1. health and fitness

Ebola virus:
virology, epidemiology, prevention &
control
Dr Gee Yen Shin
PHE Consultant Virologist
Department of Infection
The Royal London Hospital
London E1
Public Health England
Declaration of interests
• I work for Public Health England (PHE)
– PHE is an executive agency of the Department of Health
– Ergo I am a civil servant
• Honorary consultant virologist, Barts Health NHS
Trust
• Honorary clinical senior lecturer Queen Mary
University of London
• Any opinions expressed are my own & not those of
my employer(s)
Public Health England
Outline
• Ebola virus:
– Virology
– Clinical features
– History
• Epidemiology:
– Previous epidemics
– 2013-15 West African pandemic
• Prevention & control:
– PPE
– Decontamination & waste
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Ebola virus
• Ebola virus is a member of the family filoviridae
– Ebola virus genus
– Marburg virus genus
• Enveloped ssRNA virus with filamentous morphology
– Genome: 7 genes
• Zoonotic virus
– Animal reservoir thought to be bats, especially fruit bats
– Intermediate hosts e.g. non-human primates
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History
• Ebola virus infection in humans first described in a
village called Yambuku in the Ebola River region of
Zaire 1976 in outbreak of a mysterious fatal illness
• Samples sent to Antwerp in Belgium, where Peter
Piot was working: EM showed novel filamentous
virus
– Named Ebola virus as that was the nearest river to the
village
• Outbreak brought under control; 280/318 deaths
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Public Enemy Number One
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Ebola virus group
• Five known species
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Zaire Ebola virus
Sudan Ebola virus
Tai Forest Ebola virus (aka Cote d’Ivoire EboV)
Bundibugyo EboV
Reston virus
• Reston EboV causes infection in non-human primates & swine
• Current W African outbreak is Zaire EboV
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Ebola Virus Disease
• Clinical features:
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Fever
Malaise, fatigue
Headache (severe)
Myalgia
Diarrhoea and/or vomiting
Bruising and/or bleeding (late stage, rare)
Case fatality rate 25-90%
• based upon historical EboV outbreaks
– There have been reports of asymptomatic cases (Gabon)
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Ebola Virus Disease
• Transmission
– Only infectious when symptomatic
– Infectiousness increases with severity of disease
– Mucocutaneous: bodily fluids (blood, diarrhoea, vomitus)
from infected persons => mucous membranes (eyes,
mouth, broken skin, nose)
– Percutaneous: needlestick injuries/sharps injuries
– Most infectious if/when patients develop D&V and/or
bruising/bleeding (pre-terminal)
– No evidence of airborne transmission
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Ebola virus disease
• Incubation period
– Range 2-21 days
– Most common incubation period 2014 outbreak 8-10 days
(CDC)
• Quarantine period
– Contacts of EboV: 21 days
– (WHO) Countries to be declared EboV-free: 42 days
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Recovery, immunity
• 30-40% of patients in current outbreak survive
• Once patients defervesce & become asymptomatic,
they are no longer infectious, except in semen
– 7-9/52; WHO “up to 3 months” case studies
– condom use recommended for 3/12
• Upon recovery, patients are considered immune to
re-infection with the same strain “up to 10 years”
• One UK patient, WP returned to Sierra Leone to help
the humanitarian effort upon recovery
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Post-Ebola syndrome?
