3Warfare agentsProjectiles and explosives – physical injuries incompatible with lifeChemical and nuclear – poisoning incompatible with lifeEco devastation – the environment will no longer sustain human lifeCarthageGenetic imperialismRape and forced impregnation change a genome“Germ Warfare”
4Purpose of bioterrorism To instill fear, change lifestylesImmobilize populationsWaste resourcesOccupy trained personnelWeaken the Enemy
5Germ Warfare (BioWar)Different agents have different infectious dose, germ survival in the environment, effectiveness, availability & LD-50, but: all should be feared.Psychological impact almost as lethal as their physical effects.Hot zones where contracting these germs means sure but slow! and contagious! death.1 to 2 weeks turn your body into liquefied, virus - infected tissue culture. YouHemorrhage virus infected blood: potential to wipe out 20-99% of population
6The Salt Lake Tribune (5/12, May) “ if "a killer flu strikes, with several thousand sick or injured and no room to spare in understaffed hospitals, care will be denied to the sickest adults and children."Individuals "who are severely burned, have incurable and spreading cancer, fatal genetic diseases, end-stage multiple sclerosis or severe dementia will be turned away.They can be sent elsewhere for comfort care, such as painkillers, but they will not be treated for the flu, according to the guidelines.
7BioWeapons = Germ Warfare Not new: used for thousands of yearsWhat’s new is “Weaponizing”increases virulenceAssists in spread by technologyBiologic capability is relatively inexpensive and widespread.Risk of a serious bioterrorism incident.
8Serendipitous and deliberate Zoonoses in the “New World”Deliberate small pox in the New WorldActual infection is not even required: post attack, US anthrax hoaxes had many of the effects hoped-for from actual infections: Disrupting business, life styles and demoralizing the Enemy.
9Ashdod of the Philistines 1320-1000 BC I Samuel: The Philistines stole the Israelites’ Ark of the Covenant.Rats (mice) appeared, then “the Lord’s hand on the people of Ashdod and its vicinity, throwing [the city] into a great panic. He afflicted the people of the city, both young and old, with an outbreak of tumors (emerods) in the groin.”As a result, the Philistines returned the Ark of the Covenant with “five golden emerods and five golden mice.”
10Plague of Athens (430-426 BCE) Thucydides’ “The Peloponnesian War” attributed the success of the war to the plague.The plague arrived in the first days of summer, during the second year of the war, at the same time as Archidamus, son of the king of Lacedaemon.
11Plague of AthensSpartans besieging the city were not affected by the disease.Many Athenians died, and eventually capitulated.Plague probably came by boat with the alleys up from Egypt, with immune soldiers.
1214th and 15th century Europe. Armies would fling diseased and decaying cadavers (especially of slaughtered enemy soldiers) over protective town walls to demoralize and sicken the besieged cities.Tartars defeated Genoese army by catapulting plague-dead soldiers over the walls into Kaffa (Caffa), by the Black Sea1422. Lithuanians flung dead soldiers and 2000 cart loads of excrement into Carolstein.These battles contributed to the 25 million victims of the European Black Plague
13THE BLACK DEATH PANDEMIC Worst from 1346 and 1352 with outbreaks till 1800sKilled 25 million people(1/3 of the world’s population at that time)30-60% of the populations of large cities died from the diseasefinal “foray” occurred in Marseilles in 1720.Still around
14World War II Britishtested anthrax in Gruinard Island off the coasts of Scotland.Anthrax can live decades in soil.Cleaning the Island years later was very costly.
15United States, Post WWII 1950, Germany accuses US of releasing Colorado beetles over German crops.China, North Korea, and the Soviet Union accused the US of using biological weapons during the Korean War.
16Second Sino-Japanese War The Imperial Japanese Army bombed Ningbo with fleas carrying bubonic plague.1941. More plague-contaminated fleas airdropped by 40 planes onto Changde.These operations caused epidemic plague outbreaks.
