EBOLA VIRUS

ebola

1. A Seminar on Ebola Virus Disease Presenters : Dr. Joymati Oinam Dr. Shanthosh Priyan S Moderator: Dr. P. Romola Devi Associate Professor

2. OUTLINE Introduction History of past outbreaks Overview of current outbreak Case definition & Exposure risk levels Epidemiology Classification of Ebola virus Reservoir and transmission to humans Pathogenesis Clinical presentation and prognosis Diagnosis Treatment Case management Control and Prevention Guidelines for prevention 11. Conclusion

3. INTRODUCTION Ebola virus disease (also known as Ebola hemorrhagic fever) is an acute, severe, often-fatal disease caused by infection with a species of Ebola virus. The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission. The average EVD case fatality rate is around - 50% (25 % to 90% )

4. Ebola virus disease (EVD) first appeared in 1976 in 2 simultaneous outbreaks - Nzara , Sudan, and Yambuku , Zaire (Democratic Republic of Congo) near the Ebola River. Since then, outbreaks have appeared sporadically. No cure & treatment is largely supportive. Therefore, prevention of the spread of Ebola is particularly important.

5. EBOLA OUTBREAKS PRIOR TO 2014

6. OVERVIEW OF CURRENT OUTBREAKS

7. Largest and most complex Ebola outbreak. More cases and deaths in this outbreak than all others combined. Spread between countries Bushmeat is believed to be the origin of the current Ebola outbreak

8. The origin has been traced to a two-year-old child from the village of Gueckedou , south-eastern Guinea The child, dubbed Child Zero , died on 6 December 2013. Spread to a number of health care workers and then among their family members January to March 2014 First cases notified in a WHO communiqué on 23 March 2014

9. On Aug 8 , the WHO Director-General declared this outbreak a Public Health Emergency of International Concern (PHEIC) WHO estimates that some 10,141 people have contracted the disease so far. Heath officials put the death toll at around 4,922 meaning that one in two people who get Ebola in this outbreak die

10. But the true toll maybe three times as much: by a factor of 1.5 in Guinea, 2 in Sierra Leone and 2.5 in Liberia, and death rate to be 70% of all cases

11. According to the WHO the fatality rate of Ebola- infected healthcare workers is 57 per cent. This compares with an overall case fatality rate of the 2014 West Africa Ebola outbreak of 49 per cent. Around the globe, about 450 health care staffs have contracted Ebola, and a total of 244 have died.

12. Country reports fall into two categories: those with widespread and intense transmission (Guinea, Liberia, and Sierra Leone) those with or that have had an initial case or cases, or with localized transmission (Mali, Nigeria, Senegal, Spain, and USA) WHO Ebola Response Roadmap

13. EBOLA OUTBREAK IN DEMOCRATIC REPUBLIC OF THE CONGO

14. In August 2014, DRC confirmed an outbreak of EVD in the Djera area of Equateur Province The index case-patient was a pregnant woman 7 th confirmed EVD outbreak in DRC This current outbreak has no association with the ongoing outbreak in West Africa.

15. Countries with widespread transmission Country Total cases Total death CFR % Lab confirm cases Lab confirm death HCWs LIBERIA 4665 2705 58 965 1241 228(103D) SIERRA LEONE 3896 1281 33 3389 1008 127(95D) GUINEA 1553 926 60 1312 732 80(41D) TOTAL 10,114 4912 49 5666 2981 435(239D)

16. Countries that reported a case/ imported case/s Country Total cases Total deaths Prob / Suspect Lab confirm cases Lab confirm death HCWs USA 4 1 * 4 1 3(0D) SPAIN 1 * 1 1(0D) MALI 1 1 * 1 1 TOTAL 6 2 * 6 2 4

17. Outbreaks of EVD in Senegal and Nigeria were declared over on 17 October and 19 October 2014, respectively Country Total cases (HCWs) Lab confirmed cases Total deaths NIGERIA (Lagos) 20(11) 19 8(5) SENEGAL 1 1 TOTAL 21(11) 20 8(5)

