Ebola virus infection
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Patients who are identified as being at risk of infection as per the World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC) case definitions should immediately be isolated in a room with private bathroom facilities.[89][92]
All healthcare personnel attending to the patient must wear appropriate personal protective equipment (PPE) that conforms to published protocols.
All contaminated materials (e.g., clothes, bed linens) should be treated as potentially infectious.
Specimens for laboratory investigations (e.g., Ebola RT-PCR, FBC, serum creatinine and urea, 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 minimising the risk of needlestick injuries.[136]
A staffing ratio of at least one clinician (defined as nurses, clinical officers, or physicians) to four patients is recommended to allow patient assessment three times daily.[138]
Healthcare workers should facilitate communication with family and friends (e.g., use of mobile phones or the internet) in order to reduce psychological distress without increasing the risk of infection.[138]
Ebola virus infection is a notifiable disease.
Treatment recommended for ALL patients in selected patient group
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's solution.[20][91]Options include the peripheral or central intravenous route, or the intraosseous route.[138]
The volume of intravenous fluids required should be assessed based on clinical examination (i.e., level of dehydration, signs of shock) and fluid losses (i.e., volume of diarrhoea and/or vomitus). Large volumes of fluid replacement (up to 10 L/day) may be required in febrile patients with diarrhoea.[44]
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 hypovolaemia.[138]
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.[111] Electrolyte monitoring should be performed daily, and repletion given as necessary.[20] More frequent monitoring can be considered if large volumes of intravenous fluids are being administered or if there are severe biochemical abnormalities present.
Large amounts of potassium replacement (e.g., 5-10 mmol [5-10 mEq/L] potassium chloride per hour) may be required.[22][128][141]
High blood lactate levels can be a reliable measure of hypoperfusion and can help guide fluid resuscitation.[111]
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 Opens in new window
Treatment recommended for ALL patients in selected patient group
Primary options
paracetamol: children: 10-15 mg/kg orally/rectally every 4-6 hours when required, maximum 75 mg/kg/day; adults: 500-1000 mg orally/rectally every 4-6 hours when required, maximum 4000 mg/day
Secondary options
tramadol: children: consult specialist for guidance on dose; adults: 50-100 mg orally (immediate-release) every 4-6 hours when required, maximum 400 mg/day
OR
morphine sulfate: children: 0.2 to 0.4 mg/kg orally every 4-6 hours when required, or 0.05 to 0.1 mg/kg intravenously every 4-6 hours when required; adults: 2.5 to 10 mg orally/intravenously every 4 hours when required
Should be treated with paracetamol first line (for pain and fever).[137][145]
Opioid analgesics (e.g., tramadol, morphine) are preferable for more severe pain.[137][145]
Non-steroidal anti-inflammatory drugs (including aspirin) should be avoided due to their associated increased risk of bleeding and potential for nephrotoxicity.[137][145]
Analgesia may help dysphagia, if present.
Treatment recommended for ALL patients in selected patient group
Primary options
ondansetron: children: consult specialist for guidance on dose; adults: 8 mg orally every 12 hours, or 4 mg intravenously every 8 hours when required
OR
promethazine: children: consult specialist for guidance on dose; adults: 12.5 to 25 mg orally every 4-6 hours when required
Oral or intravenous anti-emetics (e.g., ondansetron, promethazine) are recommended.[137][145]
Additional treatment recommended for SOME patients in selected patient group
Primary options
atoltivimab/maftivimab/odesivimab: children and adults: 50 mg/kg of each component as a single intravenous infusion
OR
ansuvimab: children and adults: 50 mg/kg as a single intravenous infusion
The WHO strongly recommends either atoltivimab/maftivimab/odesivimab (also known as REGN-EB3) or ansuvimab (also known as mAb114) for patients with confirmed Zaire ebolavirus infection, and neonates ≤7 days of age with unconfirmed infection who are born to mothers with confirmed Zaire ebolavirus infection.[155] Efficacy has not been established for other species of Ebolavirus.
Atoltivimab/maftivimab/odesivimab and ansuvimab are approved by the Food and Drug Administration (FDA) for the treatment of Zaire ebolavirus infection in children and adults, and atoltivimab/maftivimab/odesivimab has received orphan drug designation from the European Medicines Agency.
Atoltivimab/maftivimab/odesivimab and ansuvimab probably reduce mortality compared with standard of care (moderate-certainty evidence). 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.[155] The PALM trial found that of the patients who received atoltivimab/maftivimab/odesivimab, 33.5% died at 28 days compared to 51.0% of patients in the control group (ZMapp). Of the patients who received ansuvimab, 35.1% died at 28 days compared to 49.7% of patients in the control group.[156]
Adverse effects include hypersensitivity and infusion-related reactions, fever/chills, tachycardia, tachypnoea, hypotension, and elevated hepatic enzymes.
