Ebola Virus- A Review
Hemashree S1,
Rubini K R1, Sabin Lohala2, Nithya S*
School of Pharmaceutical Sciences, Vels University (VISTAS), Velan Nagar, P.V. Vaithyalingam Road,
Pallavaram, Chennai - 600 117. Tamil Nadu, India.
*Corresponding Author E-mail: sermugapandian.nithya@gmail.com
Received on 21.03.2016
Modified on 04.04.2016
Accepted on 28.04.2016 ©
RJPT All right reserved
Research J. Pharm. and Tech. 2016; 9(5): 617-620.
DOI: 10.5958/0974-360X.2016.00118.9
ABSTRACT:
Ebola virus is
formerly designated zaire ebola virus which is one of the known genus ebola virus
caused by filoviridae. The four of five known ebolavirus including EBOV, caused
a severe and often fatal hemorrhagic(bloody) fever. In human and mammals which
are found prevalent in Guinea, Liberia, Sierra and at present epidemic in
west Africa which resulted in at least
28638 suspected cases and 11315 confirmed deaths. Ebola virus has caused
majority of human deaths from EVD. In this review we have summarized the EVD
organization, clinical manifestation and pathogenesis.
KEYWORDS: Ebola virus,
fatal, epidemic, clinical manifestation, pathogenesis.
INTRODUCTION:
A notoriously deadly virus that causes foursome
symptoms, the most prominent being high fever and massive internal bleeding
ebola virus kills as many as 90%of the people it infects. It is one of the
virus that is capable of causing
hemorrhagic(bloody) fever(1,2).
Epidemiology:
From 1976-2013, WHO reported 1716 confirmed
cases. The largest outbreak in 2014. Wes Africa Ebola virus outbreak which was
affected Guinea, Sierra Leone, Liberia, Nigeria, 2127 cases have been identified
with 1145 deaths. From 1995-2013 second major outbreak occurred(3).
Ebola virus was first isolated in 1976 during
outbreaks of Ebola hemorrhagic fever in Congo and Sudan. The Congo had one of
the highest case fatality rates of any human virus 50 to 90%. The name of the
disease originates from the Congo which lies on the Ebola river(3,4).
It is primarily considered as a local self- limiting
problem with a very high case fatality ratio. Until the end of the eighties
there were only remarkable EVD outbreaks (4–7). Changing frequency clearly
showed an increase in the risk of development of the EVD outbreak in the next
years. Some variability in Case Fatality Ration (CFR) was observed across
different outbreaks and a decrease associated with the increase in generations
of person to person passage(5,7,8). From December 2013 to August 11, 2015, a
total of 20,035 confirmed and probable cases of Ebola virus disease (EVD) were
reported in Guinea, Liberia, and Sierra Leone. There have been concerns that
the different cultural roles or physiology of male and female persons may have
resulted in the sexes being differently affected during this outbreak(9).
Sign and symptoms:
The following 2 types of exposure history are
recognized
1.
Primary exposure:This is typically involves traveler to or
work in an Ebola endemic area.(10–12)
2. Secondary
exposure: this refers to
human to human exposure(eg. Medical caregivers, family caregivers, person who
prepared diseased patient for burial primate to care for primates),or person
who collect or prepare bush meat for human consumption.
Physical findings
depend on the stage of disease at the time of presentation with African derived
ebolavirus infected. There is an incubation period (typically 3-8days) in
primary cases and slightly longer in secondary cases.
Symptoms of EVD may appear 2-21days after
exposure to the Ebola virus, according to WHO on an average however, symptoms
appear within 8-10days.
At first Ebola symptoms seems like those of
many other viruses. According to the CDC the patient will usually experience
the following symptoms.
A fever greater than 101.5degree Fahrenheit
Muscle pain
Severe headaches
Weakness
Diarrhea
Vomiting
Abdominal pain
Some patients also bleed from the nose and mouth this
is called hemorrhagic syndrome and usually occurs only in the late stages of
the disease. Typically the ebolavirus causes hemorrhagic syndrome in
30-50%.ofthe patients.
Early finding may include
· Pharyngilis
· Maculopapular rash
· Bilateral conjunctival infection
· Later finding may include
· Expressionless facies
· Bleeding from (IV) puncture sites and
mucous membrane
· Myocarditis and pulmonary edema
· In terminally ill patient tachypnea ,HTN,
anuria and coma
Diagnosis:
Symptoms that occur in advanced stages of EVD include
rash and symptoms of impaired kidney and liver function such as blood in stool
according to WHO.
