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Ebola Virus Disease: A Review of Its Past and Present

Murray, Michael J. MD, PhD

doi: 10.1213/ANE.0000000000000866
General Articles: Review Article
Continuing Medical Education

Ebola virus, the virus responsible for Ebola virus disease, has spawned several epidemics during the past 38 years. In 2014, an Ebola epidemic spread from Africa to other continents, becoming a pandemic. The virus’s relatively unique structure, its infectivity and lethality, the difficulty in stopping its spread, and the lack of an effective treatment captured the world’s attention. This article provides a brief review of the known history of Ebola virus disease, its etiology, epidemiology, and pathophysiology and a review of the limited information on managing patients with Ebola virus disease.

From Grand Canyon Anesthesia Consultants, Scottsdale, Arizona.

Accepted for publication November 18, 2014.

Funding: None.

The author declares no conflicts of interest.

Reprints will not be available from the author.

Address correspondence to Michael J. Murray, MD, PhD, Grand Canyon Anesthesia Consultants, 24311 N. 121st Pl., Scottsdale, AZ 85255. Address e-mail to

The recent epidemic of Ebola virus disease (formerly known as Ebola hemorrhagic viral disease) began in Guinea in December 2013. After March 23, 2014, the World Health Organization (WHO) became involved when notified of the scope of the problem. By August 17, 2014, the WHO declared the epidemic an international crisis. One month later, humanitarian aid workers who had contracted Ebola virus disease were transported back to their respective countries for medical care, one of whom was the source of contamination for a health care worker in Spain. She had contact with the patient while wearing personal protection equipment (PPE) on September 24 and 25, 2014. On both occasions, she is reported to have worn appropriate PPE, but on September 29, 2014, she developed a fever. On October 6, 2014, she was admitted into isolation. She survived her disease and, as of October 31, 2014, her 83 contacts had completed the 21-day monitoring period without evidence of contracting Ebola virus disease.1 The WHO requires that 42 days pass, double the known maximal incubation period, as an additional margin of safety, before declaring a country free of disease.2

In October 2014, a native of Liberia who had been in close contact with 2 patients with Ebola virus disease travelled to Dallas, Texas, where he was diagnosed with Ebola virus disease. He was hospitalized and died, but not before exposing dozens of individuals to the Ebola virus. Two health care workers contracted the disease despite wearing PPE.3

The WHO Ebola Response Team, analyzing the data from 4507 probable and confirmed cases as of September 14, 2014, predicted that if the global community did not respond with more effective methods to contain and control the disease, that by November 2, 2014, the number of infected individuals would increase from hundreds to thousands each week.4

For whatever reasons (e.g., an aggressive response of local and international communities and local educational programs), the predictions did not come to pass.5 As of this writing, the epidemic is ebbing. Figure 1 shows the total number of cases of Ebola virus disease in Guinea, Liberia, and Sierra Leone, based on May 2015 data from the Centers for Disease Control.a Figure 2 shows the weekly change in Ebola cases. The weekly case numbers peaked in late 2014 and started declining rapidly in 2015.

Figure 1

Figure 1

Figure 2

Figure 2

Although Figure 2 suggests that there are still new cases in each country, the most recent data from the WHO report just 9 total cases in the most recent week ending May 10, 2015.b Liberia is now considered free of Ebola, with no reported cases for >40 days. The difference between Figure 2 and the most recent WHO update likely relates to “reported cases,” shown in Figures 1 and 2, and confirmed cases reported in the most recent WHO Situation Report.

None of the health care workers infected in the United States has died from Ebola virus disease, so it appears that aggressive supportive care can reduce the mortality. However, there is no definitive treatment for patients with Ebola.

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Viral hemorrhagic diseases, caused by members of the Flaviviridae, Bunyaviridae, and Arenaviridae viral families, are characterized by fever and bleeding diathesis, followed by circulatory collapse and death. Flaviviridae family viruses are responsible for yellow fever and dengue fever. A Bunyaviridae family virus is responsible for Crimean-Congo hemorrhagic fever. An Arenaviridae family virus is responsible for Lassa fever. These diseases have resulted in considerable morbidity and mortality for hundreds of years if not millennia.

Table 1

Table 1

Beginning approximately 50 years ago, viral hemorrhagic disease caused by previously unrecognized viruses, Marburg virus and Ebola virus, began to appear. Marburg virus is comprised of 1 species within the genus Marburgvirus. Ebola virus consists of 5 viral species within the genus Ebolavirus. Ebolavirus and Marburgvirus comprise 2 of the 3 genera in the family Filoviridae. The third genus in the Filoviridae family is Cuevavirus, which does not appear to cause human disease. Filoviridae are in the order Mononegavirales (Table 1).6 Viruses within the order Mononegavirales are encapsulated single-stranded, negative-sense (-polarity) RNA viruses. The negative-sense RNA must first be converted to a positive-sense RNA within a cell before the gene frames encoded in the RNA can be read, producing messenger RNA, responsible for the production of viral proteins on ribosomes.

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Filoviruses have been in existence for >10 million years.7 Marburg and Ebola viruses diverged a common ancestor >10,000 years ago.8 The first documented illness caused by 1 of the 2 hemorrhagic fevers was in August 1967.9 Laboratory workers in a commercial facility in Marburg, Germany, a town just north of Frankfurt, Germany, became ill after working with African green monkeys (Cercopithecus aethiops) imported from Uganda. Other laboratories that had received shipments of the monkeys, which were to be used in polio vaccine production, were contacted. In 2 of the laboratories, 1 in Frankfurt and 1 in Belgrade, laboratory personnel also had become infected from the monkeys. Thirty-seven people ultimately contracted the illness, 9 of whom died. Their illness was manifested by fever, vomiting, diarrhea, bleeding, and circulatory shock. Virologists in Germany identified a virus that was a member of the family Filoviridae that had a unique structure. Some of the virions were long filamentous particles that measured as much as 14 μm in length and were 80 nm wide. Other virions were curved, resembling the number 6, or a hairpin10 (Fig. 3).

