Ebola Virus

 

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!

Original Editors - Leann Bruce and Kara Cannon from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Leann Bruce, Kara Cannon, Ylice Bridges, Elaine Lonnemann, Kim Jackson, 127.0.0.1, Evan Thomas, WikiSysop and Nupur Smit Shah  

Definition/Description

     “Ebola Virus Disease (EVD) is a severe, often fatal, zoonotic infection caused by a virus of the Filoviridae family (genus Ebolavirus),”¹. EVD is one type of hemorrhagic fever that is commonly found in west, central, and east Africa. The disease is caused by a single-stranded RNA Flavovirus which tends to replicate on dendritic cells, macrophages, and monocytes. The virus then uses multiple mechanisms to invade its host including migration to the spleen, liver, and lymph nodes which leads to widespread infection.¹ There are five known strains of EVD: Zaire ebolavirus, Bundibugyo virus, Sudan Virus, Taï Forest virus, and Reston virus. Of the five strains, only the Reston virus has not affected humans. The other strains have fatality rates ranging from 30-90% depending on the specific outbreak.²

     EVD originates in animals and is spread to humans through hunting and eating of bushmeat or contact with bat feces. Once a human has EVD, the virus is spread through contact with bodily fluids or reuse of needles that have not been properly decontaminated.¹ “Classification by the Centers for Disease Control as a category A agent also designates EBOV as a bioterrorism threat, making this virus a biodefense research priority”³.

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Prevalence

     The Ebola Virus has been through 25 outbreaks since the first cases were discovered in humans in 1976⁴. The epidemics have centered mainly in west African countries with some occurring in the eastern and central areas as well. There have been more than 26,000 high- fatality cases of the virus documented in western Africa⁵. “The West African outbreak of Ebola virus disease (EVD) has been described as one of the most devastating health crises of the 21st century. It has resulted in over 11,000 deaths”⁶. The three largest outbreaks have occurred in Sierra Leone, Guinea, and Liberia^5,7. The statistics available from each outbreak are variable and likely underrepresenting the disease prevalence due to a lack of healthcare reporting. Also contributing to this problem are a lack of education, recovery from civil war, a failing economy, mobile populations leading to urban overcrowding or movement to isolated, rural communities, and a lack of transportation to healthcare facilities.⁶

Source commons.wikimedia.org/wiki/File:EbolaSubmit2.png

This photo is licensed for use through creativecommons.org/licenses/by-sa/3.0/deed.en

Characteristics/Clinical Presentation

Ebola Virus is characterized by the following signs and symptoms:

1. Early Stage

• Fever (>37.5⁰C)
• Myalgia
• Diarrhea
• Vomiting
• Headache
• Fatigue
• Sore throat
• Asthenia (extreme)
• Anorexia
• Abdominal Pain
• Back Pain
• Arthralgia

2. Mid Stage

• Nausea and Vomiting
• Headache
• Confusion
• Capillary Leak
• Difficulty Breathing/Respiratory Distress
• Low Blood Pressure
• Rash (macropapular)

3. Late Stage

• Multi-Organ Failure
• Hemorrhage (internal/external)
• Hiccups
• Dilirium
• Shock (Septic and Hypovolemic)

Other symptoms of EVD, although rare, include hepatomegaly, lymphadenopathy, encephalopathy, and seizures.^1,2,4,8

Associated Co-morbidities

     The are very few studies on comorbidities found in patients with Ebola. The most common comorbidity seen in patients with Ebola is Malaria. One study of epidemiological, clinical, and outcome features found that 72% of the 90 patients with Ebola were also diagnosed with malaria. The only other comorbidity found in the study was diabetes (2% of the 90 patients).⁹

Medications

     There is currently no preventative vaccine or licensed treatment for the Ebola virus. However, recent research has focused on experimental drugs and treatments to fight the disease, and many other medications are used to treat the numerous symptoms that Ebola patients experience. The following are current medications and treatments that are used to combat the Ebola virus:

