History of Epidemics and Plagues (October 2001)

http://uhavax.hartford.edu/bugl/histepi.htm

Introduction

Every infection is a race between the microbes and the host. The microbe, following the indelible rules of evolution, strives to survive and reproduce, while the host's immune system mounts a warlike defense designed to find, destroy, and eliminate it. An agent that kills its host quickly cannot be expected to survive long enough to reproduce. Thus excessive virulence is not selected for in evolution. Germs, which can reproduce and be passed from one host to another, are favored.

Definitions

The prevalence of a disease is the number of diseased individuals at any one time (point prevalence) or over a given period (period prevalence). The incidence is the number of new cases of a disease that occur within a defined population over an established period of time. Frequently either prevalence or incidence, or both, are given as a rate, meaning the number of cases in a fixed number of people, e.g., cases per 100,000. Individual cases of disease in widely separated geographic areas or otherwise independent cases are said to be sporadic. Any excessive and related incidence of a particular disease above what is normally expected in a population is defined to be an epidemic. When an epidemic extends beyond the confines of a wide area, typically a continent, and becomes a more widespread problem, it is a pandemic. AIDS today is a pandemic disease, insofar as cases have been diagnosed on every continent, save Antarctica. Any disease with a low to moderate normal base level incidence rate in the population, but not necessarily constant, is said to be endemic. The common cold is endemic in northern latitudes.

Individuals who are infected and show either no or only mild symptoms are said to have a subclinical infection. Subclinically infected individuals with no symptoms are identified as well-carriers of the disease because they are carrying and frequently shedding the disease agent. The following table gives the incubation period (time between exposure and the first detectable symptom), latency period (time when the disease is concealed, hidden, or inactive), and infectious period (time during which the disease can be transmitted with or without contact) for several common diseases.

There are two major types of infectious diseases which can develop into epidemics: common source and host-to-host. Common source epidemics arise from a contaminated source, such as water or food, while host-to-host infections are transmitted from one infected individual to another via various, perhaps indirect, routes.

Anything causing disease is called a pathogen. A vector is an organism that serves as an intermediary in the transmission of a host-to-host disease. For instance, many infections are transmitted by mosquitoes, fleas, ticks, etc. to people. A fomite is any inanimate object that adheres to or transmits infectious material, e.g., bedding, clothing, surgical instruments, etc.

Types of Epidemics

Common source epidemics usually produce more new cases earlier and faster than host-to-host epidemics. Once the infected source is closed, sealed, or removed, the common source epidemic usually abates rapidly. Host-to-host epidemics are slower to grow and slower to diminish.

You should pay special attention to the number of common-source epidemic diseases that are due to contamination of water and food by-products of human excretion. Hikers and campers can purchase water filters that are sufficiently fine that most of the nonviral pathogens cannot pass through them.

The tables below list several common source and host-to-host epidemics, the causative agent (followed by V for virus, B for bacteria, and P for protozoa), sources of infection, and the reservoirs of the infection. Current knowledge tells us that humans are the only reservoirs for sexually transmitted diseases.

Coevolution

The colonization of a susceptible, unimmunized host by a microbe may lead to exponential growth of the parasite and an epidemic. In time the host population develops resistance and the spread of the microbe may be checked and some form of equilibrium may be reached. Genetic changes in the host could destroy the parasite or a change in the microbe could initiate another epidemic. The disease would continue until the host develops an appropriate response to check the microbes' growth. As this process continues, each agent affects the evolution of the other; in this case, the two organisms are said to be coevolving. This coevolution is a process of continuous change as both organisms follow the rules of evolution and move toward greater diversity.

