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  • Filovirus, several subtypes: infects humans and non-human primates. Cause of Ebola virus disease (EVD) also called Ebola hemorrhagic fever.
    • Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast and Ebola-Bundibugyo infect humans.
    • Ebola-Reston has only caused infection in non-human primates, Philippines.
    • Enveloped, non-segmented negative-strand RNA virus. Characteristic thread-like viral particles when viewed under electron microscopy.
  • Cause of hemorrhagic fever (HF), primarily in sub-Saharan Africa.
  • Reservoir: believed to be zoonotic, but not proven.
    • Wild animals believed to be source establishing human infection that then leads to human-human spread.
    • Traditionally outbreaks seen in Central African rain forests, more recently in major urban as well as rural environs.
  • Pathogenesis: most data from primate models. Appears that virus affects both innate and adaptive immunity. High levels of pro-inflammatory cytokines, disruption of dendritic cells and activated macrophages impairs immune responses, and triggers DIC. Extremely elevated viral loads in those with advanced infection, near death.


  • Causes epidemic disease with high mortality rate (25-90%, depending on the outbreak).
  • Ebola outbreaks continue sporadically in Democratic Republic of the Congo (DRC), Ivory Coast, Gabon, Uganda, Sudan and Republic of the Congo.
    • DRC: has had most Ebola outbreaks to date (8), most recent May 2017.
    • Largest outbreak to date (2014-16) with notable firsts: occurring in West Africa (Guinea, Liberia, Sierra Leone with surrounding countries reporting cases: Nigeria, Senegal and Mali) and occurring in urban settings.
      • Zaïre ebolavirus strain involved.
      • Statistics (Apr 2016): 28,616 reported cases, 11,310 deaths (~40% mortality rate).
        • Healthcare workers (HCW): significantly affected.
      • Mortality rate estimated to be as high as ~75% in some locales especially with limited resources but lower with intensive support.
        • Survival in first-world countries (mostly HCWs) with access to advanced/ICU care 27.8% (5 of 18 pts, Nov 2014), and interestingly 2 HCW who were secondarily infected (Dallas) both survived (so 100% of small number). This may be due to excellent supportive care/fluid and electrolyte management.
    • Cases seen due to importation of virus into U.S. Europe.
    • Local transmission to healthcare workers documented, unclear if potentially due to airborne transmission (secondary to high viral load in severely ill, advanced Ebola patients) vs. difficulties in achieving complete protection with personal protective gear.
  • Transmission has been traditionally ascribed to close contact with infected individual involving blood or secretions or contaminated objects.
    • Semen has been implicated as viral levels tend to be high and persist.
  • Incubation period 2-21 d, mean 8-10d.
  • Symptoms: no pathognomonic features, so often not suspected until cluster of unexpected deaths occur.
    • Infection may be categorized in three phases: nonspecific flu-like, GI and then death or survival
    • Initial phase: Illness starts with nonspecific fever and headache, flu-like symptoms including myalgia, arthralgia and chills.
      • Onset of fever later accompanied by sx including nausea, vomiting, abdominal pain, diarrhea, chest pain, cough, pharyngitis, photophobia, adenopathy, conjunctival injection (red eyes), jaundice, pancreatitis.
      • Rash manifesting as erythema → maculopapular may arise d5-7 and subsequently desquamate. Desquamation interestingly correlates with survival.
    • Nonspecific symptoms progress to a severe systemic inflammatory response with coagulopathy and hemorrhagic evidence (petechiae, ecchymoses and mucosal bleeding), multi-organ system failure resembling septic shock.
      • Lymphopenia common.
      • High viral load: in fatal cases 3 logs higher than survivors
    • Fatal cases often preceded by hypovolemic shock, multiple organ failure and hemorrhage (in ~50-60%).
      • 2014-16 Ebola outbreak: hemorrhagic complications seen in 30-40%, rarely the cause of death.
  • Diagnosis: suspect in seriously ill traveler returning from endemic area.
    • Ddx: important in the febrile patient from West Africa to focus not only upon Ebola, as many other infections can produce similar pictures. A number of patients have had delay in diagnosis due to Ebola considerations when they had equally life-threatening disease with falciparum malaria.
    • Lab: diagnosis in early infection may be difficult as symptoms such as rash and red eyes are nonspecific.
      • Early infection may cause leukopenia and then evolve to neutrophilia with left shift and atypical lymphocytes.
      • Transaminase elevations
      • Thrombocytopenia
      • Coagulopathy c/w DIC
    • Viral diagnostics:
      • RT-PCR (preferred for early diagnosis, contact local health department or perform via in-house platform, e.g., Biofire)
      • Serology: blood or other specimens analyzed by antigen capture ELISA IgM and IgG
      • Viral culture
      • Immunohistochemistry (tissue analysis mainly in autopsy settings)
  • Contact local health department as soon as possible if patient suspected with hemorrhagic fever syndrome.