Figure 3

Figure 3

Nine years later, in June 1976, in the Democratic Republic of the Sudan (Sudan), a man who lived in a rural area, but who worked in a factory in the township of Nzara, became febrile, with a headache and chest pain, on June 27, 1976.11 Four days later, he was admitted to the hospital. The next day, he developed bleeding from his nose and mouth, along with bloody diarrhea. The patient died on July 6, but not before infecting several of his factory coworkers and family members. Subsequent analysis of household contacts sleeping in the same room as the infected patient demonstrated that 23% of those who had touched the patient and 81% of those who had nursed the patient contracted the disease.11 Before the epidemic was brought under control, 284 people had become infected, 53% of whom died. Similar to the index case, patients initially had an influenza-like syndrome that included headache, fever, arthralgias, myalgias, diarrhea, vomiting, chest pain, sore throat, and rash. Hemorrhagic complications were observed in almost all the fatal cases and in approximately half of the patients who survived. The overall hemorrhagic complication rate was 71% (Table 2). Leukocytosis was noted in those few patients who had complete blood counts measured, and thrombocytopenia was present in the most severely ill patients. There were 2 limited postmortem examinations that demonstrated focal eosinophilic necrosis in the liver of 1 of the cadavers, tubular necrosis of the kidneys in the other. The most consistent finding in both cases was the depletion of lymphocytes in the lymphatic system, with a complimentary increase in plasma cells.11 Investigators at the WHO isolated 2 species of Ebolavirus from patients’ blood and antibodies to Ebolavirus were detected by immunofluorescence in survivors. The WHO observed that the characteristics of the disease were similar to those that patients had developed in Marburg, Germany, 9 years previously. The epidemic lasted 5 months, from June through November 1976.

Table 2

Table 2

On the basis of the available evidence, WHO hypothesized that someone from southwest Sudan who was either acutely ill with the disease, or convalescing from it, and who traveled to northeast Zaire (renamed the Democratic Republic of the Congo on May 16, 1997) to seek medical care was the index case. On the basis of the symptoms, the index patient might have received a parenteral injection of chloroquine. If so, the injection would have contaminated the needle, which might have been used on several more patients, thus spreading the disease. However, this theory was dispelled by the discovery that the epidemic that appeared in southwest Sudan was caused by a virus from a different species (now called Sudan ebolavirus) than the one that caused disease in that appeared in Zaire (now called Zaire ebolavirus).

The second epidemic of Ebola virus disease that occurred in northeast Zaire between September and October of 1976 provided many additional lessons.12 The index case patient developed symptoms and signs of the disease on September 1, 1976, after being treated for malaria with an IM injection of chloroquine. The malarial symptoms abated, but within 5 days, he developed a different set of symptoms and signs, as did several other individuals who received parenteral injections at the same facility, the Yambuku Mission Hospital (YMH) near the Ebola River. After a prodrome of a few days, individuals developed a severe sore throat, a maculopapular rash, abdominal pain, and variable abdominal symptoms (e.g., nausea, dysphagia, diarrhea, and bleeding from several sites including the gastrointestinal tract). Although diagnostic capabilities were limited, nonicteric hepatitis, acute pancreatitis, and disseminated intravascular coagulation (DIC) were diagnosed in several more patients and were considered as part of the clinical manifestations of the disease. As the scope and etiology of the epidemic became apparent, on September 30, 1976, 4 weeks after the index case was diagnosed, the YMH was closed. By then, 11 of the 17 of the hospital staff had contracted the disease and had died. An investigation of the outpatient facilities at the hospital revealed that the syringes and needles used for parenteral injections were apparently not sterilized between patients but, rather, rinsed in a pan of water.12

On October 13 and 14, 3 overseas laboratories isolated from infected individuals a virus morphologically similar to, but immunologically distinct from, the Marburg virus, the causative agent of Marburg hemorrhagic viral fever.12 On October 18, 1976, an international commission formed by Zaire’s Minister of Health convened and developed a plan to search house-to-house in >500 villages in the region to find individuals who had the disease; 55 villages had serologically confirmed cases of Ebola virus disease. The WHO estimated that approximately 5% of individuals who came in contact with an infected patient became infected, but approximately 20% of close contacts, those who slept or lived in the same room as a patient, became infected. Three hundred eighteen cases ultimately were identified, of whom 280 died (88% mortality); men and women of all ages were affected though the greatest incidence was in women 17 to 31 years of age. In these women, there was a correlation between the development of the disease and attendance at the obstetric clinic at YMH where some had received injections. The typical incubation period was 1 week, as was the duration of the disease in the 38 survivors.12

The epidemic was brought under control by closing the YMH and isolating individuals with the disease in their village. In some circumstances, patients were treated in facilities where they were isolated from other patients. Staff providing their care exercised stringent infection control measures. In 1 situation, the 3 staff providing care were themselves quarantined. Health care staff wore high-efficiency respirators, goggles, and disposable clothing. Contaminated materials, such as clothing, utensils, excreta, etc., were either burned or decontaminated by boiling or applying 2% hypochlorite (household bleach is approximately 5% sodium hypochlorite). Cadavers were wrapped in shrouds soaked in formalin or phenol and buried deeply.12

In 1989, a third species of Ebola virus, Reston ebolavirus, was isolated in cynomologus monkeys (Macaca fascicularis) imported from the Philippine Islands to Reston, Virginia, where they were intended to be used for research purposes.13 No humans were infected and, to date, there have been no infections of humans by a Reston ebolavirus. Further research demonstrated that swine are the natural host for the virus in the Philippines.14

In 1994, a virus from a fourth species was isolated, the Taï Forest ebolavirus, isolated from an ethnologist who presumably contracted Ebola virus disease while conducting an autopsy on a chimpanzee that had been found dead in the Parc National de Taï in Côte d’Ivoire.15 She survived but required a 2-week hospitalization. The fifth species, Bundibugyo ebolavirus, was discovered in Uganda in 2007. The Bundibugyo ebolavirus spawned an epidemic in which 116 people were infected, 30 of whom died (mortality rate 26%).16 There have been >20 epidemics of Ebola virus disease since 1976, almost all caused by Zaire ebolavirus and Sudan ebolavirus (Table 3).

