CDC Biowarfare Threat Categories
- Category A: Easily disseminated or transmitted. Result in high mortality rates and have the potential for major public health impact; Might cause public panic and social disruption; and require special action for public health preparedness.
- Viral Hemorrhagic Fevers
- Category B: are moderately easy to disseminate; result in moderate morbidity rates and low mortality rates; and require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance.
- Epsilon toxin of C. Perfringens
- Glanders (Burkholderia mallei)
- Melioidosis (Burkholderia pseudomallei)
- Psittacosis (Chlamydia psittaci)
- Q fever (Coxiella burnetii)
- Ricin toxin from Ricinus communis (castor beans)
- Staphylococcal enterotoxin B
- Typhus fever (Rickettsia prowazekii)
- Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis])
- Water safety threats (e.g., Vibrio cholera, Cryptosporidium parvum)
- Category C: Threat limited by availability or difficulties in production or dissemination.
- Nipah virus
Gram pos. aerobic spore forming bacillus
Weaponized by milling spores to 1-5 microns (pore of mailing envelope 20 microns), antibiotic resistance and making for greater virulence
3 forms of disease
Cutaneous-starts c pruritic macule to ulcer c vesicles then eschar (anthrax is Greek for charcoal) Not Painful
GI-onset 2 to 5 days after consuming contaminated meat
Inhalational-biphasic, first flu-like illness usually s URI symptoms then high fever, dyspnea, cp, and death
Toxins mediate the damage, antibiotics do not affect toxins: edema factor and lethal factor
DX by blood cultures.
Suspect if widened mediastinum on C-XR, get CT. Can have infiltrates on C-XR
Recommended therapy for confirmed inhalational disease is now ciprofloxacin or doxycycline plus 1 or more antibiotics from a list that includes rifampin, clindamycin, imipenem, aminoglycosides, chloramphenicol, vancomycin, cefazolin, macrolides, and linezolid.
Therapy should be parenteral as long as necessary, then switched to oral to complete a 60-day course. Because of the severity of the disease, children and pregnant women should receive ciprofloxacin or doxycycline despite possible toxicity in these groups.
Recommended therapy for mass casualty exposure is oral ciprofloxacin with alternatives of doxycycline or amoxicillin for 60 days with careful medical follow-up.
Vaccine available, but unknown efficacy against weaponized
(JAMA 287:17 review)
small, non-motile coccobacilli.
The natural reservoir is domestic herbivores such as goats, sheep, cattle, and pigs. There are four species that are pathogenic in humans: Brucella melitensis, B. abortus (cattle), B. suis (pigs), and B. canis (dogs). Humans become infected when they ingest raw infected meat or milk or inhale contaminated aerosols, or through skin contact. Human infection also is called undulant fever. Human-to-human transmission is rare
incubation period is about 8-14 days, but may be considerably longer.
Clinical disease is a nonspecific febrile illness with headache, fatigue, myalgia, anorexia, chills, sweats, and cough. The fever often rises to 105°F. Cough and pleuritic chest pain occurs in up to 20% of cases
doxycycline (100 mg bid) plus rifampin (900 mg/day) for six weeks.
Alternative therapy proposed has been doxycycline (100 mg bid) for six weeks and streptomycin (1 gm/day) for three weeks. Relapse and treatment failure is common
7-17 days of incubation then high fever, vomiting, ha, and myalgias
2-3 days later, macular rash starting on face, hands and forearms eventually forming pustular vesicles
lesions are synchronous as opposed to chicken pox (Chicken pox starts on trunk or feet, Small pox on shoulder or face)
Lesions are infective until the scabs are entirely gone
Mostly affects face and extremities, palms and soles are not spared
Vaccine available, unknown efficacy against weaponized bacteria
No treatment, respiratory isolation
Yersinia pestis-gram negative coccobacillus
If from flea bite, get bubonic plague which may progress to septic or pneumonic
Bubonic-in 2 to 8 days you get flu-like illness, lymphadenopathy, usually cervical, axillary, or inguinal called buboes. Can grow up to 10 cm. Painful, warm, and swollen
Septicemic-DIC, purpura, gangrene of digits or nose
Pneumonic-2-4 day incubation if from inhaled bacteria. Then fever c hemoptysis, dyspnea, N/V, Abd pn. Pneumonia c infiltrates
Vaccine available in limited quantities
Streptomycin 15 mg/kg IM BID x 10 days
Genta and Doxy are also probably effective
Resp Isolate for first 4 days of treatment
intoxication occurs at extremely low concentrations of toxin, is irreversible
Where botulinum toxin causes a flaccid paralysis, tetanus causes spastic paralysis. The tetanus neurotoxin migrates retroaxonally (up the nerve fiber), and by transcytosis reaches the spinal inhibitory neurons, where it blocks neurotransmitter release and thus causes a spastic paralysis. Despite the seemingly different actions of tetanus and botulism, the toxins act in a similar way at the appropriate cellular level. The clinical effect in humans is well documented and includes twitches, spasms, rictus sardonicus, and convulsions.
