INFECTIOUS DISEASE/REVIEW ARTICLE
Ebola Virus Outbreak 2014: Clinical Review for Emergency Physicians Linda Meyers, MD*; Thomas Frawley, MD; Sarah Goss, MD; Christopher Kang, MD *Corresponding Author. E-mail: [email protected], Twitter: @DrLindaMeyers.
The 2014 Ebola outbreak in West Africa is the largest in history. Ebola viral disease is a severe and fatal illness characterized by a nonspecific viral syndrome followed by fulminant septic shock and coagulopathy. Despite ongoing efforts directed at experimental treatments and vaccine development, current medical management of Ebola viral disease is largely limited to supportive therapy, thus making early case identification and immediate implementation of appropriate control measures critical. Because a case of Ebola viral disease was confirmed in the United States on September 30, 2014, emergency medicine providers should be knowledgeable about it for a number of reasons: we are being called on to answer questions about Ebola and allay public fears, we are likely to be first to encounter an infected patient, and there are increasing numbers of US emergency physicians working in Africa who risk coming in direct contact with the disease. This article seeks to provide emergency physicians with the essential and up-to-date information required to identify, evaluate, and manage Ebola viral disease and to join global efforts to contain the current outbreak. [Ann Emerg Med. 2014;-:1-8.] Please see page XX for the Editor’s Capsule Summary of this article. 0196-0644/$-see front matter Copyright © 2014 by the American College of Emergency Physicians. http://dx.doi.org/10.1016/j.annemergmed.2014.10.009
INTRODUCTION Background Ebola virus, the cause of Ebola viral disease, has drawn international attention after a recent outbreak in West Africa. Ebola virus belongs to the family of filoviruses.1 Ebola and Marburg viruses, along with the family of arenaviruses (Lassa and New World arenaviruses), bunyaviruses, and flaviviruses (eg, yellow fever), cause a viral hemorrhagic fever.2 Ebola was first recognized in 1976 when 2 unrelated outbreaks occurred in southern Sudan and the Democratic Republic of the Congo. The virus was given the name Ebola after a small river near the epicenter of the Democratic Republic of the Congo outbreak.3,4 Including the present epidemic, there have been approximately 20 recognized outbreaks of Ebola, all occurring in Africa, with fatality rates of 25% to 90%.5,6 The current Ebola outbreak that began in March 2014, initially announced by the Centers for Disease Control and Prevention (CDC) on March 25th, is the largest in history.6-8 It is associated with a new strain of Zaire species, the most deadly of the 5 Ebola species, with a reported case fatality rate of approximately 55%.9 According to the CDC, as of September 30, 2014 (the most recent information available at this article’s writing), there have been 6,574 total cases (3,626 were laboratory confirmed) across 5 countries (Guinea, Liberia, Nigeria, Senegal, and Sierra Leone) and 3,091 suspected case deaths.10 Figure 1 shows a map of the West African countries affected by the outbreak.11 The World Health Organization (WHO), however, issued a statement indicating that reported numbers “vastly Volume
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underestimate the magnitude of the outbreak” as a result of unreported deaths and undiagnosed cases occurring in communities away from health centers.12,13 On August 8, 2014, the current director-general of WHO declared the current Ebola crisis a “public health emergency of international concern,” a declaration issued only twice previously: once in 2009 in response to influenza A H1N1 and again earlier this year for polio.14 This declaration activated powers provided for under the 2005 International Health Regulations requiring countries to “develop national preparedness capacities, including the duty to report internationally significant events, conduct surveillance, and exercise public health powers, while balancing human rights and international trade.”9 At this article’s writing, initial international public health efforts directed at controlling the spread of the virus have proven inadequate. The outbreak remains in an epidemic phase, with the United Nations requesting nearly $1 billion to help sufficiently contain infection numbers and the WHO estimating that as many as 20,000 people could be infected in the coming months. On September 16, 2014, the United States committed to providing $500 million and deploying up to 3,000 military troops to the region to aid in the control effort.15 From a media perspective, intense news coverage of both the developing situation in Africa and the evacuation and treatment of a current total of 4 infected US citizens at isolation facilities at Emory University Hospital and Nebraska Medical Center16 initially brought Ebola to the forefront of national consciousness. This has resulted in not only renewed interest in the virus but Annals of Emergency Medicine 1
