Two of the most dreaded illnesses in the world are Ebola and Marburg. The names for these syndromes involves some medical geography; in the first case, a river in Uganda (the Ebola) and in the second, a city in Germany (Marburg), where each of these hemorrhagic fevers was first detected in human patients.
What is a hemorrhagic fever?
Hemorrhagic diseases are, by definition, characterized by profuse bleeding, internally or externally, and often both ways, and both Ebola and Marburg certainly qualify, although the panoply of other accompanying signs varies. (For a complete roster of possible symptoms, see Pittalis et al 2009 below ) Both Ebola and Marburg, are, however, in the early stages, primarily characterized by fever, exhaustion, and confusion in the patient. The hemorrhagic aspect is more obvious only in later stages. Patients may develop dark-blister-like growths on their face and body where blood has pooled from broken capillaries. They may then begin bleeding from the mouth, eyes, or ears. They almost always develop breakdowns in coagulation that leads to multiple sites of internal bleeding in a number of organs, leading further to localized tissue destruction. Eventually, the overall loss of sufficient internal blood supply can lead to shock and death. Fortunately for the patients suffering, they often die only after they have gone into a coma.
How lethal are these two diseases?
While there are some less deadly strains (“Sudan” and “Bundibugyo” see Gupta et al 2010 below), Ebola and Marburg kill off as high as 90% of infected patients, usually within three weeks of their contracting the responsible virus. The remaining patients of course, recover, although it is not always certain why they did so, when so many others have died.
From where did these diseases come?
They really both come from Africa, and all major outbreaks, and most individual cases, almost always are found there only, except for patients traveling to more developed countries seeking diagnosis or treatment, and medical researchers working with the virus in western countries. In addition to Uganda, Ebola has primarily broken out in Gabon, Sudan, and the Congo, with isolated cases elsewhere, including South Africa. That Marburg is connected with a town in Germany has to do with laboratories there that make vaccines. (Two other European outbreaks are based on similar circumstances.) Lab workers in Marburg had routinely been importing African green monkeys, but eventually unawares took in an infected shipment which gave this new disease to their handlers and research scientists. Natural, as opposed to laboratory, outbreaks of Marburg have occurred primarily in Angola, Congo, Kenya, South Africa and Zimbabwe.
If this disease is so deadly, why hasn’t it already wiped out large portions of sub-Saharan Africa?
The disease breaks out most often in very isolated parts of the particular countries involved. There tends to be a steeply rising number of local cases for several weeks to a few months, with a corresponding crescendo of deaths, and then a tapering off, with higher survival rates among later contractors of the virus. It is absolutely clear that quarantining patients and observing extreme measures to protect health providers, other patients and any family visitors, from contact with infective fluids, etc. is prudent and has done much to restrain the spread of outbreaks. But Ebola and Marburg, often disappear altogether from a region as suddenly and unexpectedly as they erupted.
Avoidance of Ebola and Marburg is much like avoiding running out of doors when there is a lightning storm. It’s a very good idea, but of itself does not confer immunity. Avoidance does not seem to protect you from getting the disease unexpectedly elsewhere in sub-Saharan Africa, any more than avoiding one place where lightning has struck in the past will confer immunity to thunderbolts should a storm break out elsewhere and you get caught there by surprise.
Where does the disease lurk, then, between outbreaks?
There is little doubt that these diseases persist in wild animals, where they do not necessarily make all of their natural hosts fatally sick. Rodents, bats, and various small monkeys have been implicated as natural reservoirs (See for example Leroy et al 2009 below). By contrast, chimpanzees and gorillas are known to contract Marburg and Ebola, but seem to die off very quickly much like humans do in response to infection, so they do not seem to be a likely vector, except when their dead carcasses are eaten as bush meat by native peoples. (See Bermejo et al. 2006 below). But those animals which do survive and harbor the virus, in their feces, urine, saliva, blood, and perhaps other body parts or fluids apparently contaminate the food, water, or air that is taken in by nearby humans. While vermin eradication, particularly of rodents, is recommended as a possible preventive strategy to reduce the chances of a community developing an outbreak of Ebola or Marburg, there is not a great deal of evidence that reintroduction of vermin predators (such as the revival of cat ownership which had the effect of reducing rats with bubonic plague carrying fleas) or even chemical extermination of pests has stopped an ongoing outbreak, quite possibly because, with few exceptions, (such as an Angolan episode of Marburg) they tend to be short term any way. Current laboratory experiments in search of effective therapies generally use infected lab mice, rats, guinea pigs, or monkeys. Some of these experimental animals are more disease tolerant than others, and the point of using them is to see what contributes to that tolerance. Other laboratory animals are designed to get sick and die pretty much as a model for the human experience of these diseases. There is a peculiar case in the Philippines where a variant of Ebola called Ebola-Reston (after Reston, Virginia, where a shipment of crab-eating monkeys sent to a medical research lab was found to have Ebola) has infected pigs and pig farmers near Manila, but the pigs seem not to die off quickly, and the farmers do not get sick at all, despite the fact that blood tests show that both animals and men have definitely had some sort of immune reaction indicating some level of infection (See Normile 2009 below).