17United States 1980sSeptember 1984, The Dalles, OR, dozens got food poisoning: Salmonella enterica typhimurium.1st: Shakey’s Pizza. Later, 10 more restaurants.More than 700 ill; the only hospital ran out of beds. CDC involved. Deliberate contamination was proved; the Rajneesh cult was suspected but never convicted.
18Weaponized Super-Germs vs common organisms Small inoculums will infect large populations (highly infectious)Easily transmitted from person to person: airborne better than contact.Either lethal or prolonged illness with lasting morbidity (ties up Enemy resources and diverts them from War Effort; demoralizes)Treatment: none
19Properties for “Maximum Credible Threat” highly lethal & toxiceasily produced in large quantities.environmental & aerosol stabilityDispersal capability to (1 mm to 5 mm particle size)person to person communicationno treatment or vaccine.
20Potential human biological pathogens. NATO handbook lists 39 agents including bacteria, viruses, rickettsiae, and toxins.Biologic agents spread on their own; therefore, the “dose” needed is less.Highly toxic poision, Ricin: 8 metric tons vs 1 kg anthrax for same number casualties
21 Relative Infectivity Dose ComparisonAgent TypeUntreatedMortality % Relative Infectivity Dose Incubation Period TreatmentAnthraxBact-eria801000+ Spores1-4 DaysPre Exposure Antibiotics*BotulismVirus40-90Moderate2-7 DaysSome AntibioticsPlague9010 Organisms2-3 DaysAntibioticsSmallpox75High7-14 DaysVaccineTular-emia3025 Organisms2-4 DaysV.H.F.50-90There are many different biological weapons and each one has it’s many forms which differ in strength to survive, Lethal Dose, effectiveness, and availability. All of these weapons should be feared however, a few weapons go beyond fear. These weapons have a psychological impact almost as lethal as their physical effects. These weapons create hot zones, contracting these select bacteria is a sure death. Taking on average 1 to 2 weeks to turn your entire organ systems into pure virus infected tissue which has liquefied. Hemorrhaging of blood with the virus contained in it is imminent and the epidemic will spread from person to person. Such epidemics are similar to the plague which wiped out a 1/3 of the European population and the outbreaks of smallpox around the world in the past 50 years.* Not effective after symptoms develop
22Anthrax, Plague and Smallpox: best candidates Highly lethal:Anthrax, untreated anthrax > 80% die; Variola Major: 30% of unvaccinated patients die; Septicemic Plague 100%All can be produced in quantityPlague available world wide; no need to raid containment facilitiesAnthrax & Smallpox stable for aerosol transmission;Anthrax spores survive for decades;smallpox can be freeze-dried.
23All Weaponized. Iraq produced anthrax for use in Scud missiles; former Soviet Union produced smallpox virus by the ton;Japanese weaponized plagueAll uncommon diseases with non-specific initial presentationDelayed recognition will allow for secondary spreadVaccines poor or limited in availability.
24Treaties: honored in the breach 1972 Biological Weapons ConventionSoviet Union in 1979 accidentally released anthraxIraq in 1995 had anthrax, botulinum toxin, and aflatoxin
26Soviet Union stockpile: smallpox,plague,anthrax,botulinum toxin,equine encephalitis viruses,tularemia,Q feverMarburgmelioidosisTyphus
27More details about: Plague (Yersinia pestis), Smallpox (Variola major and minor)Anthrax (Bacillus anthracis),Tularemia (Francisella tularensis)Influenza is seldom mentioned but would be an excellent BioWeaponMany diseases have been accused of being BioWeapons, including SARS, Swine Flu and HIV
35Plague 3 forms: bubonic, pneumonic and septicemic; Bubonic is classic. infected individuals die within 2 -3 daysBubonic has a mortality of %; pneumonic & septicemic forms have mortality of % respectivelySepticemic plague usually occurs secondary to bubonic or pneumonic plague.
