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Ebola: A Practice Summary for Nurse Practitioners
Ebola: A Practice Summary for Nurse Practitioners Anna Jarrett, PhD, ACNP/ACNS-BC ABSTRACT
This feature reviews pathophysiology, epidemiology, and prevention of Ebola virus disease. Information is presented that is needed to educate patients and to protect oneself, staff, and other patients in the event a patient with suspected Ebola presents for medical care. A screening tool is provided, as well as a concise method to eliminate differential diagnoses related to this dreaded disease. Diagnostic testing and initial treatment requirements are outlined. In the event a patient presents to primary care, guidance is given for initial steps and precautions necessary to contain and manage a patient with Ebola. Keywords: containment, diagnosis, Ebola virus disease, prevention, role of Nurse Practitioner in Primary Care, treatment Ó 2014 Elsevier, Inc. All rights reserved.
bola was first identified in 1975 and named after the Ebola River in the Democratic Republic of Congo (formerly Zaire). This virus is one of the Filoviridae families of viral hemorrhagic fevers (VHFs). The taxonomy of the filovirus is: Mononegavirales order; Filoviridae family; Ebolavirus genus; and 1 of 5 species. These 5 species are Zaire (EBOV), Sudan (SUDV), Reston (RESTV), Bundibugyo, and Tai Forest (TATV) or Ivory Coast (ICEBOV).1,2 The 3 Ebola virus disease (EVD) species infective to humans are the Zaire, Sudan, and Bundibugyo.3
E
PATHOPHYSIOLOGY
A virus is an infectious, intracellular parasite. The genetic make-up of a virus is either DNA or RNA. The genetic material of a virus enters a host cell and orchestrates the production of new virus particles, called virions. New virions are produced in the host cell and, from there, they transport the viral genetic material to another host cell or organism to carry out another cycle of infection.4 A filovirus is a filamentous, enveloped particle with a negative-sensed, single-strand RNA genome. It appears long and threadlike, with terminal knobs. EVD follows the 6 phases of viral replication: attachment; penetration; uncoating; replication and expression; maturation; and release.5,6 www.npjournal.org
The Ebola virus attaches to a host receptor cell. The virion penetrates the host cell through endocytosis. The virus uncoats and the nucleocapsid composed of nucleic acid surrounded by a protein shell is transcribed into positive-strand mRNA, and then translated into viral proteins. Filovirus transcription and replication are mediated by a single virus-encoded enzyme, known as a polymerase, in the cytoplasm of the infected cell. Polymerases duplicate the genetic code of the RNA.6,7 In the case of Ebola, a single glycosylated nonstructural protein is expressed by RNA editing at a specific place in the glycoprotein. This small, soluble glycoprotein is produced as a result of transcriptional editing. Editing results in multiple genetic products. New Ebola viruses bud from the cell membrane and their progeny are released. When they mature, they are infective to other cells.6 Once infected, the virus targets the host blood coagulation and immune defense systems by preventing T-cell activation, which is responsible for cell-mediated immunity.5 The host becomes immunosuppressed. As the virus disseminates throughout the body, it causes endothelial damage, resulting in hemorrhage and shock. It migrates from the lymph nodes to the liver, spleen, and The Journal for Nurse Practitioners - JNP
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adrenal glands, causing hepatocellular and adrenocortical necrosis, which is clinically present as hemorrhage and hypotension. EVD releases proinflammatory cytokines, resulting in vascular leakage and coagulopathy. The end result is multiple-organ failure with shock.8 The virus is capable of surviving in liquid or dried materials for several days. Less than 10 aerosolized organisms are sufficient to transmit the infection in humans. However, Ebola virus can be deactivated by heat, gamma irradiation, and ultraviolet radiation. Chemical sterilization can also be done using 10% sodium hypochlorite.9 EPIDEMIOLOGY
Historically, EVD has occurred in areas around the rain forests of Central Africa. However, current
outbreaks are now primarily in remote villages of Central and Western Africa (Figure 1). The spread of EVD to surrounding areas is an urgent concern. In July 2014, World Health Organization (WHO) representatives called an emergency meeting in Ghana to coordinate a more efficient response to the Ebola outbreak in West Africa. On August 8, 2014, Dr. Margaret Chan, director-general of WHO, announced the current Ebola outbreak as an international public health emergency.10,11 As of September 13, 2014, the response to EVD has been a dynamic, ongoing process. The Centers for Disease Control (CDC), WHO, the American Nurses Association, and many other national or international organizations have provided the most current information about EVD to clinicians, students, and travelers. Table 1 presents an abbreviated timeline of activities
Figure 1. Ebola Outbreak Response.
Source: World Health Organization Global Alert and Response (http://www.who.int/csr/disease/ebola/maps/en/). 2
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Table 1. Organization Responses and Guidelines to Ebola Outbreak 2014 Date
Organization
Guidelines or Response
Website
August 1, 2014
CDC
Guidelines for evaluating US patients suspected of having EVD
http://emergency.cdc.gov/han/han00364.asp
August 1, 2014
CDC
Infection prevention and control recommendations for hospitalized patients with known or suspected Ebola hemorrhage fever in US hospitals
http://www.cdc.gov/vhf/ebola/hcp/infection -prevention-and-control-recommendations.html
August 8, 2014
WHO
Announced a state of international emergency
http://www.who.int/mediacentre/news/ statements/2014/ebola-20140808/en/
August 10, 2014
CDC
Guidelines for clinicians in US health-care settings
http://www.cdc.gov/vhf/ebola/hcp/clinician -information-us-healthcare-settings.html
August 18, 2014
WHO
Activated a travel and transport task force
http://www.who.int/mediacentre/news/ statements/2014/ebola-travel-trasport/en/
August 23, 2014
CDC
Advice for humanitarian aid workers traveling to Guinea, Liberia, Nigeria, or Sierra Leone during Ebola outbreak
http://wwwnc.cdc.gov/travel/page/ humanitarian-workers-ebola
August 28, 2014
CDC
Workplace safety and health topics: Ebola
http://www.cdc.gov/niosh/topics/ebola/
August 29, 2014
CDC
Advice for colleges, universities, and students about Ebola in West Africa
http://wwwnc.cdc.gov/travel/page/advice -for-colleges-universities-and-students -about-ebola-in-west-africa
September 8, 2014
ANA
Call for nurse volunteers to respond to the Ebola crisis in West Africa
http://www.nursingworld.org/MainMenu Categories/WorkplaceSafety/Healthy-Work -Environment/DPR/Ebola-Information.html
Data compiled from Centers for Disease Control and Prevention, World Health Organization, and the American Nurses Association websites. Last accessed: September 13, 2014.
of organizations bringing information to the public as quickly as possible. It reflects the first date the announcement or response was created relative to the current EVD outbreak. The website links provide access to the most current documents or websites. Based on epidemiologic data, the 20- to 30-yearold age group seems to be more susceptible to the disease. There is no relationship between those who are predisposed to infections, such as immunosuppressed individuals, and the contagion. EVD outbreaks have a mortality incidence of 60% to 90%, depending upon time of diagnosis, availability of supportive treatment, and EVD subtype. The Zaire subtype is the most deadly. The incubation period is 2 to 21 days. It is not entirely clear, but fruit bats of the Pteropodidae family are generally considered to be the natural host of the Ebola virus. Transmission of the virus has been www.npjournal.org
documented through the handling of infected chimpanzees, gorillas, fruit bats, monkeys, forest antelope, and porcupines found ill or dead or in the rainforest. The virus is introduced into the human population through close contact with blood, secretions, organs, or other bodily fluids of infected animals. It spreads in the human population through human-to-human contact via broken skin or mucous membranes. Particular to Ebola, if a family member or caregiver has direct contact with bodies of deceased persons, it can still be transmitted. For men who have recovered from the virus, they may remain communicable for up to 7 weeks after recovery (Figure 2).1 PREVENTION
Preventing EVD poses many challenges. Prevention aims are threefold: increased awareness; rapid The Journal for Nurse Practitioners - JNP
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Figure 2. Ebolavirus ecology.
