Viral Haemorrhagic Fevers Flashcards
What can happen in Viral Haemorrhagic fevers (VHF)?
Severe multisystem syndrome
Damage to the vascular system
Haemorrhage
What is the disease spectrum for viral haemorrhagic fever?
Mild illnesses
Fatal (roughly 90% cases)
Who is the primary host for VHFs?
Humans not primary host
Range of viruses associated with VHFs
Relatively rare worldwide & not usually found in Scotland
What are some examples of VHFs in Glasgow?
Crimean-Congo haemorrhagic fever virus (2012) Ebola virus (2014 & 2015)
What are common features of VHFs?
Enveloped RNA viruses
Animal or insect hosts
Sporadic human outbreaks
Generally no effective vaccine or antivirals
What is required as a host for VHFs?
Natural reservoir
Arboviruses
Geographically restricted: determined by host species range
Why do human outbreaks occur with VHFs?
Due to contact with host species
Can be transmitted between humans
Cannot be predicted
Seasonality (rainy/warmer/trees fruiting)
What is the only VHFs with a vaccine?
Yellow fever virus vaccine
What are examples of Arenaviridae?
Lassa Machupo Junin Guanarito Sabia
What are some examples of Bunyaviridae?
Hantaan Crimean-congo Rift valley fever SFTSV Heartland
What are some examples of Flaviviridae?
Dengue (DHF)
Yellow fever (YF)
Chikungya (CHF)
What are some examples of filoviridae?
Ebola (EHF)
Marburg (MHF)
What is the Ebola virus?
Filoviridae Filo- thread like Ebola- river in DRC Filamentous, plemorpic particles Can be stained and viewed in patients blood by electron microscopy
What is the filovirus outer structure?
Outer envelope has glycoproteins (GP) on surface
What does the outer envelope of the filovirus surround?
A matrix containing the nucleocapsid (NP
What is genomic RNA encapsilated by in the filovirus?
NP
What do regulatory regions do in filovirus?
Flank the coding regions (7 genes)
Nucleoproteins (NP & VP30)
Polymerase complex (VP35 & L)
Membrane associated proteins (GP, VP40 & VP24)
What are viral proteins translated from?
Subgenomic messenger RNA
What is filovirus subgenomic mRNA transcription?
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’
What is the filovirus replication cycle?
Receptor binding
Genome transcribed & replicated in cytoplasm
Viral proteins translated
Proteins and negative strand genome packaged into particles
Virus buds from the cell
When does acute onset of Ebola occur?
2-21 days
What are the symptoms of acute onset of Ebola?
Fever, chills, myalgia
What are then the further symptoms of ebola?
Vomiting, abdominal pain, diarrhoea, chest pain, wheezing, headache, confusion, coma
Haemorrhage
Shock and convulsions (roughly 50% cases)
Where is the natural host reservoir for Ebola?
Fruit bats
Direct contact with infected animals
Fruit bats thought to infect primates
How did humans get Ebola?
Transmission from pigs to non-human primates
Where do localised outbreaks of Ebola continue to occur?
Central and West Africa
What are the number of infections in central and west africa?
1900
How many deaths have there been in central and west africa?
1300 deaths pre 2013
How many deaths were there between 2013-2016?
> 12,000 deaths
What could see the spread of Ebola?
Global warming, increased air travel
What do more outbreaks of Ebola increase?
The potential for bioterrorism
What is required urgently for Ebola?
Effective and safe vaccine
What is the ebola vaccine using glycoprotein gene?
Trialled in the UK- 72 participants
Phase 1 clinical trial vaccine/Placebo
Protected monkeys- Zaire
What is the ebola vaccine using GSK (Adenovirus+ Zaire & Sudan)
Trialled in the USA- 20 participants
Antibodies produced, well tolerated and seems effective
What work is being done for a vaccine in the national microbiology lab, Canada?
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
What is Yellow fever?
Liver disease
Jaundice a major symptom
Hence the name
1st human virus 1901
What is acute infection of yellow fever?
3-6 days incubation
Death in 20-50% of severe cases
After 7-10 days of illness
What is Dengue?
Dengue haemorrhagic fever
Fatality rates 1-10%
What is both Yellow fever and dengue?
Arboviruses
How can human to human transmission occur in HF?
Mosquito (YF)
Blood/needles (Ebola)
What is the flavivirus genome organisation?
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’
How did Yellow fever (YF) and mosquito vector spread to the US?
Via shipping
What were the original fatalities in the US due to YF?
15% in Philidelphia (1793)
28% in New Orleans (1853)
Who discovered mosquitoes caused YF?
Carlos Finlay and Walter reed (1880-1900)
What vaccine was developed for yellow fever and when?
17D vaccine developed in 1937
How many deaths were due to yellow fever?
> 10,000 deaths pa ww
What is the Yellow fever vaccine?
Live attenuated yellow fever vaccine (mutations in E)
Grown in infected chicken embryos
95% protection, 10 days p.i.
Life-long immunity
What is the safety of yellow fever vaccine?
Very few side effects (allergic reactions & some reports of neurological complications, 1 in 1,000,000)
What can not be infected orally with 17D?
Ae. Aegypti
Why can’t Ae. Aegypti be infected orally?
No natural transmission of vaccine virus
No chance of reversion to virulence
What is dengue haemorrhagic fever (DHF) vector controls?
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
Where does dengue occur?
Asia, Afria and the Americans
Where does yellow fever not occur?
Asia
What are some of the ecological changes that are risk factors in contracting a VHFs?
Travel- globalisation
Urbanisation- changing vector habitats or moving humans into new areas
Environmental manipulation- Dam building
What are some large scale changes in virus ecology introduced by humans?
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
