Ebola disease is a notifiable disease. The mainstay of treatment is early recognition of infection coupled with effective isolation and optimized supportive care in a hospital setting.
High case fatality rates may be related to the supportive care available in resource-poor, rural settings where outbreaks have occurred, and reflect the difficulties patients in these settings have in accessing basic medical care in a healthcare structure that is overwhelmed.[18]WHO Ebola Response Team. Ebola virus disease in West Africa: the first 9 months of the epidemic and forward projections. N Engl J Med. 2014 Oct 16;371(16):1481-95.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411100#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25244186?tool=bestpractice.com
[20]Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015 Jan 1;372(1):40-7.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411249#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25372658?tool=bestpractice.com
Cases imported to developed countries present a different scenario with comprehensive supportive care available in these settings, including organ support in intensive care units.[45]Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411677#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[139]Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. 2015 Apr 11;385(9976):1428-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962384-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
Despite this, the lack of specific, proven therapies means that fatalities occur even in developed countries where best supportive care is available.[107]Lyon GM, Mehta AK, Varkey JB, et al; Emory Serious Communicable Diseases Unit. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014 Dec 18;371(25):2402-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409838#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25390460?tool=bestpractice.com
[140]Parra JM, Salmerón OJ, Velasco M. The first case of Ebola virus disease acquired outside Africa. N Engl J Med. 2014 Dec 18;371(25):2439-40.
https://www.nejm.org/doi/full/10.1056/NEJMc1412662
http://www.ncbi.nlm.nih.gov/pubmed/25409262?tool=bestpractice.com
[141]Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016 Feb 18;374(7):636-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
There was previously an active debate about the suitability of moving patients with advanced disease and a poor prognosis to intensive care where the risk for nosocomial infection may be high. It was thought that failure to provide full supportive care to those who are suspected (but not confirmed) of being infected may result in substandard care for these patients, who may subsequently be shown to have a treatable disease such as malaria. It is now clear that full supportive care can reduce mortality, with a reported survival rate of 81.5% in patients managed outside the West African setting, and that it should be provided whenever possible.[142]Zacharowski K, Brodt HR, Wolf T. Medical treatment of an Ebola-infected doctor -ethics over costs? Lancet. 2015 Feb 21;385(9969):685.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60279-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25706208?tool=bestpractice.com
[143]Solano T, Gilbert GL, Kerridge IH, et al. Ethical considerations in the management of Ebola virus disease. Med J Aust. 2015 Aug 17;203(4):193-5e.1.
http://www.ncbi.nlm.nih.gov/pubmed/26268293?tool=bestpractice.com
[144]Jacobs M, Beadsworth M, Schmid M, et al. Provision of care for Ebola. Lancet. 2014 Dec 13;384(9960):2105-6.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62250-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25479694?tool=bestpractice.com
Local hospital protocols should consider how this situation would be handled for patients with suspected infection before possible transfer to the intensive care unit, and for those who have already been transferred there.[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[141]Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016 Feb 18;374(7):636-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
[143]Solano T, Gilbert GL, Kerridge IH, et al. Ethical considerations in the management of Ebola virus disease. Med J Aust. 2015 Aug 17;203(4):193-5e.1.
http://www.ncbi.nlm.nih.gov/pubmed/26268293?tool=bestpractice.com
[145]Decker BK, Sevransky JE, Barrett K, et al. Preparing for critical care services to patients with ebola. Ann Intern Med. 2014 Dec 2;161(11):831-2.
https://annals.org/article.aspx?articleid=1910124
http://www.ncbi.nlm.nih.gov/pubmed/25244048?tool=bestpractice.com
[146]Canadian Critical Care Society; Canadian Association of Emergency Physicians; Association of Medical Microbiology and Infectious Diseases of Canada. Ebola clinical care guidelines: a guide for clinicians in Canada. October 2014 [internet publication].
https://www.canadiancriticalcare.org/resources/Pictures/Ebola%20Clinical%20Care%20Guidelines_ENG.pdf
[Figure caption and citation for the preceding image starts]: Ward area at an Ebola treatment center in West Africa, 2014From the personal collection of Chris Lane, MSc; used with permission [Citation ends].