Source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP) Viral Special Pathogens Branch (VSPB). (http://www.cdc.gov/vhf/ ebola/resources/virus-ecology.html).
recognition of the disease; and having access and means to provide proper isolation when EVD is diagnosed. Increased awareness about the virus is the most important prevention measure that can be taken. Informing those who are in contact with EVD or reside in the endemic areas poses challenges as well. Knowledge of the spread of EVD is evolving. Currently, there is no ban on international travel, but recommendations for those traveling to these areas should include avoidance of the following: Contact with bodily fluids on symptomatic patients or corpses. Bush meat (meat from wild animals). Close contact with wild animals. 4
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To protect oneself from exposure, 3 basic recommendations have been made: Practice safe sex. Always wash and peel fruits and vegetables. Use a good hand-washing technique.12 If exposed to EVD, or if symptoms of EVD appear within 21 days of travel, one should seek medical attention. For health-care workers, strict barrier precautions should be used. Travelers have been encouraged to verify their insurance for medical treatment abroad.13 On August 18, 2014, WHO issued a statement announcing activation of a travel and transport task force. This task force was charged with monitoring the EVD situation and providing current information to travelers.13 Volume
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Some of the countries with recent Ebola outbreaks have been ravaged by civil war, have limited commodities to manufacture or sell products, and are among the most impoverished countries in the world. Amara Konneh, prime minister of finance for Liberia, appealed to the international business community for economic investment to support infrastructure in the African nations battling the Ebola war. So far, American businesses are leading the way. Coca-Cola, General Motors, and Ford Motor Company have pledged to support opportunities for permanent employment in Liberia.14 It seems rather simple to provide standard universal precautions to health-care workers who are treating patients with Ebola. However, Western African hospitals lack sufficient equipment and protective gear to manage the outbreak. Often patients remain at home for lack of trust of WHO healthcare workers, and thus they are cared for by family members. These family members are often unaware of the hazards of the disease. They continue to “bathe” the bodies of the deceased loved ones, as part of their cultural practices. These practices continue to spread the disease. Public education is mandatory for residents of the endemic areas. Education of communities must include the risk of wildlife-to-human transmission, the need for use of personal protective equipment when caring for patients with EVD, and quick burial of the dead. Communities need to educate their citizens about containment measures required to control the viral outbreak. Unfortunately, prevention methods are not operationalized. The current goal is to prevent outbreaks of EVD. We are struggling to contain and control the disease. Three challenges that limit the full capability to contain and control outbreaks include the vast geography involved, the weak health-care systems, and community mistrust and resistance in following restrictive guidance to prevent the spread of this dreaded disease.15 Vaccine development and production to prevent EVD and other hemorrhagic viral diseases has been slow. However, the recent international Ebola outbreak has propelled the research to advance investigational vaccines from testing on animal models to use on human subjects in the near future. www.npjournal.org
There are 2 types of Ebola vaccines in the initial stages of testing. One vaccine, the vesicular stomatitis virus (VSV) vaccine, stimulates antibody production in the host. A second vaccine, the adenovirus-based vaccine, produces innate and adaptive immunity.16 Once an infected patient becomes critically ill, however, the vaccine may not be effective.17 There is also a postexposure drug, VSV-EBOV, which has been shown to be effective in those exposed to EVD if administered within 21 days of exposure.16 The most important action a nurse practitioner should take to contain the spread of the disease is to isolate the patient and use maximum personal protective equipment. If the possibility exists that a patient has EVD, they should be isolated immediately and the local health department and CDC should both be notified. In a clinic environment, put the patient in the most isolated room and close the clinic. Cancel the day’s future appointments so additional exposure can be contained. Use health-care provider protection, which includes gloves, an impermeable gown, shoe covers, eye protection, and a face mask. Begin sanitation of items touched by the patient with a 10% solution of sodium hypochlorite (household bleach). Take names of people present in the clinic at the time of possible exposure. Contain those individuals in a separate, clean area. Treat all bodily fluids and clinical specimens as potentially infectious.18 Because of the media exposure, one would anticipate hysteria with further spread of the disease. Respond to hysteria with a calm demeanor. Reassure all patients and staff that circumstances are under control. Consider this an internal disaster and initiate a control center for communication. Assign a staff member as liaison between other patients sequestered in the clinic and provider(s) treating the isolated patient. With local or state department guidance, notify emergency medical services and allow time for both emergency workers and the receiving facility to implement Ebola containment procedures. Do not immediately collect specimens. If in an acute-care facility, use hospital policies and procedures, as well as the CDC’s Infection Prevention and Control Recommendations for Hospitalized Patients with Known or Suspected Ebola Hemorrhagic Fever in U.S. Hospitals.19 Clinical management should The Journal for Nurse Practitioners - JNP
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focus on treatment of hypovolemia, electrolyte imbalances, hypoxia, hemorrhage, shock, multiorgan dysfunction, disseminated intravascular coagulation, and presenting complications.18
Table 2. Screening Tool for Ebola Clinical Criteria Chief complaints (symptoms):
Fever >38.6 C (101.5 F)
SCREENING
EVD may seem like a remote possibility to healthcare providers in the United States, but we must be prepared to treat this illness on a global basis. We are a global community. As practitioners, raising awareness will decrease time to diagnosis. Correctly diagnosing the disease is time-consuming. In some cases, patients die prior to the diagnosis being confirmed. If providers are aware of and screen for EVD, diagnosis and supportive treatment can occur sooner and be more aggressive. Since July 2014, consumer news sources have magnified the concern for health-care consumers about EVD contagion. On August 1, 2014, the CDC published a health advisory for health-care providers. Both clinical criteria and epidemiologic risk factors are included in the alert. The most common, yet not all, inclusive signs and symptoms are important to recognize. Table 2 presents a risk assessment based on the most common clinical criteria, evidence on physical examination, and epidemiologic risk factors. Further work-up is needed if a patient presents with 2 or more symptoms, 1 sign, or if they traveled to an endemic area within the previous 3 weeks.9 ROLE OF THE PRIMARY CARE NURSE PRACTITIONER IN EBOLA
As nurse practitioners (NPs), it is vital to be knowledgeable about a wide assortment of diseases and to be alert for subtle information that can tip one off to the unlikely but possible diagnosis of EVD. Be aware of the chief complaints that individuals may present with in urgent care, emergency departments, or as outpatient clients. It is most important to remember the importance of a thorough health history, including an in-depth travel history. For NPs in primary care, the presentation may be early onset. Initially, patients may present with fever, anorexia, headache, malaise, joint/muscle aches, sore throat, and abdominal pain. Fever, anorexia, and general weakness are the most common symptoms. 6
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Severe headache Muscle or joint pain General malaise or asthenia Anorexia Weakness Sore throat Abdominal pain Diarrhea Vomiting Unexplained hemorrhage Other symptoms reported: chest pain, dyspnea, respiratory distress, dysphagia, cough Physical examination (signs): Conjunctival injection (red eyes) Rash—diffuse, erythematous, maculopapular on face, neck, trunk, arms Hiccups Epidemiologic Risk Factors (within 3 weeks prior to onset of symptoms) Contact with blood or other body fluids of patients with known or suspect EVD Travel to or reside in Congo (Zaire), Sudan, Gabon, Uganda, western Uganda, Sierra Leone, Guinea, Nigeria, and Liberia Direct handling of bats, rodents, or primates from Congo (Zaire), Sudan, Gabon, Uganda, western Uganda, Sierra Leone, Guinea, Nigeria, and Liberia Source: Rosalind P-R, Ali E, Betty M, Faridah M, Alex C, Concepta M. Ebola outbreak response; experience and development of screening tools for viral haemorrhagic fever (VHF) in a HIV Center of Excellence near to VHF Epicentres. PLoS One. 2014;9:e 100333. http://www.plosone.org/article/info%3Adoi%2F10. 1371%2Fjournal.pone.0100333#s1.
