20: Ebola Flashcards
ebola virus
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
different lab biosafety levels
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
ebola animal reservoir
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
ebola as devastating to big primates
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
first ebola outbreaks
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
jean-jacques muyembe
first encountered ebola in 1976, now leading the global search for a cure
took the first samples from victims and sent them to belgium
1976-2020 outbreaks of ebola virus in africa
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
2014 epidemic
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
larger ebola outbreak in 2014
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
ebola transmission
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
ebola human-human transmission
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
ebola transmission in healthcare settings
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
public health response
education
hygiene practices
case identification
contact tracing
prompt isolation
safe burials
aggressive support care
personal preventive equipment for caregivers
outbreak monitoring of ebola
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
ebola 2016
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
ebola vaccines
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
ebola and vesicular stomatitis virus (VSV)
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
ebola vaccine trial during 2014-2016 outbreak
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
ebola disease
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
ebola hemorrhagic fever to ebola virus disease (EVD)
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
how does ebola cause mortality
triggers vigorous inflammation to the infection
typical ebola virus disease clinical course
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
ebola treatment
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
ebola antivirals
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
immune response to ebola
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
viral clearance delayed in immunogenically protected body compartments and fluuids
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