Infection prevention and control
Infection prevention and control (IPC) is of immediate concern and local protocols should be followed. Patients who are identified as being at risk of infection as per the case definitions should immediately be isolated and personal protective equipment (PPE) should be used until the infection is either confirmed or excluded.
The WHO recommends the following IPC principles in healthcare settings.[92]World Health Organization. Infection prevention and control guideline for Ebola and Marburg disease. Aug 2023 [internet publication].
https://www.who.int/publications/i/item/WHO-WPE-CRS-HCR-2023.1
An IPC ring approach is recommended in healthcare facilities and communities during the management of cases.
In geographic areas where the virus is circulating, all people should be screened at the first point of contact with a healthcare facility, using a no-touch technique, to enable early recognition of suspected cases.
All suspected cases should be triaged to determine the severity of disease and identify patients in need of immediate care.
Patients with suspected or confirmed infection should be isolated, preferably in a single room.
Hand hygiene should be performed using an alcohol-based hand rub or soap and running water using the correct technique.
Appropriate PPE should be worn when in contact with a suspected or confirmed case.
Mucous membranes of the eyes, mouth, and nose should be completely covered. A face shield or goggles (under the head-and-neck covering) should be used. Fluid-resistant surgical or medical masks with a structured design (so that they do not collapse against the mouth) are recommended. A fluid-resistant particulate respirator should be used during aerosol-generating procedures.
Gloves and a disposable gown (or coverall) and apron made of fabric that has been tested for resistance to penetration by body fluids or blood-borne pathogens should be worn. Nitrile gloves are preferred over latex gloves.
Specific PPE requirements depend on the level of patient contact (i.e., indirect contact such as screening and triage versus direct contact of a case). PPE is not required during screening activities where a distance of at least 1 meter can be guaranteed and a no-touch approach is strictly followed.
Surfaces should be disinfected (using the wiping method) in facilities and settings that provide care to patients with suspected or confirmed infection.
All waste generated from the care of a patient with suspected or confirmed infection should be treated as infectious waste.
Healthcare workers with occupational exposure should be immediately assessed for exposure risk and managed accordingly.
More detailed IPC guidance is available from the WHO:
Key infection prevention and control measures in the World Health Organisation (WHO) guideline for Ebola. Willet V et al. BMJ 2024; 384 :p2811 doi:10.1136/bmj.p2811; used with permission
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Guidance is also available from the CDC:
Specimens for laboratory investigations (e.g., Ebola RT-PCR, CBC, serum creatinine/BUN, LFTs, ABG, coagulation studies, blood cultures, and investigations for other conditions such as malaria) should be collected and sent off according to local and national protocols. Judicious selection of investigations is important in order to reduce risk of transmission to laboratory workers and other healthcare personnel. Placement of a central line early in the patient stay (if possible) allows bloods to be taken and fluids to be given while minimizing the risk of needlestick injuries.[147]Rees PS, Lamb LE, Nicholson-Roberts TC, et al. Safety and feasibility of a strategy of early central venous catheter insertion in a deployed UK military Ebola virus disease treatment unit. Intensive Care Med. 2015 May;41(5):735-43.
http://www.ncbi.nlm.nih.gov/pubmed/25761540?tool=bestpractice.com
The CDC and WHO produce detailed guidance on specimen collection:
Optimized supportive care
Individualized and optimized supportive care is recommended for all patients.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[149]Centers for Disease Control and Prevention. Clinical guidance for Ebola disease. May 2024 [internet publication].
https://www.cdc.gov/ebola/hcp/clinical-guidance
Systematic assessment and reassessment of patients
Assess vital signs, physical exam, fluid status, and laboratory monitoring. Record and respond to change or abnormal clinical and laboratory parameters.
Patients at high risk of complications: assess at least every hour. A staffing ratio of one clinician for up to two patients is recommended.
Patients not at high risk of complications: assess at least three times per 24 hours (every 8 hours). A staffing ratio of one clinician for up to four patients is recommended.
Assess physical, social, psychologic, and spiritual wellbeing on admission and then on a daily basis.
Fluid resuscitation
Oral rehydration is recommended in patients who can drink.
Parenteral administration of appropriate fluids is recommended in those who are unable to drink or who have severe dehydration, sepsis, or shock.
Vasopressors may be required for shock if fluid resuscitation is not successful.
