The recent emergence of Zaire ebolavirus in West Africa and the scope of the 2014 EVD epidemic have come as a surprise in a region not previously known to harbor Ebola virus. However, sporadic, limited outbreaks of EVD have been documented in rural areas of central Africa for decades. This course will provide recommendations for patient care in the hospital setting that emphasize the importance of strict adherence to patient isolation and barrier precautions, including the proper use of personal protective equipment and environmental infection control measures applicable to any healthcare setting.
This course is designed for physicians, physician assistants, nurses, and allied healthcare professionals involved in the treatment and care of patients with suspected or confirmed Ebola virus disease.
NetCE is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NetCE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.
NetCE designates this enduring material for a maximum of 4 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 4 ANCC contact hour(s). NetCE designates this continuing education activity for 2 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 4.8 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 4 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.4 CEU(s) for this program.
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This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.
In spite of a growing understanding and application of effective control measures, the risk of Ebola virus transmission remains a possibility and a complex issue for communities and hospitals. The purpose of this course is to provide healthcare professionals, and those working in allied health disciplines, an overview of the clinical features, modes of transmission, epidemic potential, and important public health measures required for control of this serious infection.
Upon completion of this course, you should be able to:
- Outline the characteristics and transmission of Ebola viruses.
- Describe the pathogenesis and clinical manifestations of Ebola virus disease (EVD).
- Identify a potential case of EVD on the basis of clinical and epidemiologic considerations.
- Develop a patient management plan that includes supportive care, critical care and/or transfer to a referral hospital designated for this purpose.
- Describe the African Ebola epidemic and its potential impact on global public health.
- Discuss the implications for foreign travel and potential for introduction of Ebola into the United States.
- In the event of a known or suspect case, design a strategy for limited exposure, yet effective supportive care, by healthcare workers, utilizing contact precautions appropriate for the nature and severity of illness
- Discuss the important steps to take if a breach in protocol results in a healthcare worker exposure to Ebola.
- Evaluate and discuss the importance of proper specimen collection, environmental hygiene, handling of human remains, and management of visitors in the control of EVD.
Carol Shenold, RN, ICP, graduated from St. Paul’s Nursing School, Dallas, Texas, achieving her diploma in nursing. Over the past thirty years she has worked in hospital nursing in various states in the areas of obstetrics, orthopedics, intensive care, surgery and general medicine.
Mrs. Shenold served as the Continuum of Care Manager for Vencor Oklahoma City, coordinating quality review, utilization review, Case Management, Infection Control, and Quality Management. During that time, the hospital achieved Accreditation with Commendation with the Joint Commission, with a score of 100.
Mrs. Shenold was previously the Infection Control Nurse for Deaconess Hospital, a 300-bed acute care facility in Oklahoma City. She is an active member of the Association for Professionals in Infection Control and Epidemiology (APIC). She worked for the Oklahoma Foundation for Medical Quality for six years.
John M. Leonard, MD, Professor of Medicine Emeritus, Vanderbilt University School of Medicine, completed his post-graduate clinical training at the Yale and Vanderbilt University Medical Centers before joining the Vanderbilt faculty in 1974. He is a clinician-educator and for many years served as director of residency training and student educational programs for the Vanderbilt University Department of Medicine. Over a career span of 40 years, Dr. Leonard conducted an active practice of general internal medicine and an inpatient consulting practice of infectious diseases.
Contributing faculty, Carol Shenold, RN, ICP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
Contributing faculty, John M. Leonard, MD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
John V. Jurica, MD, MPH
Jane C. Norman, RN, MSN, CNE, PhD
The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.
Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.
It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.
- THE EBOLA VIRUS
- EBOLA VIRUS DISEASE
- THE 2014 EBOLA EPIDEMIC IN WEST AFRICA
- CLINICAL CASE MANAGEMENT: ADVANCED PLANNING
- EXPOSURE EVALUATION PROTOCOL
- DIAGNOSTIC SPECIMEN COLLECTION AND HANDLING
- ENVIRONMENTAL INFECTION CONTROL PROCEDURES
- HANDLING OF HUMAN REMAINS
- MONITORING, MANAGEMENT, AND TRAINING OF VISITORS
- PUBLIC HEALTH EDUCATION
- Works Cited
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#94080: Ebola Virus Disease
Ebola virus disease (EVD), also known as Ebola hemorrhagic fever, is a severe, often fatal illness in humans. EVD outbreaks have a case fatality rate of 50% to 90%, and have occurred primarily in remote villages in Central Africa, near tropical rainforests [1,2]. The virus is transmitted to humans from contact with small mammals and nonhuman primates, and then spreads within the population by human-to-human transmission. Fruit bats of the Pteropodidae family are considered to be one of the natural hosts of the Ebola virus. The 2014 epidemic of EVD was the first in West Africa and the first to affect densely populated urban areas, where transmission is rapid and the attack rate high, resulting in a prolonged, deadly epidemic that has caused serious global public health concerns [3,4].
Prompt identification of Ebola within a community is difficult because early EVD, like other acute infections, presents as a febrile illness with non-specific symptoms and signs. This puts healthcare workers, travelers, and families at risk of inadvertently contracting and transmitting the virus before the true import is known. Consequently, in clinical settings where the possibility for EVD exists, it is imperative that healthcare workers consistently practice stringent Standard Precautions at all times when caring for a febrile patient until the specific diagnosis is known. This requires adherence to basic hand hygiene, respiratory hygiene, personal protective equipment (PPE) according to the risk of splashes or other contact with infected materials, careful injection/infusion technique, and safe burial practices [5,6].
