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The purpose of this education is to inform the reader regarding Ebola virus disease and Marburg hemorrhagic fever as well as provide general instruction regarding the identification and treatment of the virus.
Ebola virus disease (EVD), first recognized in 1976 in the Democratic Republic of the Congo (DRC, formerly Zaire), is a serious and often fatal illness in humans and nonhuman primates caused by infection with one of six Ebola virus species, four of which can infect humans (National Institute of Allergy and Infectious Diseases [NIAID], 2019a). The worldwide average fatality rate for EVD is 50% (World Health Organization [WHO], 2019). The 2014 outbreak affected several countries and continents. During the 2014-2016 epidemic, eleven people in the United States became ill and were treated. The first travel-associated case of EVD diagnosed in the United States was confirmed by the Centers for Disease Control and Prevention (CDC, 2018a) on September 30, 2014. The index case, a man who became infected after traveling from West Africa, died in Dallas, Texas, on October 8, 2014. During his care, two of the healthcare providers in Dallas also became infected, but both were successfully treated and eventually recovered (CDC, 2018a). There are six species within the Ebolavirus genus, four of which have caused disease in humans:
- Zaïre ebolavirus (EBOV)
- Sudan ebolavirus (SUDV)
- Tai Forest virus (TAFV) (formerly known as Ebola Ivory Coast)
- Bundibugyo ebolavirus (BDBV)
- Reston ebolavirus (RESTV)
- Bombali ebolavirus (Public Health England, 2019).
Marburg virus was first recognized in 1967 when laboratory workers developed a hemorrhagic fever after being exposed to green monkeys from Africa or their tissues during research. These outbreaks occurred in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia (now Serbia). After laboratory workers became ill, the illness then spread to their caregivers, both healthcare providers and family members. Eventually, seven individuals died, and a total of 31 became ill (CDC, 2014).
Biosafety level (BSL): a set of biocontainment precautions that are standardized by the CDC to ensure safety when researching or handling potentially dangerous/infectious biological agents within a laboratory setting. There are four BSLs, increasing security from levels 1 to 4. BSL-4 is the highest level of biological safety. There are very few BSL-4 labs in the US and globally. BSL-4 labs specialize in safely handling exotic or dangerous and exotic microbes, which can be highly dangerous if mishandled and transmitted. The resulting infections may be fatal, untreatable, or without an effective vaccine. This includes the Ebola and Marburg viruses (CDC, n.d.).
Confirmed Case: “a laboratory-confirmed diagnostic evidence of Ebola virus infection” (CDC, 2019a, para. 3).
Ebola virus disease (EVD): “a rare and deadly viral illness that is reportable to the National Notifiable Disease Surveillance System (NNDSS) in all US states and territories. Early recognition of EVD is critical for infection control. Healthcare providers should be alert for and evaluate any patients suspected of having EVD” (CDC, 2019a, para. 1).
Emergency Use Authorization (EUA): “Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the US Food and Drug Administration (FDA) Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions … when there are no adequate, approved, and available alternatives. Section 564 of the FD&C Act was amended by the Project Bioshield Act of 2004 and was further amended by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), the 21st Century Cures Act of 2016, and Public Law 115-92 of 2017” (FDA, 2019, para, 2-3).
Index case: a person who first draws attention to his or her family because of having a medical condition. For example, if an eye doctor discovers a person has glaucoma, and subsequently, other cases of glaucoma are found in the person's family, that person is the index case. They are also known as propositus (if male) or proposita (if female) (Shiel, 2018a).
Laboratory Response Network (LRN): the US's “laboratory emergency response system for biological, chemical and radiological threats and other public emergencies such as natural disasters. Founded in 1999 by the Association of Public Health Laboratories (APHL), the CDC and the FBI to improve US readiness for bioterrorism, the LRN remains a valuable resource for law enforcement and public health officials. It links local, state and federal public health laboratories with sentinel clinical, food, veterinary, environmental and agricultural laboratories; and military and international laboratory centers. Over time, the US Department of Defense has become an LRN stakeholder, joining in strategic planning and supporting LRN biological response activities, notably the 2014 response to the outbreak of Ebola” (APHL, 2019, para. 2).
Marburg hemorrhagic fever (Marburg HF): a rare but severe hemorrhagic fever which affects both humans and nonhuman primates. Marburg HF is caused by Marburg virus, a genetically unique zoonotic (animal-borne) RNA virus of the filovirus family, which also includes the six species of Ebola virus (CDC, 2014).
