Key Words: Ebola
virus disease
Definition:
Ebola virus is named after the river in the former Zaire where
a haemorrhagic fever initially identified in 1976 involved
human to human transmission, as well as spread by contaminated
injection equipments [1
]. Ebola
virus causes an acute febrile illness associated with a high
mortality rate. The illness is characterized by multi-system
involvement that begins with abrupt onset of headache,
myalgia, fever and proceeds to prostration, rash, shock and
bleeding manifestation.
Epidemics usually begin with a single case acquired from an
unknown reservoir (bats suspected) and spread mainly through
close contact with sick persons or their body fluids either at
home or in the hospital.
Etiology
The family filoviridae comprises two antigenically and
genetically distinct genera Marburg virus and Ebola virus.
Ebola virus has five readily distinguishable species named for
their original sites of recognition: Zaire, Sudan, Cote
d'Ivoire, Buno Bugyo and Reston [1].
Ebola virions
Typical Filovirus particles contain single, linear negative
sense single standard RNA arranged in a helical
nucleocapsid. Virions are 790-970nm in length. They may appear
elongated or contorted forms. These viruses are destroyed by
heat (60º in 30 minutes) and by acidity but may persist for
weeks in blood at room temperature [1].
Epidemiology
Ebola virus first appeared in 1976 causing severe hemorrhagic
fever in Zaire and Sudan (550 cases). Mortality was 90% and
50% respectively. Both epidemics were associated with inter
human spread.
After 20 years, Zaire Ebola virus recurred in the Democratic
Republic of Congo in 1995 (317 cases) and in smaller epidemics
in Gabon in 1994-1996 mortality rate was 88%.
Deep forest exposure again resulted in an epidemic in Gabon in
1994 - 2003.
Present episode
Mainly five countries in West Africa - (Guinea, Liberia,
Nigeria, Senegal, and Sierra Leone) have been affected. This
epidemic began in Guinea during December 2013. WHO was
officially notified of the rapidly evolving EVD outbreak on
March 23, 2014. On August 8, the WHO declared the epidemic to
be a "public health emergency of international concern". As of
September 14, 2014, a total of 4507 confirmed and probable
cases of Ebola virus disease have been detected. 2296 deaths
from the virus, have been reported and the case fatality rate
is 50 %.
Clinical features
Patients in the age group 15 to 44 years have been involved,
with an incubation period 2 to 21 days. Principal
manifestations are fever, fatigue, headache, arthralgia,
myalgia, abdominal pain and chest pain. Dyspnoea, sore throat,
diarrhoea and loss of appetite, bleeding from puncture sites
and mucus membranes, petechiae, echymosis, pupura and finally
death is due to multi-organ dysfunction syndrome (MODS) and
septic shock can ensue [1-4].
Pathology and pathogenesis
Ebola and Marburg viruses replicate virtually in all cell
types including endothelial cells, macrophages and parenchymal
cells of multiple organs [2].
The earliest involvement is the mononuclear macrophage system
and that is responsible for initiation of the disease process.
In human disease and Macaque models upregulation of tissue
factor and disseminated intravascular coagulation are the
inciting mechanisms.
Viral replication is associated with cellular necrosis both in
vivo and vitro. In light microscopy level, the changes are
liver necrosis with councilman bodies, intracellular
inclusions of viral nucleocapsids, interstitial pneumonitis,
cerebral glial nodules and small infarcts. Antigen and virions
are abundant in fibroblasts and Interstitium. The appendages
of subcutaneous tissues also contain virions and antigen and
they escape through small breaks in the skin or possibly
through sweat glands also. Hence close contact with patients
and touching of the diseased may be avoided. Inflammatory
cells are not prominent even in necrotic areas.
Virus interacts intimately with cellular cytokine system.
There is high level of pro inflammatory cytokines which
contributes to the severity of illness.
Virus is resistant to the antiviral effects of interferon.
Viral infection of endothelial cells selectively inhibits the
expression of major histocompatibility complex class I
molecules and blocks the induction of several genes by the
interferons. In addition glycoprotein expression inhibits and
∞V integrin expression and that leads to detachment and
subsequent death of endothelial cells in vitro and that
correlates with the limited inflammatory response evident in
lesions.
How to categorize and confirm Ebola virus disease
(WHO definitions)
Suspected case: Is any person alive or dead, who
has (or had) sudden onset of high fever and had contact with a
person with a suspected, probable or confirmed Ebola case or
with a dead or sick animal OR
Any person with sudden onset of high fever and at least 3 of
the following symptoms, headache, vomiting, anorexia,
diarrhoea, lethargy, myalgia, arthralgia, dysphagia, dyspnoea,
or any person who had unexpected bleeding or who died suddenly
from an unexplained cause.
Probable case: Is any person suspected to
have EVD who was evaluated by a clinician or any person who
died from suspected Ebola and had an epidemiologic link to a
person with a confirmed case but was not tested and did not
have laboratory confirmation of the disease.
Confirmed case: A probable or suspected case is
classified as confirmed when a sample from the person was
positive for Ebola virus RNA, antigen or antibody.
Laboratory findings in Ebola virus disease
Important laboratory findings which can occur in Ebola virus
disease are leukopenia, thrombocytopenia, hypoproteinemia,
proteinuria, deranged coagulation profile due to disseminated
intravascular coagulation (DIC), increased levels of SGOT,
SGPT (mild) and increased serum amylase [3].
Differential Diagnosis
Differential diagnosis of Ebola virus disease include viral
hemorrhagic fever (Dengue), Falciparum malaria, Leptospirosis,
Rickettsial fever, Typhoid fever, Gram negative sepsis,
Cholera and Shigellosis [2].
Diagnosis
Travel and work history along with exposure to wild life
animal [1], isolating the virus by cell culture of blood, CSF
or throat washings taken during the viremic phase of illness
and from postmortem tissues in fatal cases, viral antigen by
ELISA [2], detecting the viral RNA by RT-PCR of blood or other
tissue fluids or gingival brushings [2], detecting IgM and IgG
antibodies by ELISA in recovering patients [2] are
important in diagnosis of Ebola virus disease. EBOLA eZY
screen promoted by Vedalab, an European company may prove to
be a rapid diagnostic kit for diagnosing Ebola virus disease
in 15 minutes where monoclonal anti body is reacting to the
presence of virus in a tiny sample of blood, plasma or urine.
The test is yet to be marketed.
Treatment
No specific treatment [1] is available for Ebola virus
disease. Supportive care in the form of intravenous fluids,
antipyretics, vasopressors, oxygen, fresh frozen plasma and
red cell transfusions are given as needed. Hemodialysis for
renal failure, heparin for DIC, antibiotics to prevent
secondary infections and activated protein C infusion have
been used.
Convalescent phase plasma has little in vitro neutralizing
capacity and is not protective in humans or in passive
transfer experiments in monkeys and Guinea Pig models [5].
Studies in Rhesus monkeys have shown improved survival among
animals treated with an inhibitor of Factor VIIa / tissue
factor or with activated protein C
Ebola virus disease developed in a patient who contracted the
disease in Sierra Leone and was airlifted to an isolation
facility in Hamburg, Germany, for treatment. During the course
of the illness, he had numerous complications, including
septicemia, respiratory failure, and encephalopathy. Intensive
supportive treatment consisting of high-volume fluid
resuscitation (approximately 10 liters per day in the first 72
hours), broad-spectrum antibiotic therapy, and ventilatory
support resulted in full recovery without the use of
experimental therapies [6].
Prevention
Primary prevention: Public education [2]
Secondary prevention: Standard precautions for
infection control, isolating the patient, quarantine and
contact tracing (Senegal method) are used.
Ebola vaccine
Phase 1 Studies of cAd3 - EBOV have begun in the United Stated
and the United Kingdom already. Researchers plan to begin
enrollment for trials of rVSV soon. Both vaccine candidates
have demonstrated 100% efficacy in non human primates but how
that will translate to human subjects remains unknown [7,8].
Prognosis
Death usually occurs around the 9th day of illness secondary
to hypovolumic shock and multi organ failure. The case
fatality rate is lower for Ebola Sudan (50-60%) than for Zaire
(78-90%). Even well resourced hospital settings have
demonstrated a higher rate of mortality (80-90%) especially in
Angola and the Democratic Republic of Congo for Ebola
hemorrhagic fever [9].
References
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Sprecher A. Ebola Virus Disease in West Africa - Clinical
Manifestations and Management. N Engl J Med. 2014 Nov 5.
[Epub ahead of print]
2. Marty AM, Jahrling PB, Geisbert TW. Viral Hemorrhagic
fevers, Clin Lab Med 2006; 26: 345-386.
3. Peters CJ, LeDuc JW. An introduction to Ebola: the virus
and the disease. J Infect Dis. 1999; 179 (suppl):ix-xvi.
4. Peters CJ. Filoriridae: Marburg and Ebola virus
hemorrhagic fevers, in GL Mandell et al (eds).
Principles and practice of Infectious Disease 7th ed.
Philadelphia, Churchil Livingston 2010, 2259 -2262.
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JB, Paragas J, Young HA, Fredeking TM, Rote WE, Vlasuk GP.
Treatment of Ebola virus infection with a recombinant
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Schmiedel S. A Case of Severe Ebola Virus Infection
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RA, Sullivan NJ. Chimpanzee adenovirus vaccine generates
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8. Geisbert TW, Geisbert JB, Leung A, Daddario-DiCaprio KM,
Hensley LE, Grolla A, Feldmann H. Single-injection vaccine
protects nonhuman primates against infection with Marburg
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9. Erqonul O. Crimean-Congo haemorrhagic fever. Lancet Infect
Dis. 2006;6:203-14.