Electrolyte monitoring and correction
Glucose monitoring and management
Management of potential co-infections
Nutrition
Encourage oral nutrition if possible.
Provide enteral nutrition as tolerated.
Consider intravenous dextrose in patients who cannot tolerate oral food and with evidence of hypoglycemia.
Symptomatic care
Treat fever, pain, nausea/vomiting, dyspepsia, diarrhea, anxiety, and agitation.
Prevention and management of complications
Prevent catheter-associated infections and pressure ulcers.
Manage complications, including seizures, encephalopathy, hemorrhage, acute kidney injury,metabolic acidosis, hypoxic respiratory failure, and sepsis/septic shock.
Each patient should be assessed systematically each day using a suitable checklist. An example is available from the WHO.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
More information on these management principles is detailed below.
WHO: optimized supportive care for Ebola virus disease
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Fluid and electrolyte management
The high frequency of vomiting and diarrhea means that patients are often dehydrated and hypovolemic, particularly if they present late. This is probably responsible for the high case fatality rates in outbreaks as basic clinical monitoring (i.e., temperature, respiratory rate, pulse rate, blood pressure, and fluid input/output) is essential, but often difficult in resource-poor settings.
Oral rehydration solutions can be used for patients who can tolerate oral administration and who are not severely dehydrated, but the majority of patients require intravenous fluid replacement with either normal saline or lactated Ringer solution.[20]Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015 Jan 1;372(1):40-7.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411249#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25372658?tool=bestpractice.com
[94]Hunt L, Gupta-Wright A, Simms V, et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study. Lancet Infect Dis. 2015 Nov;15(11):1292-9.
http://www.ncbi.nlm.nih.gov/pubmed/26271406?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: Oral rehydration solution supplies at an Ebola treatment center in West Africa, 2014From the personal collection of Chris Lane, MSc; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Insertion of an intravenous line in an adult with Ebola virus disease (West Africa)From the collection of Tom E. Fletcher, MBE, MBChB, MRCP, DTM&H; used with permission [Citation ends].
Markers of poor perfusion may indicate poor or inadequate oral intake and patients should be promptly switched to intravenous administration. Options include the peripheral or central intravenous route, or the intraosseous route[150]Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet. 2018 Feb 17;391(10121):700-8.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29054555?tool=bestpractice.com
The volume of intravenous fluids required should be assessed based on clinical exam (i.e., level of dehydration, signs of shock) and fluid losses (i.e., volume of diarrhea and/or vomitus). Large volumes of fluid replacement (up to 10 L/day) may be required in febrile patients with diarrhea.[45]Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411677#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[151]Perner A, Fowler R, Bellomo R, et al. Ebola care and research protocols. Intensive Care Med. 2015 Jan;41(1):111-4.
http://www.ncbi.nlm.nih.gov/pubmed/25427868?tool=bestpractice.com
[152]Roberts I, Perner A. Ebola virus disease: clinical care and patient-centred research. Lancet. 2014 Dec 6;384(9959):2001-2.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962316-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25483156?tool=bestpractice.com
Large amounts of potassium replacement (e.g., 5-10 mmol potassium chloride per hour) may also be required.[22]Schieffelin JS, Shaffer JG, Goba A, et al; KGH Lassa Fever Program; Viral Hemorrhagic Fever Consortium; WHO Clinical Response Team. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014 Nov 27;371(22):2092-100.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411680#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25353969?tool=bestpractice.com
[139]Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. 2015 Apr 11;385(9976):1428-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962384-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
[153]Clay KA, Johnston AM, Moore A, et al. Targeted electrolyte replacement in patients with Ebola virus disease. Clin Infect Dis. 2015 Sep 15;61(6):1030-1.
http://www.ncbi.nlm.nih.gov/pubmed/26056238?tool=bestpractice.com
Close supervision and frequent monitoring are required as it is important to assess response and prevent fluid overload. Patients should be checked frequently for signs of shock, dehydration, or overhydration, and the fluid rate adjusted accordingly. Systematic monitoring of vital signs (e.g., heart rate, blood pressure, urine output, gastrointestinal fluid loss) and volume status at least three times daily is required to detect hypovolemia.[150]Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet. 2018 Feb 17;391(10121):700-8.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29054555?tool=bestpractice.com
Oral loperamide may help reduce profuse diarrhea, but further evidence is required to determine its role and it is not currently recommended by the WHO.[154]World Health Organization. Manual for the care and management of patients in Ebola care units/community care centres: interim emergency guidance. January 2015 [internet publication].
