History of Epidemics and Plagues (October 2001)

Introduction

Definitions

Types of Epidemics

Coevolution

Plague

Syphilis

Cholera

Smallpox

Influenza

Diseases of Childhood

Objectives

 

Terms you need to know are written in bold blue. Added comments are in green.

 

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.

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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.

 

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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.

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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. 

 

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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 all efforts, T. pallidum has not been cultivated in the laboratory in any artificial media (one more example which defies Koch's Postulates) and it is extremely difficult to cultivate in the presence of human cells.

The disease is spread by close personal contact: either by contact with the exudate from open sores through breaks in the skin, sexual transmission, or vertical transmission from mother to developing fetus (resulting in congenital syphilis). The symptoms are highly variable. The spirochete multiplies at the initial site of entry and a characteristic primary lesion, called a chancre, forms within two to ten weeks.

The exudate from the chancre is highly infectious. Despite its rather gruesome appearance, it usually heals and leaves no scar. Primary syphilis: from one to three months after exposure the host experiences enlarged inguinal lymph nodes as the immune system mounts a defense. Secondary syphilis: a flu-like illness develops and sometimes the immune system succeeds in its efforts and there is spontaneous resolution. If the immune system does not destroy the microbes, a generalized skin rash develops and the patient will be highly infectious, but within time, the organism disappears from the secondary lesions and the skin rash. Notice the circular marks with a light halo and dark interior.

A similar sore on the tongue should be compared to the much smaller typical cold sore.

Tertiary Syphilis: Some of the treponemes spread to other parts of the body, in particular, the mucous membranes, liver, eyes, joints, bones, muscles, or the central nervous system (CNS), where they again either multiply or remain dormant. Subsequently, the course of the disease is highly variable. About 25% of the victims undergo a spontaneous cure, another 25% exhibit no further symptoms, and the remaining 50% proceed to the tertiary stage. At this stage, the symptoms depend on what organs have active pathogen replication; they range from a mild skin rash to significant central nervous system involvement resulting in paralysis and death.

 

 

 

None of these third stage gummas or ulcers will heal to their original state. When the spirochete enters the central nervous system it can affect the spinal column, resulting in a condition called tabes dorsalis. This condition causes postural instability with a staggering wide base gait that can damage the joints of the leg. The condition shown below is called Charcot's knee.

 

 

Surprisingly, there is usually no pain in the knee (Yes, that is a knee). This is a result of tabes dorsalis [sclerosis of the posterior columns of the spinal cord] which causes postural instability and concomitant swelling.

Penicillin is effective in curing the disease, although the dosage and length of treatment are functions of the extent of infection. Usually, a single injection of one million units is sufficient.

Syphilis spread throughout Europe in the 1490s and was particularly lethal in its original manifestation. The disease was fulminant and the skin eruptions were especially gruesome. It caused genital sores, advanced to a general rash, and then developed into particularly ugly abscesses and scabs over the entire body. The sores changed to open ulcers that could erode bone and destroy tissue, especially eyes, lips, nose, throat, and genitals. As with most epidemics, the victims were blamed for the disease (debauchery, lechery, etc.) and frequently ostracized.

The bellicose nature of the regimes of the time, with their many standing armies, extensive use of mercenaries, and frequent battles, was conducive to rapid and efficient spread via the usual "camp followers" of the warring parties. The disease reached Germany and Switzerland in 1495, England and Holland in 1496. Vasco da Gama's crew carried it around the Cape in 1497 causing an outbreak in India in 1498, which in turn spread eastward. China and Japan were affected in 1505, a full fifteen years before the arrival of Portuguese sailors in Canton.

As if to repeat both history and human frailty,

• the English called the disease the French Pox,
• the French called it the Neapolitan or Italian disease,
• the Italians and the Dutch called it the Spanish disease,
• Portugese called it the Castilian disease,
• Russians called it the Polish disease,
• Polish called it the Russian disease,
• Turks called it the Christian disease,
• Persians called it the Turkish disease, and
• Japanese called it either the Portugese or Chinese disease.

