Ebolavirus Outbreaks, Past and Present

Nov. 16, 2022

Scanning electron micrograph of Ebola virus budding from the surface of a Vero cell (African green monkey kidney epithelial cell line.
Scanning electron micrograph of Ebola virus budding from the surface of a Vero cell (African green monkey kidney epithelial cell line.
Source: NIAID
Ebola virus disease (EVD), a devastating hemorrhagic disease that is often fatal, has been plaguing Africa since its initial discovery in 1976. For more than 42 years, the disease has claimed the lives of over 15,000 people, with no significant changes in case fatality rates. However, as the global response to EVD evolves, we continue to learn about better ways to diagnose, treat and prevent this disease. In September of this year (2022), a new outbreak of EVD was declared in Uganda. This serves as a harsh reminder that EVD is presently impactful and that sustaining the health and wellness of communities depends strongly on collaborative public health infrastructure that includes local expertise and input.

The Mystery Disease of Yambuku

It was a hot day at the end of August in Zaire, Africa (presently known as the Democratic Republic of Congo), and Mabalo Lokela was not feeling well. The 42-year-old headmaster of the Yambuku Mission School had just returned from a 2-week mission trip in northern Zaire and was now plagued with fever and chills. Suspecting malaria, clinicians at the outpatient clinic of the Yambuku Hospital treated Lokela with an injection of chloroquine, the immunosuppressive drug used to treat the parasitic infection.

Initially, as Lokela’s fever resolved and his symptoms lessened, the treatment seemed to be working, and he appeared to be recovering. However, 1 week after presenting at the clinic, Lokela returned with a severe headache, muscle and abdominal pain and intestinal bleeding. A few days later, he died. Lokela’s infection would later be identified as EVD, the first recorded case. Since this index case in 1976, sporadic outbreaks have occurred across Africa, claiming the lives of thousands of people, with a fatality rate of over 90%, depending on strain.

Virology, Transmission Dynamics, Detection, Treatment 

Basic Virology of Ebola Virus 

Ebolavirus is a member of the family filoviridae, along with Marburg virus and the lesser-known Cuevavirus. There are 4 strains of Ebolavirus, but only 3 cause disease in humans and non-human primates: the Zaire, Ivory Coast and Sudan strains. The Zaire strain is associated with the highest mortality rate. Based on a 2014 report, the overall case fatality rates for the Ebolavirus strains are 79% for Zaire, 54% for Sudan and 32% for Bundibugyo, although these rates vary depending on setting.

Ebola Virus Transmission

EVD does not naturally occur in the human population; it is introduced after exposure to close contact with the secretions, meat or bodily fluids of animals, such as fruit bats, monkeys or other rainforest animals. Once Ebola virus enters the human population, it spreads via direct contact with an infected person's blood or other bodily fluids, or through contact with items contaminated with fluids (blood, feces or vomit) from the body of a person who died from EVD.

Healthcare workers have frequently been infected during EVD outbreaks through close contact with their patients, when strict infection control practices have not been followed, or if access to proper protective equipment was limited. For example, in the 2014-2016 outbreak across multiple countries in Africa, traditional burial ceremonies that involved direct contact with the body of a victim of EVD (i.e., washing, dressing, lying over the corpse) were significant drivers of the spread of Ebola virus.
Nurse visits the graves of 1976 Ebola Zaire victims.
Nurse visits the graves of 1976 Ebola Zaire victims.
Source: getarchive.net


It is important to note that Ebola virus is not spread through droplet or aerosol routes, as is the case for respiratory viruses, and infected individuals are generally not considered to be contagious until they are symptomatic. Although EVD is serious and often fatal, the transmission requirements (i.e., direct contact with blood, vomit and other bodily fluids) and high mortality contribute to a low disease incidence.

Ebolavirus Diagnosis 

Laboratory testing for Ebola virus is challenging and complex. Labs performing testing on individuals suspected of having EVD must have adequate stocks of appropriate personal protective equipment, an acceptable biosafety level (BSL) laboratory infrastructure and adequate training for donning and doffing of personal protective equipment. Isolation of the virus should only be performed in a maximum containment BSL-4 laboratory. Other forms of testing may be performed in lower BSL level laboratories, depending on specimen conditions and the type of testing performed.

Recommended testing includes detection of virus RNA by RT-PCR, antigen testing and/or antibody testing. The World Health Organization (WHO) states that 2 negative RT-PCR test results, at least 48 hours apart, are required for a clinically asymptomatic patient to be discharged from hospital.

Ebola Treatment 

During the 2014 outbreak of EVD, 2 therapeutics were studied in the Democratic Republic of Congo. Both therapeutics, mAB114 (Ansuvimab; Ebanga) and REGN-EB3 (Inmazeb) are monoclonal antibodies that prevent the virus from entering a patient’s cells. WHO has released formal recommendations for the use of these drugs during EVD outbreaks. In late 2020, both drugs were cleared by the U.S. Food and Drug Administration (FDA) for the treatment of Zaire ebolavirus in adults and children. In light of strong, randomized controlled trial data, demonstrating benefit and FDA clearance of both drugs, WHO has called upon the global community to improve access to these medications, which will inevitably save lives. Regardless of available therapies, supportive care, including IV rehydration, continue to be a staple in the care of EVD patients.