Clostridium perfringens alpha toxin would cause vascular leaks, pulmonary damage, thrombocytopenia, and hepatic damage. Inhaled Clostridium perfringens would cause serious respiratory distress.
Clostridium perfringens and tetanus generally are sensitive to penicillin, the current drug of choice. There are some data that treatment with either clindamycin or rifampin may decrease Clostridium perfringens toxin production and give better results.
castor bean plant and secreted in the castor seeds.
toxin is quite easy to extract from the mash left by pressing castor oil from the castor beans (about 5%). It can be prepared as a liquid, crystals, or dry powder. It can be disseminated as an aerosol, injected into a victim, or used to contaminate food or water on a small scale.
Castor bean ingestion causes rapid onset of nausea, vomiting, abdominal cramps, and severe diarrhea followed by vascular collapse. Death occurs on the third day.
Inhalation of ricin will cause nonspecific weakness, cough, fever, hypothermia, and hypotension. Symptoms occur about 4-8 hours after inhalation. The onset of profuse sweating some hours later would signify termination of the symptoms. Lethal human exposures have not been described. In the animal, respiratory symptoms, including necrosis and alveolar infiltrates, are followed by cardiovascular collapse about 24-36 hours after inhalation. Death will occur about 36-48 hours after inhalation. High doses by inhalation appear to produce severe enough pulmonary damage to cause death.
Ingestion causes necrosis within the gastrointestinal tract, local hemorrhage and intrahepatic, splenic, and renal necrosis. It does not cause lung irritation when administered by other routes.
There is no approved immunologic or chemoprophylaxis at this time
Review in Jama: JAMA, November 9, 2005Vol 294, No. 18 (
responsible for paralytic shellfish poisoning.
not destroyed by cooking.
Onset of symptoms occurs within minutes of exposure. Death may occur within 2-24 hours. If the patient survives, normal functions are regained within a few days.
There is no antidote, so symptomatic treatment is appropriate. Antibodies for tetrodotoxin frequently will protect against saxitoxin
Since they normally exert their effect on the gut, they are called enterotoxins. Staphylococcal enterotoxin B (SEB), molecular weight 28,494 daltons, is one of the toxins that commonly causes food poisoning in improperly handled or refrigerated foodstuffs. Staphylococcal food poisoning is familiar to emergency physicians.
The toxin is markedly different in action when it is inhaled. SEB causes symptoms when inhaled at very low doses in humans (< 1/100th of the dose needed to cause gastrointestinal symptoms).
The organism that produces this agent is readily available and could be tailored to produce large quantities of the toxin. Related toxins include the toxic shock syndrome (TSST-1) and exfoliative toxins (staphylococcal-mediated exfoliative dermatitis).
Clinical Effects. The disease begins 1-12 hours after exposure with the sudden onset of fever, chills, headache, myalgia, and a nonproductive cough. The cough may progress to dyspnea and substernal chest pain. In severe cases, pulmonary edema may be found. Nausea, vomiting, and diarrhea are common. GI symptoms may accompany respiratory exposure due to inadvertent swallowing of the toxin after inhalation.
With the exception of dehydration and postural hypotension, the physical examination often is normal. The only physical finding of note is conjunctival injection. In very severe cases, the chest x-ray may show infiltrates.
In food-borne SEB, fever and respiratory involvement are not found and the gastrointestinal symptoms predominate. Patients would be expected to have nausea, vomiting, and diarrhea if they swallow the toxin.
The fever may last up to five days and rise to 106°F. The patient may have chills, rigors, and prostration. Sickness may last as long as two weeks, and severe exposures may cause fatalities.
produced by fish, salamanders, frogs, octopus, starfish, and mollusks, most notably the puffer (also called the globefish or blowfish).
All organs of the freshwater puffer are toxic, with the skin having the highest toxicity, followed by gonad, muscle, liver, and intestine. In salt water puffers, the liver is the most toxic organ.
