Bioterrorism/poxvirus

Question 1

Possible indications of a biological attack

Answer 1

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

Question 2

Biowarfare (what is it and what’s the problem?)

Answer 2

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???

Question 3

What is bioterrorism?

Answer 3

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.

Question 4

What are bio-crimes?

Answer 4

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.

Question 5

Case of pt sick with Bacillus cereus G9241

Answer 5

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.

Question 6

Types of Biothreat Agents

Answer 6

Toxins – Botulinum toxin, Ricin (Castor Bean), Trichothecenes (Fungal Toxins)

Microorganisms - Bacteria, Viruses, Fungi, Parasites (?)

Question 7

Category A agents (examples and characteristics)

Answer 7

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

Question 8

Category B agents (examples and characteristics)

Answer 8

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

Question 9

History of use of biochemical weapons

Answer 9

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

Question 10

Gruinard Island

Answer 10

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!

Question 11

Sverdlovsk

Answer 11

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

Question 12

Differential for cutaneous anthrax (what else could something looking like cutaneous anthrax be?)

Answer 12

Ecthyma gangrenosum (pseudomonas)

Ulceroglandular Tularmeia (Francisella tularensis)

Plague (Yersinia pestis)

Leprosy (M. leprae)

Question 13

Differential for GI anthrax (what else could something looking like GI anthrax be?)

Answer 13

Typhoid fever

Intestinal Tularemia

Peptic ulcer

Question 14

Differential for inhalational anthrax

Answer 14

Legionnaire’s disease
Q fever
Viral PNE

Question 15

Smallpox today (as far as we know…)

Answer 15

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

Question 16

How infectious is Small Pox?

Answer 16

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

Question 17

What percentage of people infected with smallpox die? How many subclinical cases?

Answer 17

40%

NO subclinincal cases

Question 18

Pathogenesis of small pox (transmission, incubation period, onset and progression)

Answer 18

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

Question 19

Clinical features of smallpox

Answer 19

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.

Question 20

Smallpox vaccine

Answer 20

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.

Question 21

What are the 2 kinds of biothreat agents

Answer 21

Transmissible infectious agents that spread among people, animals or plants.

Toxins that affect exposed people, but do not make them contagious

Question 22

What could be the first indication of a bioweapons incident?

Answer 22

Unusual clinical presentations, clusters of cases of a previously rare disease, or appearance of a previously agriculture-associated disease in urban areas

Question 23

What virus causes smallpox?

Answer 23

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

Question 24

Anthrax

Answer 24

Bacillus anthracis, a gram-positive, non-motile soil bacterium, which expresses very potent toxins and produces spores that can survive for decades

Question 25

Are infected persons with anthrax contagious?

Answer 25

No

Question 26

Treatment of anthrax

Answer 26

Ciprofloxicin or Doxycycline

Question 27

The plague

Answer 27

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

Question 28

Tularemia

Answer 28

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

Question 29

Botulism

Answer 29

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.

Question 30

Viral hemorrhagic fevers

Answer 30

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.