The Centers for Disease Control and Prevention (CDC) website (http://cdc.gov/vhf/ebola) provides updated general information and addresses important issues of public health concern, including clinical guidance and recommendations, diagnosis, laboratory specimen transport, and protection of healthcare workers. Selected material from the CDC website that covers practical issues of case evaluation, infection control, and healthcare worker safety are reproduced in the latter portion of this course.
This course is intended to provide healthcare professionals, and those working in allied health disciplines, an overview of the clinical features, modes of transmission, epidemic potential, and important public health measures required for control of this serious infection.
Ebola virus was first described in 1976, in association with a rural outbreak of hemorrhagic fever near the Ebola River in the Democratic Republic of Congo (formerly Zaire). Subsequently, additional sporadic outbreaks of Ebola infection have been documented in sparsely populated regions of Central Africa. The 2014 outbreak began in the West Africa country of Guinea and spread rapidly to the neighboring countries of Sierra Leone and Liberia [3,7].
The Ebola virus (Ebolavirus), along with Marburgvirus, belongs to the family Filoviridae . The family name comes from the Latin term filum meaning "thread" and refers to the unique elongated (filamentous) morphology of filoviruses. The central core of the virion consists of a single-strand ribonucleic acid (RNA) molecule and its adherent nucleoproteins (the nucleocapsid), enveloped within a lipid bilayer (the viral envelope) derived from the host cell .
Five distinct species of Ebolavirus have been identified, named for the locale in which they were discovered:
Taï Forest ebolavirus
The Zaire, Sudan, and Bundibugya viruses have been associated with periodic large outbreaks in Africa, whereas the Reston and Taï Forest species have not . The Reston species, found in Philippines and the People's Republic of China, can infect humans, but no illness or death in humans from this species has been reported to date.
Both Marburgvirus and Ebolavirus cause sporadic outbreaks of hemorrhagic fever with high case fatality rates in the range of 60% to 90%. A variant strain of Zaire ebolavirus is the apparent cause of the current epidemic in West Africa .
Ebola virus infection is a true zoonosis in that a reservoir of the virus exists in the wild, combined with low-level infection in small mammals and nonhuman primates. Humans become an accidental host in the setting of deforestation, hunting, and dietary practices that lead to increased contact with small animals. The West African outbreak has been linked to a possible reservoir in fruit bats, which are consumed as a food item in some cases .
Once symptomatic human infection is introduced into a family or community, Ebola virus can be easily transmitted person-to-person through direct physical contact, specifically by exposure to bodily fluids such as saliva, vomitus, urine, feces, and blood. Unlike some viruses (e.g., influenza), however, there is no evidence of respiratory transmission among humans, nor is it transmitted by mosquitoes, ticks, or other insect vectors. Burial ceremonies in which mourners have had direct contact with the body of the deceased person have played an important role in the transmission of Ebola in West Africa. In male survivors, Ebola virus has been isolated from semen as long as 61 days after onset of illness .
The virus is somewhat resilient and has been isolated from inanimate environmental surfaces hours after contamination by infected body fluids. Therefore, unless thoroughly disinfected, contaminated surfaces such as clothing, flooring, and furniture may be sources of transmission, as for example if one touches his or her mouth, nose, or eyes after manually handling contaminated material or object .
Healthcare workers are especially vulnerable while treating patients with suspected or confirmed EVD . Exposure occurs through close contact with patients, the handling of soiled clothing or bedding, and improper environmental decontamination practices, hence the imperative of providing effective protective equipment and observing strict Contact Precautions.
Ebola virus is thought to gain entry to the human host through mucous membranes and abrasions in the skin, after which it binds to receptors and lectin on the surface of macrophages, monocytes, and dendritic cells . These mobile cells carry the virus to regional lymph nodes, where further replication occurs. From the lymph nodes, infected monocytes, macrophages, and free virions spread through lymphatic channels and the blood stream to the liver, spleen, and adrenal glands. At these sites, further amplification of infection occurs, releasing ever-increasing numbers of virions into the general circulation. Infection of surrounding hepatocytes and adrenal cortical cells leads to expanding areas of focal necrosis . Ebola virus has a trophism for multiple cell types, including endothelial cells, fibroblasts, hepatocytes, and adrenocortical cells.
Mechanisms of tissue injury are of two types: those in which viral infection of host cells results in direct damage to tissue, and those in which tissue damage is brought about indirectly through interaction between the virus and the host immune system . The virus is able to facilitate propagation and dissemination of infection by suppression of innate and adaptive immune responses. Antigen-specific immune responses are impaired, in part, by preventing T-cell activation. Lymphocytes are not infected directly, but during the course of infection there is widespread and massive apoptosis, contributing to immunosuppression .
Infected macrophages elaborate a variety of inflammatory mediators (cytokines and chemokines) that act in various ways to produce severe multisystem injury. These include cell-surface expression of tissue factors that activate the coagulation cascade and cytokine-mediated vascular endothelial injury, which together lead to disseminated intravascular coagulation (DIC), hypotension, and multi-organ failure . This syndrome resembles the septic shock caused by gram-negative bacillary endotoxemia.
As noted, EVD is an acute, severe, multisystem viral infection that is highly contagious and often fatal [1,3,8,9]. 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 by rapid onset of weakness, myalgia, headache, vomiting, diarrhea, and abdominal pain. An erythematous maculopapular rash, at first on the buttocks and trunk, then more generalized, is often seen between the 5th and 7th day of illness . Other findings include pharyngitis, lymph node enlargement, hepatomegaly, and abdominal tenderness. Early laboratory abnormalities include neutropenia with marked lymphocytopenia, thrombocytopenia, and mild-to-moderate elevations of hepatic aminotransferase enzymes.
