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.