Ebola Virus Disease is one of the most virulent pathogens of humans. Known as the T-Rex of microbes

Family of Filoviruses/associated with the Marburg virus

Ebola virus is one of at least 30 known viruses capable of causing viral hemorrhagic fever syndrome

Ebola was first identified/classified in 1967. There are 5 species of the virus.

Scientists believe first patient became infected by contact with an infected animal (spillover event)

African bush meat (wild animal meat) can become infected and subsequently spread to humans during hunting, butchering and processing stage. Most recent outbreak is likely from fruit bats

Ebola is also presumed triggered by consumption of sick animal meat in under cooked food

Spread via mammals: for ex, humans, bats, monkeys and apes

1976,1977-Zaire

1994 Gabon

1995 Democratic Republic of Congo (formerly Zaire)

1996 -1997 Gabon

1996 South Africa

1996 /2004 Russia

2001/02 Gabon

2001-2003 Republic of Congo

2007 Democratic Republic of Congo

2008/09 Democratic Republic of Congo

2014 Multiple countries

2005 outbreak resulted in 80-90 % fatalities. Current fatality rate is 70%

2014 largest outbreak in history. Noted locations: Guinea, Senegal, Nigeria, Sierra Leone, Liberia. Additional cases are now in Spain, US and Mali.

Senegal and Nigeria are considered free of disease

As of 10/25/14: 10141 cases, 4922 fatalities

450 health care workers have been infected. 244 have died

USA- 4 cases, one death

Researchers are anticipating tens of thousands of new cases and death by 12/15/14 if course continues

Uganda reports one case of Marburg virus-quickly contained

Spread by direct contact with blood, body fluids including urine, feces, saliva, emesis, breast milk, semen

Objects that have been contaminated with fluids are also a risk.

CDC notes Ebola is NOT spread by air or water

Once recovered, the patient is no longer contagious (with the exception of semen)

Incubation period is typically 8 to 10 days but can range from 2 to 21 days

Fatal disease is characterized by severe symptoms early in process, septic shock/organ failure.◦ Patients usually die within 6 to 16 days

Non fatal cases typically improve 6-11 days after the onset of treatment

All symptomatic individuals should be assumed to have high levels of virus and all safety precautions should be taken

Ebola will migrate from the point of initial infection site to regional lymph nodes, liver, spleen and adrenal glands

Triggers a release of pro-inflammatory cytokines resulting in clotting impairment, multi-organ failure and death◦ Liver cell death occurs with dysregulation of clotting factors

and subsequent bleeding disorders

◦ Adrenal cell death can be found with low blood pressure and impaired steroid synthesis

Results in a failure of adaptive immunity

Initial: Non specific, flu-like symptoms

Days 5-7: Rash in some patients

Several Days: Watery diarrhea, nausea, vomiting, abdominal pain

Later in Course: Hemorrhage (petechiae, ecchymosis/bruising, oozing from venipuncture sites, mucosal bleeding)

Other findings: Chest pain, shortness of breath, headache, confusion, seizures, cerebral edema

Fatal disease has been characterized by more severe clinical signs early during infection

“Person under investigation” (Updated 10/27/14)

◦ Elevated body temperature or

◦ Subjective fever or symptoms including headache, fatigue, muscle pain, vomiting, diarrhea, abdominal pain, unexplained hemorrhage

◦ Epidemiological risk in past 21 days before onset of symptoms noted as high risk , some risk, low (but not zero) risk, no identifiable risk

Percutaneous or mucous membrane exposure to blood or body fluids

Direct contact with blood or body fluids without personal protective equipment (PPE)

Processing blood or body fluids without PPE

Direct contact with a dead Ebola victim without PPE in a country where Ebola outbreak is occurring

Having lived in the immediate household and provided care to a victim who is symptomatic

In countries with widespread Ebola: direct contact with symptomatic person while using PPE

Close contact with a person showing symptoms of Ebola such as in a household, health care facility, or the community (no PPE worn)

Close contact is defined as a prolonged period without use of PPE within approximately 3 feet while patient is symptomatic

Having been in a country with widespread Ebola transmission within the previous 21 days and having no known exposure

Brief skin contact (shaking hands) without PPE while patient in early stage of disease

Brief proximity such as being in same room for a brief period with a person while the person was symptomatic

In countries without widespread transmission: direct contact while using appropriate PPE while person symptomatic.

Traveled on aircraft with person while symptomatic

Contact with a person who is NOT showing symptoms AFTER that person was in contact with a person with Ebola

Contact with a person with Ebola BEFORE the person was showing symptoms

Having traveled to a country with Ebola outbreak MORE than 21 days ago

Having been in a country where there is no widespread Ebola transmission (e.g., the United States), and having no other exposures to Ebola

Viral Antigens or RNA levels in blood. Case needs to be confirmed with lab

Testing Includes:

Antigen –capture enzyme-linked immunosorbent (ELISA) testing

PCR-Polymerase Chain Reaction

IgM ELISA

Will only be detected in blood AFTER onset of symptoms, generally detected 3-10 days by PCR after symptoms begins

No FDA approved vaccine or medication is available

Each patient’s presentation is specific and symptoms are treated as they appear

Standard care can include; IV fluids, maintaining respiratory/oxygen status, stabilizing blood pressure, managing blood abnormalities and treating secondary infections as they occur.

Severely ill patients can present with a full systemic inflammatory response, sepsis, organ failure/renal failure, or frank hemorrhage.