With disease progression and fluid losses, patients experience profound weakness, postural hypotension, prostration, confusion, and hemorrhagic manifestations such as gastrointestinal bleeding, ecchymoses, petechiae, and conjunctival hemorrhages [1,8]. Hemorrhagic manifestations reflect ongoing thrombocytopenia and the development of DIC. Metabolic acidosis and electrolyte abnormalities, principally hypokalemia, are common.
Those who survive beyond two weeks usually recover, though after a prolonged convalescence marked by weight loss, asthenia, easy fatigue, and hair loss . In survivors, clinical stability or improvement begins at about day 10 of illness and coincides with the appearance of antibodies and a sharp decline in circulating viral load. Ebola virus has been isolated from breast milk in female survivors and from the semen of male survivors as long as seven weeks after disease onset.
Those who do not survive die from shock, hemorrhage, renal failure, or other inter-current complications such as pneumonia, metabolic acidosis, and cardiorespiratory failure. Fatal illness is associated with persistence and increasing levels of viremia and a near-absence of virus-specific antibody formation. Autopsy studies reveal extensive atrophy of lymphoid tissue, hepatic necrosis, focal necrosis of other organs, and acute tubular necrosis of the kidney [1,8].
The clinical criteria for a presumed case of EVD have been established by the CDC and are as follows :
Elevated body temperature or subjective fever and additional symptoms such as severe headache, muscle pain, vomiting, diarrhea, abdominal pain, or unexplained hemorrhage
Epidemiologic risk factors within the past three weeks before the onset of symptoms, such as any of the following:
Contact with blood or other body fluids of a patient known to have or suspected to have EVD
Residence in—or travel to—an area where Ebola virus transmission is active
Direct handling of bats, rodents, or primates from disease-endemic areas
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, principle considerations are malaria, typhoid, shigellosis, leptospirosis, dengue fever, rickettsiosis, meningoccocal septicemia, relapsing fever, and hepatitis [1,10].
For clinical purposes, early confirmation of the diagnosis of EVD relies on detection of viral genomic material or demonstration of virus-specific antigen in a sample of blood (Table 1). Ebola virus is detectable in blood within one to three days after onset of initial symptoms by use of the reverse transcriptase polymerase chain reaction (RT-PCR). Virus detection in blood samples remains positive for 10 days or more after onset of illness. If the initial diagnostic evaluation occurs more than three days after onset of illness, a subsequent specimen for RT-PCR may be necessary to confidently exclude EVD.
LABORATORY TESTS USED IN DIAGNOSIS OF EVD
|Timeline of Infection||Diagnostic Tests Available|
|Within a few days after symptoms begin||
|Later in disease course or after recovery||IgM and IgG antibodies|
|Retrospectively in deceased patients||
An enzyme-linked immunosorbent assay (ELISA), for detection of viral antigen, is also available. This assay is slightly less sensitive than RT-PCR, usually becoming positive three to five days after onset of illness.
Specimen collection and transfer for diagnostic purposes is a serious biohazard risk. Workers have been exposed to the disease during this process, especially when strict infection control policies are not followed and enforced . (Guidelines for selection, collection, and transport of clinical specimens are discussed in detail later in the course.)
Patients with EVD should be cared for in a single-bed room separate from usual patient care areas, preferably one with an adjacent anteroom for donning and removing PPE. Ideally, designated physician and nursing staff assigned to these patients should have critical care experience or advanced knowledge and training in the care of severely ill and highly infectious patients. Adherence to strict isolation, standard contact precautions, proper utilization of PPE, and effective environmental decontamination practices are all essential for limiting transmission and protecting healthcare workers [6,11].
Because survivors can produce infectious virions for prolonged periods, strict barrier isolation in a private room away from traffic patterns should be maintained throughout the illness. Patient's urine, stool, sputum, and blood, along with any objects that have come in contact with the patient or the patient's body fluids (such as laboratory equipment), should be disinfected with a 0.5% sodium hypochlorite solution .
There is no specific antiviral therapeutic agent or vaccine currently available for treatment of EVD. Care is supportive, with special attention to aggressive fluid resuscitation, prevention of intravascular volume depletion, and correction of electrolyte and acid-base disturbances [9,11]. Severe hypokalemia and varying degrees of lactic acidosis are common. Vigilance is required in order to keep up with fluid losses from vomiting and diarrhea and prevent complications of shock (e.g., metabolic acidosis, acute renal failure, acute lung injury).
While no specific therapy is currently available, novel and experimental therapies have been tried, primarily in animal models, and do hold promise. These include therapeutic and preventive vaccines, serum or blood transfusions from convalescing patients, and monoclonal antibody combinations. ZMapp is a combination of three monoclonal antibodies having neutralizing activity against Ebola virus. In a primate treatment trial, rhesus macaques were given three doses of ZMapp, beginning at varying times up to five days after exposure. All 18 macaques survived . The efficacy of ZMapp in human infection is yet to be established. In recent months, two infected American healthcare workers who survived received ZMapp as part of their therapy.
Anti-RNA virus drugs under development for treatment of other infections have also been tested for activity against Ebola virus. Favipiravir, also designated T-705, is one such drug, an antiviral agent currently in development for treatment of influenza. This drug acts as a nucleotide analog, selectively inhibiting viral RNA-dependent RNA polymerase. Favipiravir suppresses Ebola virus replication in cell culture. In a mouse model of (lethal) Ebola infection, administration of T-705 on day 6 of infection resulted in prompt clearance of viremia and 100% survival. Recovery was associated with virus-specific antibody production and directed T-cell function .
