Ebola Virus - Cal State LA

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Ebola Virus
Case Study
By:
Shahrzad Morim
Monica Delgado
Janine Gilkes
Microbiology 401
Dr. Nancy McQueen
Fall 2007
The former Soviet Union had an active state-supported bio-weapon research and production
program from the 1970s through the mid 90’s. One branch of the program was called VECTORthe State Research Center for Virology and Biotechnology. They worked with pathogens for
which there is no known cure. While working to develop a vaccine against Ebola virus, one of
the scientists accidentally stuck herself with a needle contaminated with virus. She contracted
Ebola hemorrhagic fever and died.
1) What are the potential benefits of American aid to convert VECTOR’s bioweapon
facilities to peaceful research? What are the potential hazards?
VECTOR is a level 4 biosafety lab designed for the purpose of creating genetically
altered viruses. According to the Dallas Observer, 2000, “[In 1998], “the U.S. government
approached UT Southwestern Medical Center with the idea of forming a collaborative effort
between Dallas and Siberia [VECTOR] aimed at developing a vaccine against Ebola. The U.S.
Defense Department, in fact, is not only paying for the experiment, but now directly funds the
operations of VECTOR in Russia” (3). There are several benefits and hazards which come as a
result of this venture. Scientists are able to retain their jobs and increase scientific knowledge and
research in this field, thereby reassuring the U.S. that their knowledge and expertise of biological
weapons will not fall into the wrong hands. The US will be at the forefront of and be able to
indulge in any breakthroughs made. U.S. Aid assists in strengthening ties and diplomacy
between US and Russia. However, with increased trust, comes increased complacency. There are
four other weapons labs in Russia which go unchecked and without inspection. Additionally,
according to Miller, 2004, at the time of the accident involving the female employee, VECTOR
claimed that the research was being funded by an outside party but refused to identify their
benefactor or state the nature of the research(2). It may also be difficult to very whether or not
some former soviet scientists are using the American supported research for peaceful purposes.
There seems to be an overall lack of accountability and that may cause strain on this relatively
new relationship in the future.
2. What tissue(s) does the pathogen damage that leads to hemorrhaging?
Infection by Ebola virus mimic nonspecific flu-like symptoms such as fever, myalgia, and
malaise(8). Patients with progressed cell damage and infection exhibit severe bleeding and
coagulation abnormalities, including gastrointestinal bleeding, rash, and a range of hematological
irregularities, such as lymphopenia and neutrophilia(18). When the immune system is fighting
against this viral pathogen, cytokines signal immune cells such as T-cells and macrophages to
travel to the site of Ebola virus infection (15). The immune cells are activated by cytokines,
stimulating them to produce more cytokines. The products are then released to interact with the
virus. This rapid influx of immune cells contributes to an exaggerated inflammatory immune
response which is actually damaging to the tissues infected with virions.
Damage to the liver, combined with massive viremia, leads to disseminated intravascular
coagulopathy (14). If the infection progresses in virulence the virus will enter microvascular
endothelial cells. Extensive damage by the infiltration of immune cells leads to the terminal
stages of Ebola virus infection, which usually include diffuse bleeding, and hypotensive shock
accounts for many Ebola virus fatalities.
3) How could you have prevented this outbreak from spreading to other scientists at
VECTOR?
To prevent this outbreak from spreading to others in the lab, initially, the infected
individuals should be isolated to limit direct contact with others. Then, contaminated and waste
products should be disposed of properly. It’s important to ensure that all the used equipments
were disposed or sterilized, disinfecting those that had needed to be reused by others.
Communication with the employees and staff about the nature of the situation is another key
method in order to have them take any and all precautionary measures (1).
4) How is this virus transmitted? What precautions need to be taken when working with
this deadly virus?
The Ebola Virus is transmitted from person to person by intimate contact with infected
blood, secretions, organs, or semen (19). The infectious virus within a host can transmit to others
as long as the virus components remain within the blood stream (19). In the early stages, Ebola
may not be highly contagious. Contact with someone in early stages may not even transmit the
disease. As the illness progresses, bodily fluids from diarrhea, vomiting, and bleeding represent
an extreme biohazard(16).The infection of human cases with Ebola virus has been documented
through the handling of infected chimpanzees, gorillas, and forest antelopes, both dead and alive,
as was documented in Côte d'Ivoire, the Republic of Congo and Gabon(18). The transmission of
the Ebola Reston strain through the handling of cynomolgus monkeys has also been reported
(15).
Caution must be taken even after a patient recovers from the symptoms of this virus. The
infected person can transmit the virus to others even after they have fully recovered from illness.
Although airborne transmission of Ebola virus is probable, there is no direct evidence of this
hypothesis (8).
