Continuing Education Activity

The Ebola virus is a contagious, lethal virus causing hemorrhagic fever. A recent epidemic in Western Africa lasted three years and affected several countries outside of continental Africa. A challenging epidemic can have a devastating global impact on healthcare, economy, and society. This activity describes the evaluation and treatment of patients infected with the Ebola virus and explains the role of the healthcare team in evaluating and treating patients with this condition.

Objectives:

• Identify the etiology of Ebola virus related medical conditions and emergencies.
• Describe the evaluation of patients infected with the Ebola virus.
• Outline the management options available for the Ebola virus.

Introduction

Ebola virus belongs to the Filoviridae family. The name is derived from the Latin word "filum" meaning thread. The filamentous virus has a characteristic twisted thread shape. Filoviridae viruses are negative-strand RNA viruses. They are the most common to infect humans and primates, causing highly fatal hemorrhagic fever.[1] The most virulent virus in the family is the Marburgvirus, whereas, the third member of the family, the Ceuvavirus, thus far, only exists in bats endemic to Spain.[2] There are five subtypes of Ebolaviruses named based on topographic discovery: Zaire, Bundibugyo, Sudan, Reston, and Tai Forest. According to the World Health Organization, fruit bats belonging to the Pteropodidae family may serve as the natural host for the Ebola virus. 

Ebola virus disease, once known by, Ebola hemorrhagic fever, is defined by the iconic hemorrhagic fever, but more common symptoms are non-specific such as fever, malaise, headache, diarrhea, or vomiting.[3] The disease can quickly progress to multi-organ system failure leading to shock followed by death. The case-fatality rate ranges from 25% to 90%; the average case fatality rate is about 50%. The range is dependent primarily on the type of strain of ebolavirus, the deadliest strain being Zaire ebolavirus.[4] The main variables impacting survival-rate is early identification of disease and access to healthcare for patient stabilization and supportive medical care.

Due to the increased incidence of outbreaks with the Ebola virus disease, early detection remains vital to reduce the risk of an epidemic. Several countermeasures, such as creating a vaccine and rapid testing with immunoassays or real-time polymerase chain reaction (PCR), were taken in efforts to reduce the risk of a global pandemic or exhausting epidemic. Previously, the virus was identified in blood samples using an electron microscope. The virus is very resilient, killing the virus requires high doses of gamma irradiation and ultraviolet light, long periods of 30 minutes or more of intense heat 60 degrees Celsius (140 degrees Fahrenheit).[4] There is still no cure or prophylaxis treatment for patients with Ebola virus disease. 

Etiology

Ebola virus was named after the Ebola River, where it first emerged in 1976. The working theory of the zoonotic vector for the Ebola virus infection in humans is the consumption of meat from infected non-human primates such as monkeys, apes, and chimpanzees. Strains of the Ebolavirus can be found in bats. However, it has yet proven transmission to humans.

Infected humans can transmit the virus through contact with bodily fluids, including saliva, blood, urine, feces, sweat, breast milk, semen, or fomites. Interestingly, the Ebola virus can survive in semen for up to 21 days after the patient has recovered. To date, there is conflicting information on whether vaginal secretions harbor or spread the Ebola virus. Once infected, the virus will incubate within the host during an asymptomatic, non-contagious period, usually lasts between several days to a few weeks. An infected person exhibiting signs and symptoms resembling a typical viral illness is considered contagious. 

The virus enters the new host through mucosal membranes or broken skin. Note the mucosal membrane does not need to be damaged for the virus to enter the host. The virus can survive outside the human body for an unknown amount of time. Most often, the bedding, clothes, medical utensils utilized in patients are all burned or disposed of as medical waste to avoid contamination and the risk of spreading the virus.[5]

Epidemiology

The Ebola virus was originally discovered in 1976, considered a rare, exotic disease mostly studied in highly classified laboratories. Since its discovery, over 20 outbreaks have occurred since 1976; many outbreaks were confined to rural areas in Sudan, Democratic Republic of Congo, Gabon, Republic of the Congo, and Uganda. Endemic outbreaks of the Ebola virus, most commonly Zaire and Sudan ebolavirus, are attributed to eating contaminated monkey meat. The epidemic spread is usually due to transmission to family members, then community members, and funeral practices.[6] Several outbreaks were caused by laboratory contamination.

The most recent outbreak is considered ongoing since June 1, 2020, in the Democratic Republic of the Congo. The longest outbreak turned epidemic spanned Western Africa, parts of Europe, and the United States. This complex epidemic crippled healthcare systems in some countries and shed light on the lack of preparedness for epidemics. Most reported cases outside of Africa were in healthcare workers providing aid in regions with an active outbreak, with strict travel restrictions and effective quarantine strategies, only a few travelers were infected due to direct human contact.

The mortality rate ranges from 25% to 90% based on the strain of ebolavirus. The deadliest strain, Zaire strain, was once 90% fatal. Due to increased awareness, education, and early detection, the average mortality rate is about 50%. The Ebola virus is only infectious when a person is experiencing prodromal symptoms such as fever, chills, nausea, vomiting, or when people come in contact with infected dead bodies.[7][4] Due to its mode of transmission and alarming case-fatality rate, the virus is a feared biowarfare agent.

Pathophysiology

Once the virus infects the host, there is an incubation period of 2 to 21 days. From the onset of symptoms, death can occur very quickly, often within six days.[6] The highly virulent virus activates both the innate and adaptive immune system causing immune-mediated cell damage, which compromises organ function in multiple vital organs such as lungs, heart, kidney, liver.[8] The deleterious effects of which lead to multi-system organ failure. Patients who recover have developed specific antibodies to the Ebola virus.[9] However, long-term consequences have been identified including, hepatitis, psychosis, uveitis, spinal cord injury. 

