FREE ESSAY ON EBOLA VIRUS

EBOLA VIRUS

EBOLA VIRUS
Ebola virus, a member of the Filoviridae, burst from obscurity with spectacular outbreaks
of severe, haemorrhagic fever. It was first associated with an outbreak of 318 cases and
a case-fatality rate of 90% in Zaire and caused 150 deaths among 250 cases in Sudan.
Smaller outbreaks continue to appear periodically, particularly in East, Central and
southern Africa. In 1989, a haemorrhagic disease was recognized among cynomolgus macaques
imported into the United States from the Philippines. Strains of Ebola virus were
isolated from these monkeys. Serologic studies in the Philippines and elsewhere in
Southeast Asia indicated that Ebola virus is a prevalent cause of infection among
macaques (Manson 1989). 
These threadlike polymorphic viruses are highly variable in length apparently owing to
concatemerization. However, the average length of an infectious virion appears to be 920
nm. The virions are 80 nm in diameter with a helical nucleocapsid, a membrane made of 10
nm projections, and host cell membrane. They contain a unique single-stranded molecule of
noninfectious (negative sense ) RNA. The virus is composed of 7 polypeptides, a
nucleoprotein, a glycoprotein, a polymerase and 4 other undesignated proteins. Proteins
are produced from polyadenylated monocistronic mRNA species transcribed from virus RNA.
The replication in and destruction of the host cell is rapid and produces a large number
of viruses budding from the cell membrane. 
Epidemics have resulted from person to person transmission, nosocomial spread or
laboratory infections. The mode of primary infection and the natural ecology of these
viruses are unknown. Association with bats has been implicated directly in at least 2
episodes when individuals entered the same bat-filled cave in Eastern Kenya. Ebola
infections in Sudan in 1976 and 1979 occurred in workers of a cotton factory containing
thousands of bats in the roof. However, in all instances, study of antibody in bats
failed to detect evidence of infection, and no virus was isolated form bat tissue. 
The index case in 1976 was never identified, but this large outbreak resulted in 280
deaths of 318 infections. The outbreak was primarily the result of person to person
spread and transmission by contaminated needles in outpatient and inpatient departments
of a hospital and subsequent person to person spread in surrounding villages. In
serosurveys in Zaire, antibody prevalence to Ebola virus has been 3 to 7%. The incubation
period for needle- transmitted Ebola virus is 5 to 7 days and that for person to person
transmitted disease is 6 to 12 days. 
The virus spreads through the blood and is replicated in many organs. The histopathologic
change is focal necrosis in these organs, including the liver, lymphatic organs, kidneys,
ovaries and testes. The central lesions appear to be those affecting the vascular
endothelium and the platelets. The resulting manifestations are bleeding, especially in
the mucosa, abdomen, pericardium and vagina. Capillary leakage appears to lead to loss of
intravascular volume, bleeding, shock and the acute respiratory disorder seen in fatal
cases. Patients die of intractable shock. Those with severe illness often have sustained
high fevers and are delirious, combative and difficult to control. 
EBOLA SEROLOGY
The serologic method used in the discovery of Ebola was the direct immunofluorescent
assay. The test is performed on a monolayer of infected and uninfected cells fixed on a
microscopic slide. IgG- or IgM-specific immunoglobulin assays are performed. These tests
may then be confirmed by using western blot or radioimmunoprecipitation. Virus isolation
is also a highly useful diagnostic method, and is performed on suitably preserved serum,
blood or tissue specimens stored at -70oC or freshly collected. 
TREATMENT OF EBOLA
No specific antiviral therapy presently exists against Ebola virus, nor does interferon
have any effect. Past recommendations for isolation of the patient in a plastic isolator
have given way to the more moderate recommendation of strict barrier isolation with body
fluid precautions. This presents no excess risk to the hospital personnel and allows
substantially better patient care, as shown in Table 2. The major factor in nosocomial
transmission is the combination of the unawareness of the possibility of the disease by a
worker who is also inattentive to the requirements of effective barrier nursing. after
diagnosis, the risk of nosocomial transmission is small. 
PREVENTION AND CONTROL OF EBOLA
The basic method of prevention and control is the interruption of person to person spread
of the virus. However, in rural areas, this may be difficult because families are often
reluctant to admit members to the hospital because of limited resources and the
culturally unacceptable separation of sick or dying patients from the care of their
family. Experience with human disease and primate infection suggests that a vaccine
inducing a strong cell- mediated response will be necessary for virus clearance and
adequate protection. Neutralizing antibodies are not observed in convalescent patients
nor do they occur in primates inoculated with killed vaccine. A vaccine expressing the
glycoprotein in vaccinia is being prepared for laboratory evaluation. 