Meyers et al
Ebola Virus Outbreak 2014
Editor’s Capsule Summary
What is already known on this topic Ebola viral disease is a severe and fatal illness characterized by a nonspecific viral syndrome followed by fulminant septic shock, coagulopathy, and a mortality rate of greater than 50%. Fewer than 10,000 cases of Ebola virus disease in history are known, 70% or more occurring during the 2014 outbreak in West Africa. What question this study addressed The current medical management of Ebola virus disease is largely supportive therapy. Early case identification and early appropriate infection control are critical to ensure quality care and maintain a safe medical environment. What this study adds to our knowledge The first case of Ebola virus disease was confirmed in the United States on September 30, 2014. As frontline medical providers, emergency physicians are likely to be the ones who will first encounter cases in the United States. This article seeks to provide them with up-to-date information required to identify, evaluate, and manage Ebola virus disease. How this is relevant to clinical practice Emergency physicians must be vigilant and knowledgeable and prepared for a potential Ebola virus disease case.
also increasing concern by the US public about the possible spread of the virus to the United States.17,18 Added public agency concern has arisen from the fact that, in addition to being a virulent infectious disease, Ebola virus is classified as a category A bioterrorism agent.19 These bioterrorism concerns, however, are likely overstated.20 The possibility of Ebola viral disease presenting in the United States, initially estimated at 18%,21 became a reality on September 30, 2014, when the CDC confirmed the first case of Ebola diagnosed in the United States in Dallas, TX.22 Given their place on the front lines of patient care, emergency physicians should be knowledgeable about Ebola viral disease because there may be more cases presenting in the United States. As the number of US emergency physicians actively involved in the global health efforts in Africa continues to increase, so does the potential for contact with Ebola viral disease. Furthermore, as widespread media coverage of the African outbreak continues, emergency physicians are likely to serve as important educators for concerned patients and hospital staff in regard to risk factors, transmission, clinical presentation, and management of Ebola 2 Annals of Emergency Medicine
viral disease. Professional organizations such as the American College of Emergency Physicians have begun to provide resources for members, including sharing materials from the CDC.23 This article seeks to provide emergency physicians with an up-to-date review of essential clinical information on Ebola viral disease, including initial evaluation, management, and the latest guidelines on personal and facility control measures. Of the 5 species of Ebola virus, only 3 are of human significance and have also been implicated in large outbreaks: Zaire, Sudan, and Bundibugyo.9 Bundibugyo and Sudan have a fatality rate of approximately 25% and 50%, respectively.24 A fourth species, Côte d’Ivoire virus, was responsible for a single case in 1994 in Côte.4 The fifth species, Reston virus, was found in the Philippines and the United States25 but is not responsible for any symptomatic disease in humans to date.26 Even with significant directed field efforts and studies, the identification of Ebola’s natural reservoir host(s) remains elusive.27 A leading suspect for a potential natural reservoir has been the fruit bat.4,28-30 Yet despite the discovery of Ebola virus nucleic acid, antigen, and antibodies in bats, the virus itself has never been isolated from one and no clear case of bat-to-human transmission of Ebola has ever been proven.3,30 Furthermore, the discovery of the Reston species in pigs underscores the importance of considering the existence of other reservoir species, as well as a role for potential amplifying hosts.4 Because none of the Ebola virus species are known to be native to North America,31 a patient initially evaluated in the United States must possess both clinical symptoms and epidemiologic risk factors to be considered as having a “suspected” case of Ebola viral disease. These risk factors, as listed by the CDC, include “contact with blood or other bodily fluids or human remains of a patient known to have or suspected to have Ebola viral disease, residence in—or travel to—an area where Ebola viral disease transmission is active, or direct handling of bats or non-human primates from disease-endemic areas.”32 Furthermore, the risk factors must have been present within the 21 days preceding the onset of symptoms. Transmission of Ebola viral disease occurs by direct contact through broken skin or mucous membranes or