There are no commercially available Ebola vaccines as yet released for use in humans. At present, the leading candidate vaccines are recombinant vectored vaccines in which Ebola virus glycoprotein (GP) is encoded into a replication-incompetent chimpanzee adenovirus type 3 or a replication-competent vesicular stomatitis virus . These vaccines appear to be 100% effective in inducing protective immunity in nonhuman primates, and early results from phase 1 trials indicate that they are relatively safe and immunogenic in humans [24,25].
In one such study, a bivalent cAd3-EBO vaccine encoding the GP from Zaire and Sudan species was tested in 20 healthy adults . This vaccine was evaluated at two dosage levels, varying by one log difference in strength, in a cohort of 10 subjects each. Following a single intramuscular injection, the safety and immunogenicity (GP-specific antibody and T-cell responses) were assessed over a four-week period. While there was no serious safety concern reported, mild side effects were common. Two subjects (in the higher dose cohort) experienced fever, and transient neutropenia was observed in 20% of participants [23,24]. All 20 subjects developed GP-specific antibody. The level of antibody response and the T-cell responses were dose-dependent, being greater in those who received the higher dose vaccine. The CD8 T-cell response, which is thought to correlate well with protective immunity, was 20% at the lower dose and 70% at the higher dose. In the group receiving the higher dose vaccine, GP Zaire-specific antibody responses were in the range previously shown to provide protective immunity in nonhuman primates challenged with Ebola virus . In a ring vaccination trial involving 90 clusters (7,651 vaccinees), the investigational vaccine rVSV-ZEBOV showed an efficacy of 100% with few serious adverse events . Additional clinical trials are in progress.
Ebola first appeared in 1976 in simultaneous outbreaks in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo. The latter was in a village situated near the Ebola River, from which the disease takes its name. Since that time, there have been at least a dozen other sporadic, self-limited outbreaks of EVD confined to rural communities [1,2].
The propensity for nosocomial transmission of Ebola, after severely ill patients are admitted to an inpatient clinical unit, was evident during the 1976 outbreak. At that time, in the 120-bed Yambuku Mission Hospital, secondary cases developed promptly in other patients and staff, in part related to the use of non-sterile syringes and needles. The hospital closed, and many infected people and their contacts fled to their home villages out of fear and suspicion of the Western medicine and began seeking treatment from traditional healers .
The 2014 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 . 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 lead 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 . The estimated case fatality rate for the period reported was 71% overall, 64% among hospitalized patients and 56% among healthcare workers.
As of March 17, 2015, according to data maintained by the CDC, there have been 24,666 known or suspected cases, 14,603 confirmed cases, and 10,179 deaths from of EVD across West Africa . The virulence of Ebolavirus, ease of transmission, and rapidity of spread within large population centers have combined to overwhelm existing clinical care facilities and public health resources within these West African countries . Success in achieving infection control is further confounded by the inadequacy of usual sanitation practices within the populace with respect to care of the sick and burial of the dead.
On August 8, 2014, the WHO declared the West Africa Ebola epidemic a Public Health Emergency of International Concern, thereby invoking the powers of the 2005 International Health Regulations (IHR). In response to a potential pandemic, the IHR requires all countries to develop a national preparedness program, conduct surveillance, exercise public health measures, and report any internationally significant event . The director-general of the WHO further urged those countries with active Ebola transmission to declare a national emergency, activate disaster management plans, and establish emergency operation centers.
With international support, a coordinated effort emerged in West Africa with a strategy for clinical care and infection control aimed at curbing the spread of the epidemic. Public health countermeasures include isolation and quarantine, social distancing, public education, travel restrictions, and enhanced protection of healthcare workers . These measures embrace the following recognized priorities for an effective infection control program:
Sufficient numbers of healthcare workers, trained and properly equipped for rendering care and maintaining strict contact precautions
Rigorous identification and isolation of cases combined with surveillance of primary contacts
Rapid, safe, and culturally sensitive disposal of the dead
Education of the public and community leaders regarding the importance and the means for effective sanitation precautions and safe burial practices
The risk of the Ebola virus being transmitted during air travel is low because, unlike infections such as influenza or tuberculosis, this virus is not spread by inhalation of aerosolized particles from an infected person. Moreover, a person only becomes infectious after having developed symptoms of illness, and transmission of the virus requires direct physical contact with bodily fluids in a manner likely to be extraordinarily rare for travelers on a commercial flight.
There is the possibility that a newly infected traveller from an epidemic zone could enter the United States during the (asymptomatic) incubation period, only to become ill (and thus infectious) some days later. Such a case occurred in October 2014, when a man became ill and was hospitalized in Dallas, Texas, several days after arriving from Liberia. Shortly before his departure from Guinea he had provided bodily assistance to a severely ill woman who subsequently was diagnosed with EVD. This was the first case of EVD to be diagnosed in the United States and was followed shortly by two secondary cases among the hospital nurses who had cared for the patient. This series of events spawned a national discourse on the potential risks from Ebola and on the measures required for effective protection of healthcare workers and control of transmission in the event of an index case . This in turn lead to enhanced assistance to West Africa and to the implementation of a program for identification and surveillance of potentially infected travellers entering this country .
The CDC is assisting with active screening and education efforts on the ground in West Africa to prevent sick travelers from boarding a plane. In addition, airports in Liberia, Sierra Leone, and Guinea screen all outbound passengers during an epidemic by means of a health questionnaire, assessment for symptoms, and temperature monitoring
In October 2014, the CDC implemented an enhanced screening program at five U.S. airports that receive greater than 90% of air passengers whose travel originates from Sierra Leone, Liberia, or Guinea . Travelers from these three countries are taken to a designated area, where each is asked about health status and exposure history, observed for symptoms, and screened for fever. Those with exposure history, symptoms, or fever are evaluated further by CDC officers and referred to local and state health authorities. The remaining travelers are given health information and asked to participate in a self-monitoring, post-arrival, surveillance program .
