Ebola virus disease (EVD), formally known as Ebola hemorrhagic fever, is a severe multi-systemic illness having a high mortality risk. Periodic outbreaks of EVD with case fatality rates 40% to 60% have occurred in equatorial Africa, primarily in remote villages along tropical rainforests of Central Africa (Figure 1) [1,2,41]. Four species of Ebola virus have been identified in connection with symptomatic human infection. Zaire ebolavirus, Bundibugyo ebolavirus, and Sudan ebolavirus are the three species responsible for large outbreaks in Africa. Species Zaire ebolavirus is the most common and most lethal, with case fatality rates of 50% to 90%. Zaire ebolavirus is responsible for 18 of the 28 (64%) recorded EVD outbreaks since 1976, including the two largest EVD outbreaks in history: the 2014–2016 West Africa outbreak and the 2018 outbreak in eastern Democratic Republic of the Congo [22]. Sudan ebolavirus, with a fatality rate of 50%, has caused several outbreaks in Uganda and along the border between South Sudan and the Democratic Republic of the Congo (DRC). Bundibugyo ebolavirus, discovered in 2007, was associated with two outbreaks, one in DRC and the other on the border of DRC and Uganda. Taï Forest ebolavirus was the cause of one case identified in Côte d'Ivoire.

The natural reservoir of Ebola virus and the ecologic perturbations by which the virus emerges to infect humans are poorly understood [34]. EVD is considered a true zoonosis in that a reservoir of Ebola virus exists in the wild, combined with low-level infection in small mammals and nonhuman primates. Humans are an accidental host, increasingly so because of deforestation, hunting, and dietary practices that lead to increased contact with small animals. The 2014–2016 West Africa outbreak has been linked to consumption of fruit bats, which are sometimes used for dietary purposes [7]. Although filoviruses have been identified in bats, and EVD outbreaks have been temporally associated with bat migrations and die-offs, neither bats nor any other mammal has yet been accepted as a definitive Ebola virus reservoir [34].

Ebola virus is thought to gain entry to the human host through mucous membranes or skin abrasions, after which it binds to receptors on the surface of macrophages, monocytes, and dendritic cells [2]. Infected macrophages and monocytes migrate to regional lymph nodes, where continued viral replication and cellular propagation of infection occurs. From lymph nodes, infected monocytes, macrophages, and free virions spread through the lymphatic system to the blood stream, liver, spleen, and adrenal glands. Amplification of infection at these distant sites leads to focal areas of tissue necrosis and the release of ever-increasing numbers of virions into the general circulation [2]. The trophism of Ebola virus extends to multiple cell types, including endothelial cells, fibroblasts, hepatocytes, and adrenocortical cells.

As noted, EVD is an acute, severe, multisystem viral infection that is highly contagious and often fatal [1,3,8,9,33]. The onset of symptoms is usually 5 to 7 days after exposure, though the observed incubation period varies from 2 to 21 days. Illness begins abruptly with fever, chills, and malaise, followed soon after by the rapid onset of weakness, myalgia, headache, vomiting, diarrhea, and abdominal pain. An erythematous maculopapular rash, appearing first on the buttocks and trunk, then more generalized, is often seen between the 5th and 7th day of illness [8]. Other findings include pharyngitis, lymph node enlargement, hepatomegaly, and abdominal tenderness.

The presentation of a febrile patient in an endemic area or after foreign travel raises suspicion for a variety of common acute infections, depending on geographic locale. In residents of or travelers from Central Africa, primary considerations are malaria, typhoid, shigellosis, leptospirosis, dengue fever, rickettsiosis, meningoccocal septicemia, relapsing fever, and hepatitis [1,10].

There is no satisfactory antiviral agent for treatment of EVD. Care is supportive and initial management goals include fluid resuscitation, prevention of intravascular volume depletion, and correction of electrolyte and other metabolic abnormalities [9,11]. Severe hypokalemia and varying degrees of lactic acidosis are common. Vigilance is required for fluid resuscitation that matches losses from vomiting and diarrhea, preventing complications of shock (e.g., metabolic acidosis, acute renal failure, acute lung injury).

