Arboviruses and Prions

Question 1

Contrast the transmission cycles of arboviruses

Answer 1

See image below

**the most important thing is that the sylvatic cycle is the most common for most of the arboviruses, and you need to know which viruses replicate how

Question 2

Which protein on the Flavivirus envelope is the immunodominant antigen against which antibodies are made?

Answer 2

The E protein (envelope) is the immunodominant antigen used to generate antibodies against YFV (and I guess flavi’s in general)

Question 3

Describe the pathogenesis of yellow fever (hint: after the virus infects the human via mosquito bite, where does it go? what is the ultimate cause of death? remember there’s a reason why this is YELLOW fever)

Answer 3

mosquito bite >> viremia (w/ non specific febrile illness) >>liver hepatocyte apoptosis, jaundice >> downstream complications (mainly related to dyregulated clotting leading into DIC, hemorrhage, cytokine dyregulation, all of which eventually leads to shock >> death)

Question 4

Describe the presentation of yellow fever (again, remember that this is YELLOW FEVER)

Answer 4

Initial symptoms (viremia): High fever, myalgia, lumbosacral pain, headache, nausea

Labs: leukopenia, neutropenia

Later on (if disease doesn’t subside which it does in most cases): jaundice (+yellowing in eyes) and the blood clotting problems; convulsions (in kids); tender liver

Labs: proteinuria, elevated Abs

Question 5

How do you Dx yellow fever?

What is the Rx for yellow fever?

T/F: There is no vaccine for yellow fever

Answer 5

Primarily serology: looking for yellow fever specific IgM antibodies

There is a yellow fever vaccine that is live attenuated and made from the 17D strain

No real rx other than supportive care:

**

maintenance of nutrition

prevention of hypoglycemia

treatment of hypotension by fluid replacement

treatment of bleeding with fresh-frozen plasma

dialysis if indicated by renal failure

Question 6

___ is the most important cause of viral encephalitis in Asia

Describe the transmission of this virus

Answer 6

Japanese Encephalitis Virus

Transmission: the virus circulates between mosquitoes and birds/domestic pigs (pigs are amplifiers; birds are the natural hosts) and makes its way from mosquito to human

Question 7

Describe the initial/severe disease presentation of Japanese Encephalitis virus

Answer 7

Initial presentation is a typical febrile illness characterized by fever, diarrhea, headache, vomiting, weakness

Later presentation: standard encephalitis symptoms (mental status changes, +/- partial paralysis/stiffness, coma, seizures (esp in kids)

Question 8

How do you Dx JEV? Since JEV causes encephalitis like a million other encephalitis-causing viruses that you’ve learned about, how can you differentiate JEV from the other ones?

How do you Rx JEV?

Answer 8

Dx:

Labs: elevated WBCs, mild anemia, elevated CSF pressure

CSF/serum detection of JEV specific IgM abs - indicate recent infection

**

No real Rx except supportive care (and an inactivated vaccine)

Question 9

How is Dengue virus transmitted?

Answer 9

Via mosquito bite thru the Aedes mosqito but note that this virus engages in all 3 types of cycles (i.e. enzootic, rural epizootic and urban epidemic)

Question 10

Describe the presentation of primary dengue

Answer 10

(same for all 4 serotypes)

Sudden onset of fever, chills, severe “breakbone” ache in back, head and extremities

Rash over face, thorax

Fever lasts 2-7 days (longer fever is probably not dengue)

**

Important pathologic feature: capillary edema and leakage >> shock and bleeding

Recovery phase: high IgG/IgM as the viremia is tapering off

Question 11

Describe the presentation of secondary infection with Dengue virus

Answer 11

Dengue hemorrhagic fever

(basically a much worse version of primary infection that arises when you get a re-infection with a DIFFERENT serotype of Dengue virus following primary infection)

Shock caused by plasma leakage, low pulse and blood pressure

Question 12

What causes Dengue Hemorrhagic Fever?

Answer 12

Antibody dependent enhancement: you get infected with one strain of Dengue virus and you make Abs to it. Upon re-infection with a different strain of virus, the antibodies don’t recognize the new strain and instead promote uptake of the virus into immune cells via ADCC, which basically leads to a more severe infection

Question 13

How do you Rx Dengue virus?

Answer 13

You don’t really. No Rx except for supportive care (fluids and anti-inflammatory agents

**note that there’s a vaccine but its ltd (doesn’t confer protection against all 4 strain)**

Question 14

___ is a Flavivirus that has a propensity for growing in the neurons in the brain and can accumulate to high levels in the sperm (making it the only Flavivirus to be sexualy transmitted)?

Answer 14

Zika virus

Question 15

Which cells does Zika virus like to infect? (hint: 4 types)

Describe the clinical presentation of Zika infection.