This is followed quickly by diarrhea and vomiting. By the end of the first week, patients may develop a diffuse erythematous maculopapular rash on their face, neck, trunk, and arms.13 Photophobia may be present, but it is less common. The rash is followed by petechiae, ecchymosis, and subconjunctival hemorrhage. Volume
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If the disease has progressed to intermediate or late stages, emergency departments would most likely be the point of entry into the health-care system. In an advanced stage, hematemesis, oliguria, shock, acute renal failure, vascular decompensation, and disseminated intravascular coagulation will clarify the diagnosis.19 It is not uncommon, however, for primary-care NPs to be at the forefront of educating the public about prevention, cause, screening methods, and treatment for potential outbreaks of EVD in the United States. An initial dialog in the clinic may instigate questioning by a patient: “Good morning, sir, how are you doing today?” may be met with a response similar to “My neighbor just returned from the Congo last week. Could he give me Ebola?” Educating the public and allaying unnecessary fears is a vital part of the NP’s role. DIAGNOSIS
Diagnosing EVD is extremely difficult. It requires a meticulous, comprehensive history as well as a thorough examination. The most important question you can ask is with regard to foreign travel. Ask specifically about travel to West Africa or contact with persons who have traveled there in the past 21 days. To eliminate several differential diagnoses, inquire about all travel in the past 1 year. The vague symptoms that patients present with who have EVD are consistent with a long list of differential diagnoses. It is important to recognize major differential diagnoses with signs and symptoms common to both. It is likewise important to recognize pertinent history and disease-specific signs and symptoms of the differential diagnoses that can guide practitioners through rapid medical decision-making. With each differential diagnosis, it is encouraged to identify the disease-specific confirmatory tests to rule in or rule out the potential diagnoses. A thorough history may eliminate some of the differentials without further testing. However, if presented with the occasion, the best confirmatory test can expedite diagnosis and treatment for EVD. Table 3 shows differential diagnoses to consider in the work-up of an EBD patient. To expeditiously eliminate as many differential diagnoses as possible, it is necessary to identify www.npjournal.org
disease-specific history or signs and symptoms to eliminate outliers. If testing is indicated, notify the local or state health department. The CDC recommends that malaria diagnostics should be included in initial testing because it is a common cause of febrile illnesses in those with a travel history to affected countries.9 The absolute confirmatory tests for EVD have 3 episodes of collection. Initial testing should include an antigen-capture and IgM enzyme-linked immunosorbent assay, polymerase chain reaction, and virus isolation. Upon recovery, IgM and IgG antibodies should be collected. Posthumously, it is recommended that immunohistochemical tissue tests, polymerase chain reaction, and virus isolation be collected and studied. Collection of blood must use guidelines consistent with a Category B diagnostic specimen. Testing must be done at a Biosafety 4 Laboratory.9 Additional tests would include complete blood count, metabolic panels, liver enzymes, and coagulation studies. One would expect leukopenia and lymphopenia initially, followed by increased neutrophils and a left shift. Hepatic enzymes will be elevated and proteinuria may be present. Coagulation studies indicate prolonged prothrombin time and partial thromboplastic time, with elevated fibrin split products. From previous outbreaks, it is known that the aminotransferase, D-dimer, blood urea nitrogen, and creatinine levels are elevated, but calcium and albumin levels drop in fatal cases of EVD.18,20 TREATMENT
For decades, supportive treatment and prevention of the spread of the disease have been cornerstones of EVD treatment. In 2014, the hope of a vaccine to prevent or treat EVD is on the horizon. It has been used successfully in humans. The long-term sequelae of the disease and vaccination are currently being investigated. Recovery from the disease is dependent on the host’s immune response. Initial supportive care will require intravenous hydration and symptom management. Treat the patient’s pain as aggressively as possible. Control bleeding and begin initial resuscitation measures. Oxygen is essential. Monitor vital signs closely. Vasopressors may be indicated. Avoid intramuscular injections, aspirin, nonsteroidal anti-inflammatory The Journal for Nurse Practitioners - JNP
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Table 3. EVD and Major Differential Diagnoses Differential Diagnoses
Symptoms and Examination Findings Common to EVD
Unique History/Examination Findings
Influenza
Fever, sore throat, myalgia, headaches, fatigue, tiredness, vomiting, diarrhea (in children)
History: exposure to Influenza in past 7 days Exam findings: runny nose
Rapid influenza diagnostic tests for A and Ba; see CDC Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests
Malaria
Fever, headache, myalgia, nausea, vomiting, diarrhea
History: Travel to sub-Saharan Africa or other countries at high risk in past 12 months; updates available at CDC Traveler’s Guideb Exam findings: profuse sweating
Blood smear with Giemsa stain
Typhoid fever
Fever, headache, weakness, dry cough, loss of appetite, abdominal pain, diarrhea, rash
History: Travel in past 30 days to South Asia, Asia, Africa, Central or South America, or Caribbean Exam findings: Rash: rose-colored, flat on trunk on days 4 or 5, then disappears Constipation
Urine, stool, blood, tissue culture (bone marrow most sensitive) for bacterium Salmonella typhimurium
Shigellosis
Diarrhea, fever
History: More common in summer, in small children, and worldwide, including the US Symptoms present 1e2 days after exposure
Stool culture for 1 of 4 types of Shigella bacteria
Confirmatory Test(s)
Exam findings: stomach cramps Cholera
Vomiting, diarrhea
History: travel to areas with poor sanitation in past 5 days Exam findings: Rice-water stools Muscle cramps
Stool culture with thiosulfate citrate bile salts agar for isolation and identification of Vibrio cholerae bacteria
Leptospirosis
Fever, headache, myalgia, vomiting, conjunctival injection, abdominal pain, diarrhea, rash
History: In close contact with animals, or water/urine of animals in past 30 days Travel to Peru, Ecuador, or Hawaii in past 30 days
Serum specimen with identified Leptospira bacteria agglutination titer of 800 by microscopic agglutination test
Exam findings: Evidence of broken skin Generalized rash Jaundice Icterus Plague: bubonic, septicemic, or pneumonic
Fever, headache, weakness, abdominal pain, internal/ external bleeding
History: Travel to southwestern US Contact with rodents or contaminated water in past 6 days
Blood or lymph node biopsy to identify Yersinia pestis bacteria
continued
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Table 3. (continued ) Differential Diagnoses
Symptoms and Examination Findings Common to EVD
Unique History/Examination Findings
Confirmatory Test(s)
Exam findings (depends on type of plague): Bubonic: painful lymph nodes (buboes) Septicemic: necrotic extremities Pneumonic: respiratory distress Rickettsiosis (Rocky Mountain spotted fever)
Fever, rash, headache, nausea, vomiting, abdominal pain, myalgia, anorexia, conjunctival injection
History: Travel to Africa or Mediterranean past 2 weeks Travel to endemic areas during November through April Recent exposure to ticks or fleas in past 14 days
Treat empirically, do not wait for confirmatory tests; indirect immunofluorescence assay with Rickettsia rickettsii bacteria antigen, performed on 2 paired serum samples to demonstrate a significant (fourfold) rise in antibody titers; first sample in first week, then repeat in 2e4 weeks
Exam findings: Rash Maculopapular Vesicular Petechial Eschar At site of a bite or wound Relapsing fever (tick- or louseborne)
Fever—recurring, myalgia, joint pain, headache, nausea, vomiting, anorexia, cough (dry), rash, diarrhea
History: Worldwide, especially in North Americans traveling to Mexico in previous 26 days Exposed to contaminated water (including swimming) Exam findings: watery diarrhea
Meningitis
Fever, headache, nausea, vomiting, meningococcemia: fatigue, vomiting, myalgia, chest pain, abdominal pain, diarrhea, rash
History: Meningococcal: Worldwide but most prevalent in sub-Saharan areas in Africa in hot, dry weather Travel to endemic area in past 2 weeks