What currently can be done for patients?
Patients are typically placed in medical isolation wards whenever possible, and given comfort care. They have fluid replacement, pain and fever reducers, but often do not get whole blood transfusions because these simply bleed out so rapidly.
What do we know about the viruses responsible for Ebola and Marburg ?
The structure of both Ebola and Marburg viruses has been very well studied (See, for example, Hartman, Tower & Nichol 2010 or Noda et al 2010 below ) and they are virtually identical, although they trigger slightly different immunological responses and have slightly different means of attacking cells (See Valmas et al 2010 below). These viruses consist of a surprisingly long (for a virus) strand of RNA coated largely with lipids, with fairly short protein prongs alongside. We can detect when and how they begin to penetrate cells (See Lipkin, Paacio & Briese 2009 or Tscherne, Manicassamy & Garcia-Sastre 2010 below ) and can now visualize how these viruses bud (See Liu et al 2010, Mateo et al 2010 and Welsch et al 2010 below). We have a pretty good idea of how they evade the body’s immune defenses (See Basler & Amarasinghe 2009 and Mohamadzadeh 2009 below ) yet provoke fevers that should otherwise have helped kill them off nonetheless (See Okumura et al 2010 below), even as they induce immune cell death (See Bradfute et al 2010 below).
What are the current strategies for fighting Ebola and Marburg?
Vaccines seem to be the route of choice (See Bausch et al 2008 , Geisbert et al 2009, and Olinger et al 2009 below), in part because it does seem that the small percentage of survivors of Ebola and Marburg have developed some immunological means of fighting off the remnant viruses (See Wauquier et al 2009 below) and this suggests that the right antigen triggers will generate a survival response similar to that of these patients. Nonetheless the Food and Drug Administration has relaxed the strict rules for claims of efficacy in humans by allowing initially for a greater reliance on animal models, largely because typical Ebola (and Marburg) outbreaks are extremely unpredictable and very often short-lived and most often happen in poorly equipped remote jungle areas where the numbers of patients fluctuate wildly and setting up rigid double-blind trials is simply unworkable (See Sullivan et al 2009 below).
Some vaccine prototypes are based on evoking natural immune responses to natural Ebola strains or chemically altered Ebola mutants whose ability to replicate wildly and endanger the patient has been tamed (See Halfmann et al 2009 and Prins et al 2010 below), although using specially tailored viruses more commonly associated with the common cold or flu also seems promising (See Bukreyev et al 2010 and Pratt et al 2010 below ).
Attacking proteins necessary for cellular invasion and/or replication is a common theme (See Hood et al 2010 below), as is disrupting RNAs making proteins using antisense morpholino oligomers (See Swenson et al 2009 below) or microencapsulated “small interfering” RNA (Geisbert et al 2010) both of which block off key sites, while other approaches basically allow the viruses to enter some cells but then trap them there by halting the budding process (See Harty 2009 below).
Nightmare scenarios: Weaponization of Marburg and Ebola by the Soviets and reported attempts by terrorists to acquire it
Several websites, including that of the highly respected Federation of American Scientists (http://www.fas.org/programs/bio/factsheets/ebola.html ) give credence to the notion that some form of the Ebola virus was developed as biological weapon of mass destruction by the Soviets, and a book coauthored by a former Soviet bioweapons expert, Ken Alibek (see Alibek & Handelman 1999 below) who is currently a well-respected U.S. based bioterrorism medical expert (see Weinstein & Alibek 2003 below ) also documents the use of the Marburg virus in a similar context. Other credible websites assert that terrorists and doomsday religious cults, most notably the Japanese group Aum Shinrikyo (http://www.globalsecurity.org/wmd/intro/bio_ebola.htm ) have sought to acquire and exploit hemorrhagic viruses. (They instead, released Sarin gas in an attack on the Tokyo subway system, killing 13, wounding 50, and temporarily blinding thousands.) Preparation for medical responses to the use of Ebola and Marburg in terrorist attacks is, alas, not taken as a matter of science fiction or television action and adventure thriller episodes any longer (see DuPuy & Schmaljohn 2009 and Goffman 2010 below).
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