Biologic Weapons in War

Slides:



Advertisements
Similar presentations
Responding to the Threat of Bioterrorism: A Status Report on Vaccine Research in the United States Good Morning. Over the next 1 ½ hours of so I’ll be.
Advertisements

BW Agents: Anthrax J.A. Sliman, MD, MPH LCDR MC(FS) USN Preventive Medicine Resident Johns Hopkins Bloomberg School of Public Health.
Epidemiology of Plague in the US Skin Zoonotic Diseases VM 544 Veterinary Preventive Medicine Dr. Paul Bartlett, MPH., DVM., Ph.D.
Developed by SHS Science Department
Black Death A Study of the Plague.
BIOLOGICAL AGENTS  CDC has prioritized them in Lists A - C  A List:  Easily transmitted/disseminated  High mortality rate  Potential for public panic.
BUBONIC PLAGUE.
Plague By Kerri Kessler.
By: Samantha Hatfield & Rachel Irwing. A severe lung infection that affects humans and animals.
Yersinia pestis Bubonic Plague By: Andrea Robertson Septicemic Plague
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 110 Potential Weapons of Biologic, Radiologic, and Chemical Terrorism.
Bioterrorist Agents: Tularemia
Ch. 24 Sec. 1 Communicable Diseases. What are Communicable Diseases?  Any disease that is spread from one _______________ thing to another  Any disease.
Lesson 3 Common Communicable Diseases When you have a cold, the best thing to do is rest, eat nutritious foods, and drink plenty of fluids such as water.
Decontamination During Human Biological Incidents Presented by The Ohio Department of Health Disaster Preparedness & Response Program.
Bacillus  ~ 60 species; Gram-positive or Gram-variable bacilli Large (0.5 x 1.2 to 2.5 x 10 um) Most are saprophytic contaminants or normal flora Bacillus.
The black plague Leaving bodies in it’s wake… Lamya’a Dawud & Sammy LeBlanc.
ANTHRAX By: Justin Tursellino. Anthrax is a…. Anthrax is an infection caused by a bacterium, Bacillus anthracis. The infection can take three forms depending.
Typhus Gaol Fever, Epidemic Typhus Tabradillo, War Fever, Jail Fever.
Rickettsia, Coxiella, Ehrlichia and Anaplasma
Common Communicable Diseases
Sheep and Goat Pox.
DISEASE AND PANDEMICS Brijesh Patel.
THE BLACK PLAGUE. The Italian writer Boccaccio said the Plague’s victims often… "ate lunch with their friends and dinner with their ancestors in paradise."
Seasonal Influenza and Swine-Origin Influenza A (H1N1) Virus
Anthrax Sung Chul Hwang, M.D. Dept. of Pulmonary and Critical Care Medicine Ajou University School of Medicine.
Bloodborne Pathogens HIV, AIDS, and Hepatitis Unit 1.
Chickenpox (varicella)
Bioterrorism MLAB 2434: Microiology Keri Brophy-Martinez.
The Black Death.
Infection Control in the School Setting
Anthrax Briefing. Anthrax Briefing What is anthrax? Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis.
39187n n n
BW Agents: Tularemia J.A. Sliman, MD, MPH LCDR MC(FS) USN Preventive Medicine Resident Johns Hopkins Bloomberg School of Public Health.
The Black Death: Bubonic Plague Shada Aimadeddine, Iyobo Aimiuwu, and Hannah Barboza Health Science Project August, 31, 2012.
Vibrio cholerae Asiatic or Epidemic Cholera. Readings Question #1 Describe the Vibrio cholerae bacterium. Where is it found?
Influenza of 1918 Danielle Albin Dane van Loon Matthew Litch.
By: Brittany Horan Large, aerobic, gram-positive, non- motile, encapsulated, chain forming, rod shaped that form oval spores. It is a bacterium of the.
Approved: 9 Jun DoD Leader’s Briefing: Force Health Protection Against Anthrax.
EBOLA HAEMORRHAGIC FEVER – BLEEDING FEVER 7NEWS EBOLA UPDATE.
Create Cornell Notes based on the following slides about Epidemics and Pandemics. You do NOT need to write down everything for each of the 10 worst epidemics/pandemics.
ANTHRAX D. Goldberg, MD Ped ID Service WRAMC. Anthrax Etiology-Bacillus anthracis toxin producing gram positive encapsulated spore forming non motile.
CHICKEN POX&SMALL POX Edited by: Dr: HALA ALI ABED Lecturer of public health.
The Killer Spore Anthrax Sara Bornstein. Bacillus Anthracis Anthrax is a bacteria, with a few specific characteristics: Anthrax has a thick outer capsule,
Bacillus B. anthracis: anthrax of the animals and humans. B. cereus: food poisoning; opportunistic infections. Aerobic or facultatively anaerobic. Large.
DIPHTERIE A thick, gray membrane covering your throat and tonsils
Bacillus D.
Bacillus SaprophyticB.cereusB.subtilisB.megateriumB.CirculansPathogenicB.anthracis.
STANDARD PRECAUTIONS Clinical Internship
Rickettsia, Coxiella, Ehrlichia and Anaplasma
Chapter 32 Epidemiology the Core Understanding of Public Health.
(insert screaming now)
DISEASE: HISTORY OF DEATH BUBONIC PLAGUE Beau Benhardt Teacher page.
Influenza A, H1N1 “Swine Flu” The Facts and How to Protect Yourself.
Notes: Spread, Treatment, and Prevention of Disease
August 2005 EMS & Trauma Systems Section Office of Public Health Preparedness BIOLOGICAL AGENTS.
Anthrax Human anthrax is typically an ulcerative sore on an exposed part of the body. Constitutional symptoms are minimal, and the ulcer usually resolves.
Bioterrorism Agents Epidemiology Program Overview.
DISEASE: HISTORY OF DEATH
Bioterrorism Agents: Plague
Biological Terrorism Smallpox 5/9/01.
Bioterrorism.
Anthrax Zoonotic disease caused by Bacillus anthracis
Mustansiriyah University College of science Biology Dept
The World’s Most Famous Bacteria
Biological Agents of Warfare and Terrorism
BW Agents: Plague J.A. Sliman, MD, MPH LCDR MC(FS) USN
Presentation transcript:

