Treatment and prevention of Ebola virus disease

INTRODUCTION — The family Filoviridae includes the genera Ebolavirus and Marburgvirus, which are among the most virulent pathogens of humans [1-3]. The genus Ebolavirus consists of six species: Zaire, Sudan, Bundibugyo, Tai Forest, Reston, and Bombali [4]. Of these, only the first four have caused recognized disease in humans; all but the Reston virus are indigenous to Africa. Several other genera of filoviruses have recently been identified in animals, but there is no evidence that they cause disease in humans.

The Zaire species of Ebola virus was the first to be discovered [5]. From 1976 through 2013, it caused multiple outbreaks in the Democratic Republic of the Congo (DRC) and neighboring countries in Central Africa, with case fatality rates often approaching 90 percent. Those outbreaks usually involved fewer than 100 cases and were contained within a period of weeks to a few months. In 2014, the Zaire virus appeared in West Africa, producing an epidemic in Liberia, Guinea, and Sierra Leone that took more than two years to bring under control [6]. There were nearly 29,000 total cases (suspected, probable, or confirmed), of which more than 15,000 were laboratory confirmed, and the overall case fatality rate was approximately 40 percent. Since then, the Zaire species has been responsible for additional epidemics, including several outbreaks in the DRC [7,8]. A subsequent outbreak in Guinea in early 2021 appears to have resulted from persistent human infection since the 2014 West African epidemic, though the manner of persistence could not be determined [9,10]. (See "Epidemiology and pathogenesis of Ebola virus disease".)

The Sudan species of Ebola virus was also discovered in 1976 [11]. In five outbreaks in Uganda and Sudan, including one that ended in January 2023, case fatality rates have averaged approximately 50 percent. The Bundibugyo species has been responsible for small outbreaks in Uganda and the adjacent DRC [12], while the Ivory Coast virus has caused one nonfatal case [13]. The Reston virus, which has been found in pigs in the Philippines, and the Bombali virus, identified as viral RNA in African bats, are not known to cause disease in humans.

Epidemics typically begin when a human comes into contact with an infected animal or its body fluids [1,3]. However, the persistence of virus in persons who have recovered from Ebola virus disease may potentially be a source of infection for new outbreaks [10,14-16]. Person-to-person transmission is based upon direct physical contact with the body fluids of a living or deceased patient. Patients typically present with a nonspecific febrile syndrome that may include headache, muscle aches, and fatigue [1,3,17]. Vomiting and diarrhea frequently develop during the first few days of illness and may lead to significant volume losses. A maculopapular rash is sometimes observed. Despite the traditional name of "Ebola hemorrhagic fever," major bleeding is not found in most patients, and severe hemorrhage tends to be observed only in the late stages of disease. Some patients develop progressive hypotension and shock with multiorgan failure, which typically results in death during the second week of illness. By comparison, patients who survive infection commonly begin to show signs of clinical improvement during the second week of illness.

The experience of the 2014-2016 West African epidemic demonstrated that the mortality associated with Ebola virus disease may be reduced through adequate supportive care [6]. It also accelerated the investigation of therapies and vaccines for treatment and prevention of the Zaire species of Ebola virus [15,16]. As an example, two different monoclonal antibody therapies were found to be beneficial in the “PALM” clinical trial conducted in the North Kivu epidemic in the DRC [17]. In addition, the rVSV-ZEBOV vaccine, first found to provide significant protection in West Africa, was given to more than 300,000 people during the course of the North Kivu epidemic and to more than 30,000 people during the 2020 outbreak in the Équateur Province [8].

This topic will discuss treatment and prevention of Ebola virus disease. Detailed discussions of the epidemiology, pathogenesis, clinical manifestations, and diagnosis of Ebola virus disease, as well as the disease caused by Marburg virus, are found elsewhere. (See "Epidemiology and pathogenesis of Ebola virus disease" and "Clinical manifestations and diagnosis of Ebola virus disease" and "Marburg virus".)

TREATMENT

Approach to therapy — All health care workers involved in the care of patients with suspected or confirmed Ebola virus disease should rigorously observe infection control precautions, including the proper use of personal protective equipment. (See 'Infection control precautions during acute illness' below.)

The mainstay of treatment for Ebola virus disease involves supportive care to maintain adequate organ function (eg, cardiovascular, respiratory, renal) while the immune system mobilizes an adaptive response to eliminate the infection [18,19] (see 'Supportive care' below). Whenever possible, patients should receive care in designated treatment centers and by clinicians trained to care for such patients [20]. Treating patients with Ebola virus disease requires a multidisciplinary approach prior to, during, and following patient care [21]. Although patient care in low-resource settings has historically been limited [22], efforts to provide more frequent monitoring and advanced care to patients in West Africa progressed during the 2014-2016 epidemic [23].

Experimental antiviral therapies were administered to patients during the West African epidemic in 2014 as well as subsequent outbreaks in the Democratic Republic of the Congo (DRC). Two of these, the monoclonal antibody (mAb) preparations REGN-3 and mAb114, were effective for the treatment of Zaire ebolavirus infection and can be used in addition to supportive care. (See 'Ebola-specific therapies' below.)

Supportive care — Fundamental aspects of supportive care involve preventing intravascular volume depletion, correcting profound electrolyte abnormalities, and avoiding the complications of shock. (See "Treatment of severe hypovolemia or hypovolemic shock in adults".)

During the West African epidemic, 27 patients with Ebola virus disease were treated in the United States or Europe, where they received aggressive supportive care [24]. Among those patients, 82 percent survived. Specific lessons learned include [18,19,25-28]:

●Patients may lose large amounts of fluid through vomiting and diarrhea, requiring rapid volume replacement to prevent shock; antiemetic and antidiarrheal agents may also be beneficial [18,19,29]. Careful attention to the volume of fluid losses and intake will assist with fluid repletion targets.

●When available, patients will benefit from hemodynamic monitoring and intravenous (IV) fluid repletion [19,26]. However, patients in the early phase of illness who respond to oral antiemetic and antidiarrheal therapy may be able to take in sufficient fluids by mouth to prevent or correct dehydration [19].

●Patients may develop significant electrolyte disturbances (eg, hyponatremia, hypokalemia, hypomagnesemia, and hypocalcemia) and may require frequent repletion of electrolytes to prevent cardiac arrhythmias. (See "Overview of the treatment of hyponatremia in adults" and "Treatment of hypocalcemia" and "Hypophosphatemia: Evaluation and treatment" and "Hypomagnesemia: Evaluation and treatment".)

