Ebola Virus Infection Treatment & Management

Updated: Jan 14, 2021
  • Author: John W King, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Approach Considerations

A safe and effective vaccine is an important tool to protect and prevent the introduction and spread of Ebola.

Ebola Zaire vaccine (rVSV-ZEBOV; V920; Merck) [26]  has been approved in the United States and Europe. This vaccine is genetically engineered to express a glycoprotein from Zaire ebolavirus to provoke a neutralizing immune response. It has shown an efficacy of 97.5% in preventing infection among 90,000 individuals in an active Ebola virus outbreak in the Democratic Republic of the Congo. [2]  In the Ring vaccination study, in which patients were vaccinated during the 2014 outbreak in the Republic of Guinea, results among the people who received the vaccine showed no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine. [27, 28]

General medical support is critical and should include replacement of coagulation factors and heparin if disseminated intravascular coagulation develops. Such care must be administered with strict attention to barrier isolation. All body fluids (blood, saliva, urine, and stool) contain infectious virions and should be handled with great care.

The recombinant monoclonal antibody combination, atoltivimab/maftivimab/odesivimab (Inmazeb), was approved by the FDA in October 2020 and is the first approved treatment for Zaire ebolavirus. It is indicated for treatment of Zaire ebolavirus in adults and children, including neonates born to a mother who is reverse-transcriptase polymerase chain reaction (RT-PCR) positive for Zaire ebolavirus infection. [4]

Surgical intervention generally follows a mistaken diagnosis in which Ebola-associated abdominal signs are mistaken for a surgical abdominal emergency. Such a mistake may be fatal for the patient and for any surgical team members who become contaminated with the patient’s blood.


Supportive Care

Supportive therapy with attention to intravascular volume, electrolytes, nutrition, and comfort care is of benefit to the patient. Intravascular volume repletion is one of the most important supportive measures.

Survivors can produce infectious virions for prolonged periods. Therefore, strict barrier isolation in a private room away from traffic patterns must be maintained throughout the illness. The patient’s urine, stool, sputum, and blood, along with any objects that have come in contact with the patient or the patient’s body fluids (such as laboratory equipment), should be disinfected with a 0.5% sodium hypochlorite solution. Patients who have died of Ebola virus disease should be buried promptly and with as little contact as possible.


Pharmacologic Therapy

Nucleoside analogue inhibitors of the cell-encoded enzyme S-adenosylhomocysteine hydrolase (SAH) have been shown to inhibit Zaire ebolavirus replication in adult BALB/c mice infected with mouse-adapted Ebola virus. [29] Inhibition of SAH indirectly inhibits transmethylation reactions required for viral replication. Treatment response was dose-dependent. When doses of 0.7 mg/kg or more every 8 hours were begun on day 0 or 1 of infection, mortality was completely prevented. Even when the drug was given on day 2, 90% survived.

Smith and colleagues found that in rhesus macaques infected with a lethal dose of Ebola virus, treatment with interferon beta early after exposure led to a significant increase in survival time, though it did not reduce mortality significantly. [30] These findings suggest that early postexposure interferon-beta therapy may be a promising adjunct in the treatment of Ebola virus infection.

Passive immunity has been attempted by using equine-derived hyperimmune globulins and human-derived convalescent immune globulin preparations. In Ebolavirus-infected cynomolgus macaques, use of human recombinant interferon alfa-2b in conjunction with hyperimmune equine immunoglobulin G (IgG) delayed but did not prevent death.

Equine IgG containing high-titer neutralizing antibodies to Ebola virus protected guinea pigs and baboons but was not effective in protecting infected rhesus monkeys.

During the 1995 outbreak in Kikwit, DRC, human convalescent plasma was used to treat 8 patients with proven Ebola disease, and only 1 patient died. Subsequent studies could not demonstrate survival benefit conferred by convalescent plasma products. The survival of these patients suggests that passive immunity may be of benefit in some patients.

Four laboratory workers in Russia who had possible Ebola exposure were treated with a combination of a goat-derived anti-Ebola immunoglobulin plus recombinant human interferon alfa-2. One of these patients had a high-risk exposure and developed clinical evidence of Ebola virus infection. All 4 patients recovered.

DNA vaccines expressing either envelope GP or nucleocapsid protein (NP) genes of Ebola virus have been demonstrated to induce protection in adult mice exposed to the virus. These vaccines were administered by coating gold beads with DNA expressing the genes for either GP or NP, and they were delivered by skin particle bombardment using a PowderJect-XR gene gun. Both vaccines induced measurable antibody responses detected by enzyme-linked immunosorbent assay (ELISA) and induced cytotoxic T cell immunity.

Other experimental therapies that use available drugs, though not approved by the FDA for treatment of Ebola virus infection, may be considered. Agents that may reduce mortality without directly effecting viral replication include activated protein C [5] and a recombinant nematode anticoagulant protein (NAP) that inhibits activated factor VII-tissue factor complex. [6] NAP resulted in attenuation of the coagulopathy associated with decreased fibrinolysis and fibrin deposition with a resultant decrease in the severity of the systemic inflammatory response syndrome.