  • Bloodstream: viremia, generalized endothelial cell dysfunction leading to widespread organ damage and shock.
  • CNS: somnolence, delirium, coma
  • Skin/mucous membranes:
    • Petechiae
    • Hemorrhages
    • Ecchymoses around needle puncture sites
    • Day 5: maculopapular rash develops in most patients
  • GI: vomiting, diarrhea
  • Liver: jaundice, liver failure (secondary to shock or direct involvement by virus)
  • Kidney: renal failure, hemorrhage
  • Lung: respiratory failure due to viral infection leading to necrosis, ARDS accompanying shock
  • Gonads: orchitis, can be prolonged during convalescence
    • Limited studies suggest virus presence in semen is higher and longer than in plasma.


Supportive Care

  • Primary importance is to isolate suspected patients and institute strict infection control methods by nursing protocols including personal protective gear, respirators.
  • Antiviral treatment has not been proven to be effective or commercially available.
    • Experimental treatments have been used on some patients. Efficacy is not known since limited number. See http://www.cdc.gov… for additional information or acquisition of drugs for infected patients.
      • Current experimental approaches: include monoclonal antibodies, convalescent sera, RNA interfering drugs
        • RCT 72 pts using ZMapp (triple monoclonal ab): trend toward beneficial response, but under-powered[8].
      • DIC: heparin efficacy is unclear in human Ebola infection. Activated protein C (Xigris) has some benefit in primate model of infection, but is no longer available in U.S. Anti-coagulation protein rNAPc2 has shown 33% efficacy in non-human primate Zaire-Ebola infection.
      • Ribavirin: no effect known on filoviruses, and given drug side effects on heme system--not recommended for Ebola.
    • Patients empirically likely to get empiric anti-malarials and broad-spectrum antibiotics.
  • Fluid/electrolyte management as possible in setting, taking into account myocardial and pulmonary dysfunction. This, especially if instituted early in infection, is likely to be the most important feature that will contribute to survival.
    • Fluid losses due to vomiting or diarrhea may be substantial. Two to four liters/day described as average, reports as high as 12L/d described.
  • Other:
    • Some advocated for concurrent broad-spectrum antibiotics due to concern for bacterial gut transmigration.
    • If diagnostics not available, consider empiric antimalarial therapy, as co-infections described and believe to contribute to worse outcome.
  • Hemodialysis for renal failure or ECMO for ARDS may be employed if available and needed. Hemodialysis has appeared effective in survival (anecdotal, Emory: Atlanta, Georgia), and cannot be considered futile therapy.
  • In second week, patient either defervesces with marked improvement or dies in shock with multiorgan failure, often accompanied by anuria, DIC, liver failure.


  • Notify local hospital infection control, public health officials immediately of suspected cases. Isolate patient and follow protocols.
    • Identification of cases, epidemic.
    • For most up to date recommendations: see http://www.cdc.gov…
      • Diagnostic and transport protocols.
      • Infection control, personal protective equipment (PPE)
        • Education and strict process (donning/doffing) likely more important than actual types of gear assuming adequate protection of skin and mucous membranes.
        • PAPR recommendations and environmental cleaning now incorporated.
      • Guidance for Environmental Infection Control in hospitals
    • Infection control manual from CDC for suggestions in African setting: http://www.cdc.gov…
  • Barrier nursing in negative pressure room if available, strict contact precautions, use of respiratory precautions preferred.
  • Employ properly sterilized medical equipment.
  • Protection from body fluid/skin/mucous membrane contact during preparation of dead for funeral.
  • Vaccines: under study, numerous.
    • WHO (May 2017): ready to deploy rVSV-vectored Ebola vaccine in event of outbreak.
  • Screening: healthcare encounters, returning travelers (at certain U.S. airports for those within 21d of being in Guinea, Liberia, or Sierra Leone) with fever or GI symptoms.