Biologic Weapons in War The use of germs to kill, immobilize or demoralize the Enemy. It WILL happen. Again. Vicken Y. Totten MD, MS FACEP

Warfare agents Projectiles and explosives – physical injuries incompatible with life Chemical and nuclear – poisoning incompatible with life Eco devastation – the environment will no longer sustain human life Carthage Genetic imperialism Rape and forced impregnation change a genome “Germ Warfare”

Purpose of bioterrorism To instill fear, change lifestyles Immobilize populations Waste resources Occupy trained personnel Weaken the Enemy

Germ 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. You Hemorrhage virus infected blood: potential to wipe out 20-99% of population

The 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.

BioWeapons = Germ Warfare Not new: used for thousands of years What’s new is “Weaponizing” increases virulence Assists in spread by technology Biologic capability is relatively inexpensive and widespread. Risk of a serious bioterrorism incident.

Serendipitous and deliberate Zoonoses in the “New World” Deliberate small pox in the New World Actual 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.

Ashdod 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.”

Plague 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.

Plague of Athens Spartans 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.

14th 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. 1346 -1347. Tartars defeated Genoese army by catapulting plague-dead soldiers over the walls into Kaffa (Caffa), by the Black Sea 1422. 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

THE BLACK DEATH PANDEMIC Worst from 1346 and 1352 with outbreaks till 1800s Killed 25 million people(1/3 of the world’s population at that time) 30-60% of the populations of large cities died from the disease final “foray” occurred in Marseilles in 1720. Still around

World War II British tested anthrax in Gruinard Island off the coasts of Scotland. Anthrax can live decades in soil. Cleaning the Island years later was very costly.

United 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.

Second 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.

United States 1980s September 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.

Weaponized 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

Properties for “Maximum Credible Threat” highly lethal & toxic easily produced in large quantities. environmental & aerosol stability Dispersal capability to (1 mm to 5 mm particle size) person to person communication no treatment or vaccine.