In a rhesus macaque model of Ebola hemorrhagic fever, which carries a mortality approaching 100%, Geisbert and colleagues administered recombinant nematode anticoagulant protein, a potent inhibitor of TF-initiated coagulation. [6] One third of the monkeys given the nematode anticoagulant protein survived a lethal dose of Ebola virus, whereas 16 of the 17 (94%) control animals died. This approach targeted the hemorrhagic disease component of the infection rather than the virus itself.

In April 2016, the FDA granted orphan designation to aphidicolin for the treatment of Ebola virus infection. Aphidicolin is an inhibitor of B-family DNA polymerases, which inhibit the cell cycle at the G1/S border. If the cell is exposed to aphidicolin during S-phase, DNA replication is interrupted. [31]

In a benchtop experiment analyzing the influence of cell cycle arrest on Ebola virus infection, cells in G1/S phase were exposed to aphidicolin, a potent cell cycle inhibitor. A dose-dependent decrease in Ebola-infected cells was noted. Cells exposed to aphidicolin were allowed to resume cell cycle and then exposed to Ebola virus, which showed a time-dependent increase in infected cells. [32]

Small interfering RNA

One approach to blocking Ebola virus replication involves the use of antisense nucleotides that are complementary to sequences in the RNA polymerase complex. Shortly after a lethal challenge of Zaire Ebola virus was given, the administration of small interfering RNAs (siRNAs) packaged in stable nucleic acid-lipid particles targeting the RNA polymerase L protein protected guinea pigs [33] and macaques [34] .

More recently, third-generation synthetic antisense oligonucleotides called phosphorodiamidate morpholino oligomers (PMOs) have been shown to sterically hinder mRNA processing. Positively charged Ebola virus–specific PMOs that target VP24 and VP35 mRNA sequences (AVI-6002, a combination of AVI-7537 and AVI-7539) protect rhesus monkeys after lethal viral challenge. [35, 36] In addition, a recently completed phase I study of AVI-6002 in human volunteers showed that the drug was safe and well-tolerated. [37]

Monoclonal antibodies

Postexposure prophylaxis

Preliminary studies in cynomolgus macaques given a cocktail of 3 different murine monoclonal antibodies (mAbs; ZMab) directed against Ebola virus envelope glycoprotein epitopes demonstrated postexposure prophylactic activity 1 to 2 days after an Ebola virus challenge. [38] That result was matched by a mixture of 3 chimerized anti–Ebola virus mAbs (MB-003) having human constant regions produced in genetically modified tobacco plants. When given as postexposure prophylaxis 2 days after viral challenge, MB-003 was active both in mice and rhesus macaques. [39, 40]


The focus of mAb research is now shifting toward treatment of established infection. In that regard, 43% of rhesus macaques treated with MB-003 after onset of Ebola virus infection survived versus none of the untreated controls. [41] Established infection was defined as fever and positive Ebola virus reverse-transcription polymerase chain reaction (RT-PCR) result. Similarly, ZMab yielded a 50% survival rate in cynomolgus macaques when given starting on day 4 after viral challenge. [42]

Recently, an optimized combination of humanized mAbs produced in genetically modified tobacco plants and having specificity for 3 different Ebola virus glycoprotein epitopes rescued 100% of rhesus macaques even when given at advanced stages of disease 5 days after viral challenge (ZMapp; Mapp Biopharmaceutical, San Diego, CA, USA; and Defyrus, Toronto, Canada). [43, 44] In addition, 2 patients with Ebola virus disease in the United States who recently received ZMapp through emergency investigational new drug approval (US FDA) experienced declines in viral load and survived. [45] Subsequently, another 3 of 4 individuals treated with ZMapp survived. [46] These results suggest that ZMapp may prove useful for the treatment of established infection in humans.

The recombinant monoclonal antibody combination, atoltivimab/maftivimab/odesivimab (Inmazeb; REGN-EB3), is the first reatment for Zaire ebolavirus and was approved by the US Food and Drug Administration (FDA) in October 2020. It is indicated for treatment of Zaire ebolavirus in adults and children, including neonates born to a mother who is reverse-transcriptase polymerase chain reaction (RT-PCR) positive for Zaire ebolavirus infection. 

Another recombinant human monoclonal antibody, Ebanga (ansuvimab), was FDA-approved in December 2020. It is also indicated for treatment for Zaire ebolavirus (Ebolavirus) infection in adults and children, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection.

Both approvals were based on results from the PALM trial (n = 681). In response to the 2018 Ebola outbreak in the Democratic Republic of the Congo (DRC), global organizations (eg, WHO) assisted by offering the antibody cocktail under a compassionate use protocol in the 4-arm trial. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to IV administration of ZMapp (a different triple monoclonal antibody as the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or REGN-EB3 triple monoclonal antibody. The trial was stopped early upon results from an interim analysis, as REGN-EB3 was superior to ZMapp and remdesivir by showing lower mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the triple monoclonal antibody group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). [4]


Diet and Activity

Nutrition is complicated by the patient’s nausea, vomiting, and diarrhea.