18. DRC will therefore be declared free of EVD 42 days after the date of the second negative test if no new cases are reported. Country Total cases Lab confirm cases Prob case Sus case Total death HCWs DRC 67 38 28 1 49 8(8D)

19. Case Definition for Ebola Virus Disease (CDC)

20. - Person Under Investigation (PUI) A person who has both consistent symptoms and risk factors as follows: Clinical criteria, fever >38.6 ⁰ Celsius or 101.5 ⁰ Fahrenheit, additional symptoms such as severe headache, muscle pain, vomiting, diarrhea, abdominal pain, or unexplained hemorrhage; AND

21. 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 or nonhuman primates from disease-endemic areas.

22. Probable Case A PUI whose epidemiologic risk factors include high or low risk exposure(s ) Confirmed Case A case with laboratory-confirmed diagnostic evidence of Ebola virus infection

23. High risk exposures A high risk exposure includes any of the following: Percutaneous (e.g., needle stick) or mucous membrane exposure to blood or body fluids of EVD patient Direct skin contact with, or exposure to blood or body fluids of, an EVD patient without appropriate personal protective equipment (PPE )

24. Processing blood or body fluids of a confirmed EVD patient without appropriate PPE or standard biosafety precautions Direct contact with a dead body without appropriate PPE in a country where an EVD outbreak is occurring

25. Low risk exposures A low risk exposure includes any of the following Household contact with an EVD patient Other close contact with EVD patients in health care facilities or community settings .

26. Close contact is defined as a . being within approximately 3 feet (1 meter) of an EVD patient or within the patient’s room or care area for a prolonged period of time (e.g., health care personnel, household members) while not wearing recommended personal protective equipment (PPE) .

27. b. having direct brief contact (e.g., shaking hands) with an EVD patient while not wearing recommended personal protective equipment Brief interactions, such as walking by a person or moving through a hospital, do not constitute close contact

28. No known exposure Having been in a country in which an EVD outbreak occurred within the past 21 days and having had no high or low risk exposures

29. Ebola case-classification criteria (WHO) SUSPECT: Any person, alive or dead, who has (or had) sudden onset of high fever and had contact with a suspected, probable or confirmed Ebola case, or a dead or sick animal OR

30. any person with sudden onset of high fever and at least three of the following symptoms: headache, vomiting, anorexia/ loss of appetite, diarrhoea , lethargy, stomach pain, aching muscles or joints, difficulty swallowing, breathing difficulties, or hiccup; OR any person with unexplained bleeding OR any sudden, unexplained death.

31. PROBABLE: Any suspected case evaluated by a clinician OR any person who died from ‘suspected Ebola and had an epidemiological link to a confirmed case’ but was not tested and did not have laboratory confirmation of the disease.

32. CONFIRMED : A probable or suspected case is classified as confirmed when a sample from that person tests positive for Ebola virus in the laboratory.

33. Passenger categories (MOFWH)

34. Category I: low risk, asymptomatic, arrived or transited from the endemic countries in the past 21 days. Report in case the symptoms develop. Category II : medium risk, asymptomatic, arrived or transited from the endemic countries, history of contact with the known case of EVD or were involved in taking care of the suspect or known case in the last 21 days.

35. Category III: high risk, showing symptoms of EVD and are arriving from endemic countries with history of contact with known or suspect case or were involved in taking care of such case in the last 21 days

36. EPIDEMIOLOGY

37. CLASSIFICATION Order : Mononegavirales •Enveloped, nonsegmented , negative strand RNA viruses Long rods (800-1000 nm) Replication = 8 hours Family : Filoviridae contains 3 genera: • Ebolavirus (1976) • Marburgvirus –(1967) • Cuevavirus –(2002)

38. Ebolavirus species Zaire ebolavirus : 1976, Democratic Republic of Congo. Sudan ebolavirus : 1976, Sudan. Bundibugyo ebolavirus : 2007, Uganda. Ta ї Forest ebolavirus (formerly Côte d’Ivoire ebolavirus ): 1994, Ivory Coast. - Single case, veterinary worker handling primate. Reston ebolavirus : 1989, Philippines. - Macaques, swine. - Human lab workers seropositive but no clinical disease.