https://www.who.int/publications/i/item/manual-for-the-care-and-management-of-patients-in-ebola-care-units-community-care-centres
[155]Kendall RE, Gosser RA, Schulz LT, et al. Anti-diarrheal medication use in the treatment of Ebola virus-induced diarrhea. Travel Med Infect Dis. 2015 Mar-Apr;13(2):205-6.
http://www.ncbi.nlm.nih.gov/pubmed/25682446?tool=bestpractice.com
[156]Chertow DS, Uyeki TM, DuPont HL. Loperamide therapy for voluminous diarrhea in Ebola virus disease. J Infect Dis. 2015 Apr 1;211(7):1036-7.
https://jid.oxfordjournals.org/content/early/2015/02/04/infdis.jiv001.long
http://www.ncbi.nlm.nih.gov/pubmed/25573887?tool=bestpractice.com
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
The availability of point-of-care tests within the isolation facility makes monitoring the patient's biochemical status more efficient and reduces the risks associated with specimen transport.[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
Electrolyte monitoring should be performed daily, and repletion given as necessary.[20]Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015 Jan 1;372(1):40-7.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411249#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25372658?tool=bestpractice.com
More frequent monitoring can be considered if large volumes of intravenous fluids are being administered or if there are severe biochemical abnormalities present. High blood lactate levels can be a reliable measure of hypoperfusion and can help guide fluid resuscitation.[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
WHO guidelines should be consulted for specific recommendations on fluid and electrolyte management as well as on maintaining adequate nutrition during acute illness and the convalescent phase.
WHO: optimized supportive care for Ebola virus disease
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WHO: manual for the care and management of patients in Ebola care units/community care centres - interim emergency guidance
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WHO: clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker
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Symptomatic management
Fever and pain:
Should be treated with acetaminophen first line. Opioid analgesics (e.g., tramadol, morphine) are preferable for more severe pain. Nonsteroidal anti-inflammatory drugs (including aspirin) should be avoided due to their associated increased risk of bleeding and potential for nephrotoxicity.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
Gastrointestinal symptoms:
Oral or intravenous antiemetics (e.g., ondansetron, promethazine) are recommended for nausea/vomiting.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
Fecal management systems were used successfully in the 2014 outbreak in West Africa in patients with severe diarrhea. They were well tolerated and provided infection prevention and control benefits for healthcare workers.[117]Dickson SJ, Clay KA, Adam M, et al. Enhanced case management can be delivered for patients with EVD in Africa: experience from a UK military Ebola treatment centre in Sierra Leone. J Infect. 2018 Apr;76(4):383-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903873
http://www.ncbi.nlm.nih.gov/pubmed/29248587?tool=bestpractice.com
Heartburn/dysphagia/abdominal pain:
Patients may benefit from administration of a suitable antacid or a proton-pump inhibitor (e.g., omeprazole).[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
Seizures:
Although uncommon, seizures are a feature of advanced disease and pose a risk to healthcare workers because they increase the risk of contact with the patient's body fluids. Recognition and correction of contributing factors (e.g., high temperature, hypoperfusion, electrolyte disturbances, hypoglycemia) is essential. A benzodiazepine can be used to abort the seizure while an anticonvulsant (e.g., phenobarbital) can be given for repeated seizures.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
If there is no intravenous access, it can be given intramuscularly or rectally.
Agitation:
Although uncommon, agitation may be associated with encephalopathy, or possibly a direct effect of the virus on the brain, and can occur in advanced disease. Judicious use of a sedative (e.g., haloperidol or a benzodiazepine) is imperative for keeping the patient calm and preventing needlestick injuries in healthcare workers.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
Respiratory distress:
Oxygen should be titrated to maintain SpO2 >94%. Patients should be evaluated for pneumonia, fluid overload, wheezing, and congestive heart failure and managed accordingly.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
Intraosseous access may be required in some patients. [Figure caption and citation for the preceding image starts]: Insertion of an intraosseous line in a critically-ill adult with Ebola virus disease (West Africa)From the collection of Tom E. Fletcher, MBE, MBChB, MRCP, DTM&H; used with permission [Citation ends].
