Ebola: Care, Recommendations, and
Protecting Practitioners

The recent epidemic of the Ebola virus in West Africa has caused great concern worldwide, given the reality that within just a few hours, people can travel from the most remote areas of the world to the most populous. This most recent outbreak is believed to have been first identified in Guinea in December 2013 and garnered increased attention in March 2014. The epidemic has now progressed to over 10,000 cases, nearly 5,000 deaths, and an average case-fatality rate of 55% (with 75% reported in Guinea). The image above depicts the country-specific areas of suspected and confirmed Ebola cases.^[1,2]

Image courtesy of the CDC.

The Ebola virus is one of at least 30 known viruses capable of causing viral hemorrhagic fever. Ebola is currently classified into 5 separate species: Sudan ebolavirus, Zaire ebolavirus, Tai Forest ebolavirus, Reston ebolavirus (disease in non-human primates), and Bundibugyo ebolavirus. The current outbreak of Ebola virus in West Africa involves Zaire ebolavirus. Filoviruses such as Ebola virus share a characteristic filamentous form, with a uniform diameter of approximately 80 nm but a highly variable length. Filaments may be straight, but they are often folded on themselves.^[3-5]

Images courtesy of Wikimedia Commons (left) and David S. Goodsell /RCSB.org (right).

After infection with the Ebola virus, human and nonhuman primates experience an early period of rapid viral multiplication that, in lethal cases, is associated with an ineffective immunologic response. Viral replication is accompanied by widespread and severe focal necrosis. The most severe necrosis occurs in the liver and is associated with the formation of Councilman-like bodies similar to those seen in yellow fever. In fatal infections, the host's tissues and blood contain large numbers of Ebola virions, and the tissues and body fluids are highly infectious. With the exception of the Reston strain, Ebola virus is associated with very high morbidity and mortality in patients who present with clinical illness, though these vary according to the causative species. The most highly lethal species is Zaire ebolavirus, which has been reported to have a mortality rate as high as 89%. Sudan ebolavirus also has high reported mortality, ranging from 41% to 65%.^[5,6]

Images courtesy of Science Photo Library (left) and NIAID (right).

The 2014 Ebola epidemic is the largest in history and has affected a number of countries in West Africa, primarily Guinea, Liberia, Sierra Leone, and Nigeria. There were a small number of cases reported in Nigeria and a single case reported in Senegal; however, these cases are considered to be contained, with no further spread in these countries. The outbreaks of Ebola in Senegal and Nigeria have been declared over because 42 days have passed since the last patient in isolation tested negative for Ebola.

Table adapted from the CDC.

Ebola, a zoonotic filovirus, is transmitted from animal to human populations. This epidemic may have been transmitted from a fruit bat reservoir. Direct human contact with infected fruit bats of the Pteropodidae family or with wild animals infected by bats triggers the human-to-human transmission of Ebola. Evidence in nonhuman primates indicates that Sudan ebolavirus and Zaire ebolavirus may be transmitted by contact with mucous membrane, conjunctiva, pharyngeal, and gastrointestinal surfaces; through small breaks in the skin; and, at least experimentally, by aerosol. A history of primary exposure usually involves travel to or work in an Ebola-endemic area, such as the Democratic Republic of the Congo, Sudan, Gabon, or Côte d'Ivoire.^[5,7,8]

Image courtesy of the CDC.

Ebola virus disease first appeared in 1976 in 2 simultaneous outbreaks, one in Nzara, Sudan, and the other in Yambuku, Democratic Republic of the Congo. The latter occurred in a village near the Ebola River, from which the disease takes its name. Based on genetic analysis, the current Ebola virus is 97% identical to the Zaire Ebola virus identified in recent (earlier in 2014) cases in Gabon and the Democratic Republic of the Congo. There have been more cases and deaths in this outbreak than in all previous outbreaks combined.^[9]

Infographic adapted by Johanna Campos from information from the CDC and Medscape.

Transmission of the Ebola virus occurs through direct contact with body fluids of the febrile, live infected patient and contact during the postmortem period. In patients who have Ebola virus infection, exposure to the virus may be either primary (involving presence in an Ebolavirus-endemic area) or secondary (involving human-to-human or primate-to-human transmission). The pathogenesis of Ebola comes from direct contact with mucosal membranes, a skin break, or parenteral exposure. When exposed parenterally, the incubation period appears to be shorter (6 days). Emesis, stool, sweat, urine, semen, CSF, breast milk, and saliva are capable of viral transmission. Physical findings depend on the stage of disease at the time of presentation. Studies have demonstrated that patients who die of Ebola viral infection do not develop a humoral immune response. However, in survivors, neutralizing antibody can be detected. It is likely that a broad humoral immune response can increase the likelihood of an infected patient surviving Ebola.^[5,10]

Images courtesy of Science Photo Library.

