EBOLA VIRUS

Ebola. Mention this bug's name to any lay-person, and images of horrific bleeding and near-instant death are immediately conjured. These images were popularized by the 1995 movie Outbreak . I must admit, when I first watched this movie, (then being only 11 years old) I was thoroughly fascinated. Granted, watching it now, it almost seems comical, but this was essentially the spark that ignited my interest in the field of virology. Later, I read the book The Hot Zone by Richard Preston. This offered a bit more realistic and tangible notion of what work in this field might involve. Even then, further reading has proven some of this book to be somewhat sensationalist, but it laid out the backbone for my interest.

As I became further entrenched with high school, and subsequently college, my goal has always been to work with dangerous pathogens. Upon hearing of the University of Hawaii 's program in Tropical Medicine, I became enamored with the idea of 1. studying in Hawai'i and 2. being able to eventually work with some of the scientists doing real-life benchwork.

The Ebola virus is “a severe, often-fatal disease in humans and nonhuman primates (monkeys, gorillas, and chimpanzees) that has appeared sporadically since its initial recognition in 1976.” It belongs to the family of filoviruses (thread-like viruses). Another virus that is found within the same family is the Marburg virus, culprit in the current outbreak in northern Angola . There are four species of the Ebola virus- Ivory Coast , Sudan , Zaire , and Reston . Ebola Reston is the only species that has not been shown to cause disease in humans, although it has been shown that animal caretakers in the Hazleton Research Products warehouse found in Reston, Virginia, approximately 10 miles west of Washington DC, were in fact infected .

Fortunately, this disease has remained confined to Africa and only pops up sporadically. Unfortunately, because it is confined to the African continent, necessary resources are usually nonexistent for the further understanding of the disease, and only when there is an active and overwhelming outbreak is anything truly done.

The virus is transmitted primarily through direct contact with an infected individual, specifically body fluids. Unfortunately, due to the poverty level, and with resources lacking in the medical establishments in rural areas, as soon as an individual is infected and visits the local clinic, amplification occurs. This is due to the reuse of syringes and other forms of ineffective nursing hygiene that would normally prevent the amplification of such biological threats. These nosocomial infections can ravage a hospital very quickly, and render it useless. Additionally, due to African custom in which the body of the deceased is cleansed and washed by the family members , this virus is further disseminated. Very quickly can a whole village be infected through these burial rituals. The original introduction of this virus into the human populace has been the handling of the dead primate carcasses by boys or young men, and by the efforts to ready this meat for consumption .

Very little is known about the pathogenesis of Ebola, including the mechanisms by which they enter host cells. What is known is that Ebola attacks fibroblastic reticular cells (FRC) among the loose connective tissue under the skin and in the FRC Conduit (FRCC) in lymph nodes. This allows the virus to rapidly enter the blood and leads to disruption of lymphocyte homing at high endothelial venules. Ebola seems to be most active in infecting fibroblasts of any type. The next most frequent cell types targeted are mononuclear phagocytes: dendritic cells more so than monocytes or macrophages. These are then followed by epithelial cells of any type. However, all parts of the body can be attacked with the exception of skeletal muscle and bone.

The manner in which it causes pathology is by attaching to every cell possible, penetrating it, replicating, and eventually lysing the cell due to the high levels of new virus particles within. As it enters the bloodstream, it continues with this process until the tissue is saturated with the virus. Initially, clotting begins in the bloodstream, making the blood more viscous. Then these blood clots begin to attach to the wall of the blood vessels in a process called pavementing.

As the clotting increases, some of these become lodged in some of the smaller capillary beds, negating blood flow to these areas, and eventually causing necrosis of the surrounding tissue. This is found primarily of importance in the brain, liver, kidneys, and skin. Since Ebola has an affinity for connective tissue, it destroys the collagen, and subsequently underlying layers of epithelial tissue dies. This causes mass sloughing of these tissues. Ultimately death comes to the host is when he or she “crashes out,” when the vasculature can no longer sustain the onslaught it has received- causing a massive heart attack- this is when the person begins to bleed from every orifice, including the skin pores.

Symptoms are as follows:

"The symptoms which occur in Ebola are very similar to those which occur in many other diseases in tropical Africa . Fever, up to 40 degrees centigrade, extreme fatigue, muscle, and joint pain, headache, especially frontal headache, hiccups, (and hiccups in this case are a very bad sign.) They are associated with a very severe prognosis probably because of irritation to the diaphragm, ocular injection and in very light skinned persons a macular rash. After the sixth day, on days seven and eight, there is actually a clinical improvement in many cases and a decrease in fatigue and many persons feel extremely well during this period. For many this is only the beginning of a cure and as you know there is about a 30% survival rate in this disease. For those unfortunate ones who do not survive on day nine onwards they begin with hemorrhagic signs which you know well from having seen films from the outbreak in Zaire . Bleeding from the orifices and eventually death. So these are the signs and symptoms of Ebola which show that this disease in its early phase is very difficult to distinguish from other diseases in tropical Africa ." David L. Heymann, MD, Director of Emerging Viral and Bacterial Diseases, Surveillance and Control, World Health Organization. From his EIINet Seminar, 2 April 1996.