Sepsis/septic shock
Identification of sepsis or septic shock should be done rapidly using established criteria.
Management follows the same principles as for bacterial sepsis. Local guidance should be followed, but should include:[158]Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021 Nov 1;49(11): e1063-e1143.
https://journals.lww.com/ccmjournal/Fulltext/2021/11000/Surviving_Sepsis_Campaign__International.21.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34605781?tool=bestpractice.com
Broad-spectrum antibiotics are used in patients with infection to target the presumed translocation of gut organisms. This is not backed by any evidence, and blood cultures are difficult to do safely in infected patients. In some settings, especially in endemic areas where there is poor access to diagnostic tests, patients are routinely given broad-spectrum antibiotics as part of the management protocol.
Blood lactate levels are a useful tool to help assess perfusion and response to resuscitation.
In the absence of a response to initial management, inotropic support should be considered, preferably via a central venous catheter in an intensive care unit where invasive monitoring enables more aggressive fluid, electrolyte, and acid-base balance correction.[115]Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733-7.
https://www.atsjournals.org/doi/full/10.1164/rccm.201408-1514CP#.VEe1OvldWnA
http://www.ncbi.nlm.nih.gov/pubmed/25166884?tool=bestpractice.com
[146]Canadian Critical Care Society; Canadian Association of Emergency Physicians; Association of Medical Microbiology and Infectious Diseases of Canada. Ebola clinical care guidelines: a guide for clinicians in Canada. October 2014 [internet publication].
https://www.canadiancriticalcare.org/resources/Pictures/Ebola%20Clinical%20Care%20Guidelines_ENG.pdf
The possibility of hemorrhage should be considered, particularly in patients with skin or mucosal bleeding.
WHO guidelines should be consulted for specific recommendations on the management of sepsis/septic shock.
WHO: optimized supportive care for Ebola virus disease
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WHO: manual for the care and management of patients in Ebola care units/community care centres - interim emergency guidance
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WHO: clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker
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Significant bleeding/hemorrhage
Major bleeding occurs infrequently, but is a manifestation of advanced infection that is usually, but not always, fatal.
When available, fresh whole blood or platelet and plasma transfusions should be given according to local protocols and guided by clinical and laboratory (if available) indicators (e.g., hemoglobin, hematocrit, INR).[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
[159]Wada H, Thachil J, Di Nisio M, et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013 Feb 4;11(4):761-7.
https://onlinelibrary.wiley.com/doi/10.1111/jth.12155/full
http://www.ncbi.nlm.nih.gov/pubmed/23379279?tool=bestpractice.com
[160]Warren T, Jordan R, Lo M, et al. Nucleotide prodrug GS-5734 is a broad-spectrum Filovirus inhibitor that provides complete therapeutic protection against the development of Ebola Virus Disease (EVD) in infected non-human primates. Late breaker abstract 2. Presented at IDWeek. San Diego, 2015.
https://idsa.confex.com/idsa/2015/webprogram/Paper54208.html
Vitamin K, tranexamic acid, or a proton-pump inhibitor (for gastrointestinal bleeding) are reasonable treatment options in patients who are bleeding.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
[157]World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Feb 2016 [internet publication].
https://apps.who.int/iris/bitstream/10665/205570/1/9789241549608_eng.pdf?ua=1
Organ dysfunction
Multi-organ dysfunction is a common feature of advanced infection and includes acute kidney injury, pancreatitis, adrenal failure, and liver damage. Liver damage (e.g., hepatitis) is common; however, jaundice is not a common feature.[69]Fletcher T, Fowler RA, Beeching NJ. Understanding organ dysfunction in Ebola virus disease. Intensive Care Med. 2014 Dec;40(12):1936-9.
http://www.ncbi.nlm.nih.gov/pubmed/25366120?tool=bestpractice.com
Renal dysfunction is common, but can be reversed with adequate fluid resuscitation in the initial stages.[69]Fletcher T, Fowler RA, Beeching NJ. Understanding organ dysfunction in Ebola virus disease. Intensive Care Med. 2014 Dec;40(12):1936-9.
