Ebola Virus Disease
By
Harshit Jadav
NIPER-Gandhinagar
Harshit Jadav 1
Ebola Virus Disease (EVD)
• Ebola virus disease is a severe, fatal, zoonotic
filovirus infection
• The current outbreak in west Africa, (first case
notified in 1976)
• Fatality rates are between 80% and 100%
• This filovirus is classified as a biological class 4
pathogen
• The most severely affected countries are
Guinea, Sierra Leone and Liberia
Harshit Jadav 2
Harshit Jadav 3
Ebola virus
• Lipid-enveloped, non-segmented, negatively
stranded RNA virus
• Appears to have “spikes” due to Glycoprotein
membrane
• Belongs to the viral family Filoviridae
• The natural reservoir of the virus is unknown
• CDC found that it is a zoonotic virus mostly
found in bats
Harshit Jadav 4
Species of Ebolavirus
• The virus family Filoviridae includes 3 genera:
Cuevavirus, Marburgvirus, and Ebolavirus
• There are five species of Ebola virus
 Zaire ebolavirus
 Sudan ebolavirus
 Taï Forest ebolavirus
 Bundibugyo ebolavirus
 Reston ebolavirus
Harshit Jadav 5
– Order: Mononegavirales
– Family: Filoviridae
– Genes: Ebola virus
– Species: Zaire ebolavirus
• Zaire ebolavirus is responsible for the current
outbreak in west Africa
Harshit Jadav 6
Outbreak (in small population)
(eg. Ebola in West Africa, MERS in Soudi Arabia )
Epidemic (in specific community or region)
(eg. Cholera in India, yellow fever in Africa)
Pandemic (in very large population)
(eg. SARS , Influenza)
Harshit Jadav 7
Article information
• Journal: The New England Journal Of Medicine
• Author: WHO Ebola Response team
• Volume: 365 (16)
• Date of publication: 16th October, 2014
• Impact factor: 54.42
Harshit Jadav 8
Epidemiology
• Since December 2013 and as of 19 October
2014, WHO has reported 9936 cases of Ebola
virus disease (EVD) in West Africa including
7877 deaths
• 42% healthcare workers were infected with
EVD
Harshit Jadav 9
• Ebola hemorrhagic fever (EHF) is an acute viral
syndrome that presents with fever and an
ensuing bleeding diathesis that is marked by
high mortality in human and nonhuman
primates
Harshit Jadav 10
Transmission
• The virus is thought to be initially acquired by exposure
to body fluids or tissue from infected animals, such as
bats and non-human primates
• Human to human transmission occurs through contact
with body fluids from infected patients
• Most cases result from close physical contact or contact
with body fluids (such as sweat, blood, faeces, vomit,
saliva, genital secretions, urine, and breast milk) of
infected patients.
• The incubation period after infection is usually 5-9 days
Harshit Jadav 11
Pathophysiology
• Most of the studies were performed in non-
human primate and rodent models
• The virus genome consists of a single 19 kb strand
of negative sense RNA with seven viral genes that
are transcribed by the viral RNA dependent RNA
polymerase present in the virion.
• single strand of RNA is covered by helically
arranged viral nucleoproteins NP and VP30,
which are linked by matrix proteins VP24 and VP4
to the lipid bilayer that coats the virion
Harshit Jadav 12
Pathophysiology (cont’d)
• Tissue invasion occurs through infected fluid coming into
contact with breaks in the mucosa or skin.
• This can occur with animal to human or human to
human transmission.
• Monocytes, macrophages, and dendritic cells are the
preferred replication sites for filoviruses on initial
infection.
• Infected cells migrate to the regional lymph nodes,
liver, and spleen, thereby disseminating the infection.
Harshit Jadav 13
Who are at risk?
• Contacts of infected patients (including
healthcare workers and household contacts) -
if they were exposed to the patient’s body
fluids without protective equipment within
the past 21 days.
• Persons involved in Burial ceremonies of
infected patients
• Health-care workers
• Household persons of infected patients
Harshit Jadav 14
A contact
• A contact is defined by WHO as someone who
has slept in the same household as a patient;
– had direct physical contact with the patient during
the illness or at the funeral;
– touched the patient’s body fluids, clothes, or bed
linens during the illness; or
– been breast fed by the patient
Harshit Jadav 15
Phase of EVD
• There are typically three phases of illness
1. A few days of non-specific fever, headache, and
myalgia (5-7 days)
2. A gastrointestinal phase in which diarrhoea and
vomiting, abdominal symptoms, and
dehydration are prominent. In the second week,
the patient may recover or deteriorate (8-15
days)
3. Collapse, neurological manifestations, and
bleeding, shock, coma, death (16-21 days)
Harshit Jadav 16
Typical symptoms
• Fever ≥101°F
• Fatigue
• Nausea or vomiting
• Diarrhoea
• Headache
• Abdominal pain
• Myalgia
• Prostration
• Sore throat
• Unexplained bleeding or bruising
• Spontaneous abortion or miscarriage
• Hiccups
• Rash
All the symptoms
are common so it
mislead to flu or
malaria
Harshit Jadav 17
Clinical features
The most common symptoms reported were
fever (87.1%),
fatigue (76.4%),
loss of appetite (64.5%),
vomiting (67.6%),
diarrhoea (65.6%),
headache (53.4%),
abdominal pain (44.3%),
unexplained bleeding (18%)
Harshit Jadav 18
Diagnostic test of EVD
• Antigen capture enzyme linked immunosorbent assay
(ELISA) testing
A useful diagnostic test with high specificity
Can be used to confirm the diagnosis along with a positive
reverse transcriptase-polymerase chain reaction result
• Full blood count
Decreasing platelet count with low haemoglobin count
• Coagulation studies
Prolonged prothrombin time or activated partial
thromboplastin
Harshit Jadav 19
Diagnostic test of EVD
• Blood cultures
Negative blood cultures are helpful
• Ebola specific IgM and IgG antibodies
IgM antibodies can appear in serum as early as
day 2 after infection but results are variable up to
day 9.
They become negative between 30 and 168 days
after symptom onset
IgG response develops between days 6 and 18 and
can persist for several years
Harshit Jadav 20
Management of EVD
• There is no any specific vaccine or treatment
for EVD.
• Patients just get symptomatic treatment
• Isolation of patients is necessary to patients as
well as other personals
Harshit Jadav 21
Symptomatic treatment
• Fever and pain—Fever and pain should be
treated with paracetamol first. Opioid
analgesics (such as morphine) are preferable
for more severe pain
• Nausea and vomiting—Oral or intravenous
antiemetics (such as ondansetron and
metoclopramide) are recommended
• Heartburn, dysphagia, and upper abdominal
pain—proton pump inhibitor (such as
omeprazole) may be beneficial
Harshit Jadav 22
• Seizures - Although uncommon, seizures can be
seen in advanced disease, A benzodiazepine can
be used to abort the seizure and can be given
intramuscularly
• Agitation - haloperidol or a benzodiazepine
• Sepsis and septic shock – broad spectrum
antibiotics (such as ceftriaxone, piperacillin-
tazobactam, or meropenem) in the first hour
• Malaria should be tested for and treated with
appropriate antimalarial therapy
Symptomatic treatment (cont’d)
Harshit Jadav 23
Infection control measures for
healthcare workers
• Wear protective clothing
• Practise proper infection control and
sterilisation measures
• Isolate suspected patients from each other
• Avoid direct contact with bodies of people
who have died from Ebola, or suspected Ebola
Harshit Jadav 24
Emerging treatments
• Convalescent whole blood or plasma:
transfusion of blood from convalescent patients
showed beneficial effect in acute phase of
infection.
Harshit Jadav 25
Zmapp:
• The best known emerging treatment so far,
ZMapp, is a combination of three humanised
monoclonal antibodies targeted at three Ebola
virus glycoprotein epitopes and is engineered for
expression in tobacco plants
• ZMapp had proved protective when given to non-
human primates 24-48 hours after infection.
• It has not yet been tested in humans for safety or
efficacy
• The whole study is supported by US govt.
Harshit Jadav 26
TKM-Ebola
• TKM-Ebola consists of a combination of small
interfering RNAs that target Ebola virus RNA
polymerase L, formulated with lipid nanoparticle
technology.
• It has been shown to be protective in non-human
primates (guinea pigs and monkeys)
• The US Food and Drug Administration has
granted expanded access to this drug under an
Investigational New Drug application (INDA)
• Under emergency protocols, it had given to a
small number of patients in Zaire.
Harshit Jadav 27
Brincidofovir
• Formerly known as CMX-001, brincidofovir is
currently undergoing phase III trials for the
treatment of cytomegalovirus and adenovirus.