1. Antibiotics for the prevention and treatment of bacterial infections: ^4,5

• Cefixime
• Ceftriaxone
• Ertapenem
• Levofloxacin
• Meropenem
• Metronidazole
• Piperacillin-tazobactam
• Vancomycin

2. Antidiarrheal: ⁵

• Diphenoxylate-atropine

3. Antifungal: ⁵

• Micafungin

4. Rehydration: ⁴

• Oral rehydration solution
• Ringer lactate

5. Sedative: ⁵

• Propofol

6. Supportive care and analgesics for treatment of general symptoms: ^1,4,5

• Acetaminophen
• Diphenhydramine
• Electrolyte supplements
• Hydrocodone
• Meperidine
• Ondansetron
• Opioid analgesics (ex. morphine)
• Pantoprazole
• Paracetamol
• Phenazopyridine
• Protein-rich oral supplements
• Vitamins

The following are experimental drugs and treatments that researchers are currently testing for the therapeutic benefits towards Ebola:

Emerging treatments: 1,2

• ZMapp (best known emerging treatment to date; experimental drug that has shown therapeutic benefits against Ebola in humans)
• TKM-Ebola (proven to be protective in non-human primates and has been given to a few patients under emergency protocols)
• Brincidofovir (has shown activity against Ebola in vitro; has been given to patients under emergency protocols; future trials are planned in west Africa)
• Favipiravir (effective against Ebola in mice; future human trials are planned to start in west Africa)
• BCX-4430 (no human studies have been performed, but shown to be active against Ebola in non-human primates and rodents)
• AVI-7537 (improves survival in non-human primates infected with the Ebola virus)
• Interferons, amiodarone, clomiphene, and chloroquine (other agents that are being investigated with uncertain benefits against Ebola in humans)
• cAd3-ZEBOV and rVSV-ZEBOV (two experimental vaccines that are currently undergoing human trials in the US)
• Convalescent whole blood or plasma (limited evidence that transfusion of blood from convalescent patients might reduce mortality, but investigative trials are planned)
  
  

Diagnostic Tests/Lab Tests/Lab Values

     The diagnostic gold standard for the confirmation of Ebola is reverse transcription polymerase chain reaction (RT-PCR)⁴. It is able to detect the virus in patients in the early and late stages of the disease. Another useful diagnostic test that has a high specificity but is not universally available is the antigen capture enzyme linked immunosorbent assay (ELISA) ¹. Laboratory tests that have been used for the molecular detection of Ebola in conjunction with RT-PCR are the QIAGEN QIAamp Viral RNA Mini Kit and the MagMAX Pathogen RNA/DNA Kit (Life Technologies). Both of these methods are used to purify RNA from whole blood specimens. Assays for Ebola virus-specific antibodies (IgM and IgG) can also be performed to indicate the presence or absence of the disease.⁵

     Laboratory findings that do not confirm the presence of Ebola but may appear abnormal if the individual has the disease are: leukopenia, lymphopenia, thrombocytopenia, disseminated intravascular coagulation (DIC), hyponatremia, hypokalemia, hypocalcemia, hypoalbuminemia, hematuria, proteinuria, oliguria, elevated serum creatinine or urea levels, elevated serum glucose level, and elevated serum aspartate amino-transferase level. Chest radiography may also be performed in patients with respiratory symptoms.^1,5,10 

Etiology/Causes

     Ebola Virus Disease (EVD) is seen primarily in Africa and originates in certain species of bats along with primates such as gorillas and apes. Both hosts are known “reservoirs” of EVD and can be affected by the illness. Transmission to humans occurs through two ways: hunting and eating bush meat or eating food contaminated by bat feces. Once a human has been infected, EVD can be spread through contact of body fluids (blood, sweat, vomit, diarrhea, saliva, feces, urine, genital secretions, and breast milk). Even after the disease has run its course, due to viral shedding there is still risk of transmission through contact with semen, breast milk, saliva, stool, tears, and possibly urine. Other mechanisms of transmission include reuse of improperly sterilized needles and lack of clean water for handwashing.¹ 

     While this is the scientific explanation for the Ebola Virus there are myths that have surrounded this illness and led to distrust among people in Africa.The first myth is that a plane full of witches crashed and led to the first outbreak. The second myth is that a snake was released from a covered box by an unknowing husband, and the snake went on a killing spree.⁶ Therefore, there is a stigma surrounding this disease.