by objects such as needles. Bodily fluids, including saliva, blood, vomit, diarrhea, and semen, appear to be infectious.33 Transmission has occurred from deceased Ebola victims to family members who performed ritualistic washing of the corpse at the burial. Ebola has also been transmitted through direct contact with infected animals, especially handling animal carcasses or consuming bush meat.3 Simple physical contact with an infected individual does not appear sufficient for contracting the disease.34 In general, Ebola is not thought to be spread by droplets or airborne transmission, although the role of airborne transmission during recent outbreaks has not been entirely excluded.4,34 Thus, by comparison, it is not considered as contagious as measles or influenza. Contaminated droplets can be released briefly into the air during procedures performed on infected patients.35 In addition, Ebola virus aerosol transmission was demonstrated among nonhuman primates in an experimental setting.34,36 Unlike with measles or influenza, people do not become contagious until they have symptoms. Volume
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Meyers et al
Ebola Virus Outbreak 2014
Figure 1. Centers for Disease Control and Prevention map of 2014 Ebola outbreak in West Africa—outbreak distribution map, updated September 17, 2014.11
The pathogenesis of Ebola viral disease involves immunosuppression, increased vascular permeability, and impaired coagulation. Ebola virus enters the patient through mucous membranes and breaks in the skin and affects multiple cell types, including cells of the immune response, endothelial cells, hepatocytes, adrenal cortical cells, and epithelial cells.37 Ebola viral disease causes endothelial injury, which leads to vascular permeability and disseminated intravascular coagulation.38 Bleeding complications are likely due to a combination of hepatic damage, consumptive coagulopathy, and primary marrow injury to megakaryocytes. Ebola infection is also characterized by severe innate immunosuppression. The virus attacks the immune response along multiple pathways, which allows rapid replication of the virus and contributes to its lethality.38,39 Ebola infection is characterized by an initial nonspecific viral syndrome that is further complicated by septic shock and disseminated intravascular coagulation. Incubation time for Volume
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:
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2014
humans ranges from 2 to 21 days. Most patients become symptomatic after 8 to 9 days, and once symptoms are present, the infection is contagious.40,41 The preliminary history of the patient in Dallas appears to correlate with this time course.22 Figure 2 lists the signs and symptoms of Ebola viral disease. Early symptoms include sudden high fever, malaise, pharyngitis, headache, myalgias, and profuse vomiting and diarrhea. Clinical findings that occur after 3 to 5 days include unexplained bleeding or bruising, renal failure, encephalopathy, multisystem organ failure, hypovolemia, and disseminated intravascular coagulation. Malaria is an important alternative diagnosis to consider in any febrile patient with flulike symptoms who resides in or is returning from Africa. It is difficult to distinguish between these 2 diseases early in their presentation. Figure 3 presents a comparison of Ebola viral disease and malaria.42 Bleeding manifestations are not always present in Ebola viral disease. In a case series of 103 patients with Ebola viral disease during the 1995 outbreak in the Democratic Republic of the Annals of Emergency Medicine 3
Meyers et al
Ebola Virus Outbreak 2014 Congo, bleeding was observed in only 41% and did not correlate with outcome. This same study found that fever was the most common finding (93%) and that tachypnea was the best predictor of outcome.43 Patients who develop a severe course often die within 8 to 9 days. Those who survive beyond 2 weeks tend to survive.40,41,44 Recovery after 2 weeks may then be complicated by arthralgias, ocular disease, tinnitus, pericarditis, orchitis, and suppurative parotitis.43 Some individuals who are infected with Ebola remain asymptomatic. Why this occurs while others develop severe disease is not completely understood but suspected to be due to a complex system of virus-host interaction.45 Early recognition and rapid and accurate diagnosis of Ebola infection are crucial for the initiation, continuation, and cessation of appropriate isolation protocols. Laboratory findings can support the diagnosis of Ebola viral disease but are not specific. Figure 2 lists the laboratory findings observed in Ebola infections.24,37,46 Low calcium level (
Ebola Virus Outbreak 2014: Clinical Review for Emergency Physicians Linda Meyers, MD*; Thomas Frawley, MD; Sarah Goss, MD; Christopher Kang, MD *Corresponding Author. E-mail: [email protected], Twitter: @DrLindaMeyers.