What ascending paralysis syndrome is Zika virus ass’d with?

Answer 15

Low grade fever, pruritic rash (erythematous macules on face, trunk, extremities, palms, and soles), arthralgia (esp in joints of hands and feet) and conjunctivitis

**same symptoms in kids but for arthralgia, look for altered gait and irritability**

**note that Zika virus is ass’d w/ Guillain-Barre syndrome**

Question 16

How do you Dx Zika virus infection?

Answer 16

RT-PCR for Zika rna in serum, urine, whole blood (there’s higher rna levels in the urine)

Also do serology/ELISA using Zika virus specific antibodies

Question 17

What is a major manifestation of Zika virus infection in pregnant mothers?

Answer 17

Babies born with microcephaly and other neural defects (remember that the virus likes to infect neurons)

Question 18

Describe the pathogenesis of Chikungunya (what pathology does the virus cause)?

To what virus family does Chikungunya belong to?

Answer 18

Chikungunya causes massive joint inflammation

The virus enters thru mosquito bite >> infects fibroblasts >> disseminates to blood >> target organs (muscles, joints, skin and other organs) >> recruitment of inflammatory cells >> inflammation of joints

**Chikungunya is a Togavirus (alphavirus). It’s the C in Toga CREW**

Question 19

Describe the presentation of Chikungunya

Answer 19

Basically a typical presentation with abrupt onset of fever, rash, (others like headache, fatigue, conjunctivitis), and **severe joint pain**

Question 20

How do you Dx Chikungunya?

What is the Rx for Chikungunya infection?

Answer 20

Dx: serology most useful (can detect antigen for a long time)

Rx: none really except supportive care w/ NSAIDs

Question 21

What disease is caused by prions?

Answer 21

Prions cause Transmissible spongiform encephalopathy (TSE) aka Creutzfeldt-Jakob Disease (CJD)

Question 22

What is the hallmark of prion disease in humans?

What is this disease called in sheep?

Answer 22

Presence of microscopic vacuolization of the brain tissue called spongiform degeneration

In sheep: Scrapie

**note that prions are VERY resistant to any kind of killing you can think of (UV, heat inactivation etc)

Question 23

What is the difference between the normal prion protein and the disease causing form?

Answer 23

Normal form - has alpha helices. Disease-causing form - mostly beta sheets

Question 24

Describe the replication cycle of prions

Answer 24

The prions are self replicating. Basically they bind normal prion protein and convert that to the disease form. Once that happens, the disease form just makes more and more of itself.

**there’s also something about once the protein forms, it goes to the membrane of the cell that it infects and forms fibrils or something that then lead to formation of amyloid plaques in neuronal cells**

Question 25

Since prions are very resistant to pretty much all kinds of chemical treatments, how do you inactivate them?

Answer 25

Incineration (like you would do for surgical equipment used for pt with prion disease)

Combo if autoclaving and chemical treatment of instruments

Question 26

Name the 4 different kinds of prion diseases that affect humans

Answer 26

Sporadic prion disease

Famailial CJD

Acquired CJD

Iatrogenic CJD

Question 27

Describe the symptoms of prion diseases in humans

Answer 27

**mainly point out the ones that aren’t in any other disease learned thus far**

Rapidly developing dementia

Difficulty walking and changes in gait

Hallucinations

(others: muscle stiffness, confusion, fatigue, difficulty speaking but you could find these with the other diseases)

Question 28

Name the manifestations of familial CJD

Answer 28

fCJD

Fatal familial insomnia (the one in which you literally cannot sleep and so you die from all the effects of being ultra exhausted)

GSS

Question 29

Name the types of sporadic prion disease

Answer 29

Sporadic CJD

Sporadic fatal insomnia

Variably protease sensitive prionopathy (VPSPr) – slow developing sporadic prion disease

Question 30

Describe iatrogenic CJD

Answer 30

Literally you got the disease from an external source that was put in your body. Whether from un-inactivated surgical equipment, transplants of brain matter, cornea transplants etc

Question 31

Describe the types of acquired CJD

Answer 31

Kuru - the one from the folks in Guinea that allegedly ate the brains of the dead

Variant CJD - from eating contaminated meat (like beef from a cow that had mad cow disease)

Question 32

How do you Dx prion diseases?

Answer 32

No real way to Dx prior to a person’s passing

BUT: can do neuro exam, and sequencing of the prion protein gene to see mutations linked to familial prion diseases

Confirm (after pts passing) w/ histopathology/western blot of prion protein in brain tissue

**can do PMCA - protein misfolding cyclic amplification - you’re basically taking disease form protein and normal protein and doing a series of dilutions until all normal protein is essentially converted to disease form protein

Question 33

What is the Rx for prion disease?

Answer 33

None