Janina Joaquin
THE EBOLA VIRUS Abstract
The Ebola Virus has recently gained the attention of the world, since the outbreak in West Africa the past year. The Ebola virus is a form of viral hemorrhagic fever with a very high mortality rate, because it attacks the immune system in ways that leaves the body vulnerable, and unable to defend itself. Human transmission of the virus is typically through exposure to contaminated fluids, and tissues. To date there have 14 outbreaks of Ebola in Africa, it has infected over 2,000 people, claiming the lives of almost 1,800 people. This deadly disease currently has no vaccine, with most treatments being supportive. However, trials are in place and various options for the development of a cure for Ebola is in motion.
In this issue:
Ecology
Pathogenesis
Outbreaks
Vaccines
A brief introduction to the virus, and its effects on the environment
Insight to how the virus works, and how it spreads among the populace
A look into the history of Ebola outbreaks since the first case in 1967
What does the future hold for long term treatment and cures against the Ebola virus?
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Ecology of Ebola The Ebola virus is a form of the viral hemorrhagic fever categorized by its severe onset of disease and high mortality rate (Feldmann, 2011). Ebola has an incubation period of about a week, after which, infected patients usually develop symptoms of high fever, chills, nausea, vomiting, and diarrhea. As the infection progresses, patients will experience swelling in lymph nodes, kidneys and brain. Finally, more severe symptoms will present as organ necrosis occurs along with coagulation, hemorrhaging, and clotting in the blood, with death occurring around 2 weeks after symptoms start (Hoenen, 2006). There are currently four strains of the Ebola virus: Ebola Sudan, Ebola Zaire, Ebola Ivory Coast, and Ebola Reston. These strains, with the exception of Ebola Reston, are deadly in their infections of humans (Pourrut, 2005). Ebola is classified as a Category A pathogen because of the lack of
vaccination and treatment alternatives combined with the high fatality. The natural reservoir from which the virus originates has not been confirmed, but bats and rodents are considered potential sources. Mammals, primates, and humans are considered to be the end hosts susceptible to infection from the virus (Feldmann, 2011). The spread of Ebola from animals to humans follows two distinct pathways: humans will either contract the virus directly from the host species, or from a secondary animal species previously infected by a host (Pourrut, 2005). Transmission of the virus in humans is typically through direct contact with infected blood, tissue, and fluids. It is also possible to contract the virus from fluid exposure to the mucosa of the eye, or from hand contamination. In several fatal cases, the virus was contracted through injections using contaminated needles (Hoenen, 2006).
This figure shows the pathways of Ebola virus transmission, starting with the suspected reservoirs passing on the virus to either human or primate hosts. Transmission then spreads from ape to ape, ape to human, and finally human-‐to-‐human. Source: Groseth, 2007
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Pathogenesis
This figure shows the spread of the virus within the human body. Beginning at the site of infection to the closest lymph nodes, liver, and spleen, the virus spreads and replicates, suppressing immune responses, impairing the vascular system. Source: Feldmann, 2011
The spread of the Ebola virus within the human body starts at the initial infection site, usually through breaks in the skin or mucous membranes. The virus then targets specific cells, macrophages, endothelial cells, and dendritic cells. Once this occurs, T-‐cells cannot multiply, and lymphocytes and natural killer cells are either depleted or undergo apoptosis (Hoenen, 2006). Lymphoid tissues can be considered the primary site of the virus, even though there is little inflammation, and the lymphocytes themselves are not infected, they undergo apoptosis. Through the lymphatic system, the virus spreads to the lymph nodes, and to the spleen and liver through the blood. The infected macrophages and dendritic cells will then travel from the lymph nodes, spleen,
and liver, and infect the rest of the tissues in the body (Feldmann, 2011). One of the reasons that the Ebola virus is so fatal to those who contract it is the effect it has on the human immune system. The virus attacks at the lymph node site, infecting phagocyte systems and inhibiting the production of cytokines and antigens. This inhibits the immune response of the body, leaving the patient unable to fight off the virus (Takada, 2001). The virus also causes the vascular system of the body to be dysfunctional due to infection of the endothelium and elevated nitric oxide levels. This damage causes shock induced from the virus (Hoenen, 2006). 3
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Outbreaks The first outbreaks of Ebola emerged in 1976 concurrently in Sudan (Ebola Sudan) with a mortality rate of 53%, out of 284 victims infected with the virus, 150 were killed, and Zaire (Ebola Zaire) with a mortality rate of 89%-‐killing 284 out of 318 victims. Three years later, Sudan experienced another outbreak with a mortality rate of 65%-‐22 out of 34 died (Pourrut, 2005). After a 15-‐year hiatus, there were several outbreaks of the Ebola virus. In Kikwit 1995, Ebola Zaire had a mortality rate of 81%-‐256 out of 315 victims were killed. In varying parts of Gabon between 1994-‐1997 there were three outbreaks of Ebola Zaire with a combined mortality rate of 68%-‐killing 95 out of 140 victims (Pourrut, 2005). Other outbreaks of the Ebola Zaire virus occurred
between the years of 2001-‐2003 in Mekambo claiming the lives of 143 out of 178 victims, an 88% mortality rate (Pourrut, 2005). Outbreaks of the Ebola Sudan emerged twice between the years of 2000-‐2004. The first outbreak happened in Uganda during 2000-‐2001, causing the deaths of 173 people out of 425 victims, a 40.7% mortality rate. The second outbreak happened in Sudan, during 2004 causing 7 deaths within 17 victims, a 41% mortality rate (Pourrut, 2005). The most recent outbreak emerged in West Africa 2014, in the areas of Guinea, Liberia, and Sierra Leone. This is, to date, the largest outbreak of the Ebola virus since it’s discovery in 1976. This outbreak infected more that 964 people, killing 603 (Stephenson, 2014).