Selected Drug Comments




While no drugs have been shown to be useful in the treatment or prevention of Ebola infection, some experimental therapies such as ZMapp may be available. ZMapp had a trend toward benefit in one RCT performed to date[8].


  • Following recovery, virus has been documented in "immune-privileged" sites: testes (+ semen), eye (+ ocular fluid).
    • Unclear if this has role in continued transmission of virus.
  • Among survivors, many have sequelae that may last > 1 year[11]:
    • Ocular deficits, ocular pain
    • Hearing loss, tinnitus
    • Swallowing disorders
    • Chronic fatigue
    • Difficulty sleeping
    • Intense arthalgia
    • Memory loss, neurocognitive symptoms


  • For suspected patients, please see CDC site for comprehensive information on infection control recommendations, diagnostic methods and treatment[3].
  • In advanced cases, virus seen in all tissues, body fluids. Evidence of continued virus in semen > 3 mos after recovery (by PCR) of uncertain significance.
  • Fatality rates 50-90% typical, but strain dependent. Ebola-Bundibugyo estimated to be 25-40% in 2007 outbreak.
  • First reported case of filovirus HF 1967 in Germany, and first likely Ebola HF noted in Sudan and northern Zaire in 1976.
  • Ebola virus is a Biosafety Level 4 pathogen. Patients suspected to have infection should have barrier nursing in negative pressure room. Notify public health officials.
  • In endemic setting, causes epidemic disease, spread by direct contact with blood and body fluids.
  • Outbreaks continue to occur sporadically in sub-Saharan Africa, so watch for travelers (health care personnel) with serious febrile illness.
  • U.S. 2014-15: most states assigned certain hospitals as capable of treating Ebola-infected patients, rather than have every health facility prepared.
    • Four US federal bio-containment units [Emory/Atlanta, Nebraska, NIH, Montana] have handled majority of infected patients to date.
    • Screening important to assess risk potential during initial engagement of health care in EDs, urgent care centers, etc.

Basis for recommendation

  1. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377(9768):849-62.  [PMID:21084112]

    Comment: Review comments on the human cost with thorough overview of known epidemiology, detection methods and infection control/supportive care. Authors also point out that this virus also greatly impacts the great ape population in Africa.

  2. Guidance on Personal Protective Equipment (PPE) To Be Used By Healthcare Workers during Management of Patients with Confirmed Ebola or Persons under Investigation (PUIs) for Ebola who are Clinically Unstable or Have Bleeding, Vomiting, or Diarrhea in U.S. Hospitals, Including Procedures for Donning and Doffing PPE http://www.cdc.gov… (page last updated 8/27/15, accessed 6/7/17)

    Comment: Though spread only by body fluids, given the lethality there is heightened concern (appropriately) about the levels of infection control necessary for patients and healthcare providers. HCW must receive comprehensive training and demonstrate competancy in Ebola-related infection control practices.

  3. Centers for Disease Control and Prevention. Ebola Hemorrhagic Fever. http://www.cdc.gov… (accessed 6/6/17)

    Comment: Resource for most up to date information regarding diagnostics, management including handling ill returning air passengers regarding the 2014 West African Ebola outbreak. Review of this information needed given fast moving pace and updated guidance.


  1. Perkins MD, Dye C, Balasegaram M, et al. Diagnostic preparedness for infectious disease outbreaks. Lancet. 2017.  [PMID:28577861]

    Comment: With Ebola as a prime example, rapid diagnostics would greatly improve care and also help in control of outbreaks.

  2. Barnes KG, Kindrachuk J, Lin AE, et al. Evidence of Ebola Virus Replication and High Concentration in Semen of a Patient During Recovery. Clin Infect Dis. 2017.  [PMID:28582513]

    Comment: Single patient study finding virus in semen higher/longer than in blood suggesting another potential transmission mode.

  3. Colavita F, Biava M, Castilletti C, et al. Measles Cases during Ebola Outbreak, West Africa, 2013-2106. Emerg Infect Dis. 2017;23(6):1035-1037.  [PMID:28518027]

    Comment: Potentially an example of what happens in crises, breakdown of routine medical care, 80 patients seen for consideration of Ebola tested negative but Measles virus IgM was detected in 13 (16%) of the patients.