Recovery is dependent on the patients immune response. If recovered, newly developed antibodies can last up to 10 years or longer. The rate of reinfection is not known

Vaccine development is being coordinated with the WHO with assistance of the CDC

Expectation is that vaccines will have the most significant impact on the further evolution of the epidemic

◦ US NIH and Glaxo Smith Kline expects to have 230,000 doses by April 2015 (cAd3-ZEBOV In trials now)

◦ Canadian Public Health /New Link may have 70,000 doses by end of 2014 with millions of doses by March 2015. (VSV-EBOV)

◦ Johnson & Johnson developing a vaccine with Bavarian Nordic. Vaccine delivered in two phases. Also Collaborating with GSK. Vaccines could be combined

◦ Crucell Biopharmaceutical developing a multivalent Ebola/Marburg vaccine

No proven substance has been proven effective against Ebola

ZMAPP: contains 3 monoclonal antibodies expected to provide passive immunity. No supply now available

Brincidofovir: an antiviral in phase III clinical trials. FDA has authorized for use in Ebola patients on a case-by case basis

Convalescent Serum Transfusion therapy: with plasma of a convalescent Ebola survivor intention to stimulate immune system

Plasmapheresis is being considered but has not been put through clinical trials to date

FDA’s Emergency Use Authorization (FUA) permits unapproved products for use during emergencies when no other approved , alternatives are available

FDA can use Orphan Drug designation to encourage, expedite Ebola product development

Emergency Investigational New Drug (EIND) –allows investigators treating Ebola patients access to investigational products

2 companies supported by Dept of Defense

Biocryst Pharmaceuticals developing a nucleoside with broad spectrum antiviral activity including Ebola. Phase 1 study to start in 2014 (BCX4430)

TKM-Ebola received fast track designated. Works by interfering with RNA in certain proteins. Administered to US health care worker moved from Africa to Nebraska. Patient recovered and released. Will be made available in Africa as a clinical trial. At this time supplies are limited

Univ of Utah: Peptide Mimic-mimics a highly conserved region of an Ebola protein that controls how the virus enters the human host cell marking the start of the infection process

Thai scientists: Working on antibody development using human gene therapy

Sarpeta Therapeutics: Phase I trial using RNA–based treatment on Ebola and Marburg virus

Liberian MD using a known anti-viral (lamivudine) with some success

Vanderbilt University developing a new human antibody using blood cells from Ebola survivors.

Fujifilm: Japanese company manufacturing an anti-influenza drug for use with Ebola patients

Texas Presbyterian case-admit 9/30, died 10/8. Anticipate $500k+ in claims (~$1000 per hour)

NBC cameraman treated in Omaha: expected $500k in claims

Protective Gear: About $60 per use. Can only use for one hour at a time

Hospital estimates:◦ $8-10k for protective plastic sheeting per case

◦ Increase cost to dispose of waste

◦ Cost for quarantine estimated at $15k/day

Loss of use short/long term of costly equipment such as dialysis machine

Air Transport: Under normal conditions the cost of air transport from West Africa to the US/east coast can range from $80,000 to $200,000◦ Costs higher for special circumstance cases

Although specific guidelines are in place, currently private air transports are not accepting Ebola cases◦ One carrier has been contracted with US government. All

charges go through Dept of State: Division of Emergency Medicine.

No data available regarding insurance liability known at this time

General costs for air transport, bedside to bedside are distance based

Costs for a bedbound 42 yr old male with IV and O2 are:

Seattle to Omaha $18,200

Miami to Omaha $22,900

Phoenix to Atlanta $21,900

Full International Commercial Air Transport criteria available: http://www.icao.int/Pages/default.aspx◦ http://www.cdc.gov/vhf/ebola/hcp/guidance-air-medical-

transport-patients.html

Intense nursing can result in a 12 fold increase in nursing costs: ratio of human resource to one patient exorbitantly high

An ICU can be utilized for one case only resulting in high losses for unfilled beds

Extra equipment: beds, mattresses, blankets disposed

Construction of negative air flow rooms

German company reportedly disposed of $1M euros in 2 pieces of infected equipment rather than risk further spread of infection

World Bank estimates economic impact to West Africa economy could reach $32B

Other questions:

◦ Will hospitals face a stigma from treating patients, potentially driving other patients away from the facility?

◦ Will an Ebola stigma create personnel shortages of nurses and other health care professionals if they choose not to be present if Ebola patients show up at their facility?

◦ If providers are forced, or choose, to forego business as they manage this disease, will business interruption insurance cover these costs?

◦ Will there be lawsuits for deaths and the potential spread of the disease?

◦ Will malpractice costs go up?

All US citizens have the right to return to the US. CDC must balance public health risks to others with the rights of the individual.

US classified by CDC as “country/affected area with localized transmission”

Travel warnings leaving US are in place

CDC implementing enhanced entry screening at 5 US airports

New York, New Jersey and Illinois have enforced states’ rights forcing a quarantine period for those returning from affected regions

CDC has guidelines updated 10/28/14 “Identify, Isolate, Inform”

United Nations for the first time in its history has created a special mission to help contain the outbreak

World Health Organization has declared Ebola a public health emergency of international concern

Additional Informational Resources

◦ NIH National Institute of Health Ebola page http://www.niaid.nih.gov/topics/ebolaMarburg/understanding/Pages/overview.aspx

◦ WHO World Health Organization Ebola virus page http://www.who.int/csr/disease/ebola/en/

◦ CDC Center for Disease Control Ebola virus page http://www.cdc.gov/vhf/ebola/

FDA has sent warning letters to firms marketing products that claim to prevent, treat or cure Ebola

Decimated work force in region has escalated cost of harvest of cocoa bean-in past weeks risen $2k per ton to $3400 per ton: affects price of chocolate!

Naturally stuffed toys in the shape of Ebola are available for holiday giving as well as your own PPE!

Thank You for Attending

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