ebola virus disease

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

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Ebola Virus Disease (EVD)

And its threat for public health


EID & RID at a glance

EID : Emerging Infectious Disease

RID : Re-emerging Infectious Disease


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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.


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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


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and…Ebola


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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 construction


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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.


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Newly discovered viruses of public health importance


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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


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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


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Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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Limited scientific understanding

Highly fatal disease

Causes large outbreaks

Difficult to contain

No proven treatment or vaccine

A pandemic threat


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Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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A story – 1/3


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A story – 2/3


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A story – 3/3


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Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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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


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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


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Fruit bats


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Geographic distribution 2


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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


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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


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Transmission cycle


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Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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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

Haratian K. ,Medical virologist, Alborz

University of Medical Sciences 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


Ebola Virus Disease

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 [email protected]

Look at these pictures!

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

Control measures

Challenges

Pandemic threat


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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


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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


Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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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


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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.


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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


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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


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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


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Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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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


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Outline


History

Epidemiology


Management

Control measures

Challenges

Pandemic threat


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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


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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


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AlvinChew slideshare presentation [email protected]

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


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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


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http://www.cdc.gov/vhf/ebola/about.html

http://www.who.int/csr/disease/ebola/en/

http://ebola.thelancet.com/

Thank You


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ebola virus disease

Health & Medicine