1. DEPARTMENT OF HEALTH RESEARCH INSTITUTE FOR TROPICAL MEDICINE Ebola: the Basics and the Background Prof. Rick Speare, Dr. C. Demetria, Dr. Dessi Roman, Dr. Manolito L. Chua Training on Hospital Management for Ebola Virus Disease November 11, 2014

2. 2 RESEARCH INSTITUTE FOR TROPICAL MEDICINE A disaster! “Our people are dying, children are being orphaned, most of the dead are women and over two-thirds of those infected belong to the most economically active age category of 15 to 50. Children are not going to school; doctors and nurses are dying, and non-Ebola illnesses are adding to the toll of death and suffering due to further strains and weakening of the healthcare delivery system in the country.” DR ERNEST BAI KOROMA, PRESIDENT OF SIERRA LEONE

3. 3 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Filovirus Cycle of Transmission P Formenty, World Health Organization, April 2014 Spillover Reservoir hosts

4. 4 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Objectives To describe Ebolavirus and its natural history in the human host and in the environment To explain some communicable disease terminology and concepts useful for controlling Ebola To give an overview of the West African outbreak To highlight the importance of detecting cases rapidly and responding rapidly 4

5. 5 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Ebolavirus Filovirus family (Filoviridae) Five species –Zaire Ebolavirus (EBOV) –Sudan Ebolavirus (SUDV) –Bundibugyo Ebolavirus (BDBV) –Tai Forest Ebolavirus (TAFV) –Reston Ebolavirus (RESTV) Wikipedia Commons

6. 6 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Reston Ebolavirus (REBOV ) The Good Cousin Found in Philippines and China Causes respiratory disease in pigs Infects humans, but no disease Pig farmers, abattoir workers, others have antibodies Some cross-reaction with Zaire EBOV Are people with REBOV antibodies immune? Can REBOV antibodies be used for therapy? Will REBOV antibodies from natural infections confuse diagnosis of Ebola virus disease? 6 Miranda & Miranda 2011; Pan et al 2014

7. 7 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Ebolavirus Long narrow virus, length 1400 nm & width 80 nm Filamentous RNA with protein as inner core; matrix layer next; then membrane from host cell outside RNA codes for 8 proteins Virus takes over the cell http://visualscience.ru/en/projects/ebola/poster/

8. 8 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Natural history Virus enters the cell – any cell, but particularly uses macrophages, dendritic cells and monocytes Spreads to lymph nodes via lymphatics and then to liver and spleen via blood Secondary spread to all organs Exits the body in faeces, saliva, sweat, tears, sputum, skin cells, breast milk, semen, urine, vomitus

9. 9 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Virus in blood CDC. 2014 http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html >100 million viruses per ml

10. 10 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Martines et al. J Pathol 2014 No virus before symptoms

11. Detection of Ebola Virus in Different Human Body Fluids over Time 11

12. 12 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Pathogenesis of Ebolavirus Destroys cells – focal necrosis in many organs Suppresses inflammation Causes cytokine storm Induces clotting Multi-organ focal necrosis and disseminated intravascular coagulation with focal haemorrhage and minimal inflammation Liver with Ebolavirus (red) Martines et al J Pathol 2014

13. 13 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Survival outside host Dried – 24 hr at 25°C; 14 days at 4°C In fluids – up to 46 days at 25°C Ebolavirus is killed by: –Heat 60ºC for 1 hr –Hypochlorite (Chlorine solution) –Alcohols –3% acetic acid –1% glutaraldehyde Piercy et al J Appl Microbiol 2010;109:1531; Sagripanti et al Arch Virol 2010; 155:2035; Health Canada – PDSS - http://www.phac-aspc.gc.ca/lab- bio/res/psds-ftss/ebola-eng.php