A classic example of coevolution dates back to the 1950s. European settlers introduced rabbits to Australia in 1859. With few natural predators, the rabbits did what rabbits always do, and soon they covered most of the continent, wreaking environmental havoc. Scientists studied the myxoma virus, spread by mosquitoes, which exists in equilibrium with South American rabbits, but is deadly to European rabbits. In 1950 the virus was introduced in an attempt to control the rabbit population. The first year saw 95% of the infected rabbits dead of myxomatosis. As the weaker hosts died off, the virus mutated to a less virulent strain. At the same time, the rabbit population consisted only of those remaining that, when challenged by the virus, survived. As the two organisms coevolved over about six years, both the virus and the rabbits survived, albeit at reduced levels. What remained were the less virulent virus and the immunologically stronger rabbits. The rabbit population stabilized at about 20% of the pre-epidemic levels.

Herd immunity is the resistance of a group of organisms to invasion and spread of an infectious agent resulting from immunity of a large proportion of the members of the group. If the fraction of immune individuals is sufficiently large, the entire population will be protected from the ravages of an epidemic. This protective fraction is a function of the virulence of the pathogen, the duration of infectivity, and the general state of the host population. Fractions as low as 0.70 will suffice for diphtheria and polio, but influenza will not be stopped by herd immunity until the protected fraction is in excess of 0.90.

Not all diseases can erupt into epidemics. The microbe needs to be transmitted to new hosts in order to continue reproducing. In small towns everyone could contract the disease in such a short time that the pathogen could die out. There is a critical size for a group below which the disease cannot become an epidemic, but above which it can. Historical records seem to indicate that in human habitations this size is about 250,000. Thus major epidemics did not find their way into recorded history until cities evolved to this population size.

The dread diseases faced by past societies, and largely (but not universally) absent today include, but are not limited to, the following.

Plague

Arguably the ultimate scourge of mankind (and over 100 species of animals) was the so-called Black Death. The generic "plague" (with a lower case p) has entered the language as a descriptor for any deadly epidemic disease. Plague (with an upper case P) is caused by Yersinia pestis, a rod-shaped, Gram negative bacterium. As few as one bacterium is an infective dose! This electron micrograph is from Dennis Kunkel's webpage, which is definitely worth many a visit.

Its reservoir consists of the fleas (the Indian rat flea, Xenopsylla cheopsis, of which only adult females feed on hosts. X. cheopsis is fairly hardy and can survive for 6 to 12 months off a host in dung, an abandoned rodent's nest, textile bales, and on rodents, such as prairie dogs, rats, squirrels, gerbils, field mice, etc. The micrograph of the flea was made at the University of Queensland in Australia.

The following picture was obtained from the CDC website. It has been illuminated from the rear so that you can see that the flea's gut is filled with blood after drawing a meal from a host.

Y. pestis is enzootic; meaning it is endemic to these rodents (the reservoir), and can even survive in their burrows after an epizootic (an epidemic arising from a transfer of disease from animals).

Black rats (Rattus rattus-which were common in ancient times, but have since been supplanted by the larger and more aggressive brown rats, Norvegicus rattus) rarely move more than 200 meters from their nest and are good climbers, hence their adaptability to the thatched roof homes of either the Middle Ages, present day rural Africa, or parts of the Asian subcontinent. Normally the fleas live on the rodents in a form of equilibrium, but sometimes that equilibrium is upset when the organism multiplies rapidly in the flea's gut, eventually blocking the lumen (the space within its gut) so that the flea regurgitates infected material as it attempts to feed. This infects the rodent and it contracts a form of the fatal disease called murine or silvatic Plague. When infected, rats are asymptomatic until near death, whereupon they swell up (because the Y. pestis grow so rapidly and in such large numbers that they block the biliary duct) and stagger as if intoxicated. The fleas then leave their dying hosts and seek residence in the nearest warm-blooded animals. Considering that fleas can jump several feet, "nearest" is a relative term.

One to six days after a human receives a flea bite, the lymph nodes in the armpit (axilla) and groin become very tender and swollen (as large as an egg [They range from 1 to 10 cm in diameter.]). These very painful swollen areas are called buboes (from the Greek bubo, meaning groin). The buboes may suppurate, i.e., break and discharge a particularly fetid pus. Each of the buboes shown below are on children (to give you a perspective of size).

