Complete description on Ebola Virus Disease

1. Dr. Bharat Kalidindi
MPH 1st SEM
Padmashree School of Public Health. Bangalore

2. OVERVIEW
• Ebola is a disease of humans and other primates caused
by ebolaviruses, is a severe, often fatal illness in humans.
• The average EVD case fatality rate is around 50%. Case fatality rates
have varied from 25% to 90% in past outbreaks.
• The 2014 Ebola outbreak is the largest Ebola outbreak in history and
the first in West Africa.

3. BACKGROUND
• Ebola virus disease (EVD) first appeared in 1976 in 2 simultaneous
outbreaks, one in Nzara, Sudan, and the other in Yambuku,
Democratic Republic of Congo. The latter occurred in a village near the
Ebola River, from which the disease takes its name.
• The current outbreak in west Africa, (first cases notified in March
2014), is the largest and most complex Ebola outbreak since the Ebola
virus was first discovered in 1976. There have been more cases and
deaths in this outbreak than all others combined. It has also spread
between countries starting in Guinea then spreading across land
borders to Sierra Leone and Liberia, by air (1 traveller only) to Nigeria,
and by land (1 traveller) to Senegal.

4. • The most severely affected countries, Guinea, Sierra Leone and
Liberia have very weak health systems, lacking human and
infrastructural resources, having only recently emerged from long
periods of conflict and instability.
• On August 8 2014, the WHO Director-General declared this outbreak a
Public Health Emergency of International Concern.
• A separate, unrelated Ebola outbreak began in Boende, Equateur, an
isolated part of the Democratic Republic of Congo on 24th August
2014.

6. STORY OF ORIGIN
• August 26, 1976 in Yambuku, a town in the north of Zaïre. A
44-year-old school teacher returned from a small hike. He went
to the doctor and because of his high fever they gave him a
quinine shot which is good against malaria.
• A week later, he had uncontrolled vomiting, bloody diarrhea,
trouble breathing and then bleeding from his nose, mouth, and
anus.
• He died ~14 days after the onset of symptoms.

7. • The first outbreak of Ebola (Ebola-Sudan) infected over 284
people, with a mortality rate of 53%.
• A few months later, the second Ebola virus emerged from
Yambuku, Zaire, Ebola-Zaire (EBOZ). EBOZ, with the highest
mortality rate of any of the Ebola viruses (88%), infected 318
people.
• Despite the tremendous effort of experienced and dedicated
researchers, Ebola's natural reservoir was never identified.

8. • The third strain of Ebola, Ebola Reston (EBOR), was first identified
in 1989 when infected monkeys were imported into Reston,
Virginia, from Mindanao in the Philippines.
• Fortunately, the few people who were infected with EBOR
(seroconverted) never developed Ebola hemorrhagic fever (EHF).
• The last known strain of Ebola, Ebola Cote d'Ivoire (EBO-CI) was
discovered in 1994 when a female ethologist performing a
necropsy on a dead chimpanzee from the Tai Forest, Cote d'Ivoire,
accidentally infected herself during the necropsy.

9. Non-human primates, like gorillas and chimpanzees, have
been cited by the World Health Organization as possible
infection sources for humans, but experts have realized that
they are not the source of the problem. The apes have been
deemed “accidental hosts,” meaning that they catch the
disease and then pass it along but are not the initial “reservoir”
source that produces the virus.

10. The virus kills gorillas and
chimpanzees and other
monkeys. Because it kills apes
in such high percentage – they
are not likely to be its natural
host.

13. EBOLA TAXONOMY
Scientific Classification
 Order: Mononegavirales
 Family: Filoviridae
 Genus: Ebola like viruses
 Species: Ebola
 Subtypes
• Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast
disease in humans
• Ebola-Reston
disease in nonhuman primates
• Most mysterious virus group
• Pathogenesis poorly understood

14. • Zoonotic virus – bats the most likely reservoir, although species unknown
• Spillover event from infected wild animals (e.g., fruit bats, monkey, duiker) to
humans, followed by human-human transmission

