Bioterrorism/poxvirus Flashcards
Possible indications of a biological attack
Noticing an unusual clinical case:
not usual disease in this area
more virulent than usual
in different patient population
Unusual epidemiology:
season
mode of spread
number and clustering of cases
Biowarfare (what is it and what’s the problem?)
The offensive use of biological agents by nations to harm the military of the enemy. Problem - how are bioweapons controlled to only kill or harm enemy soldiers???
What is bioterrorism?
The intentional release or use of viruses, bacteria, fungi or their products (i.e. toxins) for the purpose of harming or killing humans, animals (e.g. livestock), plants (e.g. crops) and to influence the conduct of government or to intimidate or coerce a civilian population.
What are bio-crimes?
The use of biological agents or their products to attack or assassinate individuals.
Example: The assassination of the Bulgarian dissident writer George Markov on Waterloo Bridge in London with an umbrella that had a mechanism to inject the very potent plant toxin – Ricin.
Case of pt sick with Bacillus cereus G9241
Seemed very similar to anthrax but was from a normally indolent bug
Turned out to have a plasmid on it that encoded for a toxin similar to anthrax toxin
Designed bioterrorism agent? No.
Types of Biothreat Agents
Toxins – Botulinum toxin, Ricin (Castor Bean), Trichothecenes (Fungal Toxins)
Microorganisms - Bacteria, Viruses, Fungi, Parasites (?)
Category A agents (examples and characteristics)
Anthrax, Botulinum Toxin, Small Pox, Tularemia
easily transmissible
high mortality rates and major public health impact
might cause public panic and social disruption
require special action for public health preparedness
Category B agents (examples and characteristics)
Q-Fever, B. mallei, Ricin, Mycotoxins, Cholera
moderately easy to disseminate,
cause moderate morbidity rates and low mortality rates
require enhanced diagnostic capacity
could be genetically enhanced for use as a weapon
History of use of biochemical weapons
Ancient Times - The dumping or hurling of diseased bodies (with the plague) or parts
Colonial Times - Smallpox infested blankets to Native Americans
Civil War – Smallpox- Highly Disputed!
WW1- Anthrax (against horses), Glanders, Cholera, Plague developed as weapons by Germany
WWII - Plague, glanders, anthrax, syphilis developed by Japan for weapons. Anthrax, botulism, developed by United States, UK & Canada as “retaliatory weapons”against Germany.
1975-84 – USSR, Yellow Rain – Trichothecenes on Hmong refugees
1984 - Bhagwan Shree Rajneesh Sect contaminates salad bars in Oregon (infects 751 with Salmonella) to influence election.
1994 - Japanese Sect Aum Shinrikyo attempted to aerosolize Anthrax from the top of buildings in Tokyo. Failed – turned to Sarin Gas
Gruinard Island
In UK
British were testing anthrax bombs on sheep there during WWII because of fears that the Germans would drop anthrax
Completely contaminated the island and no people were allowed for about 50 years!
Sverdlovsk
Russian city where they were doing anthrax research
In 1979 forgot to change air filter and many people got sick and died
Russians tried to cover it up
Differential for cutaneous anthrax (what else could something looking like cutaneous anthrax be?)
Ecthyma gangrenosum (pseudomonas)
Ulceroglandular Tularmeia (Francisella tularensis)
Plague (Yersinia pestis)
Leprosy (M. leprae)
Differential for GI anthrax (what else could something looking like GI anthrax be?)
Typhoid fever
Intestinal Tularemia
Peptic ulcer
Differential for inhalational anthrax
Legionnaire’s disease
Q fever
Viral PNE
Smallpox today (as far as we know…)
Eradicated (no new natural cases since 1976)
Official stocks are only kept at the CDC in Atlanta and at the Russian Vector lab in Novosibirsk
Samples were found in July 2014 in an NIH lab probably date back to the 1950s, but tests at the CDC found that despite theirage, the smallpox virus in two of the six vials was still alive and dangerous. A similarly forgotten stock of smallpox was found in a lab in Eastern Europe in the 1990s, for instance, and more recently at the former Swiss Serum and Vaccine Institute in Bern
How infectious is Small Pox?
Ridiculously contagious
Smallpox is highly contagious disease with a long incubation period. Consequently, many people can be exposed to the virus and become infected before the carrier shows any physical symptoms.
The mode of transmission is perhaps what makes the virus spread so wide. A quick sneeze or cough from an infected person sends thousands of virus enriched particles into the air. When others inhale the infected air, they become infected themselves. That person could then infect others by coughing or sneezing, or by sharing blankets and clothing
What percentage of people infected with smallpox die? How many subclinical cases?