Locations of known infections and outbreaks of the Ebola virus. Red indicates instances of Reston Ebola virus, blue indicating Sudan Ebola virus, green indicating Zaire Ebola virus, pink indicating Bundibugyo Ebola virus, and yellow indicating the Côte d’lvoire Ebola virus. Source: Feldmann, 2011
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Vaccines So far, treatments for the Ebola virus have been strictly supportive rather than preventative. Due to the absence of antiviral drugs for Ebola treatment, patients who are infected with the disease are treated with a focus in IV fluid replacement, and analgesics (Hoenen, 2006).
vaccine; another trial was a Russian recombinant of the influenza vaccine. A third vaccine trial is a Venezuelan modified copy of Ebola combine with an equine encephalitis (Mohammadi, 2015).
However, there are also several other experimental treatments being tested on animals Alternative supportive measures implemented in to determine the effectiveness in combatting the the treatment of the Ebola virus is based on early disease. One treatment includes the use of isolation of patients, and the use of barrier anticoagulants, which when tested showed an protocols during patient interaction. These increased survival rate (33%). Another measures can also be seen as reducing the spread treatment plan implements the use of passive of the infection to the general population immunizations, however there are still debates (Feldmann, 2011). on its effectiveness. In some animals it was shown to protect, and effectively treat the The recent outbreak of Ebola in West Africa, has infection, but in other animals it only delayed the definitely spurred the search for a vaccine with onset of death (Hoenen, 2006). projections of viability as early as 2016-‐2017 (Lee, 2015). Trials for the Ebola vaccine were on track to be tested during the outbreaks. One such trial involved the use of a modified smallpox
Literature Cited Feldmann, H., & Geisbert, T. W. (2011, March). Ebola haemorrhagic fever. The Lancet, 377(9768), 5-‐11. doi:10.1016/S0140-‐6736(10)60667-‐8 Feldmann, H., Wahl-‐Jensen, V., Jones, S. M., & Stroher, U. (2004, October). Ebola virus ecology: a continuing mystery. Trends in Microbiology, 12(10), 433-‐437. doi:10.1016/j.tim.2004.08.009 Groseth, A., Feldmann, H., & Strong, J. E. (2007, September). The ecology of Ebola virus. Trends in Microbiology, 15(9), 408-‐416. doi:10.1016/j.tim.2007.08.001 Hoenen, T., Groseth, A., Falzarano, D., & Feldmann, H. (2006, May). Ebola virus: unravelling pathogenesis to combat a deadly disease. Trends in Microbiology, 12(5), 206-‐215. doi:10.1016/j.molmed.2006.03.006 Continued…
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Literature Cited (Continued)
Lee, B. Y., Moss, W. J., Privor-‐Dumm, L., Constanela, D. O., & Knoll, M. D. (2015, January). Is the world ready for an Ebola vaccine. The Lancet, 385(9964), 17-‐23. doi:10.1016/S0140-‐ 6736(14)62398-‐9 Mohammadi, D. (2015, January). Ebola vaccine trials back on track. The Lancet, 385(9964), 214-‐215. doi:10.1016/S0140-‐6736(15)60035-‐6 Pourrut, X., Kumulungui, B., Wittmann, T., Moussavou, G., Delicat, A., Yaba, P., & Nkoghe, D. (2005, June). The natural history of Ebola virus in Africa. Microbes and Infection, 7(7-‐8), 1005-‐1014. doi:10.1016/j.micinf.2005.04.006 Stephenson J. (2014, August). Largest-‐ever Ebola outbreak still simmering in West Africa. JAMA, 312(5), 476. doi:10.1001/jama.2014.9757 Takada, A., & Kawaoka, Y. (2001, October). The pathogenesis of Ebola hemorrhagic fever. Trends in Microbiology, 9(10), 506-‐511. doi:10.1016/S0966-‐842X(01)02201-‐6