http://www.ncbi.nlm.nih.gov/pubmed/25366120?tool=bestpractice.com
In patients with anuria who do not respond to fluid resuscitation, renal replacement therapy has been used, although there are no trial data to support the efficacy of this intervention. Of the 5 critically ill patients in Europe and North America with multi-organ failure who were managed with both invasive mechanical ventilation and renal replacement therapy, 3 died.[45]Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014 Dec 18;371(25):2394-401.
https://www.nejm.org/doi/full/10.1056/NEJMoa1411677#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25337633?tool=bestpractice.com
[107]Lyon GM, Mehta AK, Varkey JB, et al; Emory Serious Communicable Diseases Unit. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014 Dec 18;371(25):2402-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa1409838#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25390460?tool=bestpractice.com
[139]Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. 2015 Apr 11;385(9976):1428-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962384-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25534190?tool=bestpractice.com
[141]Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016 Feb 18;374(7):636-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504874#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26886522?tool=bestpractice.com
[161]Connor MJ Jr, Kraft C, Mehta AK, et al. Successful delivery of RRT in Ebola virus disease. J Am Soc Nephrol. 2015 Jan;26(1):31-7.
http://www.ncbi.nlm.nih.gov/pubmed/25398785?tool=bestpractice.com
Convalescent whole blood or plasma
There is limited evidence from past outbreaks that transfusion of blood from convalescent patients could be beneficial in the acute phase of infection, and may reduce mortality.[7]Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406178
http://www.ncbi.nlm.nih.gov/pubmed/21084112?tool=bestpractice.com
[162]World Health Organization. Interim guidance: potential Ebola therapies and vaccines. Nov 2014 [internet publication].
https://apps.who.int/iris/bitstream/10665/137590/1/WHO_EVD_HIS_EMP_14.1_eng.pdf?ua=1
Use of convalescent plasma is likely to be more achievable and effective than use of whole blood.[163]Kreil TR. Treatment of Ebola virus infection with antibodies from reconvalescent donors. Emerg Infect Dis. 2015 Mar;21(3):521-3.
https://wwwnc.cdc.gov/eid/article/21/3/14-1838_article
http://www.ncbi.nlm.nih.gov/pubmed/25695274?tool=bestpractice.com
[164]Gutfraind A, Myers LA. Evaluating large-scale blood transfusion therapy for the current Ebola epidemic in Liberia. J Infect Dis. 2015 Apr 15;211(8):1262-7.
https://jid.oxfordjournals.org/content/211/8/1262
http://www.ncbi.nlm.nih.gov/pubmed/25635118?tool=bestpractice.com
The WHO has issued interim guidelines on the use of convalescent blood/plasma. Trials carried out in Guinea failed to show a survival benefit in patients treated with convalescent plasma, although the treatment appeared to be safe with no severe complications documented.[165]van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med. 2016 Jan 7;374(1):33-42.
https://www.nejm.org/doi/full/10.1056/NEJMoa1511812#t=article
http://www.ncbi.nlm.nih.gov/pubmed/26735992?tool=bestpractice.com
[166]van Griensven J, De Weiggheleire A, Delamou A, et al. The use of Ebola convalescent plasma to treat Ebola virus disease in resource-constrained settings: a perspective from the field. Clin Infect Dis. 2016 Jan 1;62(1):69-74.
https://academic.oup.com/cid/article/62/1/69/2462604/The-Use-of-Ebola-Convalescent-Plasma-to-Treat
http://www.ncbi.nlm.nih.gov/pubmed/26261205?tool=bestpractice.com
WHO: use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks
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WHO: ethics of using convalescent whole blood and convalescent plasma during the Ebola epidemic
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Antiviral therapy
Therapeutic antiviral monoclonal antibodies are available. The WHO strongly recommends either atoltivimab/maftivimab/odesivimab (also known as REGN-EB3) or ansuvimab (also known as mAb114) for patients with confirmed infection with Ebola virus (species Orthoebolavirus zairense), and neonates ≤7 days of age with unconfirmed infection who are born to mothers with confirmed infection with Ebola virus (species Orthoebolavirus zairense).[167]World Health Organization. Therapeutics for Ebola virus disease - Democratic Republic of the Congo. Aug 2022 [internet publication].
https://www.who.int/publications/i/item/9789240055742
Atoltivimab/maftivimab/odesivimab
An antibody cocktail consisting of three fully human monoclonal antibodies targeted at three nonoverlapping Orthoebolavirus zairense glycoprotein epitopes. The three antibodies bind to the glycoprotein on the surface of the virus simultaneously and block the attachment and entry of the virus.