15. EBOLA VIRUS TRANSMISSION
• Virus present in high quantity in blood, body fluids, and excreta of symptomatic
EVD-infected patients
• Opportunities for human-to-human transmission
• Direct contact (through broken skin or unprotected mucous membranes) with
an EVD-infected patient’s blood or body fluids
• Sharps injury (with EVD-contaminated needle or other sharp)
• Direct contact with the corpse of a person who died of EVD
• Indirect contact with an EVD-infected patient’s blood or body fluids via a
contaminated object (soiled linens or used utensils)
• Ebola can also be transmitted via contact with blood, fluids, or meat of an infected
animal
• Limited evidence that dogs become infected with Ebola virus
• No reports of dogs or cats becoming sick with or transmitting Ebola

16. HUMAN-TO-HUMAN TRANSMISSION
• Infected persons are not contagious until onset of symptoms
• Infectiousness of body fluids (e.g., viral load) increases as patient becomes
more ill
• Remains from deceased infected persons are highly infectious
• Human-to-human transmission of Ebola virus via inhalation (aerosols) has not
been demonstrated

17. virus enters a cell through a mechanism that has yet to be determined
Once inside the host cell's cytoplasm, the filovirus uncoats itself and
releases transcriptase, which is contained in the virion
Transcriptase transcribes the viral -ssRNA into the complimentary +ssRNA
RNA will then be used as the template for the new viral genomes
Soon after the infection, the cell develops cytoplasmic inclusion bodies
that contain the highly structured viral nucleocapsid
After the nucleocapsid has been formed, the new virus will self-assemble
and bud from the cell membrane stealing some of the membrane for its
envelope.
The Filoviridae Journey

19. EBOLA PATHOGENESIS
• Direct infection of tissues
• Immune dysregulation
• Disseminated intravascular coagulation (DIC) and coagulopathy
• Hypovolemia and vascular collapse
• Electrolyte abnormalities
• Multi-organ failure, septic shock

20. INCUBATION PERIOD
• Patients with Ebola virus disease typically have an abrupt onset of
symptoms 6 to 12 days after exposure (range 2 to 21 days).
• There is no evidence that asymptomatic persons still in the incubation
period are infectious to others.
• All symptomatic individuals should be assumed to have virus in the
blood and other body fluids, and appropriate safety precautions should
be taken

21. Early Clinical Presentation
Acute onset; typically 6 – 12 days after exposure
(range 2–21 days)
Signs and symptoms
• Initial: Fever, chills, myalgias, malaise, anorexia
• After 5 days: GI symptoms, such as nausea, vomiting, watery diarrhea, abdominal
pain
• Other: Headache, conjunctivitis, hiccups, rash, chest pain, shortness of breath,
confusion, seizures
• Hemorrhagic symptoms in 18% of cases
Other possible infectious causes of symptoms
• Malaria, typhoid fever, meningococcemia, Lassa fever and other bacterial infections
(e.g., pneumonia) – all very common in Africa
Common signs and symptoms reported from the 2014-2015 West African outbreak include fever, fatigue, headache, vomiting,
diarrhoea, and loss of appetite. Reports have also described weakness, myalgias, as well as a high fever accompanied by
relative bradycardia as seen in typhoid fever.

22. CLINICAL FEATURES
• Nonspecific early symptoms progress to:
• Hypovolemic shock and multi-organ failure
• Hemorrhagic disease
• Death
• Non-fatal cases typically improve 6–11 days after symptoms onset
• Fatal disease associated with more severe early symptoms
• Fatality rates of 70% have been reported in rural Africa
• Intensive care, especially early intravenous and electrolyte management, may increase
the survival rate

24. CLINICAL MANIFESTATIONS BY ORGAN SYSTEM
IN WEST AFRICAN EBOLA OUTBREAK
Organ System Clinical Manifestation
General Fever (87%), fatigue (76%), arthralgia (39%), myalgia (39%)
Neurological Headache (53%), confusion (13%), eye pain (8%), coma (6%)
Cardiovascular Chest pain (37%),
Pulmonary Cough (30%), dyspnea (23%), sore throat (22%), hiccups (11%)
Gastrointestinal Vomiting (68%), diarrhea (66%), anorexia (65%), abdominal pain (44%), dysphagia (33%),
jaundice (10%)
Hematological Any unexplained bleeding (18%), melena/hematochezia (6%), hematemesis (4%), vaginal
bleeding (3%), gingival bleeding (2%), hemoptysis (2%), epistaxis (2%), bleeding at
injection site (2%), hematuria (1%), petechiae/ecchymoses (1%)
Integumentary Conjunctivitis (21%), rash (6%)