●Frequent nursing assessment and care may be required in order to respond to the patient's changing clinical situation.

Fluid and electrolyte replacement — Patients who experience fluid losses from vomiting and diarrhea may require five or more liters per day of a balanced crystalloid solution. Fluid and electrolyte replacement can be administered orally (eg, World Health Organization [WHO]-recommended oral rehydration salts) or intravenously (eg, 0.9% sodium chloride solution); the approach depends in part upon the stage of illness and the clinical presentation. As an example, in resource-limited settings, oral therapy to prevent or correct dehydration may be suitable [19,30], particularly in the early phase of illness. However, patients in shock and those who are unable to tolerate or manage self-directed oral replacement therapy will require IV fluids.

The approach to fluid and electrolyte replacement will also depend upon the availability of resources:

●In resource-limited areas with little or no monitoring and laboratory capacity, qualitative assessments of urine frequency, volume, and color, as well as evaluation of skin turgor and mucous membranes, may assist in guiding volume replacement in the absence of more accurate measures. (See "Etiology, clinical manifestations, and diagnosis of volume depletion in adults", section on 'Clinical manifestations'.)

●In areas with greater resources, careful attention to the volume of fluid losses and intake, as well as indirect assessments of intravascular volume status (eg, vascular ultrasound, indwelling catheters for central venous pressure monitoring), will assist with fluid repletion targets. Electrolyte replacement should be guided by plasma values since patients can present with a range of abnormalities. As an example, in a cohort study of patients admitted to a hospital in Sierra Leone in 2015, 32 of 97 presented with abnormal potassium levels, while the number who had hypokalemia or hyperkalemia was similar (19 versus 13, respectively) [31]. (See "Treatment of severe hypovolemia or hypovolemic shock in adults".)

●In resource-rich areas, clinicians may employ standard supportive measures for critically ill patients in shock, including invasive blood pressure and continuous pulse-oximetry monitoring. Hypotension may sometimes persist despite adequate volume resuscitation, requiring the use of vasopressor infusions such as norepinephrine. Aggressive volume resuscitation may contribute to the development of pulmonary edema, and acute lung injury in the setting of shock may necessitate supplemental oxygen therapy (eg, nasal cannula or face mask). (See "Evaluation and management of suspected sepsis and septic shock in adults".)

Respiratory support — Invasive mechanical ventilation (intubation) may be the best option for patients with progressive respiratory failure [32,33]. When considering the management of such patients with Ebola virus disease, clinicians should recognize that some types of respiratory support present a hazard of generating infectious aerosols. The use of noninvasive mechanical ventilation or high-flow oxygen therapy is generally not recommended given the potential for continuous aerosol production. (See "Continuous oxygen delivery systems for the acute care of infants, children, and adults".)

Additional supportive measures — Additional supportive measures may be needed depending upon the patient's clinical presentation. These include:

●Antipyretic agents (eg, acetaminophen, paracetamol) to decrease fever. Dose reduction of these agents may be needed for patients with progressive hepatic dysfunction. Nonsteroidal anti-inflammatory agents are generally avoided to help minimize the risk of renal failure, which can contribute to fatal disease. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Laboratory findings'.)

●Analgesic agents to manage pain (eg, abdominal, joint, muscle). (See "Pain control in the critically ill adult patient".)

●Antiemetic medications to control nausea and vomiting. (See "Characteristics of antiemetic drugs".)

●Antimotility agents (eg, loperamide) to control diarrhea and decrease fluid and electrolyte losses [19,29].

●Anti-epileptic medications for those with seizures. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

●Blood products (eg, packed red blood cells, platelets, fresh frozen plasma) for patients with coagulopathy and bleeding. (See "Use of blood products in the critically ill".)

●Total parenteral nutrition support for individuals with poor oral intake due to persistent nausea, vomiting, diarrhea, or abdominal pain [34]. (See "Nutrition support in intubated critically ill adult patients: Parenteral nutrition".)

●Renal replacement therapy to manage severe multifactorial acute kidney injury [35]. If dialysis is required, clinicians should refer to the Centers for Disease Control and Prevention (CDC) website for recommendations on how to safely perform acute hemodialysis in patients with Ebola virus. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)

A more detailed discussion on the clinical manifestations of Ebola virus disease is found elsewhere. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Clinical manifestations'.)

Antimicrobial therapy — As with other severely ill patients, persons with Ebola virus disease may require evaluation and/or treatment of other concomitant or possible infections (eg, typhoid fever) [18,19,25]. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Differential diagnosis'.)

In addition, empiric antimicrobial treatment should be administered to patients with clinical evidence of bacterial sepsis, which may be a late complication [18,19]:

●The choice of agent should provide adequate coverage for gram-negative pathogens [18]. (See "Gram-negative bacillary bacteremia in adults", section on 'Empiric antimicrobial therapy'.)

●Empiric gram-positive therapy should be added in certain patients, such as those with hospital-acquired pneumonia or indwelling central venous catheters. (See "Intravascular non-hemodialysis catheter-related infection: Treatment" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)

In some case series from the Ebola epidemic in West Africa, empiric antimicrobial therapy was given to all patients at the time of initial presentation or to patients who had evidence of gastrointestinal dysfunction, even if clinical evidence of bacterial sepsis was absent [25,36]. However, data to justify this approach are lacking.

Ebola-specific therapies — Atoltivimab, maftivimab, and odesivimab (REGN-EB3) and ansuvimab (mAb114) are two antibody-based therapies that are effective for the treatment of Zaire ebolavirus infection [37].

●Atoltivimab, maftivimab, and odesivimab (REGN-EB3) – In October 2020, the US Food and Drug Administration (FDA) approved the triple-monoclonal antibody (mAb) product. This combination of three mAbs targets three nonoverlapping epitopes on the Zaire Ebolavirus virus surface glycoprotein, providing potent virus neutralization [38].

●Ansuvimab (mAb114) – In December 2020, the FDA approved the monoclonal antibody ansuvimab (sold as Ebanga). This mAb was isolated from a survivor of Ebola virus disease and neutralizes the virus [37].