39Plague Septicemia Non-specific gram-negative septicemic symptoms: Flu-like illness rapidly progresses to pneumonia, hemoptysis.Blood cultures +, but no lymphadenopathy; respiratory contagion at 2 to 5 feet.Pneumonic plague is 100% fatal unless treatment is given with 24 hours of the onset of symptoms.
40Pneumonic Plague Most contagious and deadly: pneumonic plague Airborne person-to-person airborne spread.Y. pestis is not spore forming, and is viable for only 60 minutes as an aerosol.Doesn’t live long on surfaces.
42Plague Diagnosis and Treatment CXR nonspecificSuspicion, setting, environmentStandard treatment of bubonic, septicemic, or pneumonic plague is streptomycin, 30mg/kg IM q 12 h x 10 days.alternatives: chloramphenicol, gentamicin, or doxycycline.Chemoprophylaxis includes treatment with tetracycline or doxycycline.
43Plague Vaccine Not a generally viable option The Greer vaccine is an inactivated form of the disease, and requires a course of injections over 6 months.A recombinant sub-unit vaccine is being investigated.Outbreak would spur vaccine development – too late
45Smallpox Communicability Contact: fomites, person to personAerosol: communicability by aerosol requires negative-pressure isolation.One single case -> 10 to 20 others.No more than 20% of the population has any immunity from prior vaccinationNo acceptable treatment
46Smallpox: Mode of transmission Patient-to-patient transmission likelyDroplets, Large & SmallMore infectious if coughing or bleeding
47Smallpox – the Virus 2 Wild types Variola major Variola minor Variola called "smallpox" to distinguish it from Syphilis, the "great pox"Smallpox is believed to have emerged in human populations about 10,000 BC.
48Pustules up close. Note: thick covering of skin Pustules up close. Note: thick covering of skin. not like typical blisters.Here you see the pustules up close. Not that they have a thick covering of skin over them, and do not look like typical blisters.
49Small Pox Symptoms: Maculopapular rash, then Raised fluid-filled blisterscharacteristic scars, commonly on the face, which occur in 65–85% of survivors.Blindness resulting from corneal ulceration and scarring; Limb deformities due to arthritis and osteomyelitis are less common complications, 2–5% of cases.
50Variola DiseasesV. major produces a more serious disease than V. minorV. major mortality 30–35%V. minor causes a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch; kills about 1% of its victims.?Protective immunity?
52SmallpoxLesions progress simultan-eously; in Chicken pox they come in crops
53Biological Warfare Using Smallpox Ravaged Europe; surviving population relatively immuneFrequently used against American Indians:The British: June , William Trent, a local trader, wrote, “…we gave them two Blankets and an Handkerchief out of the Small Pox Hospital. I hope it will have the desired effect.“
55DiagnosisClinical setting: classic syndrome & rash is enough to make the diagnosisElectron Microscopy of vesicle; see Orthopox virus; does not prove variolaCulture definitive but SLOW. Chick membrane or cell culturePCR (ref lab) is fasterThe diagnosis of smallpox is a clinical one and in the setting of an outbreak, the classic syndrome and rash are all that is necessary for confirmation. Any suspicious rash during the setting of an outbreak must be considered smallpox until proven otherwise. Traditional confirmatory methods have included electron microscopy of vesicle fluid that can rapidly confirm the presence of an Orthopoxvirus but does not prove variola is the species. This requires culture on chick membrane or cell culture, which is specific but slow. Newer rapid tests including PCR are available at reference labs .
56Treatment Isolation!! Supportive care No proven effective antivirals Fluid balanceElectrolytesHemodynamic supportRespiratory support if neededNo proven effective antiviralsAntibiotics for secondary infectionsThe management of confirmed or suspected cases consists primarily of supportive care for those infected, and isolation. There is no specific antiviral treatment for those already showing symptoms. Supportive care is critical including careful attention to electrolyte and volume status, and ventilatory and hemodynamic support. Antibiotics are only required in the uncommon setting of secondary bacterial infections, such as Staphylococcus aureus cellulitis. Isolation of the patient is a vital component of the management of smallpox. Vaccination does not provide benefit to those truly infected who are already symptomatic, but can be considered in the treatment regimen in case the diagnosis of smallpox is wrong in a patient who was at risk of exposure .
