Viral Haemorrhagic Fever

Question 1

What can happen in Viral Haemorrhagic fevers (VHF)?

Answer 1

Severe multisystem syndrome
Damage to the vascular system
Haemorrhage

Question 2

What is the disease spectrum for viral haemorrhagic fever?

Answer 2

Mild illnesses

Fatal (roughly 90% cases)

Question 3

Who is the primary host for VHFs?

Answer 3

Humans not primary host
Range of viruses associated with VHFs
Relatively rare worldwide & not usually found in Scotland

Question 4

What are some examples of VHFs in Glasgow?

Answer 4

Crimean-Congo haemorrhagic fever virus (2012)
Ebola virus (2014 & 2015)

Question 5

What are common features of VHFs?

Answer 5

Enveloped RNA viruses
Animal or insect hosts
Sporadic human outbreaks
Generally no effective vaccine or antivirals

Question 6

What is required as a host for VHFs?

Answer 6

Natural reservoir
Arboviruses
Geographically restricted: determined by host species range

Question 7

Why do human outbreaks occur with VHFs?

Answer 7

Due to contact with host species
Can be transmitted between humans
Cannot be predicted
Seasonality (rainy/warmer/trees fruiting)

Question 8

What is the only VHFs with a vaccine?

Answer 8

Yellow fever virus vaccine

Question 9

What are examples of Arenaviridae?

Answer 9

Lassa
Machupo
Junin
Guanarito
Sabia

Question 10

What are some examples of Bunyaviridae?

Answer 10

Hantaan
Crimean-congo
Rift valley fever
SFTSV
Heartland

Question 11

What are some examples of Flaviviridae?

Answer 11

Dengue (DHF)
Yellow fever (YF)
Chikungya (CHF)

Question 12

What are some examples of filoviridae?

Answer 12

Ebola (EHF)

Marburg (MHF)

Question 13

What is the Ebola virus?

Answer 13

Filoviridae
Filo- thread like
Ebola- river in DRC
Filamentous, plemorpic particles
Can be stained and viewed in patients blood by electron microscopy

Question 14

What is the filovirus outer structure?

Answer 14

Outer envelope has glycoproteins (GP) on surface

Question 15

What does the outer envelope of the filovirus surround?

Answer 15

A matrix containing the nucleocapsid (NP)

Question 16

What is genomic RNA encapsilated by in the filovirus?

Answer 16

NP

Question 17

What do regulatory regions do in filovirus?

Answer 17

Flank the coding regions (7 genes)
Nucleoproteins (NP & VP30)
Polymerase complex (VP35 & L)
Membrane associated proteins (GP, VP40 & VP24)

Question 18

What are viral proteins translated from?

Answer 18

Subgenomic messenger RNA

Question 19

What is filovirus subgenomic mRNA transcription?

Answer 19

L protein binds at 3’ end
Subgenomic mRNA generated from transcription start signals
Terminates at stop signal
Polymerase releases at stop and reinitiates
mRNA capped and Poly (A)d
Transcriptional gradient of mRNA levels 3’ to 5’

Question 20

What is the filovirus replication cycle?

Answer 20

Receptor binding
Genome transcribed & replicated in cytoplasm
Viral proteins translated
Proteins and negative strand genome packaged into particles
Virus buds from the cell

Question 21

When does acute onset of Ebola occur?

Answer 21

2-21 days

Question 22

What are the symptoms of acute onset of Ebola?

Answer 22

Fever, chills, myalgia

Question 23

What are then the further symptoms of ebola?

Answer 23

Vomiting, abdominal pain, diarrhoea, chest pain, wheezing, headache, confusion, coma
Haemorrhage
Shock and convulsions (roughly 50% cases)

Question 24

Where is the natural host reservoir for Ebola?

Answer 24

Fruit bats
Direct contact with infected animals
Fruit bats thought to infect primates

Question 25

How did humans get Ebola?

Answer 25

Transmission from pigs to non-human primates

Question 26

Where do localised outbreaks of Ebola continue to occur?

Answer 26

Central and West Africa

Question 27

What are the number of infections in central and west africa?

Answer 27

1900

Question 28

How many deaths have there been in central and west africa?

