offensive BW program Powdered anthrax manufacturing plant Reports of anthrax epidemic in humans and animals Government claimed human cases were gastrointestinal anthrax from eating infected cattle 66 deaths from inhalation anthrax 11 survivors Bioterrorism Attacks of 2001:  Bioterrorism Attacks of 2001 Anthrax in postal system 22 cases 5 deaths US public health realm changed forever Anthrax: The Response:  Anthrax: The Response Vaccine Humans Animals Antibiotics Treatment Mass casualty vs. contained casualty Prophylaxis Disinfection Sporicidal agents, sterilization Lecture 3 Part III Bioterrorism: Plague :  Lecture 3 Part III Bioterrorism: Plague Slide53:  Yersinia pestis Rapidly progressive febrile illness Reservoir - rodents Transmitted by fleas Every continent except Australia California ground squirrel (Spermophilus beecheyi) Plague Yersinia pestis:  Yersinia pestis Nonmotile, gram-negative rod Facultatively anaerobic Various virulence factors Antiphagocytic capsule Temperature-dependent enzymes coagulase and fibrinolysin Slide55:  Robert B. Crave. Plague. Infectious Diseases, 5th ed. J.B. Lippincott Co. 1994. Plague: Flea Vectors:  Plague: Flea Vectors Can live off host for months (e.g. in burrow) Many species can transmit Oropsylla montana Rock and California ground squirrels, prairie dogs Most important flea vector in United States Will readily feed on humans Cat and dog fleas not efficient vectors Plague: Flea Cycle and Transmission:  Plague: Flea Cycle and Transmission Maintained in environment by susceptible rodents and their associated fleas Fleas ingest Y. pestis when feeding on bacteremic animals Y. pestis multiplies and block flea GI tract so flea cannot digest Fleas therefore repeatedly try to feed and regurgitate plague bacteria into host Fleas generally host-specific but will “leave sinking ship” and feed on other mammals Plague in Animals:  Plague in Animals Most rodents die readily from infection Cats can develop severe illness Many animals are serologically positive Bears, bobcats, badgers, fox, skunks, mountain lion, deer, African buffalo, camel, coyote, more … Farm animals and dogs resistant Slide59:  Spotted ground squirrel (Spermophilus spilosoma) Prairie dog (Cynomys spp.) Sylvatic Plague:  Sylvatic Plague Enzootic Plague maintained at steady level in rodent populations Low death rates Mice, voles Epizootic Large die-offs, fleas change hosts Amplifying hosts: prairie dogs, ground squirrels, rock squirrels, woodrats, chipmunks Expansion into human occupied areas Urban (Domestic) Plague:  Urban (Domestic) Plague Infected fleas or rodents move to urban area Interface areas around homes Western U.S. cities: suburban-wilderness zone Commensal (domestic) rodents Roof rat, Norway rat Rat fleas may feed on humans Poverty, filth, homelessness contribute Cats and Plague:  Cats and Plague Infection from flea bites or, more commonly, ingestion of an infected rodent Clinical signs in cats include fever, lymphadenopathy (buboes) and/or pneumonia Exudates from buboes or respiratory secretions and sputum are highly contagious to humans 1st case of cat-associated human plague in U.S. in 1977 From 1977-1998, 23 cases total (5 fatal) Owners should control fleas on their pets and keep pets away from wildlife Animal Sources of Human Infection in U.S. (319 cases) 1970 -1993:  Animal Sources of Human Infection in U.S. (319 cases) 1970 -1993 Plague: Other Transmission Routes:  Plague: Other Transmission Routes Aerosol transmission Droplet spread from person or cat with plague pneumonia Probable mode of transmission if used as bioterrorism agent Direct contact with infected tissues or contaminated fluids Plague: Pathogenesis:  Plague: Pathogenesis Flea bite inoculates up to thousands of organisms into skin Bacteria migrate through cutaneous lymphatics to regional lymph nodes Phagocytosed but resist destruction Multiply rapidly causing destruction and necrosis of lymph node architecture Bacteremia, septicemia, endotoxemia Can lead to shock, DIC, coma Plague: Clinical Disease:  Plague: Clinical Disease Bubonic - Adenitis in lymphatics draining the site of exposure. Septicemic - Bubonic form progressing to bacteremia and