14. 14 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Environmental contamination in isolation ward Sudan Ebolavirus outbreak – Uganda 2000 2 positives from 33 environmental specimens Ebolavirus was detected on a bloody glove and a bloody IV insertion site Not isolated on bedframes, chairs, stethoscopes, clean gloves, food bowl, spit bowl, body bag cleaned with bleach, body louse Suggests that environmental contamination and fomites are possible modes of transmission in an ETC. Bausch et al. J Inf Dis 2007

15. 15 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Infectious disease terminology Inoculating dose = the number of viral particles that enter the host; minimum inoculating dose of Ebolavirus is very low (1-10 viruses) Incubation period = days from when the person was exposed and symptoms first develop; aver. EBOV = 11 days (2 – 21 days)

16. 16 RESEARCH INSTITUTE FOR TROPICAL MEDICINE The Importance of Maximum Incubation Period Quarantine/ Monitoring of Asymptomatic individuals = 1 maximum incubation period since exposure; EBOV = 21 days Declaring an outbreak over = 2 maximum incubation periods since last negative test; EBOV = 42 days

17. 17 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Infectious disease terminology Attack rate = Percent of people in an exposed group who develop the disease; EBOV = 16-40% Case fatality rate = Percent of infected people who die; EBOV West Africa = 45% (817/1804) Reproduction number = Average number of new cases that occur from a single case; EBOV = 1.3 Other diseases: e.g., measles R 0 = 20; influenza R 0 = 1.4

18. 18 Values of R 0 of well-known infectious diseases DiseaseTransmission R0R0R0R0 MeaslesAirborne12–18 PertussisAirborne droplet12–17 DiphtheriaSaliva6–7 SmallpoxAirborne droplet5–7 PolioFecal-oral route5–7 RubellaAirborne droplet5–7 MumpsAirborne droplet4–7 HIV/AIDSSexual contact2–5 SARSAirborne droplet 2–5 [2] [2] Influenzae (1918 Pandemic Strain) Airborne droplet 2–3 [ [ 2014 Ebola OutbreakBodily fluid 1-2 Unless noted R0 values are from: History and Epidemiology of Global Smallpox Eradication From the training course titled "Smallpox: Disease, Prevention, and Intervention". The CDC and the World Health Organization. Slide 16-17.

19. 19 RESEARCH INSTITUTE FOR TROPICAL MEDICINE The importance of Effective Reproduction Number (R t ) If one case of EVD (on average) infects greater than one other person, R t is >1 and the epidemic grows; e.g., as in West Africa where R t was initially 3 decreasing to 1.3 If one case of EVD (on average) infects less than one other person, R t is <1 and the epidemic slows and stops; e.g., as in DRC where R t is 0.84 The aim of outbreak control is to reduce R t to less than 1

20. 20 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Case definition A set of clinical, epidemiological and laboratory criteria used to identify a person as a case of a particular disease Suspect Probable Confirmed Suspect Ebola: A person who has been in an Ebola affected area in the last 21 days and has symptoms consistent with EVD Person Under Investigation (PUI): In Ebola infected countries <21 days before

21. 21 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Ebola in West Africa Three countries with widespread transmission Guinea, Sierra Leone, Liberia

22. 22 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Country Classifications (current) Countries with Widespread Transmission –Guinea, Liberia, Sierra Leone Countries with Travel Associated Cases –Mali Countries with Travel Associated Cases and Localized Transmission –USA, Spain Countries with Localized Transmission –Democratic Republic of Congo (separate outbreak) 22

