Ebola Hemorrhagic Fever (Ebola Virus Disease)

Picture of the Ebola virus

Ebola hemorrhagic fever is a viral disease caused by Ebola virus (a member of the Filoviridae family or filoviruses) that results in nonspecific symptoms (see symptom section of this article) early in the disease and often causes internal and external hemorrhage (bleeding) as the disease progresses. Ebola hemorrhagic fever is one of the most life-threatening viral infections; the mortality rate (death rate) may be very high during outbreaks (reports of outbreaks range from about 25%-100% of people infected, depending on the Ebola strain). Because most outbreaks occur in areas where high-level intensive care supportive public health services are not available, survival rates are difficult to translate to potential outbreaks in Ebola-affected areas with more resources.

Picture of the Ebola virus, viewed with an electron microscope; SOURCE: CDC/Frederick Murphy

Ebola hemorrhagic fever first appeared in Zaire (currently, the Democratic Republic of the Congo or DRC or Congo) in 1976. The original outbreak was in a village named Yambuku near the Ebola River after which the disease was named. During that time, researchers identified the virus in person-to-person contact transmission. Of the 318 patients diagnosed with Ebola, 88% died. The second outbreak occurred in Nzara, South Sudan, in 1976, with 151 deaths.

Since that time, there have been multiple outbreaks of Ebola virus, and researchers have identified five strains; four of the strains are responsible for the high death rates. The four Ebola strains are termed as follows: Zaire, Sudan, Tai Forest, and Bundibugyo virus, with Zaire Ebola virus being the most lethal strain. Researchers have found a fifth strain termed Reston in the Philippines. The strain infects primates, pigs, and humans and causes few if any symptoms and no deaths in humans. Most outbreaks of the more lethal strains of Ebola have occurred in sub-Saharan West Africa and mainly in small- or medium-sized towns. Health care professionals believe bats, monkeys, and other animals maintain the non-human virus life cycle in the wild; humans can become infected from handling and/or eating infected animals.

Once an Ebola outbreak is recognized, African officials isolate the area until the outbreak ceases. However, in the outbreak that began in West Africa in March 2014, some of the infected people reached larger city centers before the outbreak was recognized; this caused further spread. The infecting Ebola virus detected during this outbreak was the Zaire strain, the most pathogenic strain of Ebola. Health agencies are terming this outbreak as an "unprecedented epidemic." This epidemic spread quickly in the West African countries of Guinea and Sierra Leone. In addition, countries of Liberia, Nigeria, Senegal, Uganda, and Mali all reported confirmed infections with Ebola. In addition, a few infections or flare-ups of Ebola virus infection appeared in the United States, Spain, and the United Kingdom (see for example, the case of Pauline Cafferkey, a nurse who became infected); most of the people with Ebola in these countries either were imported infections from West Africa or were newly spread infections from treating patients who originally became infected in Africa. Another outbreak occurred in the DRC in May 2018 in Bikoro, a small town 80 miles from Mbandaka, with 46 reported infections and 26 deaths. Unfortunately, the large city of Mbandaka, with over 1 million people, has recorded at least three people with Ebola. The DRC hopes to isolate or stop the spread of Ebola in the two areas by vaccinating anyone who may have had some physical contact with an infected person with a new chimeric virus vaccine that in 2015 showed good results in Ebola-infected patients.

Health officials now report over 1,000 deaths due to Ebola in areas like Butembo in the Congo (DRC) and neighboring countries in an ongoing outbreak over the last 9 months. This outbreak is difficult to control because it is happening in a war zone where cooperation between countries to control the outbreak is uncoordinated and even considered unwelcome.

The cause of Ebola hemorrhagic fever is Ebola virus infection that results in coagulation abnormalities, including gastrointestinal bleeding, development of a rash, cytokine release, damage to the liver, and massive viremia (large number of viruses in the blood) that leads to damaged vascular cells that form blood vessels. As the massive viremia continues, coagulation factors are compromised and the microvascular endothelial cells are damaged or destroyed, resulting in diffuse bleeding internally and externally (bleeding from the mucosal surfaces like nasal passages and/or mouth and gums and even from the eyes [termed conjunctival bleeding]). This uncontrolled bleeding leads to blood and fluid loss and can cause hypotensive shock that causes death in many Ebola-infected patients.

The risk factors for Ebola hemorrhagic fever are travel to areas with reported Ebola infections (see current CDC travel advisories for African countries). In addition, association with animals (mainly primates in the area with reported Ebola infections) is potentially a health risk factor according to the Centers for Disease Control and Prevention. Another potential source of the virus is eating or handling "bush meat." Bush meat is the meat of wild animals, including hoofed animals, primates, bats, and rodents. Evidence for any airborne transmission of this virus is lacking. During Ebola hemorrhagic fever outbreaks, health care workers and family members and friends associated with an infected person (human-to-human transfer) are at the highest risk of getting the disease. Researchers who study Ebola hemorrhagic fever viruses are also at risk of developing the disease if a laboratory accident occurs. Caring for infected patients who are near-death or disposing of bodies of individuals that have recently died of Ebola infection is a very high-risk factor because in these situations, the Ebola virus is highly concentrated in any blood or bodily secretions. Caregivers should wear appropriate full-length personal protective equipment (See the CDC site http://www.cdc.gov/vhf/ebola/healthcare-us/hospitals/infection-control.html for details).