Active post-arrival monitoring means that even travelers without fever or other symptoms consistent with Ebola will be followed up 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 provides 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.
If an ill passenger enters the United States, the CDC has protocols in place to protect against further disease spread. These include:
Notification to CDC of ill passengers on a plane before arrival
Investigation of ill travelers
Isolation if necessary
The CDC has also provided guidelines to airlines for managing ill passengers and crew and for disinfecting aircraft. The CDC issued a Health Alert Notice reminding U.S. healthcare workers of the importance of taking steps to prevent the spread of Ebola virus, including how to test and isolate suspected patients and how to protect themselves from infection .
There are well-established CDC protocols in place to ensure safe transport and care of patients with infectious diseases back to the United States. These procedures cover each step in the process: transport from bedside to the airport; boarding a non-commercial airplane equipped with a special transport isolation unit; and arrival at a medical facility in the United States that is appropriately equipped and staffed to minimize risk for spread of infection and to ensure that the American public is protected. The protocol is similar to that used for evacuation of patients during the severe acute respiratory syndrome (SARS) outbreak.
On October 6, 2014, the CDC issued a Health Alert Notice Advisory to remind healthcare personnel and health officials to :
Increase vigilance in inquiring about a history of travel to West Africa in the 21 days before illness onset for any patient presenting with fever or other symptoms consistent with Ebola.
Isolate patients who report a travel history to an Ebola-affected country (i.e., Liberia, Sierra Leone, and Guinea) and who are exhibiting Ebola symptoms in a private room with a private bathroom and implement Standard, Contact, and Droplet Precautions (including gowns, facemask, eye protection, and gloves).
Immediately notify the local/state health department.
Early recognition is critical to controlling the spread of Ebola virus. Healthcare personnel should examine the patient's travel history and consider the possibility of Ebola in patients who present with fever, myalgia, headache, abdominal pain, vomiting, diarrhea, or unexplained bleeding or bruising. If a patient reports a history of recent travel to one of the affected West African countries and is symptomatic, immediate action should be taken .
An active early warning approach, under the framework of a surveillance response system, for veterinary and human populations is a key element for prevention in all countries. The institution of electronic-based reporting systems based on advances in information and communication technologies is also an important tool for surveillance .
Another crucial component during an outbreak is to understand cultural practices and customs that can affect behavioral attitudes toward Ebola outbreaks. Lack of understanding about EVD and misinformation concerning hospitalization, treatment, and transmission have frustrated attempts to curtail the epidemic in West Africa. Myth, rumor, and fear have led to avoidance of healthcare centers, refusal of hospitalization, concealing of sick family members at home, and reliance upon local custom and traditional healers. These factors, taken together, have contributed to a heightened mortality risk and served to perpetuate spread of the infection [17,26].
Events surrounding the 2014 epidemic have lead to the recommendation that all inpatient facilities have a plan in place prior to possible encounter with EVD. This plan should address where these patients will be cared for, who will render that care (designated physician and nursing staff), and detailed protocols for PPE utilization and environmental decontamination procedures. The WHO and the CDC have each published clinical care guidelines for hospitals and healthcare workers at their respective websites.
Most U.S. hospitals are capable of admitting a patient to a private room (with bathroom) and observing standard isolation and Contact Precautions. With advanced planning in conformity with CDC infection control recommendations and with the availability of critical care specialists, most should be able to safely and effectively care for a patient with EVD .
Patients should be placed in a single patient room (containing a private bathroom) with the door closed. Facilities should maintain a log of all persons entering the patient's room. Consider posting personnel at the patient's door to ensure appropriate and consistent use of PPE by all persons entering the patient room.
All persons entering the patient room should wear at least:
Gown (fluid resistant or impermeable)
Eye protection (goggles or face shield)
Additional PPE might be required in certain situations (e.g., copious amounts of blood, other body fluids, vomit, or feces present in the environment), including but not limited to:
Disposable shoe covers
Healthcare personnel should don PPE before entry into patient rooms or care areas. Upon exit from the patient room or care area PPE should be carefully removed without contaminating one's eyes, mucous membranes, or clothing with potentially infectious materials and either discarded or, for re-useable PPE, cleaned and disinfected according to the manufacturer's reprocessing instructions and hospital policies. Hand hygiene should be performed immediately after removal of PPE.
Dedicated medical equipment (preferably disposable, when possible) should be used for the provision of patient care. All non-dedicated, non-disposable medical equipment used for patient care should be cleaned and disinfected according to manufacturer's instructions and hospital policies.
Limit the use of needles and other sharps as much as possible when caring for patients with known or suspected EVD. Phlebotomy, invasive procedures, and laboratory testing should be limited to the minimum necessary for essential diagnostic evaluation and medical care. All needles and sharps should be handled with extreme care and disposed in puncture-proof, sealed containers.
All aerosol-generating procedures (AGPs) should be avoided for patients with EVD if at all possible. If performing AGPs, use a combination of measures to reduce exposures. This includes prohibiting visitors during these procedures and limiting the number of healthcare personnel present to only those essential for patient care and support. Conduct the procedures in a private room, ideally in an airborne infection isolation room (AIIR) when feasible. Room doors should be kept closed during the procedure except when entering or leaving the room, and entry and exit should be minimized during and shortly after the procedure.
