A comprehensive summery of Ebola Virus Disease

1. EBOLA Virus Disease
Tahseen J. Siddiqui, M.D., MRCP
Infectious Disease Specialist
Medical Director & Chairman, Infection Control
Norwegian American Hospital & Roseland Community Hospital
Teaching Faculty, Jackson Park Hospital & Medical Center
Associate Clinical Professor, Ross University School of Medicine

2. Ebola Virus Disease (EVD) Ebola Hemorrhagic Fever (EHF)
•EVD -is caused by four of five viruses of the genus Ebolavirus
•Ebola viruses (EBOVs), belonging to the family Filoviridae, are enveloped, nonsegmented, negative- stranded RNA viruses that can cause severe viral hemorrhagic fevers in human and nonhuman primates with case fatality rates for humans of up to 90
•The four are Ebola virus (EBOV, formerly Zaire Ebola )-the most virulent,
and is responsible for major outbreaks. Bundibugyo virus (BDBV), Sudan virus (SUDV),
Taï Forest virus (TAFV)
•As all filoviruses, ebolavirions are filamentous particles that may appear in the shape of a shepherd's crook, of a "U" or of a "6," and they may be coiled, toroid or branched
•Ebola, meaning "Black River," in the local language Lingala, close to Yambuku village
in Zaire, (Democratic Republic of Congo), where in 1976 it first surfaced

3. The Viral Life CycleGenome, Entry & Replication
•EBOV particles possess a single trimeric transmembrane glycoprotein GP1,2 on the surface, that mediates virus uptake through receptor binding and subsequent fusion, and the matrix protein VP40, which is needed for particle formation.
•The entry mechanism by which the virus causes macropinocytosis most likely involves the interaction of GP with cell surface receptors.
•Many cell types, monocytes/macrophages, dendritic cells, and hepatocytes, seem to be susceptible to EBOV infection,-key factor in defining primary target cells and subsequently target organs for EBOV
•As is typical of RNA-coded viruses, the Ebola virus mutate rapidly (at mutation rate of 2.0 x 10 -3 substitutions per site per year making it as fast changing as seasonal influenza)
•This is likely to represent rapid adaptation to human hosts both within a person during the progression of disease and as the virus is repeatedly passed from human to human, pose challenges for the development of a vaccine to the virus
A scheme of EBOV illustrating the overall organization.

4. The Pathogenesis & Pathophysiology
•EBOV replicates very efficiently in monocytes, macrophages, dendritic cells, hepatocytes and endothelial cells.
•Replication of the virus in monocytes triggers the release of high levels of inflammatory chemical signals
•One of the reasons that Ebola is so deadly is that it has multiple ways of interfering with or avoiding the human immune system (suppresses interferon production,impairs T-cell activation and proliferation)
•Fatal Ebola infections are marked by unchecked viral replication combined with an inadequate antiviral response.
•During viral infection, large amounts of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) are secreted from infected macrophages and cause disruption of the endothelial barrier causing tissue destruction in multiple organs

5. How is Ebola Transmitted?
•The natural reservoir of EBOV are fruit bats - occasionally crossing over into humans
•The virus may spread to primates and humans by contact with infected bats, eating partially eaten fruits by infected bats and handling/consuming infected “bush meat” ((wild animals hunted for food)) in forested Africa
•Person to person transmission through direct contact (through broken skin or mucous membranes in, for example, the eyes, nose, or mouth) with blood or body fluids (including urine, saliva, sweat, feces, vomit, breast milk, and semen) of a person who is sick with Ebola/host animal
•Objects (like needles and syringes) that have been contaminated with the virus
•Ebola does not spread through the air or by water
•Not transmitted by asymptomatic people.
•