  4. Henao-Restrepo AM, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2017;389(10068):505-518.  [PMID:28017403]

    Comment: Vaccine proved helpful in a ring-stategy to limit Ebola. This vaccine is currently endorsed by WHO in case of outbreak although hasn’t yet been approved by any country.
    Rating: Important

  5. PREVAIL II Writing Group, Multi-National PREVAIL II Study Team. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. N Engl J Med. 2016;375(15):1448-1456.  [PMID:27732819]

    Comment: Largest RCT for Ebola, examing the monoclonal ab treatment + usual care v. only supportive care. Overall mortality in this trial was 30%. Trend toward lower mortality with ZMapp (22%) v. only supportive care (37%), but study fell short of pre-specified thresholds for statiscally proven efficacy.
    Rating: Important

  6. Holmes EC, Dudas G, Rambaut A, et al. The evolution of Ebola virus: Insights from the 2013-2016 epidemic. Nature. 2016;538(7624):193-200.  [PMID:27734858]

    Comment: Authors argue that genomic sequencing of pathogens can be very helpful in helping understand outbreaks and what actions may be needed to contain. This concept is not unique to Ebola but likely helpful as costs for this technology decline to understand that even MDR organisms seen in hospitals are local "outbreaks."

  7. Nielsen CF, Kidd S, Sillah AR, et al. Improving Burial Practices and Cemetery Management During an Ebola Virus Disease Epidemic - Sierra Leone, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(1):20-27.  [PMID:25590682]

    Comment: Work to make safer community and burial practices may help staunch tranmission of Ebola. A needs assessment and recommendations for processes at a national level.

  8. Clark DV, Kibuuka H, Millard M, et al. Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. Lancet Infect Dis. 2015;15(8):905-12.  [PMID:25910637]

    Comment: One of a number of reports documenting a significant number of survivors with post-infectious sequelae. risk of ocular deficits (retro-orbital pain [RR 4·3, 95% CI 1·9-9·6; p< 0·0001], blurred vision [1·9, 1·1-3·2; p=0·018]), hearing loss (2·3, 1·2-4·5; p=0·010), difficulty swallowing (2·1, 1·1-3·9; p=0·017), difficulty sleeping (1·9, 1·3-2·8; p=0·001), arthralgias (2·0, 1·1-3·6; p=0·020), and various constitutional symptoms controlling for age and sex. Chronic health problems (prevalence ratio [PR] 2·1, 95% CI 1·2-3·6; p=0·008) and limitations due to memory loss or confusion (PR 5·8, 1·5-22·4; p=0·010) were also reported more frequently by survivors of Bundibugyo Ebola virus.

  9. Lamontagne F, Clément C, Fletcher T, et al. Doing today's work superbly well--treating Ebola with current tools. N Engl J Med. 2014;371(17):1565-6.  [PMID:25251518]

    Comment: Helpful perspective piece that combats fear and pervading sense that providing care may be hopeless and pose gravest of risks to HCWs. More resources and diligence at providing the best supportive care may well lower fatality.

  10. Bah EI, Lamah MC, Fletcher T, et al. Clinical Presentation of Patients with Ebola Virus Disease in Conakry, Guinea. N Engl J Med. 2014.  [PMID:25372658]

    Comment: Given that little has been well describe about the clinical features of Ebola, this report from Guinea helps fill gaps and finds that diarrrhea and fluid losses are among the important features and that use of IVF and other supportive managment may be important for lowering mortality rates, 43% in this series, lower than described in outlying areas with less resources. Most patients who died did so with a mean of 8d from initial onset of symptoms [range 7-11]. Increased risk of death also witnessed in patients older than 40 years [RR 3.49].
    Rating: Important

  11. Fischer WA, Hynes NA, Perl TM. Protecting Health Care Workers From Ebola: Personal Protective Equipment Is Critical but Is Not Enough. Ann Intern Med. 2014;161(10):753-754.  [PMID:25155746]

    Comment: Authors including lead who provided care in West Africa, argue that PPE if sufficient coverage demands more on proper practice and rituals to prevent HCW contamination.

