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Ebola

Ebola: AKA Ebola Virus Disease (EVD) or Ebola Haemorrhagic Fever


Medical InBrief


by Rich Strongwater, MD and Harish Moorjani, MD

Ebola virus is named after the Ebola River in the Democratic Republic of Congo (formerly Zaire), where one of the first outbreaks of the infection occurred in 1976. Ebola virus disease is highly contagious; it is spread by direct contact with body fluids (eg, blood, saliva, mucous, vomit, feces, urine, semen, sweat, breast milk) and has a fatality rate as high as 50%. It is not spread by respiratory droplets or through the air by other means. Human-to-human transmission via semen may occur up to 2 months after initial infection.


The second most recent ebola virus outbreak 2014-2016 (28,000 people infected and 11,300 reported deaths) was larger than all of the previous epidemics combined. This epidemic started in Guinea in December 2013, and most of the cases originated from five West-African countries (ie, Guinea, Liberia, Nigeria, Senegal, and Sierra Leone).


During this outbreak, 11 patients with EVD were treated in the United States. Nine were patients brought back to the United States from West Africa. Two of these patients died. The two other patients were healthcare providers that had treated that first patient in the United States (who had contracted Ebola while traveling to West Africa). Thankfully both healthcare workers survived.

The most recent “Kivu” Ebola epidemic occurred in the Democratic Republic of the Congo (DRC) occurring between 2018 and 2020 resulted in 2299 deaths out of a total of 3481 reported cases

Causes and Risk Factors

Ebola virus disease in humans is caused by four of five viruses in the genus Ebolavirus--Bundibugyo virus, Sudan virus, Taï Forest virus, and Ebola virus (formerly Zaire Ebola virus). Ebola virus is the most dangerous and is responsible for the largest number of outbreaks. The fifth virus of this genus, Reston virus, most likely does not cause disease in humans, but has caused disease in other primates. These five viruses are closely related to Marburg viruses.


Ebola virus disease (ebola hemorrhagic fever, ebola) affects humans and other primates. Fruit bats are the natural reservoir for ebola and may directly infect a human or indirectly by contact with a living or dead animal.

Regarding fruit bats, conventional wisdom recommends the following:

  • Avoid touching dead fruit bats

  • Avoid eating the meat of a fruit bat already found dead

  • Avoid hunting a fruit bat that appears sick or is behaving strangely


Diagnostic Evaluation and Differential Diagnosis

Isolating the ebola virus by cell culture, detecting the viral RNA by polymerase chain reaction (PCR), and detecting proteins by enzyme-linked immunosorbent assay (ELISA) works best early and in those who have died from the disease. Detecting antibodies against the virus works best late in the disease and in those who recover.


During an outbreak, virus isolation is often not feasible. The most common diagnostic methods are real-time PCR and ELISA detection of proteins, which can be performed in field or mobile hospitals.

Routine blood testing in a patient with ebola virus disease may reveal a low platelet count, an initially decreased and then increased white blood cell count, elevated liver transaminase levels, and abnormal clotting often consistent with disseminated intravascular coagulation (eg, prolonged prothrombin time, partial thromboplastin time, bleeding time).


Differential diagnoses include malaria, cholera, and other viral hemorrhagic fevers.


Signs and Symptoms

Signs and symptoms of ebola virus infection start between 2 days to 3 weeks after exposure and include fever, sore throat, myalgias, and headache followed by abdominal pain, vomiting, diarrhea, rash, and decreased liver and renal function. Both internal and external hemorrhage occur. During the 2014-2016 outbreak the incubation period proved to be ~11 days, and 95% of the cases had symptom onset within 21 days after exposure. Death may occur 6-16 days after symptoms appear and is often due to shock from fluid loss or hemorrhage.


Treatment

As of February 2021 there are two drug treatments approved by the U.S. FDA to treat EVD caused by the Zaire ebolavirus. Inmazeb, approved in October 2020, is a combination of three monoclonal antibodies. The second drug, Ebanga, is a single monoclonal antibody and was approved in December 2020. Monoclonal antibodies (mAbs) are synthetic proteins that perform like natural human antibodies and inhibit viral replication after infection. Inmazeb and Ebanga bind to a glycoprotein on the surface of the ebola virus. This prevents the virus from entering the human host’s cells. Both of these treatments 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. Neither Inmazeb™ nor Ebanga™ has been evaluated for efficacy against species other than Zaire ebolavirus.