Because of the symptoms of ebola virus are so much
like those of other disease. Medical professionals use a series of tests to
diagnose EVD(13). According to WHO common tests include the
following
a. Virus isolation by cell culture
b. ELISA
c. Serum neutralization test
d. Antigen capture detection test
e. Electron microscopy
f. Reverse transcriptase polymerase chain
reaction(RT-PCR) assay
g. Basic blood tests: complete blood count
with differential bilirubin, liver enzymes, blood urea nitrogen(BUN),
creatinine, PH(16–18)
h. Studies for isolating the virus: tissue
culture(only to be performed in one of a few high containment laboratory
throughout the world), reverse transcription polymerase chain reaction (RT-PCR)
assay
i. Serologic testing: ELISA for antigens or
for IgM and IgG antibodies
Viral
reservoirs:
Perhaps the greatest mysterious regarding
filoviruses are the identity of their natural reservoir and mode of
transmission to wild apes and humans. However as the data suggest that bat are
least one of the reservoir host of ebolavirus in Africa. (14-16)
Transmission
Epidemics of ebola virus disease are generally thought
to begin when an individual becomes infected through contact with meat or body
fluids of an infected animal(17–21). Once the patients gets ill or they dies,
the virus spreads to others who come into direct contact with the infected
individuals blood, skin and other body
fluids, the studies in laboratory primates have found that animals can be
infected with ebola virus through droplet inoculation of virus into the mouth
or eyes suggesting to human infection
can result from the inadvertent transfer of virus to these sites from
contaminated hands.(22,23)
Person to person:
Person to person transmission associated with direct
contact with symptomatic individuals with ebolavirus disease and direct contact
with body fluids from patients to EVD.
Risk of transmission through different body fluids:
Transmission is mostly like to occur through direct
contact of broken skin or unprotected mucous membranes with virus containing
body fluids from a person who has sign and symptoms.
The risk of Ebola transmission also depends upon the
quantity of virus in the fluid. During the early phaseof illness the amount of
virus in the blood may be quite low but levels then increase rapidly and may
exceed 10 to the power 8 RNA copies per ml serum in severely ill patient.(24,25)
· Risk of transmission through contact with
contaminated surfaces
· Risk of airborne transmission
· Nosocomial transmission
· Transmission with animals
· Immune response to ebolavirus infection:
Ebola virus replicates at usually high rate that
overwhelms the protein synthesis apparatus of infected cells and host immune
defenses. Both the adaptive immune and inflammatory system respond to infection
at the same time that some cell types specifically monocytes and macrophages
are targets relevant to disease pathogenesis. This feature of the infection was
initially suggested bythe immune histochemical localization of ebola virus in
ivvo endothelial cells mononuclear phagocytes and hepatocytes are the main
targets of infection.(26,27)
Vaccine development:
Several animal models have been developed to study the
pathogenesis of Ebola virus infection and to assess the efficacy of various
vaccine approaches.(28–30)
Genetic immunization with plasmid DNA was developed in
the Guinea pig and that was the first vaccine for ebola virus.
In summary, an understanding the mechanisms underlying ebola virus induced
cytopathic effects has facilitated the process of vaccine and antiviral therapy
development which has in turn provided new information about pathogenesis and
the immune response.(31–35)
Prevention:
Prevention focuses on avoiding contact with the
viruses. The following precautions can help prevent infection and spread of
Ebola and Marburg.
1. Avoid areas of known outbreaks
2. Wash your hands frequently
3. Avoid bush meat
4. Avoid
contact with infected people
5. Follow infection control procedures
6. Don’t handle remains.
Treatment and drugs
No antiviral medications have proved effective in
treating infection with either virus. Supportive hospital care includes
a. Providing fluids
b. Maintaining B.P
c. Providing oxygen as needed
d. Replacing lost blood
e. Treating other infections that develop(36–38)
CONCLUSION:
Hence, the Ebola virus is studied from various review
articles and innovation of the new medication is on the way to medication. Most
of the researchers are on the way pre clinically and some of them are succeeded
but not clinically approved by FDA and WHO.