Person Under Investigation (PUI): “a person who has both consistent signs or symptoms and risk factors should be considered a PUI:
- Elevated body temperature or subjective fever or symptoms, including severe headache, fatigue, muscle pain, vomiting, diarrhea, abdominal pain, or unexplained hemorrhage; AND
- An epidemiologic risk factor within the 21 days before the onset of symptoms” (CDC, 2019a, para. 2).
Reverse Transcription-Polymerase Chain Reaction (RT-PCR): “a highly sensitive technique for the detection and quantitation of messenger RNA (mRNA). The technique consists of two parts:
• The synthesis of complementary DNA (cDNA) from RNA by reverse transcription (RT) and
• The amplification of a specific cDNA by the polymerase chain reaction (PCR).
RT-PCR has been used to measure viral load with HIV and may also be used with other RNA viruses such as measles and mumps” (Shiel, 2018b, para. 1).
Incidence and Prevalence
There were no cases or outbreaks of EVD reported between 1979 and 1994. Since that time, outbreaks have been recognized with increasing frequency (Public Health England, 2019). Between 1976 and 2014, most outbreaks of EVD occurred in remote African villages close to tropical rainforests in Central and West Africa. Most confirmed cases were reported from the DRC, Sudan, Gabon, Uganda, and the Republic of Congo (Martell, Masterson, McGreig, Michaelis, & Wass, 2019). In 2014, Ebola outbreaks occurred for the first time in Guinea, Liberia, and Sierra Leone, which are in West Africa. Transmission occurred primarily in urban areas. Ebola cases were imported into Italy, Nigeria, Mali, Senegal, Spain, the UK, and the US during this outbreak as well (Public Health England, 2019). This became the largest outbreak to date, lasting from March 2014 and June 2016 and affecting primarily Guinea, Liberia, and Sierra Leone, with over 28,000 cases recorded. The current EVD outbreak has been ongoing in the DRC since August 2018, with over 2,600 confirmed or probable cases reported by July 25, 2019. (Public Health England, 2019). This is their tenth outbreak of Ebola in 40 years in DRC. The outbreak is centered in the northeast of the country, in the North Kivu and Ituri provinces. The number of cases has now surpassed 3,000, making this the DRC's largest Ebola outbreak and the world’s second-largest Ebola outbreak ever recorded (Médecins Sans Frontières International, 2018). Please see Box 1 (below) for a chronological synopsis of the 2018 ongoing outbreak.
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- August 1, 2018: Outbreak declared by the DRC Ministry of Health.
- Early August 2018: First U.S. CDC staff deployed to North Kivu province to assist in response efforts.
- August 7-8, 2018: Genetic tests confirm outbreak; vaccination efforts begin.
- August-September 2018: U.S. government pulls back staff from outbreak area due to security concerns.
- September 21, 2018: USAID deployed a Disaster Assistance Response Team (DART) to the DRC.
- October 17, 2018: The WHO convened an Emergency Committee which recommends against a “public health emergency of international concern” (PHEIC) declaration with regard to the DRC Ebola outbreak.
- November 9, 2018: Ebola case count surpasses largest number from previous DRC outbreaks, making this the largest Ebola outbreak in the DRC’s history.
- Late November 2018: Ebola case count surpasses all but the 2014-2015 West Africa outbreak, making this the second largest Ebola outbreak ever.
- Late December 2018: Voting in the DRC elections postponed in certain Ebola-affected areas, sparking protests.
- February 24, 2019: Ebola treatment center attacked and partially burned down, leading the Medicins Sans Frontieres to suspend services at the center; another center was attacked three days later, leading the group to suspend all activities in the area.
- March 30, 2019: Ebola case count in this DRC outbreak surpasses 1,000.
- April 12, 2019: Second WHO Emergency Committee recommends for a second time against a PHEIC declaration with regard to the DRC Ebola outbreak.
- April 15, 2019: The DRC Ministry of Health reports over 100,000 people have been vaccinated in this outbreak to date.
- April 19, 2019: WHO epidemiologist from Cameroon killed when a clinic was attacked in Butembo in the DRC.
- June 5, 2019: Ebola case count in the DRC outbreak surpasses 2,000.
- June 11, 2019: Uganda confirmed first imported case of Ebola, with two additional cases reported the next day.
- June 14, 2019: Third WHO Emergency Committee recommends for a third time against a PHEIC declaration with regard to the DRC Ebola outbreak.
- July 14, 2019: The DRC government reports first case in Goma, capital of North Kivu province and a large city of 1-2 million people bordering Rwanda.