6. Signs and symptoms
•Symptoms may appear anywhere from 2 to 21 days after exposure –(average 8 to 10 days)
•Sudden influenza-like stage (feeling tired, fever, pain in the muscles and joints, headache, and sore throat)
•The fever is usually higher than 38.3 °C (100.9 °F), often followed by vomiting, diarrhea and abdominal pain.
•Next, shortness of breath and chest pain along with swelling, headaches and confusion. In about half of the cases, the skin may develop a maculopapular rash
•Internal and external bleeding typically begins five to seven days after the first symptoms. (poor prognosis)
•Recovery may begin between 7 and 14 days after the start of symptoms.
•Death, if it occurs, follows typically 6 to 16 days from the start of symptoms and is often due to low blood pressure from fluid/blood loss.
•Disease progression/outcome relate to the strength of the individual’s immune system, the strain of the virus and the viral dose the person has been exposed to
•Those who survive often have ongoing muscle and joint pain, liver inflammation and decreased hearing/vision
•People who recover from Ebola infection develop antibodies that last for at least 10 years. (Unknown protective role)
Patients can lose 15 liters of body fluid in a four or five or six hour period

7. Diagnostic Tests
•Laboratory findings -platelet count <150,000 cells, coagulopathy and/or elevated transaminases)
•Rapid diagnostic tests for Ebola detect specific RNA sequences by reverse-transcription polymerase chain reaction (RT-PCR) or viral antigens by enzyme-linked immunosorbent assay (ELISA)
•Most acute infections are determined through the use of RT-PCR.
•Viral RNA is generally detectable by RT-PCR within 3 to 10 days after the onset of symptoms

8. Laboratory Testing
•PCR testing for EVD is now available at IDPH Chicago Lab
•Testing requires pre-authorization/consultation with IDPH/CDC
•Ebola virus can be detected in blood of symptomatic patient-may take up to 3 days post onset of sx
•If EVD is suspected and blood sample is collected <3 days a subsequent sample is required to r/o EVD.
•Collect 2 lavender top (EDTA-purple) plastic tubes of whole blood, store at 4c
•Specimen collection/transportation is hospital’s responsibility. Transport instructions/submission forms will be provided by IDPH
•All results will be confirmed by viral cultures at the CDC

10. Treatment-Basic, experimental, vaccine!
•Symptomatic: Providing intravenous fluids (IV) and balancing electrolytes
•Maintaining oxygen status and blood pressure
•Treating other infections if they occur
•Experimental vaccines and treatments for Ebola are under development, but they have not yet been fully tested for safety or effectiveness. (NIH)
•ZMapp, is an experimental treatment, for use with individuals infected with Ebola virus. It has not yet been tested in humans for safety or effectiveness. The product is a combination of three different monoclonal antibodies that bind to the protein of the Ebola virus.
•Pre-and Post exposure Prophylaxis of Ebola Virus Infection in an Animal Model by Passive Transfer of a Neutralizing Human monoclonal Antibody (KZ52)---survivor's plasma
•Antiviral Brincidofovir (Cidofovir derivative) -a potent inhibitor of Ebola virus replication in cell culture. The antiviral drug is being stockpiled by the US for use in the event of a bioterrorism attack with smallpox virus. tested for safety in humans, the US FDA authorized its emergency use in the Dallas patient
•Recovery from Ebola depends on good supportive care and the patient’s immune response.

