Ebola Disease Information for Clinicians in U.S. Healthcare Settings
Key Points
- Ebola disease 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 patients with confirmed or suspected Ebola.
- Gastrointestinal symptoms may develop after about four to five days, such as severe watery diarrhea, nausea, vomiting, and abdominal pain.
- Ebolaviruses enter a person through mucous membranes, breaks in the skin, or parenterally. Healthcare personnel must prevent contact or splashes with blood and body fluids, contaminated equipment, and soiled environmental surfaces.
- Travelers with possible ebolavirus exposure 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.
Patients with Ebola disease generally have an abrupt onset of fever and symptoms typically 8 to 10 days after exposure. Initial signs and symptoms are nonspecific and may include elevated body temperature or subjective fever, chills, myalgias, and malaise. These are known as “dry symptoms”. Due to these nonspecific symptoms, particularly early in the course of the disease, Ebola disease can be confused with other more common infectious diseases such as malaria. Malaria is the most common cause of acute undifferentiated fever after travel to sub-Saharan Africa and some other tropical areas. Malaria, especially P. falciprium, can progress rapidly. If malaria is considered for a suspect Ebola patient, follow the Guidance for Malaria Diagnosis in Patients with Suspect Ebolavirus Infection in the United States, as diagnostics should be done promptly and treatment instituted immediately if malaria is diagnosed. Typhoid fever, meningococcemia, and other bacterial infections (for example, pneumonia) also have similar nonspecific symptoms and can be confused with Ebola.
After four to five days, patients can progress from the initial nonspecific symptoms to gastrointestinal symptoms, or “wet symptoms”, like severe watery diarrhea, nausea, vomiting, and abdominal pain. Other symptoms, such as chest pain, shortness of breath, headache, or confusion, 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 of disease as petechiae, ecchymosis/bruising, or oozing from venipuncture sites, mucosal hemorrhage, or blood in stool or vomitus. In a recent outbreak, unexplained bleeding was reported in only 18% of patients, most often as 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 during the 2014–2016 West Africa outbreak 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.
Pathogenesis
Ebolaviruses enter a person through mucous membranes, breaks in the skin, or parenterally and infect 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. Ebolaviruses migrate from the initial infection site to regional lymph nodes and subsequently to the liver, spleen, and adrenal gland. Although not infected by an ebolavirus, lymphocytes undergo apoptosis resulting in decreased lymphocyte counts. Hepatocellular necrosis occurs and is associated with dysregulation of clotting factors and subsequent coagulopathy. Adrenocortical necrosis can be found and is associated with hypotension and impaired steroid synthesis. Ebolaviruses appear to trigger a release of pro-inflammatory cytokines with subsequent vascular leak and impairment of clotting ultimately resulting in multiorgan failure and shock.
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).
Learn more about Laboratory Testing.
Treatment
Therapeutics
There are currently two treatments approved by the U.S. Food and Drug Administration (FDA) to treat Ebola virus disease caused by Ebola virus (EBOV; species Zaire ebolavirus) in adult and pediatric patients. The first drug approved in October 2020, Inmazeb®, is a combination of three monoclonal antibodies. The second drug, Ebanga®, 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 surface of the virus 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 virus disease 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 viruses other than Ebola virus (species Zaire ebolavirus).
Supportive Care
Clinical management of Ebola disease 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 body fluids and clinical specimens as potentially infectious.
Vaccine*
The Ebola virus (EBOV; species 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 EBOV from the vaccine because the vaccine only contains a gene from EBOV, not the whole virus. Specifically, it contains a gene for the EBOV glycoprotein that replaces the gene for the native VSV glycoprotein.ERVEBO only provides protection against EBOV (species Zaire ebolavirus). There is not cross-protection against other ebolaviruses or marburgviruses.
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 EBOV (species Zaire ebolavirus).
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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