Table 3

Table 3

Since the initial discovery of Ebola viruses, there has been extensive work to identify their natural reservoirs. Initially, this work focused on arthropods and terrestrial rodents and their ticks, but extensive investigations found no evidence that these animals carried the virus. Nonhuman primates also can be infected and develop a disease similar to humans with equally high mortality rates; however, they are clearly not a reservoir for the virus because the disease has such high lethality in nonhuman primates. Nevertheless, nonhuman primates can transmit the virus to humans.17 Likewise, dogs and pigs can be infected with Ebola virus, but they do not serve as a host.18 Several people have developed Ebola virus disease after exposure to bats.19 On the basis of that observation, it was demonstrated that fruit bats of the Pteropodidae family are indeed a reservoir for Ebola virus and, as of this writing, bats are the only known reservoir.20

Ebola virus antibodies have been identified in 3 species of bats in Central Africa21 and 4 species in West Africa.22 Using these and other data, Pigott et al.23 estimate that there are 23 countries in West and Central Africa where conditions support or would support colonies of fruit bats that could carry the disease. Transmission of Ebola virus from bats to humans must be uncommon because the potential reservoir of Ebola virus is huge.

The current model for humans acquiring Ebola virus is through contact with, or consumption of, bushmeat (from animals hunted for food). Specifically, someone could become infected while handling or preparing bats for consumption. Anyone consuming meat from bats containing live virus could become infected.24 However, any food contaminated by droppings from infected bats or any contact with infected bat droppings also could be a source of infection.25 One man became infected while spelunking in a cave with many bats but without any direct contact with the bats.26 A second mechanism for acquisition of Ebola virus is through infected primates, whether nonhuman or human (Fig. 4).27,28

Figure 4

Figure 4

The index case for the current epidemic is thought to have been a child in Guinea who had contact with a bat. Guinea had not had a previously recognized case of Ebola virus disease and is 1700 miles from Gabon, the closest country in which epidemics of Ebola virus disease had previously occurred. The specific strains of Zaire ebolavirus responsible for the current pandemic appear to have diverged from central African lineages of Zaire ebolavirus around 2004.29

The pandemic began in Guinea in December 2013 and spread through human-to-human contact to several other countries in West Africa. Mechanisms to control Ebola virus disease that had been learned in central African countries (Congo, Sudan, and Gabon) during the previous 4 decades were not put in place where Ebola virus disease was now spreading. These countries in West Africa are among the world’s poorest nations and rank among the highest nations for maternal mortality and the lowest for human development as measured by the WHO and the United Nations.30,31 They have very limited resources to deal with such a challenge. The challenges were increased further by the fact that Ebola virus disease rapidly spread to urban settings, where it was more difficult to quarantine patients and to trace contacts than in the countryside.

The epidemics also were spread because of poverty and ignorance. Several times, local populations, afraid that the disease was spread by health care workers, attacked them32 and in 1 case killed 8 of them.c In addition, families were fearful of efforts to quarantine patients and hid affected family member patients from health care workers. Barriers created by poverty, illiteracy, and distrust impaired efforts to contain the disease.33 Individuals in these communities continued handling symptomatic patients without barrier protection, and if these individuals died, customary funereal practices, which exposed additional persons to the virus, were followed.34 The ease of travel within African countries and the ease of international travel, as indicated by the patient from Liberia who flew to Dallas, Texas, transformed the epidemic into a pandemic that has spread to 3 continents.

Ebola virus is spread via bodily fluids and direct patient contact. Ebola virus disease is not contagious until infected patients become symptomatic. At that time, all body fluids, including blood, urine, emesis, stool and semen, contain the virus.35 A previously healthy individual might contract the disease if given a parenteral injection, as occurred in Zaire during the 1976 epidemic, or through secretions from the patient deposited on mucous membranes in the mouth or nose, on the conjunctiva, or through lacerations or skin abrasions. There has not been a documented human case that has contracted the disease via an aerosol. There are studies that show that nonhuman primates can be infected if Ebola virus is aerosolized by mechanical means and delivered through a nebulizer.36,37 In 1 study, 3 nonhuman primates who were in a biocontainment facility developed Ebola virus disease, even though they had no contact with other animals that had Ebola virus disease.38 The investigators speculated that it could have been through aerosolized particles but could not exclude the fact that oral secretions from an infected animal transmitted Ebola virus to another animal via its conjunctiva, mouth, or nose. However, in a recent report of a study conducted in a biosafety level-4 laboratory and designed to repeat this former study and its results, investigators found no evidence of aerosol transmission between nonhuman primates.39

In previous epidemics, some patients do not recall having direct contact with another patient with the disease.40 This does not exclude the possibility that these individuals could have acquired the virus through contact with tables, chairs, or articles in a patient’s room. Ebola virus has been found in alveoli of infected patients41 (Fig. 5). Despite the lack of scientific evidence, there is justifiable concern about aerosolized Ebola virus transmission.42

Figure 5

Figure 5

The role of the environment in the transmission of Ebola virus disease has not been fully elucidated. Under ideal conditions, Ebola virus remains viable on solid surfaces for several days.43,44 However, in another study in patients’ rooms, no virus was recovered from 33 sites that were not visibly bloody.35 There is no epidemiologic evidence of Ebola virus transmission via either the environment or fomites that could become contaminated during patient care (e.g., bed rails, door knobs, laundry). However, given the apparently low infectious dose, potential of high virus titers in the blood of ill patients, and disease severity, the highest levels of precaution are required. We need not wait for scientific proof that the virus can aerosolize or that fomites can be infective to enact appropriate precautions.45 The risks are too high, and we have limited ability to conduct rigorous studies on Ebola virus and on patients with Ebola virus disease.

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Ebola virus is most commonly transmitted when secretions from an infected patient come in contact with mucosa or conjunctiva or via percutaneous injury (e.g., a laceration or abrasion). There are no human data, but data from cynomologus monkeys show that an IM injection of as few as 10 plaque-forming units (each plaque-forming unit is assumed to represent 1 virion) results in lethal Ebola virus disease within 8 to 12 days of receiving the injection. Increasing the IM dose to 1000 plaque-forming units resulted in death within 5 to 8 days.46,47

Ebola virus replication requires attachment to a cell’s membrane, binding to specific cell receptors, and fusion with the cell’s membrane. The virion’s glycoprotein outer capsule is responsible for the attachment of the virus to the cell (Fig. 6).48,49

Figure 6

Figure 6

Several molecules have been proposed that function either as a receptor on a cell’s surface or as a mediator to facilitate viral entry into a cell, including C-type lectins, tyrosine kinase receptors, β1 integrin receptors, and Niemann Pick C1 proteins.48,50–52 Takada et al.53 have argued that, based on Ebola virus’s pantropism, the virus likely uses several different C-type lectins to gain entry into a variety of cells. Because of the virus’s marked selectivity for specific cells, some of the proposed receptors are unique to those cells (e.g., dendritic cell−specific intercellular adhesion molecule-3-grabbing nonintegrin) or human macrophage galactose- and N-acetylgalactosamine-specific C-type lectin).54–57 There also has been speculation that Ebola virus does not fuse to a cell’s membrane58 but rather activates the cell’s endocytic mechanisms, acting as a “Trojan horse” to gain entry into the cell’s cytoplasm. However, the most recent evidence suggests that the virus fuses to the cell membrane through glycoprotein 2, which can undergo conformational changes between an alpha helix and a beta layer to insert itself into the lipid bilayer that comprises the cell membrane.59