Sometimes the original bite site becomes infected and suppurates. It is not rare for the area of the bite to become gangrenous and necrotic, i.e., the tissue dies. Other symptoms include restlessness, staggering gait, mental confusion, prostration, delirium, rapid pulse, nausea, aching of the extremities and back, and a high fever (at least 40° C = 104° F). Then one of two avenues is followed. If the fever breaks, there is usually remission and the immune system has gained the upper hand over the pathogen, which it then proceeds to destroy and expel. If the fever doesn't break, the infection spreads to the blood, causing septicemia and death. This is the course of bubonic Plague.

In some cases the microbe can proceed directly to the blood stream and this septicemic Plague can occur before the formation of buboes and results in death before a diagnosis can be made. Some scientists feel that this form of Plague can even be carried by either the common human flea or the body louse. In septicemia, blood vessels break and leak under the skin causing a dark rash as the blood dries (hence the name Black Death which was given in the 1500s).

For both bubonic and septicemic Plague, there is hemorrhagic illness (bleeding), multiple system failure, and death. All of this occurs within three to seven days. The mortality rate for untreated bubonic Plague is about 50-75% and 100% for septicemic Plague.

As it rages throughout the population, Plague can change to a more virulent form and enters the lungs, whereupon the victims initially cough up a blood-spotted mucus and then graduate to coughing bloody froth, all the while spreading the disease by aerosol droplets. This pneumonic Plague has a 100% mortality rate, if untreated, and death can occur in a matter of hours. Small children having the Plague frequently went into convulsions, wherein their bodies jerked about uncontrollably prior to death-not a pleasant sight.

Streptomycin, gentamicin, and tetracycline are treatments of choice for all three varieties of Plague. Penicillin has no effect. Medication must be given within the first 18 hours of infection to be completely effective.

Quarantine (from the Italian quarentina, meaning forty days [based on no scientific reason, but rather on the number of days the bible said Christ spent in the wilderness] for the time of isolation of ships entering harbor which were suspected of carrying some form of contagion) is only somewhat effective at the outset of an outbreak. In the fourteenth century, Milan, Florence, and Venice employed quarantines with a vengeance. The homes of sufferers were sealed—well and sick left to die for lack of food and water. Of course, the human residents of such dwellings were constrained, while the rats could come and go as they pleased. Even rats aboard docked quarantined ships had easy egress, because they could climb down the mooring ropes and onto the docks.

The major Plague epidemics occurred in 540 at Pelusium, Egypt, reached Constantinople in 542 and spread into Europe and Asia (the Plague of Justinian) in the following decade; 14^th century Europe, following the caravan routes, it was in the lower Volga River basin in 1345, the Caucasus and Crimea by 1346, Constantinople by 1347, Alexandria in the autumn of 1347, Cyprus and Sicily in that year, Italy by winter 1347, Marseilles by January of 1348, Paris in spring 1348, followed by Germany and the Low Countries in that year, Norway in May 1349, eastern Europe by 1350, and finally Russia in 1351, but smaller outbreaks continued for about 200 more years; Austria in 1711; the Balkans from 1770-1772. The last major pandemic ran from 1855-1896 worldwide, but mostly in China and India, wherein more than 12 million died. Manchuria in 1910–1911 witnessed about 60,000 deaths due to pneumonic Plague with a repeat in 1920–1921; and a minor outbreak occurred as recently as the summer of 1994 in Surat, India closely following an earthquake in September 1993.

From 1150-1200 there was a major warming throughout Europe. This, coupled with the rise of the mercantile class, led to improved diet and greater population growth. By 1340, Europe was significantly overpopulated. This was followed by the so-called Little Ice Age, which ended by 1351. The resulting climate was colder and wetter than normal. With population higher than it had been in some time, and crop yields reduced, per capita caloric intake fell precipitously, general health declined, and the pest population increased. Not a welcome combination of circumstances.