• It also shows activity against Ebola virus in
vitro.
• The drug has been used in patients with Ebola
virus infection in the US under Emergency
Investigational New Drug applications
approved by the FDA.
Harshit Jadav 28
Favipiravir
• Formerly known as T-705, favipiravir
selectively inhibits viral RNA dependent RNA
polymerase
• It is active against influenza viruses, West Nile
virus, yellow fever virus, foot and mouth
disease virus, as well as other flaviviruses
arenaviruses, bunyaviruses
• It is effective against Ebola virus in mouse
models
• Human trials are started in west Africa
Harshit Jadav 29
BCX-4430
• BCX-4430 is an adenosine analogue that is
active against Ebola virus in rodents
• It is thought to act through the inhibition of
viral RNA dependent RNA polymerase
Harshit Jadav 30
AVI-7537
• AVI-7537 consists of antisense
phosphorodiamidate morpholino oligomers
(PMOs) that target the Ebola virus VP24 gene
• It confers a survival benefit to Ebola virus
infected non-human primates
• AV-7537 undergone phase I clinical studies.
Harshit Jadav 31
Other agents
• Some drugs approved for other indications,
which have known safety profiles at clinically
used doses, including chloroquine and
imatinib, have shown activity against EV in
vitro and, in some cases, in rodent models.
• They are also used in the treatment of EHF in
west Africa by some hospitals
Harshit Jadav 32
Vaccine
• cAd3-ZEBOV (also known as the NIAID/GSK
Ebola vaccine or cAd3-EBO Z) is an
experimental vaccine for two ebolaviruses,
Ebola virus and Sudan virus, developed by
scientists at GlaxoSmithKline (GSK) and tested
by National Institute of Allergy and Infectious
Disease (NIAID).
• The vaccine is derived from Chimpanzee
adenovirus, chimp adenovirus type 3(chAd3)
genetically engineered express glycoprotein
from the Zaire Harshit Jadav 33
Vaccine (cont’d)
• rVSV-EBOV is an experimental vaccine for
the Ebola filovirus, developed by scientists at
the Canadian National Microbiology
Laboratory
• rVSV-ZEBOV is an attenuated vesicular
stomatitis virus with one of its genes replaced
by an Ebola virus gene.
• Human trials have started in the US
Harshit Jadav 34

Ebola virus disease (EVD)

  • 1.
    Ebola Virus Disease By HarshitJadav NIPER-Gandhinagar Harshit Jadav 1
  • 2.
    Ebola Virus Disease(EVD) • Ebola virus disease is a severe, fatal, zoonotic filovirus infection • The current outbreak in west Africa, (first case notified in 1976) • Fatality rates are between 80% and 100% • This filovirus is classified as a biological class 4 pathogen • The most severely affected countries are Guinea, Sierra Leone and Liberia Harshit Jadav 2
  • 3.
  • 4.
    Ebola virus • Lipid-enveloped,non-segmented, negatively stranded RNA virus • Appears to have “spikes” due to Glycoprotein membrane • Belongs to the viral family Filoviridae • The natural reservoir of the virus is unknown • CDC found that it is a zoonotic virus mostly found in bats Harshit Jadav 4
  • 5.
    Species of Ebolavirus •The virus family Filoviridae includes 3 genera: Cuevavirus, Marburgvirus, and Ebolavirus • There are five species of Ebola virus  Zaire ebolavirus  Sudan ebolavirus  Taï Forest ebolavirus  Bundibugyo ebolavirus  Reston ebolavirus Harshit Jadav 5
  • 6.
    – Order: Mononegavirales –Family: Filoviridae – Genes: Ebola virus – Species: Zaire ebolavirus • Zaire ebolavirus is responsible for the current outbreak in west Africa Harshit Jadav 6
  • 7.
    Outbreak (in smallpopulation) (eg. Ebola in West Africa, MERS in Soudi Arabia ) Epidemic (in specific community or region) (eg. Cholera in India, yellow fever in Africa) Pandemic (in very large population) (eg. SARS , Influenza) Harshit Jadav 7
  • 8.
    Article information • Journal:The New England Journal Of Medicine • Author: WHO Ebola Response team • Volume: 365 (16) • Date of publication: 16th October, 2014 • Impact factor: 54.42 Harshit Jadav 8
  • 9.