- July 17, 2019: WHO Emergency Committee meets for a fourth time; WHO Director-General accepts the Committee’s assessment and declares the DRC Ebola outbreak a PHEIC.
- August 16, 2019: First Ebola cases confirmed in South Kivu province, the third province to see cases in this outbreak.
- August 29, 2019: Ebola case count in the DRC surpasses 3,000; Uganda reports a fourth imported Ebola case (The Henry J Kaiser Family Foundation, 2019, para. 9).
Of the six species within the Ebolavirus genus, only EBOV, SUDV, BDBV, and TAFV are known to be pathogenic to humans (Martell et al., 2019). Reston ebolavirus (RESTV), does not cause illness in humans but causes severe illness in nonhuman primates. It was first detected in a colony of imported monkeys from the Philippines in Reston, Virginia, in 1989. It has since caused outbreaks in other primates in Pennsylvania, Texas, and Italy. Humans working with the monkeys have been infected during these outbreaks without becoming ill. An export facility in the Philippines was found to be the source of the outbreaks, but it has not been determined how the facility was contaminated. In 2008, RESTV infected a group of pigs in the Philippines. Again, humans working with the pigs developed antibodies but remained asymptomatic (Public Health England, 2019). In August 2018, the 6th species of Ebola virus, Bombali, was identified in the the Bombali region of Sierra Leone. Currently, it is not known if the Bombali virus causes disease in humans (Martell et al., 2019).
These viruses cause severe and systemic febrile disease. Despite their notoriety concerning propensity regarding outbreaks, the pathophysiology of EVD in humans is not well understood. Specifically, very little is known about human immunity and these viruses, what features correlate most with survival, and how to elicit an immune memory of the virus to begin vaccine development. This lack of knowledge is likely related to the minimal amount of clinical and laboratory data gathered from past outbreaks (Muñoz-Fontela & McElroy, 2017). Innate antibodies developed during an infection can last ten years, possibly longer. Unfortunately, it is unclear if this confers immunity for life or also provides immunity against other Ebola species (CDC, 2019c).
Risk and Protective Factors
For most people, the risk of getting Ebola hemorrhagic fever or Marburg HF is low. The risk increases if people:
- Travel to Africa- patients who visit or work in areas where EBOV or Marburg virus outbreaks have occurred.
- Conduct animal research- people who work with monkeys imported from Africa or the Philippines.
- Provide medical or personal care- those caring for sick relatives are most at risk, as well as healthcare providers who don't use proper protective equipment and follow transmission precautions diligently.
- Prepare people for burial- those who prepare and handle bodies before burial may contract the virus from the body fluids and tissues of the recently deceased (Mayo Clinic, 2017).
Signs and Symptoms
The incubation period for EVD may be 2 to 21 days after initial contact, with an average of 8 to 10 days. Symptoms typically progress from “dry” ( fever, aches, pains, and fatigue), and to “wet” (diarrhea and vomiting) as the person becomes sicker (CDC, 2019b). Primary signs and symptoms of EVD often include:
- Aches and pains (headache, abdominal pain, or muscle and joint pain),
- Weakness and fatigue,
- Gastrointestinal symptoms including diarrhea and vomiting,
- Suspicious hemorrhaging, bleeding, or bruising (CDC, 2019b).
Later stages of the illness may present with red eyes, hiccups, and skin rash. Unfortunately, this list of symptoms is not terribly different from influenza (flu), malaria, typhoid fever, or other common viral illnesses (CDC, 2019b)
Early recognition is critical to controlling the spread of the Ebola virus. First, risk should be assessed with a thorough health history, including travel to any endemic areas or contact with any sick or infected individuals in the previous 21 days. If suspicious, the patient should be placed in a single room, with a private bathroom, and transmission precautions, as well as standard precautions, should be implemented immediately. This includes contact precautions and droplet precautions. The nurse must utilize the recommended personal protective equipment (PPE) diligently. The healthcare team should contact infection control personnel within the facility, as well as local and state health departments. The health department officials will assist in securing the appropriate confirmatory testing, identification of contacts, and notifying the CDC’s Emergency Operations Center (CDC, 2018c, 2019a).
