Transcript Ebola Virus Haemorrhagic Fever - mdCurrent

Dr. Sonu kumari Agrawal
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Introduction
History
Epidemiology
Current outbreak
Mode of transmission
Replication
Pathogenesis
Diagnosis
Prevention
Animal models
Ebola virus is pathogen of viral haemorrhagic
fever
causing severe disease and high case-fatality
rates
Nearly 40 years ago
Belgian scientist travelled to a remote part of the
Congolese rainforest
Unknown and terrifying disease
September 1976
Electron Microscope
YAMBUKU
MARBURG
VIRUS
Institute of Tropical
Medicine Antwerp
Group: Group ss RNA
Order : Mononegavirales
Family: Filoviridae
Genus: Ebola virus
• Shape of a shepherd's crook or in the shape of a "
U" or a " 6" and they may be coiled or branched
• Linear non-segmented, single-stranded RNA Virus
• 80 nm in width , but vary some what in length
Structure of Ebola genome and
proteins • 7 structural and 1 nonstructural
• 7 structural proteins • Nucleoprotein (NP)
• 4 viral/virion proteins (VP35, VP40, VP30,
VP24)
• Glycoprotein (GP)
• RNA-dependent RNA polymerase (L protein)
Mortality rate
SEBOV
40-60%
ZEBOV
60-90%
BEBOV
20-30%
CIEBOV
0%
First cases of filovirus haemorrhagic fever - 1967
Germany and the former Yugoslavia - Marburg virus
In northern Zaire, now Democratic Republic of
the Congo (DRC) -1976
EBOLA VIRUS
Year
Coutry
Cases
Death
CFR
Congo
Ebola
Species
Zaire
2005
12
10
83%
2007
DRC
Zaire
264
187
71%
2007
Uganda
Bundibugyo
149
37
25%
2008
DRC
Zaire
32
14
44 %
2011
Uganda
Sudan
1
1
100%
2012
Uganda
Sudan
24
17
71%
Initial outbreak in Guinea
6 December 2013- Guéckédou, Guinea
A 2-year-old boy died
His mother
35 cases
killed 23
March - dozens of people were
dead in eight Guinean villages
3 year-old sister
Grandmother
Funeral
Two people -carried the disease
to their village
15 March 2014 WHO reported that the
Ministry of Health of Guinea
86 suspected cases
23-27 May ,2014
Boffa, Télimélé, Boke
and Dubrék
23 May
59 deaths
23 April , confirmed cases
-242
142 deaths
Mid- Jun e
25 July
8 August ,
2014
What in the world is Zaire ebolavirus doing in West
Africa, far from its usual haunts in Central Africa?
why no Ebola virus has ever been seen before?
before?
Why now?
Poor Economy
To stay alive - to find wood to make charcoal and
deeper into mines to extract minerals -Risk of
exposure to Ebola virus
Exposures related to Hunting and consumption
of fruit bats
• Neglected health-care facility where a supply
of gloves, clean needles, and no disinfectants
• Bats are considered the most likely natural reservoir of the
EBOV
• Bats were known to reside in the cotton factory in which
the first cases for the 1976 and 1979 outbreaks were
employed
• The absence of clinical signs in these bats is characteristic of a
reservoir species
•
A wide range of hosts were infected with ebola bats
• They got infected, replicated virus, and survived infection
• Detect anti-Ebola virus antibodies and Ebola virus RNA in fruit
bat species
Could Zaire ebola virus have been recently introduced into Guinea from
Central Africa?
Introduction from a human traveler seems
Unlikely
•
45,000 Indians in the affected countries – At risk
On September 1, 1976, four days after returning from a tour of northern
Zaire
Health care worker
Contacts
& male
family
member
the index case,
a 44 year-old
teacher
at the Mission School, sought medical intervention for a febrile
illness he thought to be malaria
of the ebola virus
parenteral injection of chloroquine (an anti-malaria
YMH did not use disposable needles or sterilize the
drug) from Yambuku
Mission
Hospital
(YMH)
Mourners who have direct contact with bodies needles
Parenteral injection was the primary mode of administering nearly all medicines
disseminated into the surrounding villages
serviced by YMH
Not entirely clear how Ebola is spread
Direct contact with blood or bodily fluids
Natural host of Ebola virus
from-an infected person
fruit bats - species of the genera Hypsignathus
contact
contaminated medical
monstrosus,Epomopsfranqueti
andwith
Myonycteris
equipment, particularly needles and
torquata
Bats drop partially
eaten
fruits and pulp
syringes
No Airborne transmission
Then land mammals such as
gorillas ,chimpanzees and
duikers feed on these fallen
fruits
10 % Health care worker affected
• Incubation period: 2-21 days
• Stage I (unspecific):
Extreme asthenia (body weakness)
Diarrhea, nausea and vomiting, anorexia
Abdominal pain
Headaches , arthralgia, myalgia ,Back pain
Mucosal redness of the oral cavity, dysphagia , conjunctivitis
Rash
•
Stage II (Specific):
Hemorrhage -
Petechiae, ecchymoses, uncontrolled oozing from venepuncture sites,
mucosal haemorrhages -30 to 40%
Anuria , Tachypnea
•
Late Complications: (>2 weeks after onset)
Shock, convulsions
Migratory arthralgias
Ocular disease (unilateral vision loss, uveitis)
Orchitis, suppurative parotitis
Pericarditis
Illness-induced abortion among pregnant women
Differential diagnosis
Clinical feature
Laboratory
Diagnosis
• suspected - (alive or dead person with fever and at least
• three additional symptoms, or fever and a history of contact with a
person with hemorrhagic fever or
• a dead or sick animal, or unexplained bleeding)
• Probable - meets the suspected case definition
• and has an epidemiologic link to a confirmed or probable case
• Confirmed • suspected or probable case that also has laboratory confirmation
Category A Diseases/Agents Category B Diseases/Agents
Category C Diseases/Agents
High-priority agents include
.
