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Biodefense
Chapter 18
47
Biology
Professional
02/21/2012

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Term
What are the major differences between biological agents vs. conventional weapons?
Definition
1) Cheaper
2) Ubiquitous
3) Hard to detect
4) Dual-use technology
5) Self-perpetuating
Term
What are the 6 category A agents in bioterrorism?
Definition
1) Bacillus anthracis (spore-forming gram (+) rods)
2) Fancisella tularensis (tularemia)
3) Yersinia pestis (plague)
4) Variola major (smallpox)
5) Arenaviruses and Filoviruses (Viral hemorrhagic fevers)
6) Clostdridium botulinum toxin
Term
Which agents are the 6 "category B" agents and why are they categorized this way?
Definition
Less likely to be fatal, but still easy to access and disseminate.

2 Bs 2Rs and ES!

1) E. coli O157:H7
2) Salmonela
3) Burkholderia mallei (glanders)
4) Burkholderia pseaudomallei (melioidosis)
5) Rickettsia prowazekii (typhus fever)
6) Ricin toxin
Term
Which 3 agents are the "Category C" agents and why are they categorized this way?
Definition
Could be engineered

1) Nipah virus
2) Avian influenza virus
3) Hantavirus
Term
Which type A agent is a gram (+), spore-forming rod that is non-hemolytic, but will cause medusa's head/comet's tail colonies on blood agar?

Where is it found and what reservoirs hold it?
Definition
Anthrax (most commonly cutaneous)

Worldwide in Cattle, Sheep and Goats
Term
How can Anthrax be transmitted?
Definition
1) Cutaneous (1-7 days incubation leading to PAINLESS pruritic papule and Black eschar and localized lymphadenopathy)

2) Inhalation ("Woolsorter's" with incubation of 4-6 days with flu-like illness but NO RHINORRHEA. See bloodly pleural effusions, Mediastinal widening and hemorrhagic meningtitis)

3) GI (1-5 days incubation with Nausea, vomiting, ascites, bloody diarrhea and 40% mortality)

**Drug users!**
Term
How does Anthrax pathogenesis occur?
Definition
1) Germination of spore in environment that replicates and produces toxins.

2) Can stay in skin or disseminate.
Term
A patient presents with a flu-like illness, but no rhinorrhea.

You see bloodly pleural effusions, mediastinal widening and hemorrhagic meningtitis.

What exposure are you worried about and how do you treat?
Definition
Sounds like Inhalation Anthrax (Woolsorter's)

Treat with Doxicycline or Ciprofloxacin AND 1-2 additional antibiotics.
Term
A patient presents with Nausea and Vomiting, as well as massive ascites and hematemesis.

He admits to eating uncooked meat.

What exposure are you worried about and how do you treat?
Definition
GI Anthrax (40% mortality!)

Same as Inhalation

1) Ciprofloxacin or Doxycycline

AND

2) TWO of (rifampin, vancomycin, ampicillin, imipenem, clindamycin, clarythromycin)
Term
A patient presents with painless, black lesions and associated lymphadenopathy.

What exposure are you worried about and how do you treat?
Definition
Cutaneous anthrax

Treat with Doxycycline or Ciprofloxacin for 60 days!
Term
How can you diagnose a case of Anthrax poisoning?
Definition
1) Culture blood, CSF or effusion (EASIEST)- catalase (+), non-motile, gram-positive rods

2) Nasal swab for epidemiology

3) PCR, IHC, IgM test, 4-fold increase in IgG
Term
True or False:

There is no person:person transmission of Anthrax.
Definition
True!

It occurs through spores!
Term
How can you achieve post-exposure prophylaxis for Anthrax exposure?
Definition
3 doses of AVA vaccine and 60 days with Cipro or Doxy

Otherwise, AVA is given in 5 doses with a booster (produce Ab against "protective" antigen of spores.
Term
A patient presents with fever, chills, malaise, anorexia and lesions with lymphadenopathy.

You suspect Tularemia but want to confirm. What do you do and how might you treat?
Definition
Call Microbiology!

- Need sputum culture for gram-negative coccobacilli, a chest X-ray for inflammation and pleural effusion.