SELECTIVE PRESSURES AND CONSTRAINTS
It is of interest to determine, what, if any, limits are placed on virus variation.
Despite high mutation rates and opportunities for genetic reassortment, many factors act
to minimize emergence of new influenza A epidemics (Morse and Schluederberg 1988). even
though avian and human influenza viruses are widespread (in humans an estimated 100
million infections yearly), pandemic influenza viruses emerge infrequently (every 10-40
years). Powerful constraints appear to exist since pandemic human influenza strains vary
in their H gene, whereas the neuraminidase and most other genes are conserved. 
These constraints on viral evolution are not surprising when one considers the selective
pressures imposed by the host at each stage of the virus life cycle. Tissue tropism
determinants, include site of entry, viral attachment proteins, host cell receptors,
tissue- specific genetic elements (for example promoters), host cell enzymes (like
proteinase), host transcription factors, and host resistance factors such as age,
nutrition and immunity. Host factors contribute significantly: sequences such as
hormonally responsive promoter elements and transcriptional regulatory factors can link
viral expression to cell state. 
The interaction of virus and host is thus complex but highly ordered, and can be altered
by changing a variety of conditions. Unlike bacterial virulence, which is largely
mediated by bacterial toxins and virulence factors, viral virulence often depends on host
factors, such as cellular enzymes that cleave key viral molecules. Because virulence is
multigenic, defects in almost any viral gene may attenuate a virus. For example, some
reassortments of avian influenza viruses are less virulent in primates than are either
parental strain, indicating that virulence is multigenic (Treanor and Murphy 1990). 
Viral and host populations can exist in equilibrium until changes in environmental
conditions shift the equilibrium and favour rapid evolution (Steinhauer and Holland
1987). It seems reasonable to expect that new viruses will emerge occasionally, but the
stochastic and multifactorial nature of viral evolution makes it difficult to predict
such events. According to Doolittle, retrovirus evolution is sporadic, with retroviruses
evolving at different rates in different situations. For instance, the human endogenous
retroviral element is shared with chimpanzees, indicating no change in over 8 million
years, whereas strains of HIV have diverged in mere decades. Endogenous retroviruses
carried in the germline evolve slowly compared with infective retroviruses. Generation of
new viral pathogens is rare, and often possible only because of high mutation rates that
permit many neutral mutations to accumulate before selective pressure forces a change.
The seeming unpredictability of these events ensure that recognition of new pathogens
must await their emergence. 
CONCLUSION
The proposed American fiscal budget for 1995 allows allocations for the CDC which remain
basically the same as those for past years and the $11.5 billion budget for the National
Institutes of Health includes only a modest increase for non-AIDS infectious and
immunological diseases research (Cassell 1994). In view of the magnitude of the problem,
this budget is unacceptable. Currently, infectious diseases remain the leading cause of
death worldwide. In the United States infectious diseases directly account for 3 and
indirectly account for 5 of the 10 leading causes of death, AIDS is the ninth leading
cause. Infectious diseases account for 25% of all visits to physicians in the United
States. In total, the annual cost of AIDS and other infectious diseases reached $120
billion in 1992, about 15% of the nation's total health-care expenditure. The expanding
pool of immunodeficient patients due to the AIDS epidemic, cancer treatment, transplant
recipients, and hemodialysis has caused an explosion of opportunistic infections due to a
number of fungal, parasitic, viral and bacterial agents. 
According to the Gail H. Cassel, president of the American Society of Microbiology, the
public health system is not prepared to meet the challenges of new and re-emerging
infections. Perhaps the most obvious defect is inadequate disease surveillance and
reporting. In America, only one-quarter of the states have a professional position
dedicated to surveillance of food-borne and waterborne diseases. In 1992, only $55000 was
spent on federal, state and local levels tracking drug-resistant bacterial and viral
infections. In addition, the public health laboratories are eroding. Overall, CDC's
budget for infectious diseases unrelated to AIDS has declined approximately 20% in the
last decade. This is the case in the developed world of the United States, and we in
developing South Africa are certainly no better off in terms of disease surveillance and
concomitant protection. It should be clear that a mixture of basic and applied research
related to infectious disease is needed. Coupled with this, better diagnostic techniques,
prevention strategies and risk factor analysis is needed. Finally, enhanced communication
among health care professionals and the public is integral in coming to terms and dealing
with this issue. The American National Institute of Allergy and Infectious Diseases
(NIAID) plans to develop a research and training infrastructure to elucidate the
mechanisms of molecular evolution and drug resistance and to learn more about actual
disease transmission through molecular and environmental studies and to continue their
emphasis on vaccine development. For example, NIAID-funded research has already led to
the creation of a new Haemophilus influenzae type B vaccine which is expected to save
nearly $400 million in health-care costs each year. Similarly, the NIH spent less than
$27 million dollars to find the connection between Helicobacter pylori and chronic peptic
ulcers, yet using antibacterial therapy for the disease will save $760 million dollars in
health care costs annually. 