Between 1497 and 1501, a number of medical tracts on the disease appeared. The writings of Leonicenus were especially good, insofar as the general symptoms were enumerated, their relation to sexual transmission was recognized, and the use of mercurial salts (an old Arabian practice) was advocated for treating the associated skin eruptions. Two famous Renaissance medical leaders, Paracelsus and Fracastorius, made major contributions to the study of this disease. Paracelsus was the first medical teacher to challenge the long-held theories of Galenic medicine. Fracastorius was a true Renaissance man; he wrote on the temperature of wines, the rise of the Nile, poetries, the mind, and the soul. He was an astronomer, geographer, botanist, mathematician, philosopher, and physician. He understood the true nature of sedimentary rocks, anticipated the principle of the Mercator projection, and described a primitive telescope. In 1530 he published the poem Syphilis Sive Morbus Gallicus (Syphilis or the French Disease), from which the name of the disease was derived.

In the United States the incidence rate of all syphilis has varied from a high of 447.0 in 1943 to a low of 26.5 in 1995. Unfortunately, the rate is no longer decreasing and the rate of congenital syphilis is now substantially higher than it was in the 1980s. Worldwide there are an estimated twelve million new cases per year.

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Cholera

Cholera is caused by infestation by Vibrio cholerae, comma-shaped Gram-negative bacteria. Notice the "tail" on each of the Vibrios.

 

An infective dose varies from 10⁶ to 10¹¹ bacteria, with the higher number applying when the stomach's acidity is high (i.e., low pH), but it can go as low as 10⁴ when ingested together with an antacid or food. The standard pH of an empty stomach is between 0.9 and 3.0, generally around 1.0, and Vibrios are killed when the pH is below 2.4, so some people will not succumb to the disease.

Cholera is transmitted through contaminated water and manifests itself as an acute infection of the gastrointestinal tract. Although Vibrios are free living in water (in fact, they can survive on algae for quite some time), they cause infection only in humans. The bacteria bind to the walls of the small intestine where they secrete a potent toxin. This toxin alters the membrane transport mechanism; instead of causing the water to leave the lumen of the gut and enter the tissues, large quantities of water, chloride, and sodium are drawn into the gut.

The disease proceeds in possibly three stages (a) Invasion: at the end of the incubation period the symptoms are malaise, headache, severe diarrhea resulting in the so-called "rice water stool," (which derives its characteristic whitish color from intestinal tissue which is exfoliated (shed) and excreted along with innumerable Vibrios), anorexia, and a slight fever. This severe diarrhea can be as high as one liter per hour. The resulting loss of fluid and the accompanying electrolyte imbalance can lead to hypovolemic shock, renal failure, and cardiac failure. (b) Collapse: circulation is almost completely arrested, accelerated respiration, weak pulse, decreased systolic blood pressure, diminished or no urine output. This stage lasts from a few hours to one or two days. The mind remains clear until just before death, when coma occurs. Death follows shortly thereafter. Death can follow the onset of symptoms in little as six hours. (c) Reaction: sometimes, even when the grim reaper is about to claim victory, vomiting ceases, diarrhea becomes less frequent and less watery, and convalescence follows. Talk about your near-death experiences!

Immediate oral or intravenous rehydration is essential to survival. Of course, victims may be in no mood to radically increase their oral intake of liquids, even when sweeteners and essential minerals are added. Untreated, the mortality rate is 40-60%, whereas immediate treatment can lower this to less than 1%, even with only oral rehydration therapy. As few as 30% and as many as 80% of those infected can be asymptomatic, and hence well-carriers who shed the Vibrios in their fecal matter, thus furthering infection of the populace. Once infected, further infection with the same subtype of Vibrio usually leads to at worst a subclinical infection, i.e., no appearance of classic symptoms. Although there is a vaccine, it is of modest value, because it is effective at most 50% of the time and lasts only for 3-6 months for Vibrios of the same subtype. The dominant subtype was O1 classical, but that has now been superseded by the El Tor biotype, which is less virulent, but more long lasting and has more well-carriers. Clinical trials of newer vaccines are ongoing.

This disease has swept the world in seven major pandemics, including a major outbreak in South America, particularly Peru, as recently as 1991 (Avoid the ceviche!). Cases have also been reported along the Gulf coast of the U.S., usually the result of eating raw, infected shellfish. Cholera is endemic in India, Pakistan, Bangladesh, and the Americas.

