Ebola virus disease

Haratian K. ,Medical virologist, Alborz
University of Medical Sciences
1

Ebola Virus Disease (EVD)
And its threat for public health

EID & RID
at a glance
 EID : Emerging Infectious Disease
 RID : Re-emerging Infectious Disease
3

E.I.D. : WHO Definition
 An emerging disease is one that has
appeared in a population for the first
time, or that may have existed previously
but is rapidly increasing in incidence or
geographic range.
 An infectious disease whose incidence
has increased in the past 35 years and
could increase in the near future.
4

R.I.D. : WHO Definition
Any condition, usually an infection, that :
had decreased in incidence in the global population
was brought under control through
effective health care policy and improved living conditions,
more recently, began to resurge as a health problem
due to changes in the health status of
a susceptible population
Examples :Cholera, dengue, diphtheria, malaria, tuberculosis
5

and…Ebola
6

Contributing factors
 Microbial adaption
 Changing human susceptibility
 Climate and weather
 Change in human demographic and trade
 Economic development
 Breakdown of public health
 Poverty and social inequality
 War and famine
 Bioterrorism
 Dam and irrigation system constructionHaratian K. ,Medical virologist, Alborz
7

Emerging viral diseases (EVDs)
 Caused by viruses have assumed great public health significance
in the recent past. During the last three decades, almost 20 new
viral pathogens have been detected. Some of these (e.g. human
immunodeficiency virus (HIV) and hepatitis viruses (HBs) have
already caused substantial mortality, morbidity and economic
loss all over the world. The pandemic of serious acute respiratory
syndrome (SARS) unequivocally demonstrated the rapidity with
which new viruses can travel across the world and inflict misery.
The threat of a pandemic with one of the subtypes of influenza
virus is considered the greatest public health challenge in the
current millennium so far.
8

Newly discovered viruses of
public health importance
9

Communicable diseases
 Are leading cause of morbidity and
mortality around the world (EIDs=12%).
 When a new virus associated with an
acute respiratory illness , or bloody blood
born emerges, medical authorities around
the world are put on high alert and
vigilance
10

Ebola Virus Disease (EVD)
Dr. Kaveh Haratian
Department of Microbiology and immunology
Faculty of Medicine, Alborz University of Medical Sciences
October 2014
“Got no time for wild polemics, hung up on epidemics” – Anonymous

Outline
 Why learn about EVD?
 History
 Epidemiology
 Virological and clinical aspects
 Management
 Control measures
 Challenges
 Pandemic threat
12

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
13

Why learn about EVD?
 Limited scientific understanding
 Highly fatal disease
 Causes large outbreaks
 Difficult to contain
 No proven treatment or vaccine
 A pandemic threat
14

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
15

A story – 1/3
16

A story – 2/3
17

A story – 3/3
18

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
19

Epidemiological aspects
 Natural host - Fruit bats of
Pteropodidae family
 Reservoir – fruit bats
 Sources – bush meat, NHP,
Infected humans, fomites
 Incubation period – 2 to 21 days
 Communicability – high, virus
isolated after 90 days of recovery
 Case fatality – 50 to 90%
 Immunity – long term not
proven, deceased patients failed
to produce immune response
 No. of outbreaks – >30
20

Geographic distribution 1
 First outbreak occurred in
Zaire (Congo) in 1976
 Followed by several
outbreaks, all in Africa
(except one in Philippines,
Italy, USA)
 Latest on-going outbreak in
west Africa started in
March 2014 in Guinea
21

Fruit bats
22

Geographic distribution 2
23

http://www.cdc.gov/vhf/ebola/resources/distribution-map.html

Current Ebola Outbreak in West
Africa
 The current (2014) Ebola outbreak is occurring in the
following West African countries:
 Guinea
 Liberia
 Sierra Leone
 Nigeria

Modes of transmission
 Direct contact (through broken skin or mucous
membranes) with :
 a sick person's blood or body fluids (urine, saliva,
faeces, vomit, semen)
 objects (such as needles) that have been contaminated
with infected body fluids
 infected animals
 High risk groups – bush meat hunters, forest dwellers,
health workers, relatives of patients, funeral attendees,
corpse handlers, lab personnel
30

TRANSMISSION
•The virus is spread through direct
contact (through broken skin or mucous
membranes) with
i. sick person's blood or body fluids
(urine, saliva, feces, vomit, sweat and
semen)
ii. objects (such as needles) that have
been contaminated with infected
body fluids.
iii. Infected animals.