Laboratory diagnosis of EVD is critical in outbreak response efforts, but safe and efficient diagnostic testing for this dangerous BLS-4 pathogen in challenging environments without sufficient resources is extremely challenging. Since its discovery, diagnostic methodologies have trended toward molecular assays as they are fast and accurate. Additionally, technology has allowed for smaller, more local testing facilities that are more conveniently located near the source of an outbreak (Broadhurst, Brooks, & Pollock, 2016). The WHO (2019)currently recommends the use of nucleic acid tests (NAT) for routine diagnosis, and these may be automated or semi-automated. When these are not readily available (remote settings), rapid antigen detection tests can be used for screening purposes. Whole blood in ethylenediaminetetraacetic acid (EDTA) should be used for diagnosis, although oral fluid specimens in universal transport medium may be used in deceased patients or as a secondary alternative (WHO, 2019).
Real-time RT-PCR assays have significantly improved diagnostic capabilities for EVD; they are able to rapidly detect viral RNA in blood specimens (Cherpillod et al., 2016). In the US, presumptive testing for the Ebola virus can be accessed at over 60 LRN laboratories. These laboratories use an FDA-approved EUA assay to detect the EBOV. The nurse should remember that the virus may not reach detectable levels for three days following the initial symptoms. Samples that test positive using this RT-PCR assay are considered presumptive positive for Ebola Zaire RNA and will be submitted to the CDC for additional testing (CDC, 2018b, 2018c).
At this time, there are no licensed vaccines to prevent EVD. There are multiple investigational vaccines being tested around the world. rVSV-ZEBOV, a vaccine developed by Merck, is being tested in DRC currently. Among the test group (n=5,837) who received the vaccine, no cases of EVD were reported 10+ days after administration. Within the similarly sized control group, there were 23 cases reported (NIAID, 2019b; WHO, 2019).
Until such time as an effective vaccine can be tested and distributed, prevention campaigns are focusing on diligent infection control and education regarding risk factors. Hand hygiene is crucial for everyone, especially healthcare providers and laboratory employees who work with fluids or specimens that may be contaminated. To reduce risk, the nurse should educate those in endemic areas to avoid touching items that were in contact with anyone diagnosed with EVD. They should avoid any contact with any bodily fluids from someone diagnosed with or suspected of having EVD. They should avoid visiting hospitals or clinics where EVD patients are being treated. Sick individuals should be quarantined immediately, and patients should be encouraged to communicate quickly and openly regarding potential contacts to expedite quarantine procedures effectively. They should not engage in any funeral rituals that involve touching the bodies of EVD patients. People should also avoid contact with primates or bats and ensure any meat is fully cooked to prevent zoonotic transmission. Men who have recovered from EVD are encouraged to use condoms during sexual contact for 3-12 months following the onset of symptoms, or until two semen specimens have been negative (Cleveland Clinic, 2014; WHO, 2019).
- Healthcare providers should be mindful of always abiding by standard precautions with every patient and utilizing the appropriate PPE to avoid exposure to any blood or body fluids during their professional duties caring for patients. Disposable equipment should only be used for a single patient, and reusable equipment should be properly sterilized between patients and uses (Cleveland Clinic, 2014). As with any public health concern, triage is extremely important for minimal exposure and effective containment. It is unlikely that patients with EVD will arrive unannounced at an outpatient setting in the US, as all patients with a risk of exposure are closely monitored by state and local health departments and directed to designated facilities for evaluation if symptoms present . Nonetheless, emergency department staff should be familiar with this guidance and prepared to implement the following key steps to Identify, Isolate, and Inform.
- Staff should be aware of how to identify and treat potential patients with EVD, despite the fact that most patients who present with fever and other viral symptoms do not have any risk factors for EVD.
- Every febrile patient should be asked if they have traveled internationally in the last 21 days.
- Every febrile patient should be asked if they have had any contact with someone with EVD in the last 21 days.
- PUIs (those with suspicious symptoms AND an identified risk factor) should be isolated immediately and placed on the appropriate isolation precautions.
- The nurse should follow their institution’s policies to notify the facility’s infection control team and the corresponding health departments (CDC, 2016).
- Only laboratories and staff that are properly trained and adequately equipped to manage infectious materials safely should be used (Cleveland Clinic, 2014).
Treatment and Management
EVD is largely managed using supportive, symptomatic treatment. Basic interventions can significantly improve survival rates when implemented appropriately and early. These may include:
- Fluid and electrolyte support via fluid resuscitation and aggressive electrolyte monitoring and subsequent replenishment.
- Monitor and maintain oxygen saturation with supplemental oxygen if necessary.
- Medications to maintain blood pressure and manage vomiting or diarrhea should be given.
- Fever and pain should be treated pharmacologically with antipyretics and pain relievers as needed, as well as nonpharmacological pain interventions as available and indicated.
