BIO 1080 Case Study: Plague (Yersinia pestis)

This set of vocabulary flashcards covers the causative agent, clinical forms, treatments, and diagnostic testing for plague as discussed in the BIO 1080 Case Study.

The specific cause (genus and species) of plague? what is the gram reaction and morpholgy ?

Yersinia pestis , gram negative rods

How is the plague bacterium most commonly transmitted to humans? How do you

suppose Oscar acquired the infection?

Usually transmitted by flea bites, also direct contact or aerosol. In nature, the

reservoir is several species of rodents.

The vet in this case suspected plague because of the appearance of the neck lesion.

What are 3 DIFFERENT TYPES laboratory or medical tests that could be used to confirm

this diagnosis? NOTE: this is not an easy question, so do your best. However, an answer

like “blood test” is not sufficient – what are they testing for? The CDC web site is one

good source.

Gram stain (or other more specialized stain) on a smear or aspirate of lesion.

- PCR for detection of specific Y. pestis DNA sequences.

- ELISA or other immunological test for anti-Y. pestis Ab.

Briefly describe two distinct clinical forms of plague:

Bubonic – characterized by “bubos”, which are infected/inflamed lymph nodes

- Pneumonic – respiratory form, usually fatal

- Septicemic – spreads in body via the blood

List three antibiotics that are commonly used to treat plague. For one of these drugs,

very specifically describe its mechanism of action/target:

- streptomycin, tetracycline, chloramphenicol. See Web sites for mechanisms;

most of these interfere with protein synthesis by binding to ribosomes

Plague is considered one of the most important agents for bioterrorism. What are two

specific characteristics of plague (the bacterium or the disease) that make it so attractive

to bioterrorists?

can be spread via the air, incubation period is long enough to allow further

transmission prior to disease symptoms, respiratory form is highly fatal and scary

currently there is no FDA-approved vaccine for plague in the U.S. A killed whole-cell

vaccine was available, but the manufacturer withdrew it from the U.S. market in 1999.

What do you think might have been two possible, specific reasons for this?

- vaccine may not have been very effective, especially against the pneumonic form

- safety issues, especially local reactions

- not very profitable because of low risk of plague

Define these following terms

a. erythematous

b. conjunctival injection

c. cellulitis

d. pedal pulse

e. fasciotomy

Define the following terms:

A. redness of the skin, usually due to inflammation

b. redness due to vasodilation in epithelial layer of sclera and eyelid

c. inflammation of the skin and deep underlying tissues

d. increased blood pressure (pulse) felt at the tibial artery in ankle

e. cutting the fascia to relieve pressure

What 2 species of bacteria most commonly cause TSS?

-Staphylococcus aureus and Streptococcus pyogenes

oth types of TSS are caused by toxins. What is the major type of toxin involved in

TSS?

An exotoxin or more specifically, a superantigen

hy is the mechanism that produces fever and hypotension in TSS? (Note – although

this is a different type of toxin, the mechanism of production of fever, shock, etc. is similar to

the mechanism of endotoxin that was one of the essay question choices on Exam 2)

- superAgs cause release of proinflammatory cytokines like IL-1, IL-6, TNF, which act on

hypothalamus to induce fever, and induce massive release of histamine from mast cells,

etc., causing systemic vasodilation

What type of antibiotic is clindamycin, and what is its mechanism of activity?

A macrolide, inhibits 50s ribosome, methylation of 23S ribosomal RNA at A2503.

ompare the following terms with regard to the type of bacteria that are typically

involved, the source (how produced by the bacteria), and the (concise) mechanism by which

each causes disease

Endotoxin

Exotoxin

Gram negative, O.M. , overactivation of macrophages by__ LPS (binds to a PAMP receptor)

Gram positive, secreted , overactivation of TH cells follows large amount of TH-APC interaction

(specific mechanism of Sags)

Bacteria source mechanisim

treptococcus pyogenes also produces a virulence factor called streptokinase. What

is this toxin’s mechanism of activity, and how has streptokinase been used medically?

streptokinase dissolves blood clots (it is thrombolytic) by binding to and activating

plasminogen, which becomes plasmin, an enzyme that breaks down fibrin in clots.

What type of virus causes rabies? (viral family, type of nucleic acid, enveloped or not)

- rhabdovirus, ssRNA, enveloped

Rabies is a negative sense (antisense) virus. What specific type of enzyme must be contained in

the virus (i.e., brought into the cell) to copy the viral nucleic acid, and why?

- RNA-dependent RNA polymerase, because negative-strand viruses have RNA that has to

be converted into positive-sense before it can code for any proteins, and the host cell does

not contain such an enzyme.

How is the rabies virus most commonly transmitted? How else can humans be infected?

by bites (saliva) of infected animals; also contact between saliva of infected animal and

scratches, open wounds, or mucous membranes, and aerosol in bat caves and rabies labs

he CDC website states that “petting a rabid animal or contact with the blood, urine or feces (e.g.,

guano) of a rabid animal, does not constitute an exposure and is not an indication for prophylaxis.”