39. NATURAL RESERVIOR Suspected – Zoonotic Fruit bats  are considered the most likely natural reservoir of the Ebola virus; Bats were known to reside in the cotton factory in which the first cases for the 1976 and 1979 outbreaks were employed, and they have also been implicated in  Marburg virus infections in 1975 and 1980.

40. TRANSMISSION   EVD is believed to occur after an ebola virus is transmitted to an initial human by contact with an infected animal's body fluids. Airborne transmission has not been documented during previous EVD outbreaks

41. FRUIT BATS (?) NON HUMAN PRIMATES SUSCEPTIBLE INDIVIDUALS OTHER INDIVIDUALS Direct contact (broken skin or mucous membrane) with blood / body fluids/contaminated medical equipments like needles syringes & surfaces & materials ( bedding , clothings ) contaminated with infected fluids Blood, secretion , organs & other bodily fluids Consumption of Bushmeat (?) Partially eaten fruits

42. BUSHMEAT

43. During an outbreak - health care workers and close contacts of those with the infection Burial ceremonies can also play a role People remain infectious as long as their blood and body fluids, including semen and breast milk, contain the virus after recovery from illness Transmission through the semen can occur upto 7 weeks after recovery from illness .

44. PATHOGENESIS VIRUS CAPILLARY VESSELS LEAKAGE OF BLOOD & SERUM INVADES IMMUNE SYSTEM + TRANSPORT THE VIRUS PROFUSE & OFTEN FATAL INTERNAL BLEEDING INTERFERES WITH SIGNALING OF WBC

45. SIGNS AND SYMPTOMS The incubation period ranges from 2 to 21 days (most commonly 8-10 days) Nonspecific presentation Most common symptoms - fever (87%), fatigue (76%) vomiting (68%), diarrhea (66%), loss of appetite (65%). GIT symptoms- Respiratory symptoms- Skin-

46. Bleeding does not affect every patient with Ebola and usually presents as small subcutaneous bleeding vs frank hemorrhage. More severe symptoms at presentation - predict a higher risk for mortality.

47. Symptoms become increasingly severe – mental confusion, coma bleeding (internal & subcutaneous) shock , and multi-organ failure . Most patients with fatal disease die between days 6 and 16 of complications.

48. SIGNS & SYMPTOMS

49. Early symptoms of EVD may be similar to those of  malaria, dengue fever, typhoid, dysentery, influenza or other tropical fevers , before the disease progresses to the bleeding phase. Laboratory findings: Low WBC count, Low Platelets count, Elevated liver enzymes People are infectious as long as their blood and secretions contain the virus

50. DIAGNOSIS Difficult to distinguish EVD from other infectious diseases Medical history, especially travel and work history along with exposure The diagnosis is confirmed by isolating the virus, detecting its RNA or proteins, or detecting antibodies against the virus in a person's blood

51. 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 & IgG antibodies Retrospectively in deceased patients Immunohistochemistry testing PCR Virus isolation

52. Filovirions can be seen and identified in cell culture by  electron microscopy  due to their unique filamentous shapes Samples from patients are an extreme biohazard risk; laboratory testing on non-inactivated samples should be conducted under maximum biological containment conditions

53. TREATMENT Approach considerations: Currently, no specific therapy is available that has demonstrated efficacy General medical support is critical, which should be administered with strict attention to barrier isolation Surgical intervention generally follows a mistaken diagnosis, which may be fatal for the patient and for any surgical team members who become contaminated with the patient’s blood

54. Survivors can produce infectious virions for prolonged periods. Therefore, strict barrier isolation in a private room away from traffic patterns must be maintained throughout the illness Steroid therapy has no role No role for antibiotics unless there is evidence of secondary bacterial infection

55. Supportive care: Supportive therapy - rehydration with oral or intravenous fluids is one of the most important supportive measures For high grade fever - Tepid sponging and tablet paracetamol . No other analgesic, particularly tablet aspirin should not be given Bone marrow suppression - platelets transfusion when the count is below 20000/ cu.mm or bleeding from any sites irrespective of platelet count