There are several theories to explain the onset of Plague, but they all agree that a major source was China, Mongolia, and Hunan province, in particular. The nomadic tribesmen that populated the region seemed to know instinctively that something was amiss. A series of customs arose designed to keep the microbe in check. Trapping marmots (a host for X. cheopis) was taboo; marmots could be shot at a distance only; slow-moving animals were to be avoided; furs of certain rodents could not be used.

Around 1330 Plague affected the local residents of the Orient and following the elaborate trade routes, established in the previous two centuries, made its way west. By 1345, it was in the lower Volga; by 1346 Astrakhan, the Caucasus, and Azerbijian; by 1346 Constantinople and the Byzantine Empire; late autumn 1347 Alexandria, Egypt and southward along the Nile; India and what is now the middle east were next to be depopulated by the, soon to be ubiquitous, flea and its internal traveling companion.

During the summer of 1347 Genoese merchants and their families were living in the city of Kaffa on the Black Sea, in the Crimea, when it was subjected to a siege by Tartars. As the effects of the prolonged siege seemed to be overcoming the resistance of the residents, an outbreak of disease decimated the Tartar forces. In a fit of rage, the remains of the departing army are rumored to have catapulted corpses of the disease victims into the city. The merchants hastily departed the city in twelve vessels and set sail for Italy. October 1347 found the Genoese fleet outside the port of Messina, Sicily and the crews, or what was left of them, were found to be dying of some unknown malady. Michael of Piazza described the arrival of the sailors as "sickness clinging to their very bones." City officials sealed the vessels for two days—but, of course, this had little effect on the rats, and their accompanying fleas, who easily descended the mooring lines—and then dispatched them to their home port. Within two months nearly half of the population of Messina was dead. The disease soon spread throughout the ports of Italy and reached the inland cities by early spring; in most cases halving their populations. Reports of another Genoese merchant ship carrying the disease to Marseilles came in January 1348. By that summer, the Plague reached Paris. It then spread east to Germany and north to England, reaching London in December 1348. During this time it came to be known by the names: the Great Dying, das Grosse Sterben, the Plague of Justinian, and Magna Mortalis.

At that time, the population of England was estimated to be about four million, yet within a mere two and a half years about one third of them had died. Fully one third of the residents of Florence died in the first six months and 45%-75% in a single year. Venice lost 60% of its populace over the year and a half that the epidemic raged. Death was so rampant that the pope had to consecrate the Rhone River so corpses could be dumped into it. The death toll throughout Europe was at least 25 million out of a total population of 40 million. (In warmer months and in southern Europe, at this time, there was at least one family of black rats per household and an estimated average of three fleas per rat.)

Clergy were especially hard hit; 50% of the English clergy died; in Montpellier, of 140 Dominican friars at the outset, only seven survived; one third of the cardinals went to their eternal reward. Their numbers were slow to recover, taking several generations and some orders remained depleted until well into the seventeenth century.

This outbreak of Plague was accelerated by a total absence of sanitary procedures and lack of knowledge. For instance, the dead were heaped in piles, whereupon rats and dogs fed on the corpses and the cycle was extended. Homes were more like sties than what we would associate with buildings fit for human habitation. Roofs and walls were made of straw; floors were dirt; animals were kept inside. The streets, if that's what you could call them, of cities were barely wide enough for a single cart to pass, and they were perpetually covered with mud, garbage, and excrement. For lack of heated water, people rarely bathed and fleas were commonplace. When St. Thomas à Becket was prepared for burial in England in 1170, he was found to be wearing (from the outside in) (i) a large brown mantle, (ii) a white surplice, (iii) a coat of lambs' wool, (iv) a woolen pelisse, (v) another woolen pelisse, (vi) the black robe of the Benedictine order, (vii) a shirt, and (viii) a tight-fitting suit of coarse hair-cloth covered on the exterior with linen. During preparation for burial the cold English air stimulated so many of the critters occupying his hair suit that it "boiled over with them like water in a simmering cauldron."