So do you agree or disagree that these 90 children needed to be treated for rabies exposure? Why

or why not?

a matter of opinion, although the CDC recommendation does seem unrealistic since

parents would be very concerned about any potential exposure of their kids to rabies.

What about the cat that had the bat in its mouth? As a physician or veterinarian consulting on this

case, what is the SINGLE most important question you need to ask the cat’s owner, and what

precautions should be taken?

-the KEY question is--has the cat been vaccinated against rabies? If the cat is current on

rabies vaccinations, there should be no concern. If not, the cat may need to be quarantined,

depending on state law (especially since no evidence is given that the cat was bitten by the

bat) or possibly euthanized and tested

What are the most common symptoms of rabies infection in bats (what might raise your suspicion

that a bat has rabies)?

- a bat that is active in the daytime, or does not fear people, or otherwise acts weird and un-

bat-like.

Of the common domestic animals found in the U.S., which can contract rabies, and which cannot?

Do all those that can develop the typical “foaming at the mouth”? (see: “Old Yeller rabies scene”:

- dogs, cats, cows, horses commonly contract rabies, birds do not.

- typical rabies is called the “furious” form; many animals instead develop the “dumb” or

paralytic form

What are the most common early symptoms of rabies infection in humans? Is it always fatal?

fever, headache, fatigue, pain or numb at bite site. Later insomnia, anxiety, confusion,

agitation, hypersalivation, difficulty swallowing, hydrophobia (fear of water; this is a

PATHOGNOMONIC (unique to rabies) sign). Rabies is almost always fatal if not treated, only

one person in U.S. has survived after signs/symptoms appear.

There are two brands of rabies vaccines approved for us in the U.S. Are these vaccines

considered to be “live” attenuated, or “killed” inactivated? In general, what is one advantage, and

one disadvantage of this type of vaccine?

both are inactivated virus vaccines. Advantages include virtually no chance of reversion

to virulence (cannot cause rabies), perhaps better and longer-lasting immunity.

Disadvantages include more antigen required, usually must be adjuvanted, which can

increase local or systemic adverse effects.

The rabies vaccine is only recommended for people with what jobs? Why isn’t it one of the

required childhood vaccines?

- people at relatively high risk such as vets, animal control workers, rabies lab workers.

The risk of contracting rabies is very low in U.S. due to routine vaccination of dogs &

cats.

When a person is bitten by a rabid animal, they generally receive two treatments, rabies vaccine

plus rabies immune globulin. Which of these treatments is meant to stimulate active immunity, and

which provides passive immunity? (in your answer make sure to define the difference)

- vaccine stimulates active immunity, because the person receiving the vaccine

produces their own immune response;

- RIG provides passive immunity (I don’t like the word “stimulates” here, because it

isn’t really a “response”), which means the Abs were produced by someone else – can

provide quick immunity but only lasts maybe 3-6 weeks (BTW this is currently being

used for some patients with COVID-19)

What is rabies immune globulin (Imogam), and how is it prepared?

- Imogam is the gamma globulin fraction (mostly IgG) from serum of people vaccinated

against rabies. It is prepared by cold alcohol fractionation from pooled venous plasma

of individuals immunized with Rabies Vaccine. A heat-treatment process step (58° to

60°C, 10 hours) to inactivate viruses has been added to further reduce any risk of

blood-borne viral transmission

Upon likely exposure to rabies, when and how should Imogam be administered?

one source says the full dose of Rabies Immune Globulin (Human) (RIG) should be

thoroughly infiltrated in the area around and into the wounds. However a package insert

I found online say Imogam should be injected intramuscularly at a site distant from

vaccine administration. Maybe half and half?

What are TWO very specific immunological mechanisms by which the antibodies contained in

Imogam could prevent rabies in a person who has been infected? (NOTE these will be

covered in the lecture over Chapter 15, Host Defenses II.

- neutralization = prevention of virus binding to cellular receptors

- opsonization = increased phagocytosis of virus

- complement activation – may damage viral envelopes

- antibody-dependent cellular cytotoxicity – Abs bind to rabies virus proteins on

infected cells, NK cells recognize using Fc receptors and kill cell by apoptosis

The description of this case says the bat was confirmed to have rabies:

The classic way to do this was to demonstrate Negri bodies in sections of brain tissue. In

virology terms, what are these “bodies”?

inclusion bodies, which are a type of cytopathic effect. NOTE that Negri bodies are

pathognomonic for rabies, meaning their presence always indicates rabies. However

Negri bodies are not always present in rabies.

A fluorescent antibody test is also available for detection of rabies virus in brain sections. How

does this test work, and what is an advantage of this test over the Negri body test?

- take sections of brain, incubate with fluorescent-labeled anti-rabies virus Ab, look for

fluorescent spots where virus is present. The FA test is more sensitive; mostly because

Negri bodies are absent from the brains of some people who died of rabies.