40%
NO subclinincal cases
Pathogenesis of small pox (transmission, incubation period, onset and progression)
INHALATION ; cutaneous contact
INCUBATION PERIOD: 7-17 days; primary viremia 3-4 d, secondary at 8 +/- d -> symptoms (headache, fever, prostration) begin 3-4 days before rash
ONSET: lymphocytes -> primarily in skin and mucosa (lesions ulcerate releasing huge amounts of virus)
PROGRESSION: varies from recovery with scarring in 10-20 days, to fulminant with death in less than 5 d; Encephalitis rare
Clinical features of smallpox
Fever,headache, limb and back pain, vomiting, apprehension for 3-4 days, then…
Maculopapular rash appears on mucosa , head with spread to forearms and caudad (concentrated on distal extremities and head) and develops into…
Vesicles (1-2 days), which rapidly form pustules
Pustules are firm, tense and umbilicate (in the confluent forms of disease they blend into large areas of umbilicated pustules…
Eventually crust (8-10 days) and scar.
Hemorrhagic smallpox has rapid evolution of localized petechiae and hemorrhages (pregnant women and immunodeficient prone to this malignant form of the disease), bleeding from orifices, DIC and death. Typical rash may not develop.
Smallpox vaccine
The last case of Smallpox in the United States – 1948
Routine vaccination in the United States was discontinued in 1972.
Immunity from vaccination lasts 3-5 years.
Last case of Smallpox in the world occurred in 1977. Last vaccinations were in 1986.
Smallpox vaccine has been stockpiled and theoretically there is enough to vaccinate the entire population of the U. S. according to the CDC.
The original stockpiled vaccine was diluted and found to be still effective.
What are the 2 kinds of biothreat agents
Transmissible infectious agents that spread among people, animals or plants.
Toxins that affect exposed people, but do not make them contagious
What could be the first indication of a bioweapons incident?
Unusual clinical presentations, clusters of cases of a previously rare disease, or appearance of a previously agriculture-associated disease in urban areas
What virus causes smallpox?
variola major or smallpox virus
large, enveloped DNA virus in the orthopox family that replicates in the cytoplasm of infected cells, unlike other DNA viruses
Anthrax
Bacillus anthracis, a gram-positive, non-motile soil bacterium, which expresses very potent toxins and produces spores that can survive for decades
Are infected persons with anthrax contagious?
No
Treatment of anthrax
Ciprofloxicin or Doxycycline
The plague
Caused by Yersinia pestis, a gram-negative bacillus that infects prairie dogs and rats and is most commonly transmitted to humans by the bite of infected fleas.
3 presentations:
Bubonic: from insect bite, NOT likely means of transmission in a bioterrorism event, but can develop into pneumonic plague, which is highly transmissible.
Pneumonic: from inhaled bacteria, highly infectious, this type of infection is highly transmissible form of this organism in contrast to Tularemia, which in contrast is NOT transmitted person to person
Septicemic: fulminating onset, rapidly fatal, from swallowing Y. pestis in contaminated food or water, if patient lives long enough, can develop into pneumonic plague
Vaccine only given to people who work in labs with it
Tularemia
Caused by Francisella tularensis (gram-negative coccobacillus), which can survive for weeks in soil or water.
CANNOT spread from person to person, like pneumonic plague, and typically infects from insect bites or direct contact with infected small mammals.
Can cause waterborne outbreaks, and has been delivered as an aerosol for bioterrorism. Infectious dose can be, as few as, 10 organisms!
case fatality rate of untreated pneumonic tularemia can be 30-60%.
No approved vaccine
Botulism
Clostridium botulinum is an anaerobic, gram positive, spore-forming soil bacterium that produces one of the most potent toxins.
One gram of this toxin could kill a million people if it were efficiently delivered.
Intoxication is not transmissible from person to person.
Could be a bioterrorism agent, delivered by aerosol or in food. Botulism toxin has been made on a large scale and weaponized by several governments and terror groups.
Flaccid paralysis that has a 60-100% fatality rate.
Equine anti-toxins against types A, B and E are available in limited quantities to bind any circulating toxin, which has not yet reached the nerves, and a military vaccine against all 7serotypes is being developed.
A botulism toxoid is used to immunize people who work with C. botulinum or the toxin, but it is not available in large amounts.
Viral hemorrhagic fevers
Enveloped RNA viruses in several families (bunya, filo, arena, flavi, etc) cause VHF.
Several have been weaponized for aerosol transmission.
Fatality rates can be very high, (e.g. up to 80% for Ebola). Many are readily transmitted from human to human or from infected animals to humans, and many are spread in hospital settings to medical staff.
Febrile illness with hemorrhagic manifestations
in many tissues.