25. EXAMPLES OF HEMORRHAGIC SIGNS
Bleeding at IV Site Hematemesis
Gingival bleeding

26. LABORATORY FINDINGS
• Thrombocytopenia (50,000–100,000/mL range)
• Leukopenia followed by neutrophilia
• Transaminase elevation: elevation serum aspartate amino-transferase (AST) >
alanine transferase (ALT)
• Electrolyte abnormalities from fluid shifts
• Coagulation: PT and PTT prolonged (These changes are most prominent in severe and fatal cases.)
• Renal: proteinuria, increased creatinine

27. viremia
3
IgM
ELISA IgM
0 10
IgG
IgM: up to 3 – 6 months
ELISA IgG
IgG: 3 – 5 years or more (life-long persistance?)
days post onset of symptoms
RT-PCR
Critical information: Date of onset of fever/symptoms
Fever
EVD: Expected Diagnostic Test Results Over Time
27

28. EBOLA VIRUS DIAGNOSIS
• RT – PCR Used to diagnose acute infection
• More sensitive than antigen detection ELISA
• Identification of specific viral genetic fragments
• Performed in select CLIA-certified laboratories
• RT-PCR sample collection
• Volume: minimum volume of 4mL whole blood
• Plastic collection tubes (not glass or heparinized tubes)
• Whole blood preserved with EDTA is preferred
• Whole blood preserved with sodium polyanethol sulfonate (SPS), citrate, or with clot activator is
acceptable

29. OTHER EBOLA VIRUS DIAGNOSTICS
• Virus isolation
• Requires Biosafety Level 4 laboratory;
• Can take several days
• Immunohistochemical staining and histopathology
• On collected tissue or dead wild animals; localizes viral antigen
• Serologic testing for IgM and IgG antibodies (ELISA)
• Detection of viral antibodies in
specimens, such as blood, serum,
or tissue suspensions
• Monitor the immune response
in confirmed EVD patients

30. LABORATORIES
• CDC has developed interim guidance
for U.S. laboratory workers and other
healthcare personnel who collect or
handle specimens
• This guidance includes information
about the appropriate steps for
collecting, transporting, and testing
specimens from patients who are
suspected to be infected with Ebola
• Specimens should NOT be shipped to
CDC without consultation with CDC
and local/state health departments

31. Packaging & Shipping Clinical Specimens to CDC for Ebola Testing

32. INTERPRETING NEGATIVE EBOLA RT-PCR RESULT
• If symptoms started ≥3 days before the negative result
 EVD is unlikely  consider other diagnoses
 Infection control precautions for EVD can be discontinued unless clinical
suspicion for EVD persists
• If symptoms started <3 days before the negative RT-PCR result
 Interpret result with caution
 Repeat the test at ≥72 hours after onset of symptoms
 Keep in isolation as a suspected case until a repeat RT-PCR ≥72 hours
after onset of symptoms is negative

33. DIFFERENTIAL DIAGNOSIS
• Malaria
• Typhoid fever
In addition to the conditions listed in the differential diagnosis, other
problems to be considered include the following:
• Acute surgical abdomen (as distinct from abdominal signs of Ebola
hemorrhagic fever)
• Crimean-Congo hemorrhagic fever
• Marburg hemorrhagic fever
• Other hemorrhagic fevers
Hemorrhage is a less common and less clinically important aspect of the syndrome. Thus, the
term "Ebola virus disease" is now being used, rather than the earlier name "Ebola
hemorrhagic fever.“

34. CLINICAL MANAGEMENT OF EVD:
Supportive, but aggressive
• Hypovolemia and sepsis physiology
• Aggressive intravenous fluid resuscitation
• Hemodynamic support and critical care management if necessary
• Electrolyte and acid-base abnormalities
• Aggressive electrolyte repletion
• Correction of acid-base derangements
• Symptomatic management of fever and gastrointestinal symptoms
• Avoid NSAIDS
• Multisystem organ failure can develop and may require
• Oxygenation and mechanical ventilation
• Correction of severe coagulopathy
• Renal replacement therapy
Reference: Fowler RA et al. Am J Respir Crit Care Med. 2014