57Smallpox Infection Control Strict Universal PrecautionsPrevent inhalation of particles 5µ or smallerTransfer to appropriate isolation roomIn large epidemic, may cohort patientsLimit transportation (but use mask on patient if necessary)
58Post-Exposure Prophylaxis VaccinePartially effective up to 3 days s/p exposureReduces incidence 2-3 foldDecreases mortality by ~50%Plus Vaccinia immune globulin (VIG)3 fold decrease in incidence and mortalityPassive immunity for 2 weeks(?) Cidofovir – antiviral agent is effective in animals against other poxvirusesPost exposure prophylaxis should be provided to those who have suspected exposure prior to symptom onset. This would include persons exposed to an original aerosol or contacts of cases, defined as those in the same household or who have had direct face-to-face contact with the patient after fever onset . Vaccine is partially protective if given within 3-4 days of exposure and may reduce the incidence of disease by 2-3-fold and mortality by 50% . Administration of Vaccinia immune globulin (VIG) in conjunction with vaccination may provide up to 70% greater protection versus incidence and death versus vaccination alone if given within the first few days after exposure. The passive immunity lasts for approximately two weeks, and presumably provides protection until active immunity from the vaccine develops [32,35]. The antiviral agent cidofovir can prevent disease in animals exposed to other pox viruses and may be effective as a post exposure prophylactic option for smallpox if given within two days of exposure [27,36].
59Smallpox prevention No more wild smallpox Vaccine available Last case 20 years agoImmunization may NOT confer lifelong immunity.CDC has 10-15M doses of vaccine, can produce more fairly quickly
62Anthrax and tularemia (rabbit fever) Most infectious in aerosolcause the highest number of dead and incapacitatedgreatest downwind spread
63Anthrax & Tularemia (rabbit fever) These are the most infectious aerosolsAerosols cause the highest number of dead and incapacitatedSpread downwind & person to personAvailable in the wildWeaponized versions are Abx resistant
65Anthrax history Biblical Egyptian plague. Bacillus anthracis, a gram-positive, spore forming bacillus.Transmission by inhalation, ingestion, or skin breaks from infected animals or their products, or from terror attack.Often associated with sheep and wool
71BioWar Anthrax not newAerosol technologies for large-scale dissemination are developed and testedBrits weaponized Anthrax pre-WWII1995, Iraq acknowledged producing weaponized AnthraxSoviet Union & at least 13 other countries: Clear evidence of offensive biological weapons programs.
73US: 2001 Anthrax AttacksPowder containing Anthrax spores in at least 5 letters to Florida, New York City, and Washington, DC.22 confirmed or suspected Anthrax casesB anthracis spores in all the letters were “Ames strain” a research strainAerosol release of B anthracis would be odorless and invisible and would have the potential to travel many kilometers before dissipating.
75Types of Anthrax cutaneous, (Woolsorter's disease), gastrointestinal inhalationalCNS (meningitis)Anthrax invades the lymphatic system and causes hemorrhages, sepsis, produces necrotizing toxins & death
76Cutaneous anthrax stemming from wearing contaminated wool scarf
77Cutaneous anthrax inoculation of spores through open skin lesions. Painless, pruritic papules appear w/i 5 d.Papules develop into vesiclesBy 7 days, central necrosis developsNecrosis progresses to black eschar that eventually sloughs off.Cutaneous: Not usually fatalHalf the victims of mailed powdered anthrax 2001 got cutaneous anthrax.