Once Ebola virus gains access to the interior of the cell, viral RNA and 7 proteins including MP, VP35, VP30, glycoprotein, and L are released into the cell’s cytoplasm.10 Glycoprotein makes up the virus’s outer coat and is involved in the binding of virus to cell surface receptors.48 The L protein is an RNA polymerase that translates Ebola virus’s negative-sense RNA into positive-sense messenger RNA from which Ebola virus’s structural proteins are generated.60 In addition, because the RNA is a copy of the negative-sense Ebola virus RNA, it serves as a template for replication of Ebola virus’s RNA. The structural proteins and genomes congregate in the cytoplasm near the cell membrane, where they reassemble into new virions, after which they are released by the cell.58,61

Unique to filoviruses is their predilection for dendritic cells62 and macrophages.53 This may reflect prevalence of these cell types in mucosa, the most frequent point of entry in primates. Alternatively, Ebola virus may have adapted itself to enter an organism through its mucosa to selectively knock out these 2 cell types, both vitally important in acquired and innate immunity.63 Their early infection would be a very adaptive mechanism for inhibiting the organism’s immune system while allowing dissemination of the virus throughout the organism. Infected monocytes spread the virus from the point of entry through the lymphatic system to regional lymph nodes and via the blood to hepatic and splenic cells, where the virus continues to rapidly replicate. In the few autopsies that have been performed, livers had widespread hepatic necrosis with very little inflammation, underscoring the virus’s ability to inhibit the organism’s immune system.41,55 Infiltration of plasma cells into lymphatic tissue with corresponding loss of lymphocytes also has been seen on these postmortem examinations. Ebola virus released into blood from hepatic and lymphatic cells subsequently invades the dendritic cells and macrophages of other tissues. Destruction of these macrophages and dendritic cells renders an organism incapable of mounting an adequate immune response to Ebola virus. The effectiveness of this strategy is apparent on histologic examination of infected tissue. Typically, minimal inflammation is observed, despite the tissue having a high viral titer and evidence of the necrosis throughout the tissue.55 Electron microscopic studies confirm an abundance of viral particles, antigens, and viral RNA in areas of necrosis, with few monocytes, macrophages, and lymphocytes normally seen as part of the inflammatory response.64

Figure 7

Figure 7

In the final stages of the Ebola virus disease, widespread infection of multiple organs results in a massive release of cytokines (e.g., tumor necrosis factor-α, interleukins, nitric oxide radicals, etc).65,66 The resultant cytokine storm is manifested by systemic capillary leakage, decreased left ventricular filling pressure, hypotension, and shock (Fig. 7). Death occurs as a result of circulatory shock or, more commonly, multisystem organ dysfunction.67 In survivors, the viremia clears over several days. Nonsurvivors have a marked viremia, leukocytosis (primarily neutrophils), thrombocytopenia, lymphocytopenia, and coagulopathy. The latter is due to a number of factors, including a decrease in coagulation factors as a result of the liver damage, thrombocytopenia due to consumption and underproduction in the bone marrow, and a consumptive coagulopathy initiated by the release of tissue factor by infected macrophages.68 The net result is DIC in patients with the heaviest viral loads.

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The incubation period for Ebola virus disease is from 2 to 21 days, with shorter incubation periods correlating with exposure to a larger viral load. Viremia correlates with the abrupt onset of symptoms and signs of the disease (Fig. 8). The WHO and the Centers for Disease Control and Prevention have established criteria for making a diagnosis of Ebola virus disease that include the sudden onset of high fever and at least 3 of the following: headache, vomiting, loss of appetite, diarrhea, lethargy, stomach pain, aching muscles or joints, dysphagia, dyspnea, or hiccupping. The diagnosis is only confirmed with positive serology for Ebola virus.

Figure 8

Figure 8

Multiple serologic tests have been used to confirm the diagnosis of Ebola virus disease, with reverse- transcriptase polymerase chain reaction assay,69 antibody-capture enzyme-linked immunosorbent assay,55 and electron microscopy70 being the most widely used. Although these technologies are widely available, because of the associated biohazards, only a few laboratories in the world can safely perform them. These tests are performed in a biosafety level-4 facility because the viruses are highly virulent, could potentially be transmitted via an aerosol, and have a high mortality rate. The equipment used for the testing is not portable, and the tests take time to complete. The WHO has released a request for proposals for a portable device or devices that would not require a biosafety level-4 facility but could test for Ebola virus in <3 hours with a high degree of specificity and selectivity.71 Such a device is necessary not only to more quickly identify individuals requiring isolation but also to identify those individuals with similar symptoms who do not have the disease and whose care is currently being compromised because of concern about possible Ebola virus disease and contagion.

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Not only are there no known treatments for Ebola virus disease, but very little is known about the mechanisms by which patients develop shock and DIC. The epidemics that have occurred during the past 4 decades have been in low-income countries with limited health care resources. Most patients do not have simple laboratory tests, such as a complete blood cell count, and more costly tests, such as a coagulation panel or cardiac output measurement, are rare. In addition, tests must be performed in a biosafety level-4 laboratory.

What we know has been learned from past epidemics and studies in nonhuman primates. Treatment is supportive. Dehydration is very common, so rehydration should be attempted with an oral balanced electrolyte solution. If the patient cannot maintain fluid balance because of gastrointestinal illness, IV crystalloid fluids should be administered. Hypoxia is reported to occur with Ebola virus disease,46,47 but during the current epidemic, it is not as common as one might expect (personal [written] communication, Robert Fowler, MDCM, World Health Organization, June, 2014) unless the patient develops multisystem organ dysfunction.

There are no predictors of survival. However, as was observed in the nonhuman primate studies, the greater the viral exposure, the shorter the incubation period, and the greater likelihood of death. Therefore, anyone who develops symptoms within 3 to 5 days of contact with an infected patient will likely have a worse outcome than someone who becomes symptomatic after many days.