TRANSMISSION
 Exposure to ebola viruses can occur in
healthcare settings where hospital staff are not
wearing appropriate protective equipment, such
as masks, gowns, and gloves.
 Proper cleaning and disposal of instruments,
such as needles and syringes, is also important.

Transmission
Animal to human
• Consumption of
raw meat
• Contact wit fruit
bat, pigs, apes-
animal handlers
• Animal products
(blood, urine and
feces.)
Human to human
• Close contact with
infected patients
• Care personnels
of patient
• Health care
workers
Prompt and safe
burial of dead
bodies.
No to Autopsy
Virus contained
in dead body for
a period 4 weeks.

 Men who have recovered from the illness can still
spread the virus to their partner through their semen for
up to 7 weeks after recovery.
 Burial ceremonies in which mourners have direct contact
with the body of the deceased person have
played a role in the transmission of Ebola.

Who is most at risk?
 During an outbreak, those at higher risk of infection are:
 Health care workers.
 Family members or others in close contact with infected
people; and
 Mourners who have direct contact with the bodies of the
deceased as part of burial ceremonies.

Transmission and carrier state
36

Transmission cycle
37

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
38

Virological
aspects
• Family Filoviridae in the order
Mononegavirales
• Five species
• Zaire, Sudan, Taï, Reston,
Bundibugyo
• Enveloped, non-segmented,
negative-strand RNA virus,
filamentous
• Genes arranged linearly
coding for seven structural
proteins - NP, VP35, VP40, GP,
VP30, VP24 and L with NP
• GP, transmembrane protein
and responsible for receptor
binding and membrane
fusion
39

Clinical features
• Range from minor viral illness
to fatal haemorrhagic fever
• Ebola haemorrhagic fever
(Ebola HF) is type of Viral
Haemorrhagic Fevers
• Most common constellation
of symptoms is together
called Ebola Virus Disease
• EVD – duration 2 to 20 days,
fever, nausea, vomiting, non-
bloody diarrhoea, abdominal
pain, conjunctivitis,
weakness, severe headache
and myalgia
• E. Hemorrhagic fever -
hematemesis, epistaxis,
increased postpartum
bleeding, bleeding gums etc., Haratian K. ,Medical virologist, Alborz
40

Ebola Virus Disease
SUDDEN ONSET FEVER SORE THROAT
INTENSE WEAKNESS MUSCLE PAIN, HEADACHE
VOMITTING RASH
DIARRHOEA IMPAIRED KIDNEY AND RENAL
FUNCTION
LAB
•LOW WBC
•LOW PLATELET
•ELEVATED LIVER
ENZYMES.

Points…
 In some cases, both internal and external bleeding.
 People are infectious as long as their blood and
secretions contain the virus. Ebola virus was isolated
from semen 61 days after onset of illness in a man who
was infected in a laboratory.
 The incubation period, that is, the time interval from
infection with the virus to onset of symptoms, is 2 to 21
days.

Points…
 The patient becomes contagious once they begin to
show symptoms. They are not contagious during the
incubation period.
 Ebola virus disease infections can only be confirmed
through laboratory testing.

AlvinChew slideshare presentation
alvinworks2006@yahoo.com

 In some cases, both internal and external bleeding.
 People are infectious as long as their blood and
secretions contain the virus. Ebola virus was isolated
from semen 61 days after onset of illness in a man who
was infected in a laboratory.
 The incubation period, that is, the time interval from
infection with the virus to onset of symptoms, is 2 to 21
days.

DIFFERENTIAL DIAGNOSIS
 Malaria
 Dengue
 Typhoid fever
 Shigellosis
 Cholera
 Leptospirosis
 Rickettsiosis
 Relapsing fever
 Other viral haemorrhagic fevers.

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
51

Diagnosis
 CDC case definitions
 Person Under Investigation
 Probable case
 Confirmed case
 Non-case
 Exposure risk levels
• In early phase - Antigen-
capture ELISA, IgM ELISA,
PCR, Virus isolation
• In later phase - IgM and IgG
antibodies
• In deceased patients –
immunohistochemistry, PCR,
virus isolation
• Strict precautions during
transportation of samples
and all testing in BSL-4 lab
• Differentials – Lassa fever,
malaria, shigellosis, cholera,
leptospirosis, plague,
rickettsiosis, relapsing fever,
other viral haemorrhagic
fevers
52

 Person Under Investigation (PUI)
 A person who has both consistent symptoms and risk factors
as follows:
 1) Clinical criteria, which includes fever of greater than 38.6
degrees Celsius or 101.5 degrees Fahrenheit, and additional
symptoms such as severe headache, muscle pain, vomiting,
diarrhea, abdominal pain, or unexplained hemorrhage.