78Cutaneous Anthrax Eschar Raised, vesiculated edge, inflamed, and with a black base to the ulcer
80Gastrointestinal Anthrax Seen in poor, developing countries with food shortages or inadequate food inspection. Sub-Saharan Africa, Central Asia, Russia, India, and ThailandUsually have concurrent cutaneous cases from butchering the affected animal or handling the infected meatProbable frequency: one outbreak per 64 infected animals eaten.
81Gastrointestinal anthrax From eating contaminated meat:Starts with pharyngeal ulcers and edema.Hemorrhagic mesenteric adenitis, ascites, hematemesis, and melena may occur.Morbidity from loss of blood, fluids, electrolytes. Subsequent shock.Death from intestinal perforation or anthrax toxemia.Symptoms subside in 10 to 14 days in survivors
82Inhalational AnthraxSudden, severe, acute febrile illness in persons at risk following a specific attackFulminant course and death or acute febrile illnessExample: from 2001 attacks: postal workers, members of the news media, and politicians and their staffHalf got inhalational anthrax
83Inhalation anthraxUsually fatal. Infective dose is 8,000-15,000 spores.Flu-like symptoms for 4 days.Primary pulmonary infection rare.Endospores are engulfed by alveolar macrophages, get transported to the mediastinal and hilar lymph nodes, germinate and multiply in lymph nodes.Hemorrhagic mediastinitis, peribronchial hemorrhagic lymphadenitis, Lymphatic drainage blocked.Pulmonary edema.Toxin released into circulation.Death from septicemia, toxemia, or pulmonary bleeding/edema.
84Anthrax CXRCXR: widened mediastinum (classic but not so common), infiltrates, pleural effusionChest CT: hyperdense hilar and mediastinal nodes, mediastinal edema, infiltrates, pleural effusionHemorrhagic mediastinitis, hemorrhagic thoracic lymphadenitis, hemorrhagic meningitis;
87Diagnosis DFA stain of infected tissues Thoracentesis: hemorrhagic pleural effusionsPeripheral blood smear: gram-positive bacilli on blood smearBlood culture: large gram-positive bacilli with preliminary identification of “Bacillus species”
88Treatment: Natural strains sensitive to penicillin Doxycycline (preferred) of tetracyclinesFluroquinolones should have equivalent efficacy; Penicillin, doxycycline, & ciprofloxacin are FDA approved for inhalational anthrax.Other drugs: clindamycin, rifampin, imipenem, aminoglycosides, chloramphenicol, vancomycin, cefazolin, tetracycline, linezolid, and the macrolides.
89Anthrax ProphylaxisNatural anthrax is PCN & TCN sensitive; weaponized Anthrax is resistant.CDC recommends:Oral ciprofloxacin 500 mg q 12 hours.Prophylaxis for 60 days (unless exposure has been excluded) because disease can present 50 days or more after exposure.
90Anthrax Vaccine Poor, many side effects & limited availability. 1997: all U.S. military personnel are required to receive it.Anthrax vaccine adsorbed (AVA): inactivated cell-free product, produced by Bioport Corp, Lansing, Mich.6-dose SC series: 0, 2, & 4 weeks; then 6, 12, & 18 months; annual boosters.Peacetime / civilian safety has been questioned.
91Weaponizing AnthraxB anthracis engineered to resist tetracycline and penicillin study induced in vitro Ofloxacin resistanceAssume PCN & TCN resistance if terrorist attackFluroquinolones 1st choice. Maybe.Once susceptibility known, use most widely available, efficacious, and least toxic antibiotic
92Francisella tularensis aerobic, gram-negative, intracellular coccobacillusfound in the water, soil, and vegetation.Natural reservoir: small mammals such as rabbits, squirrels, and miceIn many ways, similar to Plague
93Tularemia Disease 3 types: Ulcero-glandular, Oro-glandular, Pneumonic. Usual humans infections from insect bites, contact with (skinning) infected rabbits or other small mammals, inhalation, & contact with contaminated environmentsThe last 2 modes of transmission are what makes F. tularensis an ideal agent for BioWar.