The 2014 Ebola outbreak in West Africa is the largest in history. Ebola viral disease is a severe and fatal illness characterized by a nonspecific viral syndrome followed by fulminant septic shock and coagulopathy. Despite ongoing efforts directed at experimental treatments and vaccine development, current medical management of Ebola viral disease is largely limited to supportive therapy, thus making early case identification and immediate implementation of appropriate control measures critical. Because a case of Ebola viral disease was confirmed in the United States on September 30, 2014, emergency medicine providers should be knowledgeable about it for a number of reasons: we are being called on to answer questions about Ebola and allay public fears, we are likely to be first to encounter an infected patient, and there are increasing numbers of US emergency physicians working in Africa who risk coming in direct contact with the disease. This article seeks to provide emergency physicians with the essential and up-to-date information required to identify, evaluate, and manage Ebola viral disease and to join global efforts to contain the current outbreak. [Ann Emerg Med. 2014;-:1-8.] Please see page XX for the Editor’s Capsule Summary of this article. 0196-0644/$-see front matter Copyright © 2014 by the American College of Emergency Physicians. http://dx.doi.org/10.1016/j.annemergmed.2014.10.009
INTRODUCTION Background Ebola virus, the cause of Ebola viral disease, has drawn international attention after a recent outbreak in West Africa. Ebola virus belongs to the family of filoviruses.1 Ebola and Marburg viruses, along with the family of arenaviruses (Lassa and New World arenaviruses), bunyaviruses, and flaviviruses (eg, yellow fever), cause a viral hemorrhagic fever.2 Ebola was first recognized in 1976 when 2 unrelated outbreaks occurred in southern Sudan and the Democratic Republic of the Congo. The virus was given the name Ebola after a small river near the epicenter of the Democratic Republic of the Congo outbreak.3,4 Including the present epidemic, there have been approximately 20 recognized outbreaks of Ebola, all occurring in Africa, with fatality rates of 25% to 90%.5,6 The current Ebola outbreak that began in March 2014, initially announced by the Centers for Disease Control and Prevention (CDC) on March 25th, is the largest in history.6-8 It is associated with a new strain of Zaire species, the most deadly of the 5 Ebola species, with a reported case fatality rate of approximately 55%.9 According to the CDC, as of September 30, 2014 (the most recent information available at this article’s writing), there have been 6,574 total cases (3,626 were laboratory confirmed) across 5 countries (Guinea, Liberia, Nigeria, Senegal, and Sierra Leone) and 3,091 suspected case deaths.10 Figure 1 shows a map of the West African countries affected by the outbreak.11 The World Health Organization (WHO), however, issued a statement indicating that reported numbers “vastly Volume
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no.