The lack of adequate personal protective equipment (PPE) and meticulous environmental cleansing remain challenges in resource-limited settings or those unaccustomed to high-level contact exposure. The Centers for Disease Control and Prevention (CDC) has issued guidance on PPE to be used by healthcare workers during management of patients with Ebola in US hospitals, including procedures for putting on (donning) and removing (doffing) PPE. Strict adherence to and appropriate resources for PPE and hand hygiene are essential for all clinicians serving in endemic areas or treating patients with known or suspected Ebola virus. For those returning to non-endemic locations after treating patients with Ebola in endemic areas, 21 days of daily monitoring is recommended by the CDC. During this ongoing monitoring period, there is no indication to isolate or quarantine asymptomatic individuals.^[11]

Images courtesy of Medscape.

According to the CDC principles, personal protective equipment (PPE) must be donned correctly in proper order before entry into the patient care area and should not be later modified while in the patient care area. Donning must be directly observed by a trained observer. Healthcare workers should perform frequent disinfection of gloved hands using an ABHR (alcohol-based hand rub). The removal of used PPE is a high-risk process that requires a structured procedure, a trained observer, and a designated area for removal to ensure protection. PPE must be removed slowly and deliberately in the correct sequence. Double gloving provides an extra layer of safety during direct patient care and during the PPE removal process.^[11]

Image courtesy of AP Images.

It is difficult to diagnose Ebola in a person who has been infected for only a few days, because the early symptoms such as fever are nonspecific and occur in more common diseases such as malaria and typhoid fever. However, if a person has the early symptoms of Ebola and has had exposure to the Ebola virus, the patient should be isolated and public health professionals notified. Commercial assays for detection of Ebola viral particles are still in development, making point-of-care testing for rapid detection unavailable at this time. Enzyme-linked immunosorbent assay (ELISA) and reverse-transcriptase polymerase-chain reaction (RT-PCR) are currently the most reliable methods to confirm disease and are available through the CDC.^[12,13]

Table adapted from the CDC (top). Images courtesy of Wikimedia Commons (bottom left, bottom right).

The maximum recorded persistence of Ebola virus RNA in the blood and other body fluids of convalescent Ebola patients varies by fluid type. In studies, Ebola virus RNA has been detected up to 101 days after symptom onset in semen; 33 days in vaginal swabs; 29 days in rectal samples; 23 days in urine; 22 days in conjunctival swabs; 21 days in blood; 15 days in breast milk; 8 days in saliva; and 6 days on skin. Airborne transmission of Ebola virus has not been demonstrated in humans. Most of the evidence regarding human-to-human transmission of Ebola virus is derived from investigations of previous Ebola outbreaks. Although the current Ebola epidemic in West Africa is unprecedented in scale, the clinical course of infection (ie, incubation period, duration of illness, case fatality rate) and the transmissibility of the virus (ie, estimations of the basic reproductive number) are similar to those in earlier Ebola outbreaks.^[14-19]

Table adapted from the CDC.

Although Ebola is only spread through direct contact with infected bodily secretions, significant fear in the general public remains. Much of the fear is propagated by the high mortality rate and modern globalization of travel. However, establishment of daily monitoring for those with contact to symptomatic Ebola patients or those at high risk of possible exposure is reasonable. Quarantine or confinement for asymptomatic individuals during a monitoring period is unfounded and should not be mandated. Media and local governmental education about the Ebola virus and actual methods of transmission are foundational to ensure appropriate concern and management.

Image courtesy of the CDC.

The onset of symptoms of Ebola virus typically occurs abruptly around 1 week post exposure but may be delayed up to 21 days. Symptoms of Ebola typically include fever, headache, myalgia, and malaise. Occasionally, an erythematous rash (maculopapular) of the face, neck, trunk, and arms develops by days 5-7. The virus migrates to lymph nodes, progressing to the liver, adrenal glands, and spleen. A cytokine inflammatory storm appears to be triggered, causing microvascular leakage, hepatocellular necrosis (leading to clotting derangements), and cellular death (apoptosis) leading to multisystem organ failure.^[5]

Image courtesy of Wikimedia Commons.