organisms
that pose a risk to
national security because they
Third highest priority agents
include emerging pathogens
that could be engineered for
mass dissemination in the
future because of
availability;
can be easily disseminated or
transmitted from person to
person
result in high mortality rates
and have the potential for
major public health impact
might cause public panic and
social disruption
require special action for public
health preparedness.
Second highest priority agents
include those that
are moderately easy to
disseminate;
result in moderate morbidity
rates and low mortality rates;
and
require specific enhancements
of CDC's diagnostic capacity and
enhanced disease surveillance
ease of production and
dissemination; and
potential for high morbidity and
mortality rates and major health
impact.
Category A
Category B
Category C
•Anthrax (Bacillus anthracis)
Brucellosis (Brucella species)
Epsilon toxin of Clostridium
perfringens
Food safety threats (e.g.,
Salmonella species, Escherichia coli
O157:H7, Shigella)
Glanders (Burkholderia mallei)
Melioidosis (Burkholderia
pseudomallei)
Psittacosis (Chlamydia psittaci)
Q fever (Coxiella burnetii)
Ricin toxin from Ricinus communis
(castor beans)
Staphylococcal enterotoxin B
Typhus fever (Rickettsia prowazekii)
Viral encephalitis (alphaviruses
[e.g., Venezuelan equine
encephalitis, eastern equine
encephalitis, western equine
encephalitis])
Water safety threats (e.g., Vibrio
cholerae, Cryptosporidium parvum)
Emerging infectious
diseases such as Nipah
virus and hantavirus
Category Definitions
•Botulism (Clostridium
botulinum toxin)
•Plague (Yersinia pestis)
•Smallpox (variola major)
•Tularemia (Francisella
tularensis)
•Viral hemorrhagic fevers
EBOLA VIRUS
Marburg]and arenaviruses
[e.g., Lassa, Machupo])
Risk Group 4 pathogens
Biosafety level -4 containment
Triple packaging using absorbent material
With cold chain
•Institute Pasteur, the European Mobile Laboratory
• CDC in Guinea
•the Kenema Government Hospital Viral Hemorrhagic Fever
•Laboratory in Sierra Leone
• Liberia Institute of Biomedical Research
Sample
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
Serology
IgM anti-bodies can appear as early as two
days post onset of symptoms and disappear
between 30 and 168 days after infection
IgG-specific antibodies develop between day 6
and 18 after onset and persist for many years
v
Virus isolation
Cell line – VeroE6 and MA104
Cells were observed for cytopathic effect for 2 weeks
Causes lytic infections in cell culture
All cell cultures were tested for viral antigen by
immunofluorescent
Molecular method
RT-PCR specific for a 419-bp region of the L gene of
the filoviruses
A confirmatory RT-PCR was performed on the
filovirus-positive samples to amplify a 428-bp
region of the EBOV NP
Other test
• Thrombocytopenia <150,000 cells/µL
•
ALT, AST
• Coagulation profile
On isolation of patients
use of strict barrier nursing procedures
Present treatment strategies are mainly symptomatic
and supportive
Hydrating the patient, maintaining their oxygen status and blood
pressure and treating them for any complicating infections
Is there any role of Ribavarin in Ebola?
No in-vitro or in-vivo effect on filoviruses
severe adverse effects associated with the drug
Ribavirin is not recommended for Ebola virus infections
What drugs exist to combat the disease?