Photo: www.cdc.gov/vhf/ebola/resources/virus-ecology.html

Systemic Involvement

Ebola Virus has the ability to affect most systems throughout the body including, but certainly not limited to: ^1,4,11

Cardiovascular system:

• Tachycardia
• coagulopathy (thrombocytopenia, reduced clotting factor, increased fibrin-degradation products)
• sepsis

Hepatic system:

• hepatitis
• liver damage
• hepatocellular necrosis
• hepatocellular lesions
• hepatomegaly

Renal system

• acute kidney injury
• renal dysfunction

Gastrointestinal system:

• GI hemorrhage (upper and lower)
• Hematemesis
• melena

Ocular System:

• conjunctival infection
• uveitis

Endocrine System:

• adrenal failure (impairs secretion of hormones resulting in hypotension, renal sodium loss, and hypovolemia)
• pancreatitis

Immune System:

• Lymphadenopathy
• systemic inflammatory response

Neurological System:

• Confusion
• Aggression
• metabolic encephalopathy
• Neurotropism
• Seizures
• hiccups
  
  

Medical Management (current best evidence)

     Medical management is a carefully guarded process of isolation, symptom management, and experimental medications and treatments. The incubation period for Ebola is up to 21 days and so a patient may be asymptomatic until that point. There are three phases of Ebola characterized by different symptoms. The first phase typically has less prominent symptoms and may include headache, myalgia, and fever >37.5℃. The second phase includes various gastrointestinal symptoms such as nausea, vomiting, diarrhea, and dehydration. The final phase is either recovery or deterioration including neurological changes, collapse, and internal or external bleeding leading to death.¹

     Once a patient is suspected of having Ebola, he/she is placed in medical isolation in order to prevent the spread of the virus. The patient then undergoes testing in order to determine if Ebola is present (see Diagnostic Tests for further details). At the same time, anybody the patient had contact with in the last 21 days is tracked down and required to perform temperature reading BID in order to detect any rise in fever which could indicate that the virus has been spread. Typically the virus does not spread until symptoms occur but with a lack of access to medical facilities and early symptoms that are not significant, EVD may not be caught until symptoms have occurred for several days.¹ “The most common symptoms reported between symptom onset and case detection in the 2014 outbreak were fever (87.1%), fatigue (76.4%), loss of appetite (64.5%), vomiting (67.6%), diarrhoea (65.6%), headache (53.4%), abdominal pain (44.3%), and unexplained bleeding (18%)”¹.

     After the patient is in isolation, a full medical screening is performed in order to rule out other illnesses and confirm the presence of Ebola Virus. The screening includes, but is not limited to, temperature, blood pressure, pulse, respiratory rate, and a physical examination. (For further information, see Diagnostic Tests).After the patient is diagnosed, symptom management begins. Fluid and electrolyte replacement is begun in order to counteract dehydration caused by vomiting and diarrhea. Medications such as paracetamol and opioid pain reliever are given in order to counteract the initial side effects of fever and myalgia. Antiemetics are given either orally or intravenously in an effort to reduce the amount of vomiting. In addition to these, other medications may be given as the virus progresses depending on what symptoms the patient develops. Currently there are no vaccines proven to prevent Ebola, but there are two vaccines in the testing phase which may be accessible to the public in the future. There are several emerging treatments that have been developed in order to fight the Ebola Virus. Most were created during the most recent outbreak of Ebola. As it was an emergency situation, many of the treatments have not been tested in order to determine if they are useful or if there are any long term side effects.¹ (For more information see Medications)

Physical Therapy Management (current best evidence)

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Differential Diagnosis

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Case Reports/ Case Studies

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Resources

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Recent Related Research (from Pubmed)

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References

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