For a clear cut diagnosis, samples need to be sent to the laboratories at either the CDC or at the USAMRIID. There they can do serology, PCR, IHC, viral isolation, or visualization. However, crude immunofluorescence can be done out in the field to determine which patients are infected and which are not. Otherwise, usually diagnosis is based on whether or not there was contact with a sick individual, and if symptoms begin to appear that correlate with the infection and the contact timeline.

Once the diagnosis has been made, the best thing that can be done is supportive treatment. Unfortunately something that is not commonly found in the jungles of central Africa . Convalescent-phase plasma has been attempted, but has only shown mixed results. For some other hemorrhagic fevers, such as Lassa, ribavirin when given early has shown positive results. However, this does not seem to be effective in the fight against Ebola. The best thing to be done with individuals that are infected is to isolate and quarantine them as best as possible. Given that most infections are transmitted within the hospital setting, effective barrier nursing must be employed.

Since the reservoir is not known, the best way to prevent further outbreaks is to discourage the local population from handling primate meat. Especially those carcasses found already dead in the forest. However, due to the practice of eating these meats is ingrained within the local culture, another form of preventive measures involves arresting the transmission at the clinic/ hospital level by using more hygienic practices (new needles/ proper sterilization) awareness of the disease, and proper barrier nursing. Regrettably, most of these clinics and hospitals are running for pennies a day, negating the proper equipment and thus allowing for the further dissemination of not only Ebola but of other diseases. Otherwise, as stated earlier, isolation of patients with the disease is imperative to prevent further contact by family members. As of yet, no vaccines have been approved for human use. However, some recent work in guinea pigs and in monkeys at the Michigan Medical Center and at the National Institutes of Health: Virus Research Center , respectively, has shown some positive results. More notably is the primate vaccine because it can potentially function as a model for the development of a human vaccine.

As is reiterated throughout this paper, and echoed in many others dealing with disease confined to developing nations, not much money is set aside for diseases in regards to treatment, research or otherwise. The economic burden that these countries in Africa face due to past colonialism or current greed on behalf of the select few makes for diseases in general to pervade the population and to run unhindered. Only when it turns into a threat to developed nations does it get any attention in the form of research and funds (the former based on the latter).

Unbelievably, it seems that the world as a whole has not realized that some of these “third world issues” need to be faced now, and essentially nipped in the bud, or else much like HIV has proven, something that is confined to Africa can easily affect us globally. Ebola may not in the long run (as the disease that we know now) act on a global scale, simply because it's quick and violent onset can easily be identified and targeted. However, as was shown in Reston , due to air traffic and the importation of animals from around the world, we are constantly encountering new viruses that would have otherwise been isolated in their own remote corner of the world. Essentially the stage is set for a disaster to occur. As was outlined in the movie Outbreak , barring the sinister government conspiracy, many factors that would have prevented the emergence of a horrible disease in our own backyards have been eliminated- making us truly a global community.

Very clearly, the future of the Ebola virus is that there are going to be sporadic outbreaks of it in the heart of Africa , at least until more is elucidated. Current theories suggest that perhaps bats are implicated in its introduction to humans and other primates. Notably those bats found in the cotton processing plant in Nzara , Sudan , Tradarida trevori . Other reservoirs being looked into are some insects. Of great interest is also the fact that perhaps Ebola could have originated from a plant. Evidence for this is demonstrated by analyzing certain plant viruses, and finding striking similarities between the two. To date, nothing has been proven, and a lot of it is simply conjecture.

My theories in regards to its origin are of course altered (and/or refined) every time that I hear new information, or new evidence points toward something new. My original theory was based on a certain generality that many hemorrhagic fevers are carried harmlessly by some form of rodent. Granted, it is a very broad assumption, and only based on the fact that I asked the question: What is it that these viruses have (receptors or otherwise) that causes such destruction within the primate body? Another theory I am looking at now is whether if it is a plant virus, if it could be picked up by some insect then transferred to the bats via being eaten, or directly to humans. All of these animals are incidental to the on-going infection within the plant. That I know of, only animals have been sampled to try to figure out where it may reside. I do not think that anyone has gone out for cuttings or even did an active experiment where these relationships have been studied. It will be interesting to see what further research reveals, and see when and where I will have a chance to perhaps test out some of these theories. Perhaps by the time I get around to doing some real work out in the field, many more details about this virus will have been illuminated. However, I think not. Simply because the current trend points to only a few people working on this, and with funds being so limited, not much incentive to go into this specific branch of virology.

CDC Website, Available at: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm

McCormick, Joseph B., Fisher-Hoch, Susan Level 4, Virus Hunters of the CDC , Barnes and Noble Books 1999

Close, William T. Ebola , A Documentary Novel of its First Explosion, New York , Ivy Books 1995

Tater Waterman, Honors Thesis, Available at: http://www.stanford.edu/group/virus/filo/filo.html

The Ebola Virus: Examining the Link Between Deforestation and Emergence of the Ebola Virus and Gene, Available at: http://www.geocities.com/mockturtl/lifecycle.html

Garrett, Laurie The Coming Plague , Penguin Books 1994