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:
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2014
underestimate the magnitude of the outbreak” as a result of unreported deaths and undiagnosed cases occurring in communities away from health centers.12,13 On August 8, 2014, the current director-general of WHO declared the current Ebola crisis a “public health emergency of international concern,” a declaration issued only twice previously: once in 2009 in response to influenza A H1N1 and again earlier this year for polio.14 This declaration activated powers provided for under the 2005 International Health Regulations requiring countries to “develop national preparedness capacities, including the duty to report internationally significant events, conduct surveillance, and exercise public health powers, while balancing human rights and international trade.”9 At this article’s writing, initial international public health efforts directed at controlling the spread of the virus have proven inadequate. The outbreak remains in an epidemic phase, with the United Nations requesting nearly $1 billion to help sufficiently contain infection numbers and the WHO estimating that as many as 20,000 people could be infected in the coming months. On September 16, 2014, the United States committed to providing $500 million and deploying up to 3,000 military troops to the region to aid in the control effort.15 From a media perspective, intense news coverage of both the developing situation in Africa and the evacuation and treatment of a current total of 4 infected US citizens at isolation facilities at Emory University Hospital and Nebraska Medical Center16 initially brought Ebola to the forefront of national consciousness. This has resulted in not only renewed interest in the virus but Annals of Emergency Medicine 1
Meyers et al
Ebola Virus Outbreak 2014
Editor’s Capsule Summary
What is already known on this topic Ebola viral disease is a severe and fatal illness characterized by a nonspecific viral syndrome followed by fulminant septic shock, coagulopathy, and a mortality rate of greater than 50%. Fewer than 10,000 cases of Ebola virus disease in history are known, 70% or more occurring during the 2014 outbreak in West Africa. What question this study addressed The current medical management of Ebola virus disease is largely supportive therapy. Early case identification and early appropriate infection control are critical to ensure quality care and maintain a safe medical environment. What this study adds to our knowledge The first case of Ebola virus disease was confirmed in the United States on September 30, 2014. As frontline medical providers, emergency physicians are likely to be the ones who will first encounter cases in the United States. This article seeks to provide them with up-to-date information required to identify, evaluate, and manage Ebola virus disease. How this is relevant to clinical practice Emergency physicians must be vigilant and knowledgeable and prepared for a potential Ebola virus disease case.
also increasing concern by the US public about the possible spread of the virus to the United States.17,18 Added public agency concern has arisen from the fact that, in addition to being a virulent infectious disease, Ebola virus is classified as a category A bioterrorism agent.19 These bioterrorism concerns, however, are likely overstated.20 The possibility of Ebola viral disease presenting in the United States, initially estimated at 18%,21 became a reality on September 30, 2014, when the CDC confirmed the first case of Ebola diagnosed in the United States in Dallas, TX.22 Given their place on the front lines of patient care, emergency physicians should be knowledgeable about Ebola viral disease because there may be more cases presenting in the United States. As the number of US emergency physicians actively involved in the global health efforts in Africa continues to increase, so does the potential for contact with Ebola viral disease. Furthermore, as widespread media coverage of the African outbreak continues, emergency physicians are likely to serve as important educators for concerned patients and hospital staff in regard to risk factors, transmission, clinical presentation, and management of Ebola 2 Annals of Emergency Medicine
viral disease. Professional organizations such as the American College of Emergency Physicians have begun to provide resources for members, including sharing materials from the CDC.23 This article seeks to provide emergency physicians with an up-to-date review of essential clinical information on Ebola viral disease, including initial evaluation, management, and the latest guidelines on personal and facility control measures. Of the 5 species of Ebola virus, only 3 are of human significance and have also been implicated in large outbreaks: Zaire, Sudan, and Bundibugyo.9 Bundibugyo and Sudan have a fatality rate of approximately 25% and 50%, respectively.24 A fourth species, Côte d’Ivoire virus, was responsible for a single case in 1994 in Côte.4 The fifth species, Reston virus, was found in the Philippines and the United States25 but is not responsible for any symptomatic disease in humans to date.26 Even with significant directed field efforts and studies, the identification of Ebola’s natural reservoir host(s) remains elusive.27 A leading suspect for a potential natural reservoir has been the fruit bat.4,28-30 Yet despite the discovery of Ebola virus nucleic acid, antigen, and antibodies in bats, the virus itself has never been isolated from one and no clear case of bat-to-human transmission of Ebola has ever been proven.3,30 Furthermore, the discovery of the Reston species in pigs underscores the importance of considering the existence of other reservoir species, as well as a role for potential amplifying hosts.4 Because none of the Ebola virus species are known to be native to North America,31 a patient initially evaluated in the United States must possess both clinical symptoms and epidemiologic risk factors to be considered as having a “suspected” case of Ebola viral disease. These risk factors, as listed by the CDC, include “contact with blood or other bodily fluids or human remains of a patient known to have or suspected to have Ebola viral disease, residence in—or travel to—an area where Ebola viral disease transmission is active, or direct handling of bats or non-human primates from disease-endemic areas.”32 Furthermore, the risk factors must have been present within the 21 days preceding the onset of symptoms. Transmission of Ebola viral disease occurs by direct contact through broken skin or mucous membranes or by objects such as needles. Bodily fluids, including saliva, blood, vomit, diarrhea, and semen, appear to be infectious.33 Transmission has occurred from deceased Ebola victims to family members who performed ritualistic washing of the corpse at the burial. Ebola has also been transmitted through direct contact with infected animals, especially handling animal carcasses or consuming bush meat.3 Simple physical contact with an infected individual does not appear sufficient for contracting the disease.34 In general, Ebola is not thought to be spread by droplets or airborne transmission, although the role of airborne transmission during recent outbreaks has not been entirely excluded.4,34 Thus, by comparison, it is not considered as contagious as measles or influenza. Contaminated droplets can be released briefly into the air during procedures performed on infected patients.35 In addition, Ebola virus aerosol transmission was demonstrated among nonhuman primates in an experimental setting.34,36 Unlike with measles or influenza, people do not become contagious until they have symptoms. Volume
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no.
