Virus Disease Transmission November 5, 2014

Key Points:

 The Ebola virus is transmitted from person to person through close personal contact with an infected individual or their blood or body fluids.

 Airborne transmission of Ebola virus has not been demonstrated in human studies.

 Individuals infected with Ebola are not infectious before the onset of symptoms.

 Individuals at the height of their illness or in the latter stages of fatal disease present the greatest risk for potential transmission.

 Strict adherence to prevention and control precautions, including the use of personal protective equipment, has been shown to be extremely effective in preventing Ebola virus transmission to health care workers.

How is Ebola transmitted?

The Ebola virus is considered a classic zoonotic pathogen with the suspected reservoir being the African fruit bat, with chimpanzees, apes, and humans being end hosts. Transmission to humans from contact with infected animals through the preparation of “bush meat” has been well documented in Africa1. Person to person transmission of the Ebola virus occurs through close personal contact with an infected individual or their blood or body fluids2. Transmission occurs from direct blood or body fluid exposure to non-intact skin or mucous membranes, or through percutaneous exposure (e.g. needle stick ).

In addition to blood, Ebola virus has been detected in other body fluids following symptom onset, including saliva, stool, semen, breast milk, urine, sweat, and tears3,4, and the World Health Organization has indicated that vomit can also be infectious5. Any body fluid from an infected patient that has blood mixed with it may potentially contain the virus.

In studies of Ebola outbreaks, transmission of Ebola from patients to household contacts has required direct contact with an infected patient or their body fluids6,7. In one study, transmission to a household contact occurred in the absence of direct contact with the infected patient, but the infected contact had slept wrapped up in a blanket left by his brother, who had just died of Ebola virus disease6. In another study of 27 primary Ebola cases and 173 household contacts, none of 78 household member contacts who did not touch the infected person during the clinical illness period were infected7.

Traditional funeral practices in African countries affected by Ebola outbreaks typically involve the cleaning and rubbing of the deceased body, which may have a high load of Ebola virus8. Contact with the bodies of deceased Ebola patients during such funeral rituals has been shown to be a significant risk factor for Ebola virus transmission7,9.

Ebola virus has been detected within the skin when skin biopsy samples have been examined using special antigen staining techniques. Specifically, virus was detected within cells in the deeper layer of the skin (dermis) and in areas surrounding sweat glands where cell breakdown (lysis) had occurred10.

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Ebola Virus Disease Transmission November 5, 2014

Using electron microscopy, no Ebola virus particles were observed in skin cells closer to the skin surface or within sweat glands10. Ebola virus has been detected in a skin swab from a patient with Ebola virus disease, but there was no microscopic examination to determine if the skin surface had been contaminated with blood or other body fluid3.

It is possible that Ebola can be transmitted through contact with environmental surfaces that are contaminated with Ebola virus (i.e. fomites), but this possibility is unlikely if the environmental surface is not visibly contaminated with blood or body fluids. Enveloped viruses such as Ebola are susceptible to a broad range of hospital disinfectants used to disinfect hard, non-porous surfaces11. An environmental sampling study took place on an ward caring for Ebola patients; this isolation ward underwent daily disinfectant cleaning of the floors, as well as disinfectant cleaning of visibly contaminated surfaces as necessary. All environmental samples were negative for Ebola virus, suggesting that the risk of transmission from fomites is low when environmental cleaning practices are followed3.

Can Ebola be transmitted by the airborne route?

Lung involvement is uncommon in Ebola virus disease12,13. Airborne transmission of Ebola virus has not been demonstrated in human studies. Studies of Ebola outbreaks to date have been consistent with transmission via close personal contact with infected individuals or their blood or body fluids6,7,14,15.

For example, in settings where household contacts have shared small confined living spaces (e.g. small and poorly ventilated huts, or slept in the same room as the infected individual) but did not have direct contact with infected individuals, no Ebola virus transmission has occurred14,15.