• Anecdotal evidence accumulating about a possible
“post Ebola syndrome”, characterised by:
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Visual disturbance
Eye pain
Arthralgia
Hair loss
Memory loss
Anxiety attacks
Lasting for several months
Not currently a formally recognised phenomenon
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Ebola Virus epidemiology
• Ebola virus is a zoonosis, animal reservoir not 100%
certain, but probably fruit bat(s)
– No human reservoir
• Sporadic outbreaks, not endemic
• It is hypothesised that epidemic triggers are either:
– contact with sick EboV infected animals OR
– Exposure to bats/bat droppings? OR
– handling infected bush meat of EboV animals e.g. nonhuman primates & bats could be the trigger event for
infection & thence an outbreak
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Evidence for bats as EboV reservoir
• Multiple field studies over many years, confirm that
wild bats are infected with Ebola virus (RNA+)
• EboV naïve bats can be experimentally infected with
EboV, virus replication occurred & bats survived
– Experimentally infected non-human primates have high
morbidity & mortality
• Several fruit bat species have anti-EboV antibodies
• Many other species (birds, rodents, insects, plants)
tested – EboV not detected; do not support EboV
infection
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African Fruit Bats, Guinea
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Bush meat markets, Gabon & Kenya
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Africa-specific socioeconomic considerations
• EboV infections occur in some of the most impoverished
(African) countries i.e. least well-equipped to deal with
cases/outbreaks
• EboV outbreaks often detected late (like this one), public
health intervention late & suboptimal
• Bush meat can be an important source of protein
• Burial practices in West Africa (hands on, close contact)
• However, if outbreaks occur in remote areas, outbreaks may
be self-contained & therefore easier to control & monitor (e.g.
DRC 2014)
• Porous borders
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Nosocomial spread
• The current EboV pandemic has reminded us of risk of
nosocomial (hospital associated) transmission
• Africa: inadequate facilities, inadequate staffing, inadequate
PPE, inadequate training
• Humanitarian facilities: even MSF workers have contracted
EboV despite very robust PPE
• Spain, USA (developed countries), nosocomial transmission
has occurred
• Doffing of contaminated PPE is a high risk activity
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Past Ebola outbreaks
• Nineteen recorded outbreaks in Africa since 1976:
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Democratic Republic of the Congo (DRC) [Zaire]
Gabon
South Sudan
Uganda
Republic of the Congo
South Africa
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Notable historical Ebola virus outbreaks
Source: CDC, USA
• Country, year
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Zaire, 1976
Sudan, 1976
DRC, 1995
Uganda, 2000-01
ROC, 2002-03
DRC, 2007
Uganda 2007-08
• Cases (CFR)
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Public Health England
318, (88%)
284 (53%)
315 (81%)
425 (53%)
128 (89%)
264 (71%)
149 (25%)
Map of Africa, 2013
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Ebola outbreak, West Africa 2013-15
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West African EboV outbreaks 2013-15
• Guinea
• Liberia
• Sierra Leone
– Mali (ended 18/1/15)
– Nigeria (Lagos, Port Harcourt): ended 20/10/14
– Senegal: ended 17/10/14
• DRC, 2014 (not linked to above)
– 66 cases outbreak over
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“Patient Zero”
• It is believed that the index case for the current
outbreak was a 2 year old child, “patient zero” in
Meliandou village near a town called Gueckedou in
Guinea who became ill in December 2013
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He died shortly afterwards (6 Dec)
Then his mother became ill & died (13 Dec)
Next, his sister became ill & died as well (29 Dec)
Finally his grandmother became ill & died (1 Jan 14)
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Map of initial Guinean outbreak
Baize et al, NEJM 371 October 2014
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Evolution of an outbreak
• These few early cases led to an outbreak of a
“mysterious illness” reported to Guinea Ministry of
Health/Medecins sans Frontieres in March 2014
• Samples taken & tested in Europe – confirmed Zaire
Ebola virus in multiple cases
• Very high genetic similarity of multiple W African
samples indicating a single introduction event into
this population with subsequent spread
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Evolution of an outbreak 2
• Ebola spread to the capital of Guinea, Conakry along
main road