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:
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2014
Meyers et al
Ebola Virus Outbreak 2014
Figure 1. Centers for Disease Control and Prevention map of 2014 Ebola outbreak in West Africa—outbreak distribution map, updated September 17, 2014.11
The pathogenesis of Ebola viral disease involves immunosuppression, increased vascular permeability, and impaired coagulation. Ebola virus enters the patient through mucous membranes and breaks in the skin and affects multiple cell types, including cells of the immune response, endothelial cells, hepatocytes, adrenal cortical cells, and epithelial cells.37 Ebola viral disease causes endothelial injury, which leads to vascular permeability and disseminated intravascular coagulation.38 Bleeding complications are likely due to a combination of hepatic damage, consumptive coagulopathy, and primary marrow injury to megakaryocytes. Ebola infection is also characterized by severe innate immunosuppression. The virus attacks the immune response along multiple pathways, which allows rapid replication of the virus and contributes to its lethality.38,39 Ebola infection is characterized by an initial nonspecific viral syndrome that is further complicated by septic shock and disseminated intravascular coagulation. Incubation time for Volume
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no.
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:
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2014
humans ranges from 2 to 21 days. Most patients become symptomatic after 8 to 9 days, and once symptoms are present, the infection is contagious.40,41 The preliminary history of the patient in Dallas appears to correlate with this time course.22 Figure 2 lists the signs and symptoms of Ebola viral disease. Early symptoms include sudden high fever, malaise, pharyngitis, headache, myalgias, and profuse vomiting and diarrhea. Clinical findings that occur after 3 to 5 days include unexplained bleeding or bruising, renal failure, encephalopathy, multisystem organ failure, hypovolemia, and disseminated intravascular coagulation. Malaria is an important alternative diagnosis to consider in any febrile patient with flulike symptoms who resides in or is returning from Africa. It is difficult to distinguish between these 2 diseases early in their presentation. Figure 3 presents a comparison of Ebola viral disease and malaria.42 Bleeding manifestations are not always present in Ebola viral disease. In a case series of 103 patients with Ebola viral disease during the 1995 outbreak in the Democratic Republic of the Annals of Emergency Medicine 3
Meyers et al
Ebola Virus Outbreak 2014 Congo, bleeding was observed in only 41% and did not correlate with outcome. This same study found that fever was the most common finding (93%) and that tachypnea was the best predictor of outcome.43 Patients who develop a severe course often die within 8 to 9 days. Those who survive beyond 2 weeks tend to survive.40,41,44 Recovery after 2 weeks may then be complicated by arthralgias, ocular disease, tinnitus, pericarditis, orchitis, and suppurative parotitis.43 Some individuals who are infected with Ebola remain asymptomatic. Why this occurs while others develop severe disease is not completely understood but suspected to be due to a complex system of virus-host interaction.45 Early recognition and rapid and accurate diagnosis of Ebola infection are crucial for the initiation, continuation, and cessation of appropriate isolation protocols. Laboratory findings can support the diagnosis of Ebola viral disease but are not specific. Figure 2 lists the laboratory findings observed in Ebola infections.24,37,46 Low calcium level (