Adapted from Ebola Virus Disease. Therapeutics. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Viral Special Pathogens Branch (VSPB). February 26, 2021


Survival is also improved by early supportive care with rehydration and symptomatic supportive treatment. These measures may include management of pain, nausea, fever, and anxiety, as well as rehydration via the oral or intravenous route. Blood products such as packed red blood cells, platelets, or fresh frozen plasma may also be used. Other regulators of coagulation have also been tried; these include heparin to prevent disseminated intravascular coagulation and clotting factors to decrease bleeding. Antimalarial medications and antibiotics are often used before the diagnosis is confirmed, although there is no evidence to suggest such treatment is helpful.


Prevention


ERVEBO® (Ebola Zaire Vaccine, Live also known as V920, rVSVΔG-ZEBOV-GP or rVSV-ZEBOV) is approved by the U.S. Food and Drug Administration (FDA) for the prevention of disease caused by Ebola virus (formerlyZaire ebolavirus) in individuals 18 years of age and older as a single dose administration. ERVEBO is a replication-competent, live, attenuated recombinant vesicular stomatitis virus (rVSV) vaccine. It is not possible to become infected with 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.
Clinical efficacy of the vaccine was supported by a 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 developed EVD 10 or more days after vaccination.
The duration of protection conferred by an initial dose of ERVEBO is also unknown. A booster dose for people who have been previously vaccinated may extend the duration of protection for ERVEBO.

Adapted from Ebola Vaccine: Information about ERVEBO® Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Viral Special Pathogens Branch (VSPB). March 8, 2022


Clinical prevention trials in combined phase II and phase III using a recombinant inactivated vaccine are under way.


 

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Sources


Vossler, H., Akilimali, P., Pan, Y. et al. Analysis of individual-level data from 2018–2020 Ebola outbreak in Democratic Republic of the Congo. Sci Rep 12, 5534 (2022). https://doi.org/10.1038/s41598-022-09564-4

Ebola: What you need to know. Scientific American Web site. https://www.scientificamerican.com/report/ebola-what-you-need-to-know1/. Accessed March 4, 2018.


Sierra Leone trial to introduce a vaccine against ebola (STRIVE). Centers for Disease Control and Prevention Web site. https://www.cdc.gov/vhf/ebola/strive/qa.html. April 20, 2016. Accessed March 4, 2018.


Ebola hemorrhagic fever. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/vhf/ebola/symptoms/index.html. November 2, 2014. Accessed March 4, 2018.


Ebola virus disease WHO fact sheet on Ebola: key facts, definition, transmission, symptoms, diagnosis, treatment, prevention, WHO response. World Health Organization Web site. www.who.int/mediacentre/factsheets/fs103/en/ Accessed March 4, 2018.


Ebola virus and Marburg virus. Symptoms and causes. Mayo Clinic Web site. https://www.mayoclinic.org/diseases-conditions/ebola-virus/symptoms-causes/syc-20356258. November 7, 2017. Accessed March 4, 2018.


Choi MJ, Cossaboom CM, Whitesell AN, et al. Use of Ebola Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020. MMWR Recomm Rep 2021;70(No. RR-1):1–12. DOI: http://dx.doi.org/10.15585/mmwr.rr7001a1external iconexternal icon.


Malenfant JH, Joyce A, Choi MJ, et al. Use of Ebola Vaccine: Expansion of Recommendations of the Advisory Committee on Immunization Practices to Include Two Additional Populations—United States, 2021. MMWR Morb Mortal Wkly Rep 2022;71:290–292. DOI: http://dx.doi.org/10.15585/mmwr.mm7108a2external icon


Ebola Vaccine: Information about ERVEBO® Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Viral Special Pathogens Branch (VSPB). Page last reviewed: March 8, 2022


Ebola Virus Disease. Therapeutics. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Viral Special Pathogens Branch (VSPB). Page last reviewed: February 26, 2021


Chakraborty C. Therapeutics development for Ebola virus disease: A recent scenario. Epub Oct 2021; 60:208-215. PMID: 34464933 DOI: 10.1016/j.coph.2021.07.020


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