These agents are administered as a single dose and can be used for treatment of adult and pediatric patients, including neonates born to mothers who are reverse-transcription polymerase chain reaction (RT-PCR) positive for Zaire ebolavirus. Patients who receive these agents should avoid the concurrent administration of live Ebola virus vaccines; the manufacturer suggests that Ebola vaccines be delayed by a minimum of three months after administration of these antibodies. More detailed information on the use of these agents can be found in the Lexicomp drug information topics within UpToDate.

The WHO included the use of these antibodies in its response to an outbreak of Ebola virus disease in the DRC in 2021, and these antibodies are approved for use by the US FDA. However, they are not approved for treatment of Sudan virus disease, and their clinical benefit for that disease, if any, is not known. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Democratic Republic of the Congo' and "Epidemiology and pathogenesis of Ebola virus disease", section on 'Uganda'.)

The efficacy of these antibodies for treatment of Zaire ebolavirus infection was demonstrated in a randomized multidrug trial conducted during the Ebola epidemic in North Kivu, DRC, from November 2018 to August 2019. The treatments evaluated in this trial consisted of REGN-EB3, mAb114, ZMapp (a combination of three mAbs targeting the Ebola virus surface glycoprotein), and the nucleotide analog prodrug remdesivir. In this trial ZMapp was considered the control arm since results from an earlier randomized trial found fewer deaths in the ZMapp arm versus placebo (22 versus 37 percent), although the results did not meet the prespecified threshold for establishment of efficacy [39].

All participants in this study received the same standard of supportive clinical care (SOC) as well as one of the above four therapies. Participants in the control arm received SOC plus three IV infusions of ZMapp three days apart. Those in the other three arms received SOC plus a single IV infusion of mAb114; a single IV infusion of REGN-EB3; or daily IV infusions of remdesivir for 10 days. The primary endpoint was survival 28 days following initiation of treatment.

The study was stopped early because an interim analysis of 499 participants found that individuals who had low levels of Ebola virus in their blood on entry, as measured by nucleoprotein Ct >22, had a greater chance of survival if they received REGN-EB3 or mAb114 rather than ZMapp or remdesivir [40]. In the final analysis, which included 673 patients, overall mortality was reduced when compared with ZMapp by 14.6 percent (95% CI -25.2 to -1.7) in those who received mAb114 and 17.8 percent (95% CI -28.9 to -2.9) in those who received REGN-EB3. However, in patients with a high viral load, as measured by nucleoprotein Ct of ≤22, mortality remained high in all groups, ranging from 63.6 percent in patients treated with REGN-EB3 to 85.3 percent in patients treated with remdesivir.

During the West African epidemic, some other experimental therapies that had demonstrated efficacy in laboratory animals were also evaluated [41]. Several therapies were administered alone or in combination to individual patients on a compassionate-use basis, and some were administered to cohorts of patients in nonrandomized trials. Many of these therapies (eg, convalescent plasma, whole blood, and the nucleoside analog prodrug favipiravir), which had shown promise in earlier studies in laboratory animals, were found to be of no or unclear benefit in patients and are no longer being investigated [42-52].

Considerations during pregnancy — Ebola virus disease has been associated with a high risk of obstetric hemorrhage, miscarriage, and perinatal death. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Pregnancy'.)

Similar to nonpregnant patients, treatment consists primarily of supportive care. (See 'Supportive care' above.)

Such patients should have access to research protocols evaluating therapeutic agents. (See 'Ebola-specific therapies' above.)

In pregnant women with acute Ebola virus disease, there are no data to suggest whether cesarean or vaginal delivery is preferred or when the fetus should be delivered. Thus, decisions regarding obstetric care must be made on a case-by-case basis.

According to WHO guidelines published in 2020, labor should not be induced. In addition, obstetric procedures (such as cesarean delivery, vacuum extraction, iatrogenic rupture of membranes, episiotomy) should only be performed for maternal indications (ie, to reduce maternal morbidity/mortality), not for fetal indications (eg, slow fetal heart rate). Additional recommendations for screening and caring for pregnant women with Ebola virus disease in United States hospitals can be found on the CDC website.

Infection control precautions during labor and delivery are reviewed below. (See 'Labor and delivery' below.)

A retrospective study evaluated the outcomes of Ebola virus disease in pregnant women versus nonpregnant women of childbearing age during the 2020 outbreak in the Democratic Republic of the Congo [53]. Although the risk of death was similar in the two groups, nearly 60 percent of the pregnant women who survived experienced loss of the fetus.

There is minimal information on the pathogenesis of pregnancy loss and neonatal death [19,26,54-56]. Some cases appear to be secondary consequences of severe maternal illness or from acquisition of infection by the newborn after birth. A case of transplacental fetal infection resulting in fetal demise in an otherwise healthy mother has also been reported [57].

Prognostic factors — Early diagnosis and prompt initiation of care increase the likelihood that a patient with Ebola virus disease will survive [19,26,58]. In contrast, patients who have already developed evidence of severe intravascular volume depletion, metabolic abnormalities, and impaired oxygen delivery by the time treatment is initiated are at high risk of death [59].

Additional demographic, clinical, and laboratory findings that affect prognosis include:

●Age – Younger age was associated with a lower case fatality rate in the outbreak in Sierra Leone [26,60]. In one study, the case fatality rate was 57 percent for patients <21 years old versus 94 percent for those >45 years of age [26].

●Gender – A study from West Africa comparing the outcome of Ebola virus disease in men and women found a slightly higher case fatality rate in men; however, this may have resulted from delays in seeking treatment by some male patients [61].

●Gastrointestinal disease – In a review of 106 patients treated in Sierra Leone, 94 percent of patients with diarrhea died, compared with 65 percent without diarrhea [26].

●Viral load – Experience from Ebola outbreaks in West Africa, Uganda, and the Democratic Republic of the Congo has shown that patients with high Ebola virus RNA levels in the bloodstream have a higher mortality [26,39,60,62,63]. As an example, in a retrospective cohort study that followed 525 patients in Sierra Leone, a viral load ≥10⁷ copies/mL was a significant predictor of mortality (odds ratio 10.8, 95% CI 6.1-19.7) [60]. Studies of blood samples collected during the outbreak of Ebola Sudan virus disease in Gulu, Uganda in 2000, in which approximately 50 percent of patients survived infection, indicates that certain biomarkers are predictive of disease outcome [64,65]. As examples, proinflammatory cytokines were associated with viremia, hemorrhage, and death, whereas soluble CD40 ligands were associated with nonfatal outcomes [64].