CBC: Leukocytosis with left shift Thrombocytopenia Elevated erythrocyte sedimentation rate Coagulation studies: Prothrombin time Partial thromboplastin time slightly increased Serum bilirubin: mild increase; antibody titers: mild to moderate comparison of acute to convalescent Borrelia-specific titers; polymerase chain reaction Bacterial: Cerebrospinal fluid culture Viral:
Naso-oropharyngeal swabs Rectal swabs Stool culture Cerebrospinal fluid Blood culture continued
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Table 3. (continued) Differential Diagnoses
Symptoms and Examination Findings Common to EVD
Unique History/Examination Findings
Confirmatory Test(s)
Viral: Most often in US Young children Immunosuppressed individuals Exam findings: Nuchal rigidity Pupuric rash Altered mental status Difficulty arousal upon awakening Hepatitis A, B
Fever, malaise, anorexia, nausea, vomiting, abdominal pain; in some cases: skin rashes, joint pain, arthritis
History: Hepatitis A: Eaten contaminated food, engaged in oral/anal sex, used recreational drugs in past 6 weeks Have clotting disorder (hemophilia) Hepatitis B: Blood, body fluid exposures in past 150 days Exam findings: Hepatitis A and B: Gray-colored stools Dark urine Jaundice Icterus
Hepatitis A: Anti-HAV IgM in serum or 4-fold rise in specific antibodies Hepatitis B: Hepatitis B surface antigen Antibody to hepatitis B core antigen Antibody to hepatitis B surface antigen IgM antibody to hepatitis B core antigen
Other viral hemorrhagic feversc
Same as EVD
History: Travel to undeveloped countries in past 21 days Specific risk factors: Unprotected sex Sharing needles Slaughtering animals Working with sick In rat-infested building Bitten by tick, mosquito, rodent, or bat in previous 21 days Exam findings: same as EVD
Same as EVD
Data included in this table are from the Center for Disease and Prevention website A-Z for each disease listed. Available at: http://www.cdc.gov/az/c.html. Accessed August 18, 2014. a Refer to CDC’s Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests, available online at: http://www.cdc.gov/flu/professionals/diagnosis/clinician_ guidance_ridt.htm#Table1. Refer to CDC’s Traveler’s Guide, available online at: http://www.cdc.gov/malaria/travelers/country_table/s.htm. c Includes Ebola and Marburg, Lassa fever, Rift Valley fever, Crimean-Congo hemorrhagic fever, Dengue, Yellow fever, Omsk hemorrhagic fever, Kyasanur Forest disease, and Alkhurma viruses. b
drugs, or any other treatment that would provoke bleeding. Avoid respiratory treatments or any aerosol-generating procedures.21 10
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There is ongoing work to find a drug to treat patients infected with EVD. Currently, there are 4 major groups of drugs being tested for use in those infected with Volume
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the virus, including RNA inhibitorebased (TMK-Ebola) agents, nucleoside analogs, monoclonal antibodies (ZMapp), and antisense-based (AVI-7537) drugs.17 ZMapp is one of the most promising drugs being tested. It is composed of 3 monoclonal antibodies produced in tobacco plants. This drug targets the expression phase of viral replication. It binds to the protein of the Ebola virus to prevent replication of the virus once introduced into the host.17 Another drug, BCX4430, may be ready for human testing within the next year. It is a broad species exhibiting antiviral activity for Marburg, Ebola, and yellow fever. The drug attacks an enzyme found in these specific viruses. In small animals, it has been shown to be effective if treatment is started within 48 hours after start of infection.22 As of September 13, 2014, there are other drugs proposed to treat patients with EVD. The off-label use of statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers has been the suggested treatment because of their ability to stimulate immunity in the infected person. Theoretically, boosting the patient’s immunity would aid in the prevention of complications such as end-stage organ failure. Other scientists support the use of interferon to treat EVD because of its antiviral properties and its past success treating patients with hepatitis C. CONCLUSION
Although EVD is unlikely to become pandemic in the United States, NPs need to be knowledgeable about this serious infection and be prepared to recognize and manage the disease. This situation regarding EVD is evolving and becoming more prescriptive on a daily basis. The United States Department of Health and Human Services and Department of State websites are constantly updated and provide excellent resources for travel advisories. Both CDC and WHO provide up-to-date information and guidance on precautions for patient care for practicing NPs.
2. Public Health Agency of Canada. Ebola virus. http://www.phac-aspc.gc.ca/lab -bio/res/psds-ftss/ebola-eng.php. Accessed August 1, 2014. 3. Lawrence G, Lucey D, Phelan A. The Ebola epidemic: a global health emergency. JAMA. http://jama.jamanetwork.com/article.aspx?articleid¼ 1897089&utm_campaign¼social_091914&utm_medium¼facebook&utm_ source¼jama_fb. Accessed August 12, 2014. 4. Mehedi M, Falzarano D, Seebach J, et al. A new Ebola virus nonstructural glycoprotein expressed through RNA editing. J Virol. 2011;85(11):9. 5. Virus Replication. Oakland University Lecture notes. In: Vital Replication in Principles of Virology. Flint J, Enquist L, Rananiello V, Krus R, eds. Vol 1. 3rd ed. Chapters 2, 4, and 5. Madison, WI: ASM; 2008. http://www2.oakland.edu/ biology/chaudhry/pics/virusreplication02web.pdf. Accessed August 5, 2014. 6. Baylor College of Medicine Virology and Microbiology. Ebola virus. https:// www.bcm.edu/departments/molecular-virology-and-microbiology/ebola. Accessed August 12, 2014. 7. Porth C. Essentials of Pathophysiology. 3rd ed. Philadelphia: Pa: Wolters Kluwer/Lippincott Williams & Wilkins; 2011:333-344. 8. Hammer, S. Viral Replication. Columbia University lecture notes. In: Virology replication. Basic Virology. Wagner E, Hewlett M, Bloom D, Camerini D eds. Lansing, MI: Blackwell;2007. http://www.columbia.edu/itc/hs/medical/ pathophys/id/2004/lecture/notes/viral_rep_Hammer. Accessed August 5, 2014. 9. Centers for Disease Control and Prevention Health Alert Network. Network CHA. Guidelines for evaluation of US patients suspected of having Ebola virus disease. http://emergency.cdc.gov/han/han00364.asp. Accessed August 13, 2014. 10. Green A. Ebola emergency meeting establishes new control centre. World Report. Vol. 384. http://www.thelancet.com/journals/lancet/article/PIIS0140 -6736%2814%2961147-8/fulltext. Accessed August 13, 2014. 11. World Health Organization. Ebola outbreak is a public health emergency. http://www.theguardian.com/society/2014/aug/08/who-ebola-outbreak -international-public-health-emergency. Accessed August 8, 2014. 12. National Travel Health Network and Center. Ebola virus disease, West Africa—update 12. Published August 2014. http://www.nathnac.org/pro/ clinical_updates/ebola_westafrica_120814.htm. Accessed August 13, 2014. 13. World Health Organization. Statement on travel and transport in relation to Ebola virus disease (EVD) outbreak. http://www.who.int/mediacentre/news/ statements/2014/ebola-travel-trasport/en/. Accessed August 18, 2014. 14. Konneh A. The economics of Ebola. Wall Street Journal. August 11, 2014; p A.13. 15. Dixon M, Schafer I. Ebola viral disease outbreak—West Africa. MMWR Morb Mort Wkly Rep. 2014;63(25):5. 16. Mullard A. Experimental Ebola drugs enter the limelight. Lancet. 2014;384(9944):649-649. 17. Enserink M. Ebola drugs still stuck in lab. Science. 2014;345:364-365. 18. Centers for Disease Control and Prevention. Ebola virus disease information for clinicians in U.S. healthcare settings. Published 2014. http://www.cdc.gov/ vhf/ebola/hcp/clinician-information-us-healthcare-settings.html. Accessed August 19, 2014. 19. Gatherer D. The 2014 Ebola virus disease outbreak in West Africa. J Gen Virol. 2014;95(Pt 8):1619-1624. 20. McElroy A, Erickson B, Flietstra T, et al. Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014;210:558-566. 21. 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. CDC 24/7: Savings lives, protecting people: 8. http://www.cdc.gov/vhf/ebola/hcp/infection-prevention-and -control-recommendations.html. Accessed August 13, 2014. 22. Ebola in West Africa. The Lancet Infectious Diseases. Vol. 14. 2014. http:// www.thelancet.com/journals/laninf/article/PIIS1473-3099 (14)70785-6/fulltext. http://dx.org/10.1016/S1473-3099(14)70785-6.
Anna Jarrett, PhD, ACNP/ACNS-BC, is an assistant professor in the Eleanor Mann School of Nursing at the University of Arkansas in Fayetteville, AR. She can be reached at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business of industry that would pose a conflict of interest.
References 1. World Health Organization. Ebola virus disease. Ebola virus disease fact sheet no. 103. Updated April 2014. http://www.who.int/mediacentre/factsheets/ fs103/en. Accessed August 4, 2014.