Ebola viruses are highly contagious once early symptoms such as fever develop. The infected patient sheds infectious viruses in all body secretions (bodily fluids); direct contact with any of these secretions may cause the virus transmission to uninfected individuals. The Centers for Disease Control and Prevention (CDC) suggests that infection with Ebola that is airborne is theoretically possible but unlikely. Although Ebola is contagious, careful hygiene and barrier techniques can make the infection low risk for contagion; measles is considered by some experts to be the fastest-spreading disease.

For those patients who survive infection, they may remain contagious for approximately 21-42 days after symptoms abate. However, health care professionals can remove the viruses from semen, breast milk, spinal column, and ocular fluids. It is unclear, according to the CDC, if these fluids can transmit viruses, although the CDC suggests that Ebola can be spread by semen and suggest male survivors of the disease abstain from sex or use a condom for all sexual activity.

Ebola virus disease symptoms and signs may appear from about 2 to 21 days after exposure (average incubation period is e8 to 10 days). It is unclear why some patients can survive and others die from this disease, but patients who die usually have a poor immune response to the virus. Patients who survive have symptoms that can be severe for a week or two; recovery is often slow (weeks to months) and some survivors have chronic problems such as fatigue and eye problems.

Unfortunately, early symptoms of Ebola virus disease are nonspecific and include

• fever,
• headache (severe),
• weakness,
• vomiting,
• diarrhea,
• stomach discomfort or pain in the abdomen,
• decreased appetite, and
• joint and muscle discomfort.

As the disease progresses, patients may develop other symptoms and signs such as

• a rash or red spots on the skin,
• eye redness,
• hiccups,
• sore throat,
• cough and/or coughing up blood,
• vomiting up blood,
• chest pain,
• mental confusion,
• bleeding both inside and outside the body (for example, mucosal surfaces, eyes), and
• difficulty swallowing and breathing.

Because Ebola infections can spread rapidly to others and because patients can easily infect health care workers, the CDC and other agencies recommend that only highly trained personnel treat Ebola patients. This treatment involves high-level barrier techniques to protect all health care professionals (hospital care workers, nurses, doctors, lab technicians, janitors, and hospital infectious-disease-control personnel). Unfortunately, these trained individuals and resources are often not available in the Ebola high-risk areas. Ideally, individuals diagnosed with Ebola in the U.S. should be treated in specific designated treatment centers and treatment monitored by the CDC. Types of specialists who may treat Ebola-infected patients are emergency medicine specialists, infectious disease specialists, critical care doctors and nurses, pulmonologists, hematologists, hospitalists, and hospital infection-control personnel.

Physicians preliminarily diagnose Ebola hemorrhagic fever by clinical suspicion due to association with other individuals with Ebola and with the early symptoms described above. Within a few days after symptoms and signs develop, tests such as ELISA (enzyme-linked immunosorbent assay based on antigen capture), RT-PCR (reverse transcription polymerase chain reaction), and/or virus isolation can provide definitive diagnosis. Later in the disease or if the patient recovers, it's possible to detect IgM and IgG antibodies against the infecting Ebola strain. Similarly, health care professionals usually perform studies using immunohistochemistry testing, PCR, and virus isolation in deceased patients for epidemiological purposes.

According to the CDC and others, standard treatment for Ebola hemorrhagic fever is still limited to supportive therapy. Supportive therapy is balancing the patient's fluid and electrolytes, maintaining their oxygen status and blood pressure, and treating such patients for any complicating infections. Any patients suspected of having Ebola hemorrhagic fever should be isolated, and caregivers should wear protective garments. Currently, there is no specific medical treatment for Ebola hemorrhagic fever according to the CDC. The CDC recommends the following medical treatments for Ebola-infected patients:

• Providing intravenous fluids (IV) and balancing electrolytes (body salts)
• Maintaining oxygen status and blood pressure
• Treating other infections if they occur

Health care professionals transport patients diagnosed with Ebola in the U.S. to special hospitals certified to treat Ebola patients. (Contact the CDC immediately for information for experimental vaccines, treatment protocols, and patient care and/or transfer to an appropriate facility.) The special hospitals were certified because of the problems experienced in a Texas hospital where the first patient in the U.S. was diagnosed with Ebola and subsequently spread the disease to hospital workers. Experimental medical treatments of Ebola infections include immune serum, antiviral drugs, possible blood transfusions, and supportive care in an intensive care hospital facility approved by the CDC to treat Ebola infections.