In laboratory settings, non-human primates exposed to aerosolized Ebola virus from pigs have become infected, however, airborne transmission of Ebola virus has not been demonstrated between non-human primates2,16.

Although this has not been demonstrated in human studies, there is a theoretical risk of transmission if one were to inhale aerosolized fluids from an Ebola patient. For this reason, airborne precautions are required when an aerosol generating medical procedure is performed on a patient infected with Ebola virus disease. Airborne precautions are also required when performing laboratory tests on specimens that may contain the Ebola virus, due to the likelihood of aerosolization during processing of samples.

How soon after being infected with Ebola can a person potentially infect others?

The period between contact with Ebola virus and the development of symptoms (incubation period) ranges from 2 to 21 days (but is usually 4 to 9 days). During the incubation period (prior to the onset of symptoms) transmission of Ebola from an infected person to another individual has not been observed. For example, in a study of household members who had close contact with infected individuals during the incubation period (including direct contact, sharing of meals, sharing a bed, etc) there was no observed risk of Ebola virus transmission7.

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Ebola virus is not detectable in the blood prior to the onset of symptoms17. Once symptoms begin, Ebola virus may be detectable in the blood at very low levels. Subsequently, the viral load in blood changes in parallel with the disease course, increasing over the first few days as symptoms escalate, and then decreasing as symptoms settle17. The risk of transmission is correlated with the quantity of circulating virus in blood and body fluids. Patients in the latter stages of fatal disease (including the post-mortem period) have high levels of the Ebola virus in their blood and body fluids, which represents the highest risk for Ebola virus transmission6,7.

Is Ebola easily transmissible?

Unprotected exposure to blood and body fluids from a symptomatic individual who is infected with Ebola virus carries a risk of disease transmission. However, it has been observed that Ebola virus is not transmitted in the context of casual contact with patients in the early stages of clinical illness, or in health care settings when appropriate infection prevention and control measures are in place. For example:

 In Gabon, 18 people who had become ill with Ebola after skinning and chopping a chimpanzee cadaver were admitted to hospital. All equipment necessary for barrier nursing and prevention of the spread of disease were provided at the hospital. No Ebola cases occurred among health care personnel, and 191 contacts were traced with no further cases of Ebola virus disease18;

 An Ebola-infected individual from Guinea travelled to Senegal by seven-person taxi on August 14, 2014. He developed fever, vomiting, and diarrhea on August 16, sought care at a neighbourhood health post on August 18, continued follow-up as an outpatient until August 25, and was admitted to hospital on August 26. Sixty- seven contacts of the patient were identified, including 33 health care workers, and none of the contacts developed Ebola virus disease19;

 An Ebola-infected individual from Liberia had traveled to Dallas, Texas, on September 20, 2014, and developed symptoms four days later. He presented to a local emergency department on September 25 with fever, abdominal pain, headache, dizziness, and nausea, and was discharged home early on September 26. On September 28, 2014, he was transported to the same hospital by ambulance, was admitted for further assessment, and was diagnosed with Ebola virus disease on September 3020. Of all the people who had close contact with this symptomatic individual in the days prior to his hospital admission - including emergency department staff, EMS workers, his fiancée, and family members - none of them became infected with the Ebola virus20,21. Although transmission did not occur early in his disease, two ICU nurses who had close contact with the Ebola-infected patient in the latter stages of his disease did become infected (both have since recovered from their ). It is not yet clear how these two nurses acquired Ebola; there is speculation about the adequacy of personal protective measures (in terms of equipment, training, and supervision), but the full details of the events at the Dallas hospital have yet to be formally disclosed.

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Why has this Ebola outbreak been so large and widespread?

The current Ebola outbreak in West Africa is the largest and most sustained Ebola outbreak in human history. Since 1976, when the Ebola virus was first identified, the largest previous outbreak involved 425 cases22. In comparison, as of October 29, 2014, there have been 13,567 reported Ebola cases, including 4,951 reported deaths23.