56. In case of severe shock and vomiting patient may be treated with intravenous fluid with crystalloid or colloid Blood transfusion - In severe gastrointestinal bleeding and shock (replacement of coagulation factors and heparin if DIC develops) Dialysis in case of renal failure Co-infection with EVD should be immediately treated with proper antibiotic

57. Pharmacologic therapy: Nucleoside analogue inhibitors of the cell encoded enzyme SAH have been shown to inhibit Zaire Ebola virus replication in adult BALB/c mice infected with mouse-adapted Ebola virus Interferon beta early after exposure led to a significant increase in survival time, in rhesus macaques infected with a lethal dose of Ebola virus Passive immunity- Equine -derived hyperimmune globulins and human-derived convalescent immune globulin preparations

58. Ebolavirus -infected cynomolgus macaques, use of human recombinant interferon alfa -2b in conjunction with hyperimmune equine immunoglobulin G ( IgG ) delayed but did not prevent death A recombinant human monoclonal antibody directed against the envelope glycoprotein (GP) of Ebola virus has been demonstrated to possess neutralizing activity DNA vaccines expressing either envelope GP or nucleocapsid protein (NP) genes of Ebola virus have been demonstrated to induce protection in adult mice exposed to the virus

59. ZMAPP Under development for treatment of EVD First used experimentally to treat some people with EVD in the present outbreak, but as of August 2014 it had not yet been tested in a clinical trial to support widespread usage in humans Like intravenous immunoglobulin therapy, ZMapp contains neutralizing antibodies that provide passive immunity to the virus by directly and specifically reacting with it in a "lock and key" fashion

60. Composed of three monoclonal antibodies ( mAbs ), chimeric monoclonal antibody c13C6 from a previously existing antibody cocktail called "MB-003" and two chimeric mAbs from a different antibody cocktail called ZMab , c2G4 and c4G7 ZMapp is manufactured in the tobacco plant Nicotiana benthamiana in the bioproduction process known as "pharming"

61. Vaccines: Currently no vaccine is available Two candidate vaccines in phase 1 clinical trial: One ( cAd3-ZEBOV) has been developed by GlaxoSmithKline in collaboration with the US National Institute of Allergy and Infectious Diseases which uses a chimpanzee-derived adenovirus vector with an Ebola virus gene inserted The second ( rVSV -ZEBOV) was developed by the Public Health Agency of Canada in Winnipeg which uses an attenuated or weakened vesicular stomatitis virus, a pathogen found in livestock; one of its genes has been replaced by an Ebola virus gene

62. CONTROL AND PREVENTION Good outbreak control relies on applying a package of interventions, namely case management, surveillance and contact tracing, a good laboratory service, safe burials and social mobilisation Community engagement is key to successfully controlling outbreaks Raising awareness of risk factors for Ebola infection and protective measures that individuals can take is an effective way to reduce human transmission

63. Risk reduction messaging should focus on: Reducing the risk of wildlife-to-human transmission Reducing the risk of human-to-human transmission Outbreak containment measures

64. Reducing the risk of wildlife-to-human transmission From contact with infected fruit bats or monkeys/apes and the consumption of their raw meat Animals should be handled with gloves and other appropriate protective clothing Animal products (blood and meat) should be thoroughly cooked before consumption

65. Reducing the risk of human-to-human transmission From direct or close contact with people with Ebola symptoms, particularly with their bodily fluids Gloves and appropriate personal protective equipment should be worn when taking care of ill patients at home Regular hand washing is required after visiting patients in hospital, as well as after taking care of patients at home

66. Interim guidelines for hospital infection control while managing the suspect / case of Ebola Virus Disease (EBVD ) Component Recommendation Comments Patient Placement  Single patient room (containing a private bathroom) with the door closed  To maintain a log of all persons entering the patient's room To ensure appropriate and consistent use of PPE by all persons entering the patient room

