MICROBIOLOGY

• Filoviridae includes several filoviruses capable of infecting humans and nonhuman primates.
  • Enveloped, non-segmented, negative-strand RNA virus. Characteristic thread-like viral particles when viewed under electron microscopy.
  • The cause of Ebola virus disease (EVD, Fig) has historically been termed Ebola hemorrhagic fever.
    
    • Zaire ebolavirus, Sudan ebolavirus, Bundibugyo ebolavirus and Taï Forest ebolavirus infect humans.
    • Ebola-Reston has only caused infection in non-human primates in the Philippines.
• Cause of severe systemic viral illness with fever, gastrointestinal disease, shock, and variable hemorrhagic manifestations ( also see hemorrhagic fever , HF), primarily in sub-Saharan Africa. Infection in primates and people by the Ebolavirus group:
• Reservoir: Fruit bats are considered the most likely natural reservoir, although definitive reservoir confirmation remains incomplete.
  • Wild animals are believed to be the source of human infection that leads to human-to-human spread.
• Pathogenesis: most data from primate models. Appears that the virus affects both innate and adaptive immunity. High levels of pro-inflammatory cytokines, disruption of dendritic cells, and activated macrophages impair immune responses and trigger DIC. Significantly elevated viral loads in those with advanced infection, near death.

CLINICAL

• Causes epidemic disease with a high mortality rate, up to 90%.
  • Case fatality rates vary substantially by species, outbreak setting, and available supportive care.
  • Outbreaks historically emerged in Central African forested regions but have also involved densely populated urban settings.
• Ebola outbreaks continue sporadically in the Democratic Republic of the Congo (DRC), the Ivory Coast, Gabon, Uganda, Sudan and the Republic of the Congo.
  • DRC, Uganda, May 2026 outbreak, Bundibugyo virus
    • Large outbreak due to difficulty diagnosing this form of Ebola virus. WHO declared a Public Health Emergency of International Concern.
      • CDC information about the "Current situation."
      • Bundibugyo ebolavirus outbreak in Uganda and DRC highlighted challenges in diagnosis, molecular assay sensitivity, and species-specific vaccine limitations.
        • Compared with Zaire ebolavirus outbreaks, hemorrhagic manifestations may be less prominent and gastrointestinal symptoms more pronounced.
        • Case fatality rates appear lower (~25–40%) than many Zaire outbreaks, although severe disease remains common.
        • Clinical recognition may be delayed because early manifestations are nonspecific, and less prompt progression to hemorrhagic features causes a delay in recognition, allowing for a greater spread.
        • Species diversity can complicate more rapid molecular diagnosis if assays are insufficiently broad, therefore adding to the delay in virus confirmation.
        • Appears that existing Zaire-directed vaccines and monoclonal antibodies may only partially and inconsistently offer protection against this variant.
        • Clinically similar in nonspecific early features; however, hemorrhage appeared less prominent in some cohorts, and severe gastrointestinal illness often predominated.
  • Other outbreaks
    • Uganda: September 2002 outbreak in the Mubende District.
      • Sudan species, the outbreak in five districts as of 10/15/22, outbreak ended in January 2023.
      • The concern is also that the Ebola vaccine does not cover this species.
    • DRC: has had the most Ebola outbreaks to date (8); an epidemic has been ongoing since May 2017 and remains active, partly due to safety and logistic concerns about providing care, immunization and prevention education.
      • In August 2022, public health authorities announced a case of Ebola virus disease in the Beni health zone in the province of North Kivu.
      • 2018-2020 outbreak, declared ended. Second-largest-ever outbreak with an overall fatality rate of 67%.
    • The largest outbreak to date (2014-16), with notable firsts, occurred in West Africa (Guinea, Liberia, Sierra Leone, with surrounding countries reporting cases: Nigeria, Senegal and Mali) and occurred in urban settings.
      • Zaïre ebolavirus strain involved.
      • Statistics (Apr 2016): 28,616 reported/possible cases, 11,310 deaths (~40% mortality rate).
        • Healthcare workers (HCWs) are significantly affected.
      • In some locales, the mortality rate is estimated to be as high as ~75%, especially with limited resources, but lower with intensive support.
        • Mortality rates were substantially lower among patients treated in high-resource settings with aggressive supportive care.
    • In the U.S. and Europe, cases are seen due to importation.
    • Transmission to healthcare workers has primarily reflected breaches in PPE or infection-control practices; aerosol-generating procedures may theoretically increase exposure risk.
• The transmission has been traditionally ascribed to close contact with infected individuals involving blood or secretions or contaminated objects, then entering through skin breaks or mucous membranes.
  • Persistent viral RNA and occasional infectious virus have been documented in semen for prolonged periods after recovery.
  • Index cases of Ebola are thought to be acquired through contact with an infected animal, e.g., a fruit bat or a nonhuman primate.
• Incubation period 2-21 d, mean 8-10d.
• Symptoms: no pathognomonic features, so often not suspected until a cluster of unexpected deaths occurs.
  