Recent Outbreaks 

Ebola virus distribution map. Outbreaks by species since 1976.
Ebola virus distribution map. Outbreaks by species since 1976.
Source: CDC

Since the first EVD outbreak in 1976, there have been multiple outbreaks of EVD across Africa. The largest outbreak ever recorded occurred between 2014-2016 in multiple countries in West Africa. It resulted in approximately 28,652 cases and over 11,000 deaths. There were 20 EVD outbreaks before 2014, and although much had been learned about the virus and how to prevent its spread, the 2014 outbreak presented multiple unique challenges.

The outbreak began in Guinea, where public health infrastructure was inadequately resourced, resulting in failed surveillance methods and undetected spread of the disease to urban centers across Guinea, Liberia and Sierra Leone. Furthermore, containment efforts were hindered by limited laboratory testing and patient treatment capacity, which further overwhelmed the healthcare system. According to the U.S. Centers for Disease Control and Prevention (CDC), nearly 4,000 staff members aided in the outbreak response, alongside others from local and international organizations. In describing the multidisciplinary effort, the CDC states that the individuals deployed to the impacted areas included “specialists in epidemiology, infection control, laboratory analysis, medical care, emergency management, information technology, health communication, behavioral science, anthropology, logistics, planning and other disciplines."

Outbreak Opportunity: Development and Study of an Ebola Vaccine 

The unprecedented nature of the 2014-2016 outbreak provided an opportunity to initiate a clinical trial to test the safety and efficacy of 2 experimental Ebola vaccines in Liberia. Data from the phase II trial demonstrate no significant safety concerns for either vaccine. Furthermore, they initiate an immune response within a month of receiving the vaccine that offers protection for at least a year.

Another clinical trial called PREVAIL 5 began in 2017 across Africa and aimed to assess the vaccine strategy that most effectively protects people, including children as young as 1 year. Results from this study demonstrated no serious adverse events and an antibody response at 1 month in patients who received the vaccine, although it is important to note that only 32% of eligible individuals consented to receive the vaccine.

Currently, 2 vaccines are licensed for use, and both protect against Zaire ebolavirus. The Ervebo vaccine was studied in the PREVAIL trial and was also used under “compassionate use” during outbreaks in 2015 and 2018-2020, which resulted in 361,000 vaccinations. The Zabdeno and Mvabea vaccine was studied in over 3,000 adults, adolescents and children and demonstrated safe and adequate protection.

Current Outbreak

An outbreak caused by Sudan ebolavirus was declared in Uganda on September 20th, 2022. By the end of September 2022, 23 deaths had been reported, and multiple non-fatal cases had been identified. It is important to note that no vaccine is available to protect against Sudan virus disease (SVD). At the national level, the risk of disease spread is considered to be high based on the following factors:
  • The severity of SVD (fatality rate has ranged from 41%-100% in past outbreaks).
  • Lack of a vaccine for the SVD strain.
  • Multiple chains of transmission have likely not been tracked.
  • Inadequate use of personal protective equipment, especially when patients initially presented with mild infection.
  • Use of traditional burial practices with large ceremonies for those who died from SVD.
  • The health system can be easily overwhelmed if the outbreak spreads to other districts and regions, particularly since the country is impacted by various other infectious disease emergencies such as Yellow fever, Valley Fever and anthrax, as well as climate crises (i.e., flooding) and food insecurity.
Isolation of Ebola virus infection. Healthcare workers wearing hazmat suit and utilizing proper personal protective equipment.
Healthcare workers utilizing proper personal protective equipment to care for patient with EVD.
Source: pxhere.com
Overall, the risk of spread of disease at regional and global levels is currently considered to be low. However, since there is a lot of population movement across borders, the possibility of international spread cannot be ignored. National agencies like the CDC have prepared Ebola response resources in the case of an outbreak outside of endemic areas (East-Central and West Africa). These planning resources include tools that help assess healthcare system preparedness, risk communication messaging, information sharing, public health interventions, laboratory testing, epidemiologic investigation and responder health.

Conclusion 

Ebola virus is a lethal pathogen that has caused significant morbidity and mortality since its discovery in 1976. While prevention and management of the disease remains a challenge, the 2014 outbreak led to new discoveries in therapeutics and vaccines, which offer a glimmer of hope for better future management of the disease.

However, public health response and equity remain core elements in preventing and treating EVD. In his book “Fevers, Feuds, and Diamonds” Dr. Paul Farmer said “most of West Africa is a public health desert, which is why Ebola spreads there, and it is a clinical desert, which is why it kills there.” This, combined with the high EVD survival rates of patients from high income countries like the U.S. serve as a strong reminder that public health infrastructure is the key to global health, and that until disease prevention and control is optimized in parts of the world with the most need, we are all at risk.

Author: Andrea Prinzi, Ph.D., MPH, SM(ASCP)

Andrea Prinzi, Ph.D., MPH, SM(ASCP)
Andrea Prinzi, Ph.D., MPH, SM(ASCP) is a field medical director of U.S. medical affairs and works to bridge the gap between clinical diagnostics and clinical practice.