Approved by the Food and Drug Administration (FDA) for the treatment of infection with Ebola virus (species Orthoebolavirus zairense) in children and adults, and has received orphan drug designation from the European Medicines Agency.[149]Centers for Disease Control and Prevention. Clinical guidance for Ebola disease. May 2024 [internet publication].
https://www.cdc.gov/ebola/hcp/clinical-guidance
Evaluated in the PALM trial, a multi-center, open-label, randomized controlled trial, as well as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during the 2018 outbreak. The primary efficacy endpoint in the trial was 28-day mortality. Of the patients who received atoltivimab/maftivimab/odesivimab, 33.5% died at 28 days compared to 51% of patients in the control group (ZMapp).[168]Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-303.
https://www.doi.org/10.1056/NEJMoa1910993
http://www.ncbi.nlm.nih.gov/pubmed/31774950?tool=bestpractice.com
Ansuvimab
The PALM trial found that ansuvimab was superior to ZMapp (see Emerging section) at reducing mortality. Of the patients who received ansuvimab, 35.1% died at 28 days compared to 49.7% of patients in the control group (ZMapp).[168]Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-303.
https://www.doi.org/10.1056/NEJMoa1910993
http://www.ncbi.nlm.nih.gov/pubmed/31774950?tool=bestpractice.com
Atoltivimab/maftivimab/odesivimab and ansuvimab probably reduce mortality compared with standard of care (moderate-certainty evidence), ZMapp, and remdesivir. However, they may have little or no effect on time to viral clearance. It is very uncertain whether they increase the risk of serious adverse events.[167]World Health Organization. Therapeutics for Ebola virus disease - Democratic Republic of the Congo. Aug 2022 [internet publication].
https://www.who.int/publications/i/item/9789240055742
[169]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 Sep;3(9):e683-92.
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(22)00123-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35803293?tool=bestpractice.com
Efficacy has not been established for other species of orthoebolaviruses.
These treatments must not be used together and should be considered alternatives to each other. Both treatments are administered as a single dose intravenous infusion, and should be given as soon as possible after diagnosis. They may be used in older people, pregnant and breastfeeding women, and children and newborns. Access to these therapeutics is challenging in many parts of the world, and choice depends on availability. They may need to be used under a compassionate use framework during an outbreak.
Malaria co-infection
Malaria should be tested for and treated with appropriate antimalarial therapy if present while keeping in mind the patient's risk for Ebola disease and the possibility of a dual infection. In endemic settings, malaria treatment is usually given as part of the routine management protocol, with or without confirmation of the infection. Give empiric antimalarial therapy until the malaria testing is negative or the treatment course is finished.[148]World Health Organization. Optimized supportive care for Ebola virus disease. July 2019 [internet publication].
https://www.who.int/publications-detail/optimized-supportive-care-for-ebola-virus-disease
Pregnant women
Nearly all pregnant women in the outbreaks between 2014 and 2020 had adverse pregnancy outcomes, although the mortality rate in pregnant women was not higher than that of the nonpregnant patients.[170]Foeller ME, Carvalho Ribeiro do Valle C, Foeller TM, et al. Pregnancy and breastfeeding in the context of Ebola: a systematic review. Lancet Infect Dis. 2020 Jul;20(7):e149-58.
https://www.doi.org/10.1016/S1473-3099(20)30194-8
http://www.ncbi.nlm.nih.gov/pubmed/32595045?tool=bestpractice.com
However, in previous outbreaks, the reported case fatality rate has been higher in pregnant women compared with nonpregnant women.[171]Mupapa K, Mukundu W, Bwaka MA, et al. Ebola hemorrhagic fever and pregnancy. J Infect Dis. 1999 Feb;179 Suppl 1:S11-2.
https://jid.oxfordjournals.org/content/179/Supplement_1/S11.long
http://www.ncbi.nlm.nih.gov/pubmed/9988157?tool=bestpractice.com
Experience during the 2014 outbreak suggests that good outcomes can occasionally be achieved.[172]Baggi FM, Taybi A, Kurth A, et al. Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014. Euro Surveill. 2014 Dec 11;19(49):20983.