Other host factors may also be associated with clinical outcomes. As an example, there was a significant association between HLA-B alleles and survival or death during the outbreak of Ebola Sudan in Gulu, Uganda [66].

Recovery and discharge from the hospital — Patients who survive Ebola virus disease typically begin to show signs of clinical improvement during the second week of illness [19]. In these patients, viremia also resolves during the second week, in association with the appearance of virus-specific IgM and IgG [62,63].

Reverse transcriptase polymerase chain reaction (RT-PCR) testing is used to help determine when a recovering patient can be discharged from a hospital. Based on studies of the West African epidemic, the WHO recommended that individuals who no longer have signs and symptoms can be discharged if they have two negative PCR tests on whole blood separated by at least 48 hours. A similar protocol was followed in a treatment center in Liberia [19].

However, a commentary published during the epidemic recommended that, in resource-limited settings, the decision to discharge a convalescent patient should be based upon the absence of symptoms of Ebola virus disease for 48 hours rather than PCR testing [67]. This approach is supported, in part, by a study that evaluated the presence of infectious virus over time in four patients [68]. Twenty-eight plasma samples were tested by RT-PCR, and isolation of the virus was subsequently attempted. Ebola virus was not isolated from plasma samples if the cycle-threshold value was >35.5 (higher cycle-threshold values indicate lower RNA levels) or if the sample was taken more than 12 days after the onset of symptoms.

Regardless of when an individual is discharged from the hospital, patients should receive information to help minimize the risk of transmission in the community (eg, counseling on safe sexual practices) since the virus can persist in a variety of body fluids (eg, urine, semen) for up to several months after the plasma tests negative for Ebola virus by RT-PCR. (See 'Sexual transmission' below and "Epidemiology and pathogenesis of Ebola virus disease", section on 'Risk of transmission through different body fluids'.)

Follow-up care — Patients should be informed that clinical sequelae (eg, joint pains, uveitis, meningitis) may develop weeks or months after the initial illness resolves. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Convalescence'.)

The WHO suggests that patients be seen in follow-up two weeks after discharge, monthly for six months, and then every three months to complete one year [69].

●Males should have semen testing during these visits until they test negative for Ebola virus RNA. A more detailed discussion of semen testing and when unprotected sexual activity can be resumed is found below. (See 'Sexual transmission' below.)

●If fever develops, patients should be tested for Ebola RNA by RT-PCR and be evaluated for other causes of infection (eg, malaria). (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Differential diagnosis'.)

●Uveitis and meningitis are suggestive of an Ebola relapse. If meningitis is suspected, a lumbar puncture should be performed (using appropriate personal protective equipment), even if the blood tests are negative for Ebola virus RNA.

Survivors with ocular findings also require follow-up vision care. In a study of 137 survivors in the West African epidemic, 50 had ocular findings. Visually significant cataracts were present in 46 patients at a median of 19 months from initial diagnosis. All patients tested negative for Ebola virus RNA by RT-PCR of ocular fluid, and 34 underwent cataract surgery, resulting in improved visual acuity [70]. In a prospective longitudinal study of 516 survivors and 586 controls, the prevalence of uveitis an average of two years following acute Ebola virus disease was greater in the survivors than controls (33 versus 15.4 percent, respectively); however no difference in the prevalence of cataracts or vision loss was observed [71].

A discussion of infection control precautions during the convalescent period is found below. (See 'Infection control precautions during convalescence' below.)

PREVENTION — Experience from the West African epidemic suggests that several concurrent strategies should be employed to prevent the spread of Ebola virus. During acute illness, strict infection control measures and the proper use of personal protective equipment are essential to prevent transmission to health care workers. In addition, individuals who have been exposed to Ebola virus should be monitored so they can be identified quickly if signs and symptoms develop. (See 'Infection control precautions during acute illness' below and 'Monitoring and travel restrictions' below.)

Patients who have recovered from Ebola virus disease may continue to have infectious virus in urine, vaginal secretions, and breast milk during early recovery when virus is no longer present in the blood. Long-term persistence of Ebola virus in semen, ocular fluid, and cerebrospinal fluid may also occur and is related to the "immune privilege" of these sites. Certain precautions should be taken to reduce the risk of transmission during convalescence, as described below. (See 'Infection control precautions during convalescence' below and 'Breastfeeding and infant care' below and 'Sexual transmission' below.)

Infection control precautions during acute illness

General approach — When caring for patients with confirmed or suspected acute Ebola virus disease, health care personnel should find and follow the most recent infection prevention and control recommendations from the United States Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). These guidelines provide control measures needed to manage patients who are known or suspected to be infected with Ebola virus or other highly pathogenic agents. For the most detailed and updated information, clinicians should refer to the CDC and WHO websites.

Infection control recommendations for patients who present with acute infection include: isolation of hospitalized patients with known or suspected Ebola virus disease; proper hand hygiene; the use of standard, contact, and droplet precautions; and the correct use of appropriate personal protective equipment (PPE). If possible, aerosol-generating procedures should be avoided. If they must be performed, and can be planned, patients should be placed in an airborne infection isolation room. Because some aerosol-generating procedures are urgent (eg, endotracheal intubation), the CDC recommends that PPE, including respirators, be worn at all times in the room of a patient with Ebola virus disease. (See 'Personal protective equipment' below and "Infection prevention: Precautions for preventing transmission of infection", section on 'Airborne precautions'.)

Additional infection control resources and a general overview of infection control principles are presented separately. (See 'Additional resources' below and "Infection prevention: Precautions for preventing transmission of infection".)

Personal protective equipment — The type of PPE used, and its careful placement (donning) and removal (doffing), are critical to preventing nosocomial transmission of Ebola virus. During the 2014-2016 epidemic in West Africa, several patients were cared for in the United States. The staff at Emory University and the National Institutes of Health Clinical Center used disposable full-body suits and powered air-purifying respirators (PAPR) to help staff work for extended periods, decrease the physical discomfort of working in multi-component PPE, and avoid difficulties like fogged face shields [72]. Another trained staff member always observed the donning and doffing of PPE, the latter to ensure no inadvertent contact with potentially contaminated external surfaces.