Recovery often requires months, and delays may be expected before full resumption of normal activities. Weight gain and return of strength are slow. Ebola virus continues to be present for many weeks after resolution of the clinical illness. Semen from men recovering from Ebola infection has been shown to contain infectious virus, and Ebola has been transmitted by sexual intercourse involving recovering men and their sex partners. Any individuals who were exposed to infected patients should be watched closely for signs of early Ebola virus disease.



Prevention in healthcare personnel

Guidance from the US Centers for Disease Control and Prevention (CDC) recommends that healthcare personnel who care for patients infected with Ebola virus (ie, physicians, nurses, other clinicians) wear personal protective equipment (PPE) that does not expose any skin. This includes a surgical hood that covers the head and neck and a single-use full face shield (rather than goggles), in addition to either a N95 respirator or powered air-purifying respirator instead of a mask.

The CDC now recommends that clinicians train rigorously at donning and doffing PPE in a stepwise manner and demonstrate competency. A trained monitor should oversee each time a clinician puts on and takes off this gear.

During patient care, the PPE should not be adjusted, and the worker’s gloved hands should be disinfected frequently using an alcohol-based hand rub (ABHR), especially after body fluids are handled. [47]


Ebola Zaire vaccine (rVSV-ZEBOV; V920; Merck) has been approved in the United States and Europe. This vaccine is genetically engineered to express a glycoprotein of a Zaire strain of Ebola virus (ZEBOV). It has shown an efficacy of 97.5% in terms of preventing infection among recipients. [28] The World Health Organization approved use of the rVSV-ZEBOV-GP vaccine during outbreaks as part of an Expanded Access/Compassionate Use protocol. From August 2018 to March 2019, 94,000 individuals, including 29,000 healthcare personnel and front-line responders, received the vaccine. Among recipients, only 71 developed Ebola virus disease, most of whom contracted the infection within 10 days of vaccination, before the vaccine is believed to confer full protection. [3]

The CDC's Advisory Committee on Immunization Practices (ACIP) recommends preexposure vaccination in the following groups [48] :

  • Persons who are responding to an outbreak of Ebola virus disease
  • Healthcare personnel at federally designated Ebola Treatment Centers in the United States
  • Laboratorians or other staff at biosafety level 4 facilities in the United States

Two vaccines have been studied in a randomized, placebo-controlled trial in Liberia—the chimpanzee adenovirus 3 vaccine and the recombinant vesicular stomatitis virus vaccine. Both vaccines elicited a sustained immune response in study participants. [49]

Work continues on a vaccine for Ebola virus infection in primates. Sullivan and colleagues reported on the combination of naked DNA vaccine capable of encoding Ebola proteins followed by a booster vaccination with a recombinant adenoviral vector expressing Ebola GP(Z). [50]

In this study, cynomolgus macaques were injected with 3 doses of the DNA vaccine, 1 dose every 4 weeks. [50] Twelve weeks later, the macaques were vaccinated with the recombinant adenoviral vector. After another 12 weeks, unvaccinated macaques and vaccinated macaques were injected with a lethal dose of Ebola virus. All of the unvaccinated macaques died, whereas none of the vaccinated macaques died.

This work indicates that primates can be vaccinated against Ebola virus and can develop both a cell-mediated response (thought to be a result of the DNA vaccine) and a humoral antibody response (thought to be a result of the recombinant adenoviral vaccine).

Other efforts to design vaccines that work in primates used strategies that were successful in mice and guinea pigs. Geisbert and colleagues studied a series of vaccines containing RNA replicon particles from an attenuated strain of Venezuelan equine encephalitis virus that expressed Ebola virus GP and NP, a recombinant vaccinia virus that expressed Ebola virus GP, liposomes containing lipid A and inactivated Ebola virus, and a concentrated, inactivated whole-virion Ebola preparation. [51]

Although these vaccines protected rodents against an Ebola virus challenge, they did not protect cynomolgus macaques or rhesus macaques against exposure to the virus.

Ebola is transmissible from person to person via direct contact with an infected patient’s blood or other body fluids. Airborne transmission of Reston ebolavirus is known to have occurred among primates; thus, although most cases in humans occur after direct contact with a patient or their blood or body fluids, transmission of Ebola virus via the airborne route cannot be dismissed.

Infection control inside and outside of medical facilities relies on barrier protection using double gloves, fluid-impermeable gowns, face shields with eye protection, and coverings for legs and shoes.



Whenever the diagnosis of Ebola or any other viral hemorrhagic fever is considered, the Centers for Disease Control and Prevention (CDC), along with local and state health officials, should be contacted. A consultation with an infectious diseases physician should be promptly obtained, and strict barrier isolation should be instituted.

No attempt should be made to culture the virus, except when culture can be performed in a maximum-containment biosafety level 4 laboratory with laboratory personnel wearing positive-pressure suits equipped with high-efficiency particulate air filters and an umbilical-fed air supply.