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1555-4155/14/$ see front matter © 2014 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2014.09.015
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This feature reviews pathophysiology, epidemiology, and prevention of Ebola virus disease. Information is presented that is needed to educate patients and to protect oneself, staff, and other patients in the event a patient with suspected Ebola presents for medical care. A screening tool is provided, as well as a concise method to eliminate differential diagnoses related to this dreaded disease. Diagnostic testing and initial treatment requirements are outlined. In the event a patient presents to primary care, guidance is given for initial steps and precautions necessary to contain and manage a patient with Ebola. Keywords: containment, diagnosis, Ebola virus disease, prevention, role of Nurse Practitioner in Primary Care, treatment Ó 2014 Elsevier, Inc. All rights reserved.
bola was first identified in 1975 and named after the Ebola River in the Democratic Republic of Congo (formerly Zaire). This virus is one of the Filoviridae families of viral hemorrhagic fevers (VHFs). The taxonomy of the filovirus is: Mononegavirales order; Filoviridae family; Ebolavirus genus; and 1 of 5 species. These 5 species are Zaire (EBOV), Sudan (SUDV), Reston (RESTV), Bundibugyo, and Tai Forest (TATV) or Ivory Coast (ICEBOV).1,2 The 3 Ebola virus disease (EVD) species infective to humans are the Zaire, Sudan, and Bundibugyo.3
E
PATHOPHYSIOLOGY
A virus is an infectious, intracellular parasite. The genetic make-up of a virus is either DNA or RNA. The genetic material of a virus enters a host cell and orchestrates the production of new virus particles, called virions. New virions are produced in the host cell and, from there, they transport the viral genetic material to another host cell or organism to carry out another cycle of infection.4 A filovirus is a filamentous, enveloped particle with a negative-sensed, single-strand RNA genome. It appears long and threadlike, with terminal knobs. EVD follows the 6 phases of viral replication: attachment; penetration; uncoating; replication and expression; maturation; and release.5,6 www.npjournal.org
The Ebola virus attaches to a host receptor cell. The virion penetrates the host cell through endocytosis. The virus uncoats and the nucleocapsid composed of nucleic acid surrounded by a protein shell is transcribed into positive-strand mRNA, and then translated into viral proteins. Filovirus transcription and replication are mediated by a single virus-encoded enzyme, known as a polymerase, in the cytoplasm of the infected cell. Polymerases duplicate the genetic code of the RNA.6,7 In the case of Ebola, a single glycosylated nonstructural protein is expressed by RNA editing at a specific place in the glycoprotein. This small, soluble glycoprotein is produced as a result of transcriptional editing. Editing results in multiple genetic products. New Ebola viruses bud from the cell membrane and their progeny are released. When they mature, they are infective to other cells.6 Once infected, the virus targets the host blood coagulation and immune defense systems by preventing T-cell activation, which is responsible for cell-mediated immunity.5 The host becomes immunosuppressed. As the virus disseminates throughout the body, it causes endothelial damage, resulting in hemorrhage and shock. It migrates from the lymph nodes to the liver, spleen, and The Journal for Nurse Practitioners - JNP
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adrenal glands, causing hepatocellular and adrenocortical necrosis, which is clinically present as hemorrhage and hypotension. EVD releases proinflammatory cytokines, resulting in vascular leakage and coagulopathy. The end result is multiple-organ failure with shock.8 The virus is capable of surviving in liquid or dried materials for several days. Less than 10 aerosolized organisms are sufficient to transmit the infection in humans. However, Ebola virus can be deactivated by heat, gamma irradiation, and ultraviolet radiation. Chemical sterilization can also be done using 10% sodium hypochlorite.9 EPIDEMIOLOGY
Historically, EVD has occurred in areas around the rain forests of Central Africa. However, current
outbreaks are now primarily in remote villages of Central and Western Africa (Figure 1). The spread of EVD to surrounding areas is an urgent concern. In July 2014, World Health Organization (WHO) representatives called an emergency meeting in Ghana to coordinate a more efficient response to the Ebola outbreak in West Africa. On August 8, 2014, Dr. Margaret Chan, director-general of WHO, announced the current Ebola outbreak as an international public health emergency.10,11 As of September 13, 2014, the response to EVD has been a dynamic, ongoing process. The Centers for Disease Control (CDC), WHO, the American Nurses Association, and many other national or international organizations have provided the most current information about EVD to clinicians, students, and travelers. Table 1 presents an abbreviated timeline of activities
Figure 1. Ebola Outbreak Response.
Source: World Health Organization Global Alert and Response (http://www.who.int/csr/disease/ebola/maps/en/). 2
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Table 1. Organization Responses and Guidelines to Ebola Outbreak 2014 Date
Organization
Guidelines or Response
Website
August 1, 2014
CDC
Guidelines for evaluating US patients suspected of having EVD
http://emergency.cdc.gov/han/han00364.asp
August 1, 2014
CDC
Infection prevention and control recommendations for hospitalized patients with known or suspected Ebola hemorrhage fever in US hospitals
http://www.cdc.gov/vhf/ebola/hcp/infection -prevention-and-control-recommendations.html
August 8, 2014
WHO
Announced a state of international emergency
http://www.who.int/mediacentre/news/ statements/2014/ebola-20140808/en/
August 10, 2014
CDC
Guidelines for clinicians in US health-care settings
http://www.cdc.gov/vhf/ebola/hcp/clinician -information-us-healthcare-settings.html
August 18, 2014
WHO
Activated a travel and transport task force
http://www.who.int/mediacentre/news/ statements/2014/ebola-travel-trasport/en/
August 23, 2014
CDC
Advice for humanitarian aid workers traveling to Guinea, Liberia, Nigeria, or Sierra Leone during Ebola outbreak
http://wwwnc.cdc.gov/travel/page/ humanitarian-workers-ebola
August 28, 2014
CDC
Workplace safety and health topics: Ebola
http://www.cdc.gov/niosh/topics/ebola/
August 29, 2014
CDC
Advice for colleges, universities, and students about Ebola in West Africa
http://wwwnc.cdc.gov/travel/page/advice -for-colleges-universities-and-students -about-ebola-in-west-africa
September 8, 2014
ANA
Call for nurse volunteers to respond to the Ebola crisis in West Africa
http://www.nursingworld.org/MainMenu Categories/WorkplaceSafety/Healthy-Work -Environment/DPR/Ebola-Information.html
Data compiled from Centers for Disease Control and Prevention, World Health Organization, and the American Nurses Association websites. Last accessed: September 13, 2014.
of organizations bringing information to the public as quickly as possible. It reflects the first date the announcement or response was created relative to the current EVD outbreak. The website links provide access to the most current documents or websites. Based on epidemiologic data, the 20- to 30-yearold age group seems to be more susceptible to the disease. There is no relationship between those who are predisposed to infections, such as immunosuppressed individuals, and the contagion. EVD outbreaks have a mortality incidence of 60% to 90%, depending upon time of diagnosis, availability of supportive treatment, and EVD subtype. The Zaire subtype is the most deadly. The incubation period is 2 to 21 days. It is not entirely clear, but fruit bats of the Pteropodidae family are generally considered to be the natural host of the Ebola virus. Transmission of the virus has been www.npjournal.org
documented through the handling of infected chimpanzees, gorillas, fruit bats, monkeys, forest antelope, and porcupines found ill or dead or in the rainforest. The virus is introduced into the human population through close contact with blood, secretions, organs, or other bodily fluids of infected animals. It spreads in the human population through human-to-human contact via broken skin or mucous membranes. Particular to Ebola, if a family member or caregiver has direct contact with bodies of deceased persons, it can still be transmitted. For men who have recovered from the virus, they may remain communicable for up to 7 weeks after recovery (Figure 2).1 PREVENTION
Preventing EVD poses many challenges. Prevention aims are threefold: increased awareness; rapid The Journal for Nurse Practitioners - JNP
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Figure 2. Ebolavirus ecology.