67. Component Recommendation Comments Personal Protective Equipment (PPE) All persons entering the patient room should wear at least: Gloves Gown (fluid resistant or impermeable) Eye protection (goggles) Facemask to prevent splashes on nose and mouth Face shield, if used, will protect eye, nose and mouth Closed shoes Additional PPE might be required in certain situations (e.g., copious amounts of blood, other body fluids, vomit, or feces present in the environment), including but not limited to: Double gloving Disposable shoe covers Leg coverings To ensure appropriate and consistent use of PPE by all persons entering the patient room

68. Component Recommendation Comments Patient Care Equipment Dedicated medical equipment (preferably disposable, when possible) should be used for the provision of patient care All non-dedicated, non-disposable medical equipment used for patient care should be cleaned and disinfected according to manufacturer's instructions The Equipment should be as far as possible dedicated to isolation rooms Patient Care Considerations Limit the use of needles and other sharp objects as much as possible Limit the use of phlebotomy and laboratory testing to the minimum necessary for essential diagnostic evaluation and patient care If the use of sharp objects cannot be avoided, ensure to follow safe injection practices. All needles and sharps should be handled with extreme care and disposed in puncture-proof, sealed containers & follow as per hospitals guidelines for disposal

69. Component Recommendation Comments Aerosol Generating Procedures on patients To be avoided as far as possible  If unavoidable follow a procedure to minimize exposures from aerosol-generating procedures when performed on Ebola HF patients  Visitors /relatives should not be present  Limit the number of health care providers present during the procedure for the activity  Conduct the procedures in a isolation room as far as possible  HCP should wear complete PPE with N95 masks during the procedure  Disinfect the room after the procedure  If re-usable equipment is used, they should be cleaned and disinfected  Collection and handling of soiled re-usable respirators must be done by trained individuals using PPE Because of the potential risk to individuals reprocessing reusable respirators, disposable filtering face piece respirators & equipment's should be preferred.  Define a list of procedures like intubation, etc.

70. Component Recommendation Comments Hand Hygiene To perform hand hygiene frequently, including before and after all patient contact, contact with potentially infectious material, and before putting on and upon removal of PPE, including gloves. Ensure that supplies for performing hand hygiene like hand rub or soap & water are freely available. Hand hygiene in healthcare settings can be performed by washing with soap and water or using alcohol-based hand rubs. If hands are visibly soiled, use soap and water, not alcohol- based hand rubs. Environmental Infection Control Environmental cleaning and disinfection and safe handling of potentially contaminated materials is paramount Health care providers performing environmental cleaning and disinfection should carry out all activities after wearing complete set of PPE & follow hospital infection control guidelines strictly Ebola virus is susceptible to all commonly used disinfectants eg . sodium hypochlorite (1%)

71. Component Recommendation Comments Safe injection practices Any injection equipment or parenteral medication container that enters the patient treatment area should be dedicated to that patient and disposed of at the point of use disposable syringes & needles are only to be used Follow safe injection practices Duration of Infection Control Precautions Till the patient is in hospital & as the patient is infectious even after he /she is asymptomatic hence even at home safety precautions to be followed till two months from the date of onset of the symptoms appeared It will help in containment Self health monitoring Recommended for all health care providers and visitors & contacts. For a period of 21 days of last exposure. Supports spread of disease & containment there off

72. Outbreak containment measures Contact tracing: Any person who has had close contact with a patient under investigation/treatment for suspected , probable or confirmed case of Ebola Virus Disease infection (should be carefully monitored for the appearance of symptoms of Ebola Virus Disease Close contact: Anyone who provided care for the patient, including a health care worker or family member, or who had other similarly close physical contact ; Anyone who stayed at the same place (e.g. lived with, visited) as a probable or confirmed case while the case was ill.