Potential 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

Relative Infectivity Dose Comparison Agent   Type Untreated Mortality %  Relative Infectivity Dose  Incubation Period  Treatment Anthrax Bact-eria 80 1000+ Spores 1-4 Days Pre Exposure Antibiotics* Botulism Virus 40-90 Moderate 2-7 Days Some Antibiotics Plague 90 10 Organisms 2-3 Days Antibiotics Smallpox 75 High 7-14 Days Vaccine Tular-emia 30 25 Organisms 2-4 Days V.H.F. 50-90 There 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

Anthrax, 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 quantity Plague available world wide; no need to raid containment facilities Anthrax & Smallpox stable for aerosol transmission; Anthrax spores survive for decades; smallpox can be freeze-dried.

All Weaponized. Iraq produced anthrax for use in Scud missiles; former Soviet Union produced smallpox virus by the ton; Japanese weaponized plague All uncommon diseases with non-specific initial presentation Delayed recognition will allow for secondary spread Vaccines poor or limited in availability.

Treaties: honored in the breach 1972 Biological Weapons Convention Soviet Union in 1979 accidentally released anthrax Iraq in 1995 had anthrax, botulinum toxin, and aflatoxin

United States 1969 stockpile: Bacillus anthracis, botulinum toxin, Francisella tularensis, Brucella suis, Venezuelan equine encephalitis virus, staphylococcal enterotoxin B Coxiella burnetti (9).

Soviet Union stockpile: smallpox, plague, anthrax, botulinum toxin, equine encephalitis viruses, tularemia, Q fever Marburg melioidosis Typhus

More 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 BioWeapon Many diseases have been accused of being BioWeapons, including SARS, Swine Flu and HIV

Plague

Plague (Yersinia pestis), gram-negative, anaerobic coccobacillus. transmitted to humans through fleas, rodents, or droplet infection. Human-to-human transmission quick Called “Black death” because the septic shock causes cyanosis, & peripheral gangrene “Blackening”

Rodents and fleas Endemic in rodents; fleas transmit but don’t sicken. The next mammal is the next victim. 10,000 years of human garbage attracting flea-ridden rats. Less a disease of nomads.

Plague – mode of transmission Natural: Fleas from infected rodents BioWar: aerosolized Large aerosol droplets contain 100-500 organisms Person-to-person transmission

Plague Worldwide: one of most feared diseases throughout history As many as 200 million deaths in last 1000 years. Not gone! India had outbreak in 1994. Endemic in US Southwest in rodents

Plague: Clinical Manifestations Cervical bubo Ecchymosis, septicemia Gangrene, septicemia Inglesby T, et al. JAMA 2000;383:2281

Plague 3 forms: bubonic, pneumonic and septicemic; Bubonic is classic. infected individuals die within 2 -3 days Bubonic has a mortality of 30 - 75 %; pneumonic & septicemic forms have mortality of 90 - 100 % respectively Septicemic plague usually occurs secondary to bubonic or pneumonic plague.

Plague: Black lesions & bubos (fingers & toes, penis & nose)

Symptoms: Bubonic Plague AMS: Hallucinations, headache, fever, chills. semiconscious to lethargic. " Madness” (agitated delirium) Hematemesis, bloody diarrhea Lymphadenopathy: swollen, tender lymph nodes (buboes) in armpits, groin; even supra-clavicular and cervical buboes rupture & suppurate Black blisters and hematemesis Recovered victims disabled: muscular tremors, “withered thighs and tongues“

Plague bubo

Plague 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.

Pneumonic 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.

Pneumonic Plague: CXR

Plague Diagnosis and Treatment CXR nonspecific Suspicion, setting, environment Standard 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.

Plague 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

Smallpox

Smallpox Communicability Contact: fomites, person to person Aerosol: 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 vaccination No acceptable treatment

Smallpox: Mode of transmission Patient-to-patient transmission likely Droplets, Large & Small More infectious if coughing or bleeding

Smallpox – 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.

Pustules 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.

Small Pox Symptoms: Maculopapular rash, then Raised fluid-filled blisters characteristic 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.

Variola Diseases V. major produces a more serious disease than V. minor V. 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?