Source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP) Viral Special Pathogens Branch (VSPB). (http://www.cdc.gov/vhf/ ebola/resources/virus-ecology.html).
recognition of the disease; and having access and means to provide proper isolation when EVD is diagnosed. Increased awareness about the virus is the most important prevention measure that can be taken. Informing those who are in contact with EVD or reside in the endemic areas poses challenges as well. Knowledge of the spread of EVD is evolving. Currently, there is no ban on international travel, but recommendations for those traveling to these areas should include avoidance of the following: Contact with bodily fluids on symptomatic patients or corpses. Bush meat (meat from wild animals). Close contact with wild animals. 4
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To protect oneself from exposure, 3 basic recommendations have been made: Practice safe sex. Always wash and peel fruits and vegetables. Use a good hand-washing technique.12 If exposed to EVD, or if symptoms of EVD appear within 21 days of travel, one should seek medical attention. For health-care workers, strict barrier precautions should be used. Travelers have been encouraged to verify their insurance for medical treatment abroad.13 On August 18, 2014, WHO issued a statement announcing activation of a travel and transport task force. This task force was charged with monitoring the EVD situation and providing current information to travelers.13 Volume
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Some of the countries with recent Ebola outbreaks have been ravaged by civil war, have limited commodities to manufacture or sell products, and are among the most impoverished countries in the world. Amara Konneh, prime minister of finance for Liberia, appealed to the international business community for economic investment to support infrastructure in the African nations battling the Ebola war. So far, American businesses are leading the way. Coca-Cola, General Motors, and Ford Motor Company have pledged to support opportunities for permanent employment in Liberia.14 It seems rather simple to provide standard universal precautions to health-care workers who are treating patients with Ebola. However, Western African hospitals lack sufficient equipment and protective gear to manage the outbreak. Often patients remain at home for lack of trust of WHO healthcare workers, and thus they are cared for by family members. These family members are often unaware of the hazards of the disease. They continue to “bathe” the bodies of the deceased loved ones, as part of their cultural practices. These practices continue to spread the disease. Public education is mandatory for residents of the endemic areas. Education of communities must include the risk of wildlife-to-human transmission, the need for use of personal protective equipment when caring for patients with EVD, and quick burial of the dead. Communities need to educate their citizens about containment measures required to control the viral outbreak. Unfortunately, prevention methods are not operationalized. The current goal is to prevent outbreaks of EVD. We are struggling to contain and control the disease. Three challenges that limit the full capability to contain and control outbreaks include the vast geography involved, the weak health-care systems, and community mistrust and resistance in following restrictive guidance to prevent the spread of this dreaded disease.15 Vaccine development and production to prevent EVD and other hemorrhagic viral diseases has been slow. However, the recent international Ebola outbreak has propelled the research to advance investigational vaccines from testing on animal models to use on human subjects in the near future. www.npjournal.org
There are 2 types of Ebola vaccines in the initial stages of testing. One vaccine, the vesicular stomatitis virus (VSV) vaccine, stimulates antibody production in the host. A second vaccine, the adenovirus-based vaccine, produces innate and adaptive immunity.16 Once an infected patient becomes critically ill, however, the vaccine may not be effective.17 There is also a postexposure drug, VSV-EBOV, which has been shown to be effective in those exposed to EVD if administered within 21 days of exposure.16 The most important action a nurse practitioner should take to contain the spread of the disease is to isolate the patient and use maximum personal protective equipment. If the possibility exists that a patient has EVD, they should be isolated immediately and the local health department and CDC should both be notified. In a clinic environment, put the patient in the most isolated room and close the clinic. Cancel the day’s future appointments so additional exposure can be contained. Use health-care provider protection, which includes gloves, an impermeable gown, shoe covers, eye protection, and a face mask. Begin sanitation of items touched by the patient with a 10% solution of sodium hypochlorite (household bleach). Take names of people present in the clinic at the time of possible exposure. Contain those individuals in a separate, clean area. Treat all bodily fluids and clinical specimens as potentially infectious.18 Because of the media exposure, one would anticipate hysteria with further spread of the disease. Respond to hysteria with a calm demeanor. Reassure all patients and staff that circumstances are under control. Consider this an internal disaster and initiate a control center for communication. Assign a staff member as liaison between other patients sequestered in the clinic and provider(s) treating the isolated patient. With local or state department guidance, notify emergency medical services and allow time for both emergency workers and the receiving facility to implement Ebola containment procedures. Do not immediately collect specimens. If in an acute-care facility, use hospital policies and procedures, as well as the CDC’s Infection Prevention and Control Recommendations for Hospitalized Patients with Known or Suspected Ebola Hemorrhagic Fever in U.S. Hospitals.19 Clinical management should The Journal for Nurse Practitioners - JNP
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focus on treatment of hypovolemia, electrolyte imbalances, hypoxia, hemorrhage, shock, multiorgan dysfunction, disseminated intravascular coagulation, and presenting complications.18
Table 2. Screening Tool for Ebola Clinical Criteria Chief complaints (symptoms):
Fever >38.6 C (101.5 F)
SCREENING
EVD may seem like a remote possibility to healthcare providers in the United States, but we must be prepared to treat this illness on a global basis. We are a global community. As practitioners, raising awareness will decrease time to diagnosis. Correctly diagnosing the disease is time-consuming. In some cases, patients die prior to the diagnosis being confirmed. If providers are aware of and screen for EVD, diagnosis and supportive treatment can occur sooner and be more aggressive. Since July 2014, consumer news sources have magnified the concern for health-care consumers about EVD contagion. On August 1, 2014, the CDC published a health advisory for health-care providers. Both clinical criteria and epidemiologic risk factors are included in the alert. The most common, yet not all, inclusive signs and symptoms are important to recognize. Table 2 presents a risk assessment based on the most common clinical criteria, evidence on physical examination, and epidemiologic risk factors. Further work-up is needed if a patient presents with 2 or more symptoms, 1 sign, or if they traveled to an endemic area within the previous 3 weeks.9 ROLE OF THE PRIMARY CARE NURSE PRACTITIONER IN EBOLA
As nurse practitioners (NPs), it is vital to be knowledgeable about a wide assortment of diseases and to be alert for subtle information that can tip one off to the unlikely but possible diagnosis of EVD. Be aware of the chief complaints that individuals may present with in urgent care, emergency departments, or as outpatient clients. It is most important to remember the importance of a thorough health history, including an in-depth travel history. For NPs in primary care, the presentation may be early onset. Initially, patients may present with fever, anorexia, headache, malaise, joint/muscle aches, sore throat, and abdominal pain. Fever, anorexia, and general weakness are the most common symptoms. 6
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Severe headache Muscle or joint pain General malaise or asthenia Anorexia Weakness Sore throat Abdominal pain Diarrhea Vomiting Unexplained hemorrhage Other symptoms reported: chest pain, dyspnea, respiratory distress, dysphagia, cough Physical examination (signs): Conjunctival injection (red eyes) Rash—diffuse, erythematous, maculopapular on face, neck, trunk, arms Hiccups Epidemiologic Risk Factors (within 3 weeks prior to onset of symptoms) Contact with blood or other body fluids of patients with known or suspect EVD Travel to or reside in Congo (Zaire), Sudan, Gabon, Uganda, western Uganda, Sierra Leone, Guinea, Nigeria, and Liberia Direct handling of bats, rodents, or primates from Congo (Zaire), Sudan, Gabon, Uganda, western Uganda, Sierra Leone, Guinea, Nigeria, and Liberia Source: Rosalind P-R, Ali E, Betty M, Faridah M, Alex C, Concepta M. Ebola outbreak response; experience and development of screening tools for viral haemorrhagic fever (VHF) in a HIV Center of Excellence near to VHF Epicentres. PLoS One. 2014;9:e 100333. http://www.plosone.org/article/info%3Adoi%2F10. 1371%2Fjournal.pone.0100333#s1.