• Subsequent cross-border spread to Liberia, Sierra
Leone
• Seeding to Nigeria, Senegal, Mali
• August 2014: WHO declared the West African Ebola
virus a global “public health emergency of
international concern”
Public Health England
WHO Ebola virus SITREP 01/04/15
• Guinea 3492 (2314)
• Liberia 9712 (4332)
• Sierra Leone 11974 (3799)
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Nigeria 20 (8)
Senegal 1 (0)
Mali 8 (6)
Spain 1 (0)
UK 1 (0)
USA 4 (1)
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WHO Ebola virus SITREP totals 1/04/15
• As of 1/04/15, Global case totals = 25,213
– Suspected, probable & confirmed cases
• Deaths = 10,460
– Crude overall case fatality rate: 41.5%
• Trend:
– Guinea: incidence “declining”, very low in inland areas
– Liberia: incidence extremely low
– Sierra Leone: incidence declining overall, few areas of
intense transmission
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EVD: HCW cases
• WHO SITREP 1/4/15
– 861 HCWs have been infected with Ebola virus
– 495 deaths
– Case fatality rate 495/861 = 57.5%
– A heavy toll
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WHO EboV SITREP W Africa 01-04-15
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Slums in Monrovia & Freetown
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Ebola victim burials, 2014
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International response
• Many countries, including the UK have devoted substantial
resources to assist the 3 affected countries
• Strategy in field:
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Develop network of Ebola Treatment Centres (new build)
Develop network of Ebola testing laboratories
Public health education e.g. burial practices, getting help for cases
Contact tracing
Epidemiology
Psychological support for cases
Safer burial teams
Military support e.g. UK, US e.g. engineers, HCWs, transpportation
Logistical support for above
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UK Ebola Treatment Centre schematic, Sierra Leone
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UK Ebola Treatment centre, Kerry Town
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Countries receiving EboV MEDEVAC cases
• UK 2 (0)
– UK will receive Australian HCW MEDEVAC
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Spain 1 (1)
Germany 3 (1)
France 1 (0)
Norway 1 (0)
USA 2 (0)
Public Health England
UK Ebola virus management capacity
• High Level Isolation Unit (HLIU) at the Royal Free
Hospital, London
• HLIU only accepts confirmed VHF patients
• Two self-contained isolation units, “Trexler units”
– Could accommodate more in conventional side rooms
• Plans to expand HLIU capacity with similar units in:
– Newcastle
– Liverpool
– Sheffield
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HLIU Royal Free Hospital
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Dedicated VHF RAF MEDEVAC ambulance
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UK VHF Diagnostic capacity
• PHE Rare & Imported Pathogens Laboratory (RIPL),
Porton Down
– Can detect all known VHFs
– Ebola, Marburg, Lassa, CCHF etc.
• 2014/5 Health Protection Scotland: has deployed
Ebola/VHF testing capability at HPS lab, Edinburgh
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PHE Ebola diagnostics 2015
• In view of the on-going international Ebola situation,
DH/PHE decided to expand UK Ebola diagnostic
capability beyond RIPL
• From February 2015, Ebola diagnostic capability has
been deployed at Public Health Laboratory (PHL)
London (at Barts Health) & Newcastle PHL
• Utilises a commercial PCR-based system (Biofire
FilmArray) which received emergency FDA & MHRA
approval for a limited period
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PHE: UK risk assessment
• Risk of Ebola cases appearing in the UK is very low
but not impossible
• Most likely scenario is UK NHS/PHE HCW or NGO aid
worker returning to the UK & becoming
febrile/unwell
– Common things are common, many such cases will have
another diagnosis e.g. malaria
– Implemented border screening at airports & surveillance
of returning HCWs
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Likely Ebola clinical scenarios
• Returning:
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UK healthcare worker (2)
UK charity/NGO/aid worker
UK military personnel (1)
UK journalist
• Should declare themselves at the airport
• If symptomatic, temperature taken +/- refer to
nearest A&E for assessment
• HCWs instructed to monitor temperature 2 x daily
Public Health England
Categorisation of UK HCWs W Africa
• Category 0: No contact with EboV, no travel to EboV affected
country
• Category 1: AeroMEDEVAC staff, lab staff in UK EV labs, travel
to EV affected area but no direct contact with cases
• Category 2: Close contact with EV cases but did NOT provide
direct clinical care; wearing PPE in clinical areas (e.g.