Smallpox versus chicken pox

Smallpox Lesions progress simultan-eously; in Chicken pox they come in crops

Biological Warfare Using Smallpox Ravaged Europe; surviving population relatively immune Frequently used against American Indians: The British: June 24 1763, 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.“

Diagnosis Clinical setting: classic syndrome & rash is enough to make the diagnosis Electron Microscopy of vesicle; see Orthopox virus; does not prove variola Culture definitive but SLOW. Chick membrane or cell culture PCR (ref lab) is faster The 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 [27].

Treatment Isolation!! Supportive care No proven effective antivirals Fluid balance Electrolytes Hemodynamic support Respiratory support if needed No proven effective antivirals Antibiotics for secondary infections The 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 [27].

Smallpox Infection Control Strict Universal Precautions Prevent inhalation of particles 5µ or smaller Transfer to appropriate isolation room In large epidemic, may cohort patients Limit transportation (but use mask on patient if necessary)

Post-Exposure Prophylaxis Vaccine Partially effective up to 3 days s/p exposure Reduces incidence 2-3 fold Decreases mortality by ~50% Plus Vaccinia immune globulin (VIG) 3 fold decrease in incidence and mortality Passive immunity for 2 weeks (?) Cidofovir – antiviral agent is effective in animals against other poxviruses Post 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 [27]. 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% [34]. 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].

Smallpox prevention No more wild smallpox Vaccine available Last case 20 years ago Immunization may NOT confer lifelong immunity. CDC has 10-15M doses of vaccine, can produce more fairly quickly

Reactions to Smallpox Vaccine

More reactions

Anthrax and tularemia (rabbit fever) Most infectious in aerosol cause the highest number of dead and incapacitated greatest downwind spread

Anthrax & Tularemia (rabbit fever) These are the most infectious aerosols Aerosols cause the highest number of dead and incapacitated Spread downwind & person to person Available in the wild Weaponized versions are Abx resistant

Anthrax

Anthrax 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

Cutaneous lesions are black

Anthrax as BioWeapon Anthrax as a Biological Weapon, 2002: Updated recommendations for management JAMA. 2002;287(17):2236-2252 (doi:10.1001/jama.287.17.2236) Thomas V. Inglesby; Tara O'Toole; Donald A. Henderson; et al. http://jama.ama-assn.org/cgi/content/full/287/17/2236

Lesion of Cutaneous Anthrax Associated With Microangiopathic Hemolytic Anemia and Coagulopathy in a 7-Month-Old Infant

Infant w Cutaneous Anthrax Previous slide photo was from hospital day 12, when 2-cm black eschar was present in the center of the cutaneous lesion. Reprinted from Freedman et al.

BioWar Anthrax not new Aerosol technologies for large-scale dissemination are developed and tested Brits weaponized Anthrax pre-WWII 1995, Iraq acknowledged producing weaponized Anthrax Soviet Union & at least 13 other countries: Clear evidence of offensive biological weapons programs.

US: 2001 Anthrax Attacks Powder containing Anthrax spores in at least 5 letters to Florida, New York City, and Washington, DC. 22 confirmed or suspected Anthrax cases B anthracis spores in all the letters were “Ames strain” a research strain Aerosol release of B anthracis would be odorless and invisible and would have the potential to travel many kilometers before dissipating.

Types of Anthrax cutaneous, (Woolsorter's disease), gastrointestinal inhalational CNS (meningitis) Anthrax invades the lymphatic system and causes hemorrhages, sepsis, produces necrotizing toxins & death

Cutaneous anthrax stemming from wearing contaminated wool scarf

Cutaneous anthrax inoculation of spores through open skin lesions. Painless, pruritic papules appear w/i 5 d. Papules develop into vesicles By 7 days, central necrosis develops Necrosis progresses to black eschar that eventually sloughs off. Cutaneous: Not usually fatal Half the victims of mailed powdered anthrax 2001 got cutaneous anthrax.

Cutaneous Anthrax Eschar Raised, vesiculated edge, inflamed, and with a black base to the ulcer

Cutaneous anthrax ulcer Antibiotics reduce systemic symptoms Antibiotics don’t alter lesion course

Gastrointestinal Anthrax Seen in poor, developing countries with food shortages or inadequate food inspection. Sub-Saharan Africa, Central Asia, Russia, India, and Thailand Usually have concurrent cutaneous cases from butchering the affected animal or handling the infected meat Probable frequency: one outbreak per 64 infected animals eaten.