35. INVESTIGATIONAL THERAPIES FOR EVD PATIENTS
• No approved Ebola-specific prophylaxis or treatment
• Ribavirin has no in-vitro or in-vivo effect on Ebola virus
• Therapeutics in development with limited human clinical trial data
• Convalescent serum
• Therapeutic medications
• Zmapp – three chimeric human-mouse monoclonal antibodies
• Tekmira – lipid nanoparticle small interfering RNA
• Brincidofovir – oral nucleotide analogue with antiviral activity
• Favipiravir – oral RNA-dependent RNA polymerase inhibitor
• Vaccines – in clinical trials
• Chimpanzee-derived adenovirus with an Ebola virus gene inserted
• Attenuated vesicular stomatitis virus with an Ebola virus gene inserted

36. PATIENT RECOVERY
• Case-fatality rate between 50-70% in the 2014 Ebola outbreak
• Case-fatality rate is likely much lower with access to intensive care
• Patients who survive often have signs of clinical improvement by the second
week of illness
• Associated with the development of virus-specific antibodies
• Antibody with neutralizing activity against Ebola persists greater than 12 years after
infection
• Prolonged convalescence
• Includes arthralgia, myalgia, abdominal pain, extreme fatigue, and anorexia; many
symptoms resolve by 21 months
• Significant arthralgia and myalgia may persist for >21 months
• Skin sloughing and hair loss has also been reported

37. Detection of Ebola Virus in Different Human Body Fluids over Time

38. INITIAL ASSESSMENT FOR EBOLA VIRUS DISEASE
Determining the risk of exposure
• The risk of exposure to Ebola virus helps to guide the evaluation and
management of both symptomatic and asymptomatic individuals.
• Patients are at risk for Ebola virus disease if they had an exposure that
occurred within 21 days before the onset of symptoms. However, the level
of exposure risk ranges from high to low to no known identifiable risk. For
healthcare workers, the level of exposure risk can vary depending upon the
intensity of the epidemic at their work site (i.e., the risk of exposure is
greater in areas of widespread Ebola virus transmission).
• The level of risk defined below is consistent with CDC recommendations,
which take into account uncertainty about the extent of Ebola virus spread
in some urban areas in West Africa.

39. EVD Risk Assessment
• **CDC Website
HIGH-RISK EXPOSURE
Percutaneous (e.g., needle stick) or mucous membrane
exposure to blood or body fluids of a person with Ebola while
the person was symptomatic
OR
Exposure to the blood or body fluids (including but not limited
to feces, saliva, sweat, urine, vomit, and semen) of a person
with Ebola while the person was symptomatic without
appropriate personal protective equipment (PPE)
OR
Processing blood or body fluids from an Ebola patient without
appropriate PPE or standard biosafety precautions
OR
Direct contact with a dead body without appropriate PPE in a
country with widespread transmission or cases in urban
areas with uncertain control measures
OR
Having lived in the immediate household and provided direct
care to a person with Ebola while the person was
symptomatic
SOME RISK EXPOSURE
In countries with widespread transmission or cases
in urban areas with uncertain control measures:
• Direct contact while using appropriate PPE with a
person with Ebola while the person was
symptomatic or with the person’s body fluids
OR
Close contact in households, healthcare facilities, or
community settings with a person with Ebola while
the person was symptomatic
• Close contact is defined as being for a prolonged
period of time while not wearing appropriate PPE
within approximately 3 feet (1 meter) of a person
with Ebola while the person was symptomatic

40. EVD Risk Assessment (continued)
• **CDC Website
LOW (but not zero) RISK EXPOSURE
Having been in a country with widespread transmission or
cases in urban areas with uncertain control measures within
the past 21 days and having no known exposures
OR
Having brief direct contact (e.g. shaking hands) while not
wearing appropriate PPE, with a person with Ebola while the
person was in the stage of disease
OR
Brief proximity, such as being in the same room for a brief
period of time, with a person with Ebola while the person was
symptomatic
OR
In countries without widespread transmission or cases in
urban settings with uncertain control measures: direct
contact while using appropriate PPE with a person with
Ebola while the person was symptomatic or with the person’s
body fluids
OR
Traveled on an aircraft with a person with Ebola while the
person was symptomatic
NO IDENTIFIABLE RISK EXPOSURE
Contact with an asymptomatic person who had contact with
person with Ebola
OR
Contact with a person with Ebola before the person developed
symptoms
OR
Having been more than 21 days previously in a country with
widespread transmission or cases in urban areas with uncertain
control measures
OR
Having been in a country with Ebola cases, but without
widespread transmission or cases in urban settings with
uncertain control measures, and not having any other exposures
as defined above
OR
Having remained on or in the immediate vicinity of an aircraft or
ship during the entire time that the conveyance was present in a
country with widespread transmission or cases in urban areas
with uncertain control measures and having had no direct
contact with anyone from the community

41. EVD CASES (UNITED STATES)
• EVD has been diagnosed in the United States in four people, one (the index patient) who
traveled to Dallas, Texas from Liberia, two healthcare workers who cared for the index
patient, and one medical aid worker who traveled to New York City from Guinea
• Index patient – Symptoms developed on September 24, 2014 approximately four days
after arrival, sought medical care at Texas Health Presbyterian Hospital of Dallas on
September 26, was admitted to hospital on September 28, testing confirmed EVD on
September 30, patient died October 8.
• TX Healthcare Worker, Case 2 – Cared for index patient, was self-monitoring and
presented to hospital reporting low-grade fever, diagnosed with EVD on October 10,
recovered and released from NIH Clinical Center October 24.
• TX Healthcare Worker, Case 3 – Cared for index patient, was self-monitoring and
reported low-grade fever, diagnosed with EVD on October 15, recovered and released
from Emory University Hospital in Atlanta October 28.
• NY Medical Aid Worker, Case 4 – Worked with Ebola patients in Guinea, was self-
monitoring and reported fever, diagnosed with EVD on October 24, recovered and
released from Bellevue Hospital in New York City November 11.

42. Practical Considerations for Evaluating Patients for
EVD in the United States
• CDC encourages all U.S. healthcare providers to
• Ask patients with Ebola-like symptoms about travel to West Africa
or contact with individuals with confirmed EVD in the 21 days
before illness onset
• Know the signs and symptoms of EVD
• Know the initial steps to take if a diagnosis of EVD is suspected
• CDC has developed documents to facilitate these evaluations

43. EVD Algorithm for Evaluation of the
Returned Traveler

44. Symptomatic patients with identifiable risk
• Clinical findings that are consistent with Ebola virus disease include fever and/or severe
headache, weakness, muscle pain, vomiting, diarrhoea, abdominal pain, or unexplained
hemorrhage. Infection control precautions should be used for all symptomatic patients
who have an identifiable risk for Ebola virus disease.
• Such patients should be isolated in a single room with a private bathroom and with the
door to the hallway closed, and all healthcare workers should use standard, contact,
and droplet precautions (Eg, gown, facemask, eye protection, and gloves).
• In patients who are suspected of having Ebola virus disease, phlebotomy and
laboratory testing should be limited to tests that are essential for care.
• Certain hospitals may be designated as "Ebola assessment hospitals," which are
prepared to evaluate and care for patients with possible Ebola virus disease until a
diagnosis can be confirmed or ruled out. Such patients who have confirmed Ebola
virus disease should be transferred to specialized Ebola treatment centers.

45. Asymptomatic individuals with identifiable risk
• Monitoring for symptoms and signs of Ebola virus disease should be performed for
asymptomatic persons who have had an exposure to Ebola virus at any risk level (i.e.,
high, some, or low risk).
• Such individuals should be monitored for 21 days after the last known exposure and
should immediately report the development of fever or other clinical manifestations
suggestive of Ebola virus disease.
• The type of monitoring (Eg, self-monitoring and reporting versus direct observation by a
designated health official), as well as the need for travel restrictions, restricted
movement within the community, and/or quarantine depend, in part, upon the exposure
risk level, and are described in detail in the CDC guidance for the monitoring and
movement of persons with Ebola virus exposure.
• Local authorities may also have specific regulations for man monitoring and movement
of persons with Ebola virus exposure management of asymptomatic individuals with
Ebola virus exposure.