Ebola hemorrhagic fever often has many complications; organ failures, severe bleeding, jaundice, delirium, shock, seizures, coma, and death (about 50%-100% of infected patients). Those patients fortunate enough to survive Ebola hemorrhagic fever still may have complications that may take many months to resolve. Survivors may experience weakness, fatigue, headaches, hair loss, hepatitis, sensory changes, and inflammation of organs (for example, the testicles and the eyes). Some may have Ebola linger in their semen for months and others may have the virus latently infect their eye(s).

Male patients may have detectable Ebola viruses in their semen for as long as six months after they survive the infection. Researchers consider the chance of being infected with Ebola from semen is very low; however, they recommend utilizing condoms for six months; some experts suggest a longer time.

It is apparent that we don't know everything about how to cure Ebola infections. A physician thought to be cured of Ebola, Dr. Ian Crozier, in fall 2014 developed burning light sensitivity in his eyes. He returned to Emory University where he was treated and after several tests, he was found to have Ebola infection in his eyes. However, only the fluid removed by needle from his eyes showed viable virus; his tears and the outer membrane of his eyes had no detectable virus. Consequently, health care professionals considered the patient not to be able to spread the virus. One of the complications was that his blue eye color turned green. Fortunately, for Dr. Crosier, treatment with steroids and antiviral agents allowed his eyes to return to normal. This unusual circumstance has suggested that follow-up eye exams are likely to be important in patients who survive Ebola infections.

The prognosis of Ebola hemorrhagic fever is often poor; the death rate of this disease ranges from 25%-100%, and those who survive may experience the complications listed above. However, early diagnosis and treatment of Ebola may greatly increase the patient's chance for survival. Unfortunately, this disease has been mainly located in countries where medical care is often difficult to obtain, especially in rural areas of Africa. Statistics available on the ongoing 2014-2016 outbreak of Ebola are summarized below:

• Total suspected, probable, and confirmed infections worldwide equal 28,616, and total deaths equal 11,310 for a death rate or death toll of approximately 41%. An occasional new infection (at a low level) and deaths of current patients are unlikely to change these numbers substantially as the epidemic outbreak has ended according to the CDC. Fortunately, this epidemic of 2014-2016 did not become a pandemic but did show how rapidly a relatively rare disease like Ebola can rapidly infect a large number of individuals in this modern-day society.

The main way to prevent getting Ebola hemorrhagic fever is to not travel to areas where it is endemic and by staying away from any patients who may have the disease. Medical caregivers may protect themselves from infection by strict adherence to barriers to the virus (wearing gloves, gowns, goggles, and a mask). People can disinfect surfaces with alcohol-based (70%) wipes.

The following are the recommendations from the CDC to prevent getting Ebola (EVD) from an infected person. Avoid the following:

• Contact with blood and body fluids (such as urine, feces, saliva, sweat, vomit, breast milk, semen, and vaginal fluids)
• Items that may have contacted an infected person's blood or body fluids (such as clothes, bedding, needles, and medical equipment)
• Funeral or burial rituals that require handling the body of someone who died from EVD
• Contact with bats and nonhuman primates or blood, fluids, and raw meat prepared from these animals (bushmeat) or meat from an unknown source
• Contact with semen from a man who had EVD until you know the virus is gone from the semen

In addition, after leaving an area affected by EVD, individuals should monitor their health for 21 days; if a person develops any symptoms, he or she should immediately seek medical care and inform the medical caregivers of his or her exposure to Ebola.

Fortunately, in December 2016, researchers reported on a human clinical trial of rVSV-ZEBOV vaccine that was apparently effective and relatively safe for vaccination against Ebola disease. The researchers used people (contacts) exposed to Ebola patients during the outbreak in a trial following similar procedures ("ring of exposure") used to eliminate smallpox. Researchers randomly assigned the Ebola case exposure patient to get the vaccine at day 0 or 21 days later after being identified as a new case exposure. Although many vaccinated people developed side effects of injection-site pain, mild headache, fatigue and muscle pain, most individuals recovered within a few days and none develop long-term problems. The study involved 11,841 people. The vaccine was 100% effective in patients who obtained the vaccine at day 0 and those day 0 individuals who had no symptoms within 10 days (due to the approximate average incubation period of Ebola). There were 23 new cases of Ebola in patients who got the vaccine 21 days later. Three adverse events occurred in the vaccinated population; one had a febrile reaction to the vaccine, one experienced anaphylaxis and one experienced flu or flu-like symptoms but all recovered and remained healthy. Consequently, many investigators consider this vaccine to be a safe and effective vaccine. There is a stockpile of 300,000 doses in reserve for future outbreaks. The vaccine is in limited supply and not licensed by the FDA. Health care professionals use this vaccine in the same way to limit the spread of Ebola in the DRC in the 2018-2019 outbreak. Time will tell if the "ring of exposure" method of vaccination will stop the outbreak.