Given the diverse nature of threats from infectious diseases, it is not adequate merely
to face each crisis as it emerges, as this may provide a strategy which proves to be too
little and too late. Instead, a more holistic approach is required. This must include a
global perspective as well as the need to address the issue of infectious disease within
the context of shared environmental responsibility. Improved health care derived from
socioeconomic betterment is crucial, as are long term policies involving systems thinking
as opposed to the limiting nature of long term over-specialization. 
Bibliography
REFERENCES
Cassel G.H. 1994. New and Emerging Infections in the Face of a Funding Crisis. ASM News
60, 5: 251-4 
Culliton B.J. 1990. Emerging Viruses, Emerging Threat. Science 247: 279- 280 
Diglisic G., Xiao S-Y., Gligic A., Obradovic M., Stojanovic R., Velimirovic D., Lukac V.,
Rossi C.A. and J.W. DeLuc. 1994. Isolation of a Puumala-like Virus from Mus musculus
Captured in Yugoslavia and Its Association with Severe Hemorrhagic Fever with Renal
Syndrome. J. Inf. Dis. 169: 204-7 
Domingo E. and J.J. Holland. 1988. High error rates, population equilibrium and evolution
of RNA replication systems. In: RNA genetics. Vol. 3. (eds. Domingo E., Holland J.J. and
P. Ahlquist). Boca Raton, FL: CRC Press. 
Doolittle R.F., Feng D.F., Johnson M.S. and M.A. McClure. 1989. Origins and evolutionary
relationships of retroviruses. Q. Rev. Biol. 64: 1-30 
Dowdle W. 1994. Dowdle Reflects on CDC, Changing Demands of Disease Surveillance. ASM
News. 60, 5:237-8 
Hahn C.S., Lustig S., Strauss E.G. and J.H. Strauss. 1988. Western equine encephalitis
virus is a recombinant virus. Proc. Natl. Acad. Sci. USA. 85: 5997-6001 
Hughes J.M. and J. R. La Montagne. 1994. The Challenges Posed by Emerging Infectious
Diseases. ASM News 60, 5: 248-50 
Hunter S. 1991. Tropical Medicine. 7th edn. W.B. Saunders Company 
Kida H., Shortridge K.F. and R.G. Webster. 1988. Origin of the hemagglutinin gene of H3N2
influenza viruses from pigs in China. Virology. 162: 160-166 
Kilbourne E.D., Easterday B.C. and S. McGregor. 1988. Evolution to predominance of swine
influenza virus hemagglutinin mutants of predictable phenotype during single infections
of the natural host. Proc. Natl. Acad. Sci. USA. 85: 8098-8101 
Lederburg J. 1994. Emerging Infections: Private Concerns and Public Responses. ASM News.
60, 5: 233 
Manson-Bahr D.E.C. and D.R. Bell. 1989. Manson's Tropical Diseases. 19th edn. Bailliere
Tindall. 
May R.M. and R.M. Anderson. 1987. Transmission dynamics of HIV infection. Nature. 326:
137-142 
Morse S.S. (ed.). 1993. Emerging Viruses. Oxford University Press. 
Morse S.S. and A. Schluederberg. 1990. Emerging Viruses: The Evolution of Viruses and
Viral Diseases. J. Inf. Dis. 162: 1-7 
Murphy F.A. 1994. Infectious Diseases. Adv.Vir. Res. 43: 2-52 
Parvin J.D., Moscona A., Pan W.T., Leider J.M. and P. Palese. 1986. Measurement of the
mutation rates of animal viruses: influenza A virus and poliovirus type 1. J. Virol. 62:
3084-3091 
Peters C.J. 1994. Molecular Techniques Identify a New Strain of Hantavirus. ASM News. 60,
5: 242-3 
Steinhauer D. and J.J. Holland. 1987. Rapid evoltuion of RNA viruses. Annu Rev.
Microbiol. 41: 409-433 
Treanor J. and B. Murphy. Genes involved in the restriction of replication of avian
influenza A viruses in primates. In: Applied virology research: virus variation and
epidemiology. Vol. 2. New York: Plenum Press (eds. Kurstak E., Marusyk R.G., Murphy F.A.
and M.H.V. van Regenmortel.