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.
Additional treatment recommended for SOME patients in selected patient group
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. If started, reassess after 48 hours.[137]
Additional treatment recommended for SOME patients in selected patient group
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.[6][150] Use of convalescent plasma is likely to be more achievable and effective than use of whole blood.[151][152]
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.[153][154]
The WHO has issued interim guidelines on the use of convalescent blood/plasma.
with heartburn/ dysphagia/ abdominal pain
Treatment recommended for ALL patients in selected patient group
Primary options
omeprazole: children ≥10 years of age and adults: 20 mg orally once daily
Patients may benefit from administration of a suitable antacid or a proton-pump inhibitor (e.g., omeprazole).[137][145] Analgesia may help with dysphagia.
with diarrhoea
Treatment recommended for ALL patients in selected patient group
Primary options
zinc: children <6 months of age: 10 mg orally once daily for 10-14 days; children ≥6 months of age: 20 mg orally once daily for 10-14 days
Zinc is recommended in children with diarrhoea.[145]
Patients should be evaluated for gastrointestinal infections and managed accordingly.[145]
Faecal management systems were used successfully in the 2014 outbreak in West Africa in patients with severe diarrhoea. They were well tolerated and provided infection prevention and control benefits for healthcare workers.[113]
Diarrhoea should be managed conservatively; the use of antimotility agents is not generally recommended.[137]
with seizures
Treatment recommended for ALL patients in selected patient group
Primary options
diazepam: children: consult specialist for guidance on dose; adults: 5-10 mg intravenously/intramuscularly initially, repeat every 10-15 minutes if required, maximum 30 mg/total dose
OR
diazepam rectal: children: consult specialist for guidance on dose; adults: 0.2 mg/kg rectally as a single dose, a second dose can be given in 4-12 hours if necessary
Secondary options
phenobarbital: children: consult specialist for guidance on dose; adults: 10 mg/kg intravenously initially, followed by 5 mg/kg every 30-60 minutes until seizures under control, maximum total loading dose 30 mg/kg
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, hypoglycaemia) is essential.
A benzodiazepine (e.g., intravenous/intramuscular or rectal diazepam) can be used to abort the seizure while an anticonvulsant (e.g., phenobarbital) can be given for repeated seizures.[137][145]
with agitation
Treatment recommended for ALL patients in selected patient group
Primary options
diazepam: children: consult specialist for guidance on dose; adults: 5 mg orally/intravenously as a single dose
OR
haloperidol: children: consult specialist for guidance on dose; adults: 5 mg intramuscularly as a single dose
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.[137][145]
Repeat doses are based on clinical response.
with respiratory distress
with sepsis/septic shock
Treatment recommended for ALL patients in selected patient group
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: broad-spectrum empirical antibiotic therapy, ideally given within one hour of recognition; rapid intravenous fluid resuscitation with assessment of response; and appropriate airway management and oxygen administration.[146]
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.[111][135]
Possibility of haemorrhage 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 Opens in new window
with organ dysfunction
Treatment recommended for ALL patients in selected patient group
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.[67]
Renal dysfunction is common in the advanced stages, but can be reversed with adequate fluid resuscitation in the initial stages.[67] 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.[44][103][128][130][149]
with significant bleeding/haemorrhage
Treatment recommended for ALL patients in selected patient group
Primary options
phytomenadione: consult specialist for guidance on dose
OR
tranexamic acid: consult specialist for guidance on dose
OR
omeprazole: children ≥10 years of age and adults: 20 mg orally once daily
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., haemoglobin, haematocrit, INR).[137][145][147]
Vitamin K, tranexamic acid, or a proton-pump inhibitor (for gastrointestinal bleeding) are reasonable treatment options in patients who are bleeding.[137][145]
with malaria
Treatment recommended for ALL patients in selected patient group
Malaria should be tested for and treated with appropriate antimalarial therapy if present while keeping in mind the patient's risk for Ebola virus infection 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 empirical antimalarial therapy until the malaria testing is negative or the treatment course is finished.[137]
pregnant
Treatment recommended for ALL patients in selected patient group
The WHO recommends the following key management principles in pregnant women: use both standard precautions and Ebola-specific infection prevention and control measures; include optimised 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; do not induce labour or perform invasive procedures for fetal indications in pregnant women with acute infection; advise women with suspected or confirmed acute infection not to breastfeed until after two negative breast milk tests (by RT-PCR) separated by 24 hours (in the meantime, infants should be separated from the mother and given a suitable breast milk substitute).[83]
Intrapartum haemorrhage and spontaneous abortion appear to be common in infected women; therefore, obstetric management should focus on monitoring for, and early treatment of, haemorrhagic complications.[21][158][160][161][162]
The CDC has produced specific guidance for caring for pregnant women and neonates:
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