73. Guidelines for healthcare providers: Health workers while taking care of these patients should observe the following, in addition to universal precautions to avoid exposure to infected blood , fluids, or contaminated environments or objects : Should use personal protection equipment Should not reuse protective equipment or clothing unless they have been properly disinfected with 1% bleach or phenolic products Should change gloves between caring for each patient suspected of having Ebola

74. Invasive procedures should be carried out under strict, safe conditions For aerosol generating procedures PPE should include respiratory protection N95 and in airborne isolation room Infected patients should be kept separate from other healthy patients Dedicated medical equipment should be used All non-dedicated, non-disposable medical equipment used for patient care should be cleaned and disinfected as per manufacturer’s instructions and hospital policies

75. Use of injections and sharps should be limited If the use of sharp objects cannot be avoided, ensure that the precautions are observed

76. Advisory for Airlines on Ebola Virus Disease (EVD) : In flight announcement as below: “ In view of the current t hreat of Ebola Virus Disease (EVD): which has high mortality and is currently reported in West African Countries , travelers who have any fever, weakness, muscle pain, headache , sore throat, vomiting, diarrhea, rash, bleeding should report immediately to the airlines crew and at the immigration /medical unit on arrival. This is important for early diagnosis for prompt management and preventing spread. In case any of these symptoms develop within 30 days of arrival in the country the traveler should seek medical assistance from the designated hospitals and also inform the airport health office.”

77. 2. All airlines should keep a. First aid kits, universal precaution kits as per the ICAO guidelines and b. A stock of triple layer masks (25 Nos.), disposable hand gloves (around 25) hand sanitizer and disposal bags: these are to be used for any passenger reporting with symptoms of Ebola Virus Disease (EVD) and co-passengers who are likely to have contacted the disease.

78. 3. Assist the staff of Health unit at the airport during disembarkation for contact tracing of travelers identified as suspect by providing Public Health Passenger Locator cards (as requested by the Airport Health officer) . 4. Follow aircraft disinfection procedures (as recommended by WHO /ICAO).

79. Advisory for specific public health measures for travelers suspected of EVD Distancing of other passengers , if possible from the symptomatic passenger(reseating) Covering nose and mouth of the patient with a surgical facemask (if tolerated ) Limiting contacts to the passenger to the minimum necessary Only one or two (if ill passenger requires more assistance) cabin crew should be taking care of the ill passenger and they should be using the Universal Precaution Kit

80. Hand washing with soap after any direct or indirect contact with the passenger Immediate notification of authorities at the destination airport in accordance with procedures promoted by the International Civil Aviation Organization (ICAO ) Immediate isolation of passenger upon arrival

81. The possibility of transmission to other co-passengers and crew on board the aircraft should be assessed by health care providers on arrival Based upon proximity to the index patient, contact tracing should be considered: Passengers and crew with reported direct contact Passengers seated in an adjacent seat to the index patient Cleaning staff of affected aircraft section

82. Conclusion Prevention of world wide outbreak lies within the education of what the virus is capable of doing, how Ebola virus can be properly treated and by performing prompt action to isolate the virus before it has dispersed Because of the nature and extent of international travel today, it is possible that importations of diseases like Marburg, Lassa and Ebola will take place Comprehensive national programs for the diagnosis, management and surveillance of such patients and their personal contacts should be developed

83. Control of person to person transmission remains as a greatest challenge in control and prevention of the infection Our approach to the future management of these problems must remain dynamic and adaptable to new developments in the epidemiology, control and prevention of these diseases

84. REFERENCES The Ebola Response Roadmap is available at: http://www.who.int/csr/resources/publications/ebola/response-roadmap/en/. Accessed October 28, 2014 WHO | Ebola virus disease. Available at: http://www.who.int/mediacentre/factsheets/fs103/en/ 1/7. Accessed October 22, 2014

85. National Institute for Communicable Diseases | Alerts | Ebola Virus Disaease Outbreak: Situation Update, 27 October 2014. Available at: http://www.nicd.ac.za/?page=alerts&id=5&rid=430. Accessed October 28, 2014. Ebola: What Clinicians Need to Know. Available at: http://www.medscape.org/viewarticle/832353?src=wnl_cme_revw. Assessed October 28, 2014. Case Definition for Ebola Virus Disease (EVD):Centers for Disease Control and Prevention . Available at : http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/distribution-map.html#areas. Accessed October 22, 2014 Advisories on (EVD) Ebola Virus Disease. Ministry of health and family welfare. Available at http://mohfw.nic.in/index1.php?lang=1&level=2&sublinkid=4362&lid= 2884 . Last accessed on October 28, 2014.

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