The CDC and the WHO have issued detailed guidelines on the use of PPE for managing patients with confirmed Ebola virus disease or persons under investigation for suspected Ebola virus disease. Clinicians should refer to these guidelines when caring for patients.

Highlights include:

●PPE should cover all clothing and skin and completely protect all mucous membranes. The specific type of PPE is generally determined by the health care facility providing care and depends, in part, on whether the patient has confirmed Ebola virus disease and on the presence or absence of diarrhea, vomiting, or bleeding.

•When caring for a patient with confirmed Ebola virus disease or a patient with suspected Ebola virus disease who has diarrhea, vomiting, or bleeding, PPE should include double gloves, boot covers, fluid-impermeable gown or coveralls, single-use disposable hoods that cover the head and neck, full face shields, and N95 respirators. PAPRs may be used in place of hoods, face shields, and N95 respirators. Although standard, contact, and droplet precautions are used when caring for patients with Ebola virus disease, health care workers who are in the patient room should use respiratory precautions that provide sufficient protection in case of an unplanned aerosol-generating procedure (eg, endotracheal intubation).

•When caring for a patient with suspected Ebola virus disease who does not have diarrhea, vomiting, or bleeding, minimum PPE includes double gloves, fluid-resistant gown or coveralls, full face shields, and face masks.

●Health care workers should have rigorous and repeated training in correct donning and doffing of PPE. The CDC has released a video that demonstrates the precise sequence and technique for donning and doffing of PPE. A trained observer should actively monitor and instruct each worker donning and doffing PPE. Trained observers should not serve as assistants for taking off PPE.

●Health care workers should also demonstrate competency in performing Ebola-related infection control practices and procedures. As an example, health care workers should perform frequent disinfection of gloved hands using an alcohol-based hand rub, particularly after touching body fluids. In addition, they should immediately disinfect any visibly contaminated PPE using approved disinfectant wipes.

The use of the recommended PPE for extended periods of time in tropical countries can potentially result in heat-related illness, which was of particular concern in West Africa. Recommendations to help prevent such complications include: staying well hydrated, working short shifts until the health care worker can adjust to the heat, taking time to rest and cool down, and watching for signs of heat-related illness.

Health care workers who are pregnant should not provide care for patients with Ebola virus disease. In addition to the increased maternal and fetal risks of Ebola virus disease during pregnancy, PPE may not be well suited for pregnant health care workers.

Labor and delivery — Strict infection control precautions must be used when caring for pregnant patients with Ebola virus disease. This should include PPE that is recommended for providers who are at high risk of exposure to bodily fluids. These precautions should be used even if the mother has recovered from infection, since data suggest that the fetus of a mother who survived Ebola virus disease while pregnant may continue to harbor virus and be infectious [73]. (See 'Considerations during pregnancy' above.)

Environmental infection control — If a patient with suspected or confirmed Ebola virus disease is being cared for in a health care setting, specific precautions should be taken to reduce the potential risk of virus transmission through contact with contaminated surfaces. This includes frequent cleaning and disinfection of the floor in the doffing area (ie, where PPE is removed) by trained staff wearing clean PPE.

The CDC has provided guidance for medical waste management, as well as specific recommendations for environmental infection control in hospitals, health care settings in West Africa, and laboratories. General advice regarding decontamination procedures is discussed elsewhere. (See "Identifying and managing casualties of biological terrorism".)

In a study that surveyed Ebola treatment centers in Sierra Leone, viral RNA was frequently detected on materials that had been in direct contact with patients [74]. As an example, Ebola virus RNA was detected on four of six gloves tested, despite lack of visible soiling. However, viral RNA was no longer detected after gloves were rinsed with chlorine solution. (See 'Infection control precautions during acute illness' above.)

Infection control precautions during convalescence — Patients who have recovered from Ebola virus disease and have been discharged from the hospital may present for medical care during the convalescent period. (See 'Recovery and discharge from the hospital' above.)

Guidance for the management of survivors of Ebola virus disease are provided by the CDC and the WHO. The types of infection control precautions that should be used depend upon the patient's signs and symptoms (table 1).

●For most survivors, only standard precautions are needed when clinical evaluation and care are performed. According to the CDC, there is no evidence that survivors of Ebola virus disease pose any special risk to health care personnel when this care involves contact with intact skin, sweat, tears, conjunctivae, saliva, and cerumen. In addition, persons who have fully recovered and are not febrile do not pose a risk of virus transmission through phlebotomy since they are not viremic. A discussion of standard precautions is presented elsewhere. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions'.)

●However, for patients who present during convalescence with late stage manifestations of Ebola disease, such as acute neurological or ocular symptoms (table 1), infection control practices recommended for evaluating persons under investigation for Ebola virus disease should be used until testing for Ebola virus is negative. (See 'General approach' above.)

●Infection control precautions used for invasive procedures require special consideration if there is potential contact with body fluids from immunologically protected sites (eg, semen, spinal or intraocular fluid). Such patients should be managed in consultation with local health departments and/or the CDC to determine appropriate PPE based upon a risk assessment of the potential exposure during the procedure. (See 'Personal protective equipment' above.)

●When a female Ebola survivor later becomes pregnant, only standard PPE is recommended during delivery since the fetus is presumed not to be infected. The CDC also suggests that no special precautions are needed for spinal anesthesia during delivery as long as the mother does not have neurologic symptoms suggestive of persistent infection. (See "Clinical manifestations and diagnosis of Ebola virus disease", section on 'Convalescence'.)

Additional considerations

Sexual transmission — Several cases of Ebola virus disease that occurred during the late phase of the 2014 to 2016 epidemic were attributed to sexual transmission, with supportive epidemiologic and molecular evidence [15,75,76]. The CDC and WHO suggest that patients with Ebola virus disease refrain from sexual activity (oral, anal, vaginal) and that condoms should be used if abstinence is not followed. In addition, hand hygiene is recommended following contact with semen.

It is not known when unprotected sexual activity can be safely resumed. The WHO has suggested that male survivors of Ebola virus disease practice safe sex (eg, abstinence or barrier protection with condoms) for 12 months from onset of symptoms or, if testing is available, until their semen tests negative twice for Ebola virus by reverse-transcription polymerase chain reaction (RT-PCR) [77].

