Ebola Virus Disease (EVD) Information for Clinicians in U.S. Healthcare Settings

Key Points

  • EVD can be confused with other more common infectious diseases such as malaria, typhoid fever, meningococcemia, and other bacterial infections. Follow CDC’s PPE guidance for confirmed Ebola patients.
  • Gastrointestinal symptoms may develop after about 5 days to develop symptoms such as severe watery diarrhea, nausea, vomiting, and abdominal pain.
  • Ebola virus enters the patient through mucous membranes, breaks in the skin, or parenterally. Healthcare personnel must prevent direct contact or splashes with blood and body fluids, contaminated equipment, and soiled environmental surfaces.
  • Travelers with possible exposure to Ebola virus may need public health monitoring and movement controls depending on the risk of exposure and clinical presentation. Clinicians should contact local or state health departments for more information.

Clinical Presentation and Course

Patients with EVD generally have an abrupt onset of fever and symptoms typically 8 to12 days after exposure (incubation period for current outbreak has a mean of approximately 9 to 11 days). Initial signs and symptoms are nonspecific and may include elevated body temperature or subjective fever, chills, myalgias, and malaise. Because of these nonspecific symptoms, particularly early in the course of the disease, EVD often can be confused with other more common infectious diseases such as malaria, typhoid fever, meningococcemia, and other bacterial infections (for example, pneumonia).

Patients can progress from the initial nonspecific symptoms after about 5 days to develop gastrointestinal symptoms such as severe watery diarrhea, nausea, vomiting, and abdominal pain. Other symptoms such as chest pain, shortness of breath, headache, or confusion also may develop. Patients often have conjunctival injection. Hiccups have been reported. Seizures may occur, and cerebral edema has been reported. Bleeding is not universally present but can manifest later in the course as petechiae, ecchymosis/bruising, or oozing from venipuncture sites and mucosal hemorrhage. Frank hemorrhage is less common. In the current outbreak, unexplained bleeding has been reported in only 18% of patients, most often blood in the stool (about 6%). Patients may develop a diffuse erythematous maculopapular rash by days 5 to 7 (usually involving the neck, trunk, and arms) that can desquamate. Pregnant women may experience spontaneous miscarriages. The most common signs and symptoms reported from West Africa during the current outbreak from symptom-onset to the time the case was detected include fever (87%), fatigue (76%), vomiting (68%), diarrhea (66%), and loss of appetite (65%).

Patients with fatal disease usually develop more severe clinical signs early during infection and die typically between days 6 and 16 of complications including multiorgan failure and septic shock (mean of 7.5 days from symptom onset to death during the 2014-2016 outbreak in West Africa). In nonfatal cases, patients may have fever for several days and improve, typically around day 6. Patients who survive can have a prolonged convalescence.

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Pathogenesis

Ebola virus enters the patient through mucous membranes, breaks in the skin, or parenterally and infects many cell types, including monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and epithelial cells. The incubation period may be related to the infection route (6 days for injection versus 10 days for contact). Ebola virus migrates from the initial infection site to regional lymph nodes and subsequently to the liver, spleen, and adrenal gland. Although not infected by Ebola virus, lymphocytes undergo apoptosis resulting in decreased lymphocyte counts. Hepatocellular necrosis occurs and is associated with dysregulation of clotting factors and subsequent coagulopathy. Adrenocortical necrosis also can be found and is associated with hypotension and impaired steroid synthesis. Ebola virus appears to trigger a release of pro-inflammatory cytokines with subsequent vascular leak and impairment of clotting ultimately resulting in multiorgan failure and shock.

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Laboratory Findings

Laboratory findings at admission may include leukopenia frequently with lymphopenia followed later by elevated neutrophils and a left shift. Platelet counts often are decreased in the 50,000 to 100,000 range. Amylase may be elevated, reflecting pancreatic involvement (inflammation/infection). Hepatic transaminases are elevated with aspartate aminotransferase (AST) exceeding alanine aminotransferase (ALT); these values may peak at more than 1,000 IU/L. Proteinuria may be present. Prothrombin (PT) and partial thromboplastin times (PTT) are prolonged and fibrin degradation products are elevated, consistent with disseminated intravascular coagulation (DIC).

For more information on laboratory testing, please see our Laboratory Testing website.

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Treatment

Therapeutics

There are currently two antiviral treatments approved by the U.S. Food and Drug Administration (FDA) to treat EVD caused by Ebola virus, species Zaire ebolavirus, in adult and pediatric patients. The first drug approved in October 2020, Inmazeb®external icon, is a combination of three monoclonal antibodies. The second drug, Ebanga®external icon, is a single monoclonal antibody and was approved in December 2020. Monoclonal antibodies (often abbreviated as mAbs) are produced in a lab or other manufacturing facility but act like natural antibodies to stop the virus from replicating after it has infected a person. These particular mAbs bind to a portion of the virus’s surface called the glycoprotein, which prevents the virus from entering the human cells.