46. Patients with no identifiable risk
• If after initial evaluation, patients are determined to have no identifiable risk for
Ebola virus infection, monitoring or diagnostic testing for Ebola virus disease is not
warranted.
• However, if patients have fever and other signs or symptoms of infection, they
should be evaluated for other causes of febrile disease (Eg, malaria, Lassa fever,
influenza).
• Appropriate infection control precautions will depend upon the patient's clinical
findings, as well as the specific pathogens that are being considered.

47. Interim Guidance for Monitoring and Movement of
Persons with EVD Exposure
• CDC has created guidance for monitoring people exposed to Ebola virus but
without symptoms
RISK LEVEL PUBLIC HEALTH ACTION
Monitoring Restricted
Public Activities
Restricted
Travel
HIGH risk Direct Active Monitoring Yes Yes
SOME risk Direct Active Monitoring
Case-by-case
assessment
Case-by-case
assessment
LOW risk
Active Monitoring
for some;
Direct Active Monitoring
for others
No No
NO risk No No No

49. Ebola virus disease (EVD) cumulative incidence*
West Africa, December 17, 2014
* Cumulative number of reported EVD cases to WHO

51. 0
1000
2000
3000
4000
5000
6000
7000
8000
9000
Total Cases, Guinea
Total Cases, Liberia
Total Cases, Sierra Leone
2014 Ebola Outbreak Reported Cases in Guinea, Liberia, and Sierra Leone
This graph shows the cumulative reported cases in Guinea, Liberia, and Sierra Leone provided in WHO situation
report beginning on March 25, 2014 through the most recent situation report on December 17, 2014.

53. Reporting Date Total Cases Confirmed Cases Total Deaths
Guinea 16 Dec 14 2,453 2,164 1,550
Liberia 14 Dec 14 7,819 3,021 3,346
Sierra Leone 17 Dec 14 8,759 6,856 2,477
United States 24 Oct 14 4 4 1
Mali 23 Nov 14 8 7 6
Nigeria** 15 Oct 14 20 19 8
Spain** 27 Oct 14 1 1 0
Senegal** 15 Oct 14 1 1 0
TOTAL 19,065 12,073 7,388
EVD Cases and Deaths*
*Reported by WHO using data from Ministries of Health
**The outbreaks of EVD in Senegal, Nigeria, and Spain were declared over on October 17, October 19, and December 2 respectively.

54. MEASURES CARRIED OUT TO REDUCE OUTBREAK
• More than 150 national and international staff are now working on the
outbreak in Sierra Leone.
• Beyond medical treatment, controlling the outbreak will require the
deployment of large numbers of people to train health care personnel in
infection control measures, to follow up with and trace cases and their
contacts, to set up an epidemiological surveillance network, and to promote
public health messages
• By setting up treatment centers and transit units close to affected villages, MSF
can treat patients quickly and reduce the risk of infection in local hospitals and
the community.

55. • Ebola creates fear inside communities, and sick people are often
stigmatized. Psychological support is provided to patients and their
families. The health workers organize participatory health promotion
activities with healed patients. To reduce fear, they are also conducting
sensitization campaigns to inform people how the virus spreads. As such,
they are encouraging people to report suspected cases of haemorrhagic
fever, to avoid contact with people sick with the virus, and to avoid
touching the dead body of someone who had been ill with Ebola.

58. India’s First Ebola Patient Has Been Quarantined
• An Indian resident who tested positive for Ebola—and was cured—has
landed in Delhi from Liberia.
• The 26-year-old man is being isolated in a facility at Delhi’s Indira Gandhi
International airport.
• The man had already been treated for Ebola in West Africa, currently does
not have symptoms and tested negative for the virus before he flew.
However, his semen tested positive for the virus.
• Semen can test positive after clinical clearance for up to three
months, according to the CDC.
• The patient in India is being kept in isolation in a health facility at the airport
until his semen tests negative.