20: Ebola

Question 1

ebola virus

Answer 1

filoviridae family
- several different species that mostly infect humans (but restonviruses kill primates)
- mostly talking about sudan and zaire viruses which enter the human population with a 50%-90% death rate

RNA virus but unusual structure and genetic sequence (filaments as opposed to octagonal or well-defined in a round shape)

virions variable in length but on average 1000nm

Question 2

different lab biosafety levels

Answer 2

BSL-1
- low risk to humans and we handle them well

BSL-2
- infectious agents causing moderate risk
- don’t make us sick even if we’re immunocompetent

BSl-3
- pathogens causing serious/lethal injections

BSL-4
- last level of security in laboratories

Question 3

ebola animal reservoir

Answer 3

found in fruit bats but also detected in carcasses of chimpanzees, gorillas and antelopes
- things hunted/used for meat consumption

also found in dogs and pigs but no indication of transmission to humans

Question 4

ebola as devastating to big primates

Answer 4

2001-2005 outbreaks where over 90% of mortality found in gorillas in central africa

bats can also contaminate primates which catch them and eat them

Question 5

first ebola outbreaks

Answer 5

DRC in 1976
- 318 cases, 218 deaths
- case fatality ratio of 88% (one of the most deadly outbreaks in history)

yambuku as the centre of the first documented outbreak
- village with no running water, electricity, radio, phone, etc.

2 spillover events for zaire and sudan epidemics

Question 6

jean-jacques muyembe

Answer 6

first encountered ebola in 1976, now leading the global search for a cure

took the first samples from victims and sent them to belgium

Question 7

1976-2020 outbreaks of ebola virus in africa

Answer 7

over 28 outbreaks
- usually 1-few hundreds of infections
- exception of the 2014-2015 epidemic

almost yearly spillover events with case fatality ranging from 25%-90%

mostly zaire strain

Question 8

2014 epidemic

Answer 8

started like other epidemic events
- few cases, then hundreds, then decline but then explosion

strain distinct from those identified in prior outbreaks

almost 20,000 infections and 10,000 deaths

Question 9

larger ebola outbreak in 2014

Answer 9

total numbers from 1976-2014 were 1850 cases and 1200 deaths
- 2014 outbreak had almost 30,000 cases and over 11,000 deaths
- worse that all other outbreaks combined (set precedent)

epidemic had 40% mortality but more spread of infection

worried about outbreaks in uganda with no treatment for the sudan strain in a population of workers known to be very mobile

Question 10

ebola transmission

Answer 10

direct contact
- blood, organs, bodily fluids of infected persons (saliva, blood, urine, faeces, vomit, sperm, sweat)
- contaminated objects (fomites) like vomit
- infected animals

R0 is not high since no transmission through aerosols

transmission only when symptomatic
- viral load rises at symptom onset
- why we are successful to keep epidemics at bay

Question 11

ebola human-human transmission

Answer 11

close family contacts or caregivers in households
- trying to take care of close family members

burial ceremonies where mourners have direct contact with the deceased
- rituals in africa washing, moving and getting into contact with the body

transmission in hospital settings
- so contagious that nurses/doctors get contaminated since they don’t know it’s ebola yet
- nosocomial transmissions as hospital-acquired infections

Question 12

ebola transmission in healthcare settings

Answer 12

infected primarily through inadequate protection
- e.g. nurses in texas infected in october 2014

outbreak can also spread to other patients

number of nosocomial infections high run ebola outbreaks than with most pathogens

Question 13

public health response

Answer 13

education

hygiene practices

case identification

contact tracing

prompt isolation

safe burials

aggressive support care

personal preventive equipment for caregivers

Question 14

outbreak monitoring of ebola

Answer 14

outbreaks must be followed up immediately with treatment and contact tracing

contact tracing as the process of identifying people exposed to the disease to prevent onward transmission
- people exposed to ebola systematically followed for 21 days (maximum incubation period for the disease) from the date of most recent exposure