Both treatments, along with two others, were evaluated in a randomized controlled trial during the 2018–2020 Ebola outbreak in the Democratic Republic of the Congo. Overall survival was much higher for patients receiving either of the two treatments that are now approved by the FDA. The efficacy of Inmazeb® and Ebanga® has not been established for species other than Zaire ebolavirus.

Supportive Care

Clinical management of EVD should focus on supportive care of complications, such as hypovolemia, electrolyte abnormalities, hematologic abnormalities, refractory shock, hypoxia, hemorrhage, septic shock, multiorgan failure, and DIC.

Recommended care includes volume repletion, maintenance of blood pressure (with vasopressors if needed), and maintenance of oxygenation, pain control, nutritional support, and treatment of secondary bacterial infections and pre-existing comorbidities. Large volumes of intravenous fluids are often required to correct dehydration due to diarrhea and vomiting. Some patients may develop profound third-spacing of fluids due to vascular leak. Some organizations suggest the addition of broad-spectrum antimicrobials, particularly in patients with evidence of septic shock. Infection prevention and control measures are a critical part of clinical management. Consider all bodily fluids and clinical specimens as potentially infectious.

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Vaccine*

The Ebola virus (Zaire ebolavirus) vaccine is a replication-competent, live, attenuated recombinant vesicular stomatitis virus (rVSV) vaccine. It is known as rVSVΔG-ZEBOV-GP Ebola vaccine (brand name Ervebo®) and manufactured by Merck. It is not possible to become infected with Zaire ebolavirus (EBOV) from the vaccine because the vaccine only contains a gene from the Ebola virus, not the whole virus. Specifically, it contains a gene for the EBOV glycoprotein that replaces the gene for the native VSV glycoprotein. Ervebo® does not provide protection against other species of Ebolavirus or Marburgvirus.

The U.S. Food and Drug Administration (FDA) approved the vaccine on December 19, 2019. On February 26, 2020, the Advisory Committee on Immunization Practices (ACIP) recommended pre-exposure vaccination with the vaccine for adults aged 18 years or older in the U.S. population who are at potential risk of exposure to the Ebola virus. This recommendation includes adults who are:

  • Responding or may respond to an outbreak of EVD,
  • Laboratorians or other staff working at biosafety-level 4 facilities in the United States, or
  • Healthcare personnel working at federally designated Ebola Treatment Centers in the United States.

Antibody measurements are often used as a surrogate test to predict when protection by a vaccine can be expected. Clinical trials have shown that the vaccine elicits rapid antibody response in 14 days after a single dose. Seroconversion in adults peaked between 28 and 35 days for most clinical trial subjects. Clinical efficacy of the vaccine was supported by a randomized cluster (ring) vaccination study during the 2014–2016 outbreak in Guinea. In this study, 3,775 people in close contact with diagnosed EVD cases (contacts) and their close contacts (contacts of contacts) received immediate vaccination. No one who was vaccinated immediately developed EVD 10 or more days after vaccination.

The correlate of protection, or the specific immune response to the Ebola vaccine that closely relates to protection against infection with EBOV, is unknown and still being studied.

The duration of protection by Ervebo® against EBOV is unknown. It is also not known whether it is effective when administered concurrently with antiviral medication, immune globulin, and/or blood or plasma transfusion.

Adverse effects following vaccination can occur. While typically mild, reported adverse effects include headache, feverishness, muscle pain, fatigue, joint pain, nausea, arthritis, rash, and abnormal sweating. Some vaccinated individuals may experience arthralgia and arthritis after vaccination. It is not possible to become infected with EBOV from the vaccine because the vaccine just contains a gene from the Ebola virus, not the whole virus. Specifically, it contains a gene for the EBOV glycoprotein that replaces the gene for the native VSV glycoprotein.

After receiving the vaccine, it is important to continue infection prevention precautions against Ebola (for example, wear PPE that covers clothing and skin and prevents any exposure of the eyes, nose, and mouth; wash hands; avoid contact with blood and body fluids) when interacting with Ebola patients or when in situations of possible exposure because the vaccine may not be 100% effective for everyone.

As a healthcare provider, you can request the vaccine for eligible patients. Learn more about Ervebo®.

*Disclaimer: The mention of any product names or non-United States Government entities on CDC Ebola websites is not meant to serve as an official endorsement of any such product or entity by the CDC, the Department of Health and Human Service, or the United States Government.

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