The 2014–2016 outbreak has been traced to an index case in Guinea involving a child hospitalized in December 2013. In March 2014, public health officials in Guinea reported more than 40 additional cases, the first formal indication of a regional outbreak [7]. It is thought that during the initial stages of the outbreak severely ill patients were taken to provincial hospitals, where unsuspecting staff and visitors came into direct contact with patients. This in turn led to secondary foci of infection, further expanding the outbreak and establishing new chains of transmission.

Contiguous regions in Liberia, Sierra Leone, and Guinea in West Africa constitute the major locus of the epidemic. A small number of cases appeared transiently in Nigeria, where control measures appear to have been effective in limiting spread. In an analysis of 4,507 cases reported for the first nine months of the outbreak, the World Health Organization (WHO) found that the majority of cases occurred in persons 15 to 44 years of age, and the mean incubation period was 11 days, with a range of 2 to 21 days [3]. Lower attack rates in young children and older adults and higher rates in women presumably reflects differences in exposures associated with caregiving for ill persons [34]. The estimated case fatality rate for the period reported was 71% overall, 64% among hospitalized patients, and 56% among healthcare workers.

During the West Africa outbreak, the CDC provided personnel to assist with active screening and education efforts on the ground in West Africa, aimed at preventing sick travelers from boarding a plane. In addition, airports in Liberia, Sierra Leone, and Guinea screened all outbound passengers by means of a health questionnaire, symptom assessment, and temperature monitoring.

Active post-arrival surveillance included travelers without fever or other symptoms consistent with Ebola, who were monitored daily by state and local health departments for 21 days from the date of their departure from West Africa. Six states (New York, Pennsylvania, Maryland, Virginia, New Jersey, and Georgia), accounting for the large majority of such travelers, implemented active post-arrival monitoring in late October 2014. The CDC also provided post-arrival surveillance assistance to state and local health departments, including information on travelers arriving in their states, and upon request, technical support, consultation, and funding.

All persons entering the patient room should wear at least:

Trained personnel, using PPE as described for routine patient care, should be in charge of collection and handling of soiled re-usable respirators. Although there are limited data available to definitively define AGPs, procedures that are usually included are bilevel positive airway pressure (BiPAP), bronchoscopy, sputum induction, intubation and extubation, and open suctioning of airways.

Healthcare personnel who develop sudden-onset fever, intense weakness or muscle pains, vomiting, diarrhea, or any signs of hemorrhage after an unprotected exposure (e.g., not wearing recommended PPE at the time of patient contact) to a patient with EVD should:

The known or estimated level of risk exposure should guide testing of persons for possible Ebola virus infection. The CDC recommends testing for all persons with onset of fever within 21 days of having a high-risk exposure. A high-risk exposure includes any of the following:

For adults, two samples of whole blood, each a minimum volume of 4 mL, is preferable. For pediatric patient samples, a minimum of 1 mL whole blood should be collected in pediatric-sized collection tubes. Blood must be collected in plastic collection tubes. Do not transport or ship specimens in glass containers or in heparinized tubes.

Public health authorities will determine where ebolavirus testing will occur. Presumptive testing for Ebola virus and Sudan virus is available at select reference laboratories throughout the United States, Specimens should be packaged and transported at 2°–8°C with cold-packs to the final testing destination. Specimens other than blood may be submitted after consultation with CDC by calling the Emergency Operations Center at 770-488-7100.

If the patient dies, handling of the body should be minimized, and the remains should not be embalmed. Instead, remains should be wrapped in sealed, leak-proof material and cremated or buried promptly in a sealed casket. If an autopsy is necessary, the state health department and the CDC should be consulted regarding appropriate precautions.

Visits should be scheduled and controlled to allow for: