Article Type : Review Article
Authors : Mohsina FP1, Nesar A, Mukim M, Roy S, Sharma P and Faheem IP
Keywords : Ebola virus disease; Ebola virus; Prevention; Management; Treatment
Ebola virus disease
(EVD) is epidemically fast-growing disease. Ebola virus (EV) was discovered by
Dr. Peter Piotin (1976, Zaire), who suspected yellow jack in blood of catholic
nun. There are five strains of EV, but the Zaire strain is the most severe
having case-fatality ?? 90%. Its genome is a 19 kb long single-helix, (-) RNA.
More than 28,000 cases and over 11,000 deaths occurred in West African
(September 2015). EV transmitted to people from wild animals and spread
frequently in the human with incubation period and infection of 2 to 21 days.
First symptoms were appeared as sudden onset of fever, fatigue, muscles pain,
headache, sore throat, gum bleeding, rectal bleeding, multi-organ disease with
damaged vascular system and body’s regulation was impaired. The defensive white
blood cells as well as platelet count can be reduced while the liver biomarker
enzymes are elevated in some patients. The EV may be treated intravenous
fluids. However, innumerable probable treatments are under preclinical and
clinical evaluation consisting of immunological therapies, blood products, and
drugs therapeutics. Also, various vaccines are under clinical trials for safety
testing, but till date no vaccines are approved for human use. There is a
challenge to understand the differences among species of Ebola virus. Moreover,
studies are required into the ecology of reservoir species and shedding
procedures. Novel targets tactics required in the pathophysiology of EV
infections with animals’ study.
The international
community has responded to the Ebola outbreak in West Africa with an approach
that could be described as ‘top down’. Small groups of elite scientists, health
policy makers, pharmaceutical company executives, and the staff of the World Health
Organization (WHO), governmental agencies, and non- governmental institutions
have decided how to implement interventions for outbreak control and
containment and develop new Ebola vaccines and treatments. These ‘top down’
interventions have built Ebola treatment units and organized the delivery of
supplies, communications, and surveillance that have been essential for
outbreak control. However, they have had only a modest impact on the survival
rate for individual patients. In most treatment units, overall case fatality
rates have been 60% or greater, and they have been even higher in patients who
have been treated in the community [1]. Ebola virus disease outbreak in West
Africa sends an alarming message to all countries in the world, to increase the
level of coordination and application of preventive measures globally to avoid
a disastrous epidemic in the World, as the current situation in West Africa is
critical especially after the WHO increased the alarming level to an emergency
in public health all over the world [2] reported systematic review on MHPSS
programs among communities affected by EVD. This study shows the need to
increase efforts to systematically document and evaluate the implemented
programs. Results also provide preliminary evidence about the value of
culturally sensitive MHPSS programs and of the implication of local mental
health professionals [3]. The first outbreak of Ebola virus was described in
1976 near the Ebola River in Zaire. The Ebola virus infected 318
cases and caused 280 deaths. Fever and bleeding were the
main symptoms observed
at that time; therefore, the EVD was initially termed Ebola hemorrhagic
fever. To date, there have been 33 sporadic outbreaks worldwide, including 23
human-to-human transmission epidemics, three laboratory-induced outbreaks, and
seven animal-to-human transmission outbreaks [4]. The Ebola virus is spread
easily through the use of filthy syringes and needles or when an infected
person comes in a close proximity with the non-infected person [5]. As per the
reports of WHO, till May 3, 2015 more than 26 628 cumulative cases of EVD and
about 11020 mortality had occurred [6]. The continued upsurge in the new cases
has been lowered in Liberia, Guinea, and Sierra Leone, showing the signs of
reversal. Since there is no specific drug treatment for the EV, extensive
research is urgently needed on new epidemiological features and EVD epidemic
developmental patterns that will eventually aid in the guidance for the proper
drug development, treatment and management of the EVD outbreak.
EVD can
transmit directly through the close contact with infected saliva, blood, sweat,
urine, and other body fluids including semen, vomit, feces, and breast milk. It
can also transmit via contact with objects infected with the various body
fluids of the diseased person [7,8]. Transmission is believed to occur via
contact with mucous membranes and non-intact skin (i.e., rashes, cuts, etc.).
Risk of infection by inhalation of contaminated aerosols by healthcare workers
has not been documented but is assumed to be low at this point supported history evidence
[9,10]. Soap, direct sunlight, bleach, or drying can directly inhibit the viral
growth. The virus has a short life span on the surfaces that are directly in
the contact with the sun [11].
Ebola
virus is an infectious, transferable, intra-cellular organism having either RNA
or DNA as a genetic background. The filamentous filovirus is a single stranded
RNA, enveloped organism having 80 nm non-segmented RNA molecules with a length
up to 1400 nm. It encodes about 7 main genes: nucleoprotein, RNA-dependent RNA
polymerase (L), VP 24, VP 30, VP35, VP40, and GP. The genomes of the five
distinct Ebola viruses (BDBV, ZEBOV, REBOV, SEBOV and TAFV) vary in sequence
and therefore the number and site of gene overlaps. Among all, viral
transactivation and replication is mediated by VP30, nucleoprotein, VP35 as
well as RNA polymerase. The viral budding and transmission is mediated by VP40
matrix protein while nucleo capsid development is associated with minor matrix
protein called VP24. Interferon signaling is obstructed by both the matrix
proteins that are VP24 and VP40. The GP is a surface protein represented as a
trimeric spike embracing two subunits GP1 and GP2 [12]. The lifecycle of EV is
divided into following phases:
· Attachment
of virus to the cell surface
· Penetration
of virus
· Uncoating
· Replication
and viral expression
· Maturation
· Viral
exocytosis
Extensive
weakness, fever, and diarrhea are the main symptoms of EVD. Elevated
transaminases, maculopapular rash, thrombocytopenia, lymphopenia are also main
abnormalities associated with the EVD. Nearly half of the patients experience
these bleeding problems mildly while severe bleeding problems are relatively rare.
It is vital to have a thorough history of travelling. The viral incubation time
is classically 5-7 days [13]. Once it is suspected that it is the Ebola virus,
the diagnosis must be confirmed. In the absence of effective healing
strategies, the analysis and diagnosis of the infection play an important role.
Molecular techniques including polymerase chain reaction (PCR) are the main
diagnostic tools. Blood samples usually present positive PCR results a day
before the clinical manifestation occur. The PCR testing is sensitive and
specific real time and it can give results within hours. The exchange of
information in real time, about the PCR results, is completely essential to
improve the response capacity. The primary detection of antigen could be
employed as a confirmatory diagnosis test for instantaneous analysis. Secondary
assays involve the antibodies detection including IgG and IgM that are
generally significant for the epidemiological surveillance. Furthermore,
confirmed deep-rooted diagnosis continues to be a vital procedure for contact
search to overcome the various difficulties for reintroducing the survivors in
the community. Ebola infected patients require an urgent and fast treatment as
well as efficient basic support in order to visualize the difference between
survival and mortality rate in the infested patient [14].
Managing
contact tracing personnel is another major challenge. Hiring a sufficient
number of appropriately trained staff, especially in heavily affected areas,
has been hindered by limited education and managerial proficiencies in the
population that necessitates the establishment of job-explicit training [15]. Furthermore,
contact tracing employees can be erroneously perceived to have an augmented danger
of obtaining EVD, leading to stigmatization. Guinea and Liberia have
employed media resources for depicting the employees as the heroes. Another
major apprehension in retentive employees is security; some of the societies have
banned the entry of contact tracing employees, occasionally intimidating
physical fierceness [16]. In response, in Liberia, security forces have been
employed to accompany contact tracing personnel into communities [17].
There is no precise remedy for EVD. Since till
date there is no efficacious vaccine or any antiviral drugs are available, the
therapeutic management of EVD patients is a major threat. The management is
basically relied on the survival support, control of organ failure as well as
on providing the symptomatic relief that focuses on the supply of adequate
nutrition and hydration along with antibiotics, and antimalarial drugs if
essential. Remdesivir developed by
Gilead Sciences in 2017 as a treatment for Ebola virus infection [18]. Severe isolation of diseased
individual along with limited nursing support is another crucial step that can
help to prevent the disease transmission. In the cases where there is an
extensive disease transmission danger from dead bodies, individual defensive
instruments as well as sanitization for surface cleansing should be employed
along with the safety guidelines recommended by CDC directions [19]. Such type
of investigation was not repeated in further outbreaks as in vitro assay
indicated that antibodies against Ebola had no neutralizing action.
Furthermore, monoclonal antibodies to the GP of Ebola virus exhibited defensive
and healing properties in mice but they were unable to protect NHP [20,21]. The
animal studies suggest that Ebola specific immunoglobulin of equine origin has
little activity in hiding viraemia and slowing disease onset in NHP. Goat
immune-globulins were evaluated in pre-clinical test on laboratory animals and
were administered to scientist assumed of gaining infection with EHF during
their investigational work. It was suggested that these immune-globulins might
be beneficial for the emergency cure of persons inadvertently infected with EHF
[22]. The Ebola virus reproduction was shown to be hindered in vitro by a series
of nine nucleoside analogue inhibitors of S-adenosyl homocysteine hydrolase and
carbocyclic 3-deazaadenosine was shown to avert death in mice infected with the
Ebolavirus [23]. Various clinical aids like injections, catheters and
parenteral interventions etc. should be reduced to avert trauma and the
increased challenge of disease spread. Several drugs specially aspirin,
non-steroidal anti-inflammatory drugs, anticoagulant therapies, and steroids
should be contraindicated [24]. The recommendations of WHO for treatment at
home have been comparatively effective if specialized care is not available
[25]. Extensive researches are registered whose primary aim is to discover an
effective the rapeutic for safe and efficient management of the EVD patients.
Presently, RNA inhibitor drugs (TKM-Ebola), nucleoside analogs, monoclonal
antibodies (ZMapp), antisense-based (AVI-7537) drugs and
phosphorodiamidatemorpholino oligomers are the major drug categories that are
under clinical evaluation for their action against EVD. Favipiravir is a
potential repurposed candidate that can suppress viral growth by inhibiting
viral replication. Another hopeful candidate is ZMapp consists of three
monoclonal antibodies obtained from plant of tobacco. The main target of the
drug is inhibition of viral replication, especially the expression phase as the
virus enters the host cellular machinery [26]. Additional drug, that is also
effective against yellow fever and Marburg is BCX4430. The drug possesses good
antiviral activity as it is capable of targeting a major enzyme present in the EV.
In preclinical studies the drug has shown significant effective results in
suppressing the infection when administered within 2 days of infection [27].
The repurposed use inhibitors of angiotensin-converting enzyme as well as
statins and blockers of angiotensin receptor have been recommended as
supportive treatment for improvising and encouraging the immune system of the
diseased person. Ebola virus is normally considered as a conceivable biological
weapon, thus there is a crucial need to develop effective antiviral drugs and
vaccines [28]. Reiter RJ et al., 2020 reported on the utility of melatonin as
a treatment for virus-mediated diseases. Of special note are the data related
to the role of melatonin in influencing Ebola virus disease. This infection and
deadly condition has no effective treatment and the published works documenting
the ability of melatonin to attenuate the severity of viral infections
generally and Ebola infection specifically are considered. The capacity of
melatonin to prevent one of the major complications of an Ebola infection,
i.e., the hemorrhagic shock syndrome, which often contributes to the high
mortality rate, is noteworthy. Considering the high safety profile of
melatonin, the fact that it is easily produced, inexpensive and can be
self-administered makes it an attractive potential treatment for Ebola virus
pathology [29].
This
epidemic may
be a tragic illustration of the importance of improving
global health security. Every day, the transmission of the disease remains
unchecked and
therefore the likelihood of spreading to unaffected
countries increases. It is also important to mention that the epidemic is
occurring in West Africa, where there had not been an Ebola outbreak before.
Ebola has grasped the level where it can be regarded as an endemic ailment due
to a very insufficient and delayed global response. For the medium term, the
risk of constant spread of the epidemic should be taken into account and the
possibility that the Ebola become endemic in West Africa shall be assumed, a
perspective never contemplated before. If this happens, West Africa could
become a reservoir for the virus to spread to other parts of Africa and beyond
[28]. The typical efforts “to control the outbreak” aren't enough any longer for
such an
enormous epidemic. What is required is action at an enormous scale,
a humanitarian strategy and a mixture of typical public health measures with
efficient and secure procedures, which include supplies and human resources,
among others [30]. Moreover, a proper response requires an appreciation of the
culture of societies in the affected countries and the implementation of
interventions with the consent of the population [31]. Paradoxically, in the
first world there is an “urgency to delete “everything related to Ebola [32].
At the same time, there is a conviction that as Western Africa is not the whole
world, but only a piece of the planet plagued by a deadly epidemic, it has now
become a threat because the disease has the potential to spread to other
countries, including the rich ones[33,34]. The self-preservation gregarious
instinct prevented honest souls in real time disclosure of what was happening
[35]. The greatest protection in contradiction of an epidemic is to prevent the
transmission at a point where it initiated, and this may be accomplished with
the support of the finest healthcare services. Africa is known to have no
well-equipped health care services for preventing the epidemic in this public
health crisis [36,37]. We have to be one step further from this outbreak, but
at this time we are five steps behind [38-40].
Tracing
process, as prompt and efficient contact tracing is important for the
identification, control, and elimination of EVD, any delay or
inefficiency may
result in ongoing response efforts and failure to get to
zero cases. Although contact tracing challenges could also be hooked in to each
country’s unique socioeconomic, geopolitical, and cultural context, there are common
issues encountered throughout the West African region. Underlying a number of
these challenges is the novelty of EVD in the region, which has contributed to
the fear, stigma, and community EVD misperceptions. Liberia, Nigeria, Senegal,
and Mali were able to overcome these challenges, successfully eliminating EVD.
The ongoing support and continuing efforts of the West African ministries of
health and in- country staff to identify and address these challenges, and
learn from these successes, will improve contact tracing efforts in West
Africa. Ultimately, this will lead to a halting of EVD transmission in the
region and the prevention of large-scale EVD outbreaks in the future.
We declare that we have no conflict of
interest.