  12. Stephenson J. Largest-ever Ebola outbreak still simmering in West Africa. JAMA. 2014;312(5):476.  [PMID:25096676]

    Comment: As of August 2014, >1000 deaths attributed to Ebola occuring in West Africa. WHO has declared a public health emergency. Most cases have occurred in Guinea, Liberia and Sierra Leone.

  13. Del Rio C, Mehta AK, Lyon Iii GM, et al. Ebola Hemorrhagic Fever in 2014: The Tale of an Evolving Epidemic. Ann Intern Med. 2014.  [PMID:25133433]

    Comment: Helpful perspectives, from West Africa to developed countries.

  14. Sobarzo A, Ochayon DE, Lutwama JJ, et al. Persistent immune responses after Ebola virus infection. N Engl J Med. 2013;369(5):492-3.  [PMID:23902512]

    Comment: Report of six survivors who all displayed neutralizing antibodies, 12 years after infection with the Gulu strain of Sudan Ebola virus. This suggests that there is likely durable immunity if one survives the infection raising hopes that perhaps a vaccine can be derived to do similar.

  15. Roddy P, Howard N, Van Kerkhove MD, et al. Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008. PLoS One. 2012;7(12):e52986.  [PMID:23285243]

    Comment: Outbreak in Bundibugyo, Uganda, November 2007-February 2008, caused by a putative new species (Bundibugyo ebolavirus) with this report including 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). In general, this virus behaved in similar fashion to earlier Ebola descriptions, although CFR is a bit lower. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%).

  16. MacNeil A, Farnon EC, Wamala J, et al. Proportion of deaths and clinical features in Bundibugyo Ebola virus infection, Uganda. Emerg Infect Dis. 2010;16(12):1969-72.  [PMID:21122234]

    Comment: Ugandan outbreak in 2007 with 56 cases documented by laboratory method; mortality rate was lower than others at 40%--unclear if this new strain of Ebola accounted for the difference from the normal 50-90% mortality rate. Risk factors for death included older age.

  17. Towner JS, Sealy TK, Khristova ML, et al. Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog. 2008;4(11):e1000212.  [PMID:19023410]

    Comment: A newly discovered Ebola virus associated with a recent outbreak in Uganda, fairly distantly related to the known Ebola viruses.

  18. Feldmann H, Jones SM, Daddario-DiCaprio KM, et al. Effective post-exposure treatment of Ebola infection. PLoS Pathog. 2007;3(1):e2.  [PMID:17238284]

    Comment: Animal model demonstration of a potential post-exposure treatment of Ebola virus infection, using injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein. This worked both in rodent and non-human primate models of infection.
    Rating: Important

  19. Martin JE, Sullivan NJ, Enama ME, et al. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006;13(11):1267-77.  [PMID:16988008]

    Comment: A phase I clinical trial with promise for development of a vaccine against Ebola virus.

  20. Daddario-DiCaprio KM, Geisbert TW, Ströher U, et al. Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment. Lancet. 2006;367(9520):1399-404.  [PMID:16650649]

    Comment: Another post-exposure treatment trial on non-human primates infected with Ebola virus infection, using a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein.
    Rating: Important

  21. Leroy EM, Kumulungui B, Pourrut X, et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005;438(7068):575-6.  [PMID:16319873]

    Comment: Possible demonstration of a zoonotic reservoir of Ebola virus.

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Last updated: July 3, 2017


Auwaerter, Paul G. "Ebola Virus." Johns Hopkins ABX Guide, The Johns Hopkins University, 2017. Johns Hopkins Guide, www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540180/all/Ebola_virus.
Auwaerter PG. Ebola virus. Johns Hopkins ABX Guide. The Johns Hopkins University; 2017. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540180/all/Ebola_virus. Accessed March 21, 2019.
Auwaerter, P. G. (2017). Ebola virus. In Johns Hopkins ABX Guide. Available from https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540180/all/Ebola_virus
Auwaerter PG. Ebola Virus [Internet]. In: Johns Hopkins ABX Guide. The Johns Hopkins University; 2017. [cited 2019 March 21]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540180/all/Ebola_virus.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Ebola virus ID - 540180 A1 - Auwaerter,Paul,M.D. Y1 - 2017/07/03/ BT - Johns Hopkins ABX Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540180/all/Ebola_virus PB - The Johns Hopkins University DB - Johns Hopkins Guide DP - Unbound Medicine ER -