  • Infection may be categorized into three phases: nonspecific flu-like, GI, and death or survival.
  • Initial phase: Illness starts with nonspecific fever and headache, flu-like symptoms including myalgia, arthralgia and chills.
    • The onset of fever is later accompanied by sx, including nausea, vomiting, abdominal pain, diarrhea, chest pain, cough, pharyngitis, photophobia, adenopathy, conjunctival injection (red eyes), jaundice, and pancreatitis.
      • Hiccups (historically common/severe disease marker)
      • Profound weakness/asthenia.
    • Rash manifesting as erythema → maculopapular may arise d5-7 and subsequently desquamate.
      • Desquamation appears to correlate 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 is common.
    • Higher viral loads correlate strongly with mortality.
  • Fatal cases are often preceded by hypovolemic shock, multiple organ failure and hemorrhage (in ~50-60%).
    • 2014-16 Ebola outbreak: hemorrhagic complications were seen in 30-40%, rarely the cause of death.
• Diagnosis: suspect in a seriously ill traveler returning from an endemic area.
  • Ddx: essential in the febrile patient from West Africa to focus not only on Ebola, as many other infections can produce similar pictures.
    • Several patients have had a delay in diagnosis due to Ebola considerations when they had an equally life-threatening disease with falciparum malaria.
    • Other severe tropical ills include malaria, typhoid fever, Shigella, meningococcemia, leptospirosis, plague, and Borrelia spp. (relapsing fever), measles, anthrax, typhus or spotted fevers, yellow fever, Chikungunya fever, Lassa fever, Dengue and severe viral hepatitis (Hepatitis A, B or E).
  • Lab: diagnosis in early infection may be complex as symptoms such as rash and red eyes are nonspecific. Consider if symptoms are suggestive + possible exposure (blood, body fluids or objects from EVD pt, infected fruit bat or primate, semen from recovered EVD pt) to EVD within 21d of symptom onset.
    
    • Early infection may cause leukopenia and then evolve into neutrophilia with left shift and atypical lymphocytes.
    • Transaminase elevations
    • Thrombocytopenia
    • Coagulopathy c/w DIC
  • Viral diagnostics:
    • RT-PCR (preferred for early diagnosis; contact the local health department or perform via an in-house platform)
      • A single negative test early in infection does not exclude.
        • Repeat in 24–72h if suspicion remains high.
      • Peak viral load days 3-7. Fatal cases with very high viremia, 10-100x that of survivors.
      • The seminal fluid remains positive for months to years after recovery from EVD.
    • Antigen detection:
      • FDA-approved OraQuick® Ebola Rapid Antigen Test (2019)
        • A rapid diagnostic test (RDT) for the Ebola virus in both symptomatic patients and recently deceased people
        • Use is only suggested when more sensitive molecular testing is not readily available.
          • A NEGATIVE TEST DOES NOT RULE OUT DISEASE
        • All test results (positive and negative) must be verified through real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing at a Laboratory Response Network (LRN) or CDC.
    • Serology: blood or other specimens analyzed by antigen-capture ELISA IgM and IgG
      • Helpful for paucisymptomatic or asymptomatic EV infections as the viral load may be very low.
      • Serology is best determined three weeks or later after acquisition (if known).
    • Viral culture (BSL-4 pathogen)
    • Immunohistochemistry (tissue analysis mainly in autopsy settings)
• Contact your local health department as soon as possible if a patient suspected with hemorrhagic fever syndrome.
  • Guidance on specimen testing and transport: http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-specimen-collection-subm...