11. Prevention of TransmissionApublic health nightmare
•According to the WHO, more than 10,000 people have been infected with Ebola in the outbreak that started last March. Nearly half of them have died, mostly from Guinea, Liberia and Sierra Leone.
•Approximately 100 people a day arrive to the United States (5-6 HCW) ~(25 at O’Hare/day) from Sierra Leone, Guinea and Liberia, most of them American citizens or permanent residents.
•About 70 percent of the people arrive to six states –New York, Maryland, Pennsylvania, Georgia, New Jersey and Virginia
•Four people have been diagnosed with Ebola in the United States, with one death -a Liberian man visiting Texas.
•The only patient now being treated for Ebola in the country is a New York doctor, Craig Spencer, who was diagnosed last Thursday.Hehad worked with Doctors Without Borders treating Ebola patients in Guinea
•Nationally, four U.S. hospitals had been considered "Ebola-ready" based on the training they gave staff and the presence of high bio containment wards for infectious disease.
•They include Emory University Hospital in Atlanta, Nebraska Medical Center in Omaha and the National Institutes of Health ClinicalCenter in Bethesda, Maryland, all of which have treated a few Ebola patients, as well as St. Patrick Hospital in Missoula, Montana.
•More than 2 dozens US hospitals are now ready to handle Ebola patients.
•CDC sets up >20 Quarantine Stations across the country
•Homeland Security-all passengers arriving in the United States whose travel originates in Liberia, Sierra Leone or Guinea will be required to fly into one of the five airports that have the enhanced screening and additional resources in place.
•Travelers are also being screened on departure from the West African nations

12. What Is the U.S Doing to Prevent the Spread of Ebola?

13. Prevention of TransmissionControversies in Quarantine
•Under new CDC guidelines, most healthcare workers returning from West Africa's Ebola hot zone would be considered to be at "some risk" for infection, submit to an in-person checkup and a phone call from a local public health authority.
•High-risk people include healthcare workers who suffer a needle stick while caring for an Ebola patient or who tend to a patient without protective gear-voluntarily isolate themselves and agree to be actively monitored for symptoms.
•Healthcare workers tending to Ebola patients at U.S. facilities would be seen as "low but non-zero" risk
•CDC says returning Ebola medical workers should not be isolated or quarantined, would have their health monitored daily by a local health department official who would check their temperature, look for signs of fatigue and review their daily activity plans to determine what activity
•New York and New Jersey imposed controversial mandatory quarantines on returning doctors and nurses
•In Virginia, such HCW to be evaluated on a case-by-case basis and may be restricted from public transportation, mass gatherings, and clinical care, and all travelers arriving from the three nations will be asked to take and record their temperature at least twice each day, with local health officials contacting them daily for three weeks to check on their condition.
•U.S. military said it was isolating troops returning from their mission to help West African countries curb Ebola even though they showed no sign of infection

14. Prevention of TransmissionChicagoans-are we prepared?

15. Safety Protocols at Chicago Hospitals and AirportsEbola Task Force
•At Rush-A core group of 21 nurses and nine physicians received specialized training
•EMT to triage and transport the suspected Ebola patients directly to the designated specialized facility
•The IDPH guidance calls for a mandatory 21-day home quarantine for any returning traveler who has had High-Risk exposures to Ebola.i-e
•Had unprotected (percutaneous or mucous membrane) contact with infectious blood or body fluids of an Ebola patient.
•Made direct skin contact with blood or body fluids of an Ebola patient without appropriate personal protective equipment (PPE).
•Processed blood or body fluids of an Ebola patient without appropriate equipment or standard biosafety precautions.
•Made direct contact with the dead body of an Ebola patient without appropriate PPE.
•Lived with or shared a household with an Ebola patient in an outbreak affected country.
•HCW returning from outbreak-affected areas and who used appropriate PPE with no known infection control breach in a “low risk” category, and specifically recommends “no quarantine, no travel restrictions and verified self monitoring-checking and reporting one’s temperature and other potential symptoms twice daily and reporting to local public health, by phone or other means.
REF: http://www.idph.state.il.us/ebola/

16. EBOLA ACTIVATION PLAN
•NorwegianAmericanHospitalhasalreadyactivated&implementeditsactionplantohandleanyEbolasuspectedcase.
•Thenegativepressureisolation/quarantineroomshavebeendesignatedandtested
•ThefrontlineHCW(ED/ICU)areprovidedCDCrecommendedpersonalprotectiveequipment(PPE)andtraining.
•Theemergencycommandcenterandthechainofcommandshasbeenestablished
•ThehospitalconstantlymonitoringtheCDCwebsite,communicatingwithMetropolitanChicagoHealthcareCouncil(MCHC),andcoordinatingwithCDPHonaregularbasisregardingtheEbolavirusactivity/spread,anditspotentialimpactonourorganization& community.
•Wewillcontinuetoadjustouractiveplanasnewinformationemerges.