Health care workers are commonly infected while treating Ebola patients. These workers
often must be in close contact with infected patients and infected equipment. The identification
and the isolation of virus infected patients is critical and must follow barrier nursing procedures
to prevent the rapid spread of this highly contagious pathogen. In countries where sanitation and
sterile techniques are not enforced or are simply unattainable, transmission of the virus via basic
care techniques is common.
Burial ceremonies where mourners have direct contact with the body of the deceased
person can play a significant role in the transmission of Ebola (17). Airborne transmission
between monkeys has been observed by an accidental outbreak in a laboratory located in
Virginia, USA.
5) What is currently believed to be the animal reservoir of Ebola virus?
It has been shown that the initial Ebola infections of humans on the African continent
have occurred due to direct contact with the carcasses of gorillas, chimpanzees, monkeys, and
forest antelopes found dead in the rainforest (8). Even though the source of infection for humans
has been non-human primates, the fact that these species had a high mortality means they are not
the reservoir for the virus (11). Other species of living organisms, such as plants, birds, and
arthropods have been considered as reservoirs as well; however, more current evidence points at
bats as the carrier for this deadly virus (10).
During the human epidemics in 2001 and 2003, Ebola virus was detected in the carcasses
of gorillas, chimpanzees, and duikers (7). During these outbreaks, researchers from French
Research Institute for Development (IRD) surveyed more than 1,000 small vertebrates in areas
that were in close proximity of carcasses of infected animals (7).After analyzing their data, IRD
researchers were the first to officially identify bats as a potential reservoir of Ebola virus. They
found the genetic sequences of Ebola virus or evidence of an immune response to the virus in
three species of fruit bats: Hypsignathus monstrosus, Epomops franqueti and Myonycteris
torquata (7). More specifically, Ebola RNA sequences were detected in the liver and spleen of
these animals, and antibodies against one of the four subtypes of Ebola was detected in their
serum. The bats did not show symptoms of infection and did not develop the disease. This fact
implies that these animals are a potential reservoir for Ebola virus (7).
Evidence has also shown that the large primates had the highest mortality rate throughout
the dry season during which there is a lot of food competition between species due to resource
deficiencies (7). In this period, species are in closer contact because of scarce food resources and
could get contaminated more easily. Furthermore, it has been known that the immune function in
bats is somehow modified during the dry season, which provides the virus with more favorable
conditions to reproduce (7).
In this proposal, bats are more likely to pass the virus onto great apes, including gorillas
and chimpanzees, which have had a high mortality rate (7). Also, bats could infect humans
directly, especially since one of the species of the discovered bats are often caught and eaten by
people who live in epidemic-prone regions (7, 10). Despite the discovery of these bats as the
potential reservoir for Ebola virus, extensive ecological investigations are still underway in the
Republic of Congo and Gabon to further confirm the reservoir for this deadly virus.
6) Compare this pathogen with smallpox as a potential bioweapon. Which could be more
dangerous as a weapon of mass destruction?
Biological weapons (BWs) deliver toxins and microorganisms, such as viruses and
bacteria, and aim to deliberately inflict disease among people, animals, and agriculture (6).
Several viruses have been identified as dangerous pathogens that can be used as bio-weapons
during wars. Smallpox (variola virus) and Ebola virus are both among the category one, the most
dangerous, agents in the classification system by the Centers for Disease Control and Prevention
(CDC). That means they are among the agents that can be easily transmitted, have high potential
for mortality, create great public panic, and require public preparedness (6). If a transmissible
agent, such as the smallpox or Ebola virus, infects someone at the site of its release, that
individual could travel and spread the agent to others. This would result in secondary infections
at areas other than the original location (6). According to an article published by National Center
for Infectious Diseases, an agent must have several qualities to be used for mass destruction. It
should be lethal and producible in large quantities. It should be communicable from person to
person, and there should not be treatments or vaccines for the developing disease (5). Even
though both Ebola virus and smallpox virus can both be turned into bio-weapons, smallpox poses
a greater danger in terms of mass destruction.
Ebola virus infection causes sudden sever onset of symptoms, has a short incubation
period, and causes death within several days (8). Therefore, individuals infected with this virus
may die before they can transmit the disease to other individuals. This results in outbreaks that
burn out quickly (12). Smallpox, on the other hand, has a longer incubation period between
contraction and the first obvious symptoms of the disease (12-14 days). The patient is not
contagious until the first symptoms arrive, however, the initial symptoms could usually be vague
and flu-like (13). Smallpox can develop into two major forms: variola major and variola minor,
with 30% and 1% rates of fatality, respectively. This disease could also occur in two rare forms
of hemorrahgic and malignant, which are both almost always fatal (13). It has been shown that
the Zaire subtype of Ebola virus has killed 80% of its victims (7).
There is not any evidence that suggests transmission of Ebola virus between humans
through the air. However, smallpox can be aerosolized, and since it’s a relatively stable virus, it
could remain infective at least several hours if there is no sunlight or UV light exposure (5,6,13).