The major cholera pandemics are generally listed as: First: 1817-1823, Second: 1829-1851, Third: 1852-1859, Fourth: 1863-1879, Fifth: 1881-1896, Sixth: 1899-1923: Seventh: 1961- 1970, and some would argue that we are in the Eighth: 1991 to the present. Each pandemic, save the last, was accompanied by many thousands of deaths. As recently as 1947, 20,500 of 30,000 people infected in Egypt died. Despite modern medicine, cholera remains an efficient killer.

The second and third pandemics were enhanced by the concomitant Industrial Revolution, subsequent migration to the cities in search of jobs, and the unregulated growth of tenements and slums. Thoughts of supplying fresh water and removing wastes from new construction was furthest from developers' minds as they cut corners in order to maximize profits (Vive la capitalisme!). If there were cesspools for buildings, they were only accessible from the ground floor. Chamber pots filled with human waste were emptied from windows in the upper stories, much to the displeasure of pedestrians who served as potential and usually rapidly moving targets. A sewer was no more than an extended cesspool with some provision for overflow, usually on one end. The excess ran into the streets or adjoining property. These so-called sewers had to be mucked out by hand, any dangers of methane poisoning or explosion notwithstanding.

Upon discovering cholera cases, most countries took immediate, if not altogether effective, action. England's first case was William Sproat of Sunderland who cast off his mortal coil on October 26, 1831. Officials were loath to quarantine ports or even incoming ships lest the emerging textile industry be harmed. The administration's spin was that there was no cholera in England. This remained in effect for almost twenty years. When in doubt, deny everything—a policy that has found its way into this century. Needless to say, this did little to ameliorate the extent of the epidemic.

When the sixth pandemic erupted in the Middle East, Russia, and other parts of Europe during the summer of 1892, American newspapers warned of the potential spread westward. This came at a time when immigration into New York was at an all-time high. The strength of the Russian epidemic and an earlier outbreak of 200 cases of typhus amongst Russian Jews who had arrived on January 30 aboard the S.S. Massilia from Marseilles only compounded the problem. Jewish passengers and their American contacts were forcibly separated from relatives and sent to North Brother Island, downwind of the garbage dump on Riker's Island, in the East River near 140th Street. Neither cabin-class passengers nor the 470 Italian immigrants who shared steerage with the Russian Jews were detained. Of the 1200 detained Jews, fully 1150 never showed any symptoms of typhus. Nevertheless, because of a lack of space, most were forced to live in tents. Soap was scarce and when available, bathing required a dip in the frigid river. Medical care was totally inadequate, resulting in at least six unnecessary deaths. Not only was there no contact with the mainland, but the Jews were deprived of kosher food. Those who died were either cremated or interred in tightly sealed metal canisters, thus violating Jewish burial laws. Only after major protests from the well-established German Jewish community were regular burials and kosher food allowed.

Many political figures argued against unrestricted immigration, especially by groups with uncommon customs and costumes. A strict quarantine had proven effective in combating the typhus epidemic, so when the S.S. Moravia arrived from Hamburg with 22 cholera deaths, of which 20 were Russian children under age 10, a strict 20 day quarantine was imposed on all steerage passengers—but not on cabin-class passengers. Other ships brought more cholera and cases were found in New York City. Sans any supporting scientific evidence, kosher butcher shops were closed for the most trivial health code violations; many immigrants were evicted from their tenements and left to fend for themselves in the streets. Measures unrelated to the germ theory of disease (long after it was well known) were taken against Jewish immigrants, mostly at the instigation of the Surgeon General, Walter Wyman. Then president Benjamin Harrison was an ardent proponent of restricting Russian Jewish immigration, urging Congress "to keep out the vicious, the ignorant, the civil disturber, the pauper, and the contract laborer..." It was not a happy time for the Jewish community of New York.

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Smallpox

Smallpox (variola) is (was) caused by a poxvirus (shown below) and is (was) spread from person to person by contact with skin lesions or via the respiratory tract.

 

Its name was derived from the small indentations, or pockmarks, on the skin that it caused. The picture of the infected baby was an official World Health Organization picture used for identifying victims.

