Common Viral Pathogens V

Question 1

RSV route and mechanism of infection

Answer 1

• Respiratory
• Invades conjunctiva/nasopharynx. Initially replicates in the nasopharynx and primarily replicates in respiratory epithelium. Spreads to lower respiratory tract by inhalation of secretions or spread by the respiratory epithelium

Question 2

RSV organs infected and consequences on clinical disease presentation

Answer 2

RSV causes severe damage to the epithelium and bronchiolar ciliary apparatus

• Results in collection of fluid in the bronchioles andalveoli
• This causes obstruction of bronchioles and alveoli, causes collapse of emphysema of airway
• Constriction of smooth muscle in bronchioles
• Ventilation / perfusion mismatch, hypoxia
• Hyperexpansion by mucous plugging

Clinically, you see:
o Respiratory distress
o Hear wheezing/rhonchi on auscultation
o Hypoxia
o Copious secretions

Question 3

Ebola route and mechanism of infection

Answer 3

Enters body through mucosal surfaces or cuts to the skin
• You only need a few virions for infection
• Ebola initially enters phagocytic cells, sends signal for more cells to come, which facilitates infecting those cells; also spreads efficiently when cells go to lymph nodes, which allows ebola to infect more immune cells
• When it infects cells:
— Replicates VERY efficiently, can get viral loads 106-108 copies/mL (up to 1010 described)
— Once in the cell, induces a massive cytokine storm – cytokines and similar molecules desctory vascular endothelium, induce disseminated intravascular coaculation (DIC)

Question 4

Ebola organs infected and consequences on clinical disease presentation

Answer 4

— After initial infection of phagocytes, then goes to infect many other cells/organs in the body including: endothelial cells, liver, spleen, lungs
— When Ebola infects parenchymal cells, get significant cell destruction/necrosis
— With infection of endothelial cells, get leakage of fluids, severe fluid loss, hypovolemic shock, organ failure (hypovolemia and direct invasion)
— People die from hypovolemia +/- organ failure
• Symptoms of Ebola are non-specific – GI, fever, fatigue/weakness; very similar to other illness which are common (malaria, typhoid, dysentery)
• People develop significant 3rd spacing, loose a lot of fluids through capillary leak, vomiting and diarrhea (can loose 5-10 liters/day)

Question 5

Ebola, in general

Answer 5

• The immune system becomes overwhelmed and, therefore, dysregulated
• Initial cytokine release signaling for more immune cells to come to the area of initial infection, helps ebola to spread
• Some antibodies may enhance cell entry of the virus
• Other immune cells are prompted to die (apoptosis)
• The liver is infected early on, which is an important organ for shutting off the immune response by clearing the cytokines from circulation

Question 6

transmission of influenza

Answer 6

respiratory or contact with infectious particles can occur by contamination of hands or inanimate objects (fomites) then touching mucosal surfaces. Virus lives on human hands for about 5 minutes, on steel or plastic for 24-48 hours, and cloth or paper tissues for 8-12 hours. (incubation 1-3 days)

Question 7

prevention of influenza

Answer 7

Vaccines, hand washing, sneezing into your arm rather than your hands

Question 8

transmission of RSV

Answer 8

large droplet spread

Question 9

prevention of RSV

Answer 9

No good vaccine!
o RSV immunoprophylaxis with Palivizumab (Respigam)
—Respigam is a human pooled antibody with high RSV titers, shown to have a decrease in disease severity and hospitalization
—A mouse monoclonal anti-RSV antibody was then developed: Palavisumab (Synagis), licensed in 1998
—Once monthly IM injection during RSV season for high-risk groups of young children
—Very expensive

Question 10

Ebola transmission

Answer 10

spillover events from animal reservoirs with subsequent human-to-human transmission (bats as reservoir host?)

• Initial cases often tied to hunters or slaughtering animals
• Then get human-to-human transmission; health care workers at very high risk

Question 11

Ebola prevention

Answer 11

-isolation = The more ill someone is, the more contagious, and Ebola can be found and body fluids and may last longer than symptoms
There are no approved Ebola-specific therapies, care is supportive:
-Fluid repletion
-dialysis, ventilation
-Critical care is associated with better outcome
Supporting patients while they mount an immune response, survivors have detectable antibodies for at least 10 years
-Mortality of ZEBOV in prior outbreaks is 42-88% (CDC)

Question 12

Influenza IIV

Answer 12

• killed
• IM injection
• 3/4 strains
• can use in 6 mo+
• safe for preg and immunocompromised

Question 13

Influenza LAIV

Answer 13

• live
• intranasal
• 4 strains
• 2-49 years
• not save in preg or immunocompromised

Question 14

RSV vaccine

Answer 14

No good vaccine!
Vaccine in the 1960s, formalin-inactivated RSV vaccine; did not produce protective immunity and children who were immunized has worse disease -> Showed risk of “priming” for an infection without developing immunity, this occurs with dengue

Question 15

Ebola vaccines

Answer 15

2 vaccines started human trials in 9/14, plan to start Phase II/III trials very soon
-GSK and NIH collaboration: cAd3-ZEBOV
-PH Agency of Canada, licensed to NewLink Genetics, who licensed to Merck: rVSV-ZEBOV
3rd vaccine is in Phase I in the UK