2) Epidemiologic risk factors within the
past 21 days before the onset of symptoms, such as
contact with blood or other body fluids or human
remains of a patient known to have or suspected to have
EVD;
 residence in—or travel to—an area where EVD
transmission is active. or direct handling of bats, rodents,
or primates from disease-endemic areas.

Probable Case
 A PUI who is a contact of an EVD case with either a high
or low risk exposure.
Confirmed Case
 A case with laboratory confirmed diagnostic evidence of
ebola virus infection.

Contacts of an EVD Case
(LEVELS OF EXPOSURE)
High risk exposures
 Percutaneous, e.g. the needle stick, or mucous
membrane exposure to body fluids of EVD patient.
 Direct care or exposure to body fluids of an EVD patient
without appropriate personal protective equipment
(PPE)
 Laboratory worker processing body fluids of confirmed
EVD patients without standard biosafety precautions.

Low risk exposures
 Household member or other casual contact with an EVD patient
 Providing patient care or casual contact without high-risk exposure
with EVD patients in health care facilities in EVD outbreak affected
countries
No known exposure
Persons with no known exposure in an EVD outbreak affected
country in the past 21 days with no low risk or high risk exposures.

DIAGNOSIS
 Ebola virus infections can be diagnosed in a laboratory
through several types of tests:
 Antibody-capture enzyme-linked immunosorbent assay
(ELISA) -NP is one of the major viral structural components
 Antigen detection tests
 Serum neutralization test
 Reverse transcriptase polymerase chain reaction (RT-PCR)
assay
 Electron microscopy
 Virus isolation by cell culture.

Be Careful!!
 Samples from patients are an extreme biohazard risk;
testing should be conducted under maximum biological
containment conditions.

CDC- Diagnosis
Timeline of Infection Diagnostic tests available
Within a few days after symptoms begin
•Antigen-capture enzyme-linked
immunosorbent assay (ELISA) testing
•IgM ELISA
•Polymerase chain reaction (PCR)
•Virus isolation
Later in disease course or after recovery •IgM and IgG antibodies
Retrospectively in deceased patients
•Immunohistochemistry testing
•PCR
•Virus isolation

When Specimens Should Be Collected
for Ebola Testing
 Ebola virus is detected in blood only after onset of symptoms,
most notably fever.
 It may take up to 3 days post-onset of symptoms for the virus
to reach detectable levels.
 Virus is generally detectable by real-time RT-PCR from 3-10
days post-onset of symptoms, but has been detected for
several months in certain secretions.

 Specimens ideally should be taken when a symptomatic
patient reports to a healthcare facility and is suspected
of having an EVD exposure
 However, if the onset of symptoms is <3 days, a
subsequent specimen will be required to completely
rule-out EVD.

From whom the samples are to be
collected?
 The samples should be collected from any person ill or
deceased who has or had fever with acute clinical symptoms
and signs of hemorrhage, such as bleeding of the gums, nose-
bleeds, conjunctival injection, red spots on the body, bloody
stools and/or melaena (black liquid stools), or vomiting blood
(haematemesis) with the history of travel to the affected area.

 OR
 Any person (living or dead) having had contact with a
clinical case of EBVD and with a history of acute fever.
 Anyone who has accidently come in contact with blood
or body fluids should be kept under quarantine and
observed for 30 days.

Preferred Specimens for Ebola Testing
 A minimum volume of 4mL whole blood / serum/ plasma
preserved with EDTA, clot activator, sodium polyanethol
sulfonate (SPS), or citrate in plastic collection tubes can be
submitted for EVD testing.
 Postmortem: Tissue sample (liver, spleen, bone marrow,
kidney, lung and brain)

 Do not submit specimens preserved in heparin tubes.

 Specimens should be stored at 4°C or frozen.
 Before dispatching the sample disinfect the outer
surface of container using 1:100 dilution of bleach or 5%
Lysol solution.