23. 23 Current Country Classifications Countries with Widespread Transmission 1 Affected Areas Guinea Liberia Sierra Leone Entire country Countries without Widespread Transmission 2 Mali 3 Spain 4 United States of America 5 Kayes Madrid Dallas, Texas, New York City Countries with No current transmission 6 Nigeria Senegal Lagos, Port Hardcourt Dakar 1 Travelers arriving from all areas of Guinea, Liberia, and Sierra Leone are at risk for exposure to Ebola. 2 Travelers to these countries are NOT at risk for exposure to Ebola, unless they report direct contact with an Ebola case. 3 There has been a single case diagnosed in Mali on October 23, 2014, that was imported from Guinea. 4 A single case occurred in a healthcare worker caring for an Ebola patient who had been transported to Spain from Liberia for care. There has been no further transmission. Travelers to Spain are NOT at risk for exposure to Ebola. 5 One travel-associated case was imported to Dallas from Liberia, and resulted in transmission to two healthcare workers. One travel-associated case from Sierra Leone was imported to New York City. Travelers to Dallas or New York City are not at risk for exposure to Ebola. 6 These countries are currently Ebola-free. One international importation from Liberia into Nigeria resulted in localized transmission (20 cases and 8 deaths), which has ceased. A single case in Senegal was imported from Guinea. Travelers to Nigeria and Senegal are not at risk for exposure to Ebola, unless they report direct contact with an Ebola case.

24. 24 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Cases: November 4 http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html

25. 25 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Deaths: Nov 4 B http://www.bbc.com/news/world-africa-28755033 4,950

26. 26 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Survivors http://www.msf.org.uk/article/my-son-is-msf-s-1-000th-ebola-survivor

27. 27 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Is EVD close to Philippines? 27

28. 28 RESEARCH INSTITUTE FOR TROPICAL MEDICINE How did it start? Ebola virus disease had not occurred before in West Africa EVD not considered as a diagnosis First case (index case) 2 year old child in village of Meliandou in Guinea died on 6 December 2013 Transmitted locally and new outbreaks started when people moved the virus across Guinea Gatherer J Gen Virol 2014

29. 29 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Effective Reproduction number >1 Spread to Liberia (Apr 2014), then Sierra Leone R t fell below 1 in June, but then rose above 1 Nishiura & Chowell Euro Surveill 2014 June August

30. 30 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Priorities for the response Dr David Heyman emphasied two priorities Hear his interview with the Lancet at http://download.thelancet.com/flatcontentassets/ audio/lancet/2014/lancet_141030.mp3 http://download.thelancet.com/flatcontentassets/ audio/lancet/2014/lancet_141030.mp3 Priority 1: Stop the outbreak; particularly involve African experts and teams with experience in managing Ebola outbreaks Priority 2: Do clinical trials of treatments (eg, blood or serum from survivors) and vaccines 30

31. 31 RESEARCH INSTITUTE FOR TROPICAL MEDICINE The importance of acting quickly If HCWs act fast and reduce the number of initial cases, epidemics can be prevented Even one infected person (index case) that is not isolated is a danger –40% chance of a major outbreak Very serious if >5 people are in the initial cluster of infected people –90% chance of a major outbreak Chowell et al. BMC Med 2014 Screening for that first Ebola case is vitally important!

32. 32 RESEARCH INSTITUTE FOR TROPICAL MEDICINE Quick action stops outbreaks Detect cases early –Screen and triage Respond rapidly –Isolate cases –Implement Ebola strategies –Do contact tracing Probability of a major outbreak decreases the faster intervention occurs 32 Quick action can save thousands of lives! For clinicians: Identify Isolate Inform

33. 33 RESEARCH INSTITUTE FOR TROPICAL MEDICINE References Bausch et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Inf Dis 2007;196:S142-147. Chowell et al. Transmission dynamics and control of Ebola virus disease (EVD): A review. BMC Med 2014;12:196. Martines et al. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg Viruses. J Pathol 2014 Epub Miranda & Miranda. Reston ebolavirus in humans and animals in the Philippines: A review. J Inf Dis 2011;204(suppl 3):S757-S760. Pan et al. Reston virus in domestic pigs in China. Arch Virol 2014; 159:1129–1132. Piercy et al. The survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol. J Appl Microbiol 2010;109:1531-1539. Nishiura & Chowell. Early transmission dynamics of Ebola virus disease (EVD), West Africa, March to August 2014. Euro Surveill 2014;19(36):pii=20894. Sagripanti et al. Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces. Arch Virol (2010);155:2035–2039. 33

34. 34 Thank you

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