Uganda's Ebola Victory: A Triumph Against Ebola virus disease Re-emergence ?

Uganda declared the end of the Ebola outbreak caused by the Sudan ebolavirus on 11 January 2023. This declaration came after 42 consecutive days without any reported cases following the release of the last patient from care. As of now, there have been no recent incidents of Ebola reported.

The Ebola virus is re-emerging, posing a significant threat due to its high fatality rate, which averages around 50% and can reach up to 90%. While it's endemic to African nations, its broad transmission methods mean it can quickly escalate from outbreaks to epidemics or even pandemics, especially in our interconnected world.

To tackle this threat effectively, are we prepared with effective antivirals, safe vaccines, and widespread public awareness about the virus?

Ebola virus causes rare but fatal lethal hemorrhagic fever. This viral infection is not limited to humans but also causes diseases in nonhuman primates (monkeys, chimpanzees).

The Ebola virus first emerged in 1976 during separate hemorrhagic fever outbreaks in Yambuku, Zaire (now Democratic Republic of Congo), and Nzara, Sudan, approximately 800km apart. The virus was isolated from a patient in Yambuku and named after the nearby Ebola River to prevent stigmatization of the town. Initially believed to be related, subsequent research confirmed they were caused by distinct strains: Ebola Zaire and Ebola Sudan, named after their respective countries of discovery.

Ebola has history of re-emergence. 

Since its discovery in 1976, Ebola has caused sporadic outbreaks primarily in Central and West Africa. The first outbreak occurred near the Ebola River, spanning what is now the Democratic Republic of Congo and South Sudan. Subsequent years saw smaller outbreaks in Central Africa, affecting countries like Sudan, DRC, Gabon, and Uganda. The largest outbreak in history occurred from 2013 to 2016 in West Africa, primarily in Guinea, Liberia, and Sierra Leone, resulting in over 28,000 cases and 11,000 deaths. Smaller outbreaks continued in subsequent years, including in the DRC in 2018 and 2018-2020 and in Guinea during 2021-2022. Efforts to contain Ebola have involved international organizations and national health agencies, facing challenges due to the virus's high mortality rate and difficulties in diagnosis and treatment.
The virus belongs to the Filoviridae family, Ebolavirus genus, which includes Zaire ebolavirus (EBOV), Reston ebolavirus (RESTV), Bundibugyo ebolavirus (BDBV), Taï Forest ebolavirus (TAFV), Sudan ebolavirus (SUDV), and Bombali ebolavirus (BOMV). EBOV, responsible for Ebola hemorrhagic fever (EHF), exhibits the highest human mortality rates, followed by SUDV and BDBV. TAFV has caused only two nonlethal human infections to date, while RESTV leads to asymptomatic human infections, primarily identified in the Philippines.
 
Fruit bats of the Pteropodidae family, including Hypsignathus monstrous, Epomops franqueti, and Myonycteris torquata, serve as natural hosts of the Ebola virus (EBOV) in Africa. Nonhuman primates can contract the virus by consuming partially eaten fruits and subsequently transmit it to humans. The virus is typically introduced into human populations in endemic African regions by handling infected animal carcasses, commonly referred to as bushmeat. Subsequent human-to-human transmission then becomes a prominent feature of any epidemic. Intimate physical contact with patients in acute disease stages and exposure to blood/fluids from deceased individuals are primary transmission modes. Traditional funeral practices in African countries involve the direct handling of bodies, significantly contributing to disease spread.

EBOV RNA can persist for up to a month in rectal, conjunctival, and vaginal discharges, and up to three months in semen, indicating the virus may persist in recovering patients.
A case of sexually transmitted EVD has been reported between a convalescent patient and a close family member.

Asymptomatic carriers of EBOV are not infectious and do not play a significant role in Ebola virus disease outbreaks. Patients can only spread the infection when they have symptoms; transmission does not occur during the incubation period.

EBOV has been detected in blood, saliva, semen, and breast milk. RNA has been isolated from sweat, tears, stool, and on skin, vaginal, and rectal swabs. Exposure to infected bodily fluids is the main mode of transmission. Eating undercooked meat from infected animals, hospital-acquired infections, and poor sanitation, have also been reported in EVD dissemination. Transmission can also occur through contaminated materials (fomites) carrying infected bodily secretions. It's not clear if the disease can spread through the air or droplets.
 
Ebola viruses entering the human body infect immune system cells (dendritic cells, monocytes, and macrophages), endothelial and epithelial cells, hepatocytes, and fibroblasts, where they replicate actively, leading to high levels of virus in the bloodstream. The virus spreads to regional lymph nodes causing swelling, then travels through the blood to the liver and spleen, triggering an intense inflammatory response. This response, driven by inflammatory chemicals (cytokines and chemokines), disrupts vascular function, leading to disseminated intravascular coagulation and multiple organ failure.

Ebola can only spread to others after symptoms appear, typically within 8 to 10 days after contact, occasionally up to 21 days. Early symptoms are nonspecific, which complicates diagnosis.

Initial Ebola Virus Disease (EVD) symptoms are nonspecific, resembling dengue, typhoid fever, malaria, and flu. They typically appear 8–11 days post-infection and include high fever, headaches, sore throat, cough, abdominal pain, nausea, vomiting, and diarrhoea. As the disease progresses, symptoms worsen with bleeding manifestations such as gum and nosebleeds, gastrointestinal bleeding, and hematuria. Severe cases can lead to dehydration, shock, multiorgan dysfunction, and death.

Reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) are the primary diagnostic tests for confirming Ebola virus disease (EVD) in laboratories.

Two licensed vaccines are available for the Ebola virus (Orthoebolavirus zairense): ERVEBO (Merck), a single-dose rVSVΔG-ZEBOV-GP vaccine approved by the FDA in the United States, and Zabdeno/Mvabea (Johnson & Johnson), a two-dose regimen of Ad26.ZEBOV and MVA-BN-Filo were used in outbreaks but were not FDA-approved in the United States.

Ebola Virus Disease (EVD) is a life-threatening condition associated with a high global mortality rate and significant chronic sequelae. Survivors often experience chronic manifestations resembling autoimmune and auto-inflammatory conditions. 

Developing antiviral medications and establishing safe and effective vaccines are crucial for preparedness in managing EBOV disease under any circumstances. Antiviral drugs can provide immediate treatment options for those infected, potentially reducing severity and mortality rates. On the other hand, vaccines play a pivotal role in prevention by priming the immune system to recognize and combat the virus before infection occurs, thus curbing transmission and preventing outbreaks mainly in endemic regions. 

These approaches are essential components of a comprehensive strategy to combat EBOV disease effectively and ensure global health security.