Encephalitis has not been reported to occur as a complication with Ebola virus disease. Brain examinations at necropsy have confirmed this finding.41

In other viral hemorrhagic diseases, circulatory collapse is thought to be secondary to capillary leakage, decreasing intravascular volume, left ventricular end-diastolic pressure, and cardiac output.72 Although no specific observations support this recommendation in Ebola virus disease, the impression of clinicians in the field is that the hypotension responds to intravascular volume, unlike vasodilatory shock as seen in sepsis, and hemorrhagic shock as observed in DIC (personal communication: Robert Fowler, MDCM, WHO).

For reasons already discussed, there is little known about the management of DIC in patients with Ebola virus disease. DIC is assumed to be similar to that seen in other conditions, with the same laboratory manifestations. However, no reports from the current pandemic confirm this assumption. The DIC, although of interest, is not the reason patients die per se. Therefore, scarce resources are not being used to further characterize or treat individuals with DIC. To limit the degree of laboratory testing when patients do require transfusion, universal donor blood typically is administered. There has been discussion of the use of tranexamic acid to treat the fibrinolysis, but there are no reports of this having been tried.

The treatment of Ebola virus disease has been hampered because Ebola virus encodes 2 glycoproteins, the first is a membrane glycoprotein present in the viral membrane that mediates viral attachment and entry into host cells and the second is a secreted, nonstructural glycoprotein. The latter elicits host non-neutralizing antibodies that cross react with glycoprotein and therefore may prevent effective neutralization of the virus.73

Many people have survived Ebola virus disease. Their convalescent serum has been administered to others who were acutely ill with Ebola virus disease with anecdotal success.74 Convalescent serum therapy is more likely to be used in high-income countries where patients with Ebola virus disease have received care.

Another promising therapy is with monoclonal antibodies. These have been shown to reverse infection in nonhuman primates and to cure infected animals after symptoms and circulating Ebola virus are present.75 A combination of monoclonal antibodies (ZMapp), derived from 2 previous experiments, rescued 100% of rhesus macaques when given 5 days postchallenge, even in the presence of advanced disease.76 As of November 2014, ZMapp has been administered to 7 patients with the disease on a case-by-case basis under a compassionate use protocol, and additional studies of it and several other treatments and vaccines are under way.77

Other therapies are being investigated to treat Ebola virus disease, including the inhibition of membrane fusion by the virus (T-20 Enfuvirtide), transcription/replication inhibitors, nucleoside analogs, antisense oligonucleotides, small-interfering RNAs, maturation inhibitors to include furin inhibitors and budding inhibitors, and modulation of the cytokine storm by a variety of cytokine inhibitors.67

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Missair et al.45 have presented information on how anesthesiologists should provide care to patients with Ebola virus disease. The current pandemic will only be brought under control with the use of the same techniques and methods that have worked in past epidemics of Ebola virus disease: early diagnosis (so that patients can be more quickly isolated), contact tracing to identify at-risk individuals and limit their contacts, patient isolation, and strict (and better) infection control procedures.

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The current Ebola virus disease pandemic has lasted longer, affected more individuals, killed more patients, and created more social havoc than all previous Ebola virus disease epidemics combined. However, to put the current pandemic in context, viral hemorrhagic fevers in toto affect >100 million and kill 60,000 annually.78 Ebola virus disease has caused so much disruption because so little is known about it because of its high mortality and because of its clinical manifestations. However, the current pandemic has not occurred because Ebola virus has mutated but, rather, because a lack of information (avoidance of bats and infected nonhuman primates), inadequate public health practices (protocols for isolation and implementations of quarantines and unsafe burial practices), ease of travel, insufficient infection control (the nurse in Spain who contracted Ebola virus disease was reported in the media to have “touched” her face with her gloved hand after caring for a patient with Ebola virus disease), and poor health care education (not following established protocols for donning and removing PPE). On the basis of past experience, it is likely that 1 year from now nothing will have changed. However, on the basis of what we have learned, we as anesthesiologists should take the necessary steps now to better prepare and educate ourselves so that we can protect our families from the sequelae of such events and provide effective treatment for those to whom we will provide care during this and subsequent epidemics.

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Name: Michael J. Murray, MD, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Michael J. Murray approved the final manuscript.

This manuscript was handled by: Steven L. Shafer, MD.

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a Available at: Accessed May 16, 2015.
Cited Here...

b Available at: Accessed May 16, 2015.
Cited Here...

c Samb S, Felix B, Pomeroy R, Wills K. Eight bodies found after attack on Guinea Ebola education team. Thomson Reuters, 2014. Available at:
Cited Here...

d Verbatim caption. Available at: Accessed May 16, 2015.

e Verbatim caption. Available at: Accessed May 16, 2015.

f Verbatim caption. Available at: Accessed May 16, 2015.

g Available at: care-workers.pptx. Accessed May 16, 2015.