dissemination. Pneumonic - Septicemic form spread to lung where sputum aerosols make patient highly infectious. Symptoms - Fever, pain, toxemia, shock, neurologic involvement Bubonic Plague:  Bubonic Plague Incubation period: 2-8 days after flea bite Sudden onset fever, chills, weakness Bubo – acutely swollen tender lymph node Typically in axilla, groin, cervical region Rarely become fluctuant and suppurate Can have secondary septicemia or pneumonia Without treatment 50-60% fatal Accounts for most cases in U.S. Pneumonic Plague:  Pneumonic Plague Primary Droplet transmission from human or cat Rare in U.S. Secondary Hematogenous spread of plague bacilli to lungs Occurred in 12% of U.S. cases in last 50 years Sever bronchopneumonia, chest pain, dyspnea, cough and hemoptysis Without treatment, 100% fatal Septicemic Plague:  Septicemic Plague Primary Rare, no discernable bubo Secondary to bubonic plague May lead to DIC, necrosis of small vessels, and purpuric skin lesions Gangrene in advanced disease Reason for the name “Black Death” Without treatment, 100% fatal Manifestations of Plague:  Manifestations of Plague Plague: Humans Diagnostics:  Plague: Humans Diagnostics Confirmed Isolation of Y. pestis from clinical specimen, OR Fourfold rise in antibody titer, OR Single titer of >1:128 with no previous plague or vaccination history Presumptive Detection by fluorescent assay of F1 antigen, AND/OR Elevated serum antibody titer (>1:10) with no previous plague or vaccination history Suspected Compatible illness, AND Small, gram-negative and/or bipolar staining coccobacilli seen on smear from affected tissues Plague: Treatment:  Plague: Treatment Treatment should be started ASAP Antibiotics Streptomycin (Treatment of choice) Gentamicin (alternative) Others Tetracyclines Chloramphenicol Fluoroquinolones +/- Isolation of person Plague: Prevention and Control:  Plague: Prevention and Control Fever watch vs. prophylaxis for individuals potentially exposed to plague + animal Insect repellents for skin & clothes Insecticide use in epizootic areas Isolate infected animals Limit number of people contacting animal Personal protection Surgical mask, gloves, eye protection Plague: Prevention and Control:  Plague: Prevention and Control Prevent animals from roaming/hunting Rodent control Eliminate rodent habitat around home Brush, food sources, firewood, junk Undertaken only after insecticide use Control fleas Dogs and cats, premises Spring to fall Slide75:  Class 1 quarantinable disease (WHO) Detention and inspection if originating from plague endemic area CDC Division of Quarantine empowered if suspect a case Reportable disease in U.S. and to WHO Vaccination Against Plague:  Vaccination Against Plague Formaldehyde-killed whole bacilli vaccine Discontinued in 1999 No longer available Shown efficacy in preventing or ameliorating bubonic plague Does NOT prevent or ameliorate the development of primary pneumonic plague Plague in California:  Plague in California Introduced into San Francisco in 1900 Last U.S. outbreak in Los Angeles in 1924 32 pneumonic cases/31 deaths Last human-to-human transmission in U.S. Occurs in foothills, plateaus, mountains, and coasts Absent from southeastern desert and Central Valley Yearly Surveillance Plague as a Biological Weapon:  Plague as a Biological Weapon WWII Japanese army, Unit 731, reported to have dropped plague-infected fleas over areas of China U.S. and former U.S.S.R aerosolized Y. pestis 1970 WHO estimate 50 kg Y. pestis released as aerosol City of 5 million 150,000 pneumonic cases 36,000 deaths Secondary cases probable Plague: The Response:  Plague: The Response Respiratory droplet precautions Gown, gloves, eye protection, surgical mask For patients prior to 48 hours of antibiotic therapy Quarantine Treatment vs. prophylaxis Contained vs. mass casualty Lecture 3 Part IV Bioterrorism: Tularemia :  Lecture 3 Part IV Bioterrorism: Tularemia Tularemia:  Tularemia Francisella tularensis Small, Gram-negative coccobacillus 2 strains with different virulence Maintained and amplified in nature Vertebrate reservoirs Arthropod vectors 100 – 200 cases annually in the U.S. History:  History “Plague-like illness” in California