The illness progression of Ebola virus may include severe watery diarrhea, nausea, vomiting, abdominal pain, dyspnea, chest pain, and confusion. It is important to recognize that not all patients will have signs of hemorrhagic fever with bleeding from the mouth, eyes, ears, stool, internal organs, or skin. Severe illness progresses to signs of sepsis and multiorgan system failure. Survivors of Ebola tend to have less severe symptoms and progressive fever and then show clinical improvement after the first week of symptom onset. People who recover from Ebola infection may develop antibodies that last for at least 10 years.

Image courtesy of the CDC.

No FDA-approved vaccine or antiviral drug is yet available for Ebola. Contact isolation and supportive medical therapy are the mainstays of treatment for both Ebola and other viral hemorrhagic fevers. The following basic interventions, when used early, can significantly improve the chances of survival: (1) providing intravenous fluids and balancing electrolytes (body salts); (2) maintaining oxygen status and blood pressure; (3) providing blood products as needed; and (4) treating concurrent infections. In addition, dialysis may be needed in cases of associated renal failure. In patients with hypoproteinemia and third spacing from liver failure, albumin may be indicated.^[20]

Image courtesy of the CDC.

On arrival to the clinical setting/triage, the patients should be assessed for fever (subjective or ≥100.4°F / 38.0°C), and it should be determined whether the patient has symptoms of Ebola, such as headache, weakness, muscle pain, vomiting, diarrhea, abdominal pain, or hemorrhage. It also needs to be identified whether the patient has been exposed to the Ebola virus by having traveled to a country with Ebola or having had contact with an Ebola patient within 21 days before onset of symptoms. Upon initial assessment, the patient should be isolated in a single room with a private bathroom and the hallway door closed; standard, contact, and droplet precautions should be implemented; the hospital infection control program must be notified; and a report must be made to the health department.^[21]

Table adapted from the CDC.

Experimental treatments using monoclonal antibodies, such as ZMapp™, block Ebola (Zaire virus strain) from entering cells; however, this treatment remains in early stages of development and is not routinely available. ZMapp™, being developed by Mapp Biopharmaceutical Inc, has not yet been tested in humans for safety or effectiveness. It is composed of 3 humanized monoclonal antibodies recombinantly manufactured in a variety of tobacco called Nicotiana benthamiana. The antibodies bind to the protein of the Ebola virus. ZMapp™ is a collaboration of Mapp Biopharmaceutical, LeafBio, Defyrus, the US Government, and the Public Health Agency of Canada. ZMapp™ has shown efficacy in a monkey model of Ebola in studies conducted by the Public Health Agency of Canada. With no proven vaccine for Ebola and with experimental treatments in short supply or having run out altogether, the World Health Organization recently prioritized research on blood transfusions for patients with Ebola from blood of persons who have survived the disease. Although there are no data to prove conclusively that "convalescent transfusions" from Ebola virus survivors helps in the recovery of others with the disease, they have been used in some patients during this epidemic and were first used to treat Ebola in 1976.^[22-24]

Image courtesy of Wikimedia Commons.

The National Institute of Allergy and Infectious Diseases (NIAID), of the National Institutes of Health (NIH), recently announced that it is expediting phase 1 clinical trials of an Ebola vaccine. The phase 1 trial includes testing of a vaccine co-developed by the NIAID and GlaxoSmithKline and is evaluating the experimental vaccine's safety and ability to generate an immune system response in healthy adults. Another experimental Ebola vaccine is being developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corp. The NIH is also supporting the Crucell biopharmaceutical company in its development of an Ebola/Marburg vaccine, as well as Profectus Biosciences in its development of an Ebola vaccine.^[25]

Images courtesy of NIH (foreground) and Wikimedia Commons (background).

The challenges to ending the current Ebola epidemic are multifactorial and reach beyond the lack of robust personal protective equipment (PPE) availability. In endemic areas, ongoing public health education to increase layperson and community understanding of the illness and transmission risks is often met with skepticism because of unfounded rumors, local practices, and mistrust of healthcare workers. The World Health Organization and other organizations continue to work to quell these fears and have noted improved community participation in the awareness and prevention of high-risk exposure practices.

Image courtesy of CDC Global.