Combines two different serums made by two different companies
San Diego firm Mapp Biopharmaceutical & ZMAb ( Canadian
company Defyrus Inc)
August 2013, Mapp Biopharmaceutical -working with the U.S. Army Medical
Research Institute of Infectious Diseases (USAMRIID)
Biological
weapon
Inject Ebola into mice, and extract three types of antibodies that fight different parts of the
virus
spliced in human DNA to produce chimera
antibodies acceptable to humans
MB-003
The next challenge was producing enough MB-003 for an effective dose.Antibodies could be
grown inside genetically engineered Nicotiana Benthamiana (Australian tobacco plant)
Testing the MB-003 serum on
monkeys
43% of the infected monkeys survived
In June 2012, Defyrus tested ZMAb in Rhesus Macaques -100% of infected monkeys survived
(24hr) & 50% survived when treated 48 hours after exposure
Before ZMapp could begin human trials
and get approval from the U.S. FDA
Ebola outbreak began in Guinea
Two American missionary workers infected with Ebola (Kent Brantly and Nancy
Writbol)
ZMapp were given
Improved
TKM-Ebola is an exprimental drug for Ebola disease
Developed by Tekmira Pharmaceuticals Corp
Small interfering RNAs targeting three of the seven
proteins in Ebola virus: L polymerase membraneassociated protein (VP24), and (VP35) – phase 1 trial
Standard precaution measures
Vaccine
• Active case identification and isolation of patients
• Identifying contacts of ill or deceased persons and tracking the
contacts daily for the entire incubation period of 21 days
•
The aim - to avoid contact with the blood or secretions of an
infected patient
Investigation of retrospective and current cases to document all
contact with
the body
the deceased
patient should be
historic Direct
and ongoing
chains
of of
virus
transmission
avoided
• Identifying deaths in the community and using safe burial
practices
• Daily reporting of cases
• Education of health-care workers -appropriate use of personal
protective equipment
•
Practice careful hygiene
•
Avoid contact with blood and body fluids
• Do not handle items that may have come in
contact with an infected person’s blood or body
fluids
• Avoid funeral or burial rituals that require
handling the body of someone who has died
from Ebola
• Avoid contact with animals and raw meat
• Avoid hospitals where Ebola patients are being
treated
• After you return, monitor your health for 21
days and seek medical care immediately if you
develop symptoms of Ebola
Hand Hygiene
• Perform hand hygiene immediately after removing PPE.
–
If hands become visibly contaminated during PPE removal, wash hands before continuing to
remove PPE
• Wash hands with soap and water or use an alcohol-based hand
rub
* Ensure that hand hygiene facilities are available at the point needed, e.g., sink or alcohol-based
hand rub
PPE Use in Healthcare Settings
PPE Used in Healthcare Settings
Gloves – protect hands
Gowns/aprons – protect skin and/or clothing
Masks and respirators– protect mouth/nose
Goggles – protect eyes
Face shields – protect face, mouth, nose, and eyes
Key Points About PPE
Before contact with the patient - generally before entering the room
Use carefully – don’t spread contamination
Remove and discard carefully, either at the doorway or immediately
outside patient room
Remove respirator outside room
Immediately perform hand hygiene
Sequence for Donning PPE
Gown first
Mask or respirator
Goggles or face shield
Gloves
Sequence for Removing PPE
• Gloves
• Face shield or goggles
• Gown
• Mask or respirator
Public Health Agency of Canada (PHAC) has donated up to 1000 doses of its
experimental VSV-EBOV candidate
Consists of transgenic vesicular stomatitis virus that expresses the Ebola glycoprotein
The vaccine, which has only been tested in animals, protected 100% of macaques
when administered 21 days before an otherwise fatal infection
when administered immediately after exposure to Ebola: when it was given to
primates 30 minutes after inoculation with the virus - four out of eight survived
NIH and GlaxoSmithKline
A recombinant adenovirus that expresses the
glycoproteins of two different strains of Ebola virus
100% protection when used prophylactically in primates
phase 1 trials
Objectives of Epidemic
Preparedness and Response
1. Anticipation/prediction
•
so that epidemics be prevented
2. Early detection
• to know when there is a
problem
3. Rapid Response
• guidelines/trained
staff/supplies
• in place before
epidemic
4. Effective Response
• appropriate control
methods
• adequate resources
and logistics
Outbreak Detection and Response
Without Preparedness
First
Case
Late
Detection
Delayed
Response
90
80
70
60
50
Opportunity
for control
40
30
20
10
DAY
39
37
35
33
31
29
27
25
23
21
19
17
15
13
11
9
7
5
3
0
1
CASES
Outbreak Detection and Response
With Preparedness
Early
Detection
Rapid
Response
90
80
70
Potential
Cases Prevented
60
50
40
30
20
10
DAY
39
37
35
33
31
29
27
25
23
21
19
17
15
13
11
9
7
5
3
0
1
CASES
Components of Epidemic Preparedness
No need to panic
"put in operation the most advanced surveillance and tracking systems" for the
hemorrhagic virus
The government is setting up centres at airports and ports to deal with travellers
showing any potential symptoms of Ebola, spread through close contact with bodily
fluids of people who who are sick.
All air passengers arriving in India from Ebola-affected countries must now fill in a
symptom-checklist form and provide addresses as the government builds a database
to track people who might develop symptoms.
Guinea pig
Syrian golden hamster
African green monkeys
Mice
Baboons
Cynomolgus monkey
Be
Prepared !
This presentation was published on mdCurrent-India with
permission from the author, Dr. Sonu Agrawal at:
http://mdcurrent.in/presentations-and-slides/ebola-virushaemorrhagic-fever-current-scenario/