This is followed quickly by diarrhea and vomiting. By the end of the first week, patients may develop a diffuse erythematous maculopapular rash on their face, neck, trunk, and arms.13 Photophobia may be present, but it is less common. The rash is followed by petechiae, ecchymosis, and subconjunctival hemorrhage. Volume
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If the disease has progressed to intermediate or late stages, emergency departments would most likely be the point of entry into the health-care system. In an advanced stage, hematemesis, oliguria, shock, acute renal failure, vascular decompensation, and disseminated intravascular coagulation will clarify the diagnosis.19 It is not uncommon, however, for primary-care NPs to be at the forefront of educating the public about prevention, cause, screening methods, and treatment for potential outbreaks of EVD in the United States. An initial dialog in the clinic may instigate questioning by a patient: “Good morning, sir, how are you doing today?” may be met with a response similar to “My neighbor just returned from the Congo last week. Could he give me Ebola?” Educating the public and allaying unnecessary fears is a vital part of the NP’s role. DIAGNOSIS
Diagnosing EVD is extremely difficult. It requires a meticulous, comprehensive history as well as a thorough examination. The most important question you can ask is with regard to foreign travel. Ask specifically about travel to West Africa or contact with persons who have traveled there in the past 21 days. To eliminate several differential diagnoses, inquire about all travel in the past 1 year. The vague symptoms that patients present with who have EVD are consistent with a long list of differential diagnoses. It is important to recognize major differential diagnoses with signs and symptoms common to both. It is likewise important to recognize pertinent history and disease-specific signs and symptoms of the differential diagnoses that can guide practitioners through rapid medical decision-making. With each differential diagnosis, it is encouraged to identify the disease-specific confirmatory tests to rule in or rule out the potential diagnoses. A thorough history may eliminate some of the differentials without further testing. However, if presented with the occasion, the best confirmatory test can expedite diagnosis and treatment for EVD. Table 3 shows differential diagnoses to consider in the work-up of an EBD patient. To expeditiously eliminate as many differential diagnoses as possible, it is necessary to identify www.npjournal.org
disease-specific history or signs and symptoms to eliminate outliers. If testing is indicated, notify the local or state health department. The CDC recommends that malaria diagnostics should be included in initial testing because it is a common cause of febrile illnesses in those with a travel history to affected countries.9 The absolute confirmatory tests for EVD have 3 episodes of collection. Initial testing should include an antigen-capture and IgM enzyme-linked immunosorbent assay, polymerase chain reaction, and virus isolation. Upon recovery, IgM and IgG antibodies should be collected. Posthumously, it is recommended that immunohistochemical tissue tests, polymerase chain reaction, and virus isolation be collected and studied. Collection of blood must use guidelines consistent with a Category B diagnostic specimen. Testing must be done at a Biosafety 4 Laboratory.9 Additional tests would include complete blood count, metabolic panels, liver enzymes, and coagulation studies. One would expect leukopenia and lymphopenia initially, followed by increased neutrophils and a left shift. Hepatic enzymes will be elevated and proteinuria may be present. Coagulation studies indicate prolonged prothrombin time and partial thromboplastic time, with elevated fibrin split products. From previous outbreaks, it is known that the aminotransferase, D-dimer, blood urea nitrogen, and creatinine levels are elevated, but calcium and albumin levels drop in fatal cases of EVD.18,20 TREATMENT
For decades, supportive treatment and prevention of the spread of the disease have been cornerstones of EVD treatment. In 2014, the hope of a vaccine to prevent or treat EVD is on the horizon. It has been used successfully in humans. The long-term sequelae of the disease and vaccination are currently being investigated. Recovery from the disease is dependent on the host’s immune response. Initial supportive care will require intravenous hydration and symptom management. Treat the patient’s pain as aggressively as possible. Control bleeding and begin initial resuscitation measures. Oxygen is essential. Monitor vital signs closely. Vasopressors may be indicated. Avoid intramuscular injections, aspirin, nonsteroidal anti-inflammatory The Journal for Nurse Practitioners - JNP
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Table 3. EVD and Major Differential Diagnoses Differential Diagnoses
Symptoms and Examination Findings Common to EVD
Unique History/Examination Findings
Influenza
Fever, sore throat, myalgia, headaches, fatigue, tiredness, vomiting, diarrhea (in children)
History: exposure to Influenza in past 7 days Exam findings: runny nose
Rapid influenza diagnostic tests for A and Ba; see CDC Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests
Malaria
Fever, headache, myalgia, nausea, vomiting, diarrhea
History: Travel to sub-Saharan Africa or other countries at high risk in past 12 months; updates available at CDC Traveler’s Guideb Exam findings: profuse sweating
Blood smear with Giemsa stain
Typhoid fever
Fever, headache, weakness, dry cough, loss of appetite, abdominal pain, diarrhea, rash
History: Travel in past 30 days to South Asia, Asia, Africa, Central or South America, or Caribbean Exam findings: Rash: rose-colored, flat on trunk on days 4 or 5, then disappears Constipation
Urine, stool, blood, tissue culture (bone marrow most sensitive) for bacterium Salmonella typhimurium
Shigellosis
Diarrhea, fever
History: More common in summer, in small children, and worldwide, including the US Symptoms present 1e2 days after exposure
Stool culture for 1 of 4 types of Shigella bacteria
Confirmatory Test(s)
Exam findings: stomach cramps Cholera
Vomiting, diarrhea
History: travel to areas with poor sanitation in past 5 days Exam findings: Rice-water stools Muscle cramps
Stool culture with thiosulfate citrate bile salts agar for isolation and identification of Vibrio cholerae bacteria
Leptospirosis
Fever, headache, myalgia, vomiting, conjunctival injection, abdominal pain, diarrhea, rash
History: In close contact with animals, or water/urine of animals in past 30 days Travel to Peru, Ecuador, or Hawaii in past 30 days
Serum specimen with identified Leptospira bacteria agglutination titer of 800 by microscopic agglutination test
Exam findings: Evidence of broken skin Generalized rash Jaundice Icterus Plague: bubonic, septicemic, or pneumonic
Fever, headache, weakness, abdominal pain, internal/ external bleeding
History: Travel to southwestern US Contact with rodents or contaminated water in past 6 days
Blood or lymph node biopsy to identify Yersinia pestis bacteria
continued
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Table 3. (continued ) Differential Diagnoses
Symptoms and Examination Findings Common to EVD
Unique History/Examination Findings
Confirmatory Test(s)
Exam findings (depends on type of plague): Bubonic: painful lymph nodes (buboes) Septicemic: necrotic extremities Pneumonic: respiratory distress Rickettsiosis (Rocky Mountain spotted fever)
Fever, rash, headache, nausea, vomiting, abdominal pain, myalgia, anorexia, conjunctival injection
History: Travel to Africa or Mediterranean past 2 weeks Travel to endemic areas during November through April Recent exposure to ticks or fleas in past 14 days
Treat empirically, do not wait for confirmatory tests; indirect immunofluorescence assay with Rickettsia rickettsii bacteria antigen, performed on 2 paired serum samples to demonstrate a significant (fourfold) rise in antibody titers; first sample in first week, then repeat in 2e4 weeks
Exam findings: Rash Maculopapular Vesicular Petechial Eschar At site of a bite or wound Relapsing fever (tick- or louseborne)
Fever—recurring, myalgia, joint pain, headache, nausea, vomiting, anorexia, cough (dry), rash, diarrhea
History: Worldwide, especially in North Americans traveling to Mexico in previous 26 days Exposed to contaminated water (including swimming) Exam findings: watery diarrhea
Meningitis
Fever, headache, nausea, vomiting, meningococcemia: fatigue, vomiting, myalgia, chest pain, abdominal pain, diarrhea, rash
History: Meningococcal: Worldwide but most prevalent in sub-Saharan areas in Africa in hot, dry weather Travel to endemic area in past 2 weeks
CBC: Leukocytosis with left shift Thrombocytopenia Elevated erythrocyte sedimentation rate Coagulation studies: Prothrombin time Partial thromboplastin time slightly increased Serum bilirubin: mild increase; antibody titers: mild to moderate comparison of acute to convalescent Borrelia-specific titers; polymerase chain reaction Bacterial: Cerebrospinal fluid culture Viral:
Naso-oropharyngeal swabs Rectal swabs Stool culture Cerebrospinal fluid Blood culture continued
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Table 3. (continued) Differential Diagnoses
Symptoms and Examination Findings Common to EVD
Unique History/Examination Findings
Confirmatory Test(s)
Viral: Most often in US Young children Immunosuppressed individuals Exam findings: Nuchal rigidity Pupuric rash Altered mental status Difficulty arousal upon awakening Hepatitis A, B
Fever, malaise, anorexia, nausea, vomiting, abdominal pain; in some cases: skin rashes, joint pain, arthritis
History: Hepatitis A: Eaten contaminated food, engaged in oral/anal sex, used recreational drugs in past 6 weeks Have clotting disorder (hemophilia) Hepatitis B: Blood, body fluid exposures in past 150 days Exam findings: Hepatitis A and B: Gray-colored stools Dark urine Jaundice Icterus
Hepatitis A: Anti-HAV IgM in serum or 4-fold rise in specific antibodies Hepatitis B: Hepatitis B surface antigen Antibody to hepatitis B core antigen Antibody to hepatitis B surface antigen IgM antibody to hepatitis B core antigen
Other viral hemorrhagic feversc
Same as EVD
History: Travel to undeveloped countries in past 21 days Specific risk factors: Unprotected sex Sharing needles Slaughtering animals Working with sick In rat-infested building Bitten by tick, mosquito, rodent, or bat in previous 21 days Exam findings: same as EVD
Same as EVD
Data included in this table are from the Center for Disease and Prevention website A-Z for each disease listed. Available at: http://www.cdc.gov/az/c.html. Accessed August 18, 2014. a Refer to CDC’s Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests, available online at: http://www.cdc.gov/flu/professionals/diagnosis/clinician_ guidance_ridt.htm#Table1. Refer to CDC’s Traveler’s Guide, available online at: http://www.cdc.gov/malaria/travelers/country_table/s.htm. c Includes Ebola and Marburg, Lassa fever, Rift Valley fever, Crimean-Congo hemorrhagic fever, Dengue, Yellow fever, Omsk hemorrhagic fever, Kyasanur Forest disease, and Alkhurma viruses. b
drugs, or any other treatment that would provoke bleeding. Avoid respiratory treatments or any aerosol-generating procedures.21 10
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There is ongoing work to find a drug to treat patients infected with EVD. Currently, there are 4 major groups of drugs being tested for use in those infected with Volume
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the virus, including RNA inhibitorebased (TMK-Ebola) agents, nucleoside analogs, monoclonal antibodies (ZMapp), and antisense-based (AVI-7537) drugs.17 ZMapp is one of the most promising drugs being tested. It is composed of 3 monoclonal antibodies produced in tobacco plants. This drug targets the expression phase of viral replication. It binds to the protein of the Ebola virus to prevent replication of the virus once introduced into the host.17 Another drug, BCX4430, may be ready for human testing within the next year. It is a broad species exhibiting antiviral activity for Marburg, Ebola, and yellow fever. The drug attacks an enzyme found in these specific viruses. In small animals, it has been shown to be effective if treatment is started within 48 hours after start of infection.22 As of September 13, 2014, there are other drugs proposed to treat patients with EVD. The off-label use of statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers has been the suggested treatment because of their ability to stimulate immunity in the infected person. Theoretically, boosting the patient’s immunity would aid in the prevention of complications such as end-stage organ failure. Other scientists support the use of interferon to treat EVD because of its antiviral properties and its past success treating patients with hepatitis C. CONCLUSION
Although EVD is unlikely to become pandemic in the United States, NPs need to be knowledgeable about this serious infection and be prepared to recognize and manage the disease. This situation regarding EVD is evolving and becoming more prescriptive on a daily basis. The United States Department of Health and Human Services and Department of State websites are constantly updated and provide excellent resources for travel advisories. Both CDC and WHO provide up-to-date information and guidance on precautions for patient care for practicing NPs.
2. Public Health Agency of Canada. Ebola virus. http://www.phac-aspc.gc.ca/lab -bio/res/psds-ftss/ebola-eng.php. Accessed August 1, 2014. 3. Lawrence G, Lucey D, Phelan A. The Ebola epidemic: a global health emergency. JAMA. http://jama.jamanetwork.com/article.aspx?articleid¼ 1897089&utm_campaign¼social_091914&utm_medium¼facebook&utm_ source¼jama_fb. Accessed August 12, 2014. 4. Mehedi M, Falzarano D, Seebach J, et al. A new Ebola virus nonstructural glycoprotein expressed through RNA editing. J Virol. 2011;85(11):9. 5. Virus Replication. Oakland University Lecture notes. In: Vital Replication in Principles of Virology. Flint J, Enquist L, Rananiello V, Krus R, eds. Vol 1. 3rd ed. Chapters 2, 4, and 5. Madison, WI: ASM; 2008. http://www2.oakland.edu/ biology/chaudhry/pics/virusreplication02web.pdf. Accessed August 5, 2014. 6. Baylor College of Medicine Virology and Microbiology. Ebola virus. https:// www.bcm.edu/departments/molecular-virology-and-microbiology/ebola. Accessed August 12, 2014. 7. Porth C. Essentials of Pathophysiology. 3rd ed. Philadelphia: Pa: Wolters Kluwer/Lippincott Williams & Wilkins; 2011:333-344. 8. Hammer, S. Viral Replication. Columbia University lecture notes. In: Virology replication. Basic Virology. Wagner E, Hewlett M, Bloom D, Camerini D eds. Lansing, MI: Blackwell;2007. http://www.columbia.edu/itc/hs/medical/ pathophys/id/2004/lecture/notes/viral_rep_Hammer. Accessed August 5, 2014. 9. Centers for Disease Control and Prevention Health Alert Network. Network CHA. Guidelines for evaluation of US patients suspected of having Ebola virus disease. http://emergency.cdc.gov/han/han00364.asp. Accessed August 13, 2014. 10. Green A. Ebola emergency meeting establishes new control centre. World Report. Vol. 384. http://www.thelancet.com/journals/lancet/article/PIIS0140 -6736%2814%2961147-8/fulltext. Accessed August 13, 2014. 11. World Health Organization. Ebola outbreak is a public health emergency. http://www.theguardian.com/society/2014/aug/08/who-ebola-outbreak -international-public-health-emergency. Accessed August 8, 2014. 12. National Travel Health Network and Center. Ebola virus disease, West Africa—update 12. Published August 2014. http://www.nathnac.org/pro/ clinical_updates/ebola_westafrica_120814.htm. Accessed August 13, 2014. 13. World Health Organization. Statement on travel and transport in relation to Ebola virus disease (EVD) outbreak. http://www.who.int/mediacentre/news/ statements/2014/ebola-travel-trasport/en/. Accessed August 18, 2014. 14. Konneh A. The economics of Ebola. Wall Street Journal. August 11, 2014; p A.13. 15. Dixon M, Schafer I. Ebola viral disease outbreak—West Africa. MMWR Morb Mort Wkly Rep. 2014;63(25):5. 16. Mullard A. Experimental Ebola drugs enter the limelight. Lancet. 2014;384(9944):649-649. 17. Enserink M. Ebola drugs still stuck in lab. Science. 2014;345:364-365. 18. Centers for Disease Control and Prevention. Ebola virus disease information for clinicians in U.S. healthcare settings. Published 2014. http://www.cdc.gov/ vhf/ebola/hcp/clinician-information-us-healthcare-settings.html. Accessed August 19, 2014. 19. Gatherer D. The 2014 Ebola virus disease outbreak in West Africa. J Gen Virol. 2014;95(Pt 8):1619-1624. 20. McElroy A, Erickson B, Flietstra T, et al. Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014;210:558-566. 21. 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. CDC 24/7: Savings lives, protecting people: 8. http://www.cdc.gov/vhf/ebola/hcp/infection-prevention-and -control-recommendations.html. Accessed August 13, 2014. 22. Ebola in West Africa. The Lancet Infectious Diseases. Vol. 14. 2014. http:// www.thelancet.com/journals/laninf/article/PIIS1473-3099 (14)70785-6/fulltext. http://dx.org/10.1016/S1473-3099(14)70785-6.
Anna Jarrett, PhD, ACNP/ACNS-BC, is an assistant professor in the Eleanor Mann School of Nursing at the University of Arkansas in Fayetteville, AR. She can be reached at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business of industry that would pose a conflict of interest.
References 1. World Health Organization. Ebola virus disease. Ebola virus disease fact sheet no. 103. Updated April 2014. http://www.who.int/mediacentre/factsheets/ fs103/en. Accessed August 4, 2014.
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1555-4155/14/$ see front matter © 2014 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2014.09.015
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