Tuesday, March 07, 2006

A history of plague

Human history is largely characterised by two major forces, warfare and infectious diseases. In many cases these have been directly linked to one another, with new pandemics closely following after a war has subsided such as the 1918 influenza pandemic. In other cases the outbreak of a disease has directly affected the outcome of a war, such as the decimation of Napoleons army by typhoid fever halting his march on Russia. Among these ranks is a disease that does not really enter the publics mind often today, the black death. Caused by Yersinia pestis, the black death (plague) was responsible for depopulating much of Europe, breaking down the feudal system and facilitating the rise of a middle class redistributing power. With the rise of antibiotics, plague ceased to be much of the threat that it once was and has mostly been eliminated from the developed world. Today, plague is a considerable threat only in developing countries and from emerging uses as a biological weap

What is the black death?

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The black death is caused by a gram-negative coccobacillus called Yersinia pestis, which actually has a few family members that can be fairly nasty also, such as Yersinia enterocolitica and Yersinia pseudotuberculosis. Like a large number of highly infectious diseases plague is an example of a zoonosis or a disease that is spread from animals to humans, in this case originating from fleas that live on rats. When the rat population becomes low, or the animals are predated on by the likes of cats, the fleas are forced to vacate home and find a new host. Very often, this host happens to be a nearby human and the bacteria are transmitted into the unfortunate person through the fleas bite.

Once inside the body, the Y. pestis is capable of very rapidly disseminating throughout the bloodstream and has a particular affinity for the lymphatic system, with the lymph nodes being the primary target. Lymph nodes are important, because the organism homes in on them and begins to disrupt normal immune function. Essentially, the organism uses a battery of virulence mechanisms to set up a catastropic immune reaction that causes large amounts of uncontrolled inflammation.

This inflammation has two primary effects. The first is to cause the large swelling that forms buboes, which is where the disease gets the name 'bubonic plague', although at the moment it's unable to spread from person to person. Secondly, the inflammation causes blood vessels to become 'leaky', normally a response to let lymphocytes pass to a site of infection but in this case causes widespread internal bleeding. Coincidentally, this is also why plague is called the "black death", because the blood pools in the extremities of the body such as fingers and around the mouth. This accumulated blood then dries under the skin and turns black, giving a solid indication of the terminal stages of the disease. Once this internal bleeding begins, Y. pestis seizes the opportunity to rapidly disseminate through the bloodstream and spread everywhere.

At this point there are generally only two possible outcomes. The first is that the victim simply dies from sceptic shock, where the loss of fluids from the internal bleeding causes a drastic drop in blood pressure and subsequent drop in circulating oxygen causing organ failure. In a cruel irony however, the second potential effect is the infected individual survives only for the organism to establish itself in the lungs. Here the bacillus cause further damage and become even more dangerous becoming penumonic plague. This form of plague is spread through exhaled aerosol droplets and can kill within hours due to being 'pre-conditioned' to the human body.

Reactions to the plague

In the modern world, when we get sick or are having a hard time with an organism you can very often get antibiotics or other treatments to solve it. After all, today we have a great appreciation of the fact diseases aren't caused by demons or sinister spirits, but rather by the interactions of infectious microorganisms and their hosts. Unfortunately, when the plague was at its worst such understanding was not available and the fearful reaction of most Europeans to infected individuals was sometimes worse than dying of plague. Many plague victims were simply buried in large mass graves and worse still, infected individuals and their entire families in London were often simply sealed into their own homes and left to die. There are towns and cities in England that have expanded over and simply built on top of these testimonials to human ignorance.

Even if you survived this wasn't a guarantee that you would make it through, as it was sometimes suspected that those not struck down by the disease were protected by the devil. The resulting fearful mob that formed simply stoned the individual to death or occasionally burnt them at the stake. Possibly the most poignant example of this ignorance leading to immensely violent reactions was the observation that Jews suffered less from the plague than others. Numerous massacres of Jews occured as a result, not just from fear of the plague but also as a reaction against the religious and political institutions the peasantry saw as having failed them. Additionally, lepers (infected with an entirely different organism, Mycobacterium leprae) and anyone else with a skin condition were also massacred as they were thought to aid the spread of the disease.

As well as violent reactions there were also those of confusion and despair that gripped your average European. Confidence in practitioners of a 'science' called alchemy waned as numerous alchemic concoctions failed to do anything or just made symptoms worse. Additionally, skepticism surrounding the claims of the Catholic Church increased with the ever rising death toll as priests failed to cure plague victims and were struck down themselves regardless of belief in God. This led to many Europeans going to other relgious sects, like the crazy flagellants which rapidly rose in popularity or alternatively seeking more secular solutions.

The effects of the plague were considerable as a result on the future leadership and direction that Europe would take. With an estimated two thirds of Europes population wiped out by the pandemic, plague had numerous key effects on the European population. The power of the Church was greatly weakened by the plagues effects, leading to the replacement of several practices with more secular ideals. Secondly, the recession caused by the plague crashed land prices and the decimation of the population increased the amount of food per individual. This resulted in a redistribution of wealth among the average peasant, which inevitably led to the rise of the middle class and the redistribution of political power as a result.

Even with this effect, it's still important to bear in mind that some 25 million people died and some completely needlessly. The devastating effects of the plague were further amplified by numerous human factors as well. The culling of cats, seen as servants of witches, in several towns in England led to the plague spreading more rapidly due to the lack of predation on rats. In many cases the plague exposed how, when faced with such immense death, people reverted to nothing more than animals full of ignorance, bigotry and fear when everything they previously relied upon (Religion, their leaders, alchemy etc) failed to provide answers.

Plague in the modern world

Today plague is largely considered a 'dead' disease in the developed world. Although still dangerous to get, it tends to be rare and most people would not encounter it on a day to day basis. Even if you did manage to contract plague, there are numerous antibiotics that are effective against the organism such as tetracycline and streptomycin. The treatment certainly isn't pleasant, intravenous injections of an antibiotic never are, but it's highly effective and the patient has an excellent chance of survival. Unfortunately, the same situation cannot be said for the developing world. There, plague continues to be a killer due to insufficient stocks of key antibiotics required to adequately treat the disease and poorer standards of hygeine, such as living in close association with rats.

Worse still, Y. pestis is one of the best potential biological weapons currently around. It's firstly very well armed already, with a battery of virulence mechanisms including several type III secretion systems, which are used to inject toxins into cells and Y. pestis can directly destroy cells of the immune system (particularly neutrophils). Additionally, antibiotic resistant forms of Y. pestis have also been found, although thankfully only in isolated cases and do not appear to be widespread. Finally, unlike numerous biological weapon candidates, like ebola or anthrax, Y. pestis has the potential to spread between people allowing it to more rapidly disseminate through a population.

So although plague may be far from its original glory days, the potential of this organism for future outbreaks and particularly from drug resistant forms, cannot simply be ignored as a mere vestige of the past.

References

Anisimov A.P., L.E. Lindler and G.B. Pier (2004). Intraspecific diversity of Yersinia pestis. Clinical microbiology reviews, 434-464

Galimand M., A. Guiyoule, G. Gerbaud, B. Rasoamanana, S. Chanteau, E. Carniel and P. Courvalin (1997). Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. The New England Journal of Medicine, 337:677-680.

Salyers A.A. and D.D. Whitt (2002). Bacterial Pathogenesis: A molecular approach 2nd edition. ASM press, Chapter 13:203-215.