There are many factors that have contributed to the size and extent of the current outbreak, for example8:

 Although historical outbreaks have occurred in remote forests of Sub-Saharan Africa, the current outbreak has reached urban areas. Sustained human-to-human transmission is more likely with the virus circulating in densely populated areas;

 The affected countries that are at the centre of the current outbreak (Sierra Leone, Guinea, Liberia) are small countries with limited health care and public health resources. This outbreak is the first time that Ebola has been identified in West Africa, and so local health care workers did not have any prior experience dealing with the virus. As well, limited surveillance and reporting systems may have delayed outbreak identification and subsequent global response;

 Fear, mistrust, and misinformation within affected communities has been identified as a challenge in the response to the outbreak. In some cases there is a distrust of medical staff, including foreign medical staff, which has resulted in people refusing to cooperate with medical personnel or helping patients “escape” from isolation wards, which is understandable in that mortality within these wards is high and little beyond symptomatic treatment is offered.

Why have Ebola outbreaks resulted in so many infected health care workers?

In Africa, health care workers have been at particular risk for Ebola infection, accounting for one-quarter of cases in prior outbreaks22. Patients become more infectious in the latter stages of the illness, when they are likely to be hospitalized and cared for by health care workers24. Close contact with infectious patients and exposure to patient body fluids, in the absence of adequate personal protective equipment (PPE) places health care workers at risk for acquiring Ebola infection.

For example, in the 1995 outbreak in the Democratic Republic of the Congo that involved 315 cases of Ebola, 67 health care workers had been infected prior to the arrival of an international aid team. The hospital conditions on arrival of the international team were described as follows: “this ward had been earmarked as an isolation ward for the treatment of suspected Ebola cases, [but] it was not physically isolated from the rest of the hospital and not clearly identifiable as a special isolation unit. The majority of patients were lying on the floor of the ward, and family members walked in and out. Bodies were lying unburied in the hospital, and used needles and other contaminated equipment were scattered about.

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The staff (1 physician and 3 nurses), who had volunteered to care for the patients, were working without adequate protection. Under these conditions, the risk of becoming infected for both health care providers and family members was judged to be extremely high” 25. “There was no running water, no electricity, and no functional waste disposal system or latrines. For nursing care and for most invasive procedures, gloves were not used” 26.

Lapses in precautionary measures have been associated with transmission of Ebola to health care workers, so strict adherence to precautionary measures, including disinfection practices and use of PPE, is necessary27. Adequate PPE and training, careful attention to donning and doffing procedures, and the use of a trained observer to minimize breaches in protocol diminish the risk of Ebola transmission to the health care worker24.

How can health care workers be protected from Ebola when caring for patients?

The history of Ebola outbreaks has demonstrated the importance of basic infection prevention and control practices in preventing infection. These measures have been extremely effective in stopping Ebola outbreaks and preventing disease transmission6,9,15,18,28,29,30.

For example, in the 1995 outbreak in the Democratic Republic of the Congo, an international aid team organized a true isolation ward, created a “clean area” for staff and family members, instituted a chlorinated water supply, a waste disposal system, showers, and latrines, instituted disinfection procedures with calcium hypochlorite solution, and provided individual PPE (including disposable gloves, surgical masks, plastic aprons, goggles, and rubber boots)25. Only 3 health care workers became infected after these measures were put in place (as compared to the 67 health care workers who were infected before the team arrived):

 An Italian nun, who was probably infected because barrier nursing methods were not always used (possibly infected prior to international team’s arrival);  A Congolese nurse who experienced a needlestick injury while re-capping;  A second Congolese nurse, who always worked with PPE but likely became infected after touching her eyes with a contaminated glove26.