Raw puffer fish, commonly called fugu, is a delicacy in several Southeast Asian countries, including Japan. Consumption of fugu causes mild tetrodotoxin intoxication with a pleasant peripheral and perioral tingling sensation. Improperly prepared fugu may contain a lethal quantity of tetrodotoxin. Fatalities have gradually decreased because of the increased understanding of the toxin and careful preparation of the puffer for food. Cooking the food will not dissipate the toxin. Tetrodotoxin is heat stable.
Tetrodotoxin is well known for its ability to inhibit neuromuscular function by blocking the axonal sodium channels. Cranial diabetes insipidus has been reported in critically ill patients. Mortality from tetrodotoxin is thought to be due to hypoxic brain damage from prolonged respiratory paralysis.
The clinical symptoms and signs of tetrodotoxin poisoning are similar to those of the acetylcholinesterase poisons. Clinical symptoms include nausea, vomiting, vertigo, perioral numbness, unsteady gait, and extremity numbness. Clinical symptoms begin within 30 minutes of ingestion. The speed of onset depends on the quantity of the toxin ingested. The symptoms progress to muscle weakness, chest tightness, diaphoresis, dyspnea, chest pain, and finally paralysis. Hypotension and respiratory failure are seen in severe poisonings. Patients frequently will complain of being cold or chilly. Paresthesias spread to the extremities, with symptoms often more pronounced distally. Death can occur within 17 minutes after ingestion of tetrodotoxin.
there is no known antidote for tetrodotoxin intoxication.
mycotoxins produced by fungi (Fusarium, a common grain mold)
yellow rain found in Laos, Cambodia, and Afghanistan.
They are the only class of toxin that causes skin damage. They cause blisters within minutes to hours after skin exposure.
Hypochlorite solution does not inactivate these toxins. They retain their bioactivity even when autoclaved.
Consumption of trichothecenes causes weight loss, vomiting, bloody diarrhea, and diffuse hemorrhage. This was found by the Russians when contaminated bread was ingested and caused alimentary toxic aleukia (AKA). Within days, the gastrointestinal symptoms progressed to bone marrow depression with neutropenia and secondary sepsis. Survivors developed bleeding from all body orifices and diffuse bleeding into the skin.
The onset of the illness occurs within hours and death may occur within 12 hours with significant inhalation exposure. Early symptoms are eye pain, tearing, redness, and a foreign body sensation in the eye. The patient may have nasal itching, burning, blistering, epistaxis, and bloody rhinorrhea. Mouth and throat exposure causes pain and blood-tinged saliva and sputum. Skin exposure may result in burning skin pain, erythema, blistering, tenderness, and progression to skin necrosis with blackening and sloughing of skin surfaces.
Inhalation exposure adds respiratory distress and failure to the picture. The patient may start with dyspnea, wheezing, and cough before progressing to respiratory distress.
Systemic toxicity occurs with any route of exposure. The patient develops weakness, prostration, dizziness, ataxia, and loss of coordination. The symptoms progress to tachycardia, hypotension, and shock. A late effect is bone marrow depression with pancytopenia and secondary sepsis and bleeding.
Ascorbic acid has been proposed to decrease the lethality. This has been studied in animals only, but because ascorbic acid has few side effects and is cheap, it should be used in all suspected cases.
Dexamethasone (1-10 mg IV) also has been shown to decrease lethality as late as three hours after exposure to these toxins.
In ingestions, charcoal or superactivated charcoal will absorb any remaining toxin and decrease lethality. The eyes should be irrigated with normal saline or water to remove toxin. The skin should be thoroughly washed with soap and water. The only protection is appropriate mask and protective clothing.
Francisella tularenis-small gram neg coccobacilli
Usually spread by insect (fly) bite. Assoc. c rabbit handlers
Can be spread by aerosol if terrorist attack
3-5 day incubation
flu symptoms then bronchitis, pneumonia, hilar lymphadenitis, sepsis
Partial protection experimental vaccine
Genta IV/IM or Cipro IV
No person to person spread
rickettsial zoonotic disease caused by Coxiella burnetii.
Spread to humans via inhalation, single inhaled organism can cause clinical illness.
incubation period is about 10-20 days
1/3 of patients will have acute hepatitis.
Other less common endocarditis, meningitis, encephalitis, and osteomyelitis.
presentation as a febrile illness with an atypical pneumonia is similar to a host of other atypical pneumonias, including mycoplasma, legionnaires disease, chlamydia pneumonia, psittacosis, or Hantavirus.