REFERENCES:
1. Grard G, Fair JN, Lee D, Slikas E, Steffen
I, Muyembe J-J, et al. A Novel Rhabdovirus Associated with Acute Hemorrhagic
Fever in Central Africa. PLoS Pathog [Internet]. 2012 Sep [cited 2016 Mar
19];8(9). Available from: http://www.ncbi.nlm.nih.gov/pmc /articles/PMC3460624/
2. Mupere E, Kaducu O, Yoti Z. Ebola
haemorrhagic fever among hospitalised children and adolescents in nothern
Uganda : Epidemiologic and clinical observations. Afr Health Sci. 2001
Dec;1(2):60–5.
3. Harrod KS. Ebola: history, treatment, and
lessons from a new emerging pathogen. Am J Physiol - Lung Cell Mol Physiol.
2015 Feb 15; 308(4):L307–13.
4. Kugelman JR, Lee MS, Rossi CA, McCarthy SE,
Radoshitzky SR, Dye JM, et al. Ebola Virus Genome Plasticity as a Marker of Its
Passaging History: A Comparison of In Vitro Passaging to Non-Human Primate
Infection. PLoS ONE [Internet]. 2012 Nov 28 [cited 2016 Mar 19];7(11).
Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509072/
5. Ebola: The Natural and Human History of a
Deadly Virus. - PubMed - NCBI [Internet]. [cited 2016 Mar 20]. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/25520259
6. De Clercq E. Interferon: ten stories in one.
A short review of some of the highlights in the history of an almost
quinquagenarian. Acta Microbiol Immunol Hung. 2005;52(3-4):273–89.
7. Li YH, Chen SP. Evolutionary history of Ebola
virus. Epidemiol Infect. 2014 Jun;142(6):1138–45.
8. Ebola Virus Disease Outbreak in Isiro,
Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and
Outcomes [Internet]. [cited 2016 Mar 19]. Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479598/
9. Hartman AL, Towner JS, Nichol ST. Ebola and
Marburg Hemorrhagic Fever. Clin Lab Med. 2010 Mar;30(1):161–77.
10. Moole H, Chitta S, Victor D, Kandula M, Moole
V, Ghadiam H, et al. Association of clinical signs and symptoms of Ebola viral
disease with case fatality: a systematic review and meta-analysis. J Community
Hosp Intern Med Perspect. 2015;5(4):28406.
11. Kratz T, Roddy P, Tshomba Oloma A, Jeffs B, Pou
Ciruelo D, de la Rosa O, et al. Ebola Virus Disease Outbreak in Isiro,
Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and
Outcomes. PloS One. 2015;10(6):e0129333.
12. Epstein L, Wong KK, Kallen AJ, Uyeki TM.
Post-Ebola Signs and Symptoms in U.S. Survivors. N Engl J Med. 2015 Dec
17;373(25):2484–6.
16. Jansen van Vuren P, Grobbelaar
A, Storm N, Conteh O, Konneh K, Kamara A, et al. Comparative Evaluation of the
Diagnostic Performance of the Prototype Cepheid GeneXpert Ebola Assay. J Clin
Microbiol. 2016 Feb;54(2):359–67.
17. Ghani AC, Burgess DH, Reynolds A, Rousseau C.
Expanding the role of diagnostic and prognostic tools for infectious diseases
in resource-poor settings. Nature. 2015 Dec 3;528(7580):S50–2.
18. Nouvellet P, Garske T, Mills HL, Nedjati-Gilani
G, Hinsley W, Blake IM, et al. The role of rapid diagnostics in managing Ebola
epidemics. Nature. 2015 Dec 3;528(7580):S109–16.
19. Park DJ, Dudas G, Wohl S, Goba A, Whitmer SLM,
Andersen KG, et al. Ebola Virus Epidemiology, Transmission, and Evolution
during Seven Months in Sierra Leone. Cell. 2015 Jun 18;161(7):1516–26.
20. Osterholm MT, Moore KA, Kelley NS, Brosseau LM,
Wong G, Murphy FA, et al. Transmission of Ebola Viruses: What We Know and What
We Do Not Know. mBio [Internet]. 2015 Feb 19 [cited 2016 Mar 19];6(2).
Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358015/
21 The Effect of Community-Based Prevention and
Care on Ebola Transmission in Sierra Leone. - PubMed - NCBI [Internet]. [cited
2016 Mar 21]. Available from: http://www.ncbi.nlm.nih. gov/pubmed/26890176
22. Mann E, Streng S, Bergeron J, Kircher A. A
Review of the Role of Food and the Food System in the Transmission and Spread
of Ebolavirus. PLoS Negl Trop Dis [Internet]. 2015 Dec 3 [cited 2016 Mar
21];9(12). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669147/
23. Lindblade KA, Kateh F, Nagbe TK, Neatherlin JC,
Pillai SK, Attfield KR, et al. Decreased Ebola Transmission after Rapid
Response to Outbreaks in Remote Areas, Liberia, 2014. Emerg Infect Dis. 2015
Oct;21(10):1800–7.
24. Agusto FB, Teboh-Ewungkem MI, Gumel AB.
Mathematical assessment of the effect of traditional beliefs and customs on the
transmission dynamics of the 2014 Ebola outbreaks. BMC Med [Internet]. 2015 Apr
23 [cited 2016 Mar 21];13. Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422472/
25. Walsh MG, Haseeb M. The landscape configuration
of zoonotic transmission of Ebola virus disease in West and Central Africa:
interaction between population density and vegetation cover. PeerJ [Internet].
2015 Jan 20 [cited 2016 Mar 21];3. Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304850/
26. Chughtai AA, Barnes M, Macintyre CR.
Persistence of Ebola virus in various body fluids during convalescence:
evidence and implications for disease transmission and control. Epidemiol
Infect. 2016 Jan 25;1–9.
27. Possible sexual transmission of Ebola virus -
Liberia, 2015. - PubMed - NCBI [Internet]. [cited 2016 Mar 21]. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/25950255
28. Folayan MO, Yakubu A, Haire B, Peterson K.
Ebola vaccine development plan: ethics, concerns and proposed measures. BMC Med
Ethics. 2016;17(1):10.
29. Fitzgerald F, Yeung S, Gibb DM, Baion DE,
Pollard A. Ebola vaccination. Lancet Lond Engl. 2015 Dec 19;386(10012):2478.
30. Foged C. Thermostable Subunit Vaccines for
Pulmonary Delivery: How Close Are We? Curr Pharm Des. 2016 Feb 2;
31. Wu X-X, Yao H-P, Wu N-P, Gao H-N, Wu H-B, Jin
C-Z, et al. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus
Disease. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol.
2015;37(5):1641–58.
32. Ohimain EI. Recent advances in the development
of vaccines for Ebola virus disease. Virus Res. 2016 Jan 4;211:174–85.
33. Murphy AA, Redwood AJ, Jarvis MA.
Self-disseminating vaccines for emerging infectious diseases. Expert Rev
Vaccines. 2016;15(1):31–9.
34. Osterholm M, Moore K, Ostrowsky J,
Kimball-Baker K, Farrar J, Wellcome Trust-CIDRAP Ebola Vaccine Team B. The
Ebola Vaccine Team B: a model for promoting the rapid development of medical
countermeasures for emerging infectious disease threats. Lancet Infect Dis.
2016 Jan;16(1):e1–9.
35. Tapia MD, Sow SO, Lyke KE, Haidara FC, Diallo
F, Doumbia M, et al. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US
adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1,
single-blind, randomised trial, a phase 1b, open-label and double-blind,
dose-escalation trial, and a nested, randomised, double-blind,
placebo-controlled trial. Lancet Infect Dis. 2016 Jan;16(1):31–42.
36. Gao R, Chen C, Wang F, Wang H, Jiang T, Sun Y,
et al. [Analysis of mechanism for international joint prevention and control of
Ebola virus disease in Sierra Leone]. Zhonghua Liu Xing Bing Xue Za Zhi
Zhonghua Liuxingbingxue Zazhi. 2015 Sep;36(9):1031–3.
37. Tambo E, Yah CS, Ugwu CE, Olalubi OA, Wurie I,
Jonhson JK, et al. Fostering prevention and care delivery services capability
on HIV pandemic and Ebola outbreak symbiosis in Africa. J Infect Dev Ctries.
2016;10(1):1–12.
38. Sodano L, Radici F, Rossini A, D’Alessandro D.
Cross-sectional study on knowledge of health care workers about Ebola Virus
Disease and its prevention: a pilot study in two hospitals in Rome (Italy). Ann
Ig Med Prev E Comunità. 2015 Dec;27(6):814–23.