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1. World Health Organization. EVD in Spain. 2014
2. World Health Organization. Determining End of an Outbreak. 2014
3. Centers for Disease Control. Cases of Ebola Diagnosed in the United States. 2014
4. WHO Ebola Response Team. . Ebola virus disease in West Africa—the first 9 months of the epidemic and forward projections. N Engl J Med. 2014;371:1481–95
5. World Health Organization. EVD: October 31 Update. 2014
6. Adams MJ, Lefkowitz EJ, King AM, Carstens EB. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2014). Arch Virol. 2014;159:2831–41
7. Taylor DJ, Leach RW, Bruenn J. Filoviruses are ancient and integrated into mammalian genomes. BMC Evol Biol. 2010;10:193
8. Suzuki Y, Gojobori T. The origin and evolution of Ebola and Marburg viruses. Mol Biol Evol. 1997;14:800–6
9. Balter M. Emerging diseases. On the trail of Ebola and Marburg viruses. Science. 2000;290:923–5
10. Kiley MP, Regnery RL, Johnson KM. Ebola virus: identification of virion structural proteins. J Gen Virol. 1980;49:333–41
11. Ebola haemorrhagic fever in Sudan, 1976. . Report of a WHO/International Study Team. Bull World Health Organ. 1978;56:247–70
12. . Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ. 1978;56:271–93
13. Jahrling PB, Geisbert TW, Dalgard DW, Johnson ED, Ksiazek TG, Hall WC, Peters CJ. Preliminary report: isolation of Ebola virus from monkeys imported to USA. Lancet. 1990;335:502–5
14. Barrette RW, Metwally SA, Rowland JM, Xu L, Zaki SR, Nichol ST, Rollin PE, Towner JS, Shieh WJ, Batten B, Sealy TK, Carrillo C, Moran KE, Bracht AJ, Mayr GA, Sirios-Cruz M, Catbagan DP, Lautner EA, Ksiazek TG, White WR, McIntosh MT. Discovery of swine as a host for the Reston ebolavirus. Science. 2009;325:204–6
15. Le Guenno B, Formenty P, Formentry P, Wyers M, Gounon P, Walker F, Boesch C. Isolation and partial characterisation of a new strain of Ebola virus. Lancet. 1995;345:1271–4
16. Towner JS, Sealy TK, Khristova ML, Albariño CG, Conlan S, Reeder SA, Quan PL, Lipkin WI, Downing R, Tappero JW, Okware S, Lutwama J, Bakamutumaho B, Kayiwa J, Comer JA, Rollin PE, Ksiazek TG, Nichol ST. Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog. 2008;4:e1000212
17. Walsh PD, Abernethy KA, Bermejo M, Beyers R, De Wachter P, Akou ME, Huijbregts B, Mambounga DI, Toham AK, Kilbourn AM, Lahm SA, Latour S, Maisels F, Mbina C, Mihindou Y, Obiang SN, Effa EN, Starkey MP, Telfer P, Thibault M, Tutin CE, White LJ, Wilkie DS. Catastrophic ape decline in western equatorial Africa. Nature. 2003;422:611–4
18. Weingartl HM, Nfon C, Kobinger G. Review of Ebola virus infections in domestic animals. Dev Biol (Basel). 2013;135:211–8
19. Adjemian J, Farnon EC, Tschioko F, Wamala JF, Byaruhanga E, Bwire GS, Kansiime E, Kagirita A, Ahimbisibwe S, Katunguka F, Jeffs B, Lutwama JJ, Downing R, Tappero JW, Formenty P, Amman B, Manning C, Towner J, Nichol ST, Rollin PE. Outbreak of Marburg hemorrhagic fever among miners in Kamwenge and Ibanda Districts, Uganda, 2007. J Infect Dis. 2011;204(Suppl 3):S796–9
20. World Health Organization. EVD: Update. 2014
21. Leroy EM, Kumulungui B, Pourrut X, Rouquet P, Hassanin A, Yaba P, Délicat A, Paweska JT, Gonzalez JP, Swanepoel R. Fruit bats as reservoirs of Ebola virus. Nature. 2005;438:575–6
22. Hayman DT, Yu M, Crameri G, Wang LF, Suu-Ire R, Wood JL, Cunningham AA. Ebola virus antibodies in fruit bats, Ghana, West Africa. Emerg Infect Dis. 2012;18:1207–9
23. Pigott DM, Golding N, Mylne A, Huang Z, Henry AJ, Weiss DJ, Brady OJ, Kraemer MU, Smith DL, Moyes CL, Bhatt S, Gething PW, Horby PW, Bogoch II, Brownstein JS, Mekaru SR, Tatem AJ, Khan K, Hay SI. Mapping the zoonotic niche of Ebola virus disease in Africa. Elife. 2014;3:e04395
24. Leroy EM, Epelboin A, Mondonge V, Pourrut X, Gonzalez JP, Muyembe-Tamfum JJ, Formenty P. Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne Zoonotic Dis. 2009;9:723–8
25. Swanepoel R, Leman PA, Burt FJ, Zachariades NA, Braack LE, Ksiazek TG, Rollin PE, Zaki SR, Peters CJ. Experimental inoculation of plants and animals with Ebola virus. Emerg Infect Dis. 1996;2:321–5
26. Smith DH, Johnson BK, Isaacson M, Swanapoel R, Johnson KM, Killey M, Bagshawe A, Siongok T, Keruga WK. Marburg-virus disease in Kenya. Lancet. 1982;1:816–20
27. Formenty P, Hatz C, Le Guenno B, Stoll A, Rogenmoser P, Widmer A. Human infection due to Ebola virus, subtype Cote d’Ivoire: clinical and biologic presentation. J Infect Dis. 1999;179(Suppl 1):S48–53
28. Georges AJ, Leroy EM, Renaut AA, Benissan CT, Nabias RJ, Ngoc MT, Obiang PI, Lepage JP, Bertherat EJ, Benoni DD, Wickings EJ, Amblard JP, Lansoud-Soukate JM, Milleliri JM, Baize S, Georges-Courbot MC. Ebola hemorrhagic fever outbreaks in Gabon, 1994–1997: epidemiologic and health control issues. J Infec Dis. 1999;179(Suppl 1):S65–75
29. Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut A, Garry RF, Khan SH, Sabeti PC. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014;345:1369–72
30. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, Gonzalez-Medina D, Barber R, Huynh C, Dicker D, Templin T, Wolock TM, Ozgoren AA, Abd-Allah F, Abera SF, Abubakar I, Achoki T, Adelekan A, Ademi Z, Adou AK, Adsuar JC, Agardh EE, Akena D, Alasfoor D, Alemu ZA, Alfonso-Cristancho R, Alhabib S, Ali R, Al Kahbouri MJ, Alla F, Allen PJ, AlMazroa MA, Alsharif U, Alvarez E, Alvis-Guzmán N, Amankwaa AA, Amare AT, Amini H, Ammar W, Antonio CA, Anwari P, Arnlöv J, Arsenijevic VS, Artaman A, Asad MM, Asghar RJ, Assadi R, Atkins LS, Badawi A, Balakrishnan K, Basu A, Basu S, Beardsley J, Bedi N, Bekele T, Bell ML, Bernabe E, Beyene TJ, Bhutta Z, Bin Abdulhak A, Blore JD, Basara BB, Bose D, Breitborde N, Cárdenas R, Castañeda-Orjuela CA, Castro RE, Catalá-López F, Cavlin A, Chang JC, Che X, Christophi CA, Chugh SS, Cirillo M, Colquhoun SM, Cooper LT, Cooper C, da Costa Leite I, Dandona L, Dandona R, Davis A, Dayama A, Degenhardt L, De Leo D, del Pozo-Cruz B, Deribe K, Dessalegn M, deVeber GA, Dharmaratne SD, Dilmen U, Ding EL, Dorrington RE, Driscoll TR, Ermakov SP, Esteghamati A, Faraon EJ, Farzadfar F, Felicio MM, Fereshtehnejad SM, de Lima GM, Forouzanfar MH, França EB, Gaffikin L, Gambashidze K, Gankpé FG, Garcia AC, Geleijnse JM, Gibney KB, Giroud M, Glaser EL, Goginashvili K, Gona P, González-Castell D, Goto A, Gouda HN, Gugnani HC, Gupta R, Gupta R, Hafezi-Nejad N, Hamadeh RR, Hammami M, Hankey GJ, Harb HL, Havmoeller R, Hay SI, Pi IB, Hoek HW, Hosgood HD, Hoy DG, Husseini A, Idrisov BT, Innos K, Inoue M, Jacobsen KH, Jahangir E, Jee SH, Jensen PN, Jha V, Jiang G, Jonas JB, Juel K, Kabagambe EK, Kan H, Karam NE, Karch A, Karema CK, Kaul A, Kawakami N, Kazanjan K, Kazi DS, Kemp AH, Kengne AP, Kereselidze M, Khader YS, Khalifa SE, Khan EA, Khang YH, Knibbs L, Kokubo Y, Kosen S, Defo BK, Kulkarni C, Kulkarni VS, Kumar GA, Kumar K, Kumar RB, Kwan G, Lai T, Lalloo R, Lam H, Lansingh VC, Larsson A, Lee JT, Leigh J, Leinsalu M, Leung R, Li X, Li Y, Li Y, Liang J, Liang X, Lim SS, Lin HH, Lipshultz SE, Liu S, Liu Y, Lloyd BK, London SJ, Lotufo PA, Ma J, Ma S, Machado VM, Mainoo NK, Majdan M, Mapoma CC, Marcenes W, Marzan MB, Mason-Jones AJ, Mehndiratta MM, Mejia-Rodriguez F, Memish ZA, Mendoza W, Miller TR, Mills EJ, Mokdad AH, Mola GL, Monasta L, de la Cruz Monis J, Hernandez JC, Moore AR, Moradi-Lakeh M, Mori R, Mueller UO, Mukaigawara M, Naheed A, Naidoo KS, Nand D, Nangia V, Nash D, Nejjari C, Nelson RG, Neupane SP, Newton CR, Ng M, Nieuwenhuijsen MJ, Nisar MI, Nolte S, Norheim OF, Nyakarahuka L, Oh IH, Ohkubo T, Olusanya BO, Omer SB, Opio JN, Orisakwe OE, Pandian JD, Papachristou C, Park JH, Caicedo AJ, Patten SB, Paul VK, Pavlin BI, Pearce N, Pereira DM, Pesudovs K, Petzold M, Poenaru D, Polanczyk GV, Polinder S, Pope D, Pourmalek F, Qato D, Quistberg DA, Rafay A, Rahimi K, Rahimi-Movaghar V, ur Rahman S, Raju M, Rana SM, Refaat A, Ronfani L, Roy N, Pimienta TG, Sahraian MA, Salomon JA, Sampson U, Santos IS, Sawhney M, Sayinzoga F, Schneider IJ, Schumacher A, Schwebel DC, Seedat S, Sepanlou SG, Servan-Mori EE, Shakh-Nazarova M, Sheikhbahaei S, Shibuya K, Shin HH, Shiue I, Sigfusdottir ID, Silberberg DH, Silva AP, Singh JA, Skirbekk V, Sliwa K, Soshnikov SS, Sposato LA, Sreeramareddy CT, Stroumpoulis K, Sturua L, Sykes BL, Tabb KM, Talongwa RT, Tan F, Teixeira CM, Tenkorang EY, Terkawi AS, Thorne-Lyman AL, Tirschwell DL, Towbin JA, Tran BX, Tsilimbaris M, Uchendu US, Ukwaja KN, Undurraga EA, Uzun SB, Vallely AJ, van Gool CH, Vasankari TJ, Vavilala MS, Venketasubramanian N, Villalpando S, Violante FS, Vlassov VV, Vos T, Waller S, Wang H, Wang L, Wang X, Wang Y, Weichenthal S, Weiderpass E, Weintraub RG, Westerman R, Wilkinson JD, Woldeyohannes SM, Wong JQ, Wordofa MA, Xu G, Yang YC, Yano Y, Yentur GK, Yip P, Yonemoto N, Yoon SJ, Younis MZ, Yu C, Jin KY, El Sayed Zaki M, Zhao Y, Zheng Y, Zhou M, Zhu J, Zou XN, Lopez AD, Naghavi M, Murray CJ, Lozano R. Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:980–1004
31. Rahi M. Human development report 2010: Changes in parameters and perspectives. Indian J Public Health. 2011;55:272–5
32. . Ebola: protection of health workers on the front line. Lancet. 2014;384:470
33. Wiwanitkit V. Ebola, fear and preparedness. Epidemiol Health. 2014;36:e2014015
34. Nishiura H, Chowell G. Early transmission dynamics of Ebola virus disease (EVD), West Africa, March to August 2014. Euro Surveill. 2014;19:pii: 20907
35. Bausch DG, Towner JS, Dowell SF, Kaducu F, Lukwiya M, Sanchez A, Nichol ST, Ksiazek TG, Rollin PE. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007;196(Suppl 2):S142–7
36. Johnson E, Jaax N, White J, Jahrling P. Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus. Int J Exp Pathol. 1995;76:227–36
37. Reed DS, Lackemeyer MG, Garza NL, Sullivan LJ, Nichols DK. Aerosol exposure to Zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology. Microbes Infect. 2011;13:930–6
38. Jaax N, Jahrling P, Geisbert T, Geisbert J, Steele K, McKee K, Nagley D, Johnson E, Jaax G, Peters C. Transmission of Ebola virus (Zaire strain) to uninfected control monkeys in a biocontainment laboratory. Lancet. 1995;346:1669–71
39. Alimonti J, Leung A, Jones S, Gren J, Qiu X, Fernando L, Balcewich B, Wong G, Ströher U, Grolla A, Strong J, Kobinger G. Evaluation of transmission risks associated with in vivo replication of several high containment pathogens in a biosafety level 4 laboratory. Sci Rep. 2014;4:5824
40. Roels TH, Bloom AS, Buffington J, Muhungu GL, Mac Kenzie WR, Khan AS, Ndambi R, Noah DL, Rolka HR, Peters CJ, Ksiazek TG. Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: risk factors for patients without a reported exposure. J Infect Dis. 1999;179(Suppl 1):S92–7
41. Martines RB, Ng DL, Greer PW, Rollin PE, Zaki SR. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses. J Pathol. 2015;235:153–74
42. Leffel EK, Reed DS. Marburg and Ebola viruses as aerosol threats. Biosecur Bioterror. 2004;2:186–91