The 2000-2001 Ebola outbreak in Uganda, with a total of 425 cases, was the largest historical outbreak prior to the current outbreak in West Africa. The Uganda outbreak demonstrated the effectiveness of basic infection prevention and control practices and the importance of precision of execution when using barrier techniques. During this outbreak, the secondary transmission of Ebola to health care workers was well studied in the Masindi district of Uganda. As noted by fellow health care workers, several violations in barrier technique occurred, leading to potential Ebola virus exposures that would have been prevented through strict adherence to proper technique:

 “Five more HCWs, however, all members of the EHF case management team, became infected after the declaration of the outbreak and the introduction of barrier nursing. The likely cause for these occupational EHF cases were violations of barrier nursing principles.

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According to fellow HCWs, such violations included: cleaning the ambulance without full protective gear after transporting suspect cases and smoking while doing so, washing soiled linen of patients without full protective gear on the Ebola ward, or answering the mobile phone while working in the contaminated section of the Ebola ward.”31

In South Africa in 1996, it took over 10 days after symptom onset to diagnose Ebola virus disease in a traveller and one local health care worker (who was likely infected via a percutaneous injury while assisting with the placement of a central venous catheter in the traveller). More than 300 contacts of these two Ebola patients, the vast majority of whom were health care workers, were placed under observation. There were no further cases of the disease, despite staff being involved in numerous hazardous procedures (the Johannesburg hospital where the individuals were treated utilized universal blood and body fluid precautions, including patient isolation and barrier nursing)30;

During the current epidemic in Liberia, hospitals that have instituted improvements in triage processes (in addition to isolation and health care worker use of personal universal precautions) have eliminated high-risk exposures of health care workers to infected patients32.

A recent editorial effectively summarized some key points with respect to protecting health care workers form Ebola virus disease: “despite its lethal nature, Ebola transmission can be interrupted with simple interventions and by focusing on basics . . . protection of health care workers in Ebola outbreaks does not happen by accident – it is achieved through the provision of adequate PPE and, more important, a focus on systems processes that enforce the safe use and removal of PPE”33.

References

1. Feldman, H., et al. Ebola haemorrhagic fever. The Lancet 2011; 377(9768): 849-862.

2. Public Health Agency of Canada. Pathogen safety data sheet – infectious substances. Ebolavirus. http://www.phac- aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php; accessed October 27, 2014.

3. Bausch, D.G., et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. The Journal of Infectious Diseases 2007; 196: S142-S147.

4. Kreuels, B., et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. New England Journal of Medicine; published online October 22, 2014: doi : 10.1056/NEJMoa1411677.

5. World Health Organization. What we know about transmission of the Ebola virus among humans. Ebola situation assessment – 6 October 2014. http://www.who.int/mediacentre/news/ebola/06-october-2014/en/

6. Francesconi, P., et al. Ebola Hemorrhagic Fever transmission and risk factors of contacts, Uganda. Emerging Infectious Diseases 2003; 9(11): 1430-1437.

7. Dowell, S.F. Transmission of Ebola Hemorrhagic Fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S87-S91.

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8. Semalulu, T., et al. What has this Ebola outbreak in West Africa been so challenging to control? Canada Communicable Disease Report; 40(14): August 14, 2014. http://www.phac-aspc.gc.ca/publicat/ccdr- rmtc/14vol40/dr-rm40-14/dr-rm40-14-ebola-eng.php

9. Wamala, J.F., et al. Ebola Hemorrhagic Fever associated with novel virus strain, Uganda, 2007-2008. Emerging Infectious Diseases 2010; 16(7): 1087-1092.

10. Zaki, S.R., et al. A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola Hemorrhagic Fever. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S36-S47.

11. U.S. Centers for Disease Control and Prevention CDC. Interim Guidance for Environmental Infection Control in Hospitals for Ebola Virus. Accessed online on November 3, 2014. http://www.cdc.gov/vhf/ebola/hcp/environmental-infection-control-in-hospitals.html

12. Bwaka, M.A., et al. Ebola Hemorrhagic Fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S1-S7.

13. WHO Ebola Response Team. Ebola virus disease in West Africa – the first 9 months of the epidemic and forward projections. New England Journal of Medicine 2014; 371(16): 1481-1495.