SITES OF INFECTION

• 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.

TREATMENT

FOLLOW-UP

• Following recovery, the virus has been documented in "immune-privileged" sites: testes (+ semen), eye (+ ocular fluid).
  
  • Likely has an occasional role in the continued transmission of the virus.
• Among survivors, many have sequelae that may last > 1 year[16]:
  • Ocular deficits, ocular pain
    • Uveitis
  • Hearing loss, tinnitus
  • Swallowing disorders
  • Chronic fatigue
  • Difficulty sleeping
  • Intense arthralgia
  • Memory loss, neurocognitive symptoms
• Recrudescence from immune-privileged sites
• Relapse-associated transmission (rare)

OTHER INFORMATION

• KEY POINTS
  • Severe GI fluid loss is a major mortality driver.
  • Hemorrhage is absent in many patients.
  • Early supportive care substantially improves survival.
  • FDA-approved therapeutics and vaccines target Zaire ebolavirus.
  • Sudan and Bundibugyo outbreaks highlight the need for broader countermeasures.
• See the CDC Clinician Ebola page for updated guidance.
• Substantial advances have been made in the ecology of Ebolavirus, transmission/prevention, vaccination effects, diagnosis and management.
  • Outbreak control may be complicated by conflict, limited healthcare infrastructure, and community mistrust.
  • Outbreaks continue to occur sporadically in sub-Saharan Africa, so watch for travelers (healthcare personnel) with febrile severe illnesses.
• For suspected patients, please see the CDC site for comprehensive information on infection control recommendations, diagnostic methods and treatment[5].
• In advanced cases, the virus was seen in all tissues and 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 was estimated at 25-40% during the 2007 outbreak.
• The first reported case of filovirus HF was in 1967 in Germany, and the first likely Ebola HF was noted in Sudan and northern Zaire in 1976.
• The Ebola virus is a Biosafety Level 4 pathogen. Patients suspected of infection should have barrier nursing in a negative-pressure room. Notify public health officials.
• In an endemic setting, it causes epidemic disease, spread by direct contact with blood and body fluids.
• During the 2014–2016 epidemic, most U.S. states designated referral centers for Ebola care rather than having every health facility prepared.
  • Specialized U.S. biocontainment units have historically managed most domestic Ebola cases.
  • Screening is essential to assess risk potential during the initial engagement of health care in EDs, urgent care centers, etc.

Basis for recommendation

1. Gao Y, Zhao Y, Guyatt G, et al. Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis. Lancet Microbe. 2022;3(9):e683-e692.  [PMID:35803293]

   Comment: Monoclonals were more effective than ZMapp or remdesivir in reducing mortality and offer a modern summary and a concise therapeutic section.
   

2. 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(1):1-12.  [PMID:33417593]

   Comment: rVSVΔG-ZEBOV-GP Ebola vaccine (Ervebo) is the first vaccine FDA-approved for this virus. The recommendations here are for adults at risk for occupational exposure in labs or biocontainment treatment centers in the US.
   

3. Malvy D, McElroy AK, de Clerck H, et al. Ebola virus disease. Lancet. 2019;393(10174):936-948.  [PMID:30777297]

   Comment: The 2013-16 outbreak offered a setting for making real advancements in the diagnosis and management of EVD, along with updates on current immunization and experimental therapeutics.
   

4. WHO 2023 Infection Prevention and Control, Ebola and Marburg Diseases. https://iris.who.int/server/api/core/bitstreams/cb212f34-2cba-43a7-9e6f-5f5ff32b18f7/content (accessed 5/21/2026)

   Comment: This document updates earlier guidance documents and offers 11 new recommendations and is the best and is the current authorative operational document.
   
   
   

5. Centers for Disease Control and Prevention. Clinical Guidance for Ebola Disease. https://www.cdc.gov/ebola/hcp/clinical-guidance/index.html [last updated 1/30/25, accessed 5/21/26].