    Epidemiology • Since December2013 and as of 19 October 2014, WHO has reported 9936 cases of Ebola virus disease (EVD) in West Africa including 7877 deaths • 42% healthcare workers were infected with EVD Harshit Jadav 9
  • 10.
    • Ebola hemorrhagicfever (EHF) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates Harshit Jadav 10
  • 11.
    Transmission • The virusis thought to be initially acquired by exposure to body fluids or tissue from infected animals, such as bats and non-human primates • Human to human transmission occurs through contact with body fluids from infected patients • Most cases result from close physical contact or contact with body fluids (such as sweat, blood, faeces, vomit, saliva, genital secretions, urine, and breast milk) of infected patients. • The incubation period after infection is usually 5-9 days Harshit Jadav 11
  • 12.
    Pathophysiology • Most ofthe studies were performed in non- human primate and rodent models • The virus genome consists of a single 19 kb strand of negative sense RNA with seven viral genes that are transcribed by the viral RNA dependent RNA polymerase present in the virion. • single strand of RNA is covered by helically arranged viral nucleoproteins NP and VP30, which are linked by matrix proteins VP24 and VP4 to the lipid bilayer that coats the virion Harshit Jadav 12
  • 13.
    Pathophysiology (cont’d) • Tissueinvasion occurs through infected fluid coming into contact with breaks in the mucosa or skin. • This can occur with animal to human or human to human transmission. • Monocytes, macrophages, and dendritic cells are the preferred replication sites for filoviruses on initial infection. • Infected cells migrate to the regional lymph nodes, liver, and spleen, thereby disseminating the infection. Harshit Jadav 13
  • 14.
    Who are atrisk? • Contacts of infected patients (including healthcare workers and household contacts) - if they were exposed to the patient’s body fluids without protective equipment within the past 21 days. • Persons involved in Burial ceremonies of infected patients • Health-care workers • Household persons of infected patients Harshit Jadav 14
  • 15.
    A contact • Acontact is defined by WHO as someone who has slept in the same household as a patient; – had direct physical contact with the patient during the illness or at the funeral; – touched the patient’s body fluids, clothes, or bed linens during the illness; or – been breast fed by the patient Harshit Jadav 15
  • 16.
    Phase of EVD •There are typically three phases of illness 1. A few days of non-specific fever, headache, and myalgia (5-7 days) 2. A gastrointestinal phase in which diarrhoea and vomiting, abdominal symptoms, and dehydration are prominent. In the second week, the patient may recover or deteriorate (8-15 days) 3. Collapse, neurological manifestations, and bleeding, shock, coma, death (16-21 days) Harshit Jadav 16
  • 17.
    Typical symptoms • Fever≥101°F • Fatigue • Nausea or vomiting • Diarrhoea • Headache • Abdominal pain • Myalgia • Prostration • Sore throat • Unexplained bleeding or bruising • Spontaneous abortion or miscarriage • Hiccups • Rash All the symptoms are common so it mislead to flu or malaria Harshit Jadav 17
  • 18.
    Clinical features The mostcommon symptoms reported were fever (87.1%), fatigue (76.4%), loss of appetite (64.5%), vomiting (67.6%), diarrhoea (65.6%), headache (53.4%), abdominal pain (44.3%), unexplained bleeding (18%) Harshit Jadav 18
  • 19.
    Diagnostic test ofEVD • Antigen capture enzyme linked immunosorbent assay (ELISA) testing A useful diagnostic test with high specificity Can be used to confirm the diagnosis along with a positive reverse transcriptase-polymerase chain reaction result • Full blood count Decreasing platelet count with low haemoglobin count • Coagulation studies Prolonged prothrombin time or activated partial thromboplastin Harshit Jadav 19
  • 20.
    Diagnostic test ofEVD • Blood cultures Negative blood cultures are helpful • Ebola specific IgM and IgG antibodies IgM antibodies can appear in serum as early as day 2 after infection but results are variable up to day 9. They become negative between 30 and 168 days after symptom onset IgG response develops between days 6 and 18 and can persist for several years Harshit Jadav 20
  • 21.
    Management of EVD •There is no any specific vaccine or treatment for EVD. • Patients just get symptomatic treatment • Isolation of patients is necessary to patients as well as other personals Harshit Jadav 21
  • 22.
    Symptomatic treatment • Feverand pain—Fever and pain should be treated with paracetamol first. Opioid analgesics (such as morphine) are preferable for more severe pain • Nausea and vomiting—Oral or intravenous antiemetics (such as ondansetron and metoclopramide) are recommended • Heartburn, dysphagia, and upper abdominal pain—proton pump inhibitor (such as omeprazole) may be beneficial Harshit Jadav 22
  • 23.