ground squirrels (1911) Named Bacterium tularense after Tulare County First clinical case in humans with F. tularensis identified – oculoglandular case in Cincinnati (1914) Renamed after Edward Francis (1947) Francisella tularensis:  Francisella tularensis Francisella tularensis subsp. tularensis (Jellison type A) holarctica (Jellison type B) mediasiatica – does not cause human infection novicida – low virulence Can persist in the environment 3-4 months Mud, water, dead animals Francisella tularensis Jellison Type A:  Jellison Type A More virulent subspecies Severe illness Higher case fatality rate Lab rabbits highly susceptible Ferments glycerol Predominately in North America Reservoir Cottontail, jack, and snowshoe rabbits; ground squirrels; ticks; others? Jellison Type B:  Jellison Type B Milder disease Europe and Asia but also in U.S. Reservoir Rodents (muskrats, mice, beaver, voles, water voles) Associated with water or aquatic animals Reservoirs:  Reservoirs Rabbits (especially members of the genus Sylvilagus) Hare Voles Muskrats Beavers Hard ticks Can infect >100 species of wild and domestic mammals 25 species of birds Several species of amphibians and reptiles Vector-borne Transmission:  Vector-borne Transmission Ticks Transovarial transmission Numerous species Dermacentor variabilis (American dog tick) Amblyomma americanum (Lone Star tick) Dermacentor andersonii (Rocky Mountain wood tick) Flies Chrysops discalis (deerfly) Mosquitoes in Scandinavia? Slide88:  Female Lone Star Tick (Amblyomma americanum) Female American Dog Tick (Dermacentor variabilis) Iowa State University Entomology Clinical Presentation in Animals:  Clinical Presentation in Animals Acute febrile illness Diverse clinical manifestations Cats more susceptible than dogs Ranges from mild illness with lymphadenopathy and fever to severe overwhelming infection and death Signs may include anorexia, dehydration, listlessness, draining abscesses, oral or lingual ulceration, pneumonia, icterus, hepatomegaly, splenomegaly Probably underrecognized Can transmit F. tularensis to humans Clinical Presentation in Large Animals:  Clinical Presentation in Large Animals Significant morbidity and mortality in sheep Associated with decreased plane of nutrition, heavy tick infestation, severe winter weather Cattle – seropositive for Abs to F. tularensis Horses – rarely described Livestock may be more important as maintenance hosts of tick vectors rather than reservoirs Clinical Presentation in Zoo Animals and Wildlife:  Clinical Presentation in Zoo Animals and Wildlife Diagnosed in numerous zoo animals, including primates Wildlife Usually present moribund Hare, cottontails, rodents behave strangely Easy prey because they are sluggish and lethargic Can therefore transmit disease to predator Tularemia in Prairie Dogs, 2002:  Tularemia in Prairie Dogs, 2002 Recognized as die-off in captured wild prairie dogs (Cynomys ludovicianus) at commercial exotic animal distributor in TX F. tularensis Type B Captured from several U.S. locations Shipped to various states, Belgium, Czech Republic, Japan, The Netherlands, Thailand Prophylaxis for those who handled prairie dogs One animal handler seroconverted Tularemia: Transmission to Humans:  Tularemia: Transmission to Humans Transmission to humans may occur by several routes: Direct contact Inhalation Ingestion Biologic or mechanical transmission by arthropods Highly infectious – 10-50 organisms Laboratory transmission Person-to-person NOT known to occur Tularemia: Direct Transmission:  Tularemia: Direct Transmission Bites or scratches Contact with tissues Skinning/dressing Cooking Necropsy Handling contaminated skins, paws Undercooked meat Contaminated water, blood, tissues Tularemia: Clinical Presentation:  Tularemia: Clinical Presentation Extremely variable, depends on: Route of inoculation Dose Virulence Incubation: 3-5 days (range: 1 – 14 d.) Febrile illness Chills, headache, myalgia, fatigue, sore throat, cough, shortness of breath, vomiting, diarrhea Prominent lymphadenopathy Tularemia: Human Clinical Symptoms:  Tularemia: Human Clinical Symptoms Ulceroglandular Glandular – no ulcer Oculoglandular – rare Oropharyngeal – rare Pneumonic – rare Septic or Typhoidal – rare Tularemia: Human Disease:  Tularemia: Human Disease Ulceroglandular Most common Ulcer at site of arthropod bite 1 week - months Prominent regional lymphadenopathy Glandular No ulcer Regional lymphadenopathy Second most common Tularemia: Human Disease:  Tularemia: Human Disease Oculoglandular Conjunctiva infected by contaminated fingers or from tissues Conjunctivitis and regional lymphadenopathy Oropharyngeal Hand-to-mouth or undercooked meat Pharyngitis, diarrhea, abdominal pain, vomiting, GI bleeding, nausea May see pseudomembrane over tonsils Tularemia: Human Disease:  Tularemia: Human Disease Septic / Typhoidal Systemic form – primary or secondary Rare in U.S. (<5% of cases) Fever and other nonspecific signs Untreated mortality rate up to 60% Pneumonic Inhalation of aerosol OR Secondary to other clinical presentation Primary Pneumonic Tularemia:  Primary Pneumonic Tularemia Inhalation Exposure Aerosolized F. tularensis After disturbing infected carcasses Exposure to aerosols of soil, dust, hay Lawnmower associated High untreated mortality rate (40-60%) Most likely BT presentation Diagnosis:  Diagnosis Clinically compatible illness Because the disease is rare and signs can be nonspecific, it is often not suspected Culture – cysteine heart agar Serology 4-fold titer change Direct fluorescent antibody (DFA) test for antigen Tularemia: Human Treatment:  Tularemia: Human Treatment Antibiotics Streptomycin (treatment of choice) Gentamicin (alternative) Chloramphenicol or tetracycline No less than 14 days Relapses are known to occur Vaccination for high risk groups (laboratory workers) Tularemia Vaccine:  Tularemia Vaccine Live attenuated vaccine from avirulent live vaccine strain Used for laboratorians under Investigational New Drug Protocol Not currently available Tularemia: Occupations at Risk:  Tularemia: Occupations at Risk Farmers Hunters Trappers Meat handlers Cooks Laboratory workers Veterinarians Epidemiology:  Epidemiology United States Reported from all states but Hawaii Most common in south central U.S. Arkansas, Missouri , South Dakota, Oklahoma >50% of cases annually Other states Wyoming, California, Utah, Nevada - deerflies Massachusetts – only reported outbreaks of primary pneumonic tularemia in the U.S. (n=2) Tularemia as a Bioweapon:  Tularemia as a Bioweapon Weaponized by numerous countries U.S., U.S.S.R., Japan WHO estimation conducted in 1969 50 kg virulent F. tularensis over city with population 5 million 250,000 ill 19,000 deaths Stable Can be aerosolized Low infective dose via inhalation Tularemia: The Response:  Tularemia: The Response Person-to-person transmission not documented Antibiotics effective if early or prophylactic Vaccine For high risk individuals Unknown efficacy against inhalation tularemia Not currently available Brucellosis: Correction :  Brucellosis: Correction Person-to-person transmission Extremely Rare Sexual Transmission Maternal Milk and Transplacentally from Infected Mother Tissue Transplantation Brucellosis: Bioterrorism:  Brucellosis: Bioterrorism Highly Infectious Easily Aerosolized Stable Long Incubation Brucellosis: Bioterrorism Bioweapon Scenario:  Brucellosis: Bioterrorism Bioweapon Scenario Aerosolized B. melitensis City of 100,000 people Infectious dose of 1,000 cells to infect 50% 50% of infected hospitalized for 7 days Outpatients required 14 visits 5% relapse rate 82,500 cases requiring extended therapy Case-fatality rate of 0.5% (413 deaths) $477.7 million in economic impact Leptospirosis- Update:  Leptospirosis- Update Fresh water – viable Brackish water Depends on conditions Limited viability Sea water Not viable Controversial Transient viability – hours to days Tsunami Low risk of Lepto (not from sea water) Rodent and human crowding and fresh water Typically fresh flood water is a risk Slide113:  CDC TAKE HOME POINTS:  TAKE HOME POINTS Bioterrorism is a real threat Many bioterrorism agents are zoonotic Awareness education is essential Risk perception and acceptance differ between people You play a critical role! Slide115:  QUESTIONS? Acknowledgements:  Acknowledgements Dr. Ben Sun

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