Chest x-ray abnormalities include patchy infiltrates typical of a viral or mycoplasma pneumonia. Hilar adenopathy may be noted.
treatment of choice is tetracycline, doxycycline, or erythromycin. Although not tested, azithromycin and Biaxin would be expected to be effective. Ciprofloxacin and other quinolones have been shown to be active and should be used in the patient unable to take the other recommended medications.
inactivated whole-cell vaccine is available
Prophylaxis is not uniformly effective. Tetracycline or doxycycline
Venezuelan Equine Encephalitis (VEE)
Western equine encephalitis (WEE) and Eastern equine encephalitis (EEE) are similar viruses. These viruses are quite difficult to distinguish clinically and share similar aspects of epidemiology and transmission. Natural infections are transmitted by the bites of a wide variety of mosquitoes. There is no evidence of human-to-human or horse-to-human direct transmission.
Presentation. VEE is a febrile incapacitating illness. Most infections are relatively mild. Only a small percentage of patients will develop encephalitis. EEE and WEE are predominantly encephalitis infections.
The onset is sudden after an incubation period of 1-6 days. The acute phase runs about 24-72 hours and is characterized by chills, spiking fevers (often high), rigors, headache, malaise, photophobia, and myalgias. Some patients may have nausea, vomiting, cough, sore throat, and diarrhea. The patient may have conjunctivitis, pharyngeal erythema, and muscle tenderness. The disease may last for 1-2 weeks.
About 4% of children and 1% or less of adults will develop signs of encephalitis. Of these, 10% of adults and up to 35% of children may die. Experimental aerosol challenges in animals suggest that CNS involvement in deliberate infections may be higher.
An outbreak of VEE may be difficult to differentiate from influenza on clinical grounds. An increased number of neurologic cases or coexisting disease in horses may be the first clue to a deliberate infection.
Therapy. There is no effective therapy for VEE and related illnesses.
Isolation is not required, since this disease is not transmitted human to human.
There are two IND human vaccines. The first (TC-83) is a live-attenuated cell vaccine produced by the Salk Institute. It has been licensed for horses and used as an IND for humans working in labs with VEE. The second (C-84) has been tested but not licensed in humans. This vaccine is used to boost non-responders to TC-83.
Dengue is the most common flavivirus infection in humans.
Aedes aegypti mosquitoes
Dengue has an incubation period of 2-10 days. The disease starts with high fever, chills, headache, back pain, anorexia, and nausea.3 Clinical findings include facial flushing, conjunctivitis, and a slow pulse relative to the high fever. The fever breaks on the third to fifth day and is associated with a diffuse maculopapular or morbilliform rash on the trunk. This rash spreads to the face and limbs. The soles and palms are not involved. Desquamation may occur while the rash is healing.
The patient can develop myocarditis and neurologic complications. Encephalitis, neuropathies, and Bells palsy can occur.
Dengue hemorrhagic fever and dengue shock syndrome are more severe forms of dengue that were first described in the early 1950s. Dengue hemorrhagic fever is defined by the presence of fever thrombocytopenia, and hemoconcentration.4 Dengue shock syndrome adds hypotension or profound shock. The disease appears to be similar to classic dengue until the second to fifth days, when the more severe symptoms start to appear. Major hemorrhagic symptoms occur in 10-15% of cases. These patients may have ptechiae, ecchymoses, pleural effusions, hepatomegaly, and hypotension. Encephalopathy may occur. Plasma leakage may cause edema, hemoconcentration, and hypoalbuminemia.
There is no effective therapy for dengue
There is no need for isolation procedures for patients infected with dengue. However, since diagnosis may be confused with hemorrhagic fevers, these patients should be treated with strict isolation until the diagnosis is confirmed.
Ebola, Marburg, Lassa, Junin
Spread by body fluid contact, ? of respiratory spread
2-21 day incubation period
High fever, HA, GI bleeding, Mucus Membrane bleeding, ptechial rash, conjunctival injection, edema, hypotension
Post-exposure prophylaxis can be provided by ribivarin
Less Toxic-Cat B
Q fever, brucellosis, glanders, Eastern and Western Equine Encephalomyelitis, Venezuelan Encephalomyelitis, Ricin, Clostridium Perfringens, GI Agents (Salmonella, Shigella, E. Coli O157:H7)
Future Agents-Cat C
Nipah Virus, Hanta Virus, Yellow Fever, Multi-drug Resist. TB
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