    • Seizures -Although uncommon, seizures can be seen in advanced disease, A benzodiazepine can be used to abort the seizure and can be given intramuscularly • Agitation - haloperidol or a benzodiazepine • Sepsis and septic shock – broad spectrum antibiotics (such as ceftriaxone, piperacillin- tazobactam, or meropenem) in the first hour • Malaria should be tested for and treated with appropriate antimalarial therapy Symptomatic treatment (cont’d) Harshit Jadav 23
  • 24.
    Infection control measuresfor healthcare workers • Wear protective clothing • Practise proper infection control and sterilisation measures • Isolate suspected patients from each other • Avoid direct contact with bodies of people who have died from Ebola, or suspected Ebola Harshit Jadav 24
  • 25.
    Emerging treatments • Convalescentwhole blood or plasma: transfusion of blood from convalescent patients showed beneficial effect in acute phase of infection. Harshit Jadav 25
  • 26.
    Zmapp: • The bestknown emerging treatment so far, ZMapp, is a combination of three humanised monoclonal antibodies targeted at three Ebola virus glycoprotein epitopes and is engineered for expression in tobacco plants • ZMapp had proved protective when given to non- human primates 24-48 hours after infection. • It has not yet been tested in humans for safety or efficacy • The whole study is supported by US govt. Harshit Jadav 26
  • 27.
    TKM-Ebola • TKM-Ebola consistsof a combination of small interfering RNAs that target Ebola virus RNA polymerase L, formulated with lipid nanoparticle technology. • It has been shown to be protective in non-human primates (guinea pigs and monkeys) • The US Food and Drug Administration has granted expanded access to this drug under an Investigational New Drug application (INDA) • Under emergency protocols, it had given to a small number of patients in Zaire. Harshit Jadav 27
  • 28.
    Brincidofovir • Formerly knownas CMX-001, brincidofovir is currently undergoing phase III trials for the treatment of cytomegalovirus and adenovirus. • It also shows activity against Ebola virus in vitro. • The drug has been used in patients with Ebola virus infection in the US under Emergency Investigational New Drug applications approved by the FDA. Harshit Jadav 28
  • 29.
    Favipiravir • Formerly knownas T-705, favipiravir selectively inhibits viral RNA dependent RNA polymerase • It is active against influenza viruses, West Nile virus, yellow fever virus, foot and mouth disease virus, as well as other flaviviruses arenaviruses, bunyaviruses • It is effective against Ebola virus in mouse models • Human trials are started in west Africa Harshit Jadav 29
  • 30.
    BCX-4430 • BCX-4430 isan adenosine analogue that is active against Ebola virus in rodents • It is thought to act through the inhibition of viral RNA dependent RNA polymerase Harshit Jadav 30
  • 31.
    AVI-7537 • AVI-7537 consistsof antisense phosphorodiamidate morpholino oligomers (PMOs) that target the Ebola virus VP24 gene • It confers a survival benefit to Ebola virus infected non-human primates • AV-7537 undergone phase I clinical studies. Harshit Jadav 31
  • 32.
    Other agents • Somedrugs approved for other indications, which have known safety profiles at clinically used doses, including chloroquine and imatinib, have shown activity against EV in vitro and, in some cases, in rodent models. • They are also used in the treatment of EHF in west Africa by some hospitals Harshit Jadav 32
  • 33.
    Vaccine • cAd3-ZEBOV (alsoknown as the NIAID/GSK Ebola vaccine or cAd3-EBO Z) is an experimental vaccine for two ebolaviruses, Ebola virus and Sudan virus, developed by scientists at GlaxoSmithKline (GSK) and tested by National Institute of Allergy and Infectious Disease (NIAID). • The vaccine is derived from Chimpanzee adenovirus, chimp adenovirus type 3(chAd3) genetically engineered express glycoprotein from the Zaire Harshit Jadav 33
  • 34.
    Vaccine (cont’d) • rVSV-EBOVis an experimental vaccine for the Ebola filovirus, developed by scientists at the Canadian National Microbiology Laboratory • rVSV-ZEBOV is an attenuated vesicular stomatitis virus with one of its genes replaced by an Ebola virus gene. • Human trials have started in the US Harshit Jadav 34