Healthcare personnel should wear gloves, a gown, disposable shoe covers, and either a face shield that fully covers the front and sides of the face or goggles and respiratory protection that is at least as protective as a National Institute for Occupational Safety and Health (NIOSH)-certified fit-tested N95 filtering face piece respirator or higher (e.g., powered air purifying respiratory or elastomeric respirator) during AGPs. Because of the potential risk to individuals reprocessing reusable respirators, disposable filtering face piece respirators are preferred.
It is important to conduct environmental surface cleaning following established procedures (discussed in detail later in this course). If re-usable equipment or PPE (e.g., powered air purifying respirator, elastomeric respirator) are used, they should be cleaned and disinfected according to manufacturer instructions and hospital policies.
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.
Facilities should develop policies for monitoring and management of potentially exposed healthcare personnel. Facilities should develop sick leave policies for healthcare personnel that are non-punitive, flexible, and consistent with public health guidance. All healthcare personnel, including staff who are not directly employed by the healthcare facility but provide essential daily services, should be aware of the sick leave policies. Persons with percutaneous or mucocutaneous exposures to blood, body fluids, secretions, or excretions from a patient with suspected EVD should stop working and immediately wash the affected skin surfaces with soap and water. Mucous membranes (e.g., conjunctiva) should be irrigated with copious amounts of water or eyewash solution. In addition, the individual should immediately contact an occupational health representative or supervisor for assessment and access to postexposure management services for all appropriate pathogens (e.g., human immunodeficiency virus, hepatitis C).
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:
Not report to work or should immediately stop working
Notify their supervisor
Seek prompt medical evaluation and testing
Notify local and state health departments
Comply with work exclusion until they are deemed no longer infectious to others
Asymptomatic healthcare personnel who had an unprotected exposure to a patient with EVD should receive medical evaluation and follow-up care, including fever monitoring twice daily, for 21 days after the last known exposure. Hospitals should consider policies ensuring twice daily contact with exposed personnel in order to discuss potential symptoms and document fever checks. Personnel may continue to work while receiving twice daily fever checks, based upon hospital policy and discussion with local, state, and federal public health officials. Consultation with an infectious diseases expert is recommended for exposed persons who develop fever within 21 days of exposure.
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:
Percutaneous or mucous membrane exposure or direct skin contact with body fluids of a person with a confirmed or suspected case of EVD without appropriate PPE
Laboratory processing of body fluids of suspected or confirmed EVD cases without appropriate PPE or standard biosafety precautions
Participation in funeral rites or other direct exposure to human remains in the geographic area where the outbreak is occurring without appropriate PPE
For persons with a high-risk exposure but without a fever, testing is recommended only if there are other compatible clinical symptoms present and blood work findings are abnormal (i.e., thrombocytopenia <150,000 cells/µL and/or elevated transaminases) or unknown.
Persons considered to have a low-risk exposure include those who spent time in a healthcare facility where patients with EVD are being treated (including healthcare workers who used appropriate PPE, employees not involved in direct patient care, and other hospital patients who did not have EVD and their family caretakers) and household members of an Ebola patient without high-risk exposures (as defined). Persons who had direct unprotected contact with bats or primates from an endemic area would also be considered to have a low-risk exposure.
Testing is recommended for persons with a low-risk exposure who develop fever with other symptoms and have unknown or abnormal blood work findings. Persons with a low-risk exposure and with fever and abnormal blood work findings in the absence of other symptoms are also recommended for testing. Asymptomatic persons with high- or low-risk exposures should be monitored daily for fever and symptoms for 21 days from the last known exposure and evaluated medically at the first indication of illness.
Persons with no known exposures but who have fever and other symptoms or abnormal bloodwork within 21 days of visiting countries where Ebola virus transmission is active should be considered for testing. Consultation with local and state health departments is recommended in these cases.
If testing is indicated, the local or state health department should be immediately notified. Healthcare providers should collect serum, plasma, or whole blood. A minimum sample volume of 4 mL should be shipped refrigerated or frozen on ice pack or dry ice (no glass tubes), in accordance with International Air Transport Association guidelines as a Category B diagnostic specimen [6,21].
Healthcare personnel should perform hand hygiene frequently, including before and after all patient contact, contact with potentially infectious material, and before putting on and taking off PPE, including gloves. Healthcare facilities should ensure that supplies for performing hand hygiene are available.
Acceptable hand hygiene in healthcare settings includes both washing with soap and water or using alcohol-based hand rubs. If hands are visibly soiled, use soap and water, not alcohol-based hand rubs.
The following section is reprinted from the CDC's Interim Guidance for Specimen Collection, Transport, Testing, and Submission for Patients with Suspected Infection with Ebola Virus Disease .
It is expected that all laboratories and other healthcare personnel collecting or handling specimens follow established standards compliant with the Occupational Safety and Health Administration bloodborne pathogens standard, which encompasses blood and other potentially infectious materials. This includes wearing appropriate PPE and adhering to engineered safeguards for all specimens regardless of whether they are identified as being infectious.
Recommendations for specimen collection include full face shield or goggles, masks to cover all of the nose and mouth, gloves, and fluid-resistant or impermeable gowns. Additional PPE may be required in certain situations.
While obtaining clinical laboratory specimens from the patient, use infection control precautions for patient care. Place specimens in sealed plastic bags, then transport them in a clearly labeled, durable, leak-proof container directly to the specimen handling area of the laboratory. Care should be taken not to contaminate the external surfaces of containers.
Process clinical specimens in a class II biological safety cabinet following biosafety level 3 practices. If possible, pretreat serum used in laboratory tests with the combination of heat-inactivation at 56° C and polyethylene glycol p-tert-octylphenyl ether (Triton X-100); treatment with 10 uL of 10% Triton X-100 per 1 mL of serum for one hour reduces the titer of hemorrhagic fever viruses in serum, although 100% efficacy in inactivating these viruses should not be assumed. For tests in which the validity is affected by the presence of a detergent in the serum, heat inactivation alone may be of some benefit in reducing infectivity.