Gastrointestinal 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

Inhalational Anthrax Sudden, severe, acute febrile illness in persons at risk following a specific attack Fulminant course and death or acute febrile illness Example: from 2001 attacks: postal workers, members of the news media, and politicians and their staff Half got inhalational anthrax

Inhalation anthrax Usually 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.

Anthrax CXR CXR: widened mediastinum (classic but not so common), infiltrates, pleural effusion Chest CT: hyperdense hilar and mediastinal nodes, mediastinal edema, infiltrates, pleural effusion Hemorrhagic mediastinitis, hemorrhagic thoracic lymphadenitis, hemorrhagic meningitis;

Diagnostic tests Toxin: ELISA Peripheral blood smear & culture: gram-positive bacilli CXR: classically, “widened mediastinum” pleural effusion, mediastinal edema (boards question) Chest CT scan: hyper-dense mediastinal and hilar lymph nodes Thoracocentesis: hemorrhagic pleural effusions

Diagnosis DFA stain of infected tissues Thoracentesis: hemorrhagic pleural effusions Peripheral blood smear: gram-positive bacilli on blood smear Blood culture: large gram-positive bacilli with preliminary identification of “Bacillus species”

Treatment: Natural strains sensitive to penicillin Doxycycline (preferred) of tetracyclines Fluroquinolones 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.

Anthrax Prophylaxis Natural 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.

Anthrax 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.

Weaponizing Anthrax B anthracis engineered to resist tetracycline and penicillin. 1999 study induced in vitro Ofloxacin resistance Assume PCN & TCN resistance if terrorist attack Fluroquinolones 1st choice. Maybe. Once susceptibility known, use most widely available, efficacious, and least toxic antibiotic

Francisella tularensis aerobic, gram-negative, intracellular coccobacillus found in the water, soil, and vegetation. Natural reservoir: small mammals such as rabbits, squirrels, and mice In many ways, similar to Plague

Tularemia 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 environments The last 2 modes of transmission are what makes F. tularensis an ideal agent for BioWar.

Ulceroglandular 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.

Oro-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 ?

Pneumonic 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%.

Tularemia Chest x-ray May 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 24-48 hours, and can make the definitive diagnosis PCR or ELISA may also be used to aid in the diagnosis.

Treatment of Tularemia Streptomycin 30mg/kg IM q 12 h x 10-14 days. Alternative gentamicin 5mg/kg IM or IV q day x 10-14 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.

Viral Hemorrhagic Fevers RNA viruses: highly lethal, high infectivity by aerosol route. 90- 100% mortality Sx: febrile illness, liver failure, DIC, hypotension, death. Highly contagious. Dx: Setting, environment, H&P Confirm: viral serologies or culture (difficult) Available in the wild; hard to handle. Weaponizable when techniques for tissue culture mature.

The Viral Hemorrhagic Fevers Ebola Hemorrhagic Fever and Marburg Disease from the Filoviridae family. Lassa Fever from the Arenaviridae family Rift Valley Fever & Crimean Congo Hemorrhagic Fever, from the Bunyaviridae family

Clinical Hallmarks of Ebola Bleeding everywhere: DIC, capillary leaks, “bleeding eyes” Nose, GI tract… Highly Infective

VHR Patient Isolator

Treating in Isolator Difficult

VHF - Treatment Mostly supportive and ineffective In a mass casualty situation, Triage (in the harshest sense of the word) For lesser numbers, consider antivirals Ribavirin for Lassa, CCHF, Rift Valley

Personal Protective Equipment (PPE) No universal standard of PPE for health care providers in BioWar. Health Care workers will be among the first infected secondarily Fear of contamination or infection may prevent some physicians from going to work At a minimum: mask, gown, gloves. Complete change of clothes and shower BEFORE LEAVING FACILITY. HCW may be isolated into workplace

Decontamination 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.

Mass Casualty Wet decontamination (undress completely, shower & with soap/detergent, contain effluent.) Isolate & decontaminate all clothing & patient goods Dilute 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 hours Solar UV radiation and desiccation to inactivate biological agents.