Simple children's' rhymes illustrate some profundities associated with the times, e.g.,

Rosies are rosary beads, presumably to gain divine intercession against this mysterious enemy. Most Plague victims emitted a rather strong and rather objectionable odor, so flowers (posies) were carried to mask the smell. Ashes are all that was left of a burnt corpse. Of course, to fall down means to die. Sometimes the second last line is replaced with "A Tishoo, a tishoo," meaning the sneezes of the victims of pneumonic Plague. To be sneezed on by them was a sure death sentence for all but the hardiest souls. [There is some debate about the relevance of this to Plague because the first printed version of this rhyme appeared in 1822, over 150 years after the last major outbreak in the British Isles.]

Throughout Europe, many areas were abandoned. Agriculture came to a virtual standstill as farmers fled or died in their fields. Consequently, food shortages compounded the problems of society. Governments ground to a halt as bureaucrats died. No civil authority remained and crime was rampant. Station in life was not an indicator of immunity. Plague attacked merchants and peasants with equal voracity. Only the very rich could afford to move to protected environs far from the disease and even that was no guarantee of survival.

Everyone feared the spreading contagion and no efforts were spared to avoid its fatal embrace. "Kinsmen held aloof, brother was forsaken by brother, oftentimes husband by wife; nay, what is more, and scarcely to be believed, fathers and mothers were found to abandon their own children to their fate, untended, unvisited as if they had been strangers," wrote Boccacio in his preface to the Decameron. The pope's physician, Guy de Chauliac characterized the period as one where "Charity is dead." What more can be said?

Unaware of the cause of the disease (or even the rudiments of Germ Theory), people took to

 burning incense,

 dipping handkerchiefs in aromatic oils,

 ringing church bells and firing cannons,

 wearing talismans,

 bathing in human urine,

 placing "stinks" (dead animals) in their dwellings,

 bleeding via leeches and bloodletting,

 drinking the pus extracted from a suppurated bubo (Total Yuck!),

 applying dried toads to relieve the pain of the buboes by absorbing the "poisons,"

 drinking liquid gold or powdered emeralds (only for the very rich, of course), and

 joining groups of flagellants.

The "order" of flagellants, also called the Brethren of the Cross, (initially active in the late 1200s) was re-formed in Germany in 1348 and initially blessed by the pope. It forbade its members from bathing, washing their heads, shaving, sleeping in a bed, having any contact with the opposite sex, or even changing their clothes during a procession without permission of the "Master". Washing of hands was allowed, but only once a day and that had to be done when kneeling. Each member had to donate funds to cover the cost of their food for the duration. As if to satisfy the ascetic needs of a squeamish populace, the groups went from town to town and whipped themselves with scourges, i.e., sticks with three or four leather tails with large knots containing sharpened iron spikes. They continued until the blood ran and even when the spikes stuck in the skin and had to be torn out. Many of them died of infections of these open wounds. They formed in bands of 50 to 300 and moved in pairs with men in the front and women in the rear of this serpentine procession. Each group's "Master" heard confessions, imposed penances, and granted absolution—all to the total horror of the local clergy, who had enjoyed an absolute monopoly (and accompanying fees) over such practices for centuries. Each procession lasted 33⅓ days, the number of years Christ was said to have spent on earth. During their travels through Germany and the Low Countries they preached anti-Semitism. Their asceticism had no effect on the state of the epidemic and their personal hygiene may have helped to carry Plague from village to village. Eventually, in October of 1349, the pope ordered the military arm of the church to force the groups to disband.