Answer 28

1300 deaths pre 2013

Question 29

How many deaths were there between 2013-2016?

Answer 29

>12,000 deaths

Question 30

What could see the spread of Ebola?

Answer 30

Global warming, increased air travel

Question 31

What do more outbreaks of Ebola increase?

Answer 31

The potential for bioterrorism

Question 32

What is required urgently for Ebola?

Answer 32

Effective and safe vaccine

Question 33

What is the ebola vaccine using glycoprotein gene?

Answer 33

Trialled in the UK- 72 participants Phase 1 clinical trial vaccine/Placebo Protected monkeys- Zaire

Question 34

What is the ebola vaccine using GSK (Adenovirus+ Zaire & Sudan)

Answer 34

Trialled in the USA- 20 participants | Antibodies produced, well tolerated and seems effective

Question 35

What work is being done for a vaccine in the national microbiology lab, Canada?

Answer 35

Phase one trial, called VSV-ZEBOV (Vesicular stomatitis virus) Volunteers reported joint pain Resumed the trial- lower dose of vaccine VSV-EBOV one gene of VSV has been replaced with GP of Zaire EBOV

Question 36

What is Yellow fever?

Answer 36

Liver disease Jaundice a major symptom Hence the name 1st human virus 1901

Question 37

What is acute infection of yellow fever?

Answer 37

3-6 days incubation Death in 20-50% of severe cases After 7-10 days of illness

Question 38

What is Dengue?

Answer 38

Dengue haemorrhagic fever | Fatality rates 1-10%

Question 39

What is both Yellow fever and dengue?

Answer 39

Arboviruses

Question 40

How can human to human transmission occur in HF?

Answer 40

Mosquito (YF) | Blood/needles (Ebola)

Question 41

What is the flavivirus genome organisation?

Answer 41

Positive sense RNA genome 10kb in length Transcribed then translated into a glycoprotein that is cleaved by viral proteases Structual genes 5’ end & NS 3’

Question 42

How did Yellow fever (YF) and mosquito vector spread to the US?

Answer 42

Via shipping

Question 43

What were the original fatalities in the US due to YF?

Answer 43

15% in Philidelphia (1793) | 28% in New Orleans (1853)

Question 44

Who discovered mosquitoes caused YF?

Answer 44

Carlos Finlay and Walter reed (1880-1900)

Question 45

What vaccine was developed for yellow fever and when?

Answer 45

17D vaccine developed in 1937

Question 46

How many deaths were due to yellow fever?

Answer 46

>10,000 deaths pa ww

Question 47

What is the Yellow fever vaccine?

Answer 47

Live attenuated yellow fever vaccine (mutations in E) Grown in infected chicken embryos 95% protection, 10 days p.i. Life-long immunity

Question 48

What is the safety of yellow fever vaccine?

Answer 48

Very few side effects (allergic reactions & some reports of neurological complications, 1 in 1,000,000)

Question 49

What can not be infected orally with 17D?

Answer 49

Ae. Aegypti

Question 50

Why can't Ae. Aegypti be infected orally?

Answer 50

No natural transmission of vaccine virus | No chance of reversion to virulence

Question 51

What is dengue haemorrhagic fever (DHF) vector controls?

Answer 51

Aedes aegypti- mosquito host for dengue and yellow fever Vector control measures collapse in 70s/80s Mosquito reinvades Emergence of epidemic dengue and dengue haemorrhagic fever Increased in yellow fever

Question 52

Where does dengue occur?

Answer 52

Asia, Afria and the Americans

Question 53

Where does yellow fever not occur?

Answer 53

Asia

Question 54

What are some of the ecological changes that are risk factors in contracting a VHFs?

Answer 54

Travel- globalisation Urbanisation- changing vector habitats or moving humans into new areas Environmental manipulation- Dam building

Question 55

What are some large scale changes in virus ecology introduced by humans?

Answer 55

``` Air conditioning Blood transfusion Xenotransplantation Long distance movement of animals Sexual practices Drug use Irrigation Deforestation Used tires Uncontrolled urbanisation Day care centres Cruise ships Rerouting of migratory patterns ```