Filoviruses (Ebola and Marbug)

Question 1

Family of Ebola and Marbug

Answer 1

Filoviridae - Ebola and Marburg are the 2 genera infect humans
Cause viral haemorrhagic fevers
Clinically similar - focus of lecture is Ebola

Question 2

Ebola Genus examples

Answer 2

Bundibugyo virus (BDBV)
Sudan Virus (SUDV)
Tai Forest Virus (TAFV)
Reston virus (RESTV)
Bombali virus (BOMV)

Question 3

Marburgvirus genus examples

Answer 3

Marburg virus (MARV)
Ravn virus (RAVV)

Question 4

Ebola structure

Answer 4

Non-segmented single stranded negative RNA viruses
Helical nucleocapsid- protects genome from endonucleases

Question 5

Ebola life cycle

Answer 5

1. Attachment
2. Endocytosis
3. Cleavage to expose receptor binding site
4. Fusion with endosomal membrane
   low pH trigger
   5 Replication
5. Transcription
   - Genome used directly as mRNA template
   - RdRp used
6. Translation in cytosol
   - GP1,2 go to ER
7. Budding from plasma membrane

Question 6

Ebola pathogenesis

Answer 6

Entry through dermal injury and direct mucosal membrane contact.
Infects macrophages/dendrictic cells - carried systemically (meaning it is carried through/affects the whole body..?) and also carried to lymph nodes
Supresses parts of the immune system - increases secondary infection rate and can be outpaced by the rest of the immune system

Question 7

Ebola transmission - zoonotic

Answer 7

first case in an outbreak is usually zoonotic - jumped from a non-human animal to humans
Often happens in remote parts of Africa

Question 8

Ebola transmission

Answer 8

First case is usually zoonotic

Fomites (inatimate objects) and body fluid for human to human

Sexual contact can transmit for months afterwards

Question 9

Phases of Ebola Infection

Answer 9

incubation, early phase, peak phase and recovery period

Question 10

Ebola virus’ typical symptomatic path through a human being

Answer 10

Days 7-9: Headache, fatigue, fever, myalgia
Day 10: High fever, vomiting blood, lethargy
Day 11: Bruised skin, brain injury, bleeding from orifices (eyes, mouth, nose anus)
Day 12: Loss of consciousness, seizures, massive internal bleeding, death
More on lab finings during incubation, early phase, peak phase and recovery period of ebola infection in notes.

Question 11

Ebola Diagnostics - Decentralised (field) approach

Answer 11

Lateral flow or PCR
Not fully validated- should still be confirmed by central/WHO lab

Question 12

Ebola Diagnostics - Centralised Approach

Answer 12

Patient must be symptomatic:
- Differential diagnosis is important
- 2 PCRs 48 hours apart can be used for asymptomatic
PCR performed on blood sample:
- Serum/plasma can be used

Question 13

Patient attitudes and transmission

Answer 13

Health seeking behaviour changes: Relatives go into hospital and don’t come out.. Hospital = death

Often foreigners running clinics - need to work within local beliefs, customs and languages

Most filovirus outbreak response teams now have: Anthropologists and Sociologists

Question 14

Epidemiology - Ebola in Uganda

Answer 14

Uganda is Bordered by (South) Sudan and DRC - Origin of 2 Ebola species
Major outbreaks every 5 -10 years - one currently ongoing/finishing.
Constant sourcing from zoonotic transmissions
Constant cross border transmissions
Can have recurring minor outbreaks.

Question 15

How to stop an outbreak

Answer 15

Not much pharmaceutical treatment available - 2mABs approved, more being evaluatd

Supportive care: Rehydration, symptom-specific treatment

Public Health Interventions: Co-ordinated response, track and trace, community mobilisation.

Question 16

Vaccine Landscape

Answer 16

1. Ervebo

Protects against EBOV
Live, attenuated recombinant vesicular stomatitis virus with EBOV glycoprotein
Single dose

2. Zabdeno-and-Mvabea

• Protects against all Ebola viruses
  Less effective than Ervebo
• Zabdeno: modified adenovirus containing EBOV glycoprotein
• Mvabea: modified vaccinia virus containg proteins from all Ebola species
• Multi dose, 8 weeks apart