Attempts to isolate or cultivate the virus should not be part of routine clinical laboratory diagnosis when EVD is suspected. If such procedures are done on specimens where EVD is suspected, biosafety level 4 facilities and procedures are required .
It is recommended that laboratory personnel take the following precautions when handling specimens for diagnostic testing: full face shield or goggles, masks to cover all of nose and mouth, gloves, fluid resistant or impermeable gowns, and use of a certified class II biosafety cabinet or Plexiglas splash guard, as well as manufacturer-installed safety features for instruments. Blood smears (e.g., for malaria) are not infectious for EVD after fixation in solvents.
Routine laboratory testing includes traditional blood chemistry and hematologic measurements, urinalysis, microbiology laboratory culture (for other pathogens), and any other laboratory testing used to support and treat patients. Precautions as described above offer appropriate protection for healthcare personnel performing laboratory testing on specimens from patients with suspected infection with Ebola virus.
When used according to the manufacturer's instructions, Environmental Protection Agency (EPA)-registered disinfectants routinely used to decontaminate the laboratory environment (e.g., bench tops and surfaces) and the laboratory instrumentation are sufficient to inactivate enveloped viruses, such as influenza, hepatitis C, and Ebola viruses.
Routine cleaning and disinfecting procedures can be used for automated analyzers. Analyzers should be disinfected after use as recommended by the manufacturer or with a 500 parts per million solution (1:100 dilution) of sodium hypochlorite (1/4 cup of household bleach to 1 gallon water).
A minimum volume of 4 mL whole blood preserved with ethylene-diamine-tetra-acidic acid, clot activator, sodium polyanethol sulfonate, or citrate in plastic collection tubes can be submitted for EVD testing. Do not submit specimens to the CDC in glass containers or preserved in heparin tubes. Specimens should be stored at 4° C or frozen. Specimens other than blood may be submitted upon consult with the CDC by calling the Emergency Operations Center (EOC) at (770) 488-7100.
Standard labeling should be applied for each specimen. The requested test only needs to be identified on the requisition and CDC specimen submission forms.
Specimens collected for EVD testing should be packaged and shipped without attempting to open collection tubes or aliquot specimens. Specimens for shipment should be packaged following the basic triple packaging system, which consists of a primary receptacle (a sealable specimen bag) wrapped with absorbent material, a secondary receptacle (watertight, leak-proof), and an outer shipping package.
The following steps outline the submission process to the CDC:
Hospitals should follow their state and/or local health department procedures for notification and consultation for Ebola testing requests and prior to contacting the CDC.
No specimens will be accepted without prior consultation. For consultation, call the EOC at (770) 488-7100.
Contact the state and/or local health department and the CDC to determine the proper category for shipment based on clinical history and risk assessment by the CDC. State guidelines may differ, and state or local health departments should be consulted prior to shipping.
Email the tracking number to EOCEVENT246@CDC.gov.
Do not ship for weekend delivery unless instructed by the CDC.
Ship to the Centers for Disease Control and Prevention, ATTN: STAT LAB: VSPB, UNIT #70, 1600 Clifton Road NE, Atlanta, GA, 30333.
Include the following information: your name, the patient's name, test(s) requested, date of collection, laboratory or accession number, and the type of specimen being shipped.
Include the CDC Infectious Disease and Viral Special Pathogens Branch form, available at http://www.cdc.gov/laboratory/specimen-submission/pdf/form-50-34.pdf.
On the outside of the box, specify how the specimen should be stored (i.e., refrigerated or frozen).
For grossly soiled surfaces (e.g., vomitus, stool), use a 1:10 dilution of household bleach for cleaning and disinfection. In all other cases, a 1:100 dilution is sufficient. Soiled linens should be placed in clearly labeled, leak-proof bags at the site of use, transported directly to the laundry area, and laundered following routine healthcare laundry procedures.
Liquid medical waste, such as feces and vomitus, can be disposed of in the sanitary sewer following local sewage disposal requirements. Care should be taken to avoid splashing when disposing of these materials.
When discarding solid medical waste (e.g., needles, syringes, tubing) contaminated with blood or other body fluids from patients with EVD, contain the waste with minimal agitation during handling. Properly contained wastes should be managed according to existing local and state regulations for ensuring health and environmental safety during medical waste treatment and disposal. On-site treatment of the waste in an incinerator or a gravity-displacement autoclave for decontamination purposes will help to minimize the risks of handling contaminated waste. Alternatively, off-site medical waste treatment resources may be used.
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.
Visitors who have been in contact with a patient with EVD before and during hospitalization are a possible source of Ebola infection for other patients, visitors, and staff. Visitor movement within the facility should be restricted to the patient care area and an immediately adjacent waiting area; avoid entry of visitors into the patient's room. Exceptions may be considered on a case-by-case basis for those who are essential for the patient's well-being. Establish procedures for monitoring, managing, and training visitors. For example, a visitor log should be kept of those who enter and exit the patient's room.
Visits should be scheduled and controlled to allow for:
Screening for active Ebola infection (e.g., fever and other symptoms) before entering or upon arrival to the hospital
Evaluating risk to the health of the visitor and ability to comply with precautions
Providing instruction before entry into the patient care area on hand hygiene, limiting surfaces touched, and use of PPE according to the current facility policy while in the patient's room
In the absence of specific treatment and a human vaccine, raising community awareness of the risk factors for Ebola infection and the protective measures individuals can take is an important means for reducing the risk of human infection and death. During EVD outbreaks in Africa, educational public health messages for risk reduction have focused on:
Reducing the risk of wildlife-to-human transmission from contact with infected animals such as fruit bats or monkeys/apes. Animals should be handled with gloves and other protective clothing. Animal products should be thoroughly cooked before consumption.