- Confirm with retrospective Antibody tests.

2) Treat with **Streptomycin** or gentamicin (IV) for 10 days

- can also try doxy, cipro or chloramphenicol (orals)
Term
How can you identify Francisella tularensis based upon bacterial morphology and biochemistry?
Definition
Naturally occurring through infected ticks REALLY INFECTIOUS

1) Gram-negative coccobacillus

2) Facultative intracellular pathogen
Term
What are the different Syndromes associated with Tularemia?
Definition
1) Ulceroglandular (most common with lesion and lymphadenopathy)

2) Oculoglandular, Pharyngeal, Glandular (lymphadenopathy), Pneumonic, Typhoidal (hardest to diagnose).
Term
Which group A toxin is a gram-negative bacillus with Bipolar staining ("safety pin")?
Definition
Yersinias pestis

You will see tender, swollen lymph nodes
Term
What virulence factors are associated with Yersinias pestis?
Definition
Disease of rodents coming from fleas.

1) Plasminogen activator: protease that promotes adhesion and coagulase in the flea mid-gut

2) Yersinia outer protein virulon: Type III secretion system

3) LPS
Term
Explain Y. pestis pathogenesis?
Definition
CONTAGIOUS- droplet for 72h

1) Fleas obtain blood meal with pathogen

2) Y. pestis multiplies and blocks flea metabolism

3) Fleas want to eat more from humans, and they throw up pathogen.
Term
What are the 3 defining symptoms of Y. pestis infection?
Definition
1) Acute febrile lymphadenitis (bubonic plague) with fevers, chills, headache and intensely painful, swelling LNs.

2) Pneumonic- lung infection with fever, cough, dyspnea and bloody sputum (50% mortality)

3) Septicemic- generalized, blood-stream infection after LN.
Term
How do you treat a case of Yersinia pestis?
Definition
Streptomycin IV for 10 days is preferred.

Can also use gentamicin, doxycycline, or cipro
Term
How can you prevent Yersinia pestis spread?
Definition
Doxy and Cipro for 7 days (oral)

NO VACCINE
Term
What are the defining features of Variola Major/minor?
Definition
1) DNA virus with human host.

2) 10-14 days incubation followed by rash 5 days later (maculopapular...vesicle...postule..crusting...scaring)

3) Severe subtypes include Hemorrhagic and Flat smallpox.
Term
True or False.

You can see maculopapular and Postule rash simultaneously in Smallpox.
Definition
False!

All the same at a time!
Term
When is Smallpox MOST contagious? When is it not contagious?
Definition
Onset of rash to first 7-10 days of rash (transmitted by aerosols, droplet nuclei, direct contact and fomites)

Infectious until scabs have healed.
Term
How and when do you isolate people with Smallpox?
Definition
Immediately in a Negative Pressure room

- Fit with N95 respirators to filter out infection.
Term
What are the differences between Variola and Varicella (smallpox vs. chickenpox)?
Definition
Variola- rash most dense on face and extremities, including palms (centrifugal) and DOESN"T ITCH.

Lesions appear over 1-2 days and evolve at same rate.

Varicella- Greater concentration on trunk (centripetal) that is rarely found on palms and is very ITCHY.

Lesions appear in different crops and different levels of maturity
Term
How long after exposure to Variola can you utilize the vaccine? How is the vaccine produced?
Definition
4 days

Before 2001: Grown on calf skin and contains polymyxn B (cell membrane disruption against gram negatives), streptomycin, tetracycline (gram positives) and neomycin.

It is live, so don't give in immunocompromised patients or in people with atopic disease.

Current: Grows in Vero cells and does not contain antibiotics. Same contraindications.
Term
How are the original (Dryvax) and current variola vaccines different?
Definition
Don't give EITHER to immunocompromised patients (HIV), Pregnant women, or those people with atopic skin disease (Eczema)!

1) Dryvax was grown on calf skin and contained antibiotics

2) Current vaccine is grown in Vero cells without antibiotics
Term
What life-threatening adverse reactions have been observed in response to the Variola vaccine?
Definition
1) Eczema vaccinatum- widespread skin infection in people with previous conditions

2) Progressive vaccinia- progressive infection at vaccination site with tissue destruction

3) Post-vaccinia encephalitis.
Term
Which viruses are known to cause Hemorrhagic Fevers and how are they spread??
Definition
1) Filovaridae- Ebola and Marburg

2) Arenaavirus- Lassa Virus and Machupo

- In animals (rodents primarily), spread by aerosol, urine, feces, fomites (objects), saliva, ocular.

- Humans have to contact blood or bodily fluids of animals.
Term
What clinical manifestations are associated with Viral Hemorrhagic Fever?
Definition
1) Fever
2) Petechiae
3) Bleeding
4) Severe illness
Term
Which Viral Hemorrhagic Fevers are contagious?
Definition
1) Ebola, Marburg- Filovirus (BATS)
2) Lassa (treat with Ribavirin/ not FDA approved)- Arenavirus (RODENTS).
3) Crimean (vector borne)
Term
Which Viral Hemorrhagic fevers response to antivirals?
Definition
Arenavirus (Lassa Fever and Machupo) respond to Ribavirin (not approved IV by FDA)
Term
True or False:

Botulism is contagious and infected people must be isolated.
Definition
False!

Spore-forming gram (+), anaerobic Baccillus is not contagious
Term
A patient presents with bilateral symmetric descending acute paralysis, but no fever or Tachycardia.

What is going on? How do you confirm/treat?
Definition
Sounds like Botulism exotoxin infection.

Botulism toxin is preventing Ach release from pre-synaptic nerve terminals.

- Confirm with culture, EIA and PCR.
- Treat with supportive care (ventilator) and give heptavalent anti-toxin (not FDA approved).
Term
1) Which group A agents are Gram (+) spore-forming bacilli?

2) Which are Gram-negative bacilli?

3) Which are RNA viruses?
Definition
1) Anthrax and Botulism
2) Tularemia (cocco-bacillus) and Y. pestis
3) VHF (arenaviridae and filoviridae)

**Variolo is an Orthopox virus**
Term
Which group A pathogens exhibit vector transmission?
Definition
1) Anthrax= livestock
2) Tularemia= rabbits, ticks, fleas
3) Y. pestis= Rodents, fleas
4) VHFs= rodents for arenaviruses (Ribavirin)
Term
What drugs are available to treat each of the group A pathogens?
Definition
1) Anthrax= PCN, Cipro, Doxycycline

2) Tularemia= Streptomycin
3) Y. pestis= Streptomycin

4) Smallpox= cidofovir?

5) Botulism= anti-toxin
Term
Which group A pathogens have available vaccines?
Definition
1) Anthrax (5 doses + yearly booster)
2) Smallpox (eradicated).
Term
Where do you find Tularemia most commonly?

What about VHFs?
Definition
1) M. Vineyard
2) Africa
Term
Which group A agents are contagious?
Definition
Y. pestis (plague), Variola and VHF's

Tularermia, Anthrax and Botulism cannot be transmitted Human:Human!
Term
Which group A pathogen has a "Medussa Head" rash?
Definition
Bacillis antracis
Term
What Virulence factors are associated with Anthrax?
Definition
1) Polyglutamic acid capsule (PGA) encoded on plasmid

2) Edema Exotoxin (protective antigen + edema factor)- adenylate cyclase

3) Lethal Exotoxin (protective antigen + lethal factor)- calmodulin-dependent zinc metalloprotease that cleaves MAPKKs.
Term
Which group A pathogens cannot be transmitted Human:Human?
Definition
Tularermia, Anthrax and Botulism cannot be transmitted Human:Human!
Term
How do methods of treatment/prevention for Y. pestis differ from F. tularemia?
Definition
Both use Streptomycin for treatment and Cipro/Doxy for prevention.

1) F. tularemia treats with Streptomycin for 10 days and prevents with Cipro/Doxy for 14 days post-exposure

2). Y. pestis treatment is for 10 days and prevention is for 7 days
Term
How is Ebola most commonly contracted and how does it exert its pathogenesis?
Definition
1) Bush meat with Bat reservoir

2) 7 genes for damage and nosocomial spread is an issue.
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