 

 

 

 

The mortality rate ranged from 20% to as high as 40% depending on the age and health of the host. The disease came in two usual forms, variola major and variola minor, with the latter being less virulent and causing only a sparse rash and a low-grade fever. The virus is extremely stable and has not changed in, what may very well be, hundreds or even thousands of years. The infective dose is 1000 virions per milliliter (essentially several drops of material sneezed or breathed in your direction. Gesundheit!). Experts claim that smallpox killed more than 100 million people prior to 1725.

There are also two rare forms of smallpox: hemorrhagic and malignant. The first is characterized by significant subcutaneous bleeding. Both are usually 100% fatal if untreated.

Some early physicians believed in the process of variolation, whereby the pus or infected scabs of pox victims were ground up and inserted under the skin. Recipients of this treatment developed a mild form of the disease and attained a permanent resistance. Also, farmers and milkmaids deliberately infected themselves with cowpox because experience had taught them that this prevented the smallpox. Cotton Mather notified Thomas Jefferson of the merits of variolation and Jefferson had everyone in his household, freemen and slaves alike, variolated.

In the late eighteenth century England, Edward Jenner noticed that milkmaids rarely came down with smallpox, but did show mild symptoms of the related disease cowpox. He reasoned that the cowpox caused immunity to the more serious disease. He concocted a mixture of extracts from the cowpox-infected milkmaid Sarah Nelmes and, contrary to the spirit of modern experimental medicine and the principle of informed consent of subjects, injected it into an unknowing eight year-old boy, John Phipps, on May 4, 1796. He found that, despite all his attempts, the boy could subsequently not be infected with variola. Almost two years later, he took an extract from the hand of Thomas Virgoe, who had been infected through contact with the heel of one of his mares. This was injected into one John Baker, who also became impervious to variola. Thus was born the smallpox vaccine. [By the way, vaccine comes from the Latin word vacca, meaning cow.]

As with all new discoveries, vaccination was very slow to take hold. Jenner had to publish the results himself, since no medical journals would accept it. 

The disease has been "completely eradicated" after instigation from the Soviet Union before the World Health Assembly in 1958. At that time, the disease claimed two million lives each year with cases in thirty-three different countries. Smallpox was "eradicated" because:

1. There were no subclinical infections, so that there were no well-carriers;
2. Victims were infectious for at most five days and the disease's effects severely limited its victim's mobility and the probability of further spread;
3. The virus was completely eliminated from the body upon recovery and resulted in total immunity to all future infection;
4. There were no animal reservoirs for the infection, hence, no vectors of transmission; humans were the only hosts;
5. The symptoms were clearly recognizable and infected cases could be readily identified;
6. An inexpensive, effective, and easily transported vaccine was available.

The eradication program began in 1967 under the direction of the American Donald Henderson working for the United Nations. Each subsequent outbreak was attended by a cadre of experts who immunized everyone (whether they wanted it or not—although that frequently took quite a bit of diplomatic cajoling) in the area. Teams operated in times of natural disasters, wars, and insurrections, from Bangladesh to Sudan to Yugoslavia (it was a single country back then) to Ethiopia, and elsewhere.

Finally during November of 1975, a three-year-old Bangladeshi girl Rahima Banu was cured in the last natural case of variola major. On October 26, 1977, Ali Maow Maslin (Merka, Somalia) was the last (cured) case of variola minor. Unfortunately, in 1978 in Birmingham, England there was a major security breach in the ventilation system of a (supposed) BSL-2 laboratory and a photographer, Janet Parker, working upstairs of the lab was infected and died of smallpox. Her mother, with whom she lived, came down with the disease but survived. On May 8, 1980, the World Health Assembly formally declared the earth free of smallpox. No other cases have been reported since.

There are only two stores of smallpox virus in the world today, the CDC BSL-4 lab in Atlanta and the Russian State Research Center of Virology and Biotechnology in Koltsovo, Novosibirsk. The stores were scheduled to be destroyed on December 31, 1996, but the US has decided against destruction because of the possibility of the virus's use in bio-warfare.

In 1969, the US and the Soviet Union signed a treaty banning biological weapons. The US has adhered to the treaty while it has been reported that Russia has not. Russia is alleged to currently have several metric tons of freeze-dried genetically engineered hemorrhagic smallpox virus.  [For more details, read Germs: Biological Weapons and America's Secret War by Miller, Engelberg, and Broad.]

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Influenza