sanitation workers, epidemiologists)
• Category 3: Direct contact with EV cases e.g. HCWs looking
after EV cases, mortuary workers, burial teams
Public Health England
Ebola virus testing algorithm 2014/5
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Follow ACDP VHF algorithm 2014
Identify & isolate possible cases ASAP
Contact Trust virologists/microbiologists ASAP
Exclude malaria
Cases discussed with PHE Imported Fever Service (IFS)
If IFS agrees to test, samples (EDTA blood, serum & urine) sent
to PHE Rare & Imported Pathogens Lab (RIPL) by approved
category A couriers
– Ebola virus PCR
– +/- other VHFs, depending on travel history e.g. Lassa fever
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Returning HCW presenting to A&E
• Hopefully picked up quickly in triage if not prealerted via 999
• Seen in pre-identified A&E side-room
– Ideally room with en-suite WC, window into corridor,
phone/telecom
– If possible negative pressure room with antechamber
– Designated area for donning & doffing of PPE
– Ideally on periphery of A&E
– An area which can be cordonned off
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NHS VHF PPE (late) 2014
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EBoV PPE
• PPE for ?EboV scenarios has evolved rapidly in light
of current EboV W African outbreak
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Training & retraining
FFP3 mask
Face mask/shield/visor/hood
Liquid-impermeable gown
Double gloves
Boots (or overshoes)
Buddy system
+/- Trained observer
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PPE donning & doffing
• Donning: putting on
• Doffing: taking off
• Both important, but doffing is particularly high-risk if
contaminated by case bodily fluids
• Follow recommended PPE protocols carefully
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Buddy system as double-check
+/- trained observer as fail-safe
Training
Posters
• Correct disposal
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Miscellaneous PPE issues
• Wearing full PPE is very hot
– Difficult to work for prolonged periods in full PPE
• Cumbersome, double gloves may affect dexterity
• Some masks/visors may restrict field of vision
• Disposal of large volumes of discarded PPE
– Identify cat A waste disposal contractor/process
• Staff with beards cannot effectively wear FFP3 masks
as they cannot achieve a seal
– Need full face visor
– Powered hood with O2/ventilation
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EboV: sharps safety
• Sharps safety is important in all clinical areas
• However in the scenario of a possible EboV/VHF case
safe sharps practice is even more important
– No licenced vaccine
– No proven therapy
– EboV c. 60-70% case fatality rate in Africa
• Patients may be agitated
• UK has repatriated at least 2 HCWs after NSI in 2015
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EboV laboratory aspects
• As per 2014 ACDP VHF guidelines
• Ebola virus & other VHFs are ACDP hazard group 4 pathogens
• Blood samples MUST NOT be sent in pneumatic chute systems
• Blood from suspected EboV/VHF patients may be tested on
automated closed-system analysers
• Malaria films may be performed on a laboratory bench (CL2)
– BMS should wear appropriate PPE i.e. lab coat, gloves, eye
protection/face visor
– Sample should be held in a sturdy rack
• Lab waste from ?VHF patients should be discarded into
separate, marked containers until VHF status clarified
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Decontamination
• EboV is an enveloped virus
• Relatively fragile; inactivated by
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Soap & water
Alcohol handwash gel
Heat inactivation
Chlorine-based agents e.g. sodium hypochlorite
Detergents, aldehydes, peroxides
UV light, sunlight
• EboV can survive on some surfaces e.g. worktops, door knobs
for “..several hours”
• EboV can survive “…in bodily fluids such as blood for several
days at room temperature.”
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Decontamination 2
• Decontamination action determined by patient’s level of EboV
risk (low-risk / high risk / confirmed VHF)
• AND by level of contamination of the environment (none /
minimal / significant)
• Trained cleaning staff with appropriate level of PPE in light of
above & guided by local risk assessment
– Low-risk patient with no diarrhoea / vomiting / bleeding = standard
cleaning & decontamination will suffice
Public Health England
EboV heat inactivation
• From CDC website:
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Heat to 60°C for 60 minutes
Heat to 72-80°C for 30 minutes
Submersing material in boiling water for 5 minutes
“Can be achieved…..in autoclave under “a validated waste
cycle of 121°C for at least 30 minutes.”
– OR incineration of contaminated material
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Public health poster, Monrovia
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“Ebola can be beaten” poster, Save the Children UK
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Public Health England
Ebola vaccine?
• From a public health point of view, it would be ideal
to have a safe, effective Ebola vaccine
• Two safety/efficacy trials of Ebola vaccines
underway:
– Chimpanzee adenovirus serotype 3 (ChAD3-ZEBOV)
– Recombinant vesicular stomatitis virus (rVSV-ZEBOV)
• If successful, will be tested in the field in West Africa
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