Upon commission of the pope in 1348, a group of learned men (and at that time only men were deemed capable of being educated and hence, learned) of the medical faculty at Paris concluded that the disaster was a result of a conjunction of Saturn, Jupiter, and Mars in the 40^th degree of Aquarius at 1:00 p.m. on March 20, 1345. This caused hot, moist conditions, which forced the earth to exhale a virulent sulfurous miasma. So much for the Age of Aquarius!

The horror and fear faced by medieval people confronted with the bizarre and almost totally unknown symptoms of Plague is inconceivable to us today. To those who believed in spirits and devils (that was most of the people of the time), this infestation was a scene from their worst nightmares; one in which they were completely unable to effect relief, no less a cure. It was as if all the monsters of their psyches were being unleashed for reasons they could not comprehend. When your worldview is limited, your options in the face of calamity are even more limited. Any explanation is believable. The pope declared that it was not divine punishment for the sins of the world, but local clergy gave that as the only reason for such horrors. As a referent, you may want to look at a copy of the leftmost part of the triptych of Heironymous Bosch's the Garden of Earthly Delights.

As with most mysterious, unknowable, and uncontrollable tragedies, the thin veneer of human rationality is peeled back to expose a dark undersurface capable of incomprehensible horrors and unimaginable evil. People sought to blame others; scapegoating was in season; xenophobia was the norm—all strangers were suspected of spreading disease. As had happened before and since, Jews were the targets of choice (even though they died of Plague at the same rate as others). Rumors of their having poisoned wells ran rampant. There were pogroms and massacres. The rabble was loose. Zurich expelled all its Jews and closed its gates to them. On a single day in 1349, 2000 Jews were burned to death by a mob in Strausborg. Even officialdom entered the fray. The canton of Basel gathered all 4500 of its Jews in a specially built structure on an island in the Rhine and burned them to death, after which the town fathers passed a law forbidding Jewish residence in the canton for 200 years. The largest Jewish community in Europe was in Mainz, Germany where at least 6,000 Jews were incinerated after they fought and killed 200 of an attacking mob. Pogroms also occurred in Baden, Brussels, Burren, Dresden, Eisenach, Erfurt, Freiburg, Gotha, Landsberg, Lindau, Memmingen, Solothurn, Speyer, Stuttgart, Ulm, Worms, and Zofingen. There were over 350 separate recorded massacres of Jews during the years of the Plague.

The approach of a group of flagellants frequently incited townsfolk to embark on pogroms and when they didn't, the Brethren proceeded posthaste to the Jewish quarter where they murdered and looted with a viciousness, ferocity, and completeness that foretold the Final Solution of the Nazis in the twentieth century. Western Europe killed or expelled the Jews even as Pope Clement VI issued papal bulls forbidding plundering and killing them. As if on cue, local clergy either instigated anti-Semitic actions or failed to stop them, likely because properties of the Jews reverted to the Catholic Church upon the death of the families. What the Church lost in clergy and followers, it gained in tangible assets.

Eastern Europe, relatively unscathed by the Plague, tolerated the Jews. King Casimir of Poland offered to protect them. Some say it was because he had a Jewish mistress, but it is more likely that his country needed the skills they possessed. A return of the Jews to their former lands in western Europe was slow.

Once it ebbed, by the end of 1351, the Plague left Europe with a sizable shortage of workers and helped to destroy the feudal system when labor found itself in a seller's market. Abandoned homes were taken over by complete strangers, as there was a default redistribution of wealth.

The most generally agreed upon mortality figure was that one in three people were killed by the Plague—a total loss of well over 20 million in Europe and perhaps as many as 40 million worldwide.

[As with all things ancient and historical, there remains room for controversy. Scott & Duncan wrote Biology of Plagues: Evidence from Historic Populations wherein they claim that the medieval plague was not due to Plague at all, but rather to some form of hemorrhagic viral disease. S. Cohn disagrees with those authors only insofar as the cause of the disease. Nevertheless, French researchers found Y. pestis in the dental pulp of bodies buried in Montpellier during the 14th century. Adding to this is a October 2001 paper of Parkhill, et al. in Nature 413:523-527. They announced the complete mapping of the bacterium's genome, all 4,653,728 base pairs (more of this in a later unit). They found 149 deactivated genes that once enabled the bacterium to thrive in the human gut, but are no longer needed.]