   Comment: Resource for the most up-to-date information regarding diagnostics and management, including handling ill returning air passengers regarding the 2014 West African Ebola outbreak. A review of this information is needed, given the fast-moving pace and updated guidance as outbreaks occur. Details and links are provided for treatment and vaccines that are only FDA-approved for the Zaire ebolavirus.
   

References

6. PREVAC Study Team, Kieh M, Richert L, et al. Randomized Trial of Vaccines for Zaire Ebola Virus Disease. N Engl J Med. 2022;387(26):2411-2424.  [PMID:36516078]

   Comment: The trial focused on immunogenicity among three vaccines against the Zaire Ebola virus. No safety issues were identified, and all generated immune responses within two weeks.
   

7. Tomori O, Kolawole MO. Ebola virus disease: current vaccine solutions. Curr Opin Immunol. 2021;71:27-33.  [PMID:33873076]

   Comment: Vaccine studies have focused on Zaire Ebolavirus outbreaks in the DRC. However, even with a relatively effective vaccine for prevention, other strategies are necessary as well as understanding approaches for non-Zaire outbreaks.
   

8. Mulangu S, Dodd LE, Davey RT, et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019;381(24):2293-2303.  [PMID:31774950]

   Comment: A [PALM] trial performed during the existing outbreak found both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. At the primary endpoint of 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P=0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P=0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and serum creatinine and aminotransferase levels each correlated with improved survival.
   

9. Perkins MD, Dye C, Balasegaram M, et al. Diagnostic preparedness for infectious disease outbreaks. Lancet. 2017;390(10108):2211-2214.  [PMID:28577861]

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

10. 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;65(8):1400-1403.  [PMID:28582513]

    Comment: A single patient study found the virus in semen was higher/more extended than in blood, suggesting another potential transmission mode.
    

11. 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: The vaccine proved helpful in a ring strategy to limit Ebola. This vaccine is endorsed by WHO in case of an outbreak, although any country hasn’t yet approved it.
    Rating: Important
    

12. PREVAIL II Writing Group, Multi-National PREVAIL II Study Team, Davey RT, et al. 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%. A trend toward lower mortality with ZMapp (22%) v. only supportive care (37%), but the study fell short of pre-specified thresholds for statistically proven efficacy.
    Rating: Important
    

13. Varkey JB, Shantha JG, Crozier I, et al. Persistence of Ebola Virus in Ocular Fluid during Convalescence. N Engl J Med. 2015;372(25):2423-7.  [PMID:25950269]

    Comment: Raises concerns about the recrudescence of this virus in immune-privileged sites, such as the eye, which in this case manifested as uveitis.
    

14. 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):20-7.  [PMID:25590682]

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

15. Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015;372(1):40-7.  [PMID:25372658]

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

16. 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 several 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.
    

17. 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: A helpful perspective piece that combats fear and pervading sense that providing care may be hopeless and pose the gravest of risks to HCWs. More resources and diligence in providing the best supportive care may lower fatalities.
    

18. 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):753-4.  [PMID:25155746]

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

19. 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 a vaccine can be derived to do similar.
    

20. 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: An outbreak in Bundibugyo, Uganda, in November 2007-February 2008 is the foundational paper for this new species (Bundibugyo ebolavirus); the report includes 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). This virus generally behaved similarly to earlier descriptions of Ebola, although the CFR is slightly lower. The most frequently experienced symptoms were non-bloody diarrhea (81%), severe headache (81%), and asthenia (77%).
    

21. 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; the mortality rate was lower than others at 40%--unclear if this new strain of Ebola accounted for the difference from the usual 50-90% mortality rate. Risk factors for death included older age. Lower mortality ≠ , lower threat!
    

22. WHO. Groundbreaking Ebola vaccination trial launches today in Uganda. https://www.who.int/news/item/03-02-2025-groundbreaking-ebola-vaccination-...Feb 3, 2025 (accessed 5/22/26)

    Comment:
    Notably , Uganda initiated the first clinical efficacy trial of a Sudan ebolavirus vaccine during an active outbreak.
    
    
    

Media

Ebola virus

Electron microscopic image of the Ebola filovirus, named after threadlike nature.
Source: CDC