94Ulceroglandular Tularemia Most common. It occurs after a bite from an infected arthropod or from handling an infected mammal.Symptoms begin as flu-like and an ulcer appears at the site of infection.Regional lymph nodes enlarge and may resemble buboes.The patient may become bacteremic.Low mortality rate, but may take quite a long time for recovery.
95Oro-glandular Tularemia Usually after ingestion of contaminated raw meat, contaminated water; occasionally from inhalation.Symptoms: stomatitis, exudative Pharyngitis or tonsillitis.Cervical or retropharyngeal lymphadenopathy will occur and also may resemble buboes.Bacteremic possible; low mortality rate, but long recovery.Immunity ?
96Pneumonic Tularemia Most severe form Inhalation of aerosolized bacteria. Or secondary to hematogenous spread from cutaneous or oral lesions.Symptoms: fever, non-productive cough, pleuritic chest pain, chills, headache, and malaise. It may resemble community-acquired pneumonia.No person to person spread; no isolation needed.Mortality rate of 30-60%.
97Tularemia Chest x-rayMay show infiltrates, hilar adenopathy, or pleural effusion.Can have TB-like miliary infiltrates.Sometimes caseating granulomas found on lung biopsy.Culture of F. tularensis will grow in about hours, and can make the definitive diagnosisPCR or ELISA may also be used to aid in the diagnosis.
98Treatment of Tularemia Streptomycin 30mg/kg IM q 12 h x days.Alternative gentamicin 5mg/kg IM or IV q day x days.Vaccination is not recommended as a post-exposure prophylaxis.No live attenuated vaccine against tularemia yet.Weaponised Tularemia: oral doxycycline or ciprofloxacin are recommended as post-exposure prophylaxis.
99Viral Hemorrhagic Fevers RNA viruses: highly lethal, high infectivity by aerosol route % mortalitySx: febrile illness, liver failure, DIC, hypotension, death. Highly contagious.Dx: Setting, environment, H&PConfirm: viral serologies or culture (difficult)Available in the wild; hard to handle.Weaponizable when techniques for tissue culture mature.
100The Viral Hemorrhagic Fevers Ebola Hemorrhagic Fever and Marburg Disease from the Filoviridae family.Lassa Fever from the Arenaviridae familyRift Valley Fever & Crimean Congo Hemorrhagic Fever, from the Bunyaviridae family
101Clinical Hallmarks of Ebola Bleeding everywhere:DIC,capillary leaks,“bleeding eyes”Nose, GI tract…Highly Infective
104VHF - Treatment Mostly supportive and ineffective In a mass casualty situation, Triage (in the harshest sense of the word)For lesser numbers, consider antiviralsRibavirin for Lassa, CCHF, Rift Valley
105Personal Protective Equipment (PPE) No universal standard of PPE for health care providers in BioWar.Health Care workers will be among the first infected secondarilyFear of contamination or infection may prevent some physicians from going to workAt a minimum: mask, gown, gloves. Complete change of clothes and shower BEFORE LEAVING FACILITY.HCW may be isolated into workplace
106Decontamination in hospital Decontamination PRIOR TO patient arrival, and AWAY from hospital ventilation ducts.Do you know where the UH decon room is?BioAgent: undress, & mask the patient. For most agents, this would be enough.Anthrax: washing the patient with soap and water reduces the likelihood of secondary aerosolization of the spores.
107Mass CasualtyWet decontamination (undress completely, shower & with soap/detergent, contain effluent.)Isolate & decontaminate all clothing & patient goodsDilute bleach solution: hypochlorite can render a biological agent harmless, is safe for equipment and most fabrics(hypochlorite is contraindicated for open wounds)Heat and radiation for durable equipment:Autoclaving and dry heat at 100 C x 2 hoursSolar UV radiation and desiccation to inactivate biological agents.