Ebola Virus Disease

What is Ebola Virus?

Ebola is also called Ebola virus disease (EVD). EVD is a deadly disease with severe complications like Ebola hemorrhagic fever and organ failure in later stages of infection. EVD was earlier known as Ebola hemorrhagic fever or EHF, but since 2014, it was named EVD as it is not only limited to febrile illness. Historically, there have been several episodes of sporadic outbreak. The first of such outbreaks was documented in 1976, but the recent outbreak in Western Africa in 2013 – 2014 was notable due to the high incidence of outbreak. In 2014, the World Health Organization (WHO) declared the outbreak as a Public Health Emergency of International Concern (PHEIC). Further, WHO seeks enhanced efforts to combat this fatal disease. The name Ebola was taken from the Ebola River in Africa, where the earliest signs of outbreak occurred. EVD is a highly contagious disease caused by the Ebola virus where the virus easily spreads (transmissible) to people coming into contact with those infected by the virus.



Symptoms

The Ebola virus is an enveloped single-stranded RNA virus. EVD occurs in both primates and humans. In humans, it is caused by four Ebola virus species, namely Zaire Ebola virus, Sudan virus, Taï Forest virus, and Bundibugyo virus. It can infect 2 to 21 days of infection. The major early symptomatic manifestations of EVD are fever, muscle pain, fatigue, sore throat with headache. Subsequently, later symptoms may arise in the form of vomiting, diarrhea, skin rash, symptoms of impaired kidney and liver functions, low platelet counts with both internal and external bleeding. EVD begins typically with a febrile illness (high fever) followed by gastrointestinal problems. In patients with high viral loads, EVD infection progresses to a complicated fatal multiple organ dysfunction syndrome.


Transmission

The transmission of EVD is both zoonotic and anthroponotic, that is from animals to humans, and humans to humans, respectively. In zoonotic transmission, humans become infected while having physical contact with infected animals or while handling bushmeat. The human-to-human transmission was reported via contact with blood and/or body fluids from infected humans. Ebola virus can also transmit through the skin, even without bruises or cuts, bodily fluids, or fomites. Due to the severity of this and devastating socioeconomic effects, the Ebola virus is considered as a Category A Priority pathogen by the National Institute of Allergy and Infectious Diseases or NIAID. Furthermore, the Ebola virus is considered a Category A threat agent by the Centers for Disease Control and Prevention (CDC). Multi-organ failure is the primary cause for mortality in EVD while electrolyte imbalances may lead to cardiac rhythm problems or coma.



Diagnosis

Clinical misdiagnosis can occur in detecting EVD as the clinical manifestations are similar to diseases like meningitis, malaria, or typhoid fever. Even symptoms of pregnancy overlap with the clinical aspects of EVD. Thus, pregnant women should be tested rapidly if they suspect an Ebola virus infection. Laboratory-based diagnosis has a huge role to play in efforts related to rapid response to outbreaks. As a traditional as well as the gold standard of diagnosis, cell culture, and propagation of isolated virus in Vero E6 African green monkey’s kidney cells and examining it under biosafety level-4 containment or BSL-4 facility by electron microscopic techniques remains the standard. However, with the advent of modern technology and analyzing tools, there are quite a few diagnostic tests utilized to detect EVD. Such diagnoses depend on three basic techniques namely serology-based, antigen-based, and other molecular tests such as reverse transcriptase-polymerase chain reactions or RT-PCRs. However, none of the tests have proven to demonstrate the capability to detect the viral load before the onset of symptoms in patients, which is still a gap in the diagnosis protocol. An early point of care diagnosis is emphasized to detect cases under field settings. In acute symptomatic patients, viral proteins can be detected at optimal levels in antigen-based tests with better accuracy than antibody or serology-based tests. Also, the use of a rapid antigen detection test is further recommended under field settings.


Associated risks

There are increased risks of contracting the disease if an individual is suffering already from malnutrition as well as co-infections like malaria. Women as caregivers and pregnant women can carry the risk of passing on the fatal infection to its offspring. Adults between 35-44 years are more susceptible to Ebola virus infection. The strong risk of transmission of the Ebola virus from one human to another is determined via contact with infected bodily fluids like breast milk, saliva, semen, urine, aqueous humor, cerebrospinal fluid, and blood. In addition, rare sexual transmission of the Ebola virus can be another risk factor. Children were observed to have a higher risk of mortality than older populations, especially children below 5 years of age. Treatment and management has emphasized supportive care such as isolating patients and providing rehydration along with rapid diagnostic testing, monitoring of vital signs, ventilation, and symptomatic administration of therapeutics. Vaccines remain the promising approach to prevent cases of mortalities. Following the 2014 outbreak, several countries raise their concerns on implementation of precautionary measures in the form of vaccines. Only during the recent outbreak in the Democratic Republic of Congo (DRC), the vaccine Ervebo® has been recommended under compassionate use protocols. Ervebo® was approved by the U.S. Food and Drug Administration (FDA) on December 19, 2019, as the first vaccine for treating the deadliest strain of Ebola virus, Zaire Ebolavirus. Efficient control of an outbreak depends on the imposition of a set of interventions, which revolves around methodical case management, contact tracing, and surveillance, as well as the establishment of good laboratory services, safe burials, and maintenance of physical distancing and responsible communication. The establishment of strategic community engagement is an additional measure to successfully control and regulate outbreaks. These organizations help to disseminate awareness of risk factors, transmission and personal protective measures which are essential to reducing human-to-human transmission.




At-risk healthcare workers are taught/provided with standard preventive measures that include maintenance of basic hand and respiratory hygiene, supply and implementation of personal protective equipment or PPE, safe injection as well as safe burial practices. Similarly, laboratory workers, who are at equal risk, are also provided protection and the protocols to maintain the highest level of biosafety precautions. The enormous number of mortalities, as well as affected health workers in the past episodes of EVD outbreak, has made it indispensable to analyze and research on both diagnostic and therapeutic aspects of EVD that are currently available along with formulating more efficient tactics to combat this virus. Currently, various novel immune therapies and drug therapies are being evaluated. On October 14, 2020, the FDA approved Inmazeb® (atoltivimab, maftivimab, and odesivimab-ebgn), a mixture of three monoclonal antibodies, as the first FDA-approved treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. While there is still some controversy, remdesivir, may also have a positive impact on reducing the effects of this deadly disease.




Written By: Souvik Datta, Ph.D. & Lawrence D. Jones, Ph.D.