17. Presentation at Hospital
•Potential patients could present anywhere on campus, including but not limited to:
•Emergency Department Information Desk
•POB Clinics
•Inpatient Units, Subway and Cafeteria, Medical Records
•Ambulatory Services (Lab,X-Ray,PT,Infusion Center, Dialysis, Cardiology, Wound Care)
•ANY patient or visitor who is coughing, sneezing, or otherwise visibly ill should be asked to wear a mask immediately

18. •Any patient, visitor, staff member or other person on campus who is presenting as ill or is visibly ill should be asked if they exhibit the following signs/symptoms:
••Fever
•Other symptoms including headache, weakness, joint/muscle pain, vomiting, diarrhea, abdominal pain,bruising,or bleeding inside or outside of the body
•Travel, or close contact with someone who has traveled to Guinea, Liberia, or Sierra Leone in the past 21 days
•If the person is positive for above signs and symptoms with h/o travel to Ebola hot zone/contact with Ebola pt:
•Immediately contact the Nursing Supervisor at Ext. 8245 (773-292-8245) and apprise them of the situation.
•Don gloves and N95 mask, and ask patient to do the same.
•If gown is available, staff and patient should don gown as well.
•Instruct the patient to remain where they are, and do not allow anyone within 3 feet of patient without full PPE in place.
•If possible, restrict access to the patient's location by closing doors.
EBOLA ACTIVATION PLANCode Triage

20. Designated Negative Pressure Rooms Located in ER and ICU

21. NOTIFICATION SYSTEM
•Upon receiving notification of a potential Ebola patient, Nursing Supervisor will immediately contact hospital COO, CEO ,and Executive Team to come in and activate the Incident Command Center.
•Nursing Supervisor will then contact ED Charge Nurse, ED Physician, and Infectious Disease Physician to notify them of a potential Ebola patient.
•If initial presentation occurs in the Emergency Department, the triage nurse will apply PPE to perform remaining Triage interview.
•RN also contacts the ER charge nurse and ER physician before conducting additional screening using the in-depth questions found in International Travel Screening for Viral Hemorrhagic Fever VHF -Ebola. (Meditec-based system in development by IT)
•If patient travel screening indicates a potential Ebola patient, Triage nurse will immediately contact the Nursing Supervisor at Ext. 8245 (773-292-8245) and apprise them of the situation.
•Nursing Supervisor will immediately contact hospital COO, CEO,and Executive Team to come in and activate the Incident Command Center.
•ER physician will contact Infectious Disease physician for consultation and next steps taken are dependent on physician decision.
•If initial presentation occurs elsewhere on the hospital campus, the ED triage nurse will don full PPE as above and transportpatient to the ED triage room for full evaluation. Security will clear the route from the patient to the ED triage room, as well as the ED triage and entrance area, prior to the patient being moved.

22. NOTIFICATION SYSTEM
•Once the patient has been relocated to the ED Triage room, access will be restricted to primary care givers wearing full PPE.
•Original location of patient presentation will remain restricted from all use until proper cleaning has been confirmed and location has been cleared as safe for use
•Nursing Supervisor (Ext 8245) notified of need for activation of Ebola Response Plan
•Nursing supervisor contacts Administrator on Call and prepares for activation of Code Triage
•Nursing supervisor serves as Incident Commander until relief obtained.
•CONTACT with MCHC,IDPH and CDC will be determined.
•Further directions will be in conjunction with external agencies.