14. Baron, R.C., et al. Ebola virus disease in southern Sudan: hospital dissemination and intrafamilial spread. Bulletin of the World Health Organization 1983; 61(6): 997-1003.

15. Khan, A.S., et al. The re-emergence of Ebola Hemorrhagic Fever, Democratic Republic of the Congo, 1995. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S76-S86.

16. Alimonti, J., et al. Evaluation of transmission risks associated with in vivo replication of several high containment pathogens in a biosafety level 4 laboratory. Scientific Reports; 4: 5824; published online July 25, 2014: doi.10.1038/srep0584.

17. Towner, J.S., et al. Rapid diagnosis of Ebola Hemorrhagic Fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. Journal of Virology 2004; 78(8): 4330-4341.

18. Georges, A.-L., et al. Ebola Hemorrhagic Fever outbreaks in Gabon, 1994-1997: epidemiologic and health control issues. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S65-S75.

19. Mirkovic, K., et al. Importation and containment of Ebola virus disease – Senegal, August –September 2014. Morbidity and Mortality Weekly Report; 63(39): October 3, 2014.

20. U.S. Energy & Commerce Committee. Examining the U.S. public health response to the Ebola outbreak. Preliminary Transcript – October 16, 2014. Accessed on November 4, 2014. http://energycommerce.house.gov/hearing/examining-us-public-health-response-ebola-outbreak

21. U.S. Centers for Disease Control and Prevention - Cases of Ebola Diagnosed in the United States. November 3, 2014. Accessed on November 4, 2014. http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states- imported-case.html

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22. Del Rio, C., et al. Ebola Hemorrhagic Fever in 2014 : the tale of an evolving epidemic. Annals of ; published online August 19, 2014. doi: 10.7326/M14-1880.

23. WHO. Ebola response roadmap situation report – 31 October 2014. Accessed on November 3, 2014. http://apps.who.int/iris/bitstream/10665/137424/1/roadmapsitrep_31Oct2014_eng.pdf?ua=1

24. Edmond, M.B., et al. Ebola virus disease and the need for new personal protective equipment. JAMA. Published online October 28, 2014. doi:10.1001/jama.2014.15497.

25. Kerstiëns, B., et al. Interventions to control virus transmission during an outbreak of Ebola Hemorrhagic Fever. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S263-S267.

26. Guimard, Y., et al. Organization of patient care during the Ebola Hemorrhagic Fever epidemic in Kikwit, Democratic Republic of the Congo, 1995. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S268-S273.

27. Forrester, J.D., et al. Cluster of Ebola cases among Liberian and U.S. health care workers in an Ebola treatment unit and adjacent hospital – Liberia, 2014. Morbidity and Mortality Weekly Report; 63(41): October 17, 2014.

28. World Health Organization. Ebola haemorrhagic fever in Zaire, 1976. Report of an International Commission. Bulletin of the World Health Organization 1978; 56(2): 271-293.

29. Ndambi, R., et al. Epidemiological and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995. The Journal of Infectious Diseases 1999; 179: (Suppl 1): S8-S10.

30. Richards, G.A., et al. Unexpected Ebola virus in a tertiary setting: clinical and epidemiological aspects. Critical Care Medicine 2000; 28(1): 240-244.

31. Borchert, M., et al. Ebola haemorrhagic fever outbreak in Masindi District, Uganda: outbreak description and lessons learned. BMC Infectious Diseases 2011; 11: 357.

32. Reaves, E.J., et al. Control of Ebola virus disease – Firestone District, Liberia, 2014. Morbidity and Mortality Weekly Report; 63(42): October 24, 2014.

33. Fischer, W.A., et al. Protecting health care workers from Ebola : personal protective equipment is critical but not enough. Annals of Internal Medicine; published online August 26, 2014. doi: 10.7326/M14-1953.

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