21 days as the incubation period since it’s mostly 10-15 days where they get symptoms after infection

Question 15

ebola 2016

Answer 15

march where there were 8 cases reported in guinea
- 1000 contacts identified, 800 vaccinated with new vaccine
- not an approved vaccine but deemed safe enough to be given on a trial basis

june where WHO declared the end of ebola in guinea and liberia
- 42 days passed since the last person confirmed to have ebola tested negative for the second time
- have to pass incubation period twice with no new cases

Question 16

ebola vaccines

Answer 16

only for zaire type and not sudan

vaccine entirely VSV apart from the envelope gp protein
- keeping the VSV but removing genes cloning for its envelope protein
- replacing it with the gene that codes for envelope gp protein of ebola

doesn’t need adjuvants since it’s self-replicating

Question 17

ebola and vesicular stomatitis virus (VSV)

Answer 17

virus as part of the same family as rabies but not rabies
- exist in animals and humans don’t get sick from it

economically significant viral disease of cattle, horses and swine
- causes blister-like lesions which swell and break, leaving raw tissue so painful that infected animals refuse to eat/drink

Question 18

ebola vaccine trial during 2014-2016 outbreak

Answer 18

vaccine under emergency use even though it wasn’t authorised
- risk lower than potential benefits of vaccination

ring vaccination method

over 3500 individuals recruited who were all close contacts, and then separated into two groups
- one group received immediate vaccination, the other had delayed vaccination (21 days after contact)

no cases observed in the immediate cluster group, compared with 10 cases in the delayed group

since, over 18000 vaccinated
- approved in 2019 for the zaire strain and to the sudan strain

Question 19

ebola disease

Answer 19

fever, headache, joint/muscle aches, sore throat, weakness, diarrhoea, vomiting and stomach pain
- can last for a few days and then 50-80% of people die

first phase where it isn’t so bad and second phase when it hits
- coagulation doesn’t work so when you have cuts, you bleed a lot

Question 20

ebola hemorrhagic fever to ebola virus disease (EVD)

Answer 20

virus is able to infect macs which are there to engulf/digest/kill pathogens
- release many cytokines upon infection which have an effect on the body

blood cannot function properly since there is not enough oxygenation in organs so organs shut down and die
- cytokine storm

liver highly targeted by the virus so liver dysfunction
- liver controls coagulation and blood clotting
- infects macs primarily in the liver
- fluid loss, hermorrhaging, liver dysfunction, low blood pressure

Question 21

how does ebola cause mortality

Answer 21

triggers vigorous inflammation to the infection

Question 22

typical ebola virus disease clinical course

Answer 22

usually lasts 7-10 days, or up to 15 days
- people have to be under observation for 21 days if susceptible to being in contact (twice the amount of time taken to develop disease)

incubation period about a week
- only transmit when symptoms begin
- symptoms are similar to influenza at first but then you can get severely ill

Question 23

ebola treatment

Answer 23

can only treat symptoms
- treated as they appear
- basic interventions when used early can significantly improve changes of survival

fluid, electrolytes, oxygen

medication to support blood pressure, reduce vomiting/diarrhea, manage fever and pain

treating other infections if they occur

Question 24

ebola antivirals

Answer 24

no antivirals, but some indevelopment

initially an indication that antibodies are protected
- two investigational treatments of monoclonal antibodies used to successfully treat patients in the 2018 DRC outbreak
- 90% success rate when administered soon after infection
- prevents virus from infecting cells but also allows virus to be targeted by immune cells

Question 25

immune response to ebola

Answer 25

those who survive are thought to be protected from re-infection (lasts longer)

IgG seems to be key to protection
- significant antibody responses in people who recover

passive transfer of IgG also shown to be beneficial to patients with active infection

Question 26

viral clearance delayed in immunogenically protected body compartments and fluuids

Answer 26

still detect ebola in tissues for a long time (few months after infection)
- virus can persist

tissues with immune privilege, where the immune system has a harder time reaching organs
- virus hides here and is not controlled by the immune system