43. Sagripanti JL, Lytle CD. Sensitivity to ultraviolet radiation of Lassa, vaccinia, and Ebola viruses dried on surfaces. Arch Virol. 2011;156:489–94
44. Sagripanti JL, Rom AM, Holland LE. Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces. Arch Virol. 2010;155:2035–9
45. Missair A, Marino MJ, Vu CN, Gutierrez J, Missair A, Osman B, Gebhard RE. Anesthetic implications of ebola patient management: a review of the literature and policies. Anesth Analg. 2015;121:810–21
46. Geisbert TW, Pushko P, Anderson K, Smith J, Davis KJ, Jahrling PB. Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg Infect Dis. 2002;8:503–7
47. Sullivan NJ, Geisbert TW, Geisbert JB, Xu L, Yang ZY, Roederer M, Koup RA, Jahrling PB, Nabel GJ. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature. 2003;424:681–4
48. Takada A, Robison C, Goto H, Sanchez A, Murti KG, Whitt MA, Kawaoka Y. A system for functional analysis of Ebola virus glycoprotein. Proc Natl Acad Sci U S A. 1997;94:14764–9
49. Niknafs N, Kim D, Kim R, Diekhans M, Ryan M, Stenson PD, Cooper DN, Karchin R. MuPIT interactive: webserver for mapping variant positions to annotated, interactive 3D structures. Hum Genet. 2013;132:1235–43
50. Takada A, Watanabe S, Ito H, Okazaki K, Kida H, Kawaoka Y. Downregulation of beta1 integrins by Ebola virus glycoprotein: implication for virus entry. Virology. 2000;278:20–6
51. Alvarez CP, Lasala F, Carrillo J, Muñiz O, Corbí AL, Delgado R. C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol. 2002;76:6841–4
52. Fisher-Hoch SP, Platt GS, Lloyd G, Simpson DI, Neild GH, Barrett AJ. Haematological and biochemical monitoring of Ebola infection in rhesus monkeys: implications for patient management. Lancet. 1983;2:1055–8
53. Takada A, Fujioka K, Tsuiji M, Morikawa A, Higashi N, Ebihara H, Kobasa D, Feldmann H, Irimura T, Kawaoka Y. Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol. 2004;78:2943–7
54. Baskerville A, Fisher-Hoch SP, Neild GH, Dowsett AB. Ultrastructural pathology of experimental Ebola haemorrhagic fever virus infection. J Pathol. 1985;147:199–209
55. Zaki SR, Goldsmith CS. Pathologic features of filovirus infections in humans. Curr Top Microbiol Immunol. 1999;235:97–116
56. Lin G, Simmons G, Pöhlmann S, Baribaud F, Ni H, Leslie GJ, Haggarty BS, Bates P, Weissman D, Hoxie JA, Doms RW. Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J Virol. 2003;77:1337–46
57. Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F, Whitbeck JC, Burke E, Buchmeier MJ, Soilleux EJ, Riley JL, Doms RW, Bates P, Pöhlmann S. DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology. 2003;305:115–23
58. Geisbert TW, Jahrling PB. Differentiation of filoviruses by electron microscopy. Virus Res. 1995;39:129–50
59. Agopian A, Castano S. Structure and orientation study of Ebola fusion peptide inserted in lipid membrane models. Biochim Biophys Acta. 2014;1838:117–26
60. Trunschke M, Conrad D, Enterlein S, Olejnik J, Brauburger K, Mühlberger E. The L-VP35 and L-L interaction domains reside in the amino terminus of the Ebola virus L protein and are potential targets for antivirals. Virology. 2013;441:135–45
61. Lu J, Qu Y, Liu Y, Jambusaria R, Han Z, Ruthel G, Freedman BD, Harty RN. Host IQGAP1 and Ebola virus VP40 interactions facilitate virus-like particle egress. J Virol. 2013;87:7777–80
62. Mahanty S, Hutchinson K, Agarwal S, McRae M, Rollin PE, Pulendran B. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J Immunol. 2003;170:2797–801
63. Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15:74–80
64. Goldsmith CS, Miller SE. Modern uses of electron microscopy for detection of viruses. Clin Microbiol Rev. 2009;22:552–63
65. Baize S, Leroy EM, Georges AJ, Georges-Courbot MC, Capron M, Bedjabaga I, Lansoud-Soukate J, Mavoungou E. Inflammatory responses in Ebola virus-infected patients. Clin Exp Immunol. 2002;128:163–8
66. Hutchinson KL, Rollin PE. Cytokine and chemokine expression in humans infected with Sudan ebolavirus. J Infect Dis. 2007;196(Suppl 2):S357–63
67. Geisbert TW, Hensley LE. Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions. Expert Rev Mol Med. 2004;6:1–24
68. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis. 2003;188:1618–29
69. Towner JS, Rollin PE, Bausch DG, Sanchez A, Crary SM, Vincent M, Lee WF, Spiropoulou CF, Ksiazek TG, Lukwiya M, Kaducu F, Downing R, Nichol ST. 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. J Virol. 2004;78:4330–41
70. Pattyn S, van der Groen G, Jacob W, Piot P, Courteille G. Isolation of Marburg-like virus from a case of haemorrhagic fever in Zaire. Lancet. 1977;1:573–4
71. World Health Organization. Target Product Profile for a Rapid Simple Test for Zaïre ebolavirus. 2014
72. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998;11:480–96
73. Basler CF. A novel mechanism of immune evasion mediated by Ebola virus soluble glycoprotein. Expert Rev Anti Infect Ther. 2013;11:475–8
74. World Health Organization. Convalescent Therapy. 2014
75. Qiu X, Kobinger GP. Antibody therapy for Ebola: is the tide turning around? Hum Vaccin Immunother. 2014;10:964–7
76. Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514:47–53
77. Butler D. Ebola drug trials set to begin amid crisis. Nature. 2014;513:13–4
78. Zapata JC, Cox D, Salvato MS. The role of platelets in the pathogenesis of viral hemorrhagic fevers. PLoS Negl Trop Dis. 2014;8:e2858
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