https://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20983
http://www.ncbi.nlm.nih.gov/pubmed/25523968?tool=bestpractice.com
Pregnant women who are not treated with investigational or compassionate use agents experience very high rates of spontaneous abortion, and fetal or neonatal death. Intrapartum hemorrhage and spontaneous abortion appear to be common; therefore, obstetric management should focus on monitoring for, and early treatment of, hemorrhagic complications.[21]Chertow DS, Kleine C, Edwards JK, et al. Ebola virus disease in West Africa - clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7.
https://www.nejm.org/doi/full/10.1056/NEJMp1413084
http://www.ncbi.nlm.nih.gov/pubmed/25372854?tool=bestpractice.com
[171]Mupapa K, Mukundu W, Bwaka MA, et al. Ebola hemorrhagic fever and pregnancy. J Infect Dis. 1999 Feb;179 Suppl 1:S11-2.
https://jid.oxfordjournals.org/content/179/Supplement_1/S11.long
http://www.ncbi.nlm.nih.gov/pubmed/9988157?tool=bestpractice.com
[173]Jamieson DJ, Uyeki TM, Callaghan WM, et al. What obstetrician-gynecologists should know about Ebola: a perspective from the Centers for Disease Control and Prevention. Obstet Gynecol. 2014 Nov;124(5):1005-10.
http://www.ncbi.nlm.nih.gov/pubmed/25203368?tool=bestpractice.com
[174]Association of Women's Health, Obstetric and Neonatal Nurses. Ebola: caring for pregnant and postpartum women and newborns in the United States: AWHONN practice brief number 3. J Obstet Gynecol Neonat Nurs. 2015 Jan-Feb;44(1):164-5.
https://onlinelibrary.wiley.com/doi/10.1111/1552-6909.12518/full
http://www.ncbi.nlm.nih.gov/pubmed/25421426?tool=bestpractice.com
[175]Kitching A, Walsh A, Morgan D. Ebola in pregnancy: risk and clinical outcomes. BJOG. 2015 Feb;122(3):287.
http://www.ncbi.nlm.nih.gov/pubmed/25585496?tool=bestpractice.com
The WHO recommends the following key management principles:
Use both standard precautions and Ebola-specific infection prevention and control measures.
Include optimized supportive care in the clinical management of all pregnant women.
Atoltivimab/maftivimab/odesivimab and ansuvimab may be offered to pregnant women in the context of rigorous research, or in accordance with local protocols; however, this recommendation is based on very low-quality evidence.
Do not induce labor or perform invasive procedures for fetal indications in pregnant women with acute infection.
Advise women with suspected or confirmed acute infection not to breast-feed until after two negative breast milk tests (by reverse-transcription polymerase chain reaction [RT-PCR]) separated by 24 hours. In the meantime, infants should be separated from the mother and given a suitable breast milk substitute.
The CDC has also produced specific guidance for caring for pregnant women and neonates.
Children
Children should be managed by teams of health care workers with pediatric expertise. Planning for the care of children in non-endemic settings is complex and early involvement of intensivists has been advocated whenever feasible.[176]Olupot-Olupot P. Ebola in children: epidemiology, clinical features, diagnosis and outcomes. Pediatr Infect Dis J. 2015 Mar;34(3):314-6.
http://www.ncbi.nlm.nih.gov/pubmed/25522340?tool=bestpractice.com
[177]Herberg JA, Emonts M, Jacobs M, et al. UK preparedness for children with Ebola infection. Arch Dis Child. 2015 May;100(5):421-3.
http://www.ncbi.nlm.nih.gov/pubmed/25694613?tool=bestpractice.com
[178]Eriksson CO, Uyeki TM, Christian MD, et al. Care of the child with Ebola virus disease. Pediatr Crit Care Med. 2015 Feb;16(2):97-103.
http://www.ncbi.nlm.nih.gov/pubmed/25647119?tool=bestpractice.com
Communication with family
Isolation in hospital affects the psychologic wellbeing of patients, including increased rates of depression, anxiety, anger, fear, and loneliness. Healthcare workers should facilitate communication with family and friends (e.g., use of cell phones or the internet) in order to reduce psychologic distress without increasing the risk of infection.[150]Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet. 2018 Feb 17;391(10121):700-8.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29054555?tool=bestpractice.com