- Aggressive management of any comorbid or subsequent infections (CDC, 2019c)
Survival depends on the strength of the response by the patient’s immune system and appropriate and timely supportive care. Long-term complications may include joint and vision problems (CDC, 2019c).
Evidence-based Nursing Practice, Implications for Nursing
According to the ANA (2019), disaster preparedness and response are integral parts of nursing care. This has been woven into the curriculum at many nursing schools to prepare future generations better to manage emergencies, including infectious outbreaks. In addition, practicing nurses are encouraged to seek out continuing professional development activities to develop and maintain competency. The ANA strongly recommends that all nurses educate themselves on Ebola preparedness, and then maintain that knowledge by reviewing nursing journals, other nursing literature, and disaster preparedness and response organizations’ websites (ANA, 2019).
Healthcare facilities should develop a preparedness plan with specific procedures and protocols to be used for identifying and caring for a patient with EVD. According to the ANA (2019), this plan should include:
- “Inpatient and ambulatory organizational policies and procedures that are in line with current CDC guidelines.
- Incorporation of appropriate screening criteria to be used during patient registration and triage.
- Rigorous training of all staff in screening procedures and what to do if a patient screens positive for suspected EVD.
- Isolation procedures to be used for patients in the ambulatory setting until transportation to an Emergency Department is facilitated, and isolation procedures to be used in the Emergency Department and inpatient setting if the patient is admitted to the hospital.
- Initial and ongoing face-to-face training plans for staff who may provide direct care to a patient with a confirmed diagnosis of EVD.
- Identification of appropriate isolation rooms and staffing plans to facilitate the care of a patient with EVD.
- Appropriate use of PPE in all health care settings when caring for a patient with a suspected or confirmed diagnosis of EVD, emphasizing the importance of proper hand hygiene.
- Environmental cleaning procedures.
- Mechanism to ensure timely reporting to local and public health officials” (ANA, 2019, para. 9)
ANA (2019) believes nurses are obligated to care for patients in a nondiscriminatory manner, with respect for all individuals. The ethical issues with Ebola are complicated, and as nurses, we must recognize that there may be limits to the personal risk healthcare providers can be expected to accept. The nurse should vocalize any concerns they may have regarding inadequate or poor planning, education, or management of any patient, regardless of diagnosis. If any conflicts of risk and responsibility present themselves, the nurse should attempt to resolve it quickly. If they feel they are not prepared or adequately equipped to care for a patient, the nurse always retains the right to refuse an assignment if they feel it is unsafe (ANA, 2019).
Research and Directives
There is currently no antiviral drug licensed by the FDA to treat EVD in people, but medications that halt viral replication are in development (CDC, 2019). During the 2018-2019 outbreak, the DRC and the WHO (2019) are conducting the first randomized control trial to evaluate the effectiveness and safety of multiple drugs (WHO, 2019). The Pamoja Tulinde Maisha (PALM [together save lives]) is a study of four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3 [Regeneron]) for the treatment of EVD. The study began in November 2018 and is monitored by an independent data and safety monitoring board (DSMB). The DSMB meets to review safety and efficacy data. Based on the data presented at their review on August 9, 2019, they recommended that the study of ZMapp and remdesivir be stopped and that all future patients be randomized to receive either REGN-EB3 (Regeneron) or mAb114. This was based on preliminary results regarding 499 patients, which showed that treatment with REGN-EB3 or mAb114 leads to significantly higher survival rates as compared to the other two medications. These results were significant enough to convince the DSMB and the study leadership to recommend and initiate these changes immediately (National Institutes of Health, 2019).
According to Stawicki et al. (2014):
Ebolavirus (EBOV) causes a severe, frequently fatal hemorrhagic syndrome in humans. Each outbreak of the Ebolavirus over the last three decades has perpetuated fear and economic turmoil among the local and regional populations in Africa. Until now, it has been considered a tragic malady confined largely to the isolated regions of the African continent, but it is no longer so. The frequency of outbreaks has increased since the 1970s. The 2014 Ebola outbreak in Western Africa has been the most severe in history and was declared a public health emergency by the WHO. Given the widespread use of modern transportation and global travel, the EBOV is now a risk to the entire Global Village, with intercontinental transmission only an airplane flight away (p. 1).
Healthcare facilities and members of the healthcare team should use standard precautions diligently, and if suspicious symptoms are present in a patient with a recent risk of exposure, they should identify and isolate those patients. Once quarantined, the facility infection control program, as well as state and local health departments, should be notified according to the CDC guidance for emergency departments (CDC, 2018c).
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