Transporting Specimens within the Hospital / Institution
 Specimens should be placed in a durable, leak-proof
secondary container for transport within a facility.
To reduce the risk of breakage or leaks, do not use any
pneumatic tube system for transporting suspected EVD
specimens.
Samples should be sent to the laboratories under cold chain
with prior intimation:

Treatment  Experimental treatments
 ZMapp – a combo of 3 monoclonal
antibodies
 TKM-Ebola – targets RNA of the
virus
 MB-2003 - prevents infection in
mice and non-human primates
when administered as post-
exposure prophylaxis within one to
two days
 BCX-4430 – RNA polymerase inh
 Favipiravir, AVI 7288
 Whole blood and convalescent
serum transfusion from recovered
patients
• No proven antiviral drug
• Symptomatic treatment only
• Providing intravenous fluids
and balancing electrolytes
(body salts)
• Maintaining oxygen status
and blood pressure
• Treating other infections if
they occur
• Barrier-nursing techniques
• Personal Protective
Equipment
• Infection control measures
• Isolation of Ebola patients
from contact Haratian K. ,Medical virologist, Alborz
68

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
69

Control measures – 1/5
 Public health measures - early
detection and isolation, contact
tracing and rigorous infection
control measures
 Screening of travellers from
affected countries in airports,
seaports and land borders
 Quarantine and observation of
suspected cases for 21 days from
exposure
 Awareness generation among
people, removing misconceptions
70

 All suspected or confirmed cases, single
closed patient room
 Avoiding contact
 A log book containing details of persons
entering
 Personal protective equipment for
caretakers
 Dedicated medical equipment
 Minimum use of sharps
 Disinfection of samples - heating to 60°C
for one hour, in 3% acetic acid
 Only BSL 4 lab should handle samples
 Hospital monitoring policy for staff
In this 2014 photo provided by the Samaritan's Purse aid organization, Dr. Kent Brantly, left, treats an Ebola patient at the Samaritan's Purse Ebola Case Management
Center in Monrovia, Liberia. On Saturday, July 26, 2014, the North Carolina-based aid organization said Brantly tested positive for the disease and was being treated at a
hospital in Monrovia.
View of an isolation center for people infected with Ebola at Donka Hospital in Conakry.
71

 Vaccines
 Virus like particles: ZEBOV (VP40, CG and NP)
 Non-replicating vectors: alpha virus, DNA vaccines, recombinant adenovirus based
vectors (rAD)
 Replication competent vectors: Recombinant Paramyxovirus-based vectors,
Recombinant vesicular stomatitis virus-based vectors (rVSV), Recombinant rabies
virus based (rRABV)
 The first vaccine platform that successfully protected NHPs from Ebola virus infection
was a recombinant adenovirus serotype 5(rAd5) vector
 Latest - chimpanzee-derived replication-defective adenovirus (ChAd) vaccine
72

 Social aspects
 Cultural practices – burial rituals
 Illiteracy and lack of awareness
 Fear of modern medicine, equipment
 False rumours and misinformation
 Ethical issues of giving experimental treatment
73

 International cooperation
 CDC, WHO, European Mobile Laboratory (EMLab) Project, African
Union
 Voluntary agencies - MSF, Samaritan’s Purse
 Staff, Outbreak response teams, lab experts, doctors, equipment,
gloves, medicines, disinfectants
 Research for medicines and vaccines
74

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
75

Challenges to control
 Lack of effective treatment and vaccine
 Weak public health infrastructure, manpower, weak labs
 Poverty and Illiteracy
 Lack of political stability
 Delayed international response
 Failure to anticipate and incorporate social aspects
 Funding problems
76

Outline
 History
 Epidemiology
 Management
 Challenges
 Pandemic threat
77

Pandemic threat
 None of the past outbreaks have developed into a pandemic
But,
 2014 outbreak – As of August 31, 2014, 3707 cases and >1800
people dead across 5 countries
 WHO’s declared ‘Public Health Emergency of International Concern’
in August 2014
 Attack rate - 12.6 cases per 10,000 inhabitants, Ro is 2.7
 No population level immunity
 Bioterrorism
78

Take home messages
 Ebola is an new and emerging infection
 Ability to cause large outbreaks with high casualty
 In the absence of proven treatments, prevention is the
main weapon
 Social aspects are very important in control
 Simple and established PH measures are sufficient
 A potential pandemic
79

Home work
 Task 1 - Learn the principles of outbreak
investigation – watch the movie
‘Contagion’ and write a one page
summary
 Task 2 - A one page summary on
conditions needed to declare a
pandemic
 Task 3 - A one page summary of how a
country is planning to respond to this
threat, the agencies involved and your
ideas for preparedness in our hospital
81

Reference materials
 CDC website http://www.cdc.gov/vhf/ebola/about.html
 WHO website http://www.who.int/csr/disease/ebola/en/
 The Lancet Ebola Resource Centre
http://ebola.thelancet.com/
 Journals - Bulletin of the WHO, NEJM and BMJ, August and
September 2014 issues
 Image courtesy – google images, CDC and WHO
82

Thank You
83

Ebola virus disease

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