This transmission through air makes this virus more communicable between individuals, and
adds to its contagiousness. This virus can also be produced in a large scale (5). Smallpox virus
infection can spread in any climate or season, while that of the Ebola infection has higher
mortality rates during certain periods (5). The fact that smallpox can be easily transmitted
between individuals poses a great risk. The natural host for variola virus is humans, unlike that
for Ebola virus, which seems to be animals (fruit bats) (13).
At this time, there is no vaccine or treatment available for the disease developing from
Ebola virus infection (1), and this could make this a dangerous pathogen as a bio-weapon.
However, it should be noted that the vaccine that was developed against smallpox in 1967 has
not been routinely provided since 1972 in the U.S., due to the fact that the risk for this disease
became minimal (5). Moreover, there is no effective treatment for smallpox. This virus was
finally eradicated in 1979 from the world. At this point, the survey by World Health
Organization (WHO) reveals the availability of approximately 90 million doses of stored
smallpox vaccine worldwide; however, the viability and storage conditions and are not known
(13). It’s been determined that the vaccine will work it it’s administered up to 4 days after the
viral exposure (13). This period is short since most serious symptoms will not show by this time.
This extreme limit on smallpox vaccine makes this virus a dangerous pathogen.
Another important point with smallpox patients is that they would not die quickly.
Therefore, their need for isolated rooms in the hospital, disposable equipments, medications, and
healthcare providers is a long-term requisite (5). During an outbreak, managing these tasks could
be quite a difficult task, which not only poses financial cost, but can also increase the risk of
transmission of infection to other healthy individuals during hospitalization.
References
1) Adamcek, K., Eanes, M., Shaw, S., Virology Project: Ebola Virus. Retrieved: 11/8/07
http://www.biosci.ohiou.edu/virology/Ebola
2) Miller, J. Russian Scientist Dies in Ebola Accident at Former Weapons Lab. The New York
Times. Published: 5/25/2004. Retrieved: 11/12/2007
http://query.nytimes.com
3) Pappalardo, J. From Russia, with bugs [US subsidizing Russian Biological Warfare Lab].
Dallas Observer. Published: 6/22/2000. Retrieved: 11/14/07
http://freepublic.com
4) “Biological Warfare.” Wikipedia: The Free Encyclopedia. Retrieved: 11/12/07
www.wikipedia.org
5) Emerging Infectious Diseases. National Center for Infectious Diseases. Vol. 5, No.4, July-Aug
1999. Retrieved 11/8/07
http://www.cdc.gov/ncidod/eid/vol5no4/pdf/v5n4.pdf
6) Tanna, J.H, Preventing “Dark Winter”-The Public Health System’s Role in Strengthening
National Security. Vol. 1, No.4, Spring 2002. Retrieved 11/8/07
http://www.carnegie.org/reporter/04/preventing/index.html
7) Leroy, E., Fruit Bats a Reservoir for Ebola Virus. Indigo Base, IRD. November 2005.
Retrieved 11/8/07 www.ird.fr/us/actualities/fiches/2005/fiche231.htm
8) World Health Organization. Ebola Haemorrhagic Fever. Retrieved 11/8/07
http://www.who.int/mediacentre/factsheets/fs103/en/
9) Hoenen et al. Ebola Virus: Unravelling Pathogenesis to Combat a Deadly Disease. Trends
Mol. Med. May 2006, 12(5): 206-215
10) Leroy, EM, Kimulugui, B, Pourrut, X et al. Fruit Bats as Reservoirs of Ebola Virus. Nature.
2005. 438:575–576
11) Pourrut, X, Kumulungui, B, Wittmann, T et al. The Natural History of Ebola Virus in Africa.
Microbes and Infection. 2005. 7:1005–1014
12) Retrieved 11/11/07
http://www.nytimes.com/packages/html/health/20030506_Ebola_COMPARE/sci_Ebola_COMP
ARE_01.html#
13) World Health Organization. Smallpox. Retrieved 11/8/07
http://www.who.int/mediacentre/factsheets/smallpox/en/
14) September 2003, p. 9733-9737, Vol. 77, No. 18
0022-538
15) BMC Microbiology 2003 3:6 doi:10.1186/1471-2180-3-6
16) www.biomedcentral.com/1471-2180/3/6/figure/F3
www.biosci.ohiou.edu/virology/Ebola/Dectec3.jpg
(Courtesy of http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Murphy/ebola_cell.htm
17) World Health Organization
http://www.who.int/mediacentre/factsheets/fs103/en/
Provisional Revision: 2007
18) Leroy, Eric M., et al. Multibple Ebola Virus Transmission Events and Rapid Decline of
Central African Wildlife. Science 303: 387 -389. 2004
19) Facts sheet: Community Health Administration
http://edcp.org/factsheets/ebola.html Journal of Virology,
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