Although the Plague no longer killed millions, it remained present on the European continent for more than three hundred years, erupting in seemingly random locations until its final gasp in Marseilles in 1720. The last major infestation of Plague (over a million died) arose in China and India in 1855 and reached Hong Kong in 1894. Estimates are that 12 million died. It was here that Alexandre Yersin and Shibasaburo Kitasato independently described the causative agent. Strangely enough, it wasn't until 1897 that P.L. Simond identified the mode of transmission.

Today Plague is endemic in various places; Madagascar, Tanzania, Brazil, Peru, Burma, and Vietnam have experienced cases almost every year since the start of the last pandemic in 1880, and rodents in the southwestern United States carry it! In fact, 40% of the U.S land area is infested by Plague-infected animals, mostly prairie dogs! Some national parks have signs saying not to feed the squirrels because they have Plague.

Since 1947, there have been 390 cases of Plague in the U.S. resulting in 60 deaths. From 1980-1994 this country has had 229 cases with 33 deaths. The last two Americans to succumb to Plague died in August 1996, both due to transmission by way of prairie dogs. A thirteen year-old Kazakhstani boy died of bubonic Plague on August 9, 1999—the first such death in that country in 25 years. Many other nonfatal cases have been reported.

Today east Africa and Hunan province in China are permanent reservoirs, called inveterate foci, for the disease. During 1965-1971, Vietnam (in addition to fighting a war against the United States) reported 25,000 cases of Plague. The World Health Organization received reports of 18,739 cases in the period from 1980-1994, of which there were 1853 deaths (that's a 10% death rate) and between 2000 and 3000 every year. What is disconcerting is that more cases were reported from 1990-1994 than in the entire previous decade (an average of 2025 cases/year versus 861 cases/year).

The last known case of human-to-human transmission occurred in Los Angeles in 1924.

The latest large, but not major, outbreak occurred on September 20, 1994 in the Indian city of Surat in the state of Gujarat. Initially the government of India did not recognize the presence of the disease until several hundred thousand people had fled the region. By October 2, there had been 2500 cases reported and official figures of 58 deaths. Considering that this strain was the highly contagious pneumonic variety, thus spread by aerosol droplets upon respiration and was amenable to treatment with tetracycline, such a low mortality figure may or may not be comforting.

A vaccine was available for those who expected to come in contact with animals that may have been infected, but it was not completely effective. The manufacturer discontinued production in 1999 and it is no longer available. It worked on bubonic Plague but not pneumonic.

Rather ominously, the September 4, 1997 issue of the New England Journal of Medicine carried a brief report from Galimand et al. describing a case of multiple antibiotic resistant bubonic Plague. The causative agent, Y. pestis, acquired a resistance plasmid from an unknown source. The thought of another worldwide pandemic of Plague that is resistant to modern medical treatment boggles the mind.

On August 26, 1999 the wire services carried a story announcing the development of a vaccine for bubonic Plague designed to protect against bio-terrorism. Human trials were to begin shortly. We await the results.

A separate issue is the use of Y. pestis for bio-warfare. 

Syphilis

Syphilis, or the Great Pox and later known as lues (named after the French kings Louis and pronounced the same), is caused by the spirochete Treponema pallidum.

This organism is extremely closely related to those treponemes that cause the nonfatal and nonsexually transmitted diseases yaws, pinta, and bejel. Although some medical historians claim the disease originated in the Western hemisphere and was brought back to Europe by Columbus's crew, others believe that it evolved (or coevolved) from yaws by mutation. Consider the question as unresolved to this day.

Its original form was more virulent than what we see today and its symptoms were more florid. Despite a