On a molecular level, the presence of the virus in the blood causes the direct release of cytokines, which activates acute phase reactants causing cell damage. The hemorrhagic aspect is more complex and involves disruption of the coagulation cascade through platelet aggregation, which sequesters platelets causing increased clots and clotting simultaneously, respectively.[4] All the while, damaging the liver, reducing the production of clotting factors.

The virus replicates after it penetrates the host cell membrane by binding with glycoproteins spikes and clathrin-mediated endocytosis. Once inside the cell, the virus releases its nucleocapsid into the host cell cytoplasm, where it replicates. Transcription and translation of the viral RNA into viral proteins is initiated by VP30 activating the start gene. Phosphorylation of VP30 by transcribed viral proteins turns of VP30, in this, VP30 seems to be a regulatory protein, and pharmaceutical research is underway to specifically target VP30.[4] The virus is released to the cell by budding from the cell membrane, causing direct damage to the cell, which can signal cell death. Currently, this process is not fully understood.

History and Physical

Persons or healthcare workers present with sudden fever, nausea, abdominal pain, vomiting, diarrhea, malaise, myalgias, bleeding from mucosal membranes, skin, eyes, nose, ears. Especially those who traveled to or came in close contact with anyone who has traveled to endemic countries with known or active outbreaks of Ebola virus within the last three weeks got infected. On physical exam, the patient may present with prodromal symptoms and stable or advanced illness and in shock.

Evaluation

The primary and most important survey will be to assess the patient and acquire a good set of vital signs, including temperature, blood pressure, heart rate, oxygen saturation, respiration rate. 

Laboratory Testing 

• CBC (complete blood count)
• CMP (comprehensive metabolic panel) will show liver and renal function
• UA (urinalysis)
• Ebola virus antigen with immunofluorescence ELISA (less sensitive than RT-PCR)[10]
• Ebola virus PCR testing
• Ebola virus antibody 
• Basic coagulation profile
• Type and screen

Treatment / Management

The cornerstone of management and treatment for patients infected with the Ebola virus and exhibiting symptoms of Ebola virus disease is supportive care. Repeating fluid loss with IV administration of fluids and electrolytes, controlling temperature with antipyretics. 

In addition to supportive care, extensive, emergency research during the last Ebola virus outbreak showed promising results. These studies focused on treatment therapies including the use of convalescent plasma, monoclonal antibodies, anti-viral drugs such as remdesivir.[11] One of the most effective treatments is prevention, several vaccines have been developed. Further prevention of spread, through imposing international travel bans and exit screenings upon departure from countries with active Ebola outbreaks is a critical non-medical intervention.[12]

Differential Diagnosis

Ebola virus disease should be differentiated from other causes of hemorrhagic fever and common viral illnesses presenting with similar prodromal symptoms and gastrointestinal symptoms.

Hemorrhagic Fever

• Marburg virus
• Lassa fever
• Dengue
• Bunyavirus

Similar Prodromal Symptoms

• Malaria
• Typhoid fever
• Influenza
• Cholera

Gastroenteritis

• Shigella
• Rotavirus
• Norovirus

Prognosis

The rate of recovery depends on early intervention and access to adequate healthcare with the administration of continuous supportive care and close-interval patient reassessment. Even with optimal treatment, the mortality rate remains 50% on average.

Complications

The main complications caused by the Ebola virus are hemorrhagic fever and multi-system organ failure leading to shock and eventually death. The dead bodies must be handled with proper PPE as it can still transmit the virus, due to its resistance to moderate temperature changes.

Deterrence and Patient Education

It is vital to educate the public to limit the number of cases spread in the community, and hence the public should be educated about the following:

Public Health

• Educate persons in rural areas to recognize the signs and symptoms of the Ebola virus disease
• Education on the dangers of eating monkey meat and bats. 
• Education on how the Ebola virus is spread
  • Bodily fluids, sexual contact, cadaverous
• Identifying and reporting findings of dead or diseased animals nearby

Patient Education

• Signs and symptoms of the disease
• Quarantine instructions
• When to go to the hospital, signs of low blood pressure, increased heart rate, uncontrolled fever
• Quarantine/isolation of family members who become sick
• Viral shedding through semen up to 21 days after recovery

Enhancing Healthcare Team Outcomes

Ebola virus remains a public health crisis. It is a complex virus causing the deadly disease that is difficult to contain. If it were not for the remote and rural locations of outbreaks, the fear of an Ebola pandemic would be more eminent. The last Ebola virus epidemic revealed the increased need to stay informed on zoonotic, rare diseases. The increasing incidence of Ebola virus outbreaks directly correlates with the risk of a pandemic, with travel being the main vector. 

Supportive care remains the determining factor for a good prognosis and outcome. Creating Ebola virus disease treatment units (ETUs) in the hospitals or converting areas to create ETUs, to provide supportive care remains a public health priority. Adjunct therapy with monoclonal antibodies and anti-virals was successful in reducing mortality from the Ebola virus disease during the recent epidemic. The PALM trial effectively targeted research showing highly targeted monoclonal antibodies were superior to a lesser specific monoclonal antibody and anti-viral remdesivir.[13] (Level I) As treatment options increase, it remains vital that healthcare providers remain vigilant in identification, containment, and educated on the use of PPE to contain the spread of the Ebola virus.