23. Personal Protective Equipment (PPE)
•Impermeable gown or suit with attached and boot covers
•Boot covers if needed
•Gloves -doubled; mid-forearm length
•Face shield
•Hood covering of head and neck
•Use buddy system to apply and remove

24. Application of PPE
•Wash hands with soap and water . Begin with gown or suit, apply shoe covers and secure all openings, add face shield and apply hood covering, and finally, add the gloves (double-glove).
•Removal of PPE: Dispose in Red Bag garbage. **(Most exposures occur during removal of contaminated PPE)
•1. Wash double-gloved hands with soap and water for 30 seconds, followed by Purell hand sanitizer.
•2.Remove outer gloves and again wash gloved hands with soap and water for 30 seconds, followed by Purell hand sanitizer.
•3.Carefully remove detachable hood covering leaving face shield in place with hood from body suit still in place.
•4.Wash gloved hands with soap and water for 30 seconds, followed by Purell hand sanitizer.
•5.Put on another pair of clean gloves.
•6.If shoe covers are separate, remove them first.
•7.Remove body suit if unconnected to the hood.
•8.Wash gloved hands with soap and water for 30 seconds, followed by Purell hand sanitizer.
•9.Remove face shield.
•10.Wash gloved hands with soap and water for 30 seconds, followed by Purell hand sanitizer.
•11.Remove gloves.
•12.Wash hands with soap and water for 30 seconds, followed by Purell hand sanitizer.

30. Patient Care and Patient Equipment
•Strict isolation maintained in negative pressure room
•NO LAB DRAWS OR INVASIVE PROCEDURES WITHOUT PHYSICIAN ORDER
•Use disposable equipment whenever possible
•Clean and disinfect equipment and surfaces with bleach wipes
•Limit use of needles and other sharps as much as possible
•Limit phlebotomy and other invasive procedures
•Use separate SHARPS container to dispose of any sharps
•Avoid use of Aerosol Generating Procedures
•Waste Management
•Body fluids can be disposed in toilets. Solid waste removal will remain in patient room for disposal under direction of external agencies.
•NO VISITORS

31. Staffing
•Volunteers will be sought to work with any patient suspected of Ebola virus and all efforts will be made to contain exposure to any hospital employee, visitor or other patients
•Monitoring of staff will start with logging all potential exposures.
•Offsite Locations
•Offsite clinics (New Life, Milwaukee, Cormac) and Pediatric Care-A-Van should follow the process as indicated and isolate the patient in question in an exam room.
•All patient care givers must now wear full PPE when in contact with the patient.
•Clinic should contact nursing supervisor at 773-292-8245 and await further instructions.
•Do not attempt to transfer the patient to NAH or any other facility without further instruction from Command Center.

32. Communications
•Communication materials regarding proper identification and management of suspected patients are developed and distributed to all NAH physicians and staff. "Front-Line" staff, including registration, physician offices, and other ambulatory and public areas received specific in-person education
•Our website will be updated with information on a regular basis should Ebola be confirmed. We are committed to protecting the patient's privacy and will work closely with CDC and other healthcare agencies to preserve life.

33. References
•http://viralzone.expasy.org/all_by_species/207.html
•Infection Mechanism of Genus Ebolavirushttps://microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_Ebolavirus
•http://en.wikipedia.org/wiki/Ebola_virus_disease
•http://jid.oxfordjournals.org/content/204/suppl_3/S957.full
•http://www.livescience.com/48234-how-ebola-got-its-name.html
•http://www.cdc.gov/vhf/ebola/diagnosis/
•http://www.uptodate.com/contents/diagnosis-and-treatment-of-ebola-and-marburg-virus-disease
•http://www.nytimes.com/2014/10/28/us/new-rules-coming-for-health-care-workers-returning-from-west-africa.html
•U.S. Department of Homeland Security, Centers for Disease Control and Prevention, Congressional Research Service, Airports Council International, The Washington Post, Los Angeles Times, Reuters
•http://www.nbcchicago.com/news/local/Health-Officials-Detail-Ebola-Prevention-in-Chicago- 279361312.html#ixzz3HVY6jB94