Reducing human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their bodily fluids. Gloves and appropriate PPE should be worn when taking care of ill patients at home. Regular hand washing is required after visiting patients in hospitals, as well as after taking care of patients at home.
Providing education to the public in communities affected by Ebola about the nature of the disease and about outbreak containment measures, including the prompt and safe burial of the dead.
The emergence of Zaire ebolavirus in West Africa and the scope of the 2014 EVD epidemic have come as a surprise in a region not previously known to harbor Ebola virus. However, sporadic, limited outbreaks of EVD have been documented in rural areas of Central Africa for decades.
The 2014 outbreak of Zaire ebolavirus in West Africa and the focal, brief cluster of cases in Dallas, Texas, demonstrate the difficult clinical challenges of effective case management and control of transmission in the hospital setting. Also in evidence is the limited preparedness of public health systems to respond to emerging, highly virulent communicable diseases. However, the medical and public health sectors, here and abroad, have moved to improve education, heighten vigilance, and put in place proven epidemiologic principles for limiting transmission and achieving control of epidemic spread.
The CDC website maintains a portfolio of information on EVD for hospitals and healthcare professionals, one that addresses all aspects of diagnosis, patient care, case management, and protection of healthcare workers. Recommendations for patient care in the hospital setting emphasize the importance of strict adherence to patient isolation and barrier precautions, including the proper use of PPE and environmental infection control measures applicable to any healthcare setting.
|Centers for Disease Control and Prevention|
|World Health Organization|
|National Institutes of Health|
|U.S. Africa Command|
2. Mahanty S, Bray M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis. 2004;4:487-498.
3. WHO Response Team. Ebola virus disease in West Africa: the first 9 months of the epidemic and forward projections. N Engl J Med. 2014;371:1481-1495.
5. Briand S, Bertherat E, Cox P, et al. The international Ebola emergency. N Engl J Med. 2014;371:1180-1183.
6. Centers for Disease Control and Prevention. Infection Prevention and Control Recommendations for Hospitalized Patients with Known or Suspected Ebola Hemorrhagic Fever in U.S. Hospitals. Available at http://www.cdc.gov/vhf/ebola/hcp/infection-prevention-and-control-recommendations.html. Last accessed March 26, 2015.
7. Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014;371:1418-1425.
8. Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011;204(Suppl 3):S810-S816.
9. 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;190:733-737.
10. Wilson ME, Weld LH, Boggild A, et al. Fever in returned travelers: results from the GeoSentinal Surveillance Network. Clin Infect Dis. 2007;44:1560-1568.
11. Funk DJ, Kumar A. Ebola virus disease: an update for anesthesiologists and intensivists. Can J Anesth. 2015;62:80-91.
12. Oestereich L, Ludtke A, Wurr S, Reiger T, Munoz-Fontela C, Gunther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014;105:17-21.
13. Centers for Disease Control and Prevention. Ebola Outbreak in West Africa. Available at http://www.cdc.gov/vhf/ebola/outbreaks/guinea/index.html. Last accessed March 18, 2015.
14. Edmond MB, Diekema DJ, Perencevich EN. Ebola virus disease and the need for new personal protective equipment. JAMA. 2014;312(23):2495-2496.
15. Gostin LO, Hodge JG, Burris S. Is the United States prepared for Ebola? JAMA. 2014;312(23):2497-2498.
16. Centers for Disease Control and Prevention. Evaluating Patients for Possible Ebola Virus Disease: Recommendations for Healthcare Personnel and Health Officials. Available at http://emergency.cdc.gov/han/han00371.asp. Last accessed February 13, 2015.
17. Tambo E, Ugwu EC, Ngogang JY. Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries. Infect Dis Poverty. 2014;3:29.
18. Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514:47-53.
19. Emond RT, Evans B, Bowen ET, Lloyd G. A case of Ebola virus infection. Br Med J. 1977;2(6086):541-544.
20. Centers for Disease Control and Prevention. Case Definition for Ebola Virus Disease (EVD). Available at http://www.cdc.gov/vhf/ebola/healthcare-us/evaluating-patients/case-definition.html. Last accessed February 12, 2015.
21. Centers for Disorder Control and Prevention. Interim Guidance for Specimen Collection, Transport, Testing, and Submission for Patients with Suspected Infection with Ebola Virus Disease. Available at http://www.cdc.gov/vhf/ebola/healthcare-us/laboratories/specimens.html. Last accessed February 12, 2015.
22. Centers for Disease Control and Prevention. Ebola Hemorrhagic Fever Information Packet. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/fact_sheets/ebola_fact_booklet.pdf. Last accessed February 13, 2015.
23. Bausch DO. One step closer to an Ebola virus vaccine. N Engl J Med. 2014; [Epub ahead of print].
24. Ledgerwood JE, DeZure AD, Stanley DA, et al. Chimpanzee adenovirus vector Ebola vaccine: preliminary report. N Engl J Med. 2014; [Epub ahead of print].
25. Rampling T, Ewer K, Boyer G, et al. A monovalent chimpanzee adenovirus Ebola vaccine: preliminary report. N Engl J Med. 2015; [Epub ahead of print].
26. Shultz JM, Baingana F, Nuria Y. The 2014 Ebola outbreak and mental health: current status and recommended response. JAMA. 2015;313(6):567-568.
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