If testing of semen is performed, the first test should be obtained three months after disease onset [78]:

●For those whose semen tests negative for Ebola virus RNA three months after disease onset, the test should be repeated one week later. Normal sexual activity can be resumed if semen has tested negative for Ebola virus twice by RT-PCR.

●For those whose semen tests positive at three months, testing should be repeated every month until their semen tests negative. The test should then be repeated with an interval of one week between tests. Normal sexual activity can be resumed if the semen has tested negative for Ebola virus twice by RT-PCR.

Although the testing approach is typically preferred, there have been cases in which males have tested negative twice and have subsequently had a positive test. In a cohort of 267 male survivors, viral RNA was detected in semen of 30 percent, an average of 19 months following acute illness [71]. In addition, 44 percent of those positive for viral RNA had two negative tests followed by a positive test; one man had viral RNA detected in semen 40 months after acute illness. Other studies evaluating the persistence of Ebola virus have also detected viral RNA in semen more than three years after disease onset [15,41,71,75,76,79-84].

An outbreak in Guinea in 2016 was linked to a male survivor who had persistent virus in seminal fluid more than 500 days after his initial diagnosis [15,83]. Another outbreak in Guinea in 2021 was determined to be a reappearance of a virus that circulated in 2014, rather than a new introduction from an animal source; however, the mechanism of persistence in humans was not identified [10].

There are fewer data on the persistence of Ebola virus in vaginal fluids. Available studies have detected viral RNA in vaginal fluids for up to 33 days [79,80].

A more detailed discussion on viral persistence and transmission is found elsewhere. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Transmission'.)

Breastfeeding and infant care — Breastfeeding women without Ebola virus disease should be offered vaccination with recombinant vesicular stomatitis virus-Zaire Ebola vaccine (rVSV-ZEBOV) if they are living in an area with an active Zaire ebolavirus outbreak. However, data on the use of vaccination during breastfeeding are limited, and vaccine should be administered in the context of a research or compassionate use protocol. (See 'The rVSV-ZEBOV vaccine' below.)

Among postpartum women with suspected or confirmed Ebola virus disease, breastfeeding should be stopped and a breast milk substitute provided; in addition, the child should be separated from the mother. Ebola virus has been isolated from breast milk, placing the infant at risk of infection. Transmission might also occur through close contact of an infected mother with her children [85,86]. When the infant is also diagnosed with Ebola virus disease, the pair should still be separated and a breast milk substitute provided. However, in this situation, continuation of breastfeeding can be considered in resource-limited settings if no breast milk substitute is available and if the infected infant is under six months of age and cannot otherwise be adequately cared for.

For those women who survive Ebola virus disease and want to resume breastfeeding, testing of breast milk for Ebola virus RNA can guide when it is safe for mothers to resume breastfeeding. Guideline recommendations suggest to withhold breastfeeding pending two consecutive negative tests separated by at least 24 hours.

Additional information on the risk of Ebola transmission through different body fluids is presented elsewhere. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Risk of transmission through different body fluids'.)

Monitoring and travel restrictions — Persons who have had a possible exposure to Ebola virus should be monitored for signs and symptoms of disease. Monitoring should continue for 21 days after the last known exposure; the development of fever and/or other clinical manifestations suggestive of Ebola virus disease should be reported immediately. (See "Clinical manifestations and diagnosis of Ebola virus disease".)

During the West African epidemic, the CDC and WHO provided information about restrictions on travel and transport of asymptomatic persons who had been exposed to Ebola virus. In the setting of an outbreak, specific information, including travel restrictions, can be found on the CDC and WHO websites.

Ebola vaccines

Protection against Zaire ebolavirus — During the epidemic in West Africa, accelerated paths were developed for vaccine testing and introduction into field use [87].

Overview of available vaccines — Two vaccine regimens are approved to provide protection against Ebola virus disease.

●rVSV-ZEBOV – The Ebola Zaire vaccine (live) is a single-dose recombinant vesicular stomatitis virus-Zaire Ebola vaccine (rVSV-ZEBOV; sold as Ervebo). This vaccine meets WHO standards for quality, safety, and efficacy and is approved for use in Europe, the United States, and several countries in Africa for the prevention of Zaire ebolavirus disease. (See 'The rVSV-ZEBOV vaccine' below.)

●The Ad26.ZEBOV/MVA-BN-Filo vaccination strategy – The Ad26.ZEBOV/MVA-BN-Filo vaccination strategy uses two different vaccines separated by eight weeks. The European Medicines Agency granted marketing authorization for the individual components of the vaccine series (recombinant adenovirus AD26.ZEBOV; sold as Zabdeno) and modified vaccinia Ankara (MVA-BN-Filo; sold as Mvabea) for individuals aged one year and older. (See 'The Ad26.ZEBOV/MVA-BN-Filo vaccine' below.)

A new version of the recombinant adenovirus/MVA prime/boost vaccine, designated Ad26.Filo/MVA-BN-Filo, is being investigated. (See 'The Ad26.Filo/MVA-BN-Filo vaccine' below.)

The choice of vaccine is based primarily upon availability. Either vaccine is preferred over no vaccination. However, if availability allows, the rVSV-ZEBOV vaccine is generally preferred, particularly in an outbreak situation, since it is designed as a one-dose vaccine and peak immunity is achieved more rapidly [88,89].

This approach to vaccination was supported in two randomized trials, one that included 1400 adults and another that included 1401 children [88]. In these trials, participants received one of four vaccine regimens (Ad26.ZEBOV/MVA-BN-Filo vaccine series; rVsV-ZEBOV followed by placebo eight weeks later; rVSV-ZEBOV followed by a booster dose of rVSV-ZEBOV eight weeks later; placebo vaccines). An antibody response was defined as an antibody concentration of at least 200 enzyme-linked immunosorbent assay units/mL and an increase from baseline in the antibody concentration by at least a factor of four.

By day 14 after the first injection, the antibody response was greater in those who received active vaccine versus those who received placebo. By day 28, the percent of adults with an antibody response was 36 and 80 percent in the Ad26–MVA group and rVSV-ZEBOV groups, respectively. In children, a vaccine response at day 28 was seen in 66 and 90 percent of those who received the Ad26–MVA and rVSV-ZEBOV, respectively. When looking at the durability of the immune response at month 12, the antibody response was greater in persons who received one of the rVsV-ZEBOV regimens.

The rVSV-ZEBOV vaccine — The Ebola Zaire vaccine (live) is a single-dose recombinant vesicular stomatitis virus-Zaire Ebola vaccine (rVSV-ZEBOV; sold as Ervebo). It is a replication-competent, live-attenuated vaccine that uses a genetically engineered version of vesicular stomatitis virus (VSV), an animal virus that primarily affects cattle (but is generally benign for humans) to carry a Zaire Ebolavirus glycoprotein gene insert. One study found that the vaccine elicits weak, transient antibody and cell-mediated immune responses to the VSV vector in some recipients [90].

●Indications – The rVSV-ZEBOV vaccine is approved for persons 12 months of age or older. Vaccination is indicated in an outbreak setting to protect persons at high risk of contracting Ebola virus. A ring vaccination strategy is often employed, in which the vaccine is provided first to close contacts of patients with Ebola virus disease.

In the United States, the Advisory Committee on Immunization Practices recommends the use of this vaccine as pre-exposure prophylaxis for individuals aged ≥18 years who are at highest risk for potential occupational exposure to the Zaire species of Ebola virus, such as those who are responding to an outbreak of Ebola virus disease, those who work as health care personnel at federally designated Ebola treatment centers in the United States, and staff who work at biosafety level 4 facilities [91]. Approval for use has been expanded to personnel involved in the care and treatment of suspected or confirmed Ebola patients at special pathogens treatment centers and personnel at Laboratory Response Network facilities [92].

The decision to vaccinate pregnant or breastfeeding adults and children must be determined on a case-by-case basis. As an example, pregnant adults were offered vaccination during the 2018 to 2020 outbreak in North Kivu, when the risk of disease was felt to outweigh risk of adverse effects of vaccination. As of May 2023, the FDA and CDC continue to recommend case-by-case evaluation. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Democratic Republic of the Congo'.)

●Dosing/administration – The vaccine is administered as a single dose intramuscularly.

As of January 2023, there are no guidelines regarding the use of booster doses. However, the CDC has initiated an investigational new drug (IND) program for institutions who wish to administer booster doses to those who are at ongoing risk of exposure to Ebola virus.

●Contraindications and adverse events – Contraindications include severe allergic reactions (eg, anaphylaxis) to any component of the vaccine, including rice protein.

Side effects of the vaccine include injection site reactions (eg, pain, swelling, and redness) as well as systemic adverse events such as headache, fever, muscle pain, fatigue, joint pain, nausea, arthritis, rash, and abnormal sweating [91].

More detailed information on vaccine administration, adverse events, and precautions can be found in the Ebola Zaire vaccine live drug monograph included in UpToDate.

Early studies found that the vaccine was generally well tolerated and immunogenic [93-96]. In a study of European and African adults, those who received a single dose of 10 to 50 million plaque-forming units were still Ebola antibody positive after two years [97]. A five-year follow-up study of 84 volunteers vaccinated between 2014 and 2015 found that 42 percent still had neutralizing antibodies [98].

The safety and efficacy of this vaccine were best demonstrated in a large trial of ring vaccination in Guinea [99]. When a new case of Ebola virus disease was diagnosed, surveillance teams identified all close contacts of the patient and all contacts of those contacts. Each of these clusters was then randomized to receive the vaccine either immediately or after 21 days; 3528 subjects were randomized and 3512 were vaccinated (2014 in the immediate arm and 1498 in the delayed arm). Among immediately vaccinated individuals, no Ebola virus disease was seen after day 10, while there were 16 new cases among those assigned to delayed vaccination, indicating a clear benefit of immediate vaccination.

During the 2014 to 2016 West African outbreak, the rVSV-ZEBOV vaccine was administered on a compassionate-use basis to close contacts of a patient with Ebola virus disease, as well as to two health care workers who sustained a percutaneous injury with a needle that had come in contact with a contaminated glove; all recipients remained well [100,101]. A subsequent report described vaccination of 26 people who had been in direct contact with a patient who developed a late reactivation of Ebola virus disease [102]; none acquired the infection, and no severe adverse events were observed.

Based on its demonstrated efficacy in West Africa, the rVSV-ZEBOV vaccine was administered to more than 4000 people during the outbreak in the Équateur Province of the DRC that occurred from May to July 2018. It was then given to 300,000 people during the North Kivu epidemic in the eastern DRC, and its preventive efficacy was determined to be 97.5 percent. It was also given to health care workers in South Sudan and Uganda, bordering the outbreak area in the DRC. A survey of recipients in the eastern DRC found that the vaccine was well tolerated and accepted by the local community [103]. The rVSV-ZEBOV vaccine was used in ring vaccination programs during outbreaks in the DRC. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Democratic Republic of the Congo'.)

An experimental quadrivalent attenuated recombinant VSV vaccine containing an equal mixture of vaccines against the Zaire, Sudan, and Bundibugyo species of Ebola virus and the Angola variant of Marburg virus has been evaluated and found to provide good protection in cynomolgus macaques [104]. Animals were given the quadrivalent vaccine and challenged with one of the four viruses seven days later. All except one challenged with the Zaire virus survived; by contrast, all control animals died. Recombinant VSV vaccines encoding the surface glycoprotein of either the Tai Forest virus or the Bundibugyo virus were protective against those agents in cynomolgus macaques [105,106].

The Ad26.ZEBOV/MVA-BN-Filo vaccine — The Ad26.ZEBOV/MVA-BN-Filo vaccination strategy is a prime-boost approach with two different vaccines administered eight weeks apart:

●The first component consists of a recombinant human adenovirus 26 encoding the Zaire ebolavirus glycoprotein.

●The second dose is a modified vaccinia Ankara virus encoding the glycoproteins of Zaire and Sudan ebolavirus and Marburg Musoke virus, as well as the nucleoprotein of the Tai Forest ebolavirus.

An MVA-BN-Filo booster vaccine should be considered for those who have completed the two-dose vaccination regimen if they are at ongoing risk of exposure to Ebola virus (eg, health care workers, those visiting areas with an ongoing Ebola virus disease outbreak) and more than four months have passed since the second dose was administered [107].

The prime-boost approach was tested in healthy volunteers during the West African epidemic [108-112] and was further evaluated in trials in Tanzania and Uganda [113]. It was also evaluated in a large study in Rwanda among residents who voluntarily received the two-dose vaccine [114]. The vaccines were found to be safe and immunogenic, both separately and in combination. The immune response to the vaccine was not impaired by the occurrence of clinical malaria before or after vaccination [115].

The Ad26.ZEBOV/MVA-BN-Filo vaccine combination was also found to be safe in children in a trial in Sierra Leone [116]. Among children who received the Ad26.ZEBOV/MVA-BN-Filo series, a booster dose of the AD26.ZEBOV vaccine was safe and immunogenic.

The DRC began using the two-dose vaccine in November 2019, during the outbreak in North Kivu [117]. In contrast to the rVSV-ZEBOV vaccine, which was employed in a ring vaccination strategy and administered to health care workers in the outbreak area, the Ad26.ZEBOV/MVA-BN-Filo vaccine was given to at-risk populations in regions with no active disease transmission. A follow-up report found the two-dose vaccine to be safe and immunogenic [118].

Clinical trials are now further examining immune responses in persons given the AD26.ZEBOV vaccine one or two years after receiving the Ad26.ZEBOV/MVA-BN-Filo series. They are also obtaining immunogenicity data in persons with HIV four years after the first series.

The Ad26.Filo/MVA-BN-Filo vaccine — A new version of the recombinant adenovirus/MVA prime/boost vaccine, designated Ad26.Filo/MVA-BN-Filo, has been developed in response to the need for multivalent vaccines against unexpected filovirus outbreaks. The adenovirus component combines three Ad26 viruses encoding the surface glycoproteins of Ebola, Sudan, and Marburg viruses. A randomized trial found this vaccine to be safe and immunogenic, whether the Ad26 component was given before or after the MVA component [119].

Protection against Sudan virus disease — There is no approved vaccine against the Sudan virus. Vaccine candidates for the Sudan virus are in preclinical or early clinical development phases [120].

Several recombinant adenovirus vector vaccines encoding the viral surface glycoprotein appear to be the leading candidates [121]. A recombinant chimpanzee adenovirus encoding the Sudan virus surface glycoprotein (CAd3-EBO S) was found to be safe and immunogenic in a trial among Ugandan adults [122]. A discussion of the 2022 outbreak of Sudan virus disease is presented elsewhere. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Uganda'.)

Post-exposure prophylaxis — Atoltivimab, maftivimab, and odesivimab (REGN-EB3) and ansuvimab (mAb114) are two antibody-based therapies that have been found to be effective for the treatment of Zaire ebolavirus infection [37]. (See 'Ebola-specific therapies' above.)

They have also been used as post-exposure prophylaxis. In one report, they were administered to 23 persons who had experienced an intermediate- or high-risk exposure to a patient with Ebola virus disease; no illness occurred [123].

The role of vaccination for post-exposure prophylaxis is discussed above. (See 'Ebola vaccines' above.)

Public health response — An effective public health response requires effective communications among government authorities, medical professionals, and the local populace to explain the need for monitoring, sample collection and testing, isolation, and other infection control measures, and to explain the potential benefits of vaccination and treatment [124-130]. Preventive interventions also include educating and supporting affected communities to modify long-standing funeral practices and to avoid contact with bush meat and bats [131]. Anthropologists and others with specialized knowledge of local cultures should therefore be included as members of response teams [132-134].

The experience of the West African epidemic demonstrated that an effective public health response and adequate resources could limit the spread of Ebola virus. Measures included access to testing as well as community care centers that were able to isolate persons awaiting test results and provide basic care to those with confirmed Ebola virus disease pending transfer to a treatment unit [20,125,135]. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'West Africa'.)

ADDITIONAL RESOURCES — Selected online resources that address the care of patients with Ebola virus include:

World Health Organization (WHO) Ebola virus page

www.who.int/csr/disease/ebola/en/

United States Centers for Disease Control and Prevention (CDC) Ebola virus page

www.cdc.gov/vhf/ebola/

The Nebraska Ebola method

www.unmc.edu/publichealth/news/ebola-community.html

Emory health care preparedness protocols

www.emoryhealthcare.org/ebola-protocol/ehc-message.html

WHO Ebola virus disease fact sheet

www.who.int/mediacentre/factsheets/fs103/en/

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ebola virus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Ebola (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Treatment

•General approach – Effective treatment of Ebola virus disease requires aggressive supportive care to correct volume losses from vomiting and diarrhea, correct electrolyte abnormalities, and prevent shock. In addition, two different monoclonal antibodies (REGN-EB3 and mAb114) improve survival in patients with Zaire ebolavirus disease. (See 'Supportive care' above and 'Ebola-specific therapies' above.)

•Prognosis and follow up – Early diagnosis and prompt initiation of care increase the likelihood of survival. Those who will survive typically show signs of clinical improvement during the second week of illness. After discharge from the hospital, survivors should be monitored for at least one year. (See 'Prognostic factors' above and 'Recovery and discharge from the hospital' above and 'Follow-up care' above.)

•Obstetrical considerations – Ebola virus disease is associated with a high risk of fetal death and pregnancy-associated hemorrhage. There are no data to suggest whether cesarean or vaginal delivery is preferred or when the baby should be delivered. Thus, decisions regarding obstetrical care must be made on a case-by-case basis. (See 'Considerations during pregnancy' above.)

●Prevention

•Infection control precautions – To prevent transmission of Ebola virus, clinicians should follow infection prevention and control recommendations from the United States Centers for Disease Control and Prevention and the World Health Organization:

-When caring for a patient with acute illness, precautions should include isolation of hospitalized patients with known or suspected Ebola virus disease; hand hygiene; the use of standard, contact, and droplet precautions; and the correct use of appropriate personal protective equipment. In addition, health care workers who are in the room of patients with Ebola virus disease should use respiratory precautions that provide sufficient protection in case of an unplanned aerosol-generating procedure (eg, endotracheal intubation). (See 'Infection control precautions during acute illness' above.)

-For most survivors, only standard precautions are needed when clinical evaluation and care are performed. However, additional precautions are needed for those who present with late stage manifestations of Ebola disease, such as acute neurological or ocular symptoms. (See 'Infection control precautions during convalescence' above.)

•Additional strategies – Additional strategies to prevent the spread of Ebola virus disease include vaccinating high-risk populations, careful monitoring of individuals after a possible virus exposure, and educating patients on how to reduce the